Hymenoptera Anaphylaxis as a Clonal Mast Cell Disorder.

Up to 7% of adult patients with Hymenoptera venom allergy may suffer from a clonal mast cell disease. Patients with clonal mast cell disease and Hymenoptera venom anaphylaxis are commonly males, without skin lesions, and anaphylaxis is characterized by hypotension and syncope in the absence of urticaria and angioedema. A normal value of tryptase does not exclude a mastocytosis. The diagnosis of a mast cell disease leads to several therapeutic consequences concerning the treatment of Hymenoptera venom allergy as matter of fact these patients have to undergo long-life venom immunotherapy, to prevent further, potentially fatal severe reactions.

Bonadonna P ，Scaffidi L 《-》

Hymenoptera Allergy and Mast Cell Activation Syndromes.

Bonadonna P ，Bonifacio M ，Lombardo C ，Zanotti R ... -  《-》

Clonal mast cell disorders in patients with severe Hymenoptera venom allergy and normal serum tryptase levels.

Systemic mastocytosis is a clonal mast cell (MC) disease that can lead to potentially fatal anaphylactic reactions caused by excessive MC mediator release. The prevalence of mastocytosis in patients with Hymenoptera venom allergy is high, and thus the disease should be suspected in patients with severe reactions caused by Hymenoptera stings and increased serum basal tryptase (SBT) levels. We sought to evaluate the presence of clonal MC disorders in patients seen at our mastocytosis center with Hymenoptera sting-induced anaphylaxis, documented hypotension, absence of urticaria pigmentosa, and normal SBT levels. Twenty-two patients with Hymenoptera sting-induced anaphylaxis, without skin lesions, and with tryptase levels of less than 11.4 ng/mL underwent bone marrow evaluation. Bone mineral density was assessed in those patients with ascertained mastocytosis. In 16 of 22 patients, a diagnosis of indolent mastocytosis could be established, and 1 patient had a monoclonal MC activation syndrome. Patients with mastocytosis had higher SBT levels (P = .03) but only rarely had angioedema/urticaria associated with hypotension (P = .004). The absence of urticaria or angioedema in severe reactions to Hymenoptera stings with hypotension might represent the most relevant factor in identifying patients with mastocytosis, regardless of their serum tryptase levels.

Zanotti R ，Lombardo C ，Passalacqua G ，Caimmi C ，Bonifacio M ，De Matteis G ，Perbellini O ，Rossini M ，Schena D ，Busa M ，Marcotulli MC ，Bilò MB ，Franchini M ，Marchi G ，Simioni L ，Bonadonna P ... -  《-》

Serum concentration of baseline mast cell tryptase: evidence for a decline during long-term immunotherapy for Hymenoptera venom allergy.

Dugas-Breit S ，Przybilla B ，Dugas M ，Arnold A ，Pfundstein G ，Küchenhoff H ，Ruëff F ... -  《-》

Anaphylactic Reactions After Discontinuation of Hymenoptera Venom Immunotherapy: A Clonal Mast Cell Disorder Should Be Suspected.

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. To evaluate whether patients who lost protection after VIT discontinuation may suffer from clonal mast cell disorders. 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 Red Española de Mastocitosis score 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. Nineteen patients (mean age, 56.3 years; 89.5% males) were evaluated. All of them had received at least 4 years of VIT and were protected. After VIT discontinuation they were re-stung and developed, in all but 1 case, severe anaphylactic reactions (12 with loss of consciousness, in the absence of urticaria/angioedema). Eighteen patients (94.7%) had a clonal mast cell disorder, 8 of them with normal tryptase. 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.

Bonadonna P ，Zanotti R ，Pagani M ，Bonifacio M ，Scaffidi L ，Olivieri E ，Franchini M ，Reccardini F ，Costantino MT ，Roncallo C ，Mauro M ，Boni E ，Rizzini FL ，Bilò MB ，Marcarelli AR ，Passalacqua G ... -  《-》