Peanut allergy: where do we stand?

 

 John Weisnagel, M.D.

 

This review of the complex issue of peanut allergy was started in Oct. 1998 following a great deal of attention given to the subject in the media at that particular time. This coincided with many publications in the medical literature as cited in the references seen below in the opening paragraphs, conclusions of the authors considered as "alarming, frightening", according to comments of some visitors scanning this article. There were articles in magazines, like Time, Newsweek, as well as in local papers on what seemed an increase in peanut allergy, on banning peanuts in schools or on commercial flights, etc.22,25. Some of the articles, and reactions to them, were posted and appear in the article, and may still be accessible (at times, they're removed without any warning). The effect of all this attention to peanut allergy resulted in a panic situation, both in the minds of the public as well as the medical community, an attitude that seems to persist.
 
Since then, things have quieted somewhat particularly in the media, but most publications on the subject in the medical literature will often begin with statements such as, "most pediatric allergists agree that the prevelance of food allergies, and peanut allergy in particular, is increasing..."107 or "peanut and nut allergy is common and the most frequent cause of severe or fatal reactions to foods..."108 or "...despite the steady advancement in our understanding of atopic immune responses and the increasing number of deaths each year from peanut anaphylaxis...119 " or..."peanut is one of the most common foods causing allergic reactions and is the most common cause of fatal and near-fatal food-related anaphylaxis.."122 all giving the impression that peanut allergy is indeed on the increase, but as Dr Hugh Sampson states in the opening paragraph of his article "What should we be doing for children with peanut allergy?"107 "appropriate epidemiological data to substantiate this belief are lacking! "
 
Recent publications on peanut allergy also note that anaphylaxis has also increased in a very substantial way.....e.g.169, or Peanut Allergy: a growing problem, a commentary by Wesley Burks, published in the J. Clin. Invest.173 He starts off his article with "Peanut allergy is one of the most serious of the immediate hypersensitivity reactions to foods in terms of persistence and severity and appears to be a growing problem." citing Sampson's 2002 article published in the N Eng J Med.154, but as mentioned by Gideon Lack, et al, in their March 13th, 2003 New England Journal of Medicine article entitled 'Factors Associated with the Development of Peanut Allergy in Childhood'..."The apparent increase in the prevalence of peanut allergy has been difficult to explain, although it parallels an overall increase in allergic diseases in childhood."171
Yet, in the J Allergy and Clin Immun, March 2003 issue, Kelso et al. report on a case of Psychosomatic peanut allergy. A 27-year old woman with a history of rhinitis and asthma, 20 min. after eating a peanut butter and jelly sandwich, developed generalized itching and hives, shortness of breath and wheezing, treated in the ER. The next day she had a similar reaction after eating a peanut butter candy. She was evaluated in the allergy clinic and both skin tests to peanut (also done with fresh peanut) and peanut-specific IgE were negative. She had an open challenge with a teaspoon of peanut butter and in fifteen minutes she complained of itching and feeling warm, developed hives, but no signs of asthma; she was treated with epinephrine and fexofenadine. Further tests failed to show any IgE binding. She underwent a double-blind, placebo-controlled challenge which was negative. She was informed of the results and subsequently had an open challenge which was also negative.172 (posted Mar 31st, 2003)
 
But the good news is that there are encouraging indications, contrary to previous publications, that allergy to peanuts can disappear. There are studies in progress in various centers evaluating the duration of this allergy, always thought of as a lifetime allergy. Of some concern though are recent reports of recurrence of the allergy in children who have outgrown peanut allergy with increasing peanut-specific IgE levels and allergic reactions, for some reason in children who have eaten peanut sparingly since their negative challenge. (posted Feb 16th, 2004)
A factor that is being studied is tthat peanuts in the western countries are for the most part roasted - roasting peanuts seems to increase their allergenicity and could be an important element in the prevalance of this allergy. (see more on this further in this article)
 
This ongoing article is updated regularly, as developments occur, hopefully not only to make everyone aware of this unpredictable allergy, but also to help ease the fear generated. All updates appear with the date of the posting and for a time (usually 3 months) preceded by this image.

(text possibly too technical in references that follow is altered, and comments added for general public access)

 

Background

Peanut (arachis hypogea) belongs to the biological family 'leguminosae' or 'legumes' which include peas, beans, lentils, vegetable gums as acacia and tragacanth, and licorice. Peanut is not a nut (although publications originating in the United Kingdom often include it when discussing nut allergy). Nuts belong to different biological families, e.g. pecan belongs to the 'judanglacea' family along with walnut, e.g. almond is of the 'drupacea' family which includes peaches, apricots, plums, nectarine and cherries, e.g. the 'anacardiacea' family groups cashews, pistachios and mangos, etc.See description in Allallergy.net and also: "Fruits called Nuts" with super photos.

According to the National Peanut Board which represents 25,000 peanut farmers in the US, americans consume more than 600 million pounds of peanuts and over 700 million pounds of peanut butter annually. Because of its nutritive value, particularly a good source of protein, peanut today is a common food in most westernized countries.

The natural history of food allergy involves the development of the sensitivity and eventual loss of it, as observed in children as well as adults. Very young children with allergy to milk proteins, soya, or eggs, tend to lose their allergies as they grow older 7, 26 even in the case of anaphylactic reactions (severe allergic reactions requiring emergency treatment; detailed further in the article) 27. However, with certain foods such as tree nuts, shellfish and peanuts, things are different. According to Bock and Atkins, children with allergy to peanuts tend to keep their allergy for many years 19.

In 1995, at the Annual Meeting of the American Academy of Allergy, Asthma and Immunology, Bock and collaborators presented their findings in the follow-up of 60 children with confirmed allergy to peanuts, aged between 3 months and 17 years. They concluded that:

1) Peanut allergy occurs with surprising frequency in young children: 17 before age one; 30 between one and two years of age; 19 between two and three years of age; and 3 between three and four years of age;
2) children do not seem to lose peanut allergy very often;
3) accidental reactions are common;
4) reactions in young children may require emergency Rx.

 

Characteristics of peanut allergy

-Peanut allergy is characterized by more severe symptoms than other food allergies and by high rates of symptoms on minimal contact. In a questionnaire study of 622 self-reported allergic subjects, a total of 406 patients (66%) reported symptoms on contact with peanut. Only 121 (19%) had been knowingly exposed to peanut before the first documented reaction implying a high frequency of occult sensitization.2(see important facts further in this article re early sensitization).

-Alt, Ramesh, and Reisman presented a paper at the 1997 American Academy of Allergy, Asthma and Immunology (AAAA&I) Annual Meeting, on anaphylaxis in a 6 month old infant, after eating a portion of a cracker containing peanut. No previous exposure to peanuts, but a RAST test showed a very high sensitivity to peanut! (RAST stands for "radioallergosorbent test", an allergy test done on a sample of blood, the aim as with skin tests, to check for allergic sensitivity to specific substances.)

-Approximately one third of emergency-room visits for anaphylaxis may be due to peanut sensitivity 8,15

-Immediate hypersensitivity to peanuts is a frequent cause of anaphylactic reactions and deaths in children and adults 3

-Severe allergic reactions caused by foodstuffs have been reported in Sweden since 1993, 60 cases, five of them fatal, occurring during the first 3-year period. More than 70% of all reactions reported were caused by peanuts, soya beans, nuts or almonds. In only 13% of reported cases were the patients over 17 years of age...with extremely severe reactions including asthma.4

 

 -In the Sept 1998 issue of Clinical and Experimental Allergy, Moneret-Vautrin, and coll. reported an evaluation of 142 observations of allergy to peanuts in France 23. The clinical features were:

-Rance F and Dutau G, co-authors of the Sept 1998 article above, published in April, 1999, "Peanut hypersensitiviy in children" which appeared in Pediatr Pulmonol Suppl. and reported the following:

-In the Dec. 1999 issue of the Anaphylaxis Network Newsletter, there was an article by Dr. Wesley Burks,University of Arkansas, on food anaphylaxis. It mentioned partway through that "It is not rare, particularly for peanut-allergic children who had minimal cutaneous (skin) and gastrointestinal symptoms as young children, to experience significant systematic anaphylactic symptoms following the ingestion of peanuts in their adolescent years." (brought to my attention by Nancy Wiebe of the Calgary Allergy Network and posted Jan 23d, 2000).  
 
 
-According to Sicherer and Sampson, in their review "Peanut and tree nut allergy" published in the Dec. 2000 issue of Pediatrics, "Allergies to these foods are common, frequently have an onset in the fist years of life, generally persist, and account for severe and potentially fatal reactions. Furthermore, the ubiquity of these foods in the diet makes avoidance difficult and accidental ingestions, with reactions, common." 101 (posted Dec 10th, 2000)
 
 

 

 
 
-Kanny, Moneret-Vautrin, Flabbee and collab. published their epidemiological study entitled"Population study of food allergy in France" in the July 2001 issue of J Allergy Clin Immunol. The study was conducted on 33,110 persons who answered a questionnaire addressed to a sample of the French population. 1129 persons with food allergy selected during phase I received a second questionnaire. Results:
 
-"Food anaphylaxis is now the leading known cause of anaphylactic reactions treated in emergency departments in the United States. Is is estimated that there are 30,000 anaphylactic reactions to foods treated in emergency deparments and 150 to 200 deaths each year. Peanuts, tree nutes, fish, and shellfish account for most severe food anaphylactic reactions...the mechanistic details responsible for symptoms of food-induced anaphylaxis are not completely understood, and in some cases, symptoms are not seen unless the patient exercises within a few hours of the ingesion." (Sampson HA) 177(posted June 25th, 2003)
 
 
-Sperget JM et al, in the Feb 2004 Ann Allergy Asthma Immunol have a comment entitled Correlation of initial food reactions to observed reactions on challenge. After a retrospective review of all food-sensitive children who underwent food challenges at the Children's Hospital of Philadelphia in a 5 year period, they concluded that "Patients will typically experience similar reaction on re-exposure to the initial reaction. However, multiple-organ system reactions can occur after any initial clinical presentation, with milk, egg, and peanut having more multiple-organ reactions than other foods." 216(posted April 25th, 2004)
 

 

Threshold doses

-The minimum dose of food protein to which subjects with food allergy have reacted in double-blind, placebo-controlled food challenges is between 50 and 100 mg. (double-blind and placebo-controlled signify that neither the patient nor physician know whether the food or a placebo [substitute] is being used [food evaluated and a substitute both appear the same], and a control non allergic individual also participates in the challenge) However, subjects with peanut allergy often report severe reactions after minimal contact with peanuts, even through intact skin. In a group of well-characterized , highly sensitive subjects with peanut allergy, the threshold dose of peanut varies. As little as 100 microg. of peanut provoke symptoms in some subjects with peanut allergy10

  -In the April, 2001 issue of Allergy , Dr Jonathan O'B Hourihane, in his paper entitled The threshold concept in food safety and its applicability to food allergies, states that "many factors may contribute to a variation of threshold in an individual exposed to an allergen during the course of his or her daily life....the most important one of these is the adequate training and awareness of manufacturers and caterers who aim to provide safe and nutritious meals to their allergic and non-allergic customers alike....Studies have not yet had the power to investigate whether peanut allergy is more commnonly associated with very low dose reactivity than other foods. This means that industry must not concentrate only on peanut and tree nuts when looking at issues of contamination just because they are associated with the majority of severe reactions. There are more milk and egg allergic children in the general population and they deserve the same protection from allergy exposure as sufferers of peanut or tree nut allergies. 118 (posted April 21st, 2001)

 -In the Jan 2002 J Allergy Clin Immunol , twelve clinical allergists and other interested parties published their conclusions following a Sept 1999 roundtable discussion. The article is entitled Factors affecting the determination of threshold doses for allergenic foods: How much is too much?

They define the threshold dose as "the amount of the offending food that would elicit mild objective symptoms (e.g. mild urticaria, erythema, and oral angioedema, in the most sensitive individual." Many factors may be involved in the reactions reported such as circumstances of exposure, the amount and type of food eaten, determined anecdotally. For peanut, based on challenges, the lowest provoking dose was 1mg (in 4 out of 309 patients) the range being 1mg to 5 gms.

Results: Considerable data were identified in clinical files relating to the threshold doses for peanut, cows' milk, and egg; limited data were available for other foods, such as fish and mustard.

Conclusions: Because these data were often obtained by means of different protocols, the estimation of a threshold dose was very difficult. Development of a standardized protocol for clinical experiments to allow determination of the threshold dose is needed. 148 (posted Feb. 11th, 2002)

-Follow-up to the above publication: A consensus protocol for the determination of the threshold doses for allergenic foods: how much is too much? was published in the May 2004 Clin Exp Allergy by the same group (plus others).225 (posted May 22nd, 2004)

-The distribution of individual threshold doses eliciting allergic reactions in a population with peanut allergy is the title of a publication in the Dec 2002 J Allergy Clin Immunol by Wensing et al. Twenty-six adult patients with a convincing history of peanut-related symptoms, a specific IgE level of 0.7kU/L, or greater, or a positive skin prick test response of 2+ or greater to peanut were included. These patients underwent double-blind, placebo-controlled food challenges with increasing doses of peanut.
Results: Threshold doses for allergic reactions ranged from a dose as low as 100 µg up to 1 gm of peanut protein. Fifty percent of the study population already had an allergic reaction after ingestion of 3 mg of peanut protein.
Conclusions of the authors: A substantial part of a population with peanut allergy will react to very low amounts of peanut, requiring accurate declaration of peanut content in consumer products. This is even more important because patients with severe reactions react at lower doses than patients with mild symptoms. 167 (posted dec 9th, 2002)
 
-Determination of no-observed-adverse-effect levels (NOAELs) and eliciting doses in a representative group of peanut-sensitized children is the title of a publication in the Feb. 2006 J Allergy Clin Immunol by Flinterman et al. As the abstract states: 'Current labeling practices for allergenic foods like peanut can be inadequate. For future regulatory and industry guidelines, information on NOAELs and eliciting doses (ED) for allergenic foods is necessary.' They evaluated a group of 27 children by questionnaires, skin prick test, determination of specific IgE, and DBPCFC (challenges) with peanut according to the international consensus protocol, with 9 doses ranging from 10 µg to 3 g peanut flour. Dietary management was evaluated over a 12 month period.
Results: 22 children (81%) had a positive challenge. The NOAEL in this group was 1 mg peanut flour, corresponding to 2 mg whole peanut. The ED for subjective symptoms was 100 mg to 3 gm. Severe reactions occurred only at high doses. EDs were not correlated to previous reactions by history, skin test, or specific IgE levels. All patients with a positive challenge were advised to follow a strict diet. During the follow-up period, 10 patients had a less strict diet likely containing traces fo peanut. In 3 cases, a mild reaction occurred with food products laeled "may contain peanut".
Conclusion: The NOAEL in a representative group of children with peanut allergy was 2 mg,. Dietary compliance in half of this group was inadequate. 257(posted May 7th, 2006)

-At the 59th annual meeting of the American College of Allergy, Asthma, and Immunology Nov. 2001 in Orlando, Florida, Dr Rosemary Hallet presented a study of a questionnaire involving people with known food allergies, "Have you ever had a reaction after touching food?" 'People with a nut allergy can have an anaphylactic reaction if they kiss someone who has recently eaten the offending substance, according to Dr Rosemary Hallet. '...we found 5% who voluntarily stated that they had had a reaction after kissing someone who had eaten a type of nut to which they were allergic. The reaction is likely more common than we found'. Fifteen of 442 respondants stated that they had a reaction, even up to 6 hours after the kisser had eaten the offending food.(But there's no description of the reaction in the report). (posted Nov. 25th, 2001)

Dr Hallett has a letter to the editor of the New England Journal of Medicine, in the June 6, 2002 issue, entitled, Food Allergies and Kissing where she specifies that the implicated foods were peanuts, walnuts, and other tree nuts; reactions began rapidly after the kiss in all interviewed subjects (all in less than a minute); all 17 reported localized itching and swelling or urticaria in the area kissed; four subjects reported the development of wheezing with at least one episode of kissing; patient 5 was kissed on the cheek by his mother right after she tasted pea soup on the stove and a large wheal immediately developed at the exact site of the kiss, followed in minutes by flushing, urticaia, angiodedema, and severe wheezing, requiring the administraion of epinephrine in the ER. (posted June 21st, 2002) 156

-In the Sept 2001 issue of Allergy, Wathrich, et collab. published an artilce entitled "Kiss-induced allergy to peanut" which is probabley similar. Unfortunately there is no abstract on Medline. 138 (posted Nov 23d, 2001)

-Here's a report of a telephone survey done by a Swedish group, reported by Nils E Eriksson (co-ordinator) Lung & Allergy Clinic, County Hospital, Halmstad, Sweden: CAN KISSES INDUCE ALLERGIC SYMPTOMS IN MORE THAN TEN PERCENT OF FOOD ALLERGIC PATIENTS? A total de1139 patients (56 children < 8 years and 1083 patients > 8 years responded and the authors' results confirm that approx. 10% of allergic individuals can react by being in close proximity to peanuts or kissing someone who has eaten peanuts, although their tables summarizing the results are difficult to interpret exactly. (I have not found said study on Medline).

 

-Kiss may have killed Quebec teen (posted Nov 28th, 2006). This has been reported throughout the world, but unfortunately without further info regarding the victim. Following a CBC report (only in French) it seems her boy-friend had eaten a peaut butter sandwich many hours before and he was not aware of his girl-friend's peanut allregy. She was also asthmatic and at 3 am, she thought she was having an asthma attack and began using her puffers without success. The Epipen was discovered only after Urgence-Santé got to the victim's residence. Was the peanut allergy-kiss responsible for the anaphylactic reaction? (posted Nov 30th, 2005)

-The latest on this story is that the autopsy revealed that it was in fact a tragic death related to a reaction to peanut.
-On March 3d, 2006, Dr Michel Miron, coroner of the district of Chicoutimi, speaking to the media, concluded that 'Christina Desfornes did not die due to an anaphylactic reaction after kissing her boyfriend after he had eaten peanut butter. The story made headlines round the world, and Mr. Miron said he wants people to know that a peanut-butter sandwich did not cause the death of Christina Desforges last November.
-On May 11th, 2006, Dr Miron held a press conference where he concluded that Christina Desforges did not die as a result of an allergic reaction to peanut, but from cerebral anoxia due to an acute asthmatic attack.
PS. Unfortunately, as happens usually following corrections or retractions, the initial report back in Nov 2005, which made headlines worldwide, for many will stand and be wrongfuly treated as a death due to peanut allergy.
-At the 2006 annual meeting of the AAAA&I held in Miami, FL Mar 3-7th, Maloney JM et al reported Peanut allergen exposure through kissing (saliva). Assessment and intervention. (J Allergy Clin Immuno, vol117, no2, abstracts, #134, p S34) The authors concluded that peanut allergic patients, particularly adolescents, must be counseled regarding the risks of kissing someone who has recently eaten peanut, even if they brushed their teeth. Practical advice may include brushing teeth PLUS waiting a number of hours before kissing, but definite recommendations must follow evaluation of cleaning routines that are underway in a larger population. (posted April 15th, 2006)
-The authors published their findings in the J Allergy Clin Immunol 2006 Sep;118(3):719-724. Epub 2006 Jul 24. Of the 38 individuals, most (87%) subjects with detectable peanut after a meal had undetectable levels by 1 hour with no interventions. None had detectable levels several hours later after a peanut-free lunch. Waiting several hours and ingesting a peanut-free meal were more effective at reducing salivary peanut protein concentration than simple, immediate interventions. (posted Sept 19th, 2006)

-Swelling of lips and tongue were reported in a card player from cards he handled which were contaminated by peanuts eaten by fellow players. Lepp U, Zabel P, Schocker F. Playing cards as a carrier for peanut allergens. Allergy 2002 Sep;57(9):864.

-Morisset M, Moneret-Vautrin D, et al in the Aug 2003 Clin Exp Allergy published Thresholds of clinical reactivity to milk, egg, peanut and sesame in immunoglobulin E-dependen allergies: evaluation by double-blind or single-blind placebo-controlled oral challenges. Data from 125 positive oral challenges to egg, 103 to peanut....were analyzed. The lowest reactive threshold has been observed at less than 5 mg of peanut....They conclude: Minimal reactive quantities show that, in order to guarantee a 95% safety for patients who are allergic to peanut...and on the basis of consumption of 100 g of food, the detection tests should ensure a sensitivity of 24 p.p.m for peanut. 190 (posted Aug 18, 2003)
-In the Nov 2003 Clin Exp Allergy, Grimshaw K et al. have a study entitled Presentation of allergen in different food preparations affects the nature of the allergic reaction - a case series. In an ongoing study that used a double-blind placebo-controlled food challenge to investigate peanut allergy and clinical symptoms, the observed reaction severity in four of the first six subjects was greater than anticipated. They hypothesized that this was due to differences in the composition of the challenge vehicle. Peanut-allergic subjects were re-challenged with a peanut preparation containing less fat. Results: 3 of 4 subjects reacted to much smaller doses of peanut protein on re-challenge (mean dose quivalence - 23 times less peanut) with the lower fat recipe. RAST inhibition and ELISA tests concurred.
Conclusion: The fat content of a challenge vehicle has a profound effect on the reaction experienced after allergen ingestion. This is another factor to be considered in assessing the risk of certain foods to food-allergic consumers and adds another dimension to clinical, research and regulatory practice. 195 (posted Nov 22nd, 2003)

 

 
-At the annual AAAA&I Meeting held in San Francisco Mar 19-23, 2004, Conover-Walker and Wood have a poster entitled The Risk of food challenges.. Chart review was performed on children who underwent food challenges to milk, egg, peanut, soy and/or wheat in a university based pediatric allergy clinic over a seven-year period: Of the 570 challenges completed, 238 (42%) experienced an allergic reaction. Failure rates were:
  • egg 50/130 (38%), milk 88/162 (54%), peanut 65/157 (41%), soy 21/76 (28%), and wheat 14/45 (32%).
  • 121 (51%) had a reaction involving 1 organ system (egg 50%, milk 51%, peanut 45%, soy 62%, wheat 64%),
  • 90 (38%) had 2 system involvement (egg 34%, milk 40%, peanut 46%, soy 24%, wheat 22%), and
  • 27 (11%) had 3 system (skin, gastrointestinal, and respiratory) involvement (egg 16%, milk 9%, peanut 9%, soy 14% and wheat 14%).
  • No patients experienced hypotension.
  • All reactions were reversible with diphenhydramine +/&endash; epinephrine and corticosteroids. No children required hospitalization and there were no deaths.
Conclusions There are risks associated with food challenges and the risks are similar for each of the foods studied. One half of the reactions involved only 1 organ system and only 11% involved 3 organ systems. Given the benefits that result from a negative challenge, these risks are reasonable when challenges are performed under the guidance of an experienced practitioner in a properly equipped setting. 211(posted Feb 16th, 2004)
 
 
 
-Update on threshold doses of food allergens: implications for patients and the food industry is the title of a publication in the June 2004 Curr Opin Allergy Clin Immunol by Moneret-Vautrin and Kenny. The purpose of their review was to bring the reader up to date on the importance of assessing a food's lowest observed adverse-effect level (LOAEL) with two aims. Firstly, to help industry choose tests with a level of sensitivity capable of detecting food allergens hidden in industrial products. Secondly, to specify protective measures for highly allergic individuals in order to prevent recurrent severe anaphylaxis.
SUMMARY: Concerning IgE-dependent food allergies, the threshold dose inducing symptoms is now known to vary a great deal according to the individual. A reactive dose of less than 65 mg characterizes16 and 18% of patients allergic to egg or peanut... 1% of these patients have a very low threshold, about 1 mg. Such data emphasize the necessity of using detection tests with a sensitivity better than 10 parts per million. The modifications of allergenicity undergone by protein ingredients that are now commonly introduced into industrially made products are not yet sufficiently known. A better knowledge of the reactive doses of these proteins is needed.221 (posted May 15th, 2004)
 
 

-At the 2006 Annual Meeting of the AAAA&I in Miami,.FL., Dr Marie-Noel Primeau from the Allergy Service of Ste Justine Hospital, Montreal, presented First reaction to nuts or peanuts from candy bars labelled 'may contain nuts/peanuts' in older chidren. ( J Allergy Clin Immuno 117:no 2 abstracts, no 146, page S 37) She described the case of a 13 yr-old boy who had his first anaphylactic reaction (abdom. pain, urticaria and respiratory distress) requiring treatment with epinephrine 30-60min. following a dinner containing a brownie labelled 'may contain traces of nuts'. Skin tests were positive to hazelnut, cashew and pistachio and negative to peanuts. An oral challenge with hazelnut was positive. He had no previous history of allergy to nuts. The second case involved a 5 yr-old boy who developed urticaria 15 min. after eating a granola bar containng almonds and labelled 'may contain traces of peanuts.' He was a nut eater but had never eaten peanuts. Skin tests were negative to nuts but positive to peanuts. An open challenge to almonds was negative, but parents refused a peanut challenge. Two yrs later his skin test was still positive to peanuts, but the RAST was negative. One hour after an open peanut challenge the patient developed rhinitis and a severe cough.

 
Conclusion: A first allergic reaction to nuts and peanuts may happen after ingestion of products labelled 'may contain traces of nuts/peanuts' in older children. (posted April 15th, 2006)

Related to the above presentation:

-In the Arch Pediatr. 2006 Jul 5, Feuillet-Dassonval C, Agne PS, Rance F, Bidat E. have an rticle entitled, [Which avoidance for peanut allergic children?]. According to the abstract: 'The benefits of a strict avoidance diet seem limited: reactions to the low doses and to the peanut oil refined are rare and most often slight. It is not proven that a strict avoidance facilitates the cure of allergy. On the other hand, strict avoidance could induce a worsening of allergy, with deterioration of quality of life, creation of food neophobia. In case of cure of allergy, it is difficult to normalize the diet after a strict avoidance. Outside of the rare sensitive patients to a very low dose of peanut, for which a strict avoidance is counseled, the report benefits risk is in favor of the prescription of adapted avoidance to the eliciting dose. For the majority of the peanut allergic children, it seems to us that the avoidance can and must be limited to the non hidden peanut.'260 (posted July 15th, 2006

 

See more on this subject in the section on "follow-up of patients with peanut allergy" further in this article.

  

 Prevalence or incidence of food allergies

The exact prevalence of food allergy, specifically peanut sensitivity, is not known. Reports vary. Here are a few going back a few years:

-The incidence of food allergy in children is approximately 1.3% and among adults 0.3% according to Chandra (1997). 5

-True food allergies are much less prevalent than is generally believed. They are more common in infants and children under age three than in older children and adults. Infant colic generally is not caused by a food allergy. In infants, urticaria, eczema or gastrointestinal bleeding may be due to foods such as milk and eggs, but clinical tolerance usually develops within a few years. Peanuts, tree nuts, seafood and seeds, as well as milk and eggs, can cause anaphylaxis in highly allergic children, and re-exposure to such foods presents the risk of life-threatening reactions7.

-Approximately 5% of children younger than 3 years and 1.5% of the general population experience food allergic disorders, indicating that about 4 million Americans suffer from food allergies 11.

-A dichotomy exists between perceived food allergy and that confirmed by appropriate challenge procedures. Only 40% of suspected food allergy has been confirmed by double-blind, placebo-controlled food challenges. . .In a recent survey of 5000 American homes, the percentage of individuals reporting peanut allergy was 7.2% 16.

-Allergy to peanuts represents 28% of food allergies and occurs under 1 year of age in 46% of cases, under 15 years of age in 93% 23.

-Ewan reported on 62 cases of peanut and/or nut allrergy evaluated in a one year period. Peanuts accounted for nearly half of the allergies, with 55% of the allergies presenting by age 2 years and 92% by age 7 years.33.

 

-Here's a publication that just may change our perception of peanut and nut allergy somewhat. The April 1999 issue of the J Allergy Clin Immunol contains an article by Sicherer, Munoz-Furlong, Burks and Sampson entitled "Prevalence of peanut and tree nut (TN) allergy in the US determined by a random digit dial telephone survey."65The title may sound nondescript, but read on- the findings are very significant:

 
 
 
-"Up to 8% of children less than 3 years of age and approximately 2% of the adult population experience food-induced allergic disorders. A limited number of foods are responsible for the vast majority of food-induced allergic reactions: milk, egg, peanuts, fish, and tree nuts in children and peanuts, tree nuts, fish, and shellfish in adults. Food-induced allergic reactions are responsible for a variety of symptoms involving the skin, gastrointestinal tract, and respiratory tract and may be caused by IgE-mediated (allergic) and non-IgE-mediated (or non-allergic) mechanisms. . .the skin and respiratory tract are most often affected by IgE-mediated food-induced allergic reactions, whereas gastrointestinal disorders are most often caused by non-IgE reactions. . . The initial history and physical examination are essentially identical for one or the other, but the subsequent evaluation differs substantially. Proper diagnoses often require screening tests for evidence of food-specific IgE and proof of reactivity through elimination diets and oral food challenges. Once diagnosed, strict avoidance of the implicated food or foods is the only form of treatment. Clinical tolerance to food allergens will develop in many patients over time, and therefore follow-up food challenges are often indicated." 71, 72 (posted June 23d, 1999)
 

-In Pediatr Allergy Immunol. 2006 Aug;17(5):356-63, Venter C et al have a publication entitled Prevalence of sensitization reported and objectively assessed food hypersensitivity amongst six-year-old children: a population-based study. This population-based cohort study recruited 798 6-year-olds resident on the Isle of Wight (UK). Sensitization rates, reported rates of FHS and objectively assessed FHS was established using food challenges. A total of 94 (11.8%) 6 yr olds reported a problem with a food or food ingredient. The rate of sensitization to the pre-defined panel of food allergens was 25/700 (3.6%). Based on open food challenge and/or suggestive history and skin tests, the prevalence of FHS was 2.5% (95% CI 1.5-3.8). Based on double-blind challenges, a clinical diagnosis or suggestive history and positive skin tests, the prevalence was 1.6% (95% CI 0.9-2.7). The rates of perception of FHS are higher than the prevalence of sensitization to main food allergens and the prevalence of FHS based on food challenges. Milk, peanut and wheat were the key food allergens amongst those with positive challenges.

