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Pediatric Allergy and Immunology :... Jan 2022Idiopathic anaphylaxis (AI) refers to anaphylaxis without a recognizable cause after a comprehensive allergic workup. The diagnostic approach usually includes an...
Idiopathic anaphylaxis (AI) refers to anaphylaxis without a recognizable cause after a comprehensive allergic workup. The diagnostic approach usually includes an accurate clinical history aimed at excluding both the most and the less frequent causes of anaphylaxis and all pathologies that may resemble anaphylaxis. AI is more common in adults than in children. The epidemiology of AI has been reduced in recent years, probably to increase knowledge and discover new clinical entities, such as the α-gal anaphylaxis. Anaphylaxis results from the massive activation of the mast cells (MCs). Thus, it is also necessary to exclude MC disorders, such as mastocytosis and mast cell activation syndrome, and α-tryptasemia, which may manifest with IA symptoms.
Topics: Adult; Anaphylaxis; Cell Count; Child; Humans; Mast Cell Activation Syndrome; Mast Cells; Mastocytosis; Tryptases
PubMed: 35080312
DOI: 10.1111/pai.13629 -
Immunology and Allergy Clinics of North... Nov 2023Patients with mastocytosis have an increased risk for mast cell activation events including anaphylaxis when exposed to certain drugs and Hymenoptera venom. Hypotension... (Review)
Review
Patients with mastocytosis have an increased risk for mast cell activation events including anaphylaxis when exposed to certain drugs and Hymenoptera venom. Hypotension and cardiovascular collapse without skin or other systemic manifestations can occur after Hymenoptera stings, during the perioperative period, and after exposure to nonsteroidal ntiinflammatory drugs, opioids, and other mast cell activating medications, including vancomycin and quinolones. This chapter reviews the epidemiology, mechanisms, diagnosis, management, and treatment options for Hymenoptera venom and drug-induced reactions in patients with mastocytosis.
Topics: Animals; Humans; Hymenoptera; Venom Hypersensitivity; Insect Bites and Stings; Mastocytosis; Anaphylaxis; Arthropod Venoms
PubMed: 37758407
DOI: 10.1016/j.iac.2023.04.002 -
Acta Clinica Belgica Aug 2023Mastocytosis is a complex heterogenous multisystem disorder that is characterized by pathologic activation or accumulation of neoplastic mast cells (MCs) in one or more... (Review)
Review
Mastocytosis is a complex heterogenous multisystem disorder that is characterized by pathologic activation or accumulation of neoplastic mast cells (MCs) in one or more organs. This clonal MC expansion is often associated with a somatic gain-of-function mutation (D816V in most of the cases) in the KIT gene, encoding for the MC surface receptor KIT (CD117), a stem cell growth factor receptor. Based on clinical and biochemical criteria, the World Health Organization (WHO) divided mastocytosis into different subclasses. The exact prevalence of mastocytosis remains elusive, but it is estimated that the disease affects approximately 1 in 10,000 persons. The clinical presentation of mastocytosis varies significantly, ranging from asymptomatic patients to a life-threatening disease with multiple organ involvement, potentially leading to cytopenia, malabsorption, hepatosplenomegaly, lymphadenopathy, ascites or osteolytic bone lesions with pathological fractures. Patients with mastocytosis may experience symptoms related to release of MC mediators, such as flushing or diarrhea or even more severe symptoms such as anaphylaxis. Recently, a new genetic trait, hereditary alpha tryptasemia (HaT), was described which involves a copy number variation in the TPSAB1-gene. Its role as standalone multisystem syndrome is heavily debated. There is emerging evidence suggesting there might be a link between HaT and due to the increased prevalence of HaT in patients with SM. The aim of this review is to provide a practical roadmap for diagnosis and management of mastocytosis and its associated entities, since there are still many misconceptions about these topics. AdvSM: Advanced systemic mastocytosis; ASM: Aggressive systemic mastocytosis; aST: acute serum tryptase; BM: Bone marrow; BMM: Bone marrow mastocytosis; bST: baseline serum tryptase; CM: Cutaneous mastocytosis; DCM: Diffuse cutaneous mastocytosis; HVA: Hymenoptera venom allergy; HaT: Hereditary alpha tryptasemia; ISM: Indolent systemic mastocytosis; MC: Mast cell; MCA: Mast cell activation; MCAS: Mast cell activation syndrome; MCL: Mast cell leukemia; MIS: Mastocytosis in the skin; MMAS: Monoclonal mast cell activation syndrome; MPCM: Maculopapular cutaneous mastocytosis; SM: Systemic mastocytosis; SM-AHN: Systemic mastocytosis with associated hematological neoplasm; SSM: Smouldering systemic mastocytosis; VIT: Venom immunotherapy.
