Nonaggressive systemic mastocytosis (SM) without skin lesions associated with insect-induced anaphylaxis shows unique features versus other indolent SM.
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.
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.
Iván
I
Alvarez-Twose
Section of Haematology, Department of Medicine, University of Verona, Verona, Italy; Multidisciplinary Outpatients Clinics for Mastocytosis, Verona, Italy.
Roberta
R
Zanotti
Spanish Network on Mastocytosis (REMA), Toledo and Salamanca, Spain; Allergy Unit, Hospital de Fuenlabrada, Madrid, Spain.
David
D
González-de-Olano
Multidisciplinary Outpatients Clinics for Mastocytosis, Verona, Italy; Allergy Unit, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.
Patrizia
P
Bonadonna
Allergy Department, Hospital de Guadalajara, Guadalajara, Spain.
Arantza
A
Vega
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.
Almudena
A
Matito
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.
Laura
L
Sánchez-Muñoz
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.
José Mário
JM
Morgado
Section of Haematology, Department of Medicine, University of Verona, Verona, Italy; Multidisciplinary Outpatients Clinics for Mastocytosis, Verona, Italy.
Omar
O
Perbellini
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.
Andrés
A
García-Montero
Multidisciplinary Outpatients Clinics for Mastocytosis, Verona, Italy; Clinical Chemistry and Haematology, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.
Giovanna
G
De Matteis
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.
Cristina
C
Teodósio
Multidisciplinary Outpatients Clinics for Mastocytosis, Verona, Italy; Section of Rheumatology, Department of Medicine, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.
Maurizio
M
Rossini
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.
María
M
Jara-Acevedo
Multidisciplinary Outpatients Clinics for Mastocytosis, Verona, Italy; Section of Dermatology, Department of Medicine, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.
Donatella
D
Schena
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.
Andrea
A
Mayado
Multidisciplinary Outpatients Clinics for Mastocytosis, Verona, Italy; Department of Pathology, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.
Alberto
A
Zamò
Spanish Network on Mastocytosis (REMA), Toledo and Salamanca, Spain; Pathology Department, Hospital Virgen de la Salud, Toledo, Spain.
Manuela
M
Mollejo
Allergy Unit, Hospital Virgen del Valle, Toledo, Spain.
Paula
P
Sánchez-López
Allergy Unit, Hospital Virgen del Valle, Toledo, Spain.
Nieves
N
Cabañes
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.
Alberto
A
Orfao
Spanish Network on Mastocytosis (REMA), Toledo and Salamanca, Spain.
Luis
L
Escribano
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000485:Allergens / Q000276:immunology; D000707:Anaphylaxis / Q000175:diagnosis / Q000276:immunology*; D000818:Animals; D001516:Bees / Q000276:immunology*; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007299:Insect Bites and Stings / Q000175:diagnosis / Q000276:immunology*; D008297:Male; D034721:Mastocytosis, Systemic / Q000175:diagnosis / Q000276:immunology*; D008875:Middle Aged; D012871:Skin Diseases / Q000175:diagnosis / Q000276:immunology*; D012882:Skin Tests; D053802:Tryptases / Q000097:blood; D014863:Wasps / Q000276:immunology*; D055815:Young Adult
D000485:Allergens; D007073:Immunoglobulin E; D053802:Tryptases
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