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Peanut Allergy: Natural History and Prospects for Treatment

Peanut Allergy: Natural History and Prospects for Treatment. Robert A. Wood, MD Professor of Pediatrics Director, Pediatric Allergy and Immunology Johns Hopkins University School of Medicine. Peanut Allergy - Overview. Common in both children and adults

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Peanut Allergy: Natural History and Prospects for Treatment

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  1. Peanut Allergy: Natural History and Prospects for Treatment Robert A. Wood, MD Professor of Pediatrics Director, Pediatric Allergy and Immunology Johns Hopkins University School of Medicine

  2. Peanut Allergy - Overview • Common in both children and adults • 3rd most common food allergy in children • Most common food allergy in adolescents and adults • Average age of onset 18 months • Reactions are often very severe • Prevalence appears to have risen sharply in recent years

  3. Peanut Allergy – Prevalence Studies • Isle of Wight – prospective study of 1218 infants – peanut allergy developed in 1.1 • 1997 - US telephone survey of 4374 households – peanut allergy reported in 0.4% of children and 0.7% of adults • 2002 – same study repeated, now with PA reported in 0.8% of children • Similar increases have occurred for other foods and other allergic diseases

  4. Food Allergy Prevalence Rates Food Young ChildrenAdults Milk 2.5% 0.3% Egg 1.3% 0.2% Peanut 0.8% 0.6% Tree nuts 0.4% 0.4% Fish 0.1% 0.4% Shellfish 0.1% 2.0% Overall 6.0% 3.7%

  5. Why Is the Prevalence Rising? • Theories include • Hygiene hypothesis • Infection • Changes in diet • Environmental factors • Immunizations • Vitamin deficiencies

  6. Peanut Allergy - Sensitization • Reactions reported to occur on 1st known exposure in 80% of cases • Possible explanations • Failure to recall prior exposures or unsuspected exposure • Exposure through topical preparations, incidental skin contact, or inhalation • In utero exposure • Exposure via breast milk

  7. Peanut Allergy - Sensitization • Does in utero exposure / sensitization occur? • 25 children with peanut allergy compared to 18 children with other food allergies • Peanut allergy was more common if mothers had ingested peanut more than once a week in pregnancy  odds ratio = 3.97 • However, peanuts were also introduced at an earlier age in those with peanut allergy (P=0.03)

  8. Peanut Allergy - Sensitization • Exposure via breast milk • Peanut (and other food) allergens pass readily into the breast milk • The prevalence of peanut allergy is higher in breast fed infants • In one study it was found that consumption of peanuts while breast feeding was more common among mothers of peanut allergic children <5 yrs versus those >5 yrs (P<0.001) and that breast feeding was associated with an earlier onset of PA

  9. Peanut Allergy – Genetic Influences • Peanut allergy is clearly more common in atopic families • Hourihane found that 8% of siblings of PA children also had peanut allergy • Sicherer found in a study of PA in twins that 10/14 monozygotic twins were concordant for PA, compared to 4/44 dizygotic twins • Overall heritability of PA estimated to be 80%

  10. Peanut Allergy – Clinical Characteristics • Accidental ingestions are common – about 50% will experience an accidental reaction in any 5 year period • Reactions range from mild to fatal and overall tend to be more severe than for other foods • Reactions often become more severe over time, but severity will vary depending on level of sensitivity, dose, and route of exposure

  11. Peanut Allergy – Clinical Characteristics (VanderLeek et al J Peds 2001) • 85 children with PN allergy, 55 followed for >5 years • 58% had at least one accidental rxn in 5 yr FU, 75% in 10 yr FU • Rxns tended to become more severe with time and 52% included potentially life-threatening Sx • Severe reactions were associated with high PN-IgE levels

  12. Fatal Food-induced Anaphylaxis • Fatal reactions are on the rise • 150 – 200 deaths per year • Usually caused by a known allergy • Three well defined risk factors: • Peanut and tree nut allergy • Asthma • Failure to treat promptly w/epinephrine • Many cases exhibit biphasic reaction

  13. Peanut Allergy – Natural History • Until recently was thought to virtually always be lifelong • Bock & Atkins 1989 • Followed 32 children 1 to 14 yrs of age with peanut allergy for 2 to 14 yrs • 24 had reactions due to accidental exposures • None appeared to lose their allergy

