Systemic mastocytosis with KIT V560G mutation presenting as recurrent episodes of vascular collapse: response to disodium cromoglycate and disease outcome
Abstract Background Mastocytosis are rare diseases characterized by an accumulation of clonal mast cells (MCs) in one or multiple organs or tissues. Patients with systemic mastocytosis (SM), whose MCs frequently arbor the activating D816V KIT mutation, may have indolent to aggressive diseases, and t...
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doaj-17071cd584064b0cbf9bb683df5a73332020-11-24T21:55:34ZengBMCAllergy, Asthma & Clinical Immunology1710-14922017-04-0113111010.1186/s13223-017-0193-xSystemic mastocytosis with KIT V560G mutation presenting as recurrent episodes of vascular collapse: response to disodium cromoglycate and disease outcomeIolanda Conde-Fernandes0Rita Sampaio1Filipa Moreno2José Palla-Garcia3Maria dos Anjos Teixeira4Inês Freitas5Esmeralda Neves6Maria Jara-Acevedo7Luis Escribano8Margarida Lima9Consulta Multidisciplinar de Linfomas Cutâneos e Mastocitoses (CMLC), Hospital de Santo António (HSA), Centro Hospitalar do Porto (CHP)Serviço de Anatomia Patológica, Hospital de Santo António (HSA), Centro Hospitalar do Porto (CHP)Serviço de Anatomia Patológica, Hospital de Santo António (HSA), Centro Hospitalar do Porto (CHP)Serviço de Anatomia Patológica, Hospital de Santo António (HSA), Centro Hospitalar do Porto (CHP)Laboratório de Citometria, Serviço de Hematologia Clínica, Hospital de Santo António (HSA), Centro Hospitalar do Porto (CHP)Serviço de Hematologia Laboratorial, Hospital de Santo António (HSA), Centro Hospitalar do Porto (CHP)Serviço de Imunologia, Hospital de Santo António (HSA), Centro Hospitalar do Porto (CHP)Servicio General de Citometría, Instituto de Biología Molecular y Celular del Cáncer, Centro de Investigación del CáncerServicio General de Citometría, Instituto de Biología Molecular y Celular del Cáncer, Centro de Investigación del CáncerConsulta Multidisciplinar de Linfomas Cutâneos e Mastocitoses (CMLC), Hospital de Santo António (HSA), Centro Hospitalar do Porto (CHP)Abstract Background Mastocytosis are rare diseases characterized by an accumulation of clonal mast cells (MCs) in one or multiple organs or tissues. Patients with systemic mastocytosis (SM), whose MCs frequently arbor the activating D816V KIT mutation, may have indolent to aggressive diseases, and they may experience MC mediator related symptoms. Indolent SM with recurrent anaphylaxis or vascular collapse in the absence of skin lesions, ISMs(−), is a specific subtype indolent SM (ISM), and this clonal MC activation disorder represents a significant fraction of all MC activation syndromes. The V560G KIT mutation is extremely rare in patients with SM and its biological and prognostic impact remains unknown. Case presentation A 15-year old boy was referred to our hospital because of repeated episodes of flushing, hypotension and syncope since the age of 3-years, preceded by skin lesions compatible with mastocytosis on histopathology that had disappeared in the late-early childhood. Diagnosis of ISM, more precisely the ISMs(−) variant, was confirmed based on the clinical manifestations together with increased baseline serum tryptase levels and the presence of morphologically atypical, mature appearing (CD117+high, FcεRI+) phenotypically aberrant (CD2+, CD25+) MCs, expressing activation-associated markers (CD63, CD69), in the bone marrow. Molecular genetic studies revealed the presence of the KIT V560G mutation in bone marrow MCs, but not in other bone marrow cells, whereas the screening for mutations in codon 816 of KIT was negative. The patient was treated with oral disodium cromoglycate and the disease had a favorable outcome after an eleven-year follow-up period, during which progressively lower serum tryptase levels together with the fully disappearance of all clinical manifestations was observed. Conclusions To the best of our knowledge this first report of a patient with ISM, whose bone marrow MCs carry the KIT V560G activating mutation, manifesting as recurrent spontaneous episodes of flushing and vascular collapse in the absence of skin lesions at the time of diagnosis, in whom disodium cromoglycate had led to long term clinical remission.http://link.springer.com/article/10.1186/s13223-017-0193-xMast cellsSystemic mastocytosisMast cell activation disordersRecurrent anaphylaxisKIT V560G mutationDisodium cromoglycate |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Iolanda Conde-Fernandes Rita Sampaio Filipa Moreno José Palla-Garcia Maria dos Anjos Teixeira Inês Freitas Esmeralda Neves Maria Jara-Acevedo Luis Escribano Margarida Lima |
