Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions tofood

Posted on: Mon, 07/12/2004 - 6:52am
ajinnj's picture
Joined: 05/13/2003 - 09:00

Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insect stings*1

abScott H. Sicherer MD, and Donald Y. M. Leung MD, PhD

From aThe Elliot and Roslyn Jaffe Food Allergy Institute, Division of Allergy and Immunology, Department of Pediatrics, Mount Sinai School of Medicine, New York, and bthe Department of Pediatrics, University of Colorado Health Sciences Center, Division of Pediatric Allergy/Immunology, National Jewish Medical and Research Center, Denver., USA

Received 12 March 2004; accepted 24 March 2004 New York, NY, and Denver, Colo Available online 2 July 2004.

This review highlights some of the research advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insect venom that were reported primarily in the Journal of Allergy and Clinical Immunology from 2002 through 2003. Among the topics highlighted are new insights into the pathogenesis of atopic dermatitis and potential strategies for more effective treatment of the atopic march. Patients should remain supine with raised legs during anaphylactic shock because upper body elevation could result in sudden death from loss of venous return to the heart. A major advance in food allergy was that humanized, monoclonal anti-IgE antibody showed protection against peanut-induced anaphylaxis. In addition to studies elucidating mechanisms of drug hypersensitivity, a clinical study showed patients with a history of prior penicillin allergy with negative penicillin allergy test results are unlikely to experience reactions or resensitization on subsequent oral courses of penicillin. Lastly, there are new recommendations for patients with convincing insect sting reaction histories but negative skin test responses to venom.

Author Keywords: Dermatology; skin disease; anaphylaxis; allergy; hypersensitivity disorders; food; drug; insect venom

AD, Atopic dermatitis; IDEC, Inflammatory dendritic epidermal cell; VIP, Vasoactive intestinal polypeptide

Article Outline
1. Anaphylaxis
2. Food allergy
3. Drug allergy
4. Insect hypersensitivity
5. Atopic dermatitis
5.1. Immune mechanisms
5.2. Role of microbes in AD
5.3. Management of AD
6. Conclusions

More than 100 articles concerning allergic skin disease, anaphylaxis, and hypersensitivity to foods, drugs, and insect venom were published in the Journal of Allergy and Clinical Immunology from October 2002 through December 2003. The current review highlights key advances in these areas reflected primarily by studies in the Journal, with additional pertinent material selected from the literature (Table I).

Table I. Key advances

1. Anaphylaxis
Simons et al[1.] analyzed prescription patterns for self-injectable epinephrine in Manitoba, Canada. Remarkably, they found that 0.95% of the population was prescribed this drug, with a peak prescription rate of 1.44% for children. Boys were prescribed epinephrine more frequently than girls, and adult women were prescribed epinephrine more than men, with the highest rate for boys aged 12 to 17 months (5.3%). These data cannot precisely reflect the rate of anaphylaxis or the percentage of the population at risk but clearly define anaphylaxis as a common disorder with a particular pattern of age and sex distribution that presents an important area of future research.

In addition to epinephrine, 2 additional therapies for anaphylaxis received attention in the Journal. Vadas and Perelman[2.] performed in vitro studies showing that activated charcoal efficiently binds peanut protein and blocked binding by peanut to IgE, as demonstrated by a sandwich ELISA, Western blotting, and reduced skin prick test responses. They also showed efficiency in binding at low pH and when food matrices were present (eg, peanut in ice cream). Although the supposition is that activated charcoal may be a good adjunct for treatment of accidental peanut ingestion (as is commonly used for poison control) and perhaps other ingested allergens, studies are needed in a more clinically relevant system because there are physiologic (absorption of the protein before and despite charcoal therapy), practical (a large volume of offensive-tasting liquid charcoal to ingest), and medical (charcoal inactivation of oral medications, dangerous if aspirated) issues that need to be evaluated.

An astute observation by Pumphrey[3.] may provide an immediate directive toward improved treatment of outpatient anaphylaxis. He noted in 10 cases of fatal anaphylaxis in which postural information was available that persons died while in an upright position. In fact, 4 of the deaths occurred within seconds of the victim being placed upright after being supine. He explains that in shock there is insufficient venous return, so that moving the patient into the upright position may result in a sudden loss of filling to the heart and a cascade of events leading to circulatory collapse and cardiac ischemia. Conversely, raising the legs while leaving the individual supine may increase blood flow by means of autotransfusion. Therefore for anaphylactic shock, forget the old adage and plan for your patient to indeed "take this lying down."