  14. Studies on the Natural History of Peanut Allergy (Skolnick et al (JACI 2001;107:367) • 223 patients between the ages of 4 and 18 yrs with a diagnosis of peanut allergy • Challenges offered to those with a PN-IgE <20 kU/L (by CAP-RAST) and no reaction in past year • Also assessed skin tests and other clinical parameters (other food allergies, other allergic diseases, severity of prior reactions) as predictors of natural history

  15. Patient Characteristics

  16. Summary of Results • 21.5% of children above the age of 4 with PN allergy were shown to have outgrown their allergy • PN-IgE levels at dx and at evaluation were signifi- cantly lower in those outgrowing their PN allergy • Negative challenges in • 61% with a PN-IgE <5 KU/L • 67% with a PN-IgE <2 • 73% with a PN-IgE <0.35 • Only 2 patients with a PN RAST >10 at diagnosis were shown to have outgrown their PN allergy

  17. Fleischer et al (JACI 2003;112:183) 84 additional patients, all with PN-IgE levels ≤ 5 at challenge Children with PN-IgE levels ≤ 2 were significantly more likely to pass than those with levels between 2 and 5 (p<0.003)

  18. Peanut Allergy: Risk of Recurrence Fleischer et al (JACI 2004;114:1195) • One patient from our previous studies with definite recurrence as well as several reported elsewhere • Also found in previous study that most patients were still avoiding peanut, though not as strictly • 68 of 96 patients (71%) from prior studies recruited • Questionnaire detailing characteristics of peanut ingestion and any reactions to peanut since passing challenge • Patients also offered repeat skin, CAP-RAST testing, and double-blind, placebo-controlled, food challenge (DBPCFC)

  19. Peanut Allergy: Risk of Recurrence Fleischer et al (JACI 2004;114:1195) • 3 definite recurrences, with an overall recurrence rate of ~ 8% • The 3 patients who had recurrences consumed peanut infrequently, compared to no recurrences in the patients who ate peanut regularly (p=0.025) • 3 other patients passed challenges in spite of significant rise in PN IgE (7.6, 17.1, and 54 kU/L) • Now recommend regular peanut consumption once tolerant

  20. The Natural History of Tree Nut Allergy (Fleischer et al, JACI 2005) • 275 children with tree nut allergy were studied • 9% of the 275 subjects (95% CI 4.7% – 13.3%) outgrew their allergy • 58% with TN-specific IgE <5 kU/L and 63% <2 kU/L passed their challenges • No one with allergy to more than 2 tree nuts outgrew their allergy • No other factors predicted who would outgrow their allergy (such as reaction severity)

  21. Natural History of Peanut Allergy - Current Approach • All children with peanut (and tree nut) allergy should be re-evaluated every 1 - 2 years, at least up to the age of 6 • The CAP-RAST is the preferred method of evaluation • Selected patients should undergo challenge • Age > 4 years • No reaction in past 1-2 years • CAP-RAST <2 kU/L

  22. Food Allergy – Possible Prevention Strategies • Avoid all peanuts and tree nuts in the last trimester of pregnancy and while breast feeding • Do not introduce peanuts, tree nuts, fish, and shellfish until age 3 years • In highly atopic families • Consider avoidance of milk and egg while breast feeding • Supplement with hypoallergenic formula • Delay intro of allergenic foods until at least age one

  23. Food Allergy - Treatment • Strict avoidance • Treatment of reactions • Immunotherapy / future therapies

  24. Peanut Allergy - Avoidance • Read all labels, avoid “may contain” products • Avoid other high risk foods • Baked goods • Ethnic (especially Asian) foods • Candies • Ice creams • ? Peanut free homes, classrooms, schools • Airlines, other sources of airborne exposure

  25. Food Allergy – Treatment of Reactions • Complete avoidance is impossible • Must always be prepared to treat a reaction • Have an emergency action plan • Keep self-injectable epinephrine on hand at all times • Train caregivers and teachers on EpiPen or Twinject use • Wear MedicAlertbracelet

  26. Approaches to the Treatment of Food Allergy • Anti-IgE antibodies (Xolair) • Immunotherapy • intact allergen • modified allergen (vaccine) • routes of delivery: • oral, subcutaneous, rectal • Chinese herbal remedy • Others

  27. Approaches to the Treatment of Food Allergy • Anti-IgE Antibody Therapy • These antibodies block the interaction of allergen with IgE and thereby reduce or prevent allergic reactions • Given by injection every 2 – 4 weeks • This has proven moderately effective in allergic asthma and allergic rhinitis • One study on the treatment of food allergy has been completed

