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 ... -  《-》

Clonal mast cell disorders in patients with systemic reactions to Hymenoptera stings and increased serum tryptase levels.

Bonadonna P ，Perbellini O ，Passalacqua G ，Caruso B ，Colarossi S ，Dal Fior D ，Castellani L ，Bonetto C ，Frattini F ，Dama A ，Martinelli G ，Chilosi M ，Senna G ，Pizzolo G ，Zanotti R ... -  《-》

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 ... -  《-》

Hymenoptera Allergy and Mast Cell Activation Syndromes.

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

Nonaggressive systemic mastocytosis (SM) without skin lesions associated with insect-induced anaphylaxis shows unique features versus other indolent SM.

Indolent systemic mastocytosis (ISM) without skin lesions (ISMs(-)) shows a higher prevalence in males, lower serum baseline tryptase levels, and KIT mutation more frequently restricted to bone marrow (BM) mast cells (MCs) than ISM with skin lesions (ISMs(+)). Interestingly, in almost one-half of ISMs(-) patients, MC-mediator release episodes are triggered exclusively by insects. We aimed to determine the clinical and laboratory features of ISMs(-) associated with insect-induced anaphylaxis (insectISMs(-)) versus other patients with ISM. A total of 335 patients presenting with MC activation syndrome, including 143 insectISMs(-), 72 ISMs(-) triggered by other factors (otherISMs(-)), 56 ISMs(+), and 64 nonclonal MC activation syndrome, were studied. Compared with otherISMs(-) and ISMs(+) patients, insectISMs(-) cases showed marked male predominance (78% vs 53% and 46%; P < .001), a distinct pattern of MC-related symptoms, and significantly lower median serum baseline tryptase levels (22.4 vs 28.7 and 45.8 μg/L; P ≤ .009). Moreover, insectISMs(-) less frequently presented BM MC aggregates (46% vs 70% and 81%; P ≤ .001), and they systematically showed MC-restricted KIT mutation. ISMs(-) patients with anaphylaxis triggered exclusively by insects display clinical and laboratory features that are significantly different from other ISM cases, including other ISMs(-) and ISMs(+) patients, suggesting that they represent a unique subgroup of ISM with a particularly low BM MC burden in the absence of adverse prognostic factors.

Alvarez-Twose I ，Zanotti R ，González-de-Olano D ，Bonadonna P ，Vega A ，Matito A ，Sánchez-Muñoz L ，Morgado JM ，Perbellini O ，García-Montero A ，De Matteis G ，Teodósio C ，Rossini M ，Jara-Acevedo M ，Schena D ，Mayado A ，Zamò A ，Mollejo M ，Sánchez-López P ，Cabañes N ，Orfao A ，Escribano L ，Spanish Network on Mastocytosis (REMA) ，Italian Network on Mastocytosis (RIMA) ... -  《-》