We may be nearer to understanding why there are persons who can eat wheat without incident unless they exercise, in which case they experience anaphylaxis. Palosuo et al[4.] showed that individuals with wheat-dependent, exercise-induced anaphylaxis have IgE antibody directed to omega-5 gliadin and, in a series of in vitro experiments and with skin prick tests, further showed that digested wheat treated with tissue transglutaminase, compared with untreated wheat, caused large peptide complexes with enhanced IgE binding. These findings raise the interesting hypothesis that an exercise-induced activation of tissue transglutaminase may be a factor in this disorder.

2. Food allergy
The notion that food allergy has increased in prevalence has been promulgated with little direct evidence. Two studies in the Journal have now documented an increase in peanut allergy in young children. Grundy et al[5.] compared a birth cohort of 1273 children on the Isle of Wight, United Kingdom, born in 1989 and followed to age 4 years with another cohort of 1218 born from 1994 through 1996 followed to age 3 years. Remarkably, the rate of positive skin test responses to peanut tripled from 1% to 3.3% (P = .001), and the rate of reported reactions doubled from 0.5% to 1% (and approximately 1.5% were estimated to have peanut allergy when allergy was evaluated in children who had not knowingly eaten peanut). Sicherer et al[6.] performed a nationwide random telephone survey in the United States in 2002 with the same methodology used in 1997 to estimate the prevalence of peanut allergy by self-report. In 2002, the rate of reported peanut allergy in children younger than 18 years of age was 0.8%, which was double the rate reported in 1997 (0.4%, P = .05). The study did not include physician evaluations, but Kagan et al[7.] performed a comprehensive evaluation of peanut allergy in Montreal schoolchildren from kindergarten to third grade that included IgE antibody tests and oral food challenges to confirm diagnoses; with conservative estimates, the rate of peanut allergy in these young children was an alarming 1.34% (95% CI, 1.08% to 1.64%).

While we await epidemiologic studies regarding prevalence rates of other common food allergies, focus on peanuts continues. Why has there been an increase? What else can be done? Rational and effective prevention strategies require data on risk factors. A variety of factors have been considered, including that roasting of peanut may enhance allergenicity,[8., 9. and 10.] that our environment may promote allergic responses (eg, the hygiene hypothesis), and that early exposure (eg, through breast milk) could be an issue, but there are few data. [11.] Lack et al [12.] reported factors associated with peanut allergy by means of analysis of a cohort of 13,971 preschool children participating in the Avon Longitudinal Study of Parents and Children. Peanut allergy was independently associated with use of soy formula (odds ratio, 2.6), complaints that may indicate atopic dermatitis (AD; odds ratio, 2.6-5.2), and the use of skin creams that contain peanut protein (odds ratio, 6.8), although such creams are not in widespread use in the United States. Interestingly, after regression analysis, the study did not support the hypotheses that maternal ingestion of peanut during pregnancy or lactation was a significant risk factor. The observation that infant skin cream with peanut but not nipple creams with peanut protein (nor maternal ingestion) were factors associated with peanut allergy raised the interesting hypothesis that skin rather than oral sensitization may be occurring in peanut allergy, but the study results must be confirmed.

Another interesting hypothesis regarding the development of food allergy is that inefficient digestion, as may be the case in neonates, may expose the immune system to a higher load of allergenic components of foods, particularly novel ones. Untersmayr et al[13.] noted that a nonatopic adult reacted to caviar after ingesting this food while using sucralfate and designed a study to test the influence of antacids on food sensitization. Attempts to sensitize BALB/c mice to caviar and recombinant parvalbumin were undertaken with and without ranitidine, omeprazole, or sucralfate; acid blockade facilitated generation of caviar-specific IgE and resulted in increased numbers of gastrointestinal eosinophils and mast cells. The effect of antacid therapies on food allergy in human subjects, in particular the use of these medications in young children with reflux symptoms, remains to be explored.

