Does severity of low-dose, double-blind, placebo-controlled food challenges reflect severity of allergic reactions to peanut in the community?

BACKGROUND: The severity of allergic reactions to food appears to be affected by many interacting factors. It is uncertain whether challenge-based reactions reflect the severity of past reactions or can predict future risk. OBJECTIVE: To explore the relationship of a subject's clinical history of past reactions to the severity of reaction elicited by a low-dose, double-blind, placebo-controlled food challenge (DBPCFC) with peanut. METHOD: Cross-sectional questionnaire assessment of community-based allergic reactions and low-dose DBPCFC in self-selected peanut-allergic subjects. Reaction severity was assessed using a novel scoring system, taking account of the dose of allergen ingested. RESULTS: Forty subjects (15 males, 23 children, 23 asthmatics by history) were studied. Only the most recent community reaction predicted the severity of reaction in the DBPCFC, but even this association was weak (r=0.37, P=0.03). Peanut-specific IgE (PsIgE) and skin prick test (SPT) weal size were not associated with community score but PsIgE level correlated well with the challenge score (r=0.6, P=0.001). Asthma did not affect the eliciting dose or challenge score directly but the association of PsIgE and challenge score was stronger in those without asthma (r=0.72, P=0.001) than in those with asthma (r=0.48, P=0.02). CONCLUSIONS: The scoring system developed appears to improve the sensitivity of assessment of reactions induced by DBPCFC. This is the first prospective study showing an association between PsIgE levels and clinical reactivity in DBPCFC, an effect that is more pronounced in non-asthmatics. This finding has important implications for the clinical care of subjects with food allergy. There is a poor correlation between the severity of reported reactions in the community and the severity of reaction elicited during low-dose DBPCFC with peanut.

Pre-natal sensitization in humans.

Allergy has a very strong hereditary component but even in identical twins, concordance for the development of allergic disease can be as low as 50%. This suggests that there is a very strong environmental influence on manifestations of sensitization. To what extent environment might have an influence on the ontogeny of sensitization antenatally has hitherto not been a focus of much research. However, circumstantial evidence suggests that this may be important.

Serological characteristics of peanut allergy.

BACKGROUND: Peanut is the most common cause of severe or fatal food-associated anaphylaxis. Studies indicate that peanut extracts contain many allergenic proteins. The identification of major and minor allergenic components is necessary for standardization of experimental and diagnostic extracts. OBJECTIVE: To identify further major and minor allergenic components of peanut extract using a large population of peanut allergics, and to relate serological findings to clinical parameters. METHODS: The crude peanut extract was fractionated by fast protein liquid chromatography and the IgE binding proteins identified by sodium dodecyl sulphate polyacrylamide gel electrophoresis followed by western blotting. Serum from 89 peanut allergics with a positive history of peanut allergy and elevated specific IgE and control serum from four atopic and four non-atopic, non-peanut allergics were used. RESULTS: Nineteen peanut proteins were found to bind IgE from peanut allergic sera. Over 70% of subjects reacted to protein bands of 63 and 17 kDa (consistent with Ara h 1 and Ara h 2, respectively), confirming the importance of these two proteins as major allergens. A high proportion of patient sera also bound proteins at 15, 10, 30, 18 and 51 kDa in decreasing order. The percentage of cases with sensitivity to a 15 kDa protein was found to be higher in patient groups with severe reactions to peanut. CONCLUSION: This study highlights the diversity of peanut allergens. Diagnostic extracts containing a high proportion of the 15 kDa component may aid in diagnosis.

An evaluation of the sensitivity of subjects with peanut allergy to very low doses of peanut protein: a randomized, double-blind, placebo-controlled food challenge study.

BACKGROUND: 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. However, subjects with peanut allergy often report severe reactions after minimal contact with peanuts, even through intact skin. OBJECTIVE: We sought to determine whether adults previously proven by challenge to be allergic to peanut react to very low doses of peanut protein. METHODS: We used a randomized, double-blind, placebo-controlled food challenge of 14 subjects allergic to peanuts with doses of peanut ranging from 10 microg to 50 mg, administered in the form of a commercially available peanut flour. RESULTS: One subject had a systemic reaction to 5 mg of peanut protein, and two subjects had mild objective reactions to 2 mg and 50 mg of peanut protein, respectively. Five subjects had mild subjective reactions (1 to 5 mg and 4 to 50 mg). All subjects with convincing objective reactions had short-lived subjective reactions to preceding doses, as low as 100 microg in two cases. Five subjects did not react to any dose up to 50 mg. CONCLUSION: Even in a group of well-characterized, highly sensitive subjects with peanut allergy, the threshold dose of peanut protein varies. As little as 100 microg of peanut protein provokes symptoms in some subjects with peanut allergy.

Clinical characteristics of peanut allergy.

BACKGROUND: Current clinical advice regarding peanut allergy is based on small series of patients. OBJECTIVE: To determine, in a large group of peanut allergic subjects, the patterns of clinical severity, symptom progression and availability and use of rescue medications. METHODS: Questionnaire study of 622 self-reported allergic subjects. RESULTS: 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. Severe symptoms were more common in adults. Abdominal symptoms were significantly associated with collapse. Fifty per cent reported reactions in the previous year. Only 82 (13%) had been admitted to hospital because of a reaction. Adrenaline was carried in some form by 65% though only 78 subjects (12.5%) had ever received injected adrenaline. Only 18/43 subjects (41%) who collapsed were given adrenaline. Skin-prick test weal size correlated weakly with severity but there were large overlaps between the groups. Peanut-specific IgE peaked in the teenage group, but did not correlate with severity. CONCLUSIONS: Peanut allergy is characterized by more severe symptoms than other food allergies and by high rates of symptoms on minimal contact. Skin-prick testing and peanut-specific IgE levels do not predict clinical severity. Avoidance of peanut is difficult. Many people suffering severe relations are inadequately treated. Sufferers need education and training in the use of rescue medication.