Mast cell-related disorders presenting with Kounis syndrome

Letter to the Editor.-- et al.Peer Reviewe

Nonaggressive systemic mastocytosis (SM) without skin lesions associated with insect-induced anaphylaxis shows unique features versus other indolent SM

Spanish Network on Mastocytosis (REMA): et al.[Background]: Indolent systemic mastocytosis (ISM) without skin lesions (ISMs-) shows a higher prevalence in males, lower serum baseline tryptase levels, and KIT mutation more frequently restricted to bone marrow (BM) mast cells (MCs) than ISM with skin lesions (ISMs+). Interestingly, in almost one-half of ISMs- patients, MC-mediator release episodes are triggered exclusively by insects. [Objective]: We aimed to determine the clinical and laboratory features of ISMs- associated with insect-induced anaphylaxis (insectISMs-) versus other patients with ISM. [Methods]: A total of 335 patients presenting with MC activation syndrome, including 143 insectISMs-, 72 ISMs- triggered by other factors (otherISMs-), 56 ISMs+, and 64 nonclonal MC activation syndrome, were studied. [Results]: Compared with otherISMs- and ISMs+ patients, insectISMs- cases showed marked male predominance (78% vs 53% and 46%; P <.001), a distinct pattern of MC-related symptoms, and significantly lower median serum baseline tryptase levels (22.4 vs 28.7 and 45.8 μg/L; P ≤.009). Moreover, insectISMs- less frequently presented BM MC aggregates (46% vs 70% and 81%; P ≤.001), and they systematically showed MC-restricted KIT mutation. [Conclusions]: ISMs- patients with anaphylaxis triggered exclusively by insects display clinical and laboratory features that are significantly different from other ISM cases, including other ISMs- and ISMs+ patients, suggesting that they represent a unique subgroup of ISM with a particularly low BM MC burden in the absence of adverse prognostic factors.Supported by Fondo de Investigaciones Sanitarias –FIS– of the Instituto de Salud Carlos III, Ministery of Economy and Competitivity, Madrid, Spain grant PS09/00032; Fundación Sociosanitaria de Castilla-La Mancha grants 2010/008 and G-2010/ C-002; Fundacióon Española de Mastocitosis grant FEM 2011; BioB-HVS is supported by grant RETICS (Redes Temáticas de Investigación Cooperativa en Salud) RD09/ 00760074 (Toledo, Spain); RTICC (Red Temática de Investigación Cooperativa en Cáncer) grants RD09/0076/00133, RD12/0036/0048; FIS; FEDER, Ministery of Economy and Competitivity, Madrid, Spain grant PI11/02399; and Fundación Ramón Areces, Madrid, Spain grant CIVP16A1806; and by Associazione Italiana Leucemie e Linfomi of Verona (AIL-Verona) and ASIMAS (Associazione Italiana Mastocitosi). L. Escribano has been supported by one or more grants from Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Fundacion Sociosanitaria de Castilla La Mancha, and from FEM. A. García-Montero has been supported by one or more grants from ISCIII. M. Mollejo and A. Orfao have been supported by one or more grants from Instituto de Salud Carlos III, Ministerio de Economía y Competitividad. L. Sánchez-Muñoz has been supported by one or more grants from Fundacion Sociosanitaria de Castilla La Mancha.Peer Reviewe

Evaluation of the WHO criteria for the classification of patients with mastocytosis

Diagnosis and classification of mastocytosis is currently based on the World Health Organization (WHO) criteria. Here, we evaluate the utility of the WHO criteria for the diagnosis and classification of a large series of mastocytosis patients (n=133), and propose a new algorithm that could be routinely applied for refined diagnosis and classification of the disease. Our results confirm the utility of the WHO criteria and provide evidence for the need of additional information for (1) a more precise diagnosis of mastocytosis, (2) specific identification of new forms of the disease, (3) the differential diagnosis between cutaneous mastocytosis vs systemic mastocytosis, and (4) improved distinction between indolent systemic mastocytosis and aggressive systemic mastocytosis. Based on our results, a new algorithm is proposed for a better diagnostic definition and prognostic classification of mastocytosis, as confirmed prospectively in an independent validation series of 117 mastocytosis patients.This work was supported by grants from the Fondo de Investigaciones Sanitarias (FIS) of the Ministerio de Ciencia e Innovación of Spain (PS09/00032 and RETICS RD06/0020/0035-FEDER); Junta de Comunidades de Castilla La Mancha (FISCAM 2007/36, FISCAM 2008/46). Junta de Castilla y León (Grant SAN1778/2009 and GR37); ACG-M is supported by a grant from FIS/FEDER (CP03/00035); CT was supported by a grant from the Fundaçcâo para a Ciência e Tecnologia (FCT) of Portugal (SFRH/BD/ 17545/2004) and by a grant from the Fondo de Investigaciones Sanitarias (FIS) of the Ministerio de Ciencia e Innovación of Spain (PI08/90881).Peer Reviewe

Venom immunotherapy in patients with mastocytosis and hymenoptera venom anaphylaxis

Systemic mastocytosis (SM) is typically suspected in patients with cutaneous mastocytosis (CM). In recent years, the presence of clonal mast cells (MCs) in a subset of patients with systemic symptoms associated with MC activation in the absence of CM has been reported and termed monoclonal MC activation syndromes or clonal systemic MC activation syndromes. In these cases, bone marrow (BM) MC numbers are usually lower than in SM with CM, there are no detectable BM MC aggregates, and serum baseline tryptase is often <20 μg/l; thus, diagnosis of SM in these patients should be based on careful evaluation of other minor WHO criteria for SM in reference centers, where highly sensitive techniques for immunophenotypic analysis and investigation of KIT mutations on fluorescence-activated cell sorter-purified BM MCs are routinely performed. The prevalence of hymenoptera venom anaphylaxis (HVA) among SM patients is higher than among the normal population and it has been reported to be approximately 5%. In SM patients with IgE-mediated HVA, venom immunotherapy is safe and effective