   This study confirms the results of a 2005 publication by the same group done amongst adolescents: Prevalence of sensitization to food allergens, reported adverse reaction to foods, food avoidance, and food hypersensitivity among teenagers. J Allergy Clin Immunol. 2005 Oct;116(4):884-92.  (posted Oct. 3d, 2006)


 Statistics

-Food allergies, particularly to peanuts, are a common cause of anaphylaxis. Here are some statistics:

 
 
-Bock, Munoz-Furlong, and Sampson, in the Jan 2001 issue of the J Allergy and Clini Immunol report on their analysis of 32 fatal cases due to anaphylactic reactions to foods, reported to a national registry, established by the American Academy of Allergy, Asthma, and Immunology....The 32 could be divided in two groups: Group 1 had sufficient data to identify peanut as the responsible food in 14 (67%) and tree nuts in 7 (33%) of cases. In group 2, 6 (55%) of the fatalities were probably due to peanut, 3 (27%) to tree nuts, and the other 2 cases were probably due to milk and fish (1 [19%] each)...most victims were adolescents or young adults, and all but one were known to have food allergy before the fatal event...all but one were known to have asthma, and most of them did not have epinephrine available at the time of their fatal reaction. Fatalities due to ingestion of allergenic foods in susceptible individuals remain a major health problem. In this series, peanuts and tree nuts accounted for more than 90% of the fatalities. Improved education of the profession, allergic individuals, and the public will be necessary to stop these tragedies.110 (posted Feb. 13th, 2001)
 
-A follow-up to this article relevant to the 'national registry', Sicherer, Furlong, Munoz-Furlong, Burks and Sampson published in the July 2001 J Allergy and Clini Immunolo A voluntary registry for peanut and tree nut allergy: Characteristics of the first 5149 registrants. (The registry was established through use of a structured questionnaire distributed to all members of the Food Allergy and Anaphylaxis Network, and to patients by allergists. Parental surrogates completed the forms for children under 18 years of age). Here are their findings:
  • registrants were primarily children (89% of registrants were younger than 18 years of age, the median age was 5 years)
  • isolated peanut allergy was reported by 3482 registrants (68%)
  • isolated tree nut allergy by 464 (9%)
  • allergy to both foods by 1203 (23%)
  • registrants were more likely to have been born in Oct. Nov or Dec.
  • the median age of reaction to peanut was 14 months (first known exposure for 74%)
  • the median age of reaction to tree nuts was 36 months (first known exposure for 68%)
  • one half of the reactions involved more than one organ system
  • more than 75% required treatment, frequently from medical personnel
  • registrants with asthma were more likely than those without asthma to have severe reactions (33% versus 21%)
  • in comparison with initial reactions, subsequent reactions due to accidental ingestion were more severe, more common outside the home, and more likely to be treated with epinephrine.

    Conclusions: Allergic reactions to peanut and tree nut are frequently severe, often occur on the first known exposure, and can become more severe over time. 126 (posted July 27th, 2001)

     
-Furlong, Desimone and Sicherer, again related to the registrants in the US Peanut and Tree Nut Allergy Registry, published in J Allergy Clin Immunol Nov 2001 "Peanut and tree nut allergic reactions in restaurants and other food establishments." ..."features of allergic reactions to peanut and tree nut in restaurant foods, and foods purchased at other private establishments, e.g. ice cream shops and bakeries. Results: details obtained from 156 episodes (29 first-time reactions) form 129 subjects/parental surrogates.
  • -most reactions were caused by peanut (67%) or tree nuts (24%)
  • -in 9% of the reactions, a combination of peanut and a nut or peanut and unknown allergen
  • -symptoms began at a median of 5 minutes after exposure and were severe in 27% of reactions
  • -overall, 86% of reactions were treated (antihistamines, 86%; epinephrine, 40%.)
  • -establishments cited: Asian food restaurants (19%) ice cream shops (14%) and bakeries/doughnut shops (13%)
  • -among meal courses, desserts were a common cause (43%)
  • -of 106 registrants with previously diagnosed allergy who ordered food specifically for ingestion by the allergic individual:
    • -only 45% gave prior notification about the allergy to the establishment.
    • -for 83 (78%) of these 106 reactions, someone in the establishment knew that the food contained peanut or tree nut as an ingredient.
    • -in 50% of these incidents, the food item was "hidden" (in sauces, dressings, egg rolls, etc), visual identification being prevented.
    • -in 23 (22%) of the 106 cases, exposures were reported from contamination caused primarily by shared cooking/serving supplies.
    • -in the remaining 21 subjects with previously diagnosed allergy, reactions resulted from ingestion of food not intended for them, ingestion of food selected from buffet/food bars, or skin contact/inhalation (residual food on tables, 2; peanut shells covering floors, 2; being within 2 feet of the cooking of the food,1)
       
      Conclusions: Restaurants and other food estblishments pose a number of dangers for peanut-and tree nut-allergic individuals, particularly with respect to cross-contamination and unexpected ingredients in desserts and Asian food. Failure to establish a clear line of communication between patron and establishment is a frequent cause of errors." 136 (posted Nov 7th, 2001)
 

-In the Dec 2001 issue of Allergy appeared the following article by Shafer et al: Epidemiology of food allergy/intolerance (FA/FI) in adults: association with other manifestations of atopy. Of the 1537 studied subjects, 20.8% reported FA/FI. Nuts, fruits, and milk most frequently led to adverse effects, and the sites of manifestations were oral (42.9%), skin (28.7%), gastro-intestinal (13%), systemic (3.2%), and multiple (12.2%). Skin tests to 10 common foods and 9 aeroallergens were done: one quarter (25.1%) were sensitized to at least one food allergen, hazelnut (17.8%), celery (14.6%), peanut (11.1%) accounting for most of the positive reactions. Food-allergic subjects (positive history and sensitization to corresponding allergen) suffered significantly more often from urticaria, asthma, atopic eczema, and especially hay fever (73.1%) than controls. Conclusions: FA/FI in adults is frequently reported and associated with other manifestations of atopy. 141 (posted Jan 14th, 2002)

 

-Woods, Stoney, and coll. published in the Jan 2002 Eur J Clin Nutr Reported adverse food reactions overestimate true food allergy in the community. Based on skin tests, only 7 out of 457 adults (aged 26-50 yrs) who reported illness to a food also had a positive skin test to that food, suggesting that most reactions are not due to IgE mediated food allergy.149 (posted Mar 6th, 2002)

 

 
-Woods and coll. also published Prevalence of food allergies in young adults and their relationship to asthma, nasal allergies, and eczema in the Feb. 2002 Ann Allergy Asthma Immunol. Out of 1141 adults (aged: 20-45 yrs) taken at random and evaluated (questionnaire, history of asthma and other allergic conditions, lung function tests, and skin tests to cow's milk, peanut, egg white, shrimp and wheat), only 1.3% had probable IgE-mediated food allergy. Those with probable IgE peanut and shrimp allergy were significantly more likely to have current asthma and doctor-diagnosed asthma.150 (posted Mar. 6th, 2002)

 

-Fatal food allergies- rare in children. BBC News report. Monday, 25 March, 2002, 01:53 GMT . Researchers from Newcastle General Hospital calculate that if 5% of children in the UK have a food allergy, the risk of that child dying because of it would be 1 in 800,000 a year. In 10 years, there were just eight deaths. They hope their findings, published in the journal Archives of Disease in Childhood, will reassure parents worried that rates of such reactions are increasing dramatically. (posted Mar 25th, 2002)
Here is the publication in question: MacDougal CF, Cant AJ, Colver AF: How severe is food allergy in childhood? The incidence of severe and fatal allergic reactions across the UK and Ireland. A retrospective search for fatalities in children 0-15 years from 1990 to February 1998 primarily of death certification at offices of national statistics was done along with a prospective survey of fatal and severe reactions from March 1998 to February 2000, primarily through the British Pediatric Surveillance Unit.
 Resultts: The UK under 16 population is 13 million. Over the past 10 years, 8 children died (incidence of 0.006 deaths per 100,000 children 0-15 years, per year). Milk caused four of the deaths. No child under 13 died from peanut allergy...Over the past two years, there were six near-fatal reactions (none caused by peanut) and 49 severe ones (10 caused by peanut), yielding incidences of 0.02 and 0.19 per 1000,000 children 0-15 years of age per year respectively. Co-existing asthma is more strongly associated with a severe reaction than the severity of previous reactions. (posted April 8th, 2002)151

 

Electronic responses to this article (reproduced here in part):

1. From Jane Salter, M.D. president of Anaphylaxis Canada:

  • The findings and conclusions of our Canadian perspective on anaphylaxis (Jane Salter MD, Saral Mehra1, James T. Cairns MD, Gordon Sussman MD, Peter Vadas MD PhD A Study of 32 Food-Induced Anaphylaxis Deaths in Ontario; 1986-2000) differ from those of the MacDougal CF et al article. The British study found that 8 chldren died from food-related anaphylaxis over a 10-year period in the UK and Ireland...peanuts /nuts did not seem to play a significant role even in non-fatal reactions.
  • In Ontario, Canada, eleven of 32 food-related deaths between 1986 and 2000 occurred in children. Unlike the British study, peanuts/nuts caused 10 of the 11 deaths...The population of Ontario age 0-15 years is below 2.5 million, less than 20% of the population size sampled in the British study. The peak age for food-related anaphylaxis deaths in Ontario was between 15 and 25 years of age. This age group was excluded from the British survey.
  • Given population differences, the lower British/Irish death rate, particularly for penaut/nut, is surprising.
  • In the British study, patients who responded to one dose of epinephrine were excluded from the severe reaction category...this is misleading as it allows treatment success to interfere with measurement of incidence.
  • The study does not underscore the potential life-saving benefits of early IM administration of epinephrine.
  • As it is not currently possible to predict who might have a fatal reaction, we recommend that all people with allergies to peanuts, tree nuts and shellfish, regardless of degree of previous reactivity, be prepared to deal with an anaphylactic emergency.
  • Parents should be reassured that, provided they obtain an accurate diagnosis and follow current, recommended guidelines, their children will be well-protected. As teens and young adults appear to be at greatest risk, early childhood is the key time to prepare children for the more challenging years ahead.  
 
2. From David M. Reading, director of patient support group, Anaphylaxis Campaign:

 

  •  The authors conclude that the risk of a fatal allergic reaction among children under 13 is small, and the inference seems to be that the problem has been vastly exaggerated.
  • No one would argue that parents of food-allergic children should be helped to lower the anxiety levels in their lives. But the danger with this report is that it goes too far the other way and may lead to a dangerous over-confidence among the families affected by severe allergy and also among doctors, schools, child carers, and the food industry.
  • Medical experts would be better qualified to discuss the flaws in the study's methodology. As a layman, I would conclude there appear to be many.
  • The authors acknowledge that the risks increase for teenagers and young adults. Perhaps this is yet another reason for remaining well-prepared while children are younger.
  • Equally worrying, GPs may become reluctant to prescribe epinephrine injection pens to children when they genuinely need them. Having an epipnephrine kit appears to provide an assurance to patients, parents and child carers alike that they are not powerless; they have a means to protect themselves.
  • It would be disastrous if this report actually increased the risks for allergic children by persuading their families - and those who care for them - that the sensible protective measures they take are unnecessary.
     
     

3. From S. Allan Bock, Jonathan Hourihane, David Reading, Pete Smith, David Hill, Gideon Lack, and Anne Munox-Furlong:

 
-Although the article by MacDougall et al. regarding the incidence of severe and fatal reactions to food would seem to be reassuring,, we would like to express some concerns and raise some questions about the data presented.
  • -The first question is whether the ascertainment of cases is really as complete as the authors suggest.
    -...the records acquired as described seem to represent the same underreporting issues as those in the US. Is it really unlikely that the BPSU misses a significant number of cases?
  • -A second concern is the reporting of cases only up to age 15.
    -As mentioned by Dr Slater above, and in the Bock, Munoz-Furlong, and Sampson study110 , of 32 fatalities, 10 occurred in youngsters up to age 15. An additional 10 occurred in adolescents aged 16 to 19. Why did Macdougall et al. not include all adolescents?
  • -A third question must always be raised when fatal food anaphylaxis is studied: is it not possible that cases of fatal asthma were actually initiated by unidentified allergic reactions to food?
    -The trigger responsible for individual asthma fatalities is not always determined.
    -What about fatalities that never reach the emergency dept and are misclassified on death certificates as asthma fatalities?
  • -Fourth: the authors' definition of severity seems incomplete.
    -Individuals with severe food reactions...often not reported, or under-reported.
  • -Fifth: the issue of the safe administration of epinephrine.
    -We disagree about the risk to children of the administration of a single dose of epinephrine as opposed to withholding that dose...overdosage certainly may occur, but it seems more likely that an overdose would be administered by medically trained personnel rather than by parents. The over prescription of epinephrine is a debatable issue, however it seems a small price to pay, with a low risk, in order to save even one young life.
  • -Finally, we are very concerned that families will interpret this paper to mean that death from food allery is very unlikely, and therefore they may relax their vigilence.
    -If families of younger allergic children become less concerned when their children become adolescents, it may be too difficult to institute a good prevention education program. This is exactly the opposite of the goal of education programs in the US (The Food allergy and Anaphylaxis Network) and UK (Anaphylaxis Campaign)
     
4. From Warner JO in his editorial in the June 2002 Pediatric Allergy and Immunology, entitled How dangerous is food allergy in childhood? he says in part:
-"what are the problems with the MacDougal paper?
  • The system used by the Pediatric Surveillance Unit, usually used to study the epidemiology of uncommon childhood disorders, has never been employed to study common disease such as food allergy.
  • It is quite clear that pediatricians are only one of many different specialists who might be called on to see such patients.
  • They also employed scrutiny of notifications of deaths but deliberately excluded asthma deaths. In fact, it is very likely that a percentage of putative asthma deaths were due to anaphylaxis....Thus there could very well be a very considerable underestimate of the number of deaths.
  • The ascertainment through pediatricians deliberately also excluded children who received only one injection of epinephrine. The authors chose to deem 'severe' as implying the need for more than one injection. It is clear, however, that early use of epinephrine is the key factor in surviving anaphylactic reactions. The early use of a single dose may well prevent further progression to life-threatening problems....two-thirds of individuals resorting to auto-injector epinephrine do not subsequently present themselves at hospital but choose to continue their own management.Thus the representation of severe and life-threatening reactions may have been under-recorded by at least 66%.
The issue as to whether to prescribe auto-injector epinephrine to an individual who has had an acute reaction, particularly to peanut....is always difficult to address...it is not possible to predict future severity in relation to past experience....it would seem prudent to err on the side of caution and issue the injector. This should be coupled with very careful advice on avoidance and reassurance about the relatively low risk of life-threatening reaction, particularly in early childhood.

There is also the issue of ensuring that in childhood all precautions are in place so that by the time the patient reaches adolescence, where there clearly is an increasing risk of life-threatening reactions, the individual has full information and a long-standing cautious approach. Introducing the concept of caution only in adolescence could be doomed to failure." (posted Nov 22nd, 2002)165

 

Response of the authors: (in part)
 
  • As to the accuracy and validity of our data: Did our paper under-ascertain deaths? We used many sources and spoke to many experts in the field.
  • We specifically studied children up to 15 years of age because this is the group we were interested in...we wanted to bring a proper paediatric perspective.
  • We are not sure we agree that children, who have self-administered epinephrine, often do not go to hospital. However, we do not know the proportion and said as much, excluding this group from our definition of severity.
  •  Finally, we agree that education of professionals and the public should continue based on the best data available. This must include those parents whose children are truly at high risk as well as those many parents that think any immediate hypersensitivity reaction to food means their child is at high risk of an allergic death; when in reality the risk, in the absence of asthma, seems vey small. Different parents will come to different views about how to proceed faced by a severe but very small risk, just as we all do in many aspects of our lives. (posted Oct 28th, 2002)  
 
 
5. A.T Clark and P.W. Ewan responded to the McDougall et al article in Arch Dis Child 2003;88:79-81 in the Correspondance section and here are the highlights:
  • "McDougall et al... conclude that the risk of death is small and play down the importance of severe food reactions. The implication is that epinephrine (adrenaline) autoinjectors are overprescribed. This paper has serious consequences for the management of children with food allergy, so the methodological problems need to be explored to provide a balanced view. The data produced are likely to be misleading by underestimating both severe and fatal reactions.
  • ...the authors incorrectly assume that all such deaths will be correctly registered as allergy (or related terms). Anaphylactic reactions are often mislabelled as asthma deaths, because of a lack of antecedent history or information. This is clear from retrospective analysis of fatal reactions.
  • The paper focuses on the tip of the iceberg since their diagnostic threshold for inclusion was too high. The diagnostic criteria used are unvalidated, unreferenced, and irrelevant to clinical practice. To be included as a severe reaction, they required one or more of the following: cardiorespiratory arrest, inotropic support, > 20 ml/kg fluid bolus, more than one dose of epinephrine, and more than one dose of nebulized bronchodilator. This is ridiculous as the majority of reactions warranting treatment with epinephrine- that is, by accepted definition severe (UK Resuscitation Council) will be missed. Furthermore, a single dose of intramuscular epinephrine, if given promptly, is usually effective for the treatment of anaphylaxis - do the authors not consider anaphylaxis severe? They will therefore have missed....severe reactions without their diagnostic criteria, e.g. where epinephrine and/or nebulized bronchodilator was used once for severe dyspnea, reactions treated in the community, reactions treated in accident and emergency departments...
  •  They state that the incidence of severe food allergic reactions is 0.19 per 100,000 children per annum, and for near-fatal (intubated) reactions, 0.02 per 100,000 children per annum. The fact that 1 in 8 were intubated suggests that their criteria for severe reactions were inappropriate. That these figures are an underestimate is shown by compaison with other data...Sheik and Alvers study: almost four-fold more,...ALSPAC data: 38-fold more...our East Anglia incidence of severe nut allergy: 62-fold more than the McDougall et al study.
  • Assessment of severity: Severity varies from trivial (facial urticaria) to life threatening. We have proposed a method of assessing severity in peanut and nut allergy which could be applied to food allergy. Reactions were graded 1-5. It is important also to consider the amount of allergen causing the reaction as this is one of the factors determining severiy. Thus, a patient with a mild or moderate reaction to trace exposure such as inhalation or contact with a food containing nuts, might have a severe reaction on ingesting a small amount of nut. This grading system emphasises the importance of respiratory symptoms which are known to be the main severe feature of food allergy. Applying this to an unselected series of 539 patients with nut allergy, half the patients have mild, predominantly cutaneous reactions (grade 1-3), 35% have mild airway involvement (grade 4), and 13% have severe (grade 5) reactions.
  • Who needs Epipen? This is the most difficult issue and there is debate. Many of those claiming Epipen is overprescribed fail to understand that Epipen should be seen as part of a complete management package. We do not claim to know the answer, and this will require extensive data on natural history and may differ in different allergies....We have devised a system in food allergy to decide whether Epipen is required and have used this over several years; those with grade 4-5 reactions receive Epipen and those with only grade 1-3 reactions do not, but receive oral antihistamines. There are variations: 1) if the patient has ongoing asthma of other cause, Epipen is prescribed. 2) If a trace exposure had caused a grade 1-3 reaction, Epipen is prescribed. Epinephrine by intramuscular injection is very safe and there are no reports of deaths in children related to Epipen. The prescription of Epipen should highlight a child at risk. Widespread provision of Epipen to all food allergic children means those at risk are less easily identified and care diluted.
  • Conclusions:
    • The McDougall et al paper has identified only the extreme end of the severe spectrum of food allergic reactions and this should not be used as the only end point to inform management.
    • The inferences drawn are of little relevance to clinical practice and are not helpful in deciding which children require an epinephrine autoinjector.
    • While we would agreee that there are not likely to be many deaths as a result of food allergy in the under 15 age group, these data should not be used to minimise the problem or reduce appropriate care.
    • There is evidence that an integrated management plan can significantly reduce further reactions in number and severity. Management requires accurate diagnosis and assessment of severity...It should be emphasised that each child is different and may require different medication...Provision for epinephrine autoinjectors is only one part of this and should not be viewed in isolation. Control of asthma and other allergies is important and retraining essential. " 168 (posted Jan 31st, 2003)
 
 
-Mcdougall, Colver, et al. have more stats in their June 2005 Acta Pediatr article, Severe food-allergic reactions in children across the UK and Ireland, 1998-2000. Taken from the abstract of the article: ...Whilst food allergy may be becoming more common, fatal reactions to food in childhood are very rare and their rate is not changing. A Prospective survey, 1998 to 2000, of hospital admissions for food-allergic reactions-conducted primarily through the British Paediatric Surveillance Unit, covering the 13 million children in the UK and Ireland.
Results:
  • 229 cases reported by 176 physicians in 133 departments, yielding a rate of 0.89 hospital admissions per 100 000 children per year. Sixty-five per cent were male,
  • 41% were under 4 years.
  • Main allergens were peanut (21%), tree nuts (16%), cow's milk (10%) and egg (7%).
  • Main symptoms were facial swelling (76%), urticaria (69%), respiratory (66%), shock (13%), gastro-intestinal (4%).
  • Fifty-eight cases were severe. Three were fatal, six near fatal, and 8 of these 9 had asthma with wheeze being the life-threatening symptom. Three near-fatal cases received excess intravenous epinephrine. None of the non-fatal reactions resulted in mental or physical impairment.
    • Seven of 171 non-severe and 6/58 severe cases might have had a worse outcome if epinephrine auto-injectors had been unavailable.
    • Six of the severe cases might have benefited if auto-injectors had been more widely prescribed.
Conclusion: In the United Kingdom and Ireland, the incidence of severe reactions is low. The study highlights that: asthma is a strongly significant risk factor for a severe reaction and therefore warrants optimal management; severe wheeze is a prominent feature of severe reactions and warrants optimal management; intravenous epinephrine should be used with great care if needed. Epinephrine auto-injectors do not always prevent death, but our study design and data do not allow a definite statement about whether overall they are beneficial.252 (posted Oct 3d, 2005)
 
 
See additional stats in the anaphylaxis section, posted Nov 13th, 2002

 

 
 
 
 
 
 
-In Allergy Clin Immunol Int - J World Allergy Org.15/5 (2003), Ebisawa, et al. have a publication entitled Food Allergy in Japan. The authors state, "We do not have any population-based prevalence figures for food allergy in Japan....After WWII, a major change occurred in the dietary habits of Japanese people with the introduction of western food....possibly being the reason for an increase in food allergy in Japan. The most common food allergen among Japanese children is hen's egg, followed by cow's milk and wheat. These three major food allergens account for about 60% of pediatric food allergy. A few new items with increasing frequency of allergic reactions among children are peanuts, sesame, and fruit. (posted Jan 26, 2004)
 
 

Personal statistics coverning the period between Sept. 1992 and Dec. 2001

 

-From Sept 1992, Dr Zave Chad, allergist-colleague and good friend, at the time also in the Allergy Section of Ste-Justine Hospital, and I decided to use a laptop computer during consultations, rather than writing long hand in the patient's chart (most often not legible). An easily legible printed hard copy was later put in the patient's chart. All patients seen at the allergy clinic at Ste Justine, as well as those seen at the office since Sept. 1992 are in a database that after almost 10 years is quite impressive. The beauty of the program used (FilemakerPro) is that it is very simple to obtain statistics of all sorts about all these patients, age, date of consultation, history, allergy tests, diagnosis, treatment, etc. Here is the first phase of the analysis:

 Incidence of peanut allergy:

 total of all patients seen in consultation: 19,020
children (< 12 years ): 7,164
adults (12 years & older): 11,856
 number of peanut-allergic patients:
 adults: 126 or 1.06%
 children: 582 or 8.12% (posted Mar. 22nd, 2002)
NB. These figures do not necessarily reflect an increase in peanut allergy, but an increase in the number of referrals for peanut allergy.
 
See: Retrospective Study (preliminary results) Powerpoint presentation (posted April 5th, 2002)
 
 

Sensitization to peanuts

 -possible during pregnancy, probable during breast feeding:
 
Dr Vadas continues, "However, the story is not quite so simple. The concentration of peanut protein, timing of exposure and frequency of exposure may lead to either allergic sensitization or to tolerization. The latter process actually protects against allergies. In some cases, exposure to peanut protein in breast milk may actually protect against later development of peanut allergy. At this stage, it would be overly simplistic to suggest that all lactating women avoid peanut products during breastfeeding. While this may protect some children from peanut sensitization, it may predispose other children to acquiring peanut allergy by preventing the process of tolerization. Instead, it may be more prudent for lactating mothers to avoid peanut products while breastfeeding hight risk infants, namely those who have a strong family history of allergies or those who already have a first degree relative with peanut allergy. (posted July 26th, 2000)
 

Other possible sources of sensitization:

  "Intrauterine and early life dietary and environmental determinants of allergy"
This is the title of an excellent conference that was presented by Dr Christine McCusker at the Seventh Bram Rose Eastern Conference held in Hull June 6-8th, 2003. Here are some of her findings regarding food allergy, and particularly peanut allergy:
-A very intersting item appeared in the Montreal Gazette on Oct. 10, 2005 entitled Forget cereal - feed baby enchiladas! written by J. M. Hirsch, AP. Some highlights from the article:
-A very interesting article appeared on the front page of the March 20th, 2006 'USA Today' giving more insight into the 'hygiene theory' alluded to a couple times elsewhere in this review: To head off allergies, expose your kids to pets and dirt early. Really.
(pdf version of article) See the pdf article"Asthmatic kids under a cloud." (posted March 20th, 2006)
 
 
 Diagnosis of food allergies

-The double-blind, placebo-controlled food challenge (DBPCFC) is the 'gold standard' for diagnosis of food hypersensitivity. Skin prick tests and RASTs [allergy tests done on blood sample of patient] are sensitive indicators of food-specific IgE antibodies but poor predictors of clinical reactivity. In other words, challenges are the only sure way of appropriately diagnosing food allergies, especially in cases of suspected food allergy 8.

-the evaluation of adverse reactions to foods depends on a careful clinical history, diagnostic studies including appropriate skin testing or in vitro testing with food extracts (1997). . . 11

Comment:

Dr. Rhoda Sheryl Kagan: Stating that positive skin prick tests are "poor predictors of clinical reactivity" in the words of the authors, one should not forget that negative tests may also be poor predictors of sensitivity. (Oct. 1998)

-The skin prick test is the most widely used test for detecting food hypersensitivity. . . using fresh foods may be more effective for detecting the sensitivity to food allergens. Fresh foods should be used for primary testing for egg, peanut, and cow's milk sensitivity, according to some authors 9,28.

Comment:

Dr. H. Blumer: (and I agree, based on personal experience) Allergy to eggs, cow's milk and peanut, will be detected by available allergy extracts, and fresh foods are not usually necessary. In cases of suspected allergy to these foods, fresh foods could be used if the tests are negative using the regular extracts. (Oct. 1998)
-Food extracts for diagnostic purposes often lack sufficient activity and consistency...divergent allergenic activities are found at times...heating of some foods remarkably reduce the activity...variations in extracting conditions...and storage stability..41.
 
-Eigenmann and Sampson evaluated a more sophisticated method of interpreting skin tests while the results of double-blind, placebo-controlled challenges were considered the 'gold-standard' for diagnosis, and found that skin prick tests are a useful procedure for evaluating clinical reactivity to egg, milk, peanut and wheat....and the usual grading method of a positive skin test recorded as a wheal diameter 3 mm greater than the negative control remains just as good a predictive value 43. (posted Feb 2, 1999)
 
-Armstrong and Rylance, in the Feb. 1999 Archives of Diseases of Children, report their findings in their study entitled "Defininte diagnosis of nut allergy." Out of 96 children referred over a 27 month period (1994-1996) for nut allergies presenting with urticaria, facial swelling, anaphylactic shock, vomiting... 16 children from a sample of 51 who were tested for nut allergy had no reaction to an oral challenge. Positive IgE against peanuts was found in 9 of these 16 children. Their conclusions were: skin prick testing and IgE measured by RAST tests are inadequate tests for nut allergy. ---the definitive diagnosis test for nut allergy in the hospital setting is direct oral challenge 69 (posted May 25th, 1999)
 
 
-Bock, at Allergy Update 1999 in Toronto, stressed that skin tests detect specific antibody. Hypersensitiviy is demonstrated by double-blind placebo-controlled food challenges. Unfortunately, reliance on positive food skin tests is much lower than on the negative skin tests in regard to predictive accuracy or value. (posted July 11th, 1999)
 

-Regarding "a careful clinical history", two observations:

-refusal or dislike of a food right from its first introduction in the child's diet could be a sign of allergy to that particular food.

-the food that may contain the allergen, either hidden or non-identified, is usually immediately spat out or vomitted if any amount was swallowed, as if by a "defense mechanism" in the allergic child. Nevertheless, in the severely allergic child, even if the food was not swallowed, a certain degree of absorption has taken place, and a reaction may occur (not in all cases): vomiting, angioedema (swelling of throat, tongue, or lips), itchiness, or hives, fortunately of short duration because of this characteristic.