Topics: Humans; Mastocytosis, Systemic; Tryptases; DNA Copy Number Variations; Mastocytosis; Mastocytosis, Cutaneous
PubMed: 36259506
DOI: 10.1080/17843286.2022.2137631 -
Immunology and Allergy Clinics of North... Feb 2022There is strong evidence of an association between severe anaphylaxis, especially hymenoptera venom induced, and mast cell (MC) disorders. It has been thought that... (Review)
Review
There is strong evidence of an association between severe anaphylaxis, especially hymenoptera venom induced, and mast cell (MC) disorders. It has been thought that intrinsic abnormalities in MCs, including the presence of the activating KIT D816V mutation in mastocytosis or of genetic trait, hereditary alpha-tryptasemia, may influence susceptibility to severe anaphylaxis. This article evaluates the potential mechanisms leading to severe MC activation, as well as the differential diagnosis of and range of symptoms attributable to MC mediator release. Also, we offer a global classification for disorders related to MC activation.
Topics: Anaphylaxis; Arthropod Venoms; Humans; Mast Cells; Mastocytosis; Tryptases
PubMed: 34823750
DOI: 10.1016/j.iac.2021.09.007 -
American Journal of Clinical Pathology Feb 2021
Review
Topics: Education; Eosinophilia; Hematologic Neoplasms; Humans; Hypereosinophilic Syndrome; Leukemia; Mastocytosis; Pathology, Clinical; Sarcoma, Myeloid
PubMed: 33367532
DOI: 10.1093/ajcp/aqaa206 -
RoFo : Fortschritte Auf Dem Gebiete Der... May 2021
Topics: Humans; Mastocytosis, Systemic
PubMed: 32898917
DOI: 10.1055/a-1224-4362 -
Immunology and Allergy Clinics of North... Nov 2023Experts of the European Competence Network on Mastocytosis (ECNM) and the American Initiative on Mast Cell Disorders have discussed and updated diagnostic criteria and... (Review)
Review
Experts of the European Competence Network on Mastocytosis (ECNM) and the American Initiative on Mast Cell Disorders have discussed and updated diagnostic criteria and the classification of mastocytosis, based on new insights in the field and data collected in recent years, mostly within ECNM registry projects in which studies on several thousand cases have been performed. Based on this proposal, the World Health Organization has updated its classification of mastocytosis. This article discusses the revised classification of mastocytosis in light of a rapidly moving field and the advent of new diagnostic parameters, new prognostication tools, and new therapies.
Topics: Humans; Mastocytosis; World Health Organization; Mast Cells
PubMed: 37758403
DOI: 10.1016/j.iac.2023.04.011 -
Medicina (Kaunas, Lithuania) Oct 2021Mastocytosis is a rare hematological neoplasm characterized by the proliferation of abnormal clonal mast cells (MCs) in different cutaneous and extracutaneous organs.... (Review)
Review
Mastocytosis is a rare hematological neoplasm characterized by the proliferation of abnormal clonal mast cells (MCs) in different cutaneous and extracutaneous organs. Its diagnosis is based on well-defined major and minor criteria, including the pathognomonic dense infiltrate of MCs detected in bone marrow (BM), elevated serum tryptase level, abnormal MCs CD25 expression, and the identification of D816V mutation. The World Health Organization (WHO) classification subdivides mastocytosis into a cutaneous form (CM) and five systemic variants (SM), namely indolent/smoldering (ISM/SSM) and advanced SM (AdvSM) including aggressive SM (ASM), SM associated to hematological neoplasms (SM-AHN), and mast cell leukemia (MCL). More than 80% of patients with SM carry a somatic point mutation of at codon 816, which may be targeted by kinase inhibitors. The presence of additional somatic mutations detected by next generation sequencing analysis may impact prognosis and drive treatment strategy, which ranges from symptomatic drugs in indolent forms to kinase-inhibitors active on . Allogeneic stem cell transplant (SCT) may be considered in selected SM cases. Here, we review the clinical, diagnostic, and therapeutic issues of SM, with special emphasis on the translational implications of SM genetics for a precision medicine approach in clinical practice.