  28. Effect of Anti-IgE Therapy in Patients with Peanut Allergy(Leung et al, NEJM 2003;348:986) • Methods • Double-blind trial comparing placebo to 3 doses of TNX-901 (150, 300, and 450 mg) • Rx given by SQ injection every 4 weeks x 4 doses • Peanut challenges done at baseline and 2 – 4 weeks after final dose • 84 patients were studied

  29. Effect of Anti-IgE on Peanut Challenge Dose of TNX-901

  30. Anti-IgE Therapy – How encouraged should we be? • TNX-901 clearly increased ability to tolerate peanut in a majority of patients (although some patients did not get any protection) • Dose related effect • At the highest dose, would protect most patients from reactions due to accidental exposures • Peanut allergy was studied but the treatment could be used for any food allergy • Must be given on a continuous basis (this is a medicine, not a vaccine)

  31. Anti-IgE Therapy – Unanswered Questions • Will it work in highly allergic patients? • Will not work if total IgE level too high (>1000) • Legal issues (TNX-901 will not be studied further) • Will Xolair be as effective as TNX-901 • Significant issues in getting Xolair approved • Safety concerns • Cost concerns • If approved, who should be treated?

  32. Approaches to the Treatment of Food Allergy Chinese Herbal Formula (FAHF-1) • Peanut allergic mice were treated with FAHF-1 for 7 weeks and then re-challenged • Peanut IgE levels and other measures of peanut allergy were markedly reduced • Allergic reactions on challenge were completed eliminated • No side effects were seen • Encouraging, but unclear how far this will go

  33. Approaches to the Treatment of Food Allergy • Immunotherapy • Induces tolerance to an allergen by giving gradually increasing doses of the allergen • In food allergy, the risks of traditional immunotherapy have far outweighed the benefits • New approaches may allow this equation to change by altering the allergen to produce the positive effect with little or no negative effect

  34. Approaches to the Treatment of Food Allergy The Peanut Allergen Ara h 2 LTILVALALF LLAAHASARQ QWELOGDRRC QSQLERQNLR PCEQHLMQKI QRDEDSYERD IgE Binding Site T Cell Binding Site Stimulates T cells but does not bind to IgE – will not cause an allergic reaction With this information, immunotherapy could be developed that only contains the relevant T cell binding segments

  35. Development of a Peanut Vaccine • Animal studies with dramatic results • The current vaccine contains epitopes from 3 major peanut allergens (named EMP-123 - Encapsulated, Recombinant Modified Peanut Proteins Ara h 1, Ara h 2, and Ara h 3) • Proposed to give rectally (suppository) by increasing doses over 8 weeks, then 3 maintenance doses given every 2 weeks • First human trials expected to start in the next 18 months • The process will be slow but this may be the best hope for an effective long term treatment

  36. Approaches to the Treatment of Food Allergy • Oral or Sublingual Immunotherapy • Induces tolerance to an allergen by giving gradually increasing doses, in this case either under the tongue or swallowed • Several preliminary studies with very encouraging results – strong evidence of at least short term desensitization • Questions as to risks and potential for long term tolerance

  37. Sublingual Immunotherapy for Hazelnut Allergy (Enrique et al, JACI 116:1073, 2005) • 23 patients with varying degree of hazelnut allergy divided into 2 treatment groups • Twenty-two patients reached the planned maximum dose at 4 days • 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 (P = .02; active group) versus 3.49 g to 4.14 g (placebo; NS) • 50% of patients who underwent active treatment reached the highest dose (20 g), but only 9% in the placebo

  38. Oral challenge tests: mean food amounts tolerated in patients with hazelnut SLIT and placebo SLIT before and after immunotherapy.

  39. Present and Future Initiatives • The Food Allergy Research Consortium - NIH sponsored consortium dedicated to the study of food allergy • 2 current studies • Observational study of infants with food allergy • Oral immunotherapy study using egg protein • Planning • Oral peanut immunotherapy study • Peanut vaccine study • Starting trial of oral milk immunotherapy next month • Two new Xolair studies are being planned to start in 2007 • Human studies of the Chinese Herbal Formula will hopefully start in the next 2 years

  40. Peanut Allergy - Summary • Peanut allergy is common, affecting about 0.6% of the US population • Accidental reactions are common and often severe • Some peanut allergy might be prevented by delaying exposure in early life • Most but not all peanut allergy is lifelong • Truly effective treatment will be possible in the next 10-20 years

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