S. Allan Bock

Work Group report: Oral food challenge testing

Oral food challenges are procedures conducted by allergists/immunologists to make an accurate diagnosis of immediate, and occasionally delayed, adverse reactions to foods. The timing of the challenge is carefully chosen based on the individual patient history and the results of skin prick tests and food specific serum IgE values. The type of the challenge is determined by the history, the age of the patient, and the likelihood of encountering subjective reactions. The food challenge requires preparation of the patient for the procedure and preparation of the office for the organized conduct of the challenge, for a careful assessment of the symptoms and signs and the treatment of reactions. The starting dose, the escalation of the dosing, and the intervals between doses are determined based on experience and the patients history. The interpretation of the results of the challenge and arrangements for follow-up after a challenge are important. A negative oral food challenge result allows introduction of the food into the diet, whereas a positive oral food challenge result provides a sound basis for continued avoidance of the food.

Soy allergy in infants and children with IgE-associated cow's milk allergy.

OBJECTIVES To determine the prevalence of soy allergy in IgE-associated cows milk allergy (CMA). STUDY DESIGN Children <3.5 years with documented IgE-associated CMA (n = 93) were evaluated for soy allergy by double-blind, placebo-controlled food challenge, open challenge, or convincing previous history of an anaphylactic reaction to soy. Children tolerant to soy at entry received soy formula and were followed up for 1 year. RESULTS Of this IgE-associated CMA cohort (ages 3 to 41 months), 14% (95% CI = 7. 7%-22.7%) were determined to have soy allergy, 12 definitely at entry and 1 possibly after 1 year of soy ingestion. The latter child experienced severe failure to thrive at enrollment and exhibited improved growth while receiving soy during follow-up but was diagnosed with eosinophilic esophagitis at study completion. Improved growth (P <.05) occurred in the non-soy-allergic cohort ingesting soy formula (579 31 mL/d) during the year of follow-up. CONCLUSIONS Soy allergy occurs in only a small minority of young children with IgE-associated CMA. As such, soy formula may provide a safe and growth-promoting alternative for the majority of children with IgE-associated CMA shown to be soy tolerant at the time of introduction of soy formula.

Oral Food Challenges in Children with a Diagnosis of Food Allergy

OBJECTIVE To assess the outcome of oral food challenges in patients placed on elimination diets based primarily on positive serum immunoglobulin E (IgE) immunoassay results. STUDY DESIGN This is a retrospective chart review of 125 children aged 1-19 years (median age, 4 years) evaluated between January 2007 and August 2008 for IgE-mediated food allergy at National Jewish Health and who underwent an oral food challenge. Clinical history, prick skin test results, and serum allergen-specific IgE test results were obtained. RESULTS The data were summarized for food avoidance and oral food challenge results. Depending on the reason for avoidance, 84%-93% of the foods being avoided were returned to the diet after an oral food challenge, indicating that the vast majority of foods that had been restricted could be tolerated at discharge. CONCLUSIONS In the absence of anaphylaxis, the primary reliance on serum food-specific IgE testing to determine the need for a food elimination diet is not sufficient, especially in children with atopic dermatitis. In those circumstances, oral food challenges may be indicated to confirm food allergy status.

Natural history of severe reactions to foods in young children

Nine children with very severe adverse reactions to foods during the first 2 years of life were followed to determine the subsequent course of their reactions. Cautious challenges were given in these children over a period of time. Three of nine children can tolerate the offending food in usual portions; four of nine can tolerate small amounts of the offending food; and two children continue to have reactions to small amounts of the offending food. At some time each of these children have exhibited significant positive wheal and flare reactions when skin tested with extracts of the offending food. This study demonstrates that some children with severe reactions to foods may lose their frightening reactivity to foods over time. Very careful challenges in these patients are thus justified to save families from prolonged anxiety about accidental ingestion, which inevitably occurs.

Food allergy in infancy.

This article discusses the current understanding of the mechanisms of food hypersensitivity and presents a practical approach to the condition. Skin testing is a useful technique if properly applied and interpreted; however, double-blind placebo-controlled food challenge is the standard for accurate diagnosis against which all other tests should be compared. Treatment still consists of avoidance of the offending food allergens; however, most children lose their reactivity, and thus regular challenges are important.

The incidence of severe adverse reactions to food in Colorado

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RBL cells expressing human FcεRI are a sensitive tool for exploring functional IgE–allergen interactions: studies with sera from peanut-sensitive patients

Rat basophilic leukemia cells (RBL SX-38) express the alpha, beta, and gamma chains of human Fc epsilon RI. Following sensitization with IgE from a subset of allergic human donors, these cells can be triggered by exposure to anti-IgE or to very low concentrations of specific allergens. We examined 18 sera from patients who were highly sensitive to peanuts by history and had anti-peanut IgE by in vitro testing. The ability of these sera to sensitize the RBL SX-38 cells for degranulation with peanut allergens correlates very well with the absolute amount of anti-peanut IgE (r=0.95; p<0.001). The most effective sera contained at least 50 kU/l of total IgE and at least 15 kU/l of peanut-specific IgE. RBL SX-38 cells sensitized with these sera degranulated optimally upon exposure to anti-IgE (net degranulation of 40+/-8%, means+/-S.D.; n=8) and to a 10(5)-10(6) dilution of crude peanut extract (CPE) (37+/-7% net degranulation; 93+/-13% of that seen with anti-IgE). This assay is quite sensitive. Cells sensitized with selected sera are activated by exposure to a 1:10(7) dilution of the CPE containing picogram amounts of peanut allergens. This assay is also quite specific. Cells sensitized with sera from patients with anti-peanut IgE and no detectable IgE against soybean, walnut or grass pollen did not degranulate following exposure to these latter antigens. The converse was also true; cells sensitized with sera from patients without anti-peanut IgE did not react to peanut. These data demonstrate that RBL cells expressing human Fc epsilon RI form the basis of a useful model system for the detection of allergens and for the study of IgE-allergen interactions.

