Selecting the Right Criteria and Proper Classification to Diagnose Mast Cell Activation Syndromes: A Critical Review

Gülen, Theo; Akin, Cem; Bonadonna, Patrizia; Siebenhaar, Frank; Broesby‐Olsen, Sigurd; Brockow, Knut; Niedoszytko, Marek; Nedoszytko, Bogusław; Elberink, H. N. G. Oude; Butterfield, Joseph H.; Sperr, Wolfgang R.; Álvarez‐Twose, Iván; Horny, Hans Peter; Sotlar, Karl; Schwaab, Juliana; Jawhar, Mohamad; Zanotti, Roberta; Nilsson, Gunnar; Lyons, Jonathan J.; Carter, Melody C.; George, Tracy I.; Hermine, Olivier; Gotlib, Jason; Órfão, Alberto; Triggiani, Massimo; Reiter, Andreas; Hartmann, Karin; Castells, Mariana; Arock, Michel; Schwartz, Lawrence B.; Metcalfe, Dean D.; Valent, Peter

doi:10.1016/j.jaip.2021.06.011

Cited by 42 publications

(85 citation statements)

References 136 publications

(223 reference statements)

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“…SCF binds to its receptor, KIT, a transmembrane tyrosine kinase-linked receptor and signal [ 36 , 37 , 38 , 39 ]. Somatic mutations in c-KIT that code for the KIT receptor (the most common of these being the D816V mutation) have been linked to the development of systemic mastocytosis, a clonal hematological disorder [ 40 ].…”

Section: Brief Overview Of Mast Cell Biologymentioning

confidence: 99%

Mastocytosis and Mast Cell Activation Disorders: Clearing the Air

Jackson

Pratt

Rupprecht

et al. 2021

IJMS

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Mast cells are derived from hematopoietic stem cell precursors and are essential to the genesis and manifestations of the allergic response. Activation of these cells by allergens leads to degranulation and elaboration of inflammatory mediators, responsible for regulating the acute dramatic inflammatory response seen. Mast cells have also been incriminated in such diverse disorders as malignancy, arthritis, coronary artery disease, and osteoporosis. There has been a recent explosion in our understanding of the mast cell and the associated clinical conditions that affect this cell type. Some mast cell disorders are associated with specific genetic mutations (such as the D816V gain-of-function mutation) with resultant clonal disease. Such disorders include cutaneous mastocytosis, systemic mastocytosis (SM), its variants (indolent/ISM, smoldering/SSM, aggressive systemic mastocytosis/ASM) and clonal (or monoclonal) mast cell activation disorders or syndromes (CMCAS/MMAS). Besides clonal mast cell activations disorders/CMCAS (also referred to as monoclonal mast cell activation syndromes/MMAS), mast cell activation can also occur secondary to allergic, inflammatory, or paraneoplastic disease. Some disorders are idiopathic as their molecular pathogenesis and evolution are unclear. A genetic disorder, referred to as hereditary alpha-tryptasemia (HαT) has also been described recently. This condition has been shown to be associated with increased severity of allergic and anaphylactic reactions and may interact variably with primary and secondary mast cell disease, resulting in complex combined disorders. The role of this review is to clarify the classification of mast cell disorders, point to molecular aspects of mast cell signaling, elucidate underlying genetic defects, and provide approaches to targeted therapies that may benefit such patients.

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Section: Brief Overview Of Mast Cell Biologymentioning

confidence: 99%

Mastocytosis and Mast Cell Activation Disorders: Clearing the Air

Jackson

Pratt

Rupprecht

et al. 2021

IJMS

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“…Diagnosis of systemic mastocytosis/MMAS was based on the WHO diagnostic criteria, taking morphological, histopathological/immunohistochemical, immunophenotypic, molecular and analytical (serum baseline tryptase, ImmunoCAP Tryptase, Phadia/Thermo Fisher Scientific Inc., Uppsala, Sweden) data into account [ 15 , 16 , 27 , 28 , 29 ]. Regarding the molecular criteria, KIT D816V mutation was assessed by allele-specific polymerase chain reaction (ASOqPCR), in peripheral blood, bone marrow or both.…”

