Demonstration of an aberrant mast-cell population with clonal markers in a subset of patients with “idiopathic” anaphylaxis

Akin, Cem; Scott, Linda M.; Kocabaş, Can Naci; Kushnir-Sukhov, Nataliya M.; Brittain, Erica; Noël, Pierre; Metcalfe, Dean D.

doi:10.1182/blood-2006-06-028100

Cited by 215 publications

(175 citation statements)

References 21 publications

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“…Another potential contributor in this regard is the proportion of patients enrolled via allergy clinics where there is a higher index of suspicion for underlying SM. The aforementioned observations are also consistent with detection of low-burden clonal mast cells in symptomatic patients in specific clinical contexts (e.g., "idiopathic anaphylaxis") [15,16], where some patients are found to satisfy only 1 or 2 minor SM diagnostic criteria, with this entity being termed "monoclonal mast cell activation syndrome" or "subdiagnostic SM" [17,18]. The highest proportion of patients without mast cell aggregates (60%) in the study by Pieri et al belonged to the ISM subgroup without skin involvement (ISM-).…”

supporting

confidence: 82%

Systemic mastocytosis: evolving lessons from large patient registry datasets

Pardanani

2016

American J Hematol

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Systemic mastocytosis (SM) is a clinically heterogeneous and relatively infrequent chronic myeloproliferative neoplasm [1]. In the Danish nationwide cohort study, the incidence and prevalence rates were 0.89 per 100,000 inhabitants per year and 9.59 per 100,000 inhabitants, respectively, for the period between 1997 and 2010 [2]. Similarly, in the Groningen region, The Netherlands, prevalence of indolent SM (ISM) was estimated at 13 per 100,000 inhabitants, albeit with a roughly five-to sixfold increase in cases from 1998 to 2010, the latter likely relating to a recent increased awareness of SM combined with advances in diagnostic testing and expertise in specialized centers for this disease [3]. The increasing number of cases diagnosed with SM at least partly reflects the development of standardized diagnostic, classification and treatment-response criteria by international collaborative organizations such as the World Health Organization (WHO) and European Competence Network on Mastocytosis (ECNM) [4][5][6]. Prior to these larger-scale projects, most SM related data emerged from single center or single country registry studies, which despite their inherent limitations helped establish the early foundational principles of SM evaluation and treatment [7][8][9][10][11][12][13]. The article by Pieri et al. in the current issue of the American Journal of Hematology represents a large study of SM patients from 10 Italian centers with dedicated mastocytosis programs participating in the Italian Registry of Mastocytosis [14].There are two aspects of special note related to the study by Pieri et al. First, it represents the largest study of SM patients diagnosed by WHO 2008 criteria ever published [5]. Second, patients in this study were diagnosed relatively recently, with 75% being diagnosed between the years 2009 and 2014. The latter aspect ensured the use of relatively state-of-the-art diagnostic testing in the current study, which is not the case in older studies wherein a significant subset of patients was diagnosed prior to the development of such tests. A downside, however, of the recency bias in the article by Pieri et al. is the short patient follow up which limits the conclusions one might draw regarding clinical outcomes in SM patients.There are several additional observations that flow from the above two points: first, while the study by Pieri et al. includes 460 patients, as compared with the erstwhile largest study of 342 patients from the Mayo Clinic group [8], it is unclear whether either study is generalizable to the SM patient at large. While both were multidisciplinary studies, the former is predominantly a study of ISM patients (89% of all cases), likely reflecting a bias toward patient enrollment via dermatology and/or allergy clinics (73% had allergy/anaphylaxis symptoms). In contrast, the study by Lim et al. exhibited a hematology bias with 46% and 40% presenting with ISM and SM with associated clonal non-mast cell lineage disease (SM-AHNMD), respectively. This has to be taken into account when ex...