-We occasionally see children in our practice that have always disliked and refused peanut butter or foods containing peanut, but had never had any allergic reaction; skin tests, however, to peanut are sometimes very positive. (personal comment, posted Jan 13th, 2000)

 

 
 
 
  Predictive value of skin tests (to peanuts or other foods):
 
in children who have never previously eaten peanuts:

-Skin-prick testing and peanut-specific IgE (immunoglobulin E) antibody levels done by the RAST [radio-allergo-sorbent test] blood test) do not predict clinical severity (1997) 2. (skin tests and blood tests identifying peanut-specific antibody are not good predictors of the intensity of the allergy)

-Zimmerman and coll. reported in 1989 a positive RAST test to peanut in 64 % of children who gave no history of having eaten peanuts 37.

-At the annual meeting of the AAAA&I held Mar 3-8th, 2000 in San Diego, Hayami and Kagan presented a retrospective study to assess the use of prick skin tests (PST) as a diagnostic tool for peanut allergy in children who have never knowingly ingested peanuts, also specificity, sensitivity, and positive and negative predictive values of PSTs to peanuts in children who have undergone a blinded, placebo controlled challenge. PSTs were considered positive if the wheal was 3mm > negative control. All subjects had a positive skin test to peanut despite no prior history of peanut ingestion, and all have practiced strict avoidance of peanuts. The testing was done because of family history of peanut allergy, parental request, atopic dermatitis, or as part of other allergy tests. Food challenges were offered to patients to determine if the PST was indicative of true allergy. The mean age of children undergoing food challenge was 5.5 yrs. Of the 20 subjects, 6 had positive challenges. The mean wheal diameter of children with negative challenges was 7.57 mm (range 3-15mm). The mean wheal diameter of children with positive challenges was 10.66 mm (range 7-14mm). The positive predictive value of a peanut skin test > 3mm was 33.3%. The positive predictive value increased to 46.1% when only skin tests > 6mm were considered. All of the subjects with a positive challenge had wheals > 6mm. There was a trend to larger mean wheal diameters in children with positive challenges. No correlation was found between the presence of asthma, atopic dermatitis, or other food allergy. The poor predictive value of the PST in children without a clinical history of peanut allergy reaffirms the need to conduct oral challenges prior to the designation of peanut allergy. There is a suggestion that PST < 6mm may predict negative challenges.(posted Mar 9th, 2000)

 -"Interstingly, the detection of food-specific IgE antibody is not sufficient to diagnose clinical reactivity to a food; that is, an individual may have no clinical reaction upon ingestion of a food to which there is a positive allergy skin test or radioallergosorbent test (RAST)." 101 (posted Dec 10th, 2000)

- In the Jan 2001 Clin Exp Allergy, Pucar, Kagan, Lim and Clarke authored Peanut challenge: a retrospective study of 140 patients. The authors state that accurate diagnosis of peanut allergy is essential given that it is a lifelong and possibly fatal food allergy, and that diagnosis relies on patient history, prick skin test (PST), and in many situations, food challenge. The aims of their study were: a) to assess the safety of food challenges, b) to estimate the sensitiviy, specificity, and the positive and negative predictive values of PST to peanut performed in those who underwent a peanut challenge. On the 140 peanut challenges performed on 140 patients:
Given the poor positive predictive value and the specifity of the PST, a peanut challenge is usually required to diagnose peanut allergy with certainty when the PST is positive. When the history is strongly suggestive and the PST is borderline positive, i.e. 3 or 4 mm, peanut challenge is generally necessary to confirm the diagnosis.
 
Given the excellent negative predictive value and sensitivity of PST, a blinded peanut challenge is unnecessary in the context of a negative PST except for patients with a history strongly suggestive of immediate hypersensitivity. These patients should be individually assessed for the need to undergo a blinded challenge.111 (posted Feb. 13th, 2001)
 
A further study by Kagan R et al, published in the Ann Allergy Asthma Immunol. in June 2003, entitled "The predictive value of a positive prick skin test to peanut in atopic, peanut-naive children". 47 children, between 1994 and 2001 were identified who had a positive peanut prick skin test (PST), no previous peanut ingestion, and had undergone a peanut challenge.

Results:

  • 49% of the challenges were positive.
  • at a PST cutoff of > or = 5mm, the sensitivity and positive predictive value was 100% whereas
  • the specificity and positive predictive value was between 12.5% and 52.3% in children with a PST less than 5mm.
  • there was a trend to increased atopic features in the positive challenge group
  • those with a negative challenge had a lower PST wheal diameter.
  • the mean range peanut-specific IgE value of nine subjects in the negative challenge group was 0.63kU/L compared with 13.1kU/L for the five subjects in the positive challenge group.
Conclusions of the authors: We show that 49% of atopic, peanut-naive children sensitized to peanut developed allergic symptoms during oral provocation with peanut. Although the sensitivity of the PST at > or = 5mm for the detection of peanut allergy in this study was 100%, our small sample size limits the applicability of this value. Further investigation is needed to determine whether children with wheal diameters of 3 or 4 mm, perhaps coupled with low peanut-specific IgE, could undergo less resource-intensive, accelerated challenges. .186 (posted Aug 4th, 2003)
Personal comment: It is a known fact that if skin prick tests are done in the general population at random, approx. 40% will show positive skin tests, half of them not clinically significant seeing that approx. 20% of people are allergic. Secondly, the size of the SPT is to be taken into consideration, along with a peanut-specific IgE which would predictably be elevated.
Question: Because more than 70% of initial allergic reactions to peanut in children occur following first contact with the food, should all allergic (atopic) children be tested to peanuts if this food is not yet part of their diet, either because of a family history of peanut allergy, or being allergic and considered at risk, the introduction of highly allergenic foods such as peanut was recommended only at a age 4 or 5? Close to 50% of initial allergic reactions to peanut could be prevented! (posted Aug 4th, 2003)

 The authors state in the discussion of the paper, "Because a PST is generally used to confirm suspected food allergy following symptoms consistent with an IgE-mediated allergic reaction, and because sensitization in the absence of clinical symptoms is not clinically relevant, performing a PST before known ingeston of a food is not generally recommended. However, peanut allergy appears to differ, as most allergic children react on their first known ingestion. Additionally, because peanut allergy has been associated with a sgnificant risk of anaphylaxis, identifying the "at-risk" children would be useful before the first "field" reaction."105 ..."Furthermore, although the majority of children under the age of 5 years react to their first exposure to peanut, some children may only develop peanut allergy upon subsequent exposure. It is possible, therefore, that sensitization occurred during the challenge, suggesting a negative challenge may not preclude peanut allergy with certainty. Incomplete data are available on the follow-up of these patients, and many families have chosen to introduce only precautionary-labeled peanut products, while continuing to avoid overtly peanut-containg foods." (posted Aug 22nd, 2003)

 
 
-In the March 2001 J Allergy and Clnin Immunol, Drs Zimmerman and Urch wrote a letter to the editor entitled Peanut Allergy: Children who lose the positive skin test response in which they report on a study undertaken on 96 children who had shown a positive skin test to peanut, regardless of whether they had had a clinical reaction to peanut, who were seen one year later and characterized. Of the 96 patients, 66 had a history of clinical reaction to peanut, including one or more of hives, erythema, angioedema, vomiting, and respiratory symptoms; the rest were found to have positive skin test reactions without ever knowingly having had peanut. At visit 2, 10 patients had lost the positive skin test response (8 of whom had a prior history of clinical reaction to peanut), had negative responses to RAST testing, had fewer positive tests to other allergens, and successfully underwent oral challenge without reacting. The data confirm that some children lose the positive skin test response to peanut and are less atopic than those who retain the positive response. Although they represent only 10% of the patients who had positive peanut skin results at visit one, it is important to identify them and perform the oral challenge because peanut can be re-introduced into their diet.114 (posted April 14th, 2001)

 

-In the Jan 2001 Curr Allergy Rep, (posted in Medline only in April, 2002 for some reason)Williams has an article entitled Skin testing and food challenges for the evaluation of food allergy in which he states "skin prick tests for the common food allergens are excellent tools for identifying those at very low risk of reaction on eating the food, but are of variable value in identifying patients who will be positive on challenge...Skin tests to less common food allergens, especially fruits, are less well characterized and may require use of the food item itself as the source of allergen rather than a commercially prepared extract. For a few foods, the CAP system fluorescent enzyme immunoassay (Pharmacia, Peapack, NJ) recently has been shown to have good ability to identify patients at very high probability of reaction on oral challenge." see Sampson's reference, below. (posted April 29th, 2002)152

 See also predictive value of RAST tests (IgE titers) below.
-Rance, Abbal and Lauwers-Cances published Improved screening for peanut allergy by the combined use of skin prick tests and specific IgE assays, in the June 2002 J Allergy Clin Immunol. The aim of the study was to develop a new strategy for diagnosing peanut allergy while reducing the need for DBPCFCs (double-blind, placebo-controlled food challenges). They studied 363 children referred for evaluation of suspected food hypersensitivity. Performance characteristics of skin tests (using commercial and fresh food preparations) and of the IgE assay were assessed compared with the challenges.
Results:-according to the challenges: 177 children were allergic to peanut, and 186 were not.
-the performance characteristics of the skin tests were superior using raw extracts because the negative predictive value was 100% (if the wheal diamater was less than 3mm, they could be quite certain the child was not allergic). On the other hand, if the wheal diamater was larger than 3mm, the predicive value was only 74%. If the skin test wheal was 16mm or larger in diameter, the predictive value was 100% that the child was allergic.

-specific IgE concentrations of 57 kU(A)L or greater were associated with a positive predictive value of 100%.

Conclusion: Peanut DBPCFCs can be avoided when skin tests done with raw extracts resulted in wheals of 3mm or less and a specific IgE concentration of less than 57 kU(A)L and also when wheal diameters were 16mm or more or specific IgE values 57 kU or greater. Otherwise DBPCFCs were indispensable for the unequivocal diagnosis of peanut allergy. 159 (posted July 6th, 2002)
 

-Hill DJ, Heine RG, Hosking CS in the Oct 2004 Pediatr Allergy Immunol. published The diagnostic value of skin prick testing in children with food allergy. The authors state, "we developed diagnostic cut-off levels for SPT (skin prick tests) in children with allergy to cow milk, egg and peanut. Based on 555 open food challenges in 467 children (median age 3.0 yrs) we defined food-specific SPT wheal diameters that were '100% diagnostic' for allergy to cow's milk (>/=8 mm), egg (>/=7 mm) and peanut (>/=8 mm). In children <2 yr of age, the corresponding wheal diameters were >/=6 mm, >/=5 mm and >/=4 mm, respectively. These SPT cut-off levels were prospectively validated in 90 consecutive children </=2 yrs with challenge-proven food allergy. In young infants under 6 months of age who have not previously been exposed to a particular food item, the SPT were often negative or below the diagnostic cut-off but reached the diagnostic cut-off at the time of challenge in the second year of life....When applying published 95%-positive predictive CAP values, the diagnostic accuracy of SPT and IgE antibody levels was similar for cow's milk, but SPT was more sensitive in diagnosing allergy to egg (p < 0.0001) and peanut (p < 0.0001)."235 (posted Oct. 18th, 2004)

 
-Dr Jay M. Portnoy, co-chairman of a panel on 'practice parameters of food allergies', published in the March 2006 Annals of Allergy, Asthma and Immunology said to WebMD, 'I see patients all the time who go to a doctor, skin-test positive to lots of different foods, and are advised to avoid all of these foods. It makes their life miserable. And it turns out that they're not truly allergic to all these foods after all." See pdf version of the WebMd article. See also Food Allergy Guidelines in the section 'Dealing with peanut allergy, (posted March 31st, 2006)

-In Pediatr Allergy Immunol. 2007 May;18(3):224-3, Nolan et al published 'Skin prick testing predicts peanut challenge outcome in previously allergic or sensitized children with low serum peanut-specific IgE antibody concentration'. Children allergic to peanut and having a serum IgE titer of <10 k UA/L and had a positive skin test = or > 7mm had a 97% chance of having a positive challenge. (posted May 26th, 2007) 270

 

 
 
Recent studies on the predictive value of IgE titers
 
-In the May, 2001 J Allergy Clin Immunol, Dr Hugh Sampson, published a study entitled Utility of food-specific IgE concentrations in predicting symptomatic food allergy. Using the Pharmacia CAP System FEIA to quantify food-specific IgE antibody concentrations of the sera of 100 consecutive children and adolescents referred for evaluation of food allergy, he found the test useful for diagnosing symptomatic allergy to egg, milk, peanut and fish, and could eliminate the need to perform double-blind, placebo-controlled food challenges in a significant number of children.121 (posted June 12th, 2001)
 
-Somewhat similar to the above article, Hill et al report in the Nov 2000 Clin Exp Allergy 31(7); 1031-1035 on their experience comparing their "100% diagnostic skin positive test levels", (where an 8mm diametre skin test reaction or more was 100% predictive of a positive food challenge)124 to two IgE blood determinations (EAST or enzyme allergo-sorbent test, and CAP test). In their findings, they found that the predictability of their "100% diagnostic skin positive test levels" was superior to the IgE tests.125 (posted July 13th, 2001)
 
-Van Odijk and collaborators in their article entitled"Specific IgE antibodies to peanut in western Sweden- has the occurrence of peanut allergy increased without an increase in consumption?" that appeared in the June 2001 Allergy, found the following when they looked at all IgE specific tests for peanut during a 5-year period (2417 tests) and the connection with age, sex, symptoms and other atopic manifestations:
  • there was an increased prevalence of detectable IgE antibodies
  • more than 80 individuals under 2 years of age were sensitized to peanut
  • individuals with detectable IgE antibodies reported a shorter reaction time after eating peanuts than indiviudals with normal IgE antibody levels
  • patients with normal or low IgE antibody levels were not always free of symptoms even though their risk of allergic symptoms was reduced.127 (posted July 31st, 2001)
-See also :
 
 
Immuno CAP test specific IgE blood test.
 
UniCap InvitroSight  version 3.1 (posted Oct 6th, 2003)

 

 
 
 
-In the Oct 2002 Current Paediatrics, A. Ives and J. O'B. Hourihane have an excellent article entitiled Evidence-based diagnosis of food allergy. The summary reads as follows:
"There is an increasing body of robust, evidence-based practice allowing refinement of current diagnostic approaches outside the setting of research-oriented practice. The diagnosis of IgE-associated food allergy is a synthesis of history, examination, serum-specific IgE, skin tests and food challenge/elimination diets. Food challenges remain the gold standard for diagnosis, but these can be avoided in those with a good histroy and positive skin tests or positive specific IgE, especially if these levels are above the 95% positive predictive value (PPV). Negative tests are very important in ruling out possible triggers, due to the excellent negative predictive value (NPV) of both specific IgE and skin-prick tests."
-The history is an essential part of any diagnosis....is the problem allergic or one of the many possible differential diagnoses? Sometimes multiple foods are implicated, but it is very unusual for anyone to have IgE-associated reactions to more than three foods. The history can be notoriously inaccurate, care should be taken in its interpretation....False association between food allergy and chronic problems, e.g. chronic fatigue syndrome, or rhumatoid arthritis, in which no good evidence exists to support their association with food allergy.

-Particular attention in the examination needs to be paid to the skin, respiratory tract and gastro-intestinal tract (rashes, ENT problems, and chest abnormalities)...atopic dermatitis, asthma and rhino-conjunctivitis need to be looked for...Examination is crucial before a food challenge as subtle changes of appearance...may be important early signs of reactivity after allergen exposure.

-Skin prick testing is one of the main investigations used in allergy diagnosis.... it is the in-vivo counterpart of serum-specific IgE... measuring the presence of allergen-specific IgE in the skin....very safe. Is is also important to note that the degree of skin reactivity does not correlate with the severity of the clinical reaction on ingestion of the food. It has a negative predictive accuracy of approaching 100%, meaning that if the skin prick test is negative then it is very unlikely that the patient will react if the food in question is ingested. A food challenge is therefore not always required as it is likely to be negative. Unfortunately, the positive predictive accuracy of the test is only in the range of 50-60%, meaning that a positive reaction will only predict a positive food challenge in 50-60% of patients. The remainder are sensitized but do not react clinically and can therefore usually tolerate the food in question. High-quality extracts should be used, a good test technique and accurate measurement of the results. In some cases, tests should be done with fresh foods.
-Serum-specific IgE levels, like skin tests, have a similar predictive value- a negative specific IgE has an excellent negative predictive value for excluding IgE-mediated food reactions, but a positive specific IgE does not imply that clinical reactivity will occur. Studies have shown that it is possible to quantify levels of specific IgE above which the positive predictive value is over 95% as long as results are expressed as absolute levels of IgE, not RAST scores (see references above).

-Food challenges are performed to clarify which substances are causing an allergic reaction, to identify which foods may no longer cause a reaction, to assess non IgE-mediated reactions, to refute a history of supposed allergy, to assess cases where the skin tests or IgE are positive but there is no history of ingestion, or a poor history, and to assess reactions to other components of the diet, e.g. additives, colorings, etc.

-Elimination diets can be performed with the help of a dietician...they help diagnosis also in non IgE mediated reactions...should be followed by a food challenge.

-Beware of controversial diagnostic procedures, unproven, that are being made available to the general public, such as applied kinesiology, cytotoxic testing, tests involving other immunoglobulins, electrodermal (Vega) testing, etc166. (posted Dec 13th, 2002)

 
 -In the April 2003 Allerg Immunol (Paris) Moneret-Vautrin, Kanny and Fremont have an aricle entitled Laboratory tests for diagnosis of food allergy: advantages, disadvantages and future perspectives. ..."Prick tests are closer to clinical symptoms than biological tests. However, the diagnosis of food allergy is based on standardized oral challenges. Exceptions are high levels of specific IgEs to egg (> 6kUl/l), peanut (>15kUl/l), fish (>20 kUl/l) and milk (>32kUl/l), reaching a 95% predictive positive value...Research developments will have impact on the development of new diagnostic tools: allergen mixes reinforcing a food extract by associated recombinant major allergens, multiple combination of recombinant allergens (chips) or tests with synthetic epitopes aimed at the prediction of recovery. 176 (posted June 25th, 2003)
 
 
 -In a similar study by Clark AT and Ewan PW. Interpretation of tests for nut allergy in one thousand patients, in relation to allergy or tolerance, published in the Aug 2003 Clin Exp Allergy. The authors state in their abstract: "In the US, 7.8% are sensitized (have nut-specific IgE), but not all those sensitized are allergic. "(NB. In the UK, nuts include peanuts) "Lack of data makes interpretation of tests for nut-specific IgE difficult. This is the first study to investigate the clinical significance of test results for peanut and tree nut allergy in allergic or tolerant patients. Findings are related to the severity of the allergy. An observational study of 1000 children and adults allergic to at least one nut was done. History of reactions (severity graded) or tolerance to up to five nuts was obtained and skin prick test (SPT) and seum-specific IgE (CAP) performed.
RESULTS:
  • There was no correlation between SPT size and graded severity of worst reaction for all nuts combined or for peanut, hazelnut, almond and walnut.
  • For CAP, there was no correlation for all nuts.
  • Where patients tolerated a nut, 43% had a positive SPT of 3-7mm and 3% >/= 8mm. For CAP, 35% were positive (0.35-14.99kU/L) and 5% >/=15 kU/l.
  • In SPT range 3-7mm, 54% were allergic and 46% were tolerant.
  • There was poor concordance between SPT and CAP (66%).
  • Of patients with a clear nut-allergic history, only 0.5% had negative SPT, but 22% negative CAP.
CONCLUSIONS:
  • Magnitude of SPT or CAP does not predict clinical severity, with no difference between minor urticaria and anaphylaxis.
  • SPT is more reliable than CAP in confirming allergy.
  • 46% of those tolerant to a nut have positive tests >/= 3mm (sensitized but not allergic)
  • One cannot predict clinical reactivity from results in a wide 'grey area' of SPT 3-7mm; 22% of negative CAPs are falsely reassuring and 40% of positive CAPs are misleading. This emphasizes the importance of history. Understanding this is essential for accurate diagnosis.
  • Patients with SPT >/= 8mm and CAP >/= 15 kU/L were rarely tolerant so these levels are almost always (in >/= 95%) diagnostic. 192 (posted Aug 18th, 2003)
 
In the July 2004 J Allergy Clin Immunol , Perry et al published a study entitled The relationship of allergen-specific IgE levels and oral food challenge outcome. For the 173 peanut challenges, 59% passed, and the medians for those who passed or failed were 0.5 kUA/L and 1.9 kUA/L, respectively (P < .001).
-For patients with a clear history of a peanut reaction , the trend for increasing failure rate with increasing peanut-specific IgE level was statistically significant (P < .01), with 76% of patients passing the challenge with an IgE level of less than 0.35 kUA/L, 44% passing with a level between 0.36 and 2 kUA/L, 40% passing with a level between 2 and 4.9 kUA/L, and none passing with a level greater than 5 kUA/L.
-For those patients without a clear reaction history, 88% of patients passed with a negative peanut-specific IgE level of less than 0.35 kUA/L, 71% passed with a level of 0.36 to 2 kUA/L, 33% passed with a level of 2 to 4.9 kUA/L, and 77% passed with a level greater than 5 kUA/L.
Conclusions: For peanut, we recommend that patients with a clear history of reaction be challenged when the IgE level is less than 2 kUA/L, whereas a cutoff level of 5 kUA/L is recommended for those without a clear history of reaction. Cutoff levels for these 2 reaction groups most likely differ because many patients who were avoiding peanut solely on the basis of a positive test result might never have truly had peanut allergy. Allergen-specific IgE concentrations to peanut serve as useful predictors of challenge outcome and should be considered when selecting patients for oral challenge to these foods.228 (posted July 12th, 2004)
 
 
-L'allergie à l'arachide: une observation exemplaire202 (Allergy to peanuts: a perfect example) is the title of an article published in Revue Française d'Allergologie et d'Immunologie Clinique vol 43, numéro 8, 2003 by Scaramuzza et coll. According to the authors, "it enderlines the need to analyse the characteristics of this food allergy:
The oral challenge was open with increasing doses of peanut every 20 minutes. It was positive at the cumulative dose of 777 mg. Fifteen minutes following the provoking dose (1/2 a peanut) Eric became lethargic, had a fall in blood pressure, abdominal pain and generalized urticaria. He was treated with an injection of epinephrine, loratadine, and betamethasone orally. A second injection of epinephrine was administered one hour later because of recurrence of anaphylaxis, along with salbutamol for associated asthma. Eric was discharged five hours later with Anapen (epinephrine kit for self administration) and told to avoid nuts, peanuts and peanut oil.
Discussion:
-The prevalence of peanut allergy in France is 1%128
-It is the 2nd cause of food allergy in children under 3 years of age after egg, and the first cause after age three.

-Food allergy seems to be a condition occurring in developped countries, a notion attributed to the hygiene hypothesis and to different ways of processing peanuts, roasted or raw peanuts being more allergenic than fried or boiled. 120

-Sensitization at an earlier age to peanut has become more and more frequent in the last ten years..33, 13, 163 Incriminating factors being: peanut has become a staple food in a big way everywhere, in particular by pregnant and breast-feeding women,2, 115 and its introduction at a much earlier age in the diet of children, also use of body creams containing peanut oil or almond oil, and of topical medications containing peanut oil..33 Other risk factors: atopic personal and family history- siblings have a 7% chance of becoming allergic to peanut. The risk increases in homozygous twins up to 64%.

-Authors' conclusion: The diagnosis of peanut allergy is based on the history, allergy skin tests, specific IgE titres. It must be concluded with an oral challenge under strict hospital supervision in a patient having never reacted to or eaten peanut, with a positive skin test and peanut-specific IgE less than 14kU/l, as in the case of our young patient. A positive skin test (which has an excellent negative predictive value) could only indicate sensitization. An IgE titre of more than 14 kU/l has a predictive positive value of 95%, but if the IgE titre is less than 0.35kU/l its predicitve negative value is NOT 100%.121 (posted Dec 15th, 2003)

 
-Dr Ham Pong presented his clinical research findings on Peanut allergy at the XI International Food Allergy Symposium held at the American College of Allergy, Asthma & Immunology meeting in New Orleans in 2003. The research is summarized in the Allergy and Asthma News, issue 2, 2004 of the Allergy/Asthma Information Association:

 

-'Research has found that peanut allergy can resolve in up to 20% of children.
-Knowing which children will outgrow their peanut allergy and who should be given a peanut challenge is a constant trial for allergists...'
-Dr Pong chose to do a study to attempt to further delineate which children can be safely challenged.
-60 children , aged 4 to 13, were chosen on the following criteria:
-the peanut-specific IgE (p-IgE) was less or equal to 5ku/L
-history of immediate IgE type allergic reaction and a positive prick skin test (PST) to peanut OR a positive PST but the child had never ingested peanut
-the child has had no allergic reaction in the past two years.
-The majority of the challenges started as a single blind challenge for the first four doses and proceeded to open challenges when the dose of peanut equalled or exceeded one peanut.
-A negative challenge was indicated by tolerance of a cumulative dose of 21-28 peanuts over a three hour period, with a single final dose of 12 peanuts.
-A challenge was considered positive if there were objective signs suggestive of an IgE-mediated allergy e.g. urticaria (hives), angioedema (swelling), bronchospasm (wheezing), immediate vomiting, etc. Positive oral challenges occurred in 17 of the 60 children, or 28% of the cases. There was one equivocal challenge from the group.
-Negative oral challenges occurred in 42 of the 60 children, or 70% of the cases. In this group, 31 or 74% had a positive SPT. As a group, these children had lower SPTs and p-IgE than the positive challenges. On an individual basis, PSTs and/or p-IgE did not separate those with negative or positive challenges, or anaphylaxis except for a negative SPT that always resulted in a negative challenge.
-Of the 60 children, 28 had negative p-IgE. Six of these 28 had positive challenges. Therefore a negative p-IgE still resulted in a positive challenge in 21% of the children. While a negative p-IgE often implies that the peanut allergy may be gone, it is not always so.

-Of the 6 children with a negative p-IgE who had reactions on challenge, 3 resulted in mild anaphylaxis, easily reversed with treatment.

Final result of the study found that Unicap testing predicted a larger number of peanut allergy resolvers than prick skin testing. In general, PST size and p-IgE were lower in the negative challenge versus the positive challenge groups. However, on an individual basis, neither were predictive of negative challenges, or anaphylactic response during a positive challenge. The only exception was a negative PST which predicted a negative challenge, irrespective of the p-IgE....This study clearly confirms that 70% of children who have not had a reaction for over two years and who also meet the criteria for lowered p-IgE and based on prick skin testing may have outgrown their peanut allegy....follow-up of these apparent peanut resolvers is important to ensure they have truly outgrown their allergy. (posted July 26th, 2004)

 

 
 
 
 
-At the AAAA&I Annual Meeting in San Antonio, March 18-22, 2005, Te Pas, et al presented Predicting the resolution of peanut allergy in children using skin prick testing and RAST: A systematic review. Of the 567 articles reviewed....a negative skin prick test was slightly better than a negative RAST at predicting which children have outgrown their peanut allergy. However, they concluded, using these cutoffs, one misses approx. 40% of kids who have a positive test but would pass a peanut challenge. (posted April 22nd, 2005)

 

-At the same meeting (San Antonio, Texas, 2005), Borici-Mazi et al. presented Monitoring of peanut allergic patients with serum-specific. IgE. They looked at the optimum frequency of measuring the levels of the peanut-specific IgE. Based on their results looking at 118 patients, from 1997 till present, they concluded that "it is probably adequate to measure the levels every 3 to 5 years as part of screening for developing of tolerance to ingested peanut and predict the results of future peanut challenges." (posted April 24th, 2005)

 

- In the June, 2005 J Allergy Clin Immunol, Roberts G and Lack G published Diagnosing peanut allergy with skin prick and specific IgE testing. Objective: To determine the predictive value of a wheal >/= 8 mm or serum specific IgE >/= 15 kU A /L for clinical allergy and investigate whether results are generalizeable. Results: a skin prick result >/= 8 mm or a specific IgE >/= 15 kU A /L have a high predictive value for clinical allergy to peanut and that these cutoff figures appear generalizeable to different populations of children undergoing an assessment for peanut allergy.246 (posted June 12th, 2005)

 

In the July 2003 J Allergy Clin Immunol, Beyer et al had a publication (which should have been posted much earlier) entitled Measurement of peptide-specific IgE as an additional tool in identifying patients with clinical reactivity to peanuts. As the authors note in the abstract of the article,"Diagnostic decision levels of food-specific IgE antibody concentrations have been described" (as seen in the above postings). "However, many patients still need to undergo oral peanut challenges because their IgE levels are in the nondiagnostic level".The aim of their study was to determine whether differences exist in IgE-binding epitope recognition between sensitized children with and without symptomatic peanut allergy. Eight peptides representing the immunodominant sequential epitopes on Ara h 1, 2, and 3 were synthesized ... Individual patient labeling was performed with sera from 15 patients with symptomatic peanut allergy and 16 patients who were sensitized but tolerant. Ten of these 16 patients had "outgrown" their allergy.