Section: Methodsmentioning

confidence: 99%

“…Mechanisms for immediate hypersensitivity/anaphylaxis to these vaccines are still a matter of debate, and may include IgE hypersensitivity to excipients (notably, polyethylene glycol, PEG/polysorbate [ 9 ], and tromethamine [ 12 ]), complement anaphylatoxin-derived mast cell (MC) activation [ 13 ] or direct MC activation through membrane or intracytoplasmic pattern recognition receptors (Toll-like receptors 3, 7 and 8 [ 9 ], and retinoic-acid-inducible gene-1, RIG-1 [ 14 ]). One might intuitively link the latter two mechanisms to an increased risk of immediate hypersensitivity/anaphylaxis in patients with clonal MC disorders, a heterogeneous group of diseases characterized by overactivation (monoclonal MC activation syndromes, MMAS) [ 15 ] and accumulation of clonal MC in one or more tissues (mastocytosis) [ 16 ]. These patients show not only an increased risk for anaphylaxis [ 17 ], but also an increased risk of exacerbation/elicitation of MC activation caused by vaccination, especially in children with cutaneous mastocytosis (CM) [ 18 , 19 , 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

COVID-19 Vaccination Is Safe among Mast Cell Disorder Patients, under Adequate Premedication

et al. 2022

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Reported cases of anaphylaxis following COVID-19 vaccination raised concerns about the safety of these vaccines, namely in patients suffering from clonal mast cell (MC) disorders—a heterogenous group of disorders in which patients may be prone to anaphylaxis caused by vaccination. This study aimed to assess the safety of COVID-19 vaccines in patients with clonal MC disorders. We performed an ambidirectional cohort study with 30 clonal MC disorder patients (n = 26 in the prospective arm and n = 4 in the retrospective arm), that were submitted to COVID-19 vaccination. Among these, 11 (37%) were males, and median age at vaccination date was 41 years (range: 5 y to 76 y). One patient had prior history of anaphylaxis following vaccination. Those in the prospective arm received a premedication protocol including H1- and H2-antihistamines and montelukast, while those in the retrospective arm did not premedicate. Overall, patients received a total of 81 doses, 73 under premedication and 8 without premedication. No MC activation symptoms were reported. COVID-19 vaccination seems to be safe in patients with clonal mast cell disorders, including those with prior anaphylaxis following vaccination. Robust premedication protocols may allow for vaccination in ambulatory settings.

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“…The clinical impact and robustness of these MCAS criteria have been confirmed in several validation studies and are regarded as widely accepted standard [48][49][50]. Depending on the etiology of MCAS, 3 major variants have been defined: primary (clonal = monoclonal) MCAS, secondary (reactive) MCAS, and idiopathic MCAS (Table 3) [19][20][21][22]47]. In patients with primary (monoclonal) MCAS, MC are (mono)clonal cells, often increase in number, and may appear hyper-reactive against IgE-dependent and/or IgE-independent triggers of anaphylaxis [19][20][21][22].…”

Section: Diagnostic Criteria and Classification Of Mcasmentioning

confidence: 96%

Mast Cell Activation Syndromes: Collegium Internationale Allergologicum Update 2022

Valent¹,

Hartmann²,

Bonadonna³

et al. 2022

Int Arch Allergy Immunol

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Mast cell activation syndromes (MCASs) are defined by systemic severe and recurrent mast cell activation, usually in form of anaphylaxis, a substantial, event-related increase of the serum tryptase level beyond the individual’s baseline and a response of the symptomatology to drugs directed against mast cells, mast cell-derived mediators, or mediator effects. A number of predisposing genetic conditions, underlying allergic and other hypersensitivity states, and related comorbidities can contribute to the clinical manifestation of MCASs. These conditions include hereditary alpha tryptasemia, mastocytosis with an expansion of clonal <i>KIT</i>-mutated mast cells, atopic diathesis, and overt IgE-dependent and IgE-independent allergies. Several of these conditions have overlapping definitions and diagnostic criteria and may also develop concomitantly in the same patient. However, although criteria and clinical features overlap, each of these conditions is characterized by a unique constellation of variables and diagnostic criteria. Since two, three, or more conditions can coexist in the same patient, with obvious clinical implications, it is of crucial importance to diagnose the variant of MCAS precisely and to take all accompanying, underlying and potentially complicating conditions, and comorbidities into account when establishing the management plan. Indeed, most of these patients require multidisciplinary investigations and only a personalized treatment approach can lead to an optimal management plan providing an optimal quality of life and low risk of anaphylaxis.

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Selecting the Right Criteria and Proper Classification to Diagnose Mast Cell Activation Syndromes: A Critical Review

Cited by 42 publications

References 136 publications

Mastocytosis and Mast Cell Activation Disorders: Clearing the Air

Mastocytosis and Mast Cell Activation Disorders: Clearing the Air

COVID-19 Vaccination Is Safe among Mast Cell Disorder Patients, under Adequate Premedication

Mast Cell Activation Syndromes: Collegium Internationale Allergologicum Update 2022

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