Although advances are being made in stemming the rising tide of food allergy, important advances have also been made that have practical management implications, some immediate and some emerging. With respect to peanut allergy, Fleischer et al[14.] re-evaluated their approach to young patients with the possibility of resolved peanut allergy. Eighty children at a median age of 6 years with peanut IgE concentrations of 5 kIU/L or less were evaluated, and 55% overall and 63% of those with levels of 2 kIU/L or less passed challenges, confirming that young children with peanut allergy deserve evaluations for possible resolution. The study also found 2 children who may have subsequently reacquired their allergy, and therefore caution is advised, particularly if the children do not regularly consume peanut.

Families with children with peanut allergy often harbor anxiety regarding reactions from casual exposure. Simonte et al[15.] exposed children highly allergic to peanut to inhalation of peanut butter for 10 minutes and to skin contact with a small amount of peanut butter for 1 minute and found no reactions aside from local ones from contact. They concluded with 96% confidence that 90% of children highly allergic to peanut would not have a reaction from similar contact with peanut butter. Although the result does not indicate a change in approach to the management of peanut allergy, the study may alleviate some of the anxiety. The issue of ingestion of peanut is, of course, a more serious issue. Wensing et al [16.] studied 26 adults with peanut allergy and found that reactions could be elicited by as little as 100 g, and 50% of the adults had reacted by the time they ingested 3 mg. Patients with more severe reaction histories were sensitive to lower doses. These findings have strong implications for industry and food safety and the need for sensitive assays to detect peanut protein in foods. [17.]

Another common clinical condition is oral allergy syndrome. Ma et al[18.] surveyed allergists and found a wide range of practice responses regarding the care of patients with this syndrome. For example, about 50% recommended complete avoidance of fruits causing this reaction, whereas 9% never did, and 3% always prescribed self-injectable epinephrine, whereas 30% never did. The authors suggested that the term pollen food allergy syndrome be used to express the scenario of mild oral symptoms to fruits caused by homologous but labile proteins to which sensitization developed initially after respiratory exposure to pollen. However, a uniform practice approach will not be easily forthcoming until we are better able to differentiate persons with or without a risk for severe reactions. Major headway toward this type of diagnostic ability is being reported through the study of specific triggering proteins and epitopes.[19., 20., 21. and 22.]

Perhaps one of the greatest leaps in treatment of food allergy was reported in the New England Journal of Medicine.[23.] A double-blind, randomized, dose-ranging trial of a humanized monoclonal anti-IgE antibody (TNX-901) was conducted in adults with peanut allergy. At the highest dose of anti-IgE tested, the threshold of peanut sensitivity increased from about one half to almost 9 peanuts. The study proved the concept that this treatment could provide a potential safety net for persons undertaking peanut avoidance. However, practical use of this treatment has not reached fruition because about 20% of the subjects experienced no protection at the highest dose, a significant problem that must be addressed, and the antibody tested has become commercially unavailable (a commercially available anti-IgE product may have different properties than the one studied). However, anti-IgE remains a tenable approach to peanut and other food allergies, albeit not curative. In one of several current research approaches to more definitive therapy, Li et al [24.] reported the results of immunotherapy with heat-killed Escherichia coli producing recombinant peanut proteins (altered to reduce IgE binding) injected per rectum in a murine model of peanut allergy. At maximal doses, this therapy suppressed peanut-induced anaphylaxis nearly completely out to 22 weeks, with significant reduction in peanut IgE levels, and altered TH2 to TH1 cytokine profiles were observed. While various therapies must move from animals to human subjects, an additional important advance is the use of additional animal models, such as the atopic dog, to evaluate food allergy.[25.]

3. Drug allergy
Several studies have addressed common clinical concerns in the area of drug hypersensitivity. Gyllfors et al[26.] evaluated the potential for reactions to COX-2

Posted on: Tue, 07/13/2004 - 2:57am
dgood's picture
Joined: 03/27/2004 - 09:00

Thank you for posting this...I printed it out and look forward to reading it!!

Posted on: Tue, 07/13/2004 - 7:43am
synthia's picture
Joined: 10/05/2002 - 09:00

Thank you,good info.
Is there a link?
Love this site

Posted on: Tue, 07/13/2004 - 9:09am
deegann's picture
Joined: 07/27/2003 - 09:00

[This message has been edited by deegann (edited August 26, 2004).]

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