 

RESULTS:
CONCLUSIONS: Determination of epitope recognition provides an additional tool to diagnose symptomatic peanut allergy, especially in children with peanut-specific IgE below diagnostic decision levels. (posted only March 14th, 2004)214 
 
-In the Oct. 2004 Pediatr Allergy Immunol. Odijk J. et al have an article entitled Specific immunoglobulin E antibodies to peanut over time in relation to peanut intake, symptoms and age. The authors found that..."Increased IgE antibody levels during follow-up was related to age...Exposure to peanut during the study did not seem to affect the result... During the follow-up period 34% increased their IgE antibody class...The subjects over 6 yrs of age showed a decrease in peanut-specific IgE class over a 5-yr period...our results suggest that follow-up and renewed testing is recommended, since there may be a change in IgE antibody classes and clinical sensitivity over time."234 (posted Oct. 18th, 2004)

-At the annual AAAA&I meeting held in San Diego, CA Feb. 23-27, 2007, Naimi et al. presented The Utility of Combining Skin Prick and specific IgE Antibody Testing as a Predictor of Clinical Reactivity to Milk, Egg and Peanut. For peanut, the specific IgE levels of <3kU/L and skin prick test wheal size of <5mm were associated with a 89% chance of passing an oral challenge to peanut. The authors conclude that by this combination they establish values for peanut with excellent predictive value but with higher cut-off values than has previously been reported. With these criteria, many children who are not truly allergic to peanut will be more likely to undergo a negative challenge, thereby preventing the unnecessary avoidance of the food (posted May 5th, 2007)

-Wainstein BK et al have an article entitled Combining skin prick, immediate skin application and specific-IgE testing in the diagnosis of peanut allergy in children in Pediatr Allergy Immunol. 2007 May;18(3):231-9. In their study, skin prick test specificity was 67% at >or=8 mm and 100% at >or=15 mm. The I-SAFT was 82% specific. A peanut specific-IgE level of 0.37 kU/l was 98% sensitive but 33% specific. A level of 10 kU/l was 100% specific. Combinations of a skin prick test of >or=8 mm with a positive I-SAFT (immediate skin application food test) and a peanut specific-IgE >or=0.37 kU/l were 88% specific with a sensitivity of 38%. Using challenge outcomes as the standard, available in vitro and in vivo diagnostic tests for peanut allergy have poor sensitivity and specificity and combining them does not significantly improve their clinical usefulness. Previously described diagnostic cut-off levels do not have general applicability. Allergy practitioners may need to interpret results of allergy tests in the context of their own practices. (posted May 27th, 2007)271


Previous studies have suggested various diagnostic cut-offs of allergy tests for the diagnosis of clinical peanut allergy in children. There are few data relating to the use of combinations of these tests in children. We aimed to determine the validity of previously reported diagnostic cut-off levels of peanut allergen skin tests and peanut specific-immunoglobulin (Ig) E, as well as the usefulness of combinations of these, for predicting clinical peanut allergy in our Allergy Clinic. Children attending the Allergy Clinic with a positive peanut skin prick test (SPT; n = 84) were included in the study. Immediate skin application food tests (I-SAFT) using 1 g of peanut butter (positive if any wheals were detected at 15 min), peanut specific-IgE levels and open-label peanut food challenges were performed. Fifty-two of 85 peanut challenges were positive.

 
 

Increase (?) in the frequency and severity of reactions to peanuts.

-The current increase in the prevalence of food allergies appears to have several causes including better screening, improved diagnosis and changes in both the techniques used by food manufacturers and eating habits (1997).1

-Experience over the past decade suggests that the ready availability and early introduction of highly allergenic foods (e.g. peanuts and nuts) into the diet will only increase the number of individuals suffering from hypersensitivity reactions to foods. 11

-Peanut and tree nut allergies are potentially life-threatening. . . and appear to be increasing in prevalence 13.

-Increase in frequency of peanut allergy and fatal cases have been reported 23.

Comment:

Dr. Rhoda Sheryl Kagan: The known prevalence of the frequency and severity of reactions to peanuts is 0.6%-1.0%. The medical literature suggests an increase, but no figures are given. Bock, in a talk given in Montreal last June (1998) said that the prevalence has not changed. (posted Oct. 1998)

-According to Emmett, Angus, Fry. et Lee, from Surrey, UK . . . Peanut allergy is reported by 1 in 200 of the population and is commoner in those reporting other allergies. The fact of similar rates in children and adults argues against a recent marked rise in prevalence.. . . . 73 (posted July 12th, 1999)

-Zeiger, in the Jan 2000 J Pediatr Gastroenterol Nutr writes. . ."food allergy has increased in prevalence during the past decade, and thus represents a major burden to our young. . . Identifying and developing effective strategies to prevent food and other allergic diseases represents a high priority for medicine at this time because of the unbridled increase in the prevalence and morbidity attributed to them." 90 (posted Jan 23d, 2000)

-The prevalence has increased substantially, one in two-hundred 4-year-olds32 ...related probably to the doubling and trebling of the prevalence of allergic asthma, rhinitis and eczema in certain, mainly "westernized," populations, according to Pamela W. Ewan33.

-Drs Gideon Lack, and Jean Golding, in a letter published in the British Medical Journal of Aug 1996, made the following comments about her article, " Pamela W. Ewan makes the important statement that the incidence of peanut and nut allergy is rising and that sensitisation seems to occur early in life. Regrettably, she does not provide any evidence to back her recommendation that "young allergic children should avoid peanuts and nuts to prevent the development of this allergy" and her extraordinary suggestion that avoidance should be practised until the age of 7. There is no evidence that avoiding foods during lactation or early childhood prevents allergic sensitisation to these foods. 96 (posted July 26th, 2000)

-As mentioned earlier in this article, Dr Hugh A. Sampson, in the editorial entitled, 'What should we be doing for children with peanut allergy?' published in the Dec 2000 Journal of Pediatrics begins with these words: "Most pediatric allergists agree that the prevalance of food allergies, and peanut allergy in particular, is increasing, although appropriate epidemiologic data to substantiate this belief are lacking. The reason for this apparent rise continues to elude us." 107 (posted Jan 6th, 2001)

-Rising prevalence of allergy to peanut in children: Data from 2 sequential cohorts is the title of a study published in the Nov 2002 J Allergy Clin Immunol, by Grundy et al. To determine whether allergy to peanut is on the increase, the authors looked at changes in 2 sequential cohorts in the same geographic area 6 years apart. Of 2878 children born between Sept 1994 and Aug. 1996, living on the Isle of Wight, 1273 completed questionnaires, 1246 had skin prick tests at the age of 3 and 4 years. Those with positive skin tests to peanut were subjected to oral challenges, unless there was a history of immediate systemic reaction. The data was compared with information on sensitization and clinical allergy to peanut available from a previous cohort born in 1989 in the same geographical area32.

Results: There was a two-fold increase in reported peanut allergy (0.5%[6/1218] to 1.0%[13/1273], but the difference was nonsignificant. Peanut sensitization increased 3-fold, with 41 (3.3%) of 1246 children sensitized in 1994 to 1996 compared with 11 (1.1%) of 981 sensitized 6 years ago. Of 41 sensitized children in the current study, 10 reported a convincing clinical reaction to peanut, and 8 had positive oral challenge results, giving an overall estimate of peanut allergy of 1.5% (18/1246). Conclusions: Sensitization to peanut had increased between 1989 and 1994 to 1996. There was a strong but statistically nonsignificant trend for increase in reported peanut alleregy.163
-At the EAACI (European Academy of Allergology and Clinical Immunology), Dr Arshad, co-author of the above study, presented their findings as reported in DG Dispatch by Jill Stein: Peanut Allergy May Decrease with Age . He stated that contrary to public opinion, peanut allergy does not necessarily start early in life and children who are sensitized to peanuts at an early age often lose this sensitivity in later childhood.' (posted June 20th, 2003)
 
 
Press Release, Dec 9th, 2003: Prevalence of Peanut and Tree Nut allergies on the rise:New research from the Journal of Allergy and Clinical Immunology

The above press release is a follow-up to the following two articles published in the Dec, 2003 Journal of Allergy and Clinical Immunology:

1. Prevalence of peanut and tree nut allery in the United States determined by means of a random digit dial telephone survey: A 5-year follow-up study by Sicherer, Munoz-Furlong and Sampson. .... in 2002 by sex and age and to compare the results with prevalence estimates obtained 5 years earlier.65 Out of 13,493 individuals involved, peanut allergy, tree nut alleregy, or both was self-reported in 166 individuals (1.2%). The overall prevalence rates were similar to those reported in 1997, also as far as severity, Applying conservative rules to adjust for persons with unconvincing reactions and a false-positive rate of the survey instrument, a final prevalence estimate of 1.04% was obtained...Although the rate of peanut allergy, tree nut allergy, or both was not significantly different from 1997 to 2002 among adults, the rate increased from 0.6% to 1.2% among children, primarily as a result of an increase in reported allergy to peanut (0.4% in 1997 [12 of 2998] to 0.8% [26 of 3127] in 2002).198
2. The second article is by Kagan, et al, entitled Prevalence of peanut allergy in primary-school children in Montral, Canada. The prevalence of peanut allergy was estimated by administering questionnaires re peanut allergy to children in kindergarten through grade 3 in randomly selected schools. The respondants were stratified as follows: (1) peanut tolerant, (2) never-rarely ingested peanut, (3) convincing history of peanut allergy, and (4) uncertain history of peanut allergy. Groups 2, 3, and 4 underwent peanut skin prick tests (SPTs), and if the responses were positive in groups 2 or 4, measurement of peanut-specific IgE were undertaken. Children in group 3 with a positiv SPT response were considered allergic to peanut without further testing. Children in groups 2 and 4 with peanut-specific IgE levels of less than 15kU/l underwent oral peanut challenges.
Results: Of the 7768 children surveyed, 4339 responded, 94.6% in group 1. The prevalence of peanut allergy was 1.50%. When multiple imputation was used to incorporate data on those responding to the questionnaire but withdrawing before testing, the estimated prevalence increased to 1.76%. When data re the peanut allergy status of nonresponders (as declared to the school before the study) were also incorporated, the estimated prevalence was 1.34%.199
 
Conclusion of the authors: Our prevalence study is the first in North America to corroborate history with confirmatory testing and the largest worldwide to incorporate these techniques. We have shown that, even with conservative assumptions, prevalence exceeds 1.0%

In the discussion of the paper, the authors state:

 

"Our study shows that the prevalence of peanut allergy is higher than what has previously been reported in the only other North american study65 (mentioned in the Sicherer et al study summarized above) and in three European surveys, one of which is Tariq et al reporting a 1.2% incidence of peanut allergy in children32, another is Emmett et al study that concludes that "Peanut allergy is reported by 1 in 200 of the population and is commoner in those reporting other allergies. The fact of similar rates in children and adults argues against a recent marked rise in prevalence.. . . 73, and the third being the Kanny et al 2001 paper where the authors conclude that the prevalence of food allergy is estimated at 3.24% in France, the study emphasizing the increasing risk of food allergy...128.

 
They further state: It is possible that our study suggests that the increasing peanut allergy prevalence reported on the Isle of Wight is also occurring in Norh America. The study they refer to is the Grundy et al, paper entitlled Rising prevalence of allergy to peanut in children: Data from 2 sequential cohorts published in the Nov 2002 J Allergy Clin Immunol. There was a two-fold increase in reported peanut allergy (0.5%[6/1218] to 1.0%[13/1273], but the difference was statistically nonsignificant. 163 (posted Dec 11th, 2003)

 

 
 
-Here's an answer to a question posted on the Net in June 2003. "Are peanut allergies for real?" It makes for a good read. Take a look. here are some hightlights.
 
-"Peanut allergies have been around forever, but peanut phobia blew up out of nowhere. Ninety-four percent of the journal articles I turned up by searching on "peanut" and "allergy" in an on-line medical database (165 out of 176) were published since January 1995. Now a week doesn't go by without some new sign that peanut butter is to the 21st century what fleas and rats were to the 14th."

 

 
-"Is the danger real or just hype? Probably both. The number of deaths in the U.S. due to food-related anaphylactic shock is small, at most 200 annually, 80 percent of which are due to peanuts or "tree nuts" (walnuts, pistachios, pecans, etc). One UK study estimates that the annual risk that a food-allergic child will die from a reaction is 1 in 800,000. Food allergies aren't as common as people think. Surveys have found that as many as 30 percent of respondents believe they have a food allergy of some kind; the actual prevalence is 4 to 8 percent for kids and 1 to 2 percent for adults. Still, that's a lot of people. An estimated 1.5 million Americans have peanut allergies, and emergency rooms treat about 30,000 cases of food-related anaphylactic shock each year. "

-"Are peanut allergies becoming more common? Many researchers think so, but the evidence isn't overwhelming." (posted Jan 23d, 2004)

 
 
-Grundy et al. presented a paper at the annual AAAA&I Meeting held in San Francisco, Mar 19-23, 2004 entitled Sensitization rates to food and aeroallergens amongst 1 year olds in UK &endash; a population based study. The authors state: "The reported prevalence of various manifestations of atopy appears to be increasing. Early sensitization to various allergens would be expected to parallel this rise. Many studies have described the rates of sensitization in high-risk populations but there is a paucity of large population based studies. We undertook a whole population cohort study, investigating the rates of sensitization to foods and aeroallergens in an unselected population at the age of 1 year. Conclusion Despite the rising prevalence of reported atopic manifestations, the rates of sensitization to food and aeroallergens remain low in an unselected population at the age of one year." 219 (posted April 26th, 2004)
 
-"The apparent increase in peanut allergy has occurred along with the apparent increase in allergic diseases in children. This opinion was expressed by Gideon Lack, MD, of the Imperial College, London, in The New England Journal of Medicine (2003; 348:977-985) article on peanut allergy in childhood. 171

-At the annual general meeting of the Canadian Society of Allergy and Clinical Immunology (CSACI) held in Montreal Oct. 26-29, 2006, Dr Scott Sicherer in his conference entitled 'Peanut Allergy: New Insights with Practical Implications for Diagnosis and Management' commented that the apparent increase in peanut allergy is not an isolated increase but a reflection of the increase in allergy in general, including food and respiratory allergies. (posted Oct 29, 2006)

-Here's an item that I just happened to hit on, that appeared in the Boston Globe Jan 30th, 2006: Peanut allergy epidemic may be overstated
By Dr. Darshak Sanghavi . In case the link is no longer accessible, here's a pdf version. (posted Oct 13th, 2007)

 
 
The impact of peanut allergy on children and adults
 
-At a poster session during the Annual Meeting of the AAAA&I, Feb 26-March 3, 1999 in Orlando, MN Primeau, RS Kagan, C. Dufresne, Y. St-Pierre, H. Lim, and A. Clarke presented their evaluation of the impairment in quality of life and family relations experienced by individuals with a confirmed diagnosis of peanut allergy (PA) based on history and skin test or RAST , compared with the impairment experienced by patients with a chronic musculoskeletal disease (MSD). Impairment of quality of life was assessed by the vertical visual analogue scale (VVAS) [anchored from 0 (no disruption of daily activities) to 100 (most disruption imaginable) and the Impact on Family Questionnaire [0 (no impact) to 24 (maximum impact)]. One hundred and thirty eight PA children with disease duration of 4 years were compared with 61 MSD children and 37 PA adults and 41 MSD adults. . . Peanut allergic children compared to MSD children with little physical disability have much more impairment in their quality of life and family relations. More importantly, even when compared with MSD children overall, the impairment of peanut-allergic children is greater, attesting to the substantial impact of peanut allergy.
 
-A second element of this aspect was to evaluate which factors were involved. Their conclusions were:
Younger age of the children, closeness to the first reaction, past history of anaphylactic reaction and presence of other atopic conditions were all associated with increased impairment of quality of life or family relations. Age at the first allergic reaction, severity of the first allergic reaction, presence of asthma and presence of other food allergies were not associated with the severity of impairment of quality of life and family relations. (posted March 13th, 1999)
 
Dr. Marie-Noël Primeau asked to make the following changes to the work cited above, i.e. that the patients in their control group of musculoskeletal disease did not have MSD. The adults ( >80%) had disseminated lupus erythematosus (LED or SLE) and the children, (>70%), juvenile rheumatoid arthritis.(posted March 24th, 1999)
 

This study has now been published in Clin Exp Allergy, in Aug. 2000: The psychological burden of peanut allergy as perceived by adults with peanut allergy and the parents of peanut-allergic children. The authors conclude: "Given the considerable disruption in daily activities and family relations reported by the parents of peanut-allergic children, accurate diagnosis of peanut allergy is essential. Our work should make health care professionals dealing with children with confirmed peanut allergy more aware of the support that these families may require. Furthermore, we hope to motivate the food industry to offer more 'peanut free' products to decrease the dietary restrictions of these patients while minimizing their potential for accidental ingestion. " 97 (posted Aug. 23d, 2000)

 
-The following comment was published in the Dec 2001 Ann Allergy Asthma Immunol by Sicherer et al: Parental perceptions of physical and psychological functioning were measured with the Children's Health Questionnaire. "Childhood food allergy has a significant impact on general health perception, on the parents, and limitation on family activities. Factors that influence reductions in theses scales include associated atopic disease and the number of foods being avoided."143 (posted Jan. 18th, 2002)

 

-"Assessment of quality of life in children with peanut allergy" is the title of an Oct. 2003 article in Pediatric Allergy and Immunology by Avery NJ et al. The authors measured the quality of life (QoL) of 20 children with peanut allergy (PA) and 20 children with insulin-dependent diabetus mellitus (IDDM) using two disease-specific QoL questionnaires. Cameras were given to the subjects to record how their QoL is affected over a 24 hr. period. Mean ages of subjects was 9.0 and 10.4 years for PA and IDDM. Results:
-Children with PA reported a poorer quality of life than children with IDDM.
-PA children reported more fear of an adverse event and more anxiety about eating, especially when eating away from home.
-Most photographs related to food and management issues and revealed difficulties for both groups regarding food restrictions.

-PA subjects felt more threatened by potential hazards within their environment, felt more restricted by their PA regarding physical activities, and worried more about being away from home. However, they felt safe when carrying epinephrine kits and were positive about eating at familiar restaurants.

 
The authors concluded: The quality of life in children with PA is more impaired than in children with IDDM. Their anxiety may be considered useful in some situations, promoting better adherence to allergen avoidance advice and rescue plans. 197.
 

-At the annual AAAA&I Meeting held in San Francisco Mar 19-23, 2004, Stone et al have a poster entitled Parental coping with childhood food allergies. Rationale Food allergies affect up to 8% of children. Childhood food allergy can create parental anxiety and alter family dynamics. A better understanding of the extent of this problem is important for developing improved educational and support methods for these families. Questionnaires were distributed to parents attending a private allergy office (n=135) or a food allergy support group (n=155). In addition to demographic data, the questionnaires contained 20 questions relating to parental coping. Three open-ended questions were also asked regarding strengths and weaknesses of attending lectures on food allergies. Results:

Conclusions: While most parents in this survey think about their children's food allergies frequently, most actively seek information on food allergies and appear to be reassured by this information. Availability of educational material and support groups is an important aspect of improving the care of children with food allergy. 212 (posted Feb.16th, 2004)
 

 

-ANTONIA C. LYONS & EMER M. E.FORDE, from Massey University, New Zealand and Aston University, UK, in July 2004 published Food Allergy in Young Adults: Perceptions and Psychological Effects in the Journal of Health Psychology.
The study examined the differences in awareness and perceptions of food allergy and anxiety between young people with and without a food allergy. Participants completed a questionnaire which asked about their perceptions and knowledge of allergies, perceived health competence and anxiety. Of the 162 participants, 24 reported they were allergic to at least one food; these people perceived that their allergy had significantly less of an impact on their lives than others believed it would. Allergy status interacted with perceived health competence to affect anxiety. People with an allergy and with high health competence reported the greatest anxiety levels. Very few of the sample knew the meaning of the term 'anaphylaxis'. Findings are discussed in terms of health education implications and possibilities.238 (posted Nov 20th, 2004)

 

-At the annual AAAA&I meeting held in San Antonio, Texas, Mar.18-22, 2005, Verreault, Kagan, Hourihane et al presented Quality of life of Children with peanut allergy. Using the QoL1(Quality of Life) Peanut Allergy Questionnaire developed by Hourihane (Pediatric Allergy and Immunology 2003;14:378-382) for children aged 4-6 yrs, a parental perception of the child's QoL was elicited, and for children > 7 yrs, the child's own perspective was elicited. Children were considered peanut allergic if they had a clinical reaction or a preanut-specific IgE > 14kU/L. Of 129 participants, 42 were aged 4-6 yrs; 21 had never ingested peanut, 27 had a mild reaction, 55 a moderate, and 26 a severe. The mean age was 8.5 yrs. For all participants, the mean QoL1 was 58.2 (range 25-100; 100= worst outcome). Two visual analog scales (QoL2 and QoL3) were also used (range 0-100; 100 = worst outcome). Results: 32.9 and 23.5 respectfully.
Conclusions: Peanut allergic children experience impaired quality of life. Best predictors of quality of life did not include any characteristics of previous allergic reactions or any demographic features. (posted April 24th, 2005)
 

 

 
Is it a lifelong allergy?

Contrairy to previous publications, peanut allergy is not necessarily life-long.The following are publications that appeared since 1998, studies that have shown that peanut allergy can be outgrown:

1) to determine whether there are any differences between children who remain mildly or moderately allergic to peanut (15 subjects) and children with similar histories but a negative reaction on challenge with peanut (also 15 subjects) Hourihane and coll. (1998) found that of the children that had lost their allergy , 13 had allergy tests and 8 showed no allergy, the other 5 still showed a positive test but reactions were not > than 5 mm. IgE levels were the same in both groups. The group still allergic showed allergies to other foods more so than the negative group. The conclusion was: appropriately trained clinicians must be prepared to challenge preschool children with peanut as some will be tolerant despite a history of reactions to peanut and a positive skin prick test to peanut 12. See complete article

Electronic responses to this article:

Comments:
2) L'Actualité (Vol: 23 No: 10 15 juin 1998 62) in their section on Health and Medicine, had a short paragraph entitled: "Une allergie reversible?" (A reversible allergy?) The translation reads as follows: "Is your child allergic to peanuts? Do not despair: he/she has a 40% chance of not being allergic to peanuts at age four. British researchers followed 14,210 children from birth to four years of age. One out of 200 infants becomes allergic to peanuts by 20 months of age.Nevertheless, at age four, two out of five spontaneously outgrew the allergy.25
 
A search of Medline did not reveal any mention of this study, but:
the study (ALSPAC or Avon Longitudinal Study of Pregnancy and Childhood birth cohort study) was presented at the annual AAAA&I meeting in Washington, DC, in March, 1998 by Golding, Fox and Lack on 14,210 children born over 21 months collated via questionnaires. Peanut allergy was identified on the basis of questionnaires, skin testing and/or anti-IgE to peanut, and confirmed by double-blind placebo-controlled food challenges (DBPCFC).
  • The cumulative prevalence of peanut allergy at 24 months was 0.21% and at 48 months was +/- 0.31%.
  • The mean age at first reaction was 20.5 months.
  • All allergic children reacted upon first known exposure to peanuts.
  • 75% of reactions were due to eating and 25% to touching peanut.
  • Peanut butter was responsible for 40% of reactions, whole nut for 41% and peanut containing foods for 19%.
  • 11% of the group had siblings with peanut allergy.
  • Allergy to other foods was reported by 50% and 38% of children had egg allergy.
  • The most common symptoms on DBPCFC were:
    • nasal symptoms (62%),
    • urticaria (hives) (54%),
    • vomiting (31%).
    • wheeze (15%)
    • and stridor (difficult breathing) (7%).
  • Two patients required intramuscular epinephrine and one patient had a late-phase reaction.
  • 41% (9/22) of children challenged were demonstrated to have outgrown their allergy.
  • Children who outgrew their allergy tended to present earlier than those with persistent peanut allergy.
  • The ones not having outgrown their allergy were significantly more allergic with
    • higher rates of eczema (100% vs 44%)
    • asthma (85% vs 11%) and
    • other food allergies (70% vs 33%) and they were more sensitive on allergy tests.
       
Conclusions:

Peanut allergy represents a significant problem by 2 years of age and that by 5 years nearly half of these children will lose their allergy. (posted March 13th, 1999)

This is not quite what was reported in an earlier study, Bock and Atkins in 1989 published their evaluation of 32 patients that had a positive DBPCFC as well as a positive skin test to peanuts. Follow-up challenges, conducted 2 to 14 years after the original challenge, showed that all retained their sensitivity, confirming the peanut sensitivity can be quite long-lasting 17

Peanut and tree nut allergies are potentially life-threatening, rarely outgrown . . 13 56.

3) At the 1999 American College of Allergy, Asthma & Immunology Annual Meeting held in Chicago, Nov 11-17th, among the New Findings in Food Allergy Research presentations, Dr Sami Bahna reported on:"Outgrowing" Peanut Allergy. Recent studies indicate that peanut allergies, which afflict approximately 1% of the US population, can be "outgrown" by adolescence.12 Indeed, findings presented by J.M. Spergel, MD, PhD, suggest that resolution is more likely to occur in patients with smaller skin test reactions and clinical reactions limited to the epidermis. Spergel's group subjected 38 patients with a clinical history of reaction prior to evaluation and with a positive skin test, to peanut challenge. Twenty-one patients persisted with positive challenge (PC) and 18 patients had a negative challenge (NC) despite positive skin tests. One patient became tolerant by challenge while another patient's reaction went from positive to negative. Both PC and NC groups had equivalent medical backgrounds although none of the patients with anaphylaxis became tolerant within the follow-up period of 2 to 6 years. The most significant difference occurred, however, in the size of the skin test -- the PC group experienced larger wheal and flare (P < .005).This study confirms the findings of a few other recent reports demonstrating that peanut sensitization can be outgrown. Favorable factors include onset during childhood, low degree of reactivity, and clinical manifestations other than systemic anaphylaxis. (posted Nov 18th, 1999)

This study has since been published in the Dec 2000 Annals of Allergy, Asthma and Immunology 109 (posted Jan 21, 2001)

 4) "The natural history of food allergy documents that allergy to cow's milk, egg and soy frequently remit whereas allergy to peanut, nuts and fish typically persist to adulthood, although exceptions exist. Food allergen avoidance subsequent to sensitization and manifestation of symptoms appears to hasten tolerance; however, the immunologic mechanism responsible for tolerance to one food group and not another is poorly understood.90 (posted Jan 23d, 2000)

5) At the annual meeting of the AAAA&I held in San Diego, Mar 3-8th, 2000, Vander, Leek, Liu and Brock state: "Previous studies have shown that peanut allergy is rarely outgrown, although recent observations suggest that younger children with milder reactions may lose their reactivity." The objectives of the study they report on, were to "observe the frequency and nature of adverse reactions due to accidental peanut exposure in young children with previous clinical hypersensitivity, and to determine the potential value of serum peanut-specific IgE antibody levels for ongoing follow-up." Eight-two (82) children were identified with clinical peanut hypersensitivity diagnosed before their 4th birthday. All had positive skin tests. They were followed over a median 5.6 yrs (range 1.2 to 22.1 yrs), contacted yearly to track adverse reactions due to accidental peanut exposure. IgE antibody levels were obtained in 42/82 subjects.

The majority of young children with clinical peanut hypersensitivity will have adverse reactions due to accidental peanut exposure within 3 yrs of their initial evaluation. In addition, it appears that young children who present with only skin reactions are at risk for respiratory and/or gastrointestinal involvement with subsequent peanut exposure. Children who have had only cutaneous reactions to peanut have lower peanut-IgE levels than those who have respiratory and/or gastrointestinal involvement. (posted Mar 9th,2000)

6) A joint group from Johns Hopkins (Skolnik et al) with H. Sampson from Mont Sinai, at the annual AAAA&I meeting in San Diego, Mar 3-8th, 2000, also reported on the duration of peanut allergy in a study whose purpose was to determine the number of children diagnosed with peanut allergy who became tolerant later in life. Peanut-specific IgE (PN-IgE) quantification was done and the ones with a titre of < 20 kU/L and no history of reaction in the past year were asked to participate in a double-blind placebo-controlled peanut challenge (DBPCPC) (unless the previous reaction was severe, in which case a cut-off of < 10 kU/L was used.) Some patients had open challenges. To date, 103 patients, age range 4-17.5 yrs (median 6.5) have participated in the study. These patients were diagnosed with peanut allergy from age 2 months to 10 yrs (median 1.5 yrs). Forty-four patients (43%) were identified as definitely peanut allergic since their PN-IgE was > 20kU/L. Twenty-one patients with a PN-IgE < 20 kU/L refused the challenge. The remaining 38 patients participated in either a DBPCFC or an open challenge. Skin tests were repeated before the challenge in 13/38 patients and four had turned negative. The median range of PN-IgE of the patients challenged was 0.75 kU/L (range < 0.35 (undetectable) to 20.4 kU/L). Overall, 26 patients had a negative challenge and are believed to have outgrown their peanut allergy (ages 4-11.5 yrs (median 6), PN-IgE < 0.35 to 20.4kU/L (median 0.54). The remaining 12 experienced a positive challenge (ages 4-9.5 yrs ; median 5), PN-IgE < 0.35 to 11.6 (median 1.24 kU/L). 71% of patients with a PN-IgE < 2 kU/L had a negative challenge. Of those challenged, PN-IgE level for those who passed versus those who failed were not different at the time of diagnosis or challenge. The severity of the initial reactions were also similar, with both groups including patients with moderate to severe anaphylaxis.

Conclusion : This study demonstrates that peanut allergy is not necessarily life-long. Patients with very low PN-IgE levels should be challenged in a medical setting to determine whether they can now tolerate peanuts. (posted Mar 9th, 2000)

This study was continued and published in the Feb 2001 J Allergy Clin Immunol issue by Skolnik, Conover-Walker, Barnes Koerner, Sampson, Burks, and Wood.106

  • A total of 223 patients were evaluated, and of those,
  • 85 participated in an oral peanut challenge.
  • Forty-eight (21.5%) had a negative challenge, and were believed to have outgrown their peanut allergy (aged 4-17.5 years [median 6 years]).
  • Thirty seven failed the challenge (aged 4-13 years [median 6.5 years]) Both groups had an IgE level less than 20 kU/L.
  • 41 patients with levels of IgE less than 20 kU/L declined to undergo the challenge
  • 97 were not eligible because their IgE levels were higher than 20 kU/L or they had had a recent reaction
  • 67% of patients with IgE levels less than 2 kU/L and 61% with levels less than 5 kU/L had negative challenge results.
 
