Iván Alvarez-Twose1, Roberta Zanotti2, David González-de-Olano3, Patrizia Bonadonna4, Arantza Vega5, Almudena Matito6, Laura Sánchez-Muñoz6, José Mário Morgado6, Omar Perbellini2, Andrés García-Montero7, Giovanna De Matteis8, Cristina Teodósio7, Maurizio Rossini9, María Jara-Acevedo7, Donatella Schena10, Andrea Mayado7, Alberto Zamò11, Manuela Mollejo12, Paula Sánchez-López13, Nieves Cabañes13, Alberto Orfao7, Luis Escribano14. 1. Instituto de Estudios de Mastocitosis de Castilla La Mancha (CLMast), Hospital Virgen del Valle, Toledo, Spain; Spanish Network on Mastocytosis (REMA), Toledo and Salamanca, Spain. Electronic address: ivana@sescam.jccm.es. 2. Section of Haematology, Department of Medicine, University of Verona, Verona, Italy; Multidisciplinary Outpatients Clinics for Mastocytosis, Verona, Italy. 3. Spanish Network on Mastocytosis (REMA), Toledo and Salamanca, Spain; Allergy Unit, Hospital de Fuenlabrada, Madrid, Spain. 4. Multidisciplinary Outpatients Clinics for Mastocytosis, Verona, Italy; Allergy Unit, Azienda Ospedaliera Universitaria Integrata, Verona, Italy. 5. Allergy Department, Hospital de Guadalajara, Guadalajara, Spain. 6. Instituto de Estudios de Mastocitosis de Castilla La Mancha (CLMast), Hospital Virgen del Valle, Toledo, Spain; Spanish Network on Mastocytosis (REMA), Toledo and Salamanca, Spain. 7. Spanish Network on Mastocytosis (REMA), Toledo and Salamanca, Spain; Centro de Investigación del Cáncer/IBMCC (USAL/CSIC) and IBSAL, Departamento de Medicina and Servicio General de Citometría, University of Salamanca, Salamanca, Spain. 8. Multidisciplinary Outpatients Clinics for Mastocytosis, Verona, Italy; Clinical Chemistry and Haematology, Azienda Ospedaliera Universitaria Integrata, Verona, Italy. 9. Multidisciplinary Outpatients Clinics for Mastocytosis, Verona, Italy; Section of Rheumatology, Department of Medicine, Azienda Ospedaliera Universitaria Integrata, Verona, Italy. 10. Multidisciplinary Outpatients Clinics for Mastocytosis, Verona, Italy; Section of Dermatology, Department of Medicine, Azienda Ospedaliera Universitaria Integrata, Verona, Italy. 11. Multidisciplinary Outpatients Clinics for Mastocytosis, Verona, Italy; Department of Pathology, Azienda Ospedaliera Universitaria Integrata, Verona, Italy. 12. Spanish Network on Mastocytosis (REMA), Toledo and Salamanca, Spain; Pathology Department, Hospital Virgen de la Salud, Toledo, Spain. 13. Allergy Unit, Hospital Virgen del Valle, Toledo, Spain. 14. Spanish Network on Mastocytosis (REMA), Toledo and Salamanca, Spain.
Abstract
BACKGROUND: 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. OBJECTIVE: We aimed to determine the clinical and laboratory features of ISMs(-) associated with insect-induced anaphylaxis (insectISMs(-)) versus other patients with ISM. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: 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. OBJECTIVE: We aimed to determine the clinical and laboratory features of ISMs(-) associated with insect-induced anaphylaxis (insectISMs(-)) versus other patients with ISM. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Keywords:
BM; Bone marrow; CLMast; Hymenoptera; ISM; ISMs(+); ISMs(−); Indolent systemic mastocytosis; Indolent systemic mastocytosis with skin lesions; Indolent systemic mastocytosis without skin lesions; Instituto de Estudios de Mastocitosis de Castilla La Mancha, The Clinical Reference Centre of the Spanish Network on Mastocytosis (REMA); MC; MCAS; Mast cell; Mast cell activation syndrome; REMA; SM; Serum baseline tryptase; Spanish Network on Mastocytosis; Systemic mastocytosis; VIT; Venom immunotherapy; WHO; World Health Organization; anaphylaxis; insect; insect sting anaphylaxis; mastocytosis; sBT
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