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Clonal mast cell disease should be suspected in patients presenting with recurrent hypotensive syncopal or near-syncopal episodes without urticaria or angioedema.
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Patients with severe systemic reactions to hymenoptera and elevated baseline tryptase levels should be investigated for presence of mastocytosis. These patients should be considered for life-long venom immunotherapy if evidence for IgE-mediated venom sensitization is found.
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Mast cell activation syndrome is a multisystem disorder with
Mast Cell Activation Syndromes Presenting as Anaphylaxis
Section snippets
Key points
Global classification of mast cell disorders
Mast cell disorders can be broadly divided into those involving proliferation and those involving activation, often with a substantial overlap. Most patients with a proliferative mast cell disease such as mastocytosis come to clinical attention because of symptoms caused by mast cell activation.3 Akin and colleagues2 recently proposed a global classification scheme for disorders associated with mast cell activation based on whether the mast cells have a primary genetic defect or are simply
Primary (clonal) mast cell disorders
Primary (clonal) mast cell disorder includes mastocytosis and its limited variant monoclonal mast cell activation syndrome (MMAS). These disorders are associated with clonal expansion of mast cells carrying genetic defects in the receptor tyrosine kinase c-kit (most often D816V point mutation). Mastocytosis is characterized by pathologic accumulation of mast cells in various tissues, such as skin and bone marrow, and has a strong proliferative feature in which the proliferative component and
Anaphylaxis in clonal mast cell disease
It has been clearly established that the incidence of anaphylaxis is increased in mastocytosis. Several reports from Europe and the United States point to an average incidence of 30% lifetime risk of anaphylaxis in patients with mastocytosis.17, 18, 19 Anaphylaxis in mastocytosis and MMAS may be due to an IgE-mediated event, may be caused by direct mast cell activation, or may have no clear triggers. Among IgE-mediated triggers, the risk of hymenoptera anaphylaxis is the best studied. It seems
Mast cell activation syndrome
The presence of a disorder that is distinct from mastocytosis and is characterized by recurrent mast cell activation episodes has been considered for many years and diagnostic criteria have been recently proposed (Box 2).2, 30 Because of the nonspecific nature of many symptoms experienced in a mast cell activation episode and the lack of histopathologic findings, it is important to objectively document a marker of mast cell activation during a symptomatic state. The serum marker that is most
Management of recurrent anaphylaxis associated with mast cell activation syndrome
In patients with recurrent anaphylaxis associated with MCAS, the most important step is to clarify if the patient has a clonal, an IgE-mediated, or an idiopathic mast cell disorder. Management of IgE-mediated disorders relies heavily on trigger avoidance, availability of multiple doses of self-injected epinephrine, and desensitization in certain circumstances such as with venom anaphylaxis. Patients with clonal and idiopathic MCAS are generally placed on a maintenance H1-antihistamine therapy
Future directions
Despite increased awareness and recognition of MCAS in the last decade, much remains to be elucidated regarding its pathogenesis, disease markers, and treatment. Prospective multicenter trials are needed to validate the proposed diagnostic criteria and identify patient subgroups that may respond differently to therapy. The incidence and subtypes of MCAS in the pediatric population have not been systematically investigated. Although tryptase is the most specific marker for mast cell activation,
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Cited by (38)
Advances in mast cell biology
2022, Journal of Allergy and Clinical ImmunologyCitation Excerpt :All 10 patients for whom DNA samples were available had duplications in the TSAB1 allele. Thus, patients with HAT and clinical symptoms consistent with MC activation may display aberrant bone marrow MC distribution and morphology that is distinct from the clustered, elongated MCs reported in SM and clonal MC disorders driven by the KIT D816V mutation.35 Because many patients with HAT lack clinical symptoms,32 and no asymptomatic patients were examined in this study, the causative role of the TPSAB1 duplication per se to the bone marrow findings and MC activation–related symptoms remains to be proven.
Selecting the Right Criteria and Proper Classification to Diagnose Mast Cell Activation Syndromes: A Critical Review
2021, Journal of Allergy and Clinical Immunology: In PracticeMast Cell Activation: When the Whole Is Greater than the Sum of Its Parts
2020, Medical Clinics of North AmericaDoctor, I Think I Am Suffering from MCAS: Differential Diagnosis and Separating Facts from Fiction
2019, Journal of Allergy and Clinical Immunology: In PracticeCitation Excerpt :A number of different clinical conditions and disorders can mimic MCAS.17-20 Typical differential diagnoses are cardiac disorders (myocardial infarction, myocarditis), septicemia (eg, bacterial sepsis), pharmacologic side effects (eg, hypotension with antihypertensive drugs, tachycardia and gastrointestinal hypomotility with antihistamine overdose, flushing and skin rashes with glucocorticosteroids), dehydration with hypovolemic shock, and endocrinology emergencies (eg, adrenal crisis) (Table II).18-21 In other patients, one or more of the following symptoms are found: acute skin rash, chronic flushing, headache, gastrointestinal cramps, and diarrhea.
The Data Registry of the European Competence Network on Mastocytosis (ECNM): Set Up, Projects, and Perspectives
2019, Journal of Allergy and Clinical Immunology: In PracticeCitation Excerpt :Third, the ECNM registry data set will be used to start a call for basic science projects aimed at defining novel mechanisms of disease progression or the occurrence of certain clinically relevant comorbidities. One special focus in these projects will be primary MC activation syndromes (MCAS) defined by severe symptoms induced by MC-derived mediators.44-48 The ECNM registry will include data on MCAS parameters and will try to capture prognostic variables and clinical end points in patients with MCAS as well as responses of patients with MCAS to various therapies.
Nonclonal Mast Cell Activation Syndrome: A Growing Body of Evidence
2018, Immunology and Allergy Clinics of North America
Disclosure: Consultancy agreements with Novartis, Patara Pharma, and Blueprint Medicines.