Mammalian milk allergy: avoidance strategies and oral desensitization.

PURPOSE OF REVIEW: To address what is currently the most significant, fundamental question in the management of milk-allergic patients: is the best pathway to developing tolerance to milk via complete avoidance or by regular intentional exposure to the offending agent? RECENT FINDINGS: The current standard of care for the management of milk-allergic patients, and food-allergic patients in general, remains avoidance of suspected allergens. However, there is growing evidence that regular oral exposure to gradually increasing amounts of an allergenic food can lead to a desensitized state in most food-allergic children. A limited number of studies have attempted to demonstrate permanent tolerance induction. In those cases, a minority of participants has achieved this. Mechanisms of action have not been extensively evaluated, but when serologic studies have been reported, changes have been similar to those seen with standard subcutaneous immunotherapy. That is, food-specific IgE is typically unchanged or slightly decreased, whereas food-specific IgG4 increases substantially. SUMMARY: Consumption of extensively heated cow's milk and treatment with orally or sublingually administered milk immunotherapy are promising therapeutic approaches. It remains to be determined whether or not the majority of milk-allergic patients can be permanently tolerized through these methods and what the mechanisms of action are for both desensitization and tolerization.

Towards a cure for food allergy.

Over the past two decades, food allergies have become both more prevalent and long lasting. This burgeoning problem has not been met with any therapeutic options to date, and patients must attempt to avoid known allergenic foods and treat any allergic reactions with 'as-needed' medications. There are a number of promising emerging therapeutic modalities for food allergy, including allergen-specific and allergen non-specific immunotherapeutic approaches. Although the allergen-specific approaches have some distinct differences, they all attempt to induce tolerance by exposing the patient to an allergen via the mucosal route (oral tolerance induction). Allergen non-specific approaches include biologics to suppress free total IgE levels (e.g. anti-IgE antibody) or to induce more general immune suppression (Chinese herbal medication).

A randomized, double-blind, placebo-controlled study of milk oral immunotherapy for cow's milk allergy.

BACKGROUND: Orally administered, food-specific immunotherapy appears effective in desensitizing and potentially permanently tolerizing allergic individuals. OBJECTIVE: We sought to determine whether milk oral immunotherapy (OIT) is safe and efficacious in desensitizing children with cow's milk allergy. METHODS: Twenty children were randomized to milk or placebo OIT (2:1 ratio). Dosing included 3 phases: the build-up day (initial dose, 0.4 mg of milk protein; final dose, 50 mg), daily doses with 8 weekly in-office dose increases to a maximum of 500 mg, and continued daily maintenance doses for 3 to 4 months. Double-blind, placebo-controlled food challenges; end-point titration skin prick tests; and milk protein serologic studies were performed before and after OIT. RESULTS: Nineteen patients, 6 to 17 years of age, completed treatment: 12 in the active group and 7 in the placebo group. One dropped out because of persistent eczema during dose escalation. Baseline median milk IgE levels in the active (n = 13) versus placebo (n = 7) groups were 34.8 kUa/L (range, 4.86-314 kUa/L) versus 14.6 kUa/L (range, 0.93-133.4 kUa/L). The median milk threshold dose in both groups was 40 mg at the baseline challenge. After OIT, the median cumulative dose inducing a reaction in the active treatment group was 5140 mg (range 2540-8140 mg), whereas all patients in the placebo group reacted at 40 mg (P = .0003). Among 2437 active OIT doses versus 1193 placebo doses, there were 1107 (45.4%) versus 134 (11.2%) total reactions, with local symptoms being most common. Milk-specific IgE levels did not change significantly in either group. Milk IgG levels increased significantly in the active treatment group, with a predominant milk IgG4 level increase. CONCLUSIONS: Milk OIT appears to be efficacious in the treatment of cow's milk allergy. The side-effect profile appears acceptable but requires further study.

Peanut and tree nut allergy in childhood.