spellingShingle |
Iolanda Conde-Fernandes Rita Sampaio Filipa Moreno José Palla-Garcia Maria dos Anjos Teixeira Inês Freitas Esmeralda Neves Maria Jara-Acevedo Luis Escribano Margarida Lima Systemic mastocytosis with KIT V560G mutation presenting as recurrent episodes of vascular collapse: response to disodium cromoglycate and disease outcome Allergy, Asthma & Clinical Immunology Mast cells Systemic mastocytosis Mast cell activation disorders Recurrent anaphylaxis KIT V560G mutation Disodium cromoglycate |
author_facet |
Iolanda Conde-Fernandes Rita Sampaio Filipa Moreno José Palla-Garcia Maria dos Anjos Teixeira Inês Freitas Esmeralda Neves Maria Jara-Acevedo Luis Escribano Margarida Lima |
author_sort |
Iolanda Conde-Fernandes |
title |
Systemic mastocytosis with KIT V560G mutation presenting as recurrent episodes of vascular collapse: response to disodium cromoglycate and disease outcome |
title_short |
Systemic mastocytosis with KIT V560G mutation presenting as recurrent episodes of vascular collapse: response to disodium cromoglycate and disease outcome |
title_full |
Systemic mastocytosis with KIT V560G mutation presenting as recurrent episodes of vascular collapse: response to disodium cromoglycate and disease outcome |
title_fullStr |
Systemic mastocytosis with KIT V560G mutation presenting as recurrent episodes of vascular collapse: response to disodium cromoglycate and disease outcome |
title_full_unstemmed |
Systemic mastocytosis with KIT V560G mutation presenting as recurrent episodes of vascular collapse: response to disodium cromoglycate and disease outcome |
title_sort |
systemic mastocytosis with kit v560g mutation presenting as recurrent episodes of vascular collapse: response to disodium cromoglycate and disease outcome |
publisher |
BMC |
series |
Allergy, Asthma & Clinical Immunology |
issn |
1710-1492 |
publishDate |
2017-04-01 |
description |
Abstract Background Mastocytosis are rare diseases characterized by an accumulation of clonal mast cells (MCs) in one or multiple organs or tissues. Patients with systemic mastocytosis (SM), whose MCs frequently arbor the activating D816V KIT mutation, may have indolent to aggressive diseases, and they may experience MC mediator related symptoms. Indolent SM with recurrent anaphylaxis or vascular collapse in the absence of skin lesions, ISMs(−), is a specific subtype indolent SM (ISM), and this clonal MC activation disorder represents a significant fraction of all MC activation syndromes. The V560G KIT mutation is extremely rare in patients with SM and its biological and prognostic impact remains unknown. Case presentation A 15-year old boy was referred to our hospital because of repeated episodes of flushing, hypotension and syncope since the age of 3-years, preceded by skin lesions compatible with mastocytosis on histopathology that had disappeared in the late-early childhood. Diagnosis of ISM, more precisely the ISMs(−) variant, was confirmed based on the clinical manifestations together with increased baseline serum tryptase levels and the presence of morphologically atypical, mature appearing (CD117+high, FcεRI+) phenotypically aberrant (CD2+, CD25+) MCs, expressing activation-associated markers (CD63, CD69), in the bone marrow. Molecular genetic studies revealed the presence of the KIT V560G mutation in bone marrow MCs, but not in other bone marrow cells, whereas the screening for mutations in codon 816 of KIT was negative. The patient was treated with oral disodium cromoglycate and the disease had a favorable outcome after an eleven-year follow-up period, during which progressively lower serum tryptase levels together with the fully disappearance of all clinical manifestations was observed. Conclusions To the best of our knowledge this first report of a patient with ISM, whose bone marrow MCs carry the KIT V560G activating mutation, manifesting as recurrent spontaneous episodes of flushing and vascular collapse in the absence of skin lesions at the time of diagnosis, in whom disodium cromoglycate had led to long term clinical remission. |
topic |
Mast cells Systemic mastocytosis Mast cell activation disorders Recurrent anaphylaxis KIT V560G mutation Disodium cromoglycate |
url |
http://link.springer.com/article/10.1186/s13223-017-0193-x |
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