Conclusion:
This study demonstrates that peanut allergy is outgrown in about 21.5% of patients.Patients with low IgE levels should be offered a peanut challenge in a medical setting to demonstrate whether they can now tolerate peanuts.112 (posted Feb. 14th, 2001)

7) Rommy Koetzler, M.D. and Alexander C. Ferguson, M.D. published their study entitled Outcome of Peanut Allergy in Infancy: An Oral Challenge Study in School Age Children, in the Canadian Journal of Allergy & Clincal Immunology, July 2000, Vol. 5 No.6. Fifteen children with documented peanut reactions, and positve skin tests as infants were challenged with increasing doses of emulsified peanut butter in serial doses of 10 µg to 5 g. increasing until symptoms or signs developed, or the maximum dose reached. Results: 8 children had a mild reaction, 3 moderate, and none severe. Reactivity was unrelated to age at first peanut contact or to current age. Current skin test size (wheal diameter) was smaller in those with negative challenges, and anti-peanut IgE was lower. Symptoms were elicited by doses of 10µg or greater (abdominal pain, tingling tongue, itchy throat, nausea, itchy lips) whereas objective signs (vomiting, urticaria, pruritis, facial oedema, and cough) required 100mg or more of peanut butter. One subject had no reaction, and three had symptoms but no objective signs with a 5 gm dose. If objective signs are taken as evidence of persistent peanut allergy, 4/15 (27%) subjects appeared to be tolerant to peanut. They conclude that "whereas allergy to peanut tends to persist, the severity of reactions decreases - more than trace amounts may be required to elicit a significant reaction and a substantial proportion of children may be tolerant. A much larger cohort of children and repeated challenge testing will be required to confirm and validat theses findings. " (posted July 27th, 2000)

8) At the Sept.8-10, 2000 Annual Meeting of the Canadian Society of Allergy and Clinical Immunology, Kerr PE and Kagan RS, from the Dept of Allergy and Immunology, Montreal Children's Hospital, presented, at the Poster Session, Resolution of Peanut Allergy: A Case Report, the abstract of which appeared in the Canadian Journal of Allergy and Clinical Immunology, Vol 5, No 7, Sept 2000.

They report the case of a 9-year-old boy who was diagnosed with peanut allergy at 18 months of age (swelling and erythema of the face, eyes, mouth, and lips 15 minutes after ingestion of peanut butter; skin prick test was positive: 15/22 wheal/flare) Since diagnosis, he had avoided all nuts and peanut products completely. Recently, he ingested a sauce with a small amount of peanut in it and had no reaction. His parents requested a re-assessment....A repeated skin prick test at age 9 remained positive for peanut: 9/18...At the family's request, the child underwent an oral challenge. He tolerated graded amounts of peanut flakes and subsequently ate a portion of peanut butter on cookies without any symptoms. Since then, he has resumed eating peanuts with no adverse reactions. This case illustrates that a diagnosis of peanut allergy based on clinical history and skin test can disappear over time. Further studies are needed to identify the determinants of lifelong versus resolving peanut allergy in order to guide physicians as to which patients can safely be retested and challenged. (posted Sept 12th, 2000.)

-This study was published in the Feb 2002 Annals of the RCPSC (Royal College of Physicians and Surgeons of Canada)

9) In the Oct 2000 J Allergy and Clin Immunol , Dr. J. M. Kelso reports on the Resolution of peanut allergy in a 3 year-old girl, diagnosed with documented peanut allergy at 8 months of age after having reacted to peanut butter with generalized urticaria. She was seen after having eaten a food made with peanut flour. The test done with commercial peanut extract and crude peanut were negative. She was challenged with peanut butter to which she did not react. Dr Kelso "advised the parents to re-introduce peanut products in her diet but to continue to be prepared, for the time being, to treat a reaction." (see 'worsening of reaction after prolonged avoidance has been described', below) ...that although previous studies have suggested that peanut allergy is usually life-long, this patient suggests that in rare cases the allergy can in fact resolve. It will be interesting to see whether peanut allergy re-develops in this child. Given the large burden that peanut avoidance imposes on children and families (e.g. reading labels and carrying epinephrine), it would seem reasonable to repeat peanut skin tests in children allergic to peanut at some interval, especially if they believe they have had uneventful accidental ingestions in the interim." 98 (posted Oct 29th, 2000)

10) In the Dec. 2000 Pediatrics, Bock et coll. followed 84 children with clinical peanut hypersensitivy diagnosed before their fourth birthdays, contacted yearly for 5 years to track adverse peanut reactions. Serum peanut-specific IgE levels were determined in 51 of 83 subjects.

Results: fifty-eighy percent (31/53) of subjects followed up to 5 years experienced adverse reactions from accidental peanut exposure. Regardless of the nature of their initial reaction, the majority with subsequent reactions (52%, 31/60) experienced potentially life-threatening symptoms. The group with isolated skin symptoms (11/51, 22%) had lower serum peanut-specific IgE levels than the group with respiratoiry and/or gastrointestinal symptoms. (40/51, 78%)... Four selected subjects had negative double-blind placebo-controlled food challenge responses to peanuts during follow-up.105 (posted Dec. 21st, 2000)

11) At the Oct 2001 annual meeting of the CSACI (Canadian Society of Allergy and Clinical Immunology) Dr. Rhoda Kagan of the Allergy and Immunology Division, Montral Children's Hospital, gave a talk on The Natural History of Food Allergy. Some of the highlights: "8% of young children have food allergies but less than 2% of adults, suggesting that many children outgrow their allergies as they get older. It varies with individual foods and its mechanism remains unclear. Previously held beliefs that some food allergies are always life-long have recently been challenged, leaving a greater sense of optimism for the resolution of food allergy presenting in early childhood." She cites Hourihane's article that appeared in 1998 and other studies since (see postings above). "The evolving recognition of the natural history of peanut allergy offers a glimmer of optimism for families and individuals with peanut allergy. Because individuals with peanut allergy and their families carry the burden of anaphylaxis risk and its attendant psychological consequences, the possibility of resolution is encouraging." (taken from Anaphylaxis Canada Newsletter- Winter 2001) (posted Dec 7th, 2001)

12) Spergel and Fiedler in the Dec 2001 Current Opinion in Pediatrics published 'Natural history of peanut allergy' in which they state..."studies in the past year have shown that a subset of patients with peanut allergy can become tolerant to peanut. The patients with the milder reactions on presentation have a better chance to develop tolerance to peanuts than the patients whose first reaction is anaphylaxis...the natural history of peanut allergy is evolving."139 (posted Dec 31st, 2001)

See also: Prognosis of Severe Food Allergies
Discussion on outgrowing peanut sensitivity by Dr. Barry Zimmerman

13) "Peanut allergy may resolve in approximately 15% of selected children atttending an allergy clinic run by general paediatricians in a district general hospital. Food challenge constitutes the appropriate way of removing the burden that comes with a diagnosis of peanut allergy and enables dietary restriction to cease." according to Rangaraj S et al, authors of a publication in Pediatr Allergy Immunol Oct. 2004.232 (posted Oct. 18th, 2004)

14)"Resolution of peanut allergy following bone marrow transplantation for primary immunodeficiency" is the title of a publication by Hourihane, JO et al, in Allergy April 2005. They report the case of "a boy with peanut allergy who required a bone marow transplant (BMT) for combined immunodeficiency. A food challenge, 2 years after transplant, showed that his peanut allergy had resolved. Allergic disorders constitute a form of immune deviation and while we do not advocate BMT as a treatment for peanut allergy, we believe this case provides an insight into the basic mechanisms involved in food allergy." 244 (posted May 9th, 2005)

-Early clinical predictors of remission of peanut allergy in children. Ho MH, Wong WH, Heine RG, Hosking CS, Hill DJ, Allen KJ. studied consecutive patients less than 2 years of age with peanut allergy were identified on the basis of skin prick test (SPT) wheal size of 95% positive predictive value or greater. Baseline SPT responses to peanuts, tree nuts, and sesame and serum peanut-specific IgE antibody levels were documented, and follow-up studies were conducted at 1- to 2-year intervals for up to 8 years. Peanut food challenges were performed when SPT responses decreased to less than the 95% positive predictive value for peanut allergy.

RESULTS: SPT wheal diameters to peanut extract of 6 mm or greater and peanut-specific IgE antibody of 3 kUA/L or greater before the age of 2 years were independent predictors of persistent peanut allergy. Mean SPT wheal diameters of nonremitters increased whereas those of remitters decreased between 1 and 4 years of age. Twenty-one percent of young children with peanut allergy became clinically tolerant by age 5 years.

CONCLUSIONS: Remission of peanut allergy can be predicted by low levels of IgE antibodies to peanut in the first 2 years of life or decreasing levels of IgE sensitization by the age of 3 years. 283(posted Feb 17th, 2008)

 

Peanut Allergies, Thought Outgrown, Can Return

-(HealthScoutNews)=followiing the Nov 7, 2002 correspondance in the New England Journal of Medicine by Sicherer SH et al. entitled Recurrent peanut allergy where the authors offer an institutionally approved research protocol for double-blind, placebo-controlled oral food challenges for use in children older than 3.5 yers of age who have been allergic to peanuts and who have a clinical profile consistent with potential resolution of peanut allergy, as defined by the absence of recent reactions and a serum peanut-specific IgE antibody concentration of less than 10 kU/:L.112

They describe 3 patients who tolerated peanuts during such a challenge...who went on to have recurrence of peanut allergy. In the year after having no allergic reaction on oral challenge, the boys ate peanuts infrequently and in small quantities. The recurrence of peanut allergy was documented in one patient by a repeated challenge that elicited a generalized reaction, in the second patient by repeated mild reactions and a concentration of peanut-specific IgE antibody (15kU/l) that was highly (>95%) predictive of clinical reactions, and in the third patient by a severe reaction and recurrence of sensitization.
The authors can only speculate as to why these children became resensitized. Although they were not reactive, they were ingesting only small amounts of peanut intermittently - a regimen that is typically considered to be sensitizing. This regimen contrasts with typical regimens designed to build tolerance (which entail the continuous administration of small doses or the intermittent administration of large doses). These 3 patients were evaluated after 44 children entered the authors' ongoing study of the resolution of peanut allergy. At that time, 26 children had no allergic reaction on oral challenge, and follow-up (mean duration, 15 months) in 21 children revealed that only 10 routinely ate peanuts. This observation is worrisome if the aforementioned hypothesis is correct.
The clinical ramifications of the authors' observations are profound and may apply to other foods as well as to peanuts. Recurrence of peanut allregy is possible even when it has been shown to have resolved. It seems prudent to maintain access to emergency medications, such as self-injectable epinephrine, for patients with resolved peanut allergy until peanuts are routinely tolerated in relevant quantities for at least one to two years. 164 (posted Nov 15th, 2002)
 
-Here's an interesting item that appeared in The Medical Post April 8, 2003: Tell kids who outgrow allergy to eat more peanuts. Continued exposure may keep them from becoming allergic again. "Recent studies have shown about 20% of children outgrow their allergy to peanuts. However, new evidence is emerging that some of those children become allergic again. To avoid that, Dr. Jeffrey Factor thinks kids who outgrow their allergy should eat more peanuts." (posted July 4th, 2003)

Monthly Ingestion Appears To Boost Peanut Tolerance In Children Who Outgrow Peanut Allergy. According to researchers at the Johns Hopkins Children's Center, children who outgrow peanut allergy have a slight chance of recurrence, but the risk is much lower in children who frequently eat peanuts or peanut products. J Allergy and Clin Immunol Nov 2004: Peanut allergy: Recurrence and its management-David M. Fleischer, MD, Mary Kay Conover-Walker, Lynn Christie, MS, RD, LD, A. Wesley Burks, MD, Robert A. Wood, MD237 (posted Nov 10th, 2004)

 -In the July 2003 J Allergy Clin Immunol, Fleischer et al have an article entiltled The natural progression of peanut allergy: Resolution and the possibility of recurrence where they extend the data reporting that 20% of youngsters with peanut allergy, especially when diagnosed at a young age, might lose their reactivity over time (summerized above106) They report the loss of reactiviy at various levels of specific peanut antibody in serum.

Patients with peanut-IgE levels of 5 or less were offered a peanut challenge. Those who passed were further evaluated by questionnaire to assess reintroduction of peanut into their diet and whether any recurrence has occurred.
Results:
-Eighty-four patients were evaluated, and 80 underwent complete analysis.
-Fifty-five percent with peanut-IgE levels of 5 or less and 63% with peanut-IgE levels of 2 or less passed challenges, compared to 61% and 67%, respectively, in our previous study.

-The 4 additional patients passed peanut challenges in this study after previously failing.

-Three patients with initial anaphylactic reactions and 2 patients with initial peanut-IgE levels greater than 70 passed their challenge.

Follow-up of those who passed in both studies showed that the majority of patients reintroduced peanut into their diet, but that continued label reading, infrequent/limited ingestion, and aversion to peanut were all common in this population. Two patients had suspected subsequent reactions to peanut after passing their challenge.

Conclusions:
Patients with a history of peanut allergy and peanut-IgE levels of 5 or less have at least a 50% chance of outgrowing their allergy. Recurrence of peanut allergy may occur but appears to be uncommon.178 (posted July 11, 2003)

 

 
 
 
-At a poster session at the AAAA&I Annual Meeting held in San Francisco Mar 19-23d, 2004, Kerr PE and Ham Pong A presented Peanut re-sensitiztion after negative skin tests and negative oral challenge. They report 4 patients, three of which had never ingested peanut but had positive prick-skin tests between the ages of 13 months and 3 years. The fourth patient had hives with peanut and a positive skin test at 13 months. All patients developed negative skin tests at ages 4-5.5 yrs at which time they all tolerated oral challenge. Three patients refused to eat peanuts after the challenge but between 1-6 yrs later ingested peanut and had allergic reactions... nausea, vomiting, wheezing and sore throat, or throat swelling. The fourth patient tolerated peanut twice within a week of the oral challenge then developed abdominal cramps and vomiting on two further ingestions of peanut.
Discussion: ...These cases highlight the need for parent and patient education regarding the possibility of re-sensitization after negative prick-skin tests and negative challenge. Patients need to be instructed to continue to carry epinephrine until they are regularly consuming peanut without reactions.208 (posted Feb 15th, 2004)
 
-At the same AAAA&I Meeting in San Francisco, Mar 19-23, 2004, Lidman, Watson, Simons and Becker had a poster, Reactions to food in children recurs after negative oral challenge.  To determine if patients sensitized to food remain tolerant after negative food challenge, they looked at 302 children < 16 years of age who had negative food challenges between 1996 and 2003. They randomly reviewed 107 of them (35%) with 121 challenges. 14 (12%) < 6 months from challenge were excluded. 28 (23%) were lost to follow-up. Complete data were available for 59 (47%):
  • 40/59 (68%) regularly ate the food with no problem.
  • 4/59 (7%) subsequently reacted, all with egg (4/18; 22%), and all to raw or less well cooked egg;
  • 1/4 completely avoided egg and 3/4 tolerated egg in baked goods.
  • In spite of no reaction, 2/26 previously peanut allergic continued to completely avoid peanut and 10/26 had peanut < weekly.
  • All 15 patients with negative milk challenge tolerated and continued to regularly consume milk.
 
Conclusions: Subjects with negative egg challenge were more likely to react again than subjects with negative peanut or milk challenge. Peanut allergy remains a concern for many patients, even with a negative challenge. Allergists should consider a second challenge for egg and/or peanut allergic patients. 209 (posted Feb 15th, 2004)
 
-Again, at a poster session of the same AAAA&I Annual meeting, Mar 19-23, 2004, Fleischer, Conover-Walker and Wood presented Peanut allergy: Recurrence and its management. Rationale: Since peanut allergy may recur and recurrence risk may be increased due to limited consumption of peanut after allergy resolution, they re-examined children who outgrew their allergy over the past 7 years to determine their current allergy status. Thirty-one patients (aged 5.5-21.4 years) with a follow-up period of 0.8-5.7 years (after a negative challenge) were evaluated.
  • One patient with a peanut IgE level of 1.1 kU/l at initial challenge at age 4.5 years and who rarely consumed peanut after resolution, had anaphylaxis to peanut 1.8 years later and has a current peanut-IgE level > 100.
  • Seven patients with peanut -IgE levels from <0.35 to 17.1 eat peanut frequently and continue to tolerate it.
  • Six patients with peanut-IgE levels from < 0.35 to 54 and eat peanut rarely passed DBPCFCs to peanut.
  • Seventeen patients with peanut-IgE levels from 0.35 to 7.3 eat peanut rarely, have yet to undergo a DBPCFC.
 
Conclusions: Children with resolved peanut allergy may be at risk for recurrence. Monitoring peanut CAP-RASTs of children with resolved peanut allergy may not be useful because some children continue to be peanut tolerant despite high peanut-IgE levels. 210 (posted Feb 15th, 2004)
The authors (along with Christie L.and Burks AW) published their findings in the Nov 2004 J Allergy Clin Immunol. Their results:
  • Sixty-eight patients were evaluated. Forty-seven patients continued to tolerate peanut, of whom 34 ingested concentrated peanut products at least once per month and 13 ate peanut infrequently or in limited amounts but passed a DBPCFC.
  • The status of 18 patients was indeterminate because they ate peanut infrequently or in limited amounts and declined to have a DBPCFC.
  • After excluding 12 patients originally diagnosed with peanut allergy based solely on a positive skin prick test or peanut-specific IgE level, 3 of 15 patients who consumed peanut infrequently or in limited amounts had recurrences, compared with no recurrences in the 23 patients who ate peanut frequently ( P = .025). The recurrence rate was 7.9 (95% CI, 1.7% to 21.4%).
CONCLUSION: Children who outgrow peanut allergy are at risk for recurrence, and this risk is significantly higher for patients who continue largely to avoid peanut after resolution of their allergy. On the basis of these findings, we now recommend that patients eat peanut frequently and carry epinephrine indefinitely until they have demonstrated ongoing peanut tolerance.239 (posted Dec 6th, 2004) 

-In Pediatr Allergy Immunol. 2006 Dec;17(8):601-5. Eigenmann et al have an article entitled Continuing food-avoidance diets after negative food challenges. Here's part of the abstract: 'Negative food challenges for follow-up in patients previously diagnosed with food allergy should logically be followed by a normal diet. However, all patients do not reintroduce the food.Patients with a negative food challenge were sent a questionnaire by mail. Items in the questionnaire included the symptoms at diagnosis, the duration of the diet, the fear of an accidental reaction during the avoidance diet and how it influenced the social life. Patients were also asked if the food was reintroduced after the negative food challenge, and if not, for which reasons. In 25.4% of the questionnaires (18/71) respondents reported that the food was not reintroduced. Patients with a previous diagnosis of peanut allergy tended to reintroduce the food less frequently than patients allergic to other foods. However, neither the severity of the initial reaction, the anxiety of an accidental reaction during the avoidance diet, nor a prolonged avoidance diet did influence the decision to reintroduce the food. Among other reasons listed, fears of persistence of allergies, with recurrent pruritus or non-specific skin rashes after eating the food, were reported in 12.7% of the total number of questionnaires. Patients who reintroduced the food reported that their social life generally improved. One quarter of previously allergic patients continue a food avoidance diet despite a negative challenge. We suggest reassessing food consumption in all patients after a negative food challenge, and in those still avoiding the specific food to consider a repeated challenge test. (posted Jan. 5th, 2007)

 

  -Worsening of reaction after prolonged avoidance:

-An interesting feature of food allergy in general, although unusual, "worsening of reaction after prolonged avoidance has been described.27 . .David reported 4 children with atopic dermatitis (eczema) who had foods to which they were allergic re-introduced into their diets, and they experienced anaphylactic reactions74. . ." These are comments made by the authors (Oppenheimer JJ, and Bock, SA) in a report about an 8 year-old child with a history of milk-induced exacerbation of atopic dermatitis who, after 18 months of avoidance, experienced significant increase in her reactivity. The communication is titled"The ice cream parlor challenge could be a killer" published in the J Allergy Clin Immunol 1998;102:325-6. 75 (posted July 8th, 1999)

 

Link between asthma and peanut allergy

Is there a link between having asthma and the intensity of the allergic reaction caused by peanut?
According to the medical publications on this aspect, particularly regarding anaphylactic reactions reported to peanuts, the severity of the reaction seems to be directly related to the atopy the patient has (presence of total allergies), in other words, the most severe reactions reported occurred in patients that had other food allergies and environmental allergies, the latter ones responsible in great part for the asthma.
 

What about reactions occurring by simply being in the presence of peanuts or exposed to the odor of peanuts?

-There's no mention in the above references regarding contact with peanuts other than by ingestion and by contact with intact skin10 , although Hourihane refers to "anecdotal reports (not supported by challenge studies) of subjects reacting strongly to the smell of peanuts or to being in the vicinity of an open jar of peanut butter. 58. 59 The dose of presumably airborne peanut protein involved in these reactions must be very low. The more common scenario is an allergic reaction after a minimal contact with peanuts 2 , through intact skin (e.g., being touched by someone who has handled peanuts, accidental ingestion of small amounts of peanut protein, or eating bread buttered with a knife previously used to make a peanut butter sandwich for someone else)." (1996)

-In the May 2001 Ann Allergy Asthma Immunol , Tan, Sher, Good, and Bahna report on "Severe food allergies by skin contact." According to the authors, "while ingestion is the principal route for food allergens, yet some highly sensitive patients may develop severe symptoms upon skin contact." Five cases, infants, are described with severe reactions to milk, egg white, lentils, peas, and peanut butter occurring by skin contact, or inhalation, while being breast-fed in four cases. The symptoms reported range from eczema, urticaria, angioedema and breathing problems. Each case had a strong family history of allergy, early age of onset, very high total serum IgE, and strong reactivity to the foods involved by skin prick test or RAST.

Conclusion: Severe food allergic reactions can occur from exposure to minute quantities of allergen by skin contact or inhalation.129 (posted Aug 1st, 2001)

-On Feb 23d, 2002, the AQAA (Association Québécoise des Allergies Alimentaires) held its annual Allergy Day at Hôpital Ste-Justine de Montréal. Dr Marie-Noël Primeau, pediatric allergist of the hospital, gave a talk on Anaphylaxis and adverse reactions to the odor of foods. "ANAPHYLAXIE ET RÉACTION À L'ODEUR DES ALIMENTS". The question of adverse reactions to the odor of certain foods is not clear. Firstly, there is little information on this in the medical literature. Furthermore, because such reactions are rare, the data reported can be applied to only a small number of allergic individuals. Management and recommendations cannot be defined specifically at this point in time. Each case must be evaluated separately. Studies have shown that allergenic particles of certain foods could be air-borne. But this does not mean that these particles will cause a reaction in individuals allergic to the particular food by inhalation. Dr Primeau's conclusion was that adverse reactions can occur by simply being exposed to the odor of foods, but they are exceptional. Because this type of reaction is usually mild, limited to the skin or respiratory system, Dr Primeau suggested that the approach in the treatment of such reactions should be conservatory, and no strict avoidance measures undertaken especially if the allergic individual has never reacted to the odor or being in the presence of the food in question. If this type of reaction does occur, it should be brought to the attention of the allergist who will be able to assess its importance and prescribe accordingly. (translation of comments posted at the Allergique.org website Mar 11, 2002) (posted here Mar 22, 2002)

-In the July 2003 J Allergy Clin Immunol, Simonte et al report a study, Relevance of casual contact with peanut butter in children with peanut allergy the objective being to determine the clinical relevance of exposure to peanut butter by means of inhalation and skin contact in children with peanut allergy. Children with significant peanut allergy (recent peanut-specific IgE antibody concentration >50 kIU/L or evidence of peanut-specific IgE antibody and one of the following: clinical anaphylaxis, a reported inhalation-contact reaction, or positive double-blind, placebo-controlled oral challenge result to peanut) underwent double-blind, placebo-controlled, randomized exposures to peanut butter by means of contact with intact skin (0.2 mL pressed flat for 1 minute) and inhalation (surface area of 6.3 square inches 12 inches from the face for 10 minutes). Placebo challenges were performed by using soy butter mixed with histamine (contact), and scent was masked with soy butter, tuna, and mint (inhalation).
Results: Thirty children underwent the challenges (median age, 7.7 years; median peanut IgE level, >100 kIU/L; 13 with prior
history of contact and 11 with inhalation reactions). None experienced a systemic or respiratory reaction. Erythema (3 subjects),
pruritus without erythema (5 subjects), and wheal-and-flare reactions (2 subjects) developed only at the site of skin contact
with peanut butter. From this number of participants, it can be stated with 96% confidence that at least 90% of highly sensitive children with peanut allergy would not experience a systemic-respiratory reaction from casual exposure to peanut butter.
Conclusions: Casual exposure to peanut butter is unlikely to elicit significant allergic reactions. The results cannot be generalized to larger exposures or to contact with peanut in other forms (flour and roasted peanuts).180 (posted July 11th, 2003)
 
-In the Bangor News, Sept 28, 2004, Dr.Paul A.Shapero, M. D., an allergist in Bangor, Maine wrote "Some perspectives on peanut allergy". where he states "inhalation of peanut protein can cause allergic reactions but usually not systemic anaphylaxis while odors can cause conditioned physiologic responses... odors are not capable of causing allergic reactions." (posted Oct 1st, 2004)
 

Commercial airlines and peanuts

-At the annual meeting of the AAAA&I (Feb. 1999 in Orlando) Sicherer, Furlong, DeSimone, and Sampson presented a paper entitled: "Peanut Allergic Reactions on Commercial Airlines." The purpose of the study was to describe the clinical characteristics of allergic reactions to peanut (PN) on airplanes. Participants in the National Peanut and Tree Nut Allergy Registry (PAR) who indicated an allergic reaction were interviewed by telephone.

 

Conclusion: Food (peanut and nut) allergic reactions occurred during commercial flights but airline personnel were notified in only 33% of cases. Reactions were frequently severe, requiring medication including epinephrine. Severe reactions were primarily due to accidental ingestion, but respiratory reactions occurred from inhalation when many passengers were consuming PN. (posted April 2nd, 1999)

I e-mailed Dr. Hourihane, asking his opinion on the importance of peanut odor, and this was his response: "I am not personally aware of proven anaphylaxis associated with the smell but it is often related by parents that the child has become lethargic and clingy after entering a room with peanuts open in the room. This cannot be called anaphylaxis with any confidence. My feeling is that some people really do degranulate on inhaled exposure (Dr. Hourihane is referring to degranulation of cells involved in allergic reactions, specifically mastocytes, meaning they have a typical allergic reaction) but the reactions are minor - usually upper airway and eyes with some urticaria (hives) maybe. The major problem when exposed like this is panic especially on planes and in other confined spaces." (posted April 8th, 1999)

The paper presented at the Orlando Meeting of the AAAA&I (summarized above) has now been published in the J Allergy and Clin Immunol, July 1999, vol 104, 186-9.

Further comments from the authors: Allergic reactions to peanuts and tree nuts caused by accidental ingestion, skin contact, or inhalation occur during commercial flights. . . most of the inhalation reactions described were not life-threatening. However, when one considers the whole group experiencing acute allergic reactions by ingestion and inhalation to peanuts or tree nuts while on commercial airliners, the importance of exercising caution and having emergency medication available becomes apparent. 76(posted Aug. 1st, 1999)

-In the same issue of the journal, John M. James, M.D. summarizes the 'airline-peanut allergy' problem in an artilcle entitled Airline snack foods: Tension in the peanut gallery. Here are some of his remarks:

-. . . "there has been increasing concern and debate about the potential for individuals with peanut allergy to experience an allergic reaction while on a commercial airplane that is serving peanuts and/or peanut-containing food. . . .The cabin of a plane in flight is certainly a less than ideal environment in which to recognize and properly manage a potentially severe allergic reaction. . . In mid-1998, the Department of Transportation (DOT) issued a proposal that would have mandated that the 10 major US commercial airlines must provide "peanut-free zones" for passengers with allergic reactions to peanuts. . . This met great resistance from the Air Transportation Association. . . the US Congress. . .the mandate was never implemented, one of the reasons cited by members of the Congress was the lack of published, scientific data describing passengers with peanut allergy who had experienced allergic reactions caused by airborne peanut allergen on commercial airliners."

-Citing the paper by Sicherer and co-workers summarized above, Dr James underlines that this paper "represents the first published investigation describing the clinical characteristics of allergic reactions to peanuts on commercial airliners in subjects with peanut allergy. . . the self-reported allergic reactions, however, were very consistent with allergy. . .this investigation does not provide all the data needed to resolve this ongoing debate, but it certainly provides a solid foundation to better address these potentially life-threatening exposures and allergic reactions."

-"There are some disturbing findings in this investigation. First, why was there such a low level of notification of flight crews and airline personnel?. . .Second, could other potential irritants (eg. strong perfumes, passive tobacco smoke on clothing of smokers, and cleaning agents) have contributed to the inhalation reactions in some of the subjects, especially those with asthma? . . Finally, 5 subjects received epinephrine while in flight to manage severe allergic reactions. This observation relates to another relevant debate focusing on the availability of injectable epinephrine on board commercial airliners and the availability of trained flight personnel to administer this medication."