Peanut and tree nut allergies present multiple challenges in their presentation and management. These challenges have become increasingly relevant in recent years, as these allergies appear to have become more common. An estimated 1-2% of the population in the USA is allergic to peanut or tree nuts. Peanut allergy typically presents with symptoms in one of the first few exposures to peanut. Diagnosis is based on clinical history along with skin prick test, or quantitation of allergen-specific immunoglobulin E (IgE), and oral food challenges when indicated. Once the diagnosis is confirmed, the only current management approach is strict avoidance of the food. This is clearly an imperfect option as it can be difficult to avoid completely peanut and tree nuts and accidental exposures are not uncommon. Only about 20% of those with peanut allergy, and <10% of those with tree nut allergy, are reported to acquire tolerance. Additionally, peanut allergy can recur, with one study finding a recurrence rate of 8%. Peanut and tree nuts are the foods most frequently associated with fatal episodes of anaphylaxis. This is of particular concern in adolescents and young adults, among whom life-threatening and fatal food allergy-related reactions are most common.

The natural history of egg allergy.

BACKGROUND: Egg allergy is very common, affecting 1% to 2% of children. It is generally thought that the majority of children with egg allergy develop tolerance in early childhood; however, this has not been examined in a large cohort with egg allergy. OBJECTIVE: The purpose of the study was to estimate the proportion of children with egg allergy who develop egg tolerance and to identify predictors of tolerance development. METHODS: Retrospective chart review of patients with egg allergy seen in a tertiary referral clinic. Patients were considered to have developed egg tolerance if they tolerated concentrated egg. RESULTS: Kaplan-Meier analysis predicted resolution in 4% of patients with egg allergy by age 4 years, 12% by age 6 years, 37% by age 10 years, and 68% by age 16 years. Patients with persistent egg allergy had higher egg IgE levels at all ages to age 18 years. A patient's highest recorded egg IgE, presence of other atopic disease, and presence of other food allergy were significantly related to egg allergy persistence. CONCLUSION: A majority of patients with egg allergy will develop egg tolerance, although the rate of tolerance development is slower than described previously. Egg IgE is predictive of allergy outcome and should be used in counseling patients on prognosis. CLINICAL IMPLICATIONS: Most patients with egg allergy are likely to develop egg tolerance by late childhood, with the exception of patients with an egg IgE greater than 50 kU/L, who are unlikely to develop egg tolerance.

The natural history of IgE-mediated cow's milk allergy.

BACKGROUND: Cow's milk allergy (CMA) is the most common food allergy in infants and young children, affecting 2% to 3% of the general population. Most studies have shown the prognosis of developing tolerance to cow's milk to be good, with most outgrowing their allergy by age 3 years. OBJECTIVE: To define the natural course of CMA and identify the factors that best predict outcome in a large referral population of children with CMA. METHODS: Clinical history, test results, and final outcome were collected on 807 patients with IgE-mediated CMA. Patients were considered tolerant after they passed a challenge or experienced no reactions in the past 12 months and had a cow's milk IgE (cm-IgE) level <3 kU/L. RESULTS: Rates of resolution were 19% by age 4 years, 42% by age 8 years, 64% by age 12 years, and 79% by 16 years. Patients with persistent allergy had higher cm-IgE levels at all ages to age 16 years. The highest cm-IgE for each patient, defined as peak cm-IgE, was found to be highly predictive of outcome (P < .001). Coexisting asthma (P < .001) and allergic rhinitis (P < .001) were also significant predictors of outcome. CONCLUSION: The prognosis for CMA in this population is worse than previously reported. However, some patients developed tolerance during adolescence, indicating that follow-up and re-evaluation of CMA patients is important in their care. cm-IgE level is highly predictive of outcome. CLINICAL IMPLICATIONS: The increasing potential for persistence of CMA, along with cm-IgE level's effect on prognosis, should be considered when counseling families regarding expected clinical course.