A critical evaluation of clinical trials in adverse reactions to foods in children

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Oral food challenge practices among allergists in the United States.

To the Editor: The recently published National Institute of Allergy and Infectious Diseases–sponsored ‘‘Guidelines for the diagnosis and management of food allergy in the United States’’ and the ‘‘Work group report’’ both state that oral food challenge (OFC) is a critical procedure for the evaluation of food allergy. Fleischer et al reported that OFCs were crucial in identifying children who were otherwise following unnecessary dietary restrictions based on the results of in vitro testing. A subgroup of the Adverse Reactions to Foods Committee of the American Academy of Allergy, Asthma & Immunology (AAAAI) conceived and designed a survey to collect data about allergists’ use of this important diagnostic procedure. The anonymous survey, distributed to AAAAI member allergists whose primary practice site was located in the United States or its territories, was conducted in December 2009 by using Survey Monkey. There were 670 respondents in total whose practices were located in the District of Columbia, Puerto Rico, and all states except Alaska and Wyoming. Among them, 35% reported being in practice for more than 20 years, whereas 27% practiced for less than 5 years. Thirty-five percent of respondents were in group allergy/immunology practices, 23% were in solo practices, and 16% were in group multispecialty practices; 19% were in academics, and 5% were hospital based. More than half (52%) of respondents had residency training in pediatrics, 39% trained in internal medicine, and 9% reported a combined medicine-pediatrics residency. Only 45% reported having personally performed OFCs during fellowship training. A majority of respondents (85.5% [n 5 568]) indicated that they currently perform office-based OFCs. Those who did not (14.5% [n5 96]) were instructed not to continuewith the rest of the survey. The rest of the data in this report are limited to those who indicated that they perform OFCs in their offices. The majority (69.9%) of respondents generally perform 1 to 5 OFCs per month; 12.7% perform less than 1, 11.8% perform 6 to 10, and 5.6% perform more than 10 per month. Open nonblinded challenges aremost commonly performed (87.6%of respondents); 8.2% of OFCs are single-blind, 1.1% are double-blind without placebo, and 3.2% are double-blind, placebo-controlled OFCs. More than half (53.6%) of respondents obtain written informed consent for OFCs. Fifty-seven percent stated that their office staff is involved in preparation of the food to be used in OFCs. Table I shows specific issues related to effort in conducting OFCs. The survey also inquired about coding and reimbursement. When asked how they code for OFCs, 59.4% submit both an Evaluation and Management (E and M) and ingestion challenge procedure code (Current Procedural Terminology [CPT] code 95075); 29.4% use only CPT code 95075, and 7.1% use only an E and M code. In response to the question ‘‘If you receive reimbursement from third party payors, do you feel it is adequate?,’’ 76.9% responded no. Despite the perceived barriers (Table II), 98.7% of respondents indicated that they saw a need to perform OFCs in their clinical practice. In summary, 85.5% of respondents report that they perform OFCs. However, there is a large discrepancy in the number of OFCs being performed, with a very small proportion (5.6%) of allergists performing more than 10 OFCs per month and 70% performing 1 to 5 OFCs per month. The top 3 perceived barriers to performing OFCs were time, inadequate reimbursement, and risk of an adverse event. Indeed, the survey disclosed that the duration of the procedure is most often 3 to 4 hours, with significant use of the allergist and additional office staff for preparation and supervision. The reported lack of adequate reimbursement (77%) for the time-intense procedure represents another important barrier, which likely explains the low rate of use. The survey also disclosed underperformance of written informed consent and discrepancies regarding the manner of coding. A troubling finding was that fewer than half of the respondents had personally performed OFCs during allergy/ immunology training. The survey has limitations, including self-selected participation and self-report. For example, lack of adequate training in the performance of OFCs could be a self-selecting factor. However, it is likely that nonparticipants would comprise allergists who find barriers to performing OFCs to be insurmountable, biasing the TABLE I. Effort and personnel involved in OFCs

Evaluation of a patient with both aquagenic and cholinergic urticaria

An 11-yr-old girl presented with a history of urticaria induced by warm or cool showers, exercise, and emotional stimuli. During evaluation she repeatedly developed generalized punctate urticaria, pruritus, palpitations, and headaches after warm baths or exercise, and she had a positive methacholine skin test. She developed similar lesions and pruritus after local application of sterile water, tap water, ethanol, normal saline, or 3% saline. The diagnosis of combined aquagenic and cholinergic urticaria was made and presented a unique opportunity to study and compare mediator release and clinical symptoms in both conditions. The patient was submerged in bath water at either 37 degree or 41 degree C to induce either aquagenic or cholinergic urticaria, respectively. Histamine was released into the systemic circulation in both conditions in a similar time course; however, systemic symptoms occurred only after the 41 degree C bath. After failure to induce tolerance to the 41 degree C bath water, hydroxyzine therapy was instituted. One week later she was rechallenged; few symptoms appeared, and a rise in serum histamine was not detected as had been shown in previous challenges. The data suggest that in our patient, hydroxyzine may have contributed to the inhibition of both histamine release and the appearance of symptoms during hot bath challenging.