-"Two things are very clear to me as this debate continues to develop: education and preparedness should prevail. . . In the final analysis, more objective data and proper education will help guide us in the ultimate resolution of this important debate and lower the tension in the peanut gallery." 77 (posted Aug. 1st, 1999)

-See also:
-Out of the Blue: Peanut allergies are a little-known danger (posted April 1st, 2002)
 
 
Peanut oil

-refined peanut oil (heat processed) is not allergenic (in other words, it will not cause an allergic reaction in the peanut-allergic individual). Of 10 peanut-allergic patients challenged with peanut oil, none reacted to the protein-free oils. Subsequent reports have indicated that oils contaminated with peanut protein may indeed produce significant allergic reactions in peanut-sensitive individuals. Cold-pressed oils are more likely to contain peanut proteins than hot-pressed oils. (1997) 15

-Hourihane and co-workers evaluated two grades of peanut oil for a large group of subjects with proven allergy to peanuts, in a double-blind, crossover food challenge with crude peanut oil and refined peanut oil. None of the 60 subjects reacted to the refined oil; six (10%) reacted to the crude oil. They concluded that crude peanut oil should continue to be avoided. Refined peanut oil did not pose a risk to any of the subjects. Change in labeling to distinguish the two grades are recommended 18.

-Another later study confirms these findings, and examined several brands of walnut, almond, hazelnut, pistachio, and macadamia nut oils. The oil extracts known to be from oils that had undergone less processing at lower temperatures tended to demonstrate qualitatively greater IgE binding (blood test proof of peanut-specific antibody) and higher protein concentrations, posing a threat to patients with allergy 19.

-On the other hand, Olszewski and coll. reported an allergy to peanut oil by skin test, and by double-blind placebo controlled challenges, concluding the presence of residual allergenic proteins in crude and refined peanut oil, and that the increase consumption of allergens in the form of peanut oil and fats can contribute to the occurrence or persistence of symptoms and may be suspected to increase the risk of sensitization 23,24.

 

-How about peanut oil in vitamin A and D preparations: according to a Feb 1999 Swedish study, sensitization to peanut during childhood through consumption of vit A adn D in oil-based solution seems unlikely.78
 
-In a 1994 J Allergy Clin Immunol paper, Hoffman and Collins-Williams studied various makes of peanut oil, and found that refined, hot-pressed peanut oils are free of protein but cold-processed peanut oils could cause reactions in peanut allergic individuals. They concluded that: "Highly reactive individuals should avoid foods prepared in or with peanut oils, especially "health foods," which may be prepared with cold-pressed or unrefined peanut oil that may be contaminated with peanut protein." 95 (posted June 10th, 2000)
 
-On June 7th, 2001, there was a item in the Montreal Gazette entitled, "Doctors skeptical about peanut-allergy theory." It dealt with comments by two Montreal doctors (Dr. M. Katz and B. Moroz) regarding the theory proposed by Dr Gideon Lack, from St Mary's Hospital in London, Eng. following the findings of his study of children with peanut allergy. He told the Royal Society of London that 9 out 10 children with peanut allergy had previously suffered from eczema...and that children who developed peanut allergies were 8 times more likely to have been treated with creams containing peanut oil than kids who were allergy-free. The peanut oil containing creams would be an ideal way of setting up the allergy *. Lack also dismissed the widespread belief that expectant mothers who eat nuts during pregnancy risk passing the allergy to their babies. In fact, he argued that avoiding peanuts during pregnancy might have the opposite effect- encouraging the emergence of allergies when children come into contact with nuts (this based on a follow-up of 14,000 mothers-to-be since 1991)...He estimates that peanut allergy affects one in 100 children. (posted June 9th, 2001)
 *-See chapter above on 'sensitization to peanut - other possible sources of sensitiztion'. Lack and others presented a paper on this at the March 1998 Annual Meeting of the AAAA&I held in Washington, DC.
 
-In the Aug. 2001 publication of Cutis, Yunginger and Calobrisi analyzed a topical cream containing fluocinolone and refined peanut oil, among other ingredients and reactivity in 14 peanut-allergic subjects. No immediate or delayed skin test reactivity was demonstrated in any of the subjects tested. This suggests that a refined peanut oil-containing dermatologic preparation is safe to use, even in persons who are sensitive to peanuts.132 (posted Sept 20th, 2001)
 
 
 

 Link between peanuts and other legumes, tree nuts, and soy

re other legumes:
 -peanut is a legume along with peas, beans, soy, lentils, alfalfa. The very allergic individual may also react to one or more of the other legumes, mostly to peas. Avoiding all the legumes in the peanut allergic individual is not warranted, and will not change the peanut sensitivity.
-A peanut-allergic subject usually tolerates most members of the legume family 36, 67 (posted April 18th, 1999).
-In the Dec 2001 issue of the J Allergy Clin Immunol, Sicherer SH in his article 'Clinical implications of cross-reactive food allergens' has a guide depicting the likelihood of reacting to a related food based on studies with DBPCFC (challenges). If one is allergic to a legume, the risk of reaction to at least one other legume is 5%. If allergic to a tree nut, the risk of reaction to at least one other tree nut is 37%.144 (posted Jan 29th, 2002)
 

 

 re nuts:

-A questionnaire survey, examination, and blood levels of peanut-specific IgE antibody of a total of 122 patients (63% males; median age 8 years at time of study) with convincing histories of at least one acute reaction (and at least one organ system involved within 60 minutes of ingestion) reported in July 1998 by Sicherer, Burks and Sampson, showed the following:

Conclusions:
 
-In the July 2005 Ann Allergy Asthma Immunol., Goetz DW, Whisman BA, Goetz AD published Cross-reactivity among edible nuts: double immunodiffusion, crossed immunoelectrophoresis, and human specific igE serologic surveys.
OBJECTIVE: To survey serologic cross-reactivities among 7 tree nuts (walnut, pecan, hazelnut, cashew, Brazil nut, pistachio, and almond) and peanut.
RESULTS: Among tree nuts, 2 groups with allergen cross-reactivity were defined: (1) walnut, pecan, and hazelnut and (2) hazelnut, cashew, Brazil nut, pistachio, and almond...the same groupings of cross-reactive tree nuts identified several less prominent nut-nut antigen cross-reactivities between groups and with peanut.
CONCLUSION: With few exceptions (notably limited peanut cross-reactivity with pistachio and walnut), peanut antigens did not serologically cross-react with tree nuts.
Walnut, pecan, and hazelnut form a group of strongly cross-reactive tree nuts. Hazelnut, cashew, Brazil nut, pistachio, and almond form a group of moderately cross-reactive tree nuts. Cross-reactivities between these groups are less pronounced (notably limited cross-reactivity of walnut and pecan with Brazil nut). The strongest cross-reactivities among tree nuts follow botanical family associations: (1) walnut and pecan in the family juglandaceae and (2) cashew and pistachio in the family anacardiaceae.256 (posted Nov 14th, 2005)

See also: "Prevalence of peanut and tree nut (TN) allergy in the US determined by a random digit dial telephone survey."65 (further down)

 
-Pumphrey and coll. in the Sept 1999 Clin Exp Allergy, "explored the pattern of specific IgE to three distantly related nuts in patients of all ages with nut allergy (peanut, hazelnut and brazil nut). From 1994 to 1998: 731 patients (age 7 months to 65 years, median 6.6 yrs) had specific IgE (> 0.35kUA/L) to at least one of these three nuts: 282 had IgE to one nut, 130 to two nuts, and 319 to all three nuts. . . very similar patterns were found in all subgroups. .
Conclusion: the probability of a patient with nut allergy having specific IgE to a particular combination of peanut, hazelnut and brazil nut is similar, whatever their age or sex. The apparent increase in multiple nut reactivity with increasing age may therefore be due to exposure of previously unchallenged sensitivity. The frequency of multiple-nut specificity is sufficiently high that patients should always be tested for allergy to a range of nuts if they have a history of reacting to any nut. " 83 (posted Sept 6th, 1999)

 

 
The natural history of tree nuts
 
-Fleischer et al have an article with the above title in the Nov 2005 J Allergy Clin Immunol. The abstract reads...'Although 20% of children outgrow peanut allergy, the natural history of tree nut (TN) allergy has not been well studied... Two hundred seventy-eight patients with TN allergy were identified. One hundred one (36%) had a history of acute reactions, 12 (12%) of whom had reactions to multiple tree nuts and 73 (63%) of whom had a history of moderate-to-severe reactions. Nine of 20 patients who had previously reacted to a TN passed challenges, so that 9 (8.9%; 95% CI, 4% to 16%) of 101 patients with a history of prior tree nut reactions outgrew their allergy. Fourteen of 19 who had never ingested TNs but had detectable TN-specific IgE levels passed challenges. One hundred sixty-one did not meet the challenge criteria, and 78 met the criteria but declined challenges. Looking at specific TN-IgE cutoffs, 58% with TN-IgE levels of 5 kU(A)/L or less and 63% with TN-IgE levels of 2 kU(A)/L or less passed challenges.
CONCLUSIONS: Approximately 9% of patients outgrow tree nut allergy, including some who had prior severe reactions. Although ideal cutoffs for challenge cannot be firmly recommended on the basis of these data, patients aged 4 years or older with all tree nut-IgE levels of 5 kU(A)/L or less should be considered for challenge.' 255 (posted Nov 14th, 2005)

-In the Dec 2003 issue of Allergy, Rance F. et al. are the authors of Cashew allergy: observations of 42 children without associated peanut allergy. The mean age at diagnosis of cashew allergy was 2.7 years. One in five children (12%) had a prior history of exposure to cashew nuts. Clinically 56% had skin reactions, 25% respiratory, 17% digestive. Eighteen children had associated food allergies: pistachio, seven (same biological family as cashew nuts); egg, five; mustard, three; shrimp, two, cow's milk, one.

Conclusion: The increase in cashew allergy is worrying because it affects young children who may have a reaction without ever having been exposed to cashews..196 (posted Nov 22, 2003)

-According to the publication in the Oct 2005 Arch Dis Child by Davoren M and Peake J. Cashew nut allergy is associated with a high risk of anaphylaxis. The abstract reads: Cashew allergy is an evolving clinical problem. A retrospective chart review of 213 children with peanut or tree nut allergy was undertaken over a 42 month period. Anaphylaxis to cashew nut was more common than to peanut (74.1% v 30.5%). Children with cashew allergy are at risk of anaphylaxis.251 (posted Sept 26th, 2005)

- Clark AT, Anagnostou K, Ewan PW published in Allergy. 2007 Aug;62(8):913-6, Cashew nut causes more severe reactions than peanut: case-matched comparison in 141 children.

Results: A total of 47 children in the cashew group were matched to 94 in the peanut group. There were no differences in clinical features between groups for matching criteria, except asthma (more prevalent in the peanut group). Wheezing and cardiovascular symptoms were reported more frequently during reactions in the cashew compared with the peanut group...

Conclusions: Previous studies show cashew nut can cause severe reactions; this is the first study to show by case-matching that severe clinical reactions occur more frequently in cashew compared with peanut allergy. The nut type which caused the worst reaction to date should be considered when providing emergency medication.274 (posted Aug. 3d, 2007)

 

 re macademia nuts :

-At the Annual AAAA&I meeting in San Diego, Mar 3-8th, 2000 RM Harris,MD reported on a case of macademia nut induced anaphylaxis (macademia nut is an Australian tree nut, originating from macademia intergrifolia, tetraphylla, and their hybrids). Macademia nut oil is reportedly used as a dietary sutbstitute for its health benefits. No testing extracts of macademia were available and skin tests were done using fresh food. A 4+ positive result was obtained not from the outer surface of the nut but from the pulp of the nut. This is the first reported case of macademia nut anaphylaxis, and it points out the need to consider "fresh food testing" when prepared testing resources are not available. (posted March 9th, 2000)102

-At the same meeting, Sutherland M. et al, also reported on anaphylaxis in an 18 year old female after eating a flourless orange cake made with macademia meal. Skin test to raw macademia nut was very positive (wheal of 30mm) one month later and immunolgic immunoblot experiments showed the presence of a protein related partly to hazelnut. The authors recommend that macademia allergic patients should also avoid hazelnuts. (posted March 9th, 2000).
The author had previously published this report in Oct. 1999, in the J Allergy Clin Immunol 1999;104:889-890, and had found no cross-reactivity with peanut protein 103 (posted Dec 10th, 2000)

-In the Sept-Oct 2000 Allergy & Clinical Immunology International , Falk et al report two cases of severe allergic reactions following ingestion of macadamia nuts. The first patient, a 48 year-old woman, had no other nut or peanut allergies but did have a history of asthma and perennial allergic rhinitis, related to cat dander, house dust mite, and grass pollen; she reacted with oral allergy symptoms within minutes after eating 6-8 macadamia nuts, and in 10 minutes developed palpitations, dyspnea, dizziness, flushing and severe itch. Allergy tests showed a strong positive reaction to macadamia nut, but nothing to other nuts and peanut. The second case was a 34 year-old man, with a known allergy to tree nut allergy, including hazelnut, who reacted within minutes after eating one single macadamia nut, with tongue swelling, itchy hot palms, swollen hands, and throat tightness, which resolved without specific treatment. His skin tests revealed a strong allergy to hazelnut, macadamia nut, and smaller, borderline, reactions to Brazil nut and peanut.104 (posted Dec 21st, 2000)

-Another case of allergy to macadamia nuts was reported by Pallares in the Nov. 2000 Annals of Allergy, Asthma and Immunology. No mention of a link with peanut is mentioned, and contrary to a link with hazelnuts mentioned by Sutherland in their report posted above, this patient tolerated hazelnuts.123 (posted June 28th, 2001)

-In the Sept 2005 Pediatr Allergy Immunol , Clark AT and Ewan PW have a publication entitled The development and progression of allergy to multiple nuts at different ages. Seven hundred and eighty four nut-allergic children, with evidence of sensitization (presence of nut-specific IgE and positive skin prick tests (SPT) to peanut, Brazil, almond, hazel and walnut were prospectively enrolled. By 2 years of age at least 19% were multi-sensitized, and 2% multi-allergic. Increasing proportions were exposed to multiple nut types with increasing age (23% at 2 yr to 73% by 10 yr) and greater proportions were multi-sensitized (19% at 2 yr to 86% at 5-14 yr) and multi-allergic (2% at 2 yr to 47% at 14 yr). This study is the first to define the natural history of multiple nut allergies in childhood. New findings are that a large proportion of those aged 0-1 yr with nut allergy are already sensitized (have specific IgE) to multiple nut types, implying in utero or early life sensitization; those who present later in childhood are increasingly likely to be sensitized and clinically allergic to multiple nuts. This is related to increased duration of allergy and exposure to multiple nut types with age. Children with nut allergy should avoid all nut types from the onset. 249 (posted Sept 25th, 2005)

 

re soy:
-From Sweden, a survey on severe food allergies, published in 1999 by Foucard T, and Malmheden Yman I: A study on severe food reactions in Sweden--is soy protein an underestimated cause of food anaphylaxis? 68 The abstract reads as follows:
"Because of a fatal case of soy anaphylaxis occurring in Sweden in 1992, a study was started the following year in which all physicians were asked to report fatal and life-threatening reactions caused by food. The results of the first 3 years of the study are reported here, including results from another ongoing study on deaths from asthma during the same period.
RESULTS: In 1993-6, 61 cases of severe reactions to food were reported, five of them fatal. Peanut, soy, and tree nuts seemed to have caused 45 of the 61 reactions, and four of them were fatal. If two cases occurring less than a year before our study started are included, we are aware of two deaths caused by peanuts and four deaths caused by soy. All four youngsters who died from soy anaphylaxis with asthma were severely allergic to peanuts but had no previously known allergy to soy. In most cases, there was a rather symptom-free period for 30-90 min between early mild symptoms and severe and rapidly deteriorating asthma.

CONCLUSIONS: Soy has probably been underestimated as a cause of food anaphylaxis. Those at risk seem to be young people with asthma and peanut allergy so severe that they notice symptoms after indirect contact. " (posted May 13th, 1999)

 
-In an article published in Revue Française d'Allergologie et d'Immunologie Clinique, Vol. 43, no. 8, 2003, entitiled Allergie à l'arachide, la cacahuète est-elle dangereuse?203 (Peanut allergy: are peanuts dangerous?) Bidat et al. report a reaction that occurred in two children with an almost identical history, aged 9 and 12 years,. They each have asthma caused by environmental allergies, with a known peanut allergy, one reacting also to peas, the other with a dislike of other legumes, and both having a sensitivity to soy (not by skin tests which were negative, but by elevalted soy-specific IgE titres). Neither one has ever knowingly eaten or reacted to soy products. They both had an anaphylactic reaction (asthma with generalized urticaria) after eating lamb meat balls for lunch at school. The lamb meat balls were later reported to have contained a 27% mixture of "vegetable proteins derived from rehydrated soy".
Discussion: -In peanut allergic individuals, sensitization to soy is frequent, (10-53%) but this sensitisation is manifested clinically in only 2.3 to 11% of sensitized children. They underline the risks of soy allergy and such accidents in peanut allergic individuals reported in the Swedish study that is summarized above.(posted Dec 15th, 2003)
 

Link with lupine

-At the annual AAAA&I meeting held in San Diego, Mar 3-8,2000, Kanny reported on Acute asthma due to lupine (lupinus albus, a legume) in a patient allergic to peanuts. The patient has a severe allergy to peanuts, presenting as acute asthma. Lupine flour is present in certain foods, authorized in France in 1997. Skin tests to raw and cooked lupine flour were positive as well as a high specific IgE titre to lupine flour. An oral challenge test was also positive with 965 mg of lupine flour (this quantity is present in 100 grams of bread.) Also published in Rev Med Interne 94. (posted April 2nd, 2000)

-A search of Medline resulted in a few publications re the association of lupine and peanut allergy:

-Hefle, Lemanske, and Bush reported an Adverse reaction to lupine-fortified pasta in 1994 in a 5-year-old girl with peanut allergy, in the form of urticaria and angioedema after ingesting a spaghetti-like pasta fortified with sweet lupine seed flour. The pasta was extracted and used in immunologic studies in patients with peanut sensitivity to determine whether such individuals are at similar risk. Skin prick tests done with lupine pasta extract were positive in 5 of 7 peanut-allergic subjects, also reporting adverse reactions to green peas; RAST tests were also highly positive, and immunologic studies corroborated this allergy in peanut sensitive individuals. 91 (posted Mar 12th, 2000)

-Toxicity to lupine was also reported.

-In Oct 1999, in the J Allergy Clin Immunol, Moneret-Vautrin et al studied the risk of cross-allergy to lupine in patients allergic to peanut and lupine allergenicity. Results: the skin prick test responses with lupine flour were positive in 11 of 24 subjects (44%); challenges positive in 7 of 8 subjects; the major lupine flour allergen (mol. wt, 43kd) is present in peanuts.
Conclusion: the risk of peanut-lupine allergy is high, contrary to the risk with other legumes. The inclusion of 10% lupine flour in wheat flour without mandatory labeling makes lupine a hidden allergen, presenting a major risk of cross-reaction in subjects already allergic to peanut products. A high sensitizing potential can also be postulated for this legume.92 (posted March 12th, 2000)

-In Nov 1999, a group from Spain (Matheu et al) published in the Annals of Allergy, Asthma and Immunology, a case of lupine-induced anaphylaxis. Skin tests and immunological work-up showed a positive skin prick test to lupine and cross-reactivity with other legumes, yet the patient tolerated a peanut challenge as well a a green bean challenge, but not with pea.The authors conclude that "discrepancies were found between the clinical aspect and in vitro study of peanut allergy. Factors determining the wide variability in cross-reactivity among individuals are still obscure." 93(posted March 11th, 2000)

-Occupational allergic symptoms were also reported after exposure to lupine seed flour. 131 (posted Sept 3d, 2001)

 -Monert-Vautrin in a discussion published in the Bull Acad Natl Med 2001;185(5):943-57, again brings up the lupine flour-peanut association, and the increased use of lupine flour in baked goods.140 (posted Jan 14th, 2001)

-In the July 2004 Int Arch Allergy Immunol. Faeste et al have a publication entitled A Case of Peanut Cross-Allergy to Lupine Flour in a Hot Dog Bread. In a case monitored by the Norwegian National Register for Severe Allergic Reactions to Food, a patient with peanut allergy experienced an allergic reaction after eating a particular brand of hot dog bread. Extracts from the hot dog bread and reference material from peanut, lupine and lupine-fortified food products were analysed by immunochemical methods with patient serum and a new polyclonal anti-lupine antibody.
Results: Evidence could be provided that the hot dog bread contained proteins from lupine but not from peanut.
Conclusion: Crossed peanut-lupine allergy can have clinical significance. A peanut-allergic patient reacted against hidden lupine protein in a hot dog bread. Presented with our results, the producer confirmed the use of lupine flour and changed the ingredient list. (posted Aug. 7th, 2004)231
 
-Moreno-Ancillo et al have a publication in the Sept 2005 Pediatr Allergy Immunol entitled Lupine inhalation induced asthma in a child. Here's part ot the abstract:
The ingestion of lupine seed flour has been reported as a cause of allergic reactions. There is some evidence of its allergenic potential after inhalation. An 8-year-old asthmatic child, who was allergic to peanut, was studied in our clinic because he suffered an asthma attack while playing with his brother, who had been eating lupine seed as a snack....The skin tests showed a positive result with Lupinus albus extract, peanut, garbanzo bean, navy bean, pea, green bean, lentil, soy, Olea europea pollen, grass pollen and Plantago lanceolata pollen. The prick-by-prick tests both from dried seeds and those preserved in salt and water were strongly positive. Serum specific IgE antibodies were positive to Lupine albus (1.43 kU/l), peanut (4.32 kU/l), soy (2.15 kU/l), lentil (3.12 kU/l) and garbanzo (0.7 kU/l). After informed consent, salbutamol was well tolerated but the patient had asthma in 5 min of manipulation of the lupine seeds. In our case, reactivity with other legumes was also demonstrated, but only peanut allergy was relevant because boiled legumes were tolerated. It is also notorious that anamnesis is so important to assess the true etiological agents of asthma.250 (posted Sept 26th, 2005)

- In the J Allergy Clin Immunol. 2007 Jul 14 Peeters KA et al published Lupine allergy: Not simply cross-reactivity with peanut or soy.

CONCLUSION: Lupine allergy can occur either separately or together with peanut allergy, as demonstrated by 3 patients who are cosensitized to peanut and lupine. CLINICAL IMPLICATIONS: Lupine flour is allergenic and potentially cross-reactive with peanut allergen, thus posing some risk if used as a replacement for soy flour. 273(posted Aug 3d, 2007)

-Wassenberg J, Hofer M in Ann Allergy Asthma Immunol. 2007 Jun;98(6):589-90, published Lupine-induced anaphylaxis in a child without known food allergy. The authors conclude ' To our knowledge, we describe the first case of an anaphylactic reaction after ingestion of lupine flour in a child without known allergy. In the case of peanut allergy or any anaphylactic reaction without evident cause, especially after industrially prepared food ingestion, lupine should be considered in the list of allergens tested. Lupine is increasingly used in industrially prepared food but is not regularly declared in the composition, leading to difficulties in allergen avoidance.' 275(posted Aug. 3d, 2007)

-In the J Dtsch Dermatol Ges. 2007 Sep;5(9):who 774-6, Brennecke S et al published Anaphylactic reaction to lupine flour. The authors report a case of a 52-year-old woman developed facial and mucosal edema, followed by dizziness and shortness of breath a few minutes after ingestion of a nut croissant containing lupine flour; she required emergency care. Allergy diagnostic tests revealed a total IgE of 116 kU/l, a highly elevated concentration of IgE specific for lupine seed (42.9 kU/l) and birch pollen IgE of 2.57 kU/l. Skin prick test with native lupine flour was strongly positive. Allergy against lupine seeds may develop de novo or via cross-reactivity to legumes, particularly peanuts, the latter being detectable in up to 88% of cases, founded on a strong sequence similarity between lupine and peanut allergens. In our patient, no cross-reactivity could be detected indicating a rare monovalent sensitization to lupine flour. Treatment consists of avoidance of lupine flour-containing products. Patients with proven peanut allergy should also avoid lupine flour because of the major risk of cross-reaction. (posted Oct 6th, 2007) 279

 
 
 
What about sesame seeds and oil?
 

-Birnaum and coll. presented a case of a 52 year old woman having had hives on several occasions after eating sesame seeds, Indian bread, Chinese, Greek or Indian meals in restaurants, and facial swelling after local application of creams which were found to contain sesame oil. She tested positive to sesame on skin tests but not by RAST. (AAAA&I Annual Meeting, 1997) (posted Feb 13th, 1999)

-Levy and coll. made a survey of sesame allergy in Israel by doing RAST tests and skin tests on 234 patients referred for food allergy evaluation during 1995-1996. RAST test results: 13 (5.5%) were positive to sesame. Of patients referred to a food allergy clinic with a history of angioedema, 15 of 61 were found to be skin test positive. Six patients from this group, aged 14 months to 26 years, were open challenged with sesame. Five were positive: urticaria (5), rhinitis/conjunctivitis (3), nausea and tachycardia (1). (AAAA&I Annual Meeeting, 1998) (posted Feb 13th, 1999)

-Sesame allergy, although less common than peanut allergy, can be every bit as severe. Sesame is used extensively in the food industry, and the seeds present a danger because of their versatility 51. With the increasing demand for vegetarian food, the consumption of vegetable burgers as an alternative to beef burgers has now become widespread 52.Sesame seed and sesame seed oil contain masked allergens of growing importance 53and a cause of occupational asthma54. (posted Feb 13th, 1999)

NB. There was no mention of sesame being related to peanut in any of these papers, but:
  • allergy to kiwi, poppy seeds, and/or sesame seeds often occurs in patients with a simultaneous sensitization to nuts and flour 45.
  • A review of the database of results of allergen skin tests by the dept of Allergy, Royal Children's Hospital, Melbourne, Australia during 1990-96, sensitization to peanut was found in 1601 infants and children, to a tree nut (almond, brazil, cashew, hazelnut, or walnut) in 590; 491 to both: representing a combined prevalence of sensitization of at least 0.2%. Sensitization occurred early: 920 children aged under 24 months were sensitized to peanut and 270 to a tree nut. But 531 children were found allergic to sesame seed, higher than the number sensitized to any tree nut; sensitivity occurred in 60% of the children (317) before age 2. 55 (posted Feb 13th, 1999)
  • A comment by Dr Rhoda Kagan, submitted in Oct. 1998. when this article was started, was posted in the section on 'peanut oil'. It is now added to this section on sesame:
    Sesame oil, derived from sesame (which is not a nut) used frequently, will often contain considerable amounts of peanut proteins.
 
-In the Nov 24th, 2001 The Pharmaceutical Journal, vol. 267, Maggie Spirito Perkins has an article entitled, Raising Awareness of Sesame Allergy, where she states....'it is not uncommon for sesame allergy to co-exist with peanut allergy.' (posted Nov 20th, 2002)

 

-In the Aug 2003 Pediatr Allergy Immunol, Binson et al published The pattern of sesame sensitivity among infants and children. ...although the main clinical manifestation was urticaria/angioedema, anaphylaxis was the presenting symptom in 30% of cases, all of them younger than one year. 70% were found to be allergic to other foods, and other atopic diseases were identified in 78%. These patients outgrew their allergy within 1-2 years....Early exposure may cause sesame to share eventually the same 'noteriety and fate' as peanut . No mention is made of a relationship between sesame and peanut. 189 (posted Aug 15th, 2003)
 

-In the Ann Allergy Asthma Immunol. 2006 Oct;97(4):443-5, Beausoleil, JL, and Spergel JM have a publication entitled 'Late diagnosis of tree nut and sesame allergy in patients previously sensitized but tolerant to peanut.' Quoted from their abstract:

Recent studies have indicated that tolerance to peanut can occur in patients with a history of peanut allergy. Tree nut and sesame allergies have been reported to occur at increased incidence in patients with peanut allergy. Although the coexistence may be simply due to a predisposition to food allergy in these individuals, cross-reactivity has been demonstrated between peanut and tree nuts and between peanut and sesame seed. OBJECTIVE: To describe 3 patients previously sensitized but tolerant to peanut who were subsequently diagnosed as having either tree nut or sesame allergy. METHODS: All the patients had a clinical history of peanut sensitivity and underwent follow-up peanut skin testing to commercial extracts using a bifurcated needle followed by a graded peanut challenge. One patient had a previous positive radioallergosorbent test reaction to sesame and underwent a graded sesame challenge. RESULTS: All the patients had negative peanut challenge results. Two patients subsequently had exposure to tree nuts at home and had systemic reactions and positive skin test reactions to the incriminated tree nut. One patient had a positive challenge reaction to sesame. CONCLUSION: Demonstration of tolerance to peanut may falsely reassure patients and physicians that patients no longer need to avoid tree nuts or sesame. Tree nut and sesame allergies can exist or develop in patients despite the development of tolerance to peanut. (posted Nov 1st, 2006)

 
 
What about sunflower seeds and oil? 
-Sunflower seeds have been reported causing severe allergic reactions in sensitive individuals48 Sunflower oil is not allergenic to sunflower seed-sensitive patients 49.
-Hefle et al at the AAAA&I Annual Meeting in 1997 presented a paper about their experience in the identification and characterization of sunflower seed allergens: scant knowledge so far. Relationship of sunflower pollen and other pollens of the Compositae family, including short ragweed50(posted Feb 13th, 1999)

 

 
What about coconut?
 
-In the June 1999 J Allergy Clini Immunol, issue, Teuber et Peterson report a "Systemic allergic reaction to coconut (Cocos nucifera) in 2 subjects with hypersensitivity to tree nut and demonstration of cross-reactivity to legumin-like seed storage proteins: new coconut and walnut food allergens.". . . The reduced coconut protein. . . was previously shown to be immunologically similar to soy glycinin.They conclude that coconut allergy in patients with tree nut allergy is rare; these are the first two patients ever reported, and therefore there is no general indication to advise patients eith tree nut allergy to avoid coconuts. 70. (posted June 14th, 1999))
 
 

Identification of the allergenic peanut proteins

 
-According to Clarke and coll., in the Oct. 1998 Clinical Experimental Allergy, there are 19 peanut proteins. . . the major ones being Ara h 1 and Ara h 2 to which 70% of subjects reacted. Their study, however, highlights the diversity of the peanut allergens, and because the percentage of cases with sensitivity to a 15kDa protein was found to be higher in patient groups with severe reactions to peanut, they conclude that diagnostic extracts containing a high proportion of this 15kDa component may aid in diagnosis39.
 