Topics: Humans; Leukemia, Mast-Cell; Mastocytosis, Systemic; Mutation; Precision Medicine; Proto-Oncogene Proteins c-kit; Tryptases
PubMed: 34833353
DOI: 10.3390/medicina57111135 -
Frontiers in Immunology 2023The HMC-1.2 human mast cell (huMC) line is often employed in the study of attributes of neoplastic huMCs as found in patients with mastocytosis and their sensitivity to...
The HMC-1.2 human mast cell (huMC) line is often employed in the study of attributes of neoplastic huMCs as found in patients with mastocytosis and their sensitivity to interventional drugs and . HMC-1.2 cells express constitutively active KIT, an essential growth factor receptor for huMC survival and function, due to the presence of two oncogenic mutations (D816V and V560G). However, systemic mastocytosis is commonly associated with a single D816V-KIT mutation. The functional consequences of the coexisting KIT mutations in HMC-1.2 cells are unknown. We used CRISPR/Cas9-engineering to reverse the V560G mutation in HMC-1.2 cells, resulting in a subline (HMC-1.3) with a single mono-allelic D816V-KIT variant. Transcriptome analyses predicted reduced activity in pathways involved in survival, cell-to-cell adhesion, and neoplasia in HMC-1.3 compared to HMC-1.2 cells, with differences in expression of molecular components and cell surface markers. Consistently, subcutaneous inoculation of HMC-1.3 into mice produced significantly smaller tumors than HMC-1.2 cells, and in colony assays, HMC-1.3 formed less numerous and smaller colonies than HMC-1.2 cells. However, in liquid culture conditions, the growth of HMC-1.2 and HMC-1.3 cells was comparable. Phosphorylation levels of ERK1/2, AKT and STAT5, representing pathways associated with constitutive oncogenic KIT signaling, were also similar between HMC-1.2 and HMC-1.3 cells. Despite these similarities in liquid culture, survival of HMC-1.3 cells was diminished in response to various pharmacological inhibitors, including tyrosine kinase inhibitors used clinically for treatment of advanced systemic mastocytosis, and JAK2 and BCL2 inhibitors, making HMC-1.3 more susceptible to these drugs than HMC-1.2 cells. Our study thus reveals that the additional V560G-KIT oncogenic variant in HMC-1.2 cells modifies transcriptional programs induced by D816V-KIT, confers a survival advantage, alters sensitivity to interventional drugs, and increases the tumorigenicity, suggesting that engineered huMCs with a single D816V-KIT variant may represent an improved preclinical model for mastocytosis.
Topics: Humans; Animals; Mice; Mastocytosis, Systemic; CRISPR-Cas Systems; Proto-Oncogene Proteins c-kit; Mastocytosis; Mutation; Cell Line
PubMed: 37025992
DOI: 10.3389/fimmu.2023.1078958 -
International Journal of Molecular... Oct 2023Advanced systemic mastocytosis (SM) is a heterogeneous group of myeloid neoplasms characterized by an uncontrolled expansion of mast cells (MC) in one or more internal... (Review)
Review
Advanced systemic mastocytosis (SM) is a heterogeneous group of myeloid neoplasms characterized by an uncontrolled expansion of mast cells (MC) in one or more internal organs, SM-induced tissue damage, and poor prognosis. Advanced SM can be categorized into aggressive SM (ASM), MC leukemia (MCL), and SM with an associated hematologic neoplasm (SM-AHN). In a vast majority of all patients, neoplastic cells display a mutation, mostly D816V and rarely other variants. Additional mutations in other target genes, such as , , or , may also be identified, especially when an AHN is present. During the past 10 years, improved treatment approaches have led to a better quality of life and survival in patients with advanced SM. However, despite the availability of novel potent inhibitors of KIT D816V, not all patients enter remission and others relapse, often with a multi-mutated and sometimes D816V-negative disease exhibiting multi-drug resistance. For these patients, (poly)chemotherapy, antibody-based therapies, and allogeneic hematopoietic stem cell transplantation may be viable treatment alternatives. In this article, we discuss treatment options for patients with drug-resistant advanced SM, including novel KIT-targeting drugs, antibody-based drugs, and stem cell-eradicating therapies.
Topics: Humans; Quality of Life; Mastocytosis; Mastocytosis, Systemic; Mast Cells; Mutation; Proto-Oncogene Proteins c-kit
PubMed: 37894806
DOI: 10.3390/ijms242015125