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confidence: 82%

Systemic mastocytosis: evolving lessons from large patient registry datasets

Pardanani

2016

American J Hematol

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“…Thus, in this group of patients, the presence of clonal proliferation markers of the mast cells should be determined. 4 It is believed that mast cells in mastocytosis patients may have an intrinsic defect lowering the threshold for activation and/or increasing its sensitivity to allergens. 3 Anaphylactic reactions occur in 30% of all patients with mastocytosis and in 50% of patients with systemic mastocytosis (SM).…”

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confidence: 99%

Risk factors for anaphylaxis in patients with mastocytosis

Górska¹,

Niedoszytko²,

Lange³

et al. 2015

Polish Archives of Internal Medicine

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“…Mast cell activation syndrome usually develops on the basis of a known underlying systemic disease, which can be an IgE-dependent disorder, another inflammatory disease, or a mast cell neoplasm (20)(21)(22)(23)(24)(25)(26)(27). In most patients, the mast cell neoplasm, if detected, is classified as systemic mastocytosis (SM).…”

Section: Underlying Disorders and Classification Of Mcasmentioning

confidence: 99%

“…More recently, however, MCA has also been studied in the context of other diseases, including systemic mastocytosis (21)(22)(23)(24)(25). During the past 3 years, criteria for MCA and MCAS have been developed by a consensus panel consisting of experts in the fields of allergy, dermatology, hematology, pathology, and molecular medicine (25)(26)(27).…”

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confidence: 99%

Mast cell activation syndromes: definition and classification

Valent

2013

Allergy

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Mast cell activation (MCA) occurs in a number of different clinical conditions, including IgE-dependent allergies, other inflammatory reactions, and mastocytosis. MCA-related symptoms may be mild, moderate, severe, or even life-threatening. The severity of MCA depends on a number of different factors, including genetic predisposition, the number and releasability of mast cells involved in the reaction, the type of allergen, presence of specific IgE, and presence of certain comorbidities. In severe reactions, MCA can be documented by a substantial increase in the serum tryptase level above baseline. When symptoms are recurrent, are accompanied by an increase in mast cell-derived mediators in biological fluids, and are responsive to treatment with mast cell-stabilizing or mediator-targeting drugs, the diagnosis of mast cell activation syndrome (MCAS) is appropriate. Based on the underlying condition, these patients can further be classified into i) primary MCAS where KIT-mutated, clonal mast cells are detected, ii) secondary MCAS where an underlying inflammatory disease, often in the form of an IgE-dependent allergy, but no KIT-mutated mast cells, is found, and iii) idiopathic MCAS, where neither an allergy or other underlying disease, nor KITmutated mast cells are detectable. It is important to note that in many patients with MCAS, several different factors act together to lead to severe or even lifethreatening anaphylaxis. Detailed knowledge about the pathogenesis and complexity of MCAS, and thus establishing the exact final diagnosis, may greatly help in the management and therapy of these patients.Mast cells are tissue-fixed effector cells of allergic and other inflammatory reactions (1-5). In common with blood basophils, mast cells express high-affinity IgE-binding sites and store numerous proinflammatory and vasoactive mediators in their metachromatic granules (1-3). During a severe anaphylactic reaction, allergen-induced cross-linking of IgE-binding sites on mast cells is followed by an explosive release of granular mediators (1-3, 5-7). In addition, activated mast cells release newly synthesized membrane-derived (lipid) mediators of allergic reactions into the extracellular space. Blood basophils also participate in allergic and other inflammatory reactions in the same way as mast cells (1,8,9). However, not all allergic reactions involve both cell types, even if the reaction is systemic. In addition, some of the mediators relevant to anaphylactic reactions are produced and released primarily in mast cells but not in basophils, or only in blood basophils but not in tissue mast cells.The capacity of mast cells and basophils to release mediators of anaphylaxis in response to cell activation, also termed 'releasability', depends on a number of different factors, including the primary underlying disease, number and type of (pre)activated receptors and signaling cascades, and the genetic background (9-13). The severity of an anaphylactic reaction is determined by additional factors, including the number...

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Demonstration of an aberrant mast-cell population with clonal markers in a subset of patients with “idiopathic” anaphylaxis

Cited by 215 publications

References 21 publications

Systemic mastocytosis: evolving lessons from large patient registry datasets

Systemic mastocytosis: evolving lessons from large patient registry datasets

Risk factors for anaphylaxis in patients with mastocytosis

Mast cell activation syndromes: definition and classification

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