-". . . following our characterization of the two peanut allergens Ara h 1 and Ara h 2, we have isolated a cDNA clone encoding a third peanut allergen, Ara h 3. . . recognized . . .by serum IgE from approximately 45% of our peanut-allergic patient population . . . " 57 (posted March 12th, 1999)
 
-Kleber-Janke, and coll. report in Int Arch Allergy Immunol Aug 1999, that sera of 40 peanut-allergic individuals detected at least one of six identified recombinant allergens which can be used to establish individual patients' reactivity profiles. A comparison of these profiles with the clinical data will possibly allow a further insight into the relationship between clinical severity of the symptoms and specific IgE levels toward the six peanut allergens. 82 (posted Sept 6th, 1999)
-In the Apr 2004 Clin Exp Allergy, Koppelman SJ et al have a publication entitled Relevance of Ara h1, Ara h2 and Ara h3 in peanut-allergic patients, as determined by immunoglobulin E Western blotting, basophil-histamine release and intracutaneaous testing: Ara h2 is the most important peanut allergen....'previously identified peanut proteins with molecular weights of somewhat smaller than 15 kDa may be important allergens as well....'215 (posted April 10th, 2004)

-Current developments in peanut allergy is the title of a pulication in the June 2006 Curr Opin Allergy Clin Immunol. by Palmer K, Burks W. Citing the abstract, 'Peanut sensitization may be both a Th1- and Th2-driven process, and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) may play a role in regulating the response intensity. Preliminary work shows that the food matrix is important in the immune response to peanut and that purified peanut allergens may have little intrinsic stimulatory capacity. Studies characterizing peanut allergens have revealed Ara h 1 and Ara h 2 as the most potent allergens, but Ara h 3 may be more allergenic than previously thought. There appears to be a relationship between the diversity of IgE-binding patterns and the severity of clinical symptoms. 259 (posted May 26th, 2006)

- In Clin Exp Allergy. 2007 Jan, Peeters et al published 'Does skin prick test reactivity to purified allergens correlate with clinical severity of peanut allergy?'The authors concluded: Ara h 2 and Ara h 6 appeared to be more potent than Ara h 1 and Ara h 3. Both SPT reactivity to low concentrations of Ara h 2 and Ara h 6 and to higher concentrations of Ara h 1 and Ara h 3 were shown to be indicative of severe symptoms. (posted May 26th, 2007)


-  In Clin Exp Allergy. 2007 Aug;37(8):1221-8, Flinterman AE et al in their study concluded that Children with peanut allergy recognize predominantly Ara h2 and Ara h6, which remains stable over time. 272 (posted Aug 3d, 2007)

 

 
Effect of roasting on peanuts
 
-According to a study reported in the Oct. 2000 J Allergy Clin Immunol, thermal processing such as roasting, may play a part in enhancing the allergenic properties of peanuts. 99 (posted Oct. 29th, 2000)
 
-In the June 2001 J Allergy Clin Immuno, Beyer et al reported on the "Effects of cooking methods on peanut allergenicity". Their concluson is that the methods of frying and boiling peanuts, as practiced in China, appear to reduce the allergenicity of peanuts compared with the method of dry roasting practiced widely in the United States. Roasting uses higher temperatures that appararently increase the allergenic properties of peanut proteins and may help explain the difference in prevalence of peanut allergy observed in the the two countries. 120(posted June 10th, 2001)
 
-Because of the serology of peanut allergy seeming to be different in vaious parts of the world, a study from The Netherlands showed that peanuts of different varieties contain similar proteins, including Ara h 1 and Ara h 2. 113 (posted Feb. 15th, 2001)

 

-See CBS news 'Cracking a peanut's deadly secrets' and video on research being done on some 14,000 different types of peanuts. (posted Dec 4th, 2002)
 
  -Maleki et al in the July 2003 J Allergy Clin Immunol have an article entitled The major peanut allergen, Ara h 2,
functions as a trypsin inhibitor, and roasting enhances this function.
Results: Ara h 2 purified from peanuts is homologous to and functions as a trypsin inhibitor. Roasting caused a 3.6-fold increase in trypsin inhibitory activity. Functional and structural comparison of the Ara h 2 purified from roasted peanuts to native and reduced Ara h 2 from raw peanuts revealed that the roasted Ara h 2 mimics the behavior of native Ara h 2 in a partially reduced form.
Conclusions: The data indicate that thermal processing might play an important role in enhancing the allergenic properties of peanuts. Not only has it previously been shown to affect the structural and allergic properties of peanut proteins but also, for the first time, the functional characteristics of an allergen. These structural and functional alterations are likely to influence the allergenicity of peanuts.181 (posted July 12th, 2003)

 

-Maleki et al. have another publication in the July 2003 J Agric Food Chem: Linking peanut allergeniciy to the processes of maturation, curing, and roasting. Besides roasting (as reported above) that seems to have an effect on allergenicity, Other processes (maturation and curing) were evaluated.

Results showed that mature roasted peanuts exhibited a higher IgE binding and advanced glycation end adducts (or AGEs) than immature roasted peanuts.... so did curing at higher temperatures.187 (posted Aug 3d, 2003)

 
-In the Revue française d'allergologie et d'immunologie clinique 2003 - Volume 43 - Numéro 8 - pp: 486-491, Mondoulet et al. have an article entitled Influence des procédés thermiques sur l'allergénicité de l'arachide (Influence of thermal processing on the IgE binding capacity of peanut allergens). The authors found that roasting peanuts does not modify their allergenicity while boiling decreases it considerably. This decrease of boiled peanut allergenicity comes from a loss of some allergens into the boiling water. It may also be due to structural modifications of peanut proteins that occur in boiling water. 201 (posted Dec. 14th, 2003)
 
-At the Annual AAAA&I meeting held in San Francisco, Mar 19-23, 2004, Maleki et al had a poster entitled Roasting may alter the IgE binding epitopes and sensitizing ability of peanut allergens. Their results indicate that many of the IgE binding, digestion resistant fragments are modified with sugar by-products that occur as a result of roasting. Also, in some occasions roasting alters the IgE-binding fragments that survive digestion, and therefore, quite possibly, the allergenic epitopes. These altered epitopes may be responsible for in vivo data that demonstrate mice are more likely to be sensitized to roasted than raw peanuts.220 (posted April 28th, 2004)

 

-In the July 2004 J Agric Food Chem. Chung SY, Maleki SJ, Champagne ET. have a publication called Allergenic properties of roasted peanut allergens may be reduced by peroxidase. The authors have shown that a significant decrease was seen in the levels of the major allergens, Ara h 1 and Ara h 2, in roasted peanuts after peroxidase treatment...helping to reduce the allergenic properties of roasted peanut allergens.230 (posted July 20th, 2004)

 

-Kopper et al published Peanut protein allergens: the effect of roasting on solubility and allergenicity in the Jan 2005 Int Arch Alleergy Immunol: "Progressive roasting of peanuts results in a significant decrease in protein solubility...The presence of these insolubilized proteins provides a continuous source of major allergens to the gastrointestinal mucosal immune system." (posted April 22nd, 2005)243

  

Immunotherapy (hyposensitization or desensitization)

-The question of desensitization (immunotherapy) has been brought up many times because of the increasing problem of peanut allergy, to try and help the patients diminish their allergy to peanuts, one reason being the large number of accidental ingestions. Over the years, trials have been published, the last one by Nelson, Bock et al, in June 1997. They recruited 12 patients with immediate hypersensitivity to ingestion of peanuts. Half were treated with injections of peanut extract: a maintenance level of tolerance was first achieved by a rush protocol, then maintained with weekly injections for at least a year. The other six were untreated control subjects. All patients underwent double-blind, placebo-controlled, oral peanut challenges initially, after approximately 6 weeks, and after 1 year. Only three patients remained tolerant of the full maintenance dose. The increased tolerance to oral peanut challenge was maintained in the three subjects who received full maintenance doses, but there was partial or complete loss of protection in the patients who required dose reduction because of systemic reactions (allergic symptoms following desensitization injections). The authors conclude that injections of peanut extract increase the tolerance of patients with peanut allergy to oral ingestion of peanuts. Injections result in repeated systemic reactions in most patients, even during maintenance injections. For clinical application of this method of treatment, a modified peanut extract is needed3.

In summary: at this point in time, desensitization for peanut allergy, although promising, is not recommended because of the dangers involved during treatment in the form of severe reactions. More research is needed before such treatment can be considered.
-In a communication in the Nov 1998 issue of the Canadian Journal of Allergy & Clinical Immunology, Dr. Joseph Greenbaum recounts his experience with food immunotherapy, including one case of peanut immunotherapy. Although the author was encouraged with the results, the editor of the journal, Dr. Gordon Sussman, warns in his note, that "although well tolerated and appearing efficacious in this report, several pitfalls and possible dangers of this type of treatment need to be addressed...It is impossible to assess efficacy without a control population...The major concern is patient safety. Food immunotherapy may be an extremely dangerous procedure and can create a false sense of security. Several severe reactions and deaths have been reported using food immunotherapy, even in well-designed studies. Food immunotherapy, as outlined in these case studies sets a dangerous precedent which could have disastrous consequences. We agree that the treatment of food anaphylaxis using avoidance is not ideal -- but it is presently the only proven treatment we have. Let's work together to develop a better treatment through properly designed research protocols that give us reliable and reproducible information." 40. (posted Dec 8th, 1998)
 
 
-"Scientists develop vaccine strategy for peanut allergy" is a commentary by Scott Gottlieb, from New York, published in the April 3d, 1999 British Medical Journal 60, referring to the work of Dr Kam Leong, and associates at the Johns Hopkins School of Medicine in Baltimore, reported in Nature Medicine 66 "Researchers believe that they may be close to developing a new strategy to combat anaphylactic allergies - such as the increasingly common allergy to peanuts- in which doctors induce tolerance using an oral formulation containing a gene from the offending allergen. . .the DNA from peanut was administered orally to mice. . . the severity of anaphylaxis was blunted. . .the findings are a long way from being used in clinical applications." . . "The immune system of mice is also quite different from that of man. . . One can envision that this model would be an interesting approach to generate mucosal immunity for a variety of allergens" said Dr Leong. (posted April 5th and 18th, 1999)
 
To see an example how such research could be interpreted differently:
BBC News on line, April 1st, 1999
Also, relevant news stories:
Food producers play safe with nuts(20 Jul 98 | Health .
Food allergy clinic opens for mums-to-be (29 Jun 98 | Health.
Women can 'pass peanut allergy to their children' (01 Apr 99 | Health.
 (posted April 6th, 1999)
 

-In the Aug. 1999 J Allergy Clin Immunol, Hong, Michael, Fehringer and Leung report on their experience with a pepsin-digested peanut extract that could eventually be used in desensitization. Previous immunotherapy (desensitization) studies of peanut-allergic patients (one of which is summarized above) showed a high incidence of systemic allergic reactions during treatment, making such treatment very dangerous, and not practical at this point in time. Researchers are constantly looking for a modified peanut extract to lower allergenic properties (in other words, resulting in much less systemic reactions.) Laboratory evaluation of this extract suggests that it may be useful in peanut immunotherapy because "pepsin digestion eliminates IgE reactivity but maintains T-cell reactivity" (less systemic reactions yet still effective)81 (posted Aug 23d, 1999)

-Bannon et al, in their Jan 2001 article in Int Arch Allergy Immunol: entitled Engineering, Characterization and in vitro Efficacy of the Major Peanut Allergns for Use in Immunotherapy, report their results with modification of the peanut proteins and conclude that ..."These modified genes and proteins should provide a safe immunotherapeutic agent for the treatment of peanut allergy.".119

- Wild LG and Lehrer SB, in the Jan 2001 Curr Allergy Rep, (posted in Medline only in April 2002,!?) summarize the ongoing research on desensitization in food allergy in their artilcle Immunotherapy for food allergy. "With better characterization of allergens and better understanding of the immunologic mechanism, investigators have developed several therapeutic modalities that potentially are applicable to the treatment and prevention of food allergy. Therapeutic options currently under investigation include peptide immunotherapy, DNA immunization, immunization with immunostimulatory sequences, anti-IgE therapy, and genetic modification of foods. These exciting developments hold promise for the safe and effective treatment and prevention of food allergy in the next several years."153 (posted April 29th, 2002)

-See: Effect of Anti-IgE Therapy in Patients with Peanut Allergy. (discussed below in the section on "Recent studies" posted Mar 28th, 2003.

-From the San José Mercury News, in the Nov 2004 on line edition of Allergy, lead researcher Dale T. Umertsu describes its canine vaccines, the first to block food allergens in an animal larger and more complex than a mouse...Researchers manipulated the immune system of the dogs to mimic a human allergic response. Before being vaccinated, the dogs could barely eat one peanut before breaking out in a skin rash. But 10 weeks after immunization, the animals devoured, on average, more than 37 peanuts before developing symptoms....This vaccine could one day enable millions of food allergy sufferers to fearlessly bite into a peanut butter sandwich. The study appears in the Feb 2005 Allergy entitlled, Allergen immunotherapy with heat-killed Listeria monocytogenes alleviates peanut and food-induced anaphylaxis in dogs. Heat-killed Listeria monocytogenes (HKL) potently stimulates interferon (IFN)-gamma production in CD4 T-lymphocytes, and when used as adjuvant for immunotherapy, reduces immunoglobulin (Ig)E production and reverses established allergen-induced airway hyperreactivity (AHR) in a murine model of asthma. We asked if such treatment could decrease established peanut-induced anaphylaxis.. in highly food-allergic dogs.The dogs were then vaccinated once subcutaneously with peanut or milk and wheat with HKL emulsified in incomplete Freund's adjuvant.

Conclusions: Thus, HKL plus allergen treatment markedly improved established food allergic responses in dogs, suggesting that such an immunotherapy strategy in humans might greatly improve individuals with food allergy and anaphylaxis.240 (posted Jan 15th, 2005)

-Dr Wesley Burks, chief of the division of Pediatric Allergy and Immunology at Duke University Medical Center, is working on desensitization (similar to the above Nov. 1998 report, by Dr J. Greenbaum, commented by Dr Sussman) by progressively administering increasing quantities of peanut protein (2005). See Fighting Food Allergies. (includes audio) (posted April 30th, 2005).

-More on Dr Wesley Burks's encouraging study : Can Deadly Peanut Allergies Be Cured ? (ABC News, including a video) June 23d, 2006) (posted June 26th, 2006)

-At the annual AAAA&I meeting held in San Diego,CA in Feb 2007, Dr Burks' group presented Oral Peanut Immunotherapy for Peanut Allergic Patients. It's presumably a report of the work posted above in 2005. The study included children with a convincing history of peanut allergy and an IgE >7kU/L . The study protocol was divided into three phases: a modified rush initial day of multiple doses (0.1 mg to 50mg peanut doses), a build up phase of daily doses, increasing the dose every 2 weeks, and a daily maintenance phase of up to 18 months (dose of 300 mg peanut protein). An open food challenge to peanut flour (7.8 gms) was performed at the end of the study...Eight children completed the initial protocol and have undergone an open food challenge. Seven tolerated the maximum dose in the challenge. One subject had mild allergic symptoms treated with antihistamines after 4.2 gms of peanut flour. During the modified rush phase most subjects had mild symptoms but some subjects had more significant, systemic allergic symptoms. Adverse events related to the build up or maintenance phases were minimal. The initial mean peanut-specific IgE was 62.64kU/L with a significant decrease at 24 months to 21.92 kU/L. The authors conclude: ...peanut oral immunotherapy is safe and effective for decreasing the risk of a significant reaction with peanut ingestion... and a peanut-specific IgE level decrease. (posted May 6th, 2007)

-In the Nov 2005 J Allergy Clin Immunol, Enrique E et al have a publication entitled Sublingual immunotherapy for hazelnut food allergy: a randomized, double-blind, placebo-controlled study with a standardized hazelnut extract. Efficacy was assessed...after 8-12 weeks of treatment.
Results: Systemic reactions were observed in only 0.2% of the total doses administered. Mean hazelnut quantity provoking symptoms increased from 2.29 g to 11.56 g in the active group versus 3.49 g to 4.14 g in the placebo group. Moreover, almost 50% of patients who underwent active treatment reached the highest dose (20g), but only 9% in the placebo.
Conclusion: Our data confirm significant increases in tolerance to hazelnut after sublingual immunotherapy....258 (posted May 7th, 2006)

-In the Dec 2005 Curr Opin Allregy Clin Immunol, Pons, Palmer and Burks published Towards immunotherapy for peanut allergy.

Taken from the abstract: Based on extensive characterization of food allergens and a better understanding of the immunological mechanisms underlying allergic disease, promising therapeutic modalities for food allergy treatment and prevention are being developed. RECENT FINDINGS: Immunotherapeutic strategies include peptide immunotherapy, mutated protein immunotherapy and DNA immunization, which all strive to decrease the deleterious Th2 response. Another approach already in clinical trials for peanut allergy is the anti-IgE therapy which prevents circulating IgE from binding to effector cells, consequently decreasing clinical symptoms after peanut ingestion. In order to be applicable, these strategies must be well tolerated, inexpensive and easily administered. Realistic treatment options would likely involve a combination of different approaches.254 (posted Nov 11th, 2005)

 

Dealing with peanut allergy:

position statements.
 
More on anaphylaxis:
Obviously, there were many responses to this publication (all, by the way, accessible) by Toni Wolff, Jonathan Hourihane, June Abay, Pamela Ewan, et al ). Here are some highlights:
 
-This remains a difficult and touchy question.
-There is no question that epinephrine administered by means of a subcutaneous or intramuscular injection is the treatment of choice for anaphylaxis;84, 85, 62 Other medications such as antihistamines, inhaled asthma medications, or steroids, that subsequently may be given by physicians in treating anaphylaxis should not be regarded as first-line medications. (Position statement 34 of the AAAA&I (American Academy of Allergy, Asthma and Immunology) Board of Directors: Anaphylaxis in Schools and other childcare settings) This position of the AAAA&I, an endorsement of a consensus statement originally drafted by the Canadian Society of Allergy and Clinical Immunology (CSACI) with its provincial affiliates and allergy organizations in 1996, further states "epinephrine is the first drug that should be used in the emergency management of a child having a potentially life-threatening allergic reaction. . .
-In patients who have had anaphylactic reactions, it is recommended that epinephrine be given at the start of any reaction occurring in conjunction with exposure to a known or suspected allergen. In situations where there has been a history of a severe cardiovascular collapse to an allergen, the physician may advocate that epinephrine be administered immediately after ingestion of the offending food and before any reaction has begun.Anaphylaxis in schools and other childcare services (CSACI) (now available in pdf format).
 
-The CSACI consensus further states in the Appendix 2 section dealing with the Management of Specific Allergens, specifically peanut, re: "Suspected or actual contact with a known allergen": The child should be under close and constant supervision for 4 hours after the suspected ingestion. Administer the epinephrine auto-injector as soon as the child develops any one of the following symptoms and take him or her immediately to hospital. If no serious reaction occurs within 4 hours it is unlikely to occur.
-The Allergy Section of the Canadian Pediatric Society, in 1994 had published a similar position statement in the Journal of the Canadian Medical Association: Fatal anaphylactic reactions to food in children. Here is part of the statement:
The goals of pharmacologic treatment are to maintain airway patency and systolic blood pressure. An epinephrine injection is the initial treatment of choice for anaphylaxis: it suppresses release of mediators of inflammation from mast cells and basophils, and it directly decreases vasodilation, oedema and bronchoconstriction. Epinephrine must be administered promptly at the first warning symptoms, such as itching or swelling of the lips or mouth, tightening of the throat or nausea, and before respiratory distress, stridor or wheezing occur.
 
-See also:
-Dr Hugh Sampson in an editorial in the British Medical Journal in April 1996, entitled "Managing peanut allergy" and in his Dec. 1997 publication on Food Allergy in the JAMA suggests that "food allergic individuals at increased risk for severe anaphylactic reactions --that is, patients with histories of previous severe anaphylactic reactions or asthma, or both -- should be provided with self injectable adrenaline 11 (such as Ana-Kit or Epi-Pen) and an antihistamine (liquid diphenhydramine (Benadryl™) or hydroxyzine (Atarax™).46 Dr Sampson further states "Laryngeal or pulmonary symptoms following an inadvertent food exposure should be treated immediately with epinephrine.63 In the June 1999 issue of the J Allergy Clin Immunol, Dr Sampson repeats this same indication for epinephrine, and adds that "it must be stressed to all caregivers that treatment must be initiated without delay in high-risk patients, and they must be transported to an emergency facility for further evaluation and treatment. . ." 72
 
-In the Aug. 1999 J Allergy Clin Immunol, Yocum and coll. report on "Epidemiology of anapyhylaxis in Olmstead County: A population-based study." 87 To classify an event as anaphylaxis, they required:
-one symptom of generalized mediator release, such as flushing, itchiness or numbness or tingling of lips, armpits, hands or feet, generalized itchiness, hives or angioedema (oral or throat swelling), and red, itchy eyes,
-and at least one of the following additional symptoms:
  • oral and gastro-intestinal symptoms such as: oral mucosal itchiness, oral swelling, swollen tongue, palate or throat, nausea, vomiting, difficulty swallowing, abdominal cramps or diarrhea.
  • respiratory symptoms: rhinitis (sneezing, runny nose) throat tightness, cough, wheezing, hoarseness, change in voice, shortness of breath, throat swelling, cyanosis
  • cardiovascular symptoms: chest pain, irregular pulse, lowered blood pressure, rapid pulse, fainting, slow pulse, orthostasis (unsteadiness or dizziness), seizures and shock.

-In the editorial entitled, 'What should we be doing for children with peanut allergy' by Hugh A Sampson, published in the Dec. 2000 Journal of Pediatrics, he has this to say: "The findings reported by Vander Leek et al105 i.e. having found that the symptoms in the initial allergic reaction are not predictive of subsequent reactions and that patients who experience minor symptoms initially may be as likely to develop life-threatening symptoms during subsequent reactions as patients who experience more severe intial reactions... ALL patients with peanut allergy need self-injectable epinephrine immediately available to treat future, unavoidable reactions."107 (posted Jan 6th, 2001)

-In Europe, the attitude is somewhat different. Dr Etienne Bidat, Paris and Boulogne, on the AllergieNet website, in Prise en charge du choc anaphylactique (Management of anaphylactic shock) suggests the following:

-"Anaphylaxis is a major emergency in allergy, there is no time to waste; intervention must be immediate. Anaphylactic shock is often preceded by signs that need immediate treatment. These signs may be discreet, and may begin during or soon after a meal, and treatment should be initiated immediately. . . rather that wait for progression towards anaphylaxis!
-These first signs can be: itchiness or swelling of lips, hives, sneezing or runny nose, red eyes or abdominal cramps. At this point, an antihistamine is advised taken orally and medical help sought.
-At times, the symptoms may be more dramatic as: cough, wheezing, or vomiting in addition to the above-mentioned signs. An antihistamine must be taken as well as a bronchodilator for the respiratory symptoms. In any case, if these signs are not rapidly ameliorated or stabilized by the treatment, cortisone taken orally is suggested and medical help sought immediately. If the reaction is more severe, with general malaise, loss of consciousness associated with an asthmatic episode, injection of epinephrine is the first-line treatment." (posted Sept 24th, 1999)

-According to Moneret-Vautrin and Kanny's article entitled "Anaphylaxis in schools and other child-care settings --the situation in France" in the May 1999 Allerg Immunol (Paris), things are changing. The "Projet d'Accueil Individualisé" an emergency health care form is being used by allergologists, and countersigned by the treating physician in charge of the School Health Department, with description of symptoms, directives and treatment to be used. They state that "epinephrine is the first drug to be used."86 (posted Sept. 24th, 1999)

-In England, treatment of an allergic reaction to food is similar. Inhaled epinephrine, now withdrawn in Europe, was often used. Antihistamines are recommended for mild, urticarial reactions. Epinephrine is reserved for large dose ingestion of the implicated food and reactions that are not settling after 5-10 minutes, with the patient taken to a medical facility. Reactions may settle with antihistamines but epinephrine should be administered if the reaction seems to progress. (posted Sept 24th, 1999)
 
-In the Jan 13, 2001 issue of the Lancet, P W Ewan, and AT Clark (from the Dept of Allergy and Clinical Immunology, Addenbrooke's Hospital, Hill's Road, Cambridge, UK) reported in their article entititled 'Long-term prospecive observational study of patients with peanut and nut allergy after participation in a management plan'. The abstract reads as follows:

"Current advice is poor --doctors give an epinephrine injector to patients, without training or advice on nut avoidance--so that further reactions are common and deaths occur. We devised and assessed a management programme providing advice on nut avoidance and emergency medication. Unselected referrals with confirmed peanut or tree-nut allergy were recruited. Severity of the allergy was graded 1-5 and emergency medication allocated accordingly, oral antihistamine with or without inhaled or injected epinephrine. Patients, parents, and school staff received verbal and written advice on nut avoidance as well as training in recognition and self-treament of reactions, with a written treatment plan. At follow-up (more than 13,610 patient months) retraining was given and details of further reactions obtained." Their findings are somewhat different from figures mentioned in the editorial by Hugh A Sampson (see above, posting of Jan 6th, 2001):

-88 (15%) of 567 patients had a follow-up reaction of reduced severity.
-62 of 88 were mild (grades 1-3, mainly cutaneous) and
-49 patients used oral antihistamine,
-6 inhaled adrenaline
-10 took no treatment
-12 of 12 patients with a moderate follow-up reaction improved after inhaled epinephrine.
-Only 3 (0.5%) of 567 patients, aged 27-40 years, had a severe follow-up reaction (involving dyspnea) [or shortness of breath] compared with -12% initially.
-Only one of 567 patients changed from a mild index reaction to a severe follow-up reaction.
-Patients with a moderate/severe (grade 4-5) reaction were older (median 18 years vs 9 years) and 9 of 26 received injected epinephrine which was always effective.
-85% of patients had no further reactions.
-Severity was related to the amount of nut (or peanut) eaten.
Interpretation: "Self-treatment was effective (inhaled epinephrine for early laryngeal oedema and an epinephrine injector for severe reactions) but provision of this treatment, including who should carry epinephrine, required assessment of allergy severity. Our management plan was effective, and our results indicate that patients should be referred to specialist allergy centres for advice on nut avoidance."108
 
-In the Lancet published later, in May 2001, Bauge, Cooper, et al. sent a letter to the editors, Management of peanut allergy, in which they comment, in part:
"We are unsure about parts of the study....exact duration...concern that there is no control group...without such a group, results would be limited....presentation of the results are confusing. We understand the imporance of this study and the apparent usefulness of education and advice.
-Reply of the authors (Ewan and Clark): the duration of the study was 7 years and follow-up reached 13,610 patient-months. 21 of 23 patients with moderate reactions used an epinephrine inhaler for mild laryngeal oedema, which was always successful. Nine of 26 patients with a moderate or severe reaction received an epinephrine injection...all patients are accounted for....re control group: acknowledged as a study limitation. A control group of patients cannot justifiably be left to fend for themselves when the frequency of follow-up reactions are so high. Our study underscores the importance of providing a complete management package for nut allergy, including detailed advice on nut avoidance together with a treatment plan and medication for self-administration in case of further reactions. (posted belatedly Nov 2, 2002)

 

 
 
Dosage of epinephrine
 
Adults:
Epinephrine USP 1:1000, 0.3 mg (0.3 mL) In the Nov 2001 J Allergy Clin Immunol , Estelle Simons studied the absorption of epinephrine in adults and recommends "the intramuscular injection into the thigh as the preferred route and site of injection of this life-saving medication in the initial treatment of anaphylaxis."145 (posted Jan 31st, 2002)
 

Children:

The dosage recommended is 0.01mg / kilo. What is available today is Epipen (which delivers 0.3mg or 2ml. of a 1:1000 concentration) and Epipen Jr. (delivering 0.15mg or 2 ml of 1:2000 concentration). Ana-Kit (apparently no longer manufactured) delivered 0.05, 0.1, 0.15, 0.2, or 0.3 mg, and dispensed for infants as young as 4 months. Twinject is available since 2005, in the identical dosages, but with a second dose if needed. (see below)

-The Canadian Pediatric Society in their 1994 paper entitled Fatal anaphylactic reactions to food in children. recommended the following dosage schedule: EpiPen Jr for children weighing 12-25 kg and 0.3 mg IM (regular dose) for children > 25 kg.

