Anaphylactic reactions after discontinuation of hymenoptera venom immunotherapy: a clonal mast cell disorder should be suspected.

BACKGROUND: Up to 75% of patients with severe anaphylactic reactions after hymenoptera sting are at risk of further severe reactions if re-stung. Venom immunotherapy (VIT) is highly effective in protecting individuals with ascertained hymenoptera venom allergy (HVA) and previous severe reactions. After a 3- to 5-year VIT course, most patients remain protected after VIT discontinuation. Otherwise, a lifelong treatment should be considered in high-risk patients (eg, in mastocytosis). Several case reports evidenced that patients with mastocytosis and HVA, although protected during VIT, can re-experience severe and sometimes fatal reactions after VIT discontinuation. OBJECTIVE: to evaluate whether patients who lost protection after VIT discontinuation may suffer from clonal mast cell disorders. METHODS: the survey describes the characteristics of patients who received a full course of VIT for previous severe reactions and who experienced another severe reaction at re-sting after VIT discontinuation. Those with a REMA scpre of 2 or more or a serum basal tryptase level of more than 25 ng/ml underwent a hematological workup (bone marrow biopsy, KIT mutation, expression of aberrant CD25) and/or skin biopsy. RESULTS: 19 patients (mean age 56,3 yy; 89,5% males) were evaluated. All of them had received at least 4 year of VIT and were protected. After VIT discontinuation, they were res-stung and developed, in all but 1 case,severe anaphylactic reactions (12 with loss of consciouness, in the absence of urticaria/angioedema). 18 patients (94,7%) had a clonal mast cell disorder, 8 of them with normal tryptase. CONCLUSIONS: looking at this selected population, we suggest that mastocytosis should be considered in patients developing severe reactions at re-sting after VIT discontinuation and, as a speculation, patients with mastocytosis and HVA should be VIT-treated lifelong