-The rule that is mostly now followed is the recommendation in The Canadian Society of Allergy and Clinical Immunology paper published in 1998, Anaphylaxis in schools and other childcare services (now available in pdf format):
-EpiPen Jr. for those weighing 15 kg (33 lb.) or less.
-EpiPen for those weighing more than 15 kg (33 lb.)
-When dealing with infants, a problem arises of potentially overdosing the patient, so the practice was prescribing an epinephrine ampule along with a sterile syringe/needle and instructions. The question has been raised, "When hands are shaking and a needle is exposed, will nervous parents end up dosing epinephrine from an ampule correctly?" Estelle Simons published her study in the Dec 2001 J Allergy Clin Immunol of a group of 18 parents who were "given written instructions to draw up 0.90ml of epinephrine. They were timed and results compared with a control group that comprised 18 resident physicians, 18 general duty nurses and 18 emergency dept nurses.
The conclusions were: Most parents were unable to draw up an infant epinephrine dose rapidly or accurately. Most health professionals drew up the dose rapidly; however, their accuracy was compromised by inherent variations of epinephrine concentrations in the ampules, and the inherent difficulty of measuring low volumes of epinephrine. User-friendly premeasured epinephrine doses suitable for infants should be developed."146 (posted Jan 31st,, 2002)
 
 
-Estelle Simons again, in J Allergy Clin Immunol, Jan 2002, compared the use of "Epipen Jr versus Epipen in young children weighing 15 to 30 kg at risk for anaphylaxis". Children aged 5.4+/- yrs, weighing on the average 18+/- kgs, injected with Epipen Jr, were compared with children aged 6.6+/- yrs and weighing 25.4+/- kgs, injected with Epipen.
Conclusions: Epipen raised the systolic pressure more than did the Epipen Jr, but also caused more side effects (palpitations or other cardiovascular effects, with headache and nausea, beside the usual tremor, pallor and anxiety). Dr Simons states that the beneficial pharmacologic effects and the adverse pharmacological effects of epinephrine cannot be dissociated. For the out-of-hospital treatment of anaphylaxis, additional premeasured, fixed doses of epinephrine would facilitate more precise dosing in young children.147 (posted Jan 31st, 2002.)

-King Pharma Canada Ltd. bought the rights to sell Epipen in Canada. Working with Health Canada, they have updated the product monograph. They now recommend Epipen Jr for children 15-30 kg (rather than 0-15 kg as previously recommended.) The regular Epipen covers 30 kg and up. (posted Jan 5th, 2007)

-First-aid treatment of anaphylaxis to food: Focus on epinephrine was published in the May 2004 J Allerg Clin Immuol by Estelle R. Simons. Here's part of her abstract: A therapeutic dilemma is examined: the issue of epinephrine dose selection in an individual for whom no optimal fixed-dose auto-injector formulation exists, and a therapeutic controversy: the issue of epinephrine injection versus an oral H(1)-antihistamine in anaphylaxis episodes that appear to be mild.

Only two fixed doses of epinephrine (0.15 mg and 0.30 mg) are available. The latter auto-inecttor is used for adults, and recommended for children weighing 15 kilos or more. The dosage for children is 0.01mg per kilo, so for children weighing less than 15 kilos, using Epipen Jr would be overdosing. Likewise, in children weighing between 15 and 30 kilos, Epipen Jr would be underdosing, and regular Epipen overdosing. Until the pharmaceutical industry comes up with auto-injectors containing 0.05mg, 0.10mg, 0.20mg and 0.25 mg Dr Simons recommends:
 
The decision so use Epipen rather than Epien Jr in a case study of a child weighing 22.5 kilos may be guided by the presence of one or more of the following:
  • Concurrent diagnosis of asthma
  • Peanut, tree nut, milk, egg, fish or seafood anaphylaxis
  • Poor access to emergency medical services, e.g. living or vacationing in a remote rural area
  • Dysfunctional/chaotic family situation
  • No reliable transporation available
  • History of previous life-threatening reaction (note, however, that absence of a history of life-threatening reaction does not eliminate the possibility of such a reaction in the future)
 
 
As for the role of antihistamines, Dr Simons concludes: The onset of activity of orally ingested antihistamines does not occur until 40 to 60 minutes after ingestion, and maximal activity is not achieved until 4 hours. In anaphylaxis, there are no clinical trials of oral antihistaminies or the algorithms for their use. In advance, there is no way to identify individuals whose anaphylaxis manifestations will be limited to the skin and for whom an antihistamine will suffice...In three different cohorts, adverse reactions to peanut and tree nut became more severe with time in 1/3 or more of individuals. The detailed algorithms developed to help physicians decide whether to give epinephrine or an antihistamine in anaphylaxis are useful in health care settings; however, in the first-aid treatment of anaphylaxis in the community, placing the burden of decision making on individuals without medical training or resuscitation team backup may not be appropriate. Judgment may be clouded by fear, panic, denial..We must not forget that the median time to respiratory or cardiac arrest in individuals with anaphylaxis from food is 30 minutes. 226 (posted May 24th, 2004)
 
Twinject auto-injector is now available in Canada. As the name indicates, it comes with a back-up dose. See video of step by step directions and video by Dr. Peter Vadas. (posted Oct. 14th, 2005)
 
 
What about outdated Epipens?
Nancy Wiebe, webmaster of the Calgary Allergy Network. has brought this question to my attention. Dr Estelle Simons published an article addressing this question in the May 2000 J Allerg Clin Immuol entitlled Outdated EpiPen and EpiPen Jr autoinjectors: past their prime? The abstract reads as follows: Twenty-eight EpiPen and 6 EpiPen Jr autoinjectors were studied 1 to 90 months after the stated expiration date. Most were not discolored and did not contain precipitates. Epinephrine bioavailability from the outdated EpiPen autoinjectors was significantly reduced compared with epinephrine bioavailability from the in-date autoinjectors. Her conclusions were:
"For prehospital treatment of anaphylaxis, we recommend the use of EpiPen and EpiPen Jr autoinjectors that are not outdated. If, however, the only autoinjector available is an outdated one, it could be used as long as no discoloration or precipitates are apparent because the potential benefit of using it is greater than the potential risk of a suboptimal epinephrine dose or of no epinephrine treatment at all." (posted Dec 10th, 2003)
Should beta-blockers be given to patients with heart disease and peanut-induced anaphylaxis? A decision analysis. In the May 2004 J Allergy Clin Immunol, Tenbrook, JA et al asked this question and arrived at this conclusion: For peanut-allergic patients who are postmyocardial infarction or who have congestive heart failure, the heart disease benefit of beta-blockers outweighs the increased likelihood of dying from anaphylaxis. Their results suggest that for these patients, beta-blocker use should still improve survival. However, the epidemiology of anaphylaxis and effects of beta-blocker therapy on anaphylaxis incidence and mortality require further study. 222 (posted May 15th, 2004)

-At the annual AAAA&I meeting held in San Diego,CA in Feb. 2007, Oren et at presented Food-Induced Anaphylaxis and Repeat Epinephrine Treatments. The authors reviewed 40 charts of patients who presented with food-related acute allergic reactions to the Massachusetts General Hospital emergency dept over a one-year period. Of the 40 patients, 35 had an anaphylactic reaction. Forteen of the patients who had an anaphylactic reaction received at least one dose of epinephrine. Of those who received epinephrine, 3 were given a second dose... and these were in peanut and nut related reactions. Concl: among patients presenting to the emergency dept with food-induced anaphylaxis, approx. 21%  of those receiving epineprhine were given a second dose. This supports the recommendation that patients at risk for food-induced anaphylaxis should carry two doses of epineprhine. (posted May 5th, 2007)

 
 
  
Dealing with peanut allergy in schools
 
- Peanut sniffing dog. A teenage from Jacksonville, FL asked her mom for a service dog to deal with her peanut allergy. See the article and the video. (posted June 12th, 2005)
-See Peanut Detector Dogs.

Follow-up of peanut allergic patients, following initial reaction:

 
 

In summary:

-An excellent article by Dr. Hugh Sampson published April 25th, 2002 in the N Engl J Med, in the Clinical Practice section, summarizes Peanut Allergy as it is today. Here are some parts quoted that are worth underlining:

N.B. Regarding the item above on the fact that peanut allergy is rare in China,

In Clin Exp Allergy. 2007 Jul;37(7):1055-61, Chiang WC, Kidon MI, Liew WK, Goh A, Tang JP, Chay OM, reported The changing face of food hypersensitivity in an Asian community. The authors conclude: In contrast to previously reported low peanut allergy rates in Asia, in our review, peanut sensitization is present in 27% (62/227) of food-allergic children, mostly in patients with multiple food protein sensitizations. Temporal patterns of first exposure of infants to fish and shellfish are unique to the Asian diet. Shellfish are a major sensitizing food source in Asian children, especially in allergic rhinitis patients sensitized to cockroaches.  276  (posted Aug 3d, 2007)

 
-In the April 2002 of Ann Allergy Asthma Immunol, Dr SH Sicherer published Clinical update of peanut allergy in which English language articles were selected from PubMed searches and selected abstracts with a bias toward recent (3 years) studies judged to have immediate, practical clinical implications. Results:

 

 
 
 Recent studies:
 
Anti IgE drug: new treatment for peanut allergy?
 
-During the month of Dec. 1999, a new drug for asthma was reported in the media, an anti-IgE monoclonal antibody, described as acting directly on the allergic component of asthma, IgE, following a publication the the New England Journal of Medicine: Treatment of Allergic Asthma with Monoclonal Anti-IgE Antibody89. On Dec. 28th, the Peanut Allergy Site (PeanutAllergy.com) posted information about a clinical trial of the drug in severe peanut allergy: "Tanox announces start of anti-IgE clinical trial." In the same posted announcement, comments are reproduced from members as well as from Dr Donald Leung, and Dr Hugh Sampson, both involved in the trial. "In this study we are attempting to determine whether or not anti-IgE therapy will be effective in preventing anaphylactic reactions to peanuts. If it is effective in peanut allergic patients, it is very likely that it will actually protect allergic patients from all food allergies. . . We are very optimistic about this medication. . . " (posted Dec 31st, 1999)
-Sept 24th, 2002: FDA Grants Tanox's Peanut Allergy Drug Fast Track Status....it means that the FDA will facilitate the development and expedite the review of a drug if it is intended for the treatment of a serious or life-threatening condition and demonstrates the potential to address unmet medical needs for such a condition.
Fast track status enables a pre-BLA (Biologics License Application) meeting with the FDA to discuss and achieve agreement on critical issues, allows for early submission of portions of the BLA in order to expedite review and presents performance goals for priority review of the BLA in six months for the specified indication. (posted Oct. 7th, 2002)
-In the Montreal Gazette of Sat. Oct. 5th, 2002, appeared a Canadian Press item entiltled: 'U.S. fast tracks peanut-allergy drug', a follow-up to the above announcement. The article states that
"there currently is no treatment for peanut allergy, one of the most severe forms of food allergies... According to a conservative estimate, two per cent of Canadians (about 600,00 people) might be affected by potentially life-threatening allergies. The incidence might be higher in children and it has increased dramatically in the last decade.
For many people with peanut allergies, contact with even trace amounts of peanut protein can bring on a life-threatening attack of anaphylactic shock. People suffering an allergic reaction to peanut must be given an immediate jab with an Epi-pen, a device that dispenses epinephrine.

TNX-901, administered by injection, would protect against reactions to accidental peanut exposure by binding to the allergic antibody and blocking it from circulating through the system.

Despite the fast-tracking, it could still be years before the drug passes through all the necessary trials and hists the market.(posted Oct. 7th, 2002)
 
-Also in the Boston Globe, Oct 7th, 2002: 'Scientists make gains against peanut allergy'...''I think that, within five years, there will be treatments that will do two things,'' said Dr. Wesley Burks of the University of Arkansas, who is working on the vaccine. ''One will lessen the chances significantly that an accidental ingestion would be life-threatening, and the second is that, if the vaccines work appropriately, there are chances the child would eventually no longer have the disease.''....

'It's the first time that we have been able to look to the future and actually believe that a cure or a treatment is within reach,'' said Anne Munoz-Furlong, founder of the Food Allergy and Anaphylaxis Network, a national advocacy group that educates the public about food allergies. ''It's a very exciting time. Ten years ago, we were still trying to figure out how big the problem was, and many people didn't believe it was serious.''

 

-At the 60th Anniversary Meeting of the AAAA&I held in Denver, Colo. March 7-12, 2003, Dr Leung presented the results of the first study on the Effect of Anti-IgE Therapy in Patients with Peanut Allergy..coincidingly published in the March 13th, 2003 New England Journal of Medicine. A double-blind, randomized, dose-ranging trial was conducted in 84 patients with a history of immediate hypersensitivity to peanut. Three different doses (150, 300 or 450 mg of TNX-901)were given to randomly assigned groups every four weeks for four doses. The patients underwent a final oral challenge within two to four weeks after the fourth injection of the vaccine.

Results and conclusions: A 450 mg dose of TX-901 significantly and substantially increased the threshold of sensitivity to peanut on oral food challenge from a level equal to approximately half a peanut (178 mg) to one equal to almost nine peanuts (2805 mg), an effect that should translate into protection against most unintended ingestions of peanuts.
The authors conclude that "although these results are highly encouraging, TNX-901 is still an experimental drug, and approval for general use will require confirmation of these results in additional studies."170 (posted Mar 28th, 2003)
-Comments from Drs RA Nicklas, and BA Chowdhury, Division of Pulmonary, Allergy and Drug Products, US Food and Drug Administration, published as a guest editorial in Annals of Allergy, Asthma and Immunology, entitiled Effect of anti-IgE therapy in patients with food allergy include the following:
-"....the study contains several imporant potential biases....which could lead to false expectations on the part of both physicians and patients.
-Two patients with negative food challenges were entered in the study.

-Open challenges were used, which automatically introduces bias, both on the part of patients and investigators.

-The fact that 3 of the investigators were not blinded to the study results enters further bias into the study.

-There is concern that physicians will conclude from these data that TNX-901 may offer protection for all patients. In fact, 76% of pateints were not protected against a reaction after ingestion of 8 g. of peanut flour (equivalent to 24 peanuts), and approximately 25% were not protected after ingesting as low a dose as 0.5 g of peanut flour (approx. equal to 1.5 peanuts), despite being pretreated with the highest dose of TNX-901.

-Even if it is expected that TNX-901 has a beneficial effect...it cannot be expected to protect every patient sensitized to peanut from an anaphylactic reaction after ingestion of even small amounts of peanut allergen...Unless those patients who are not sufficiently protected can be identified, physicians will have to assume that all patients are at risk and will still need to carry injectable epinephrine as well as assiduously avoid exposure to food allergens to which they are sensitized. (posted Nov 8th, 2003)
 

  A chinese herbal formula studied in a mouse model

 -In the Oct 2001 J Allergy Clin Immunol, Li and coll. published their study entitled "Food Allergy Herbal Formula-1 (FAHF-1) blocks peanut-induced anaphylaxis in a murine model." Laboratory findings suggest that this Chinese herbal formula may prove valuable for the treatment of peanut allergy.134 (posted Nov 7th, 2001)

-The same authors (Li, Sampson and coll.) published a follow-up study in the Jan 2005 J Allergy Clin Immunol entitled The Chinese herbal medicine formula FAHF-2 completely blocks anaphylactic reactions in a murine model of peanut allergy. They removed two herbs from the original formula (FAHF-1) and found that the new product, FAHF-2, completely eliminated anaphylaxis in mice allergic to peanut challenged as long as 5 weeks posttherapy. Acc'g to the abstract, 'this result was associated with downregulation of TH2 responses. FAHF-2 may be a potentially effective and safe therapy for peanut allergy.' 241 (posted Jan. 15th, 2005)

 

Study on oral administration of IL-12
 

-Lee, and coll. in the Nov 2001 Clin Immunol published their study entitled "Oral administration of IL-12 suppresses anaphyactic reactions in a murine model of peanut hypersensitivity." They also conclude that this preparation has therapeutic as well as preventive effects on peanut allergy. 135 (posted Nov 7th, 2001)

 

-In the 2002 Spring Newsletter of Anaphylaxis Canada, Dr. Peter Vadas' presentation at the Canadian Society of Allergy and Clinical Immunology meeting held in Oct. 2001 is summarized in the Current Research section.

"All in all, the future looks very bright. Dr Vadas believes that we will start to see the application of some these experimental treatments within the next few years. The major areas of international research are;
  • Modified peanut protein vaccine The major peanut proteins can be modified so that they do not bind with IgE (bypassing IgE) but still stimulating an immune response blocking a reaction should unmodified peanut protein be introduced at a later date.
  • DNA vaccines: There are four DNA-based modalities that are currently being investigated. In one study it was found that when mice were given the major peanut allergen gene by mouth (i.e. the gene that directs production of one of the major peanut protein allergens), the gene began to function within the cells of the gut and these mice showed a reduction in the development of anaphytlaxis to peanut.
  • A chinese herbal remedy: referring to the posting above. Studies are currently underway to understand the mechanism and determine the role that this derivative could play in anaphylaxis treatment of humans.
  • Anti-IgE vaccine: following the research mentioned in the above posting (going back to Dec 1999) a medication that was developed for the treatment of asthma and allergic rhinitis may find a new application in the pevention of anaphylaxis. This vaccine may be capable of reducing the severity of an anaphylactic reaction through blocking IgE. Clinicl trials are underway and will be starting in Toronto shortly.
  • Th1-Th2 shift: Certain probiotic bacteria, such as lactobacillus, that do not cause infection in humans, may provide some degree of protection against the development of allergy. This is in keeping with the 'hygiene hypothesis' of allergy whereby it is believed that the presence of certain bacteria can shift the immune system away from the allergy pathway... the so-called Th1-Th2 shift.' " (posted April 18th, 2002)

See also:

 

-CBS news and video on the effect of roasting peanuts, and more on a vaccine for peanut allergy-interview with Dr. Hugh Sampson (posted Dec. 4th, 2002) At the same page, see another video: 

-In the June 2002 Curr Opin Allergy Clin Immunol, Dr JO Hourihane has an article entitled appropriately Recent advances in peanut allergy. (Abstract) Highlights:

He suggests:
It is important to remember that the allergenicity of peanuts is altered by the way peanuts are prepared; roasting seems to increase the allergenicity compared to boiling or frying.
An encouraging note is that immunotherapy with modified peanut allergens et DNA vaccines are near the clinical study stage. 157 (posted July 14th, 2002)
 
 -Likewise, Shimamoto and Bock, in the same June 2002 Curr Opin Allergy Clin Immuno issue, have Update on the clinical features of food-induced anaphylaxis. It is a review on food-induced anaphylaxis, its prevalance, proposed etiology, a discussion on exercise-induced anaphylaxis that may be triggered by specific foods, at times not, an attempt at identification of specific food antigens responsible, and current treatment options available (patient education, food avoidance, acute symptom recognition, and early use of self-administered epinephrine.) Additionally, they discuss outcome data regarding the morbidity and mortality related to food allergy and anaphylaxis, and information regarding experimental immunomodulatory therapy. 158 (posted July 6th, 2002)
 
 -Update on food allergy. Sampson HA May 2004 of J Allergy Clin Immunol. Here's the abstract:
 
"Tremendous progress has been made in our understanding of food-based allergic disorders over the past 5 years. Recent epidemiologic studies suggest that nearly 4% of Americans are afflicted with food allergies, a prevalence much higher than appreciated in the past. In addition, the prevalence of peanut allergy was found to have doubled in American children less than 5 years of age in the past 5 years. Many food allergens have been characterized at the molecular level, which has contributed to our increased understanding of the immunopathogenesis of many allergic disorders and might soon lead to novel diagnostic and immunotherapeutic approaches. The management of food allergies continues to consist of educating patients on how to avoid relevant allergens, to recognize early symptoms of an allergic reaction in case of an accidental ingestion, and to initiate the appropriate emergency therapy. However, the recent successful clinical trial of anti-IgE therapy in patients with peanut allergy and the number of immunomodulatory therapies in the pipeline provide real hope that we will soon be able to treat patients with food allergy." 224 (posted May 15th, 2004)
 
-In the Oct 2004 BMJ , Wendy Hu, Andrew Kemp and Ian Kerridge, from the School of Public Health and Community Medicine, University of New South Wales, from the Dept of Allergy, Immunology and Infectious Diseases, Childrens' Hospital of Westmead, and from the Centre for Values, Ethics, and the Law in Medicine, Sidney, Australia, published 'Making clinical decisions when the stakes are high and the evidence unclear'.
The article is worth downloading- it addresses many issues related to dealing with peanut allergy particularly its management. In the words of the authors, 'Children with peanut allergy are often provided with adrenaline (epinephrine) in case of a severe reaction. The probability of a life-threatening reaction is low, however, and the criteria for provision are controversial. How should the costs and benefits be balanced?' (posted Oct. 9th, 2004)
 
-Burks W, Lehrer SB, Bannon GA. have a publication in Clin Rev Allergy Immunol. 2004 Nov; entitled New approaches for treatment of peanut allergy: chances for a cure. Here's part of the abstract:
"Strict avoidance of specific foods is accepted treatment of food-induced allergic reactions but is often an unrealistic therapeutic strategy for the treatment and prevention of food-induced hypersensivity reactions for many reasons. Desirable therapeutic strategies for the treatment and prevention of the food allergies must be safe, relatively inexpensive, and easily administered. Recent advances in the understanding of the immunological mechanisms underlying allergic disease and better characterization of food allergens have greatly expanded the potential therapeutic option for future use. Several different forms of immunodulatory therapies are currently under investigation: peptide immunotherapy, mutated protein immunotherapy, allergen DNA immunization, vaccination with immunostimulatory DNA sequences, and anti-immunoglobulin E-therapy."242 (posted Jan. 19th, 2005)

 

 
 
 
 

Questions:

 
The question that everyone is asking, and to which there is no clear-cut answer is: will all children that have reacted to peanuts by having urticaria only, usually on the face, of short duration that resolved without any treatment, that show a positive skin test to peanut, progress to life-threatening anaphylaxis, after accidental ingestion?
 
Jan 28th, 1999. When seeing siblings of peanut allergic children particularly, but not necessarily, allergists are often asked to check to see if they are allergic to peanuts, or nuts. They have no history of reaction of any kind to peanuts, or nuts, and in many cases, arising from fear, or for any other reason, they have never eaten peanuts or nuts. Based on the recent medical literature, with initial reactions occurring in more than 70% of cases without previous contact, should they be tested for peanut allergy?
 
If the test is negative, the sibling is considered not allergic, what are the recommendations? Should she/he eat peanuts?
Answer: According to Dr. Anne Des Roches: if the sibling with a negative history of peanut or other food allergy, has a negative skin test, in the case of a very young child, introduction of peanuts not before age 5. (posted April 18th, 1999)
 
If on the other hand, the test is positive, and strongly positive perhaps, the child obviously is considered allergic, and continues not eating peanuts or nuts. Can one conclude that the child would have had an allergic reaction, possible even anaphylactic, had he or she eaten peanut, and doing the test in such cases is a preventive measure?
 
 To help answer these questions:
 
Some questions that were asked of Dr Pamela W. Ewan following her article: Clinical study of peanut and nut allergy in 62 consecutive patients: new features and associations, published in the BMJ 33 in 1996, found on the Internet at Mediconsult.com are reproduced here:  

 

 
1. Could eliminating exposure to peanuts and nuts in childhood prevent the development of allergies?
 
That's difficult to answer. We need much more data over a long period of time to be certain. One of our hypotheses is that the early introduction of peanuts is an important factor responsible for the increase in peanut allergy. If that's right, delaying introduction might lead to prevention of this
allergy. It's known for certain in other allergies that small children, if exposed to a potent allergen, seem to be more likely to react. We have not seen this large number of young children with peanut allergy until recently, so something has changed, and one of a number of things that have changed is
diet.
 
2. Have you seen cases of adults who have been eating peanuts all their lives, and suddenly get a reaction?
 
Very few. We do see that, but it's uncommon, although allergies can develop at any age.
 

3. Can skin tests be dangerous to young children?

 
Skin tests are very safe, but it's important that they be done in expert hands, because occasionally you get a reaction. We tested large numbers of nut-allergic people, including very young ones, and we saw no adverse reactions.
 
4. Do genetic factors predispose to nut allergy or other allergies?
 
That's certainly true of other allergies, and I presume that it will apply to nut allergy as well. It has been known for a very long time that if one parent is allergic, there's a good chance the child will be, and if both parents are, the chance is even greater. But it's not a direct inheritance. It's very complex trying to disentangle the link between genes and the development of allergic antibody responses. In
this study, almost all of the patients who were nut-allergic also had other common allergies, so they were clearly of a background genetically predisposed to allergy.
 
5. Can an infant be sensitized through breast milk?
 
Probably. We know that proteins from the maternal diet can get into breast milk. This has been established with other foods, so there's no reason it couldn't happen with peanuts, although as far as I know this hasn't been properly demonstrated. You must have been previously exposed in order
to produce the antibody which causes the allergic reaction, so theoretically it couldn't occur on your first exposure. Cases where the mother is sure that a reaction occurred the very first time the baby was given peanut in any form raise issues like "Could it have been from breast milk?". It's
postulated that tiny amounts of the protein in the mother's milk might be enough to sensitize the baby -- in other words, cause him to manufacture the harmful allergic antibody to the protein. Another possible way could be across the placenta, in utero. If the mother is eating a lot of peanuts
during pregnancy, it's theoretically possible for the proteins to cross the placental barrier into the baby.
 
6. To what factors do you attribute the increase in allergies?
 
In the last 10 to 20 years, there has been a huge increase in the number of allergic disorders. Earlier or more frequent exposure to allergens is one important factor, but I don't think it's the only one. Another is atopy, the tendency to form allergic antibodies. An atopic child exposed to peanut butter is at much greater risk of developing peanut allergy than a normal child. We found atopy in 96% of the patients in the study by carrying out skin prick tests to other common allergens. The same number had other common allergic disease -- allergic asthma or rhinitis, or atopic eczema. One
theory is that it's in part to do with modern living. The way we live now, in enclosed environments with central heating, carpets and double-glazed windows, favours the growth of the house dust mite, which is one of the commonest causes of asthma, rhinitis and eczema. That may be a very
important factor, and there may be others that we don't yet have data on.
 
Comment from Dr. Ewan:
 
One thing our study suggests is that if you have a child with a common allergy, it's very unwise to give that child peanuts or nuts. It may well be that the same advice is valid even for children who aren't allergic, but we don't yet have data to support that. But if you have an allergic child, there are
very strong reasons for at least delaying the introduction of peanuts and nuts, and certainly to not give them to very young children. It's a fearsome allergy -- it's a very dangerous thing to have. It can have such terrible consequences, so if there's any way of avoiding it, that would be sensible to
do. (posted April 21st, 1999)
See also: Ewan PW, Clark AT: Long-term prospective observational study of patients with peanut and nut allergy after particiption in a management plan. Lancet 2001;357: 111-115.
 

 
Related links:
-Allergy Haven (very informative site)
-'Don't go nuts (UK) Nut Allergy Information & Forum for the UK & Beyond.
-No Nuts for me'-interactive video for kids.
-Practical aspects of adverse reactions to peanut by Karen du Plessis and Harris Steinman. Current Allergy& Clinical Immunology, March 2004 Vol 17, No. 1
 -Peanut allergy (pdf document from Australia)
-Tree nut allergy by Susanne Teuber. See also her video: Food Allergy : Challenges for Physicians , Food Scientists and the Food Industry
-Peanut and Other Food Allergies -- Scott Sicherer, MD -- 07/24/03.
-Allergens in food, by Wesley Burks, from the 2002 Postgraduate Sessions of the AAAA&I Meeting.-Peanut allergy huge challenge for parents
-Peanut and nut allergies- The facts (Brochure from the AAIA)
-Peanut allergy - No small thing- Video of conference given by Dr Rhoda Kagan. (posted June 30th, 2003)
-Penaut allergy: an overview. Excellent review by Saleh Al-Muhsen, Ann E. Clarke and Rhoda S. Kagan (full text available)
-Peanut allergy...;how much do you know? Michigan State University extension
-Peanut allergy - UK Dept of Health 47 page document by the Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment.
-Sicherer SH, and Sampson HA: Peanut and tree nut allergy: Current opinion in Pediatrics 2000;12:567-573
-Peanut Allergy by prof. P. Potter (Allergy Society of South Africa) 
 
-Understanding food allergy
-Food Allergy and Anaphylaxis Network-Peanut Aware
-Peanutallergy.com
-Peanut allergy links
-MedicAlert
-Ident-Id
-"Kids with food allergies" is an online support group for parents of children with severe food allergies and anaphylaxis  
-Peanut allergy information for families
-Cracking it? Peanut allergy - is an answer close? (Hourihane, JO)
-Severe food allergies in kids on rise-Experts say peanuts responsible for about half the problem (video) (posted May 12th, 2002)
-Food Allergen Consumer Protection act (posted May 12th, 2002)
-$10M Granted in First Plaintiff Victory in Food Allergy Case (posted May 12th, 2002)
 
-Food allergy- a review by Scott H. Sicherer, Lancet 2002;360:701-10
-A Snapshot of Federal Research on Food Allergy : Implications for Genetically Modified Food-Food Allergy Initiative
-Primary Care Approaches: Peanut Allergy: An Increasing Health Risk for Children, from Pediatric NursingPatricia L. Jackson
-Guidelines, Recommendations on Peanut Allergy from the American Academy of Family Physicisans
 
-Awareness of Peanut or Nut Allergies amongst Canadians
-Food Allergies and School : What Every Parent Should Know
 
 
 
 
 
 

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John Weisnagel, M.D. formerly of the Allergy Service, Dept. of Pediatrics, Hôpital Ste Justine, Montreal, Qué. until Dec. 2000, is a pediatrician and allergist in private practice since 1962, now at Polyclinique Médicale Concorde, 300 est boul. de la Concorde, Laval, Qué. H7G 2E6. Past president, for many years, of the Association of Allergists and Immunologists of Quebec (AAIQ). Member of the Canadian Society of Allergy and Clinical Immunology (CSACI), and of the American Academy of Allergy, Asthma and Immunology (AAAA&I). The 2002 CSACI recipient of the Jerry Dolovich Award for Contributions to Allergy and Clinical Immunology in Canada.
 
 
 

(Article originally posted Oct 2nd, 1998. Updated regularly. Any comments and modifications are welcome.)

Last update: Oct. 27th, 2009

 

This article is continued in part 2

J.W

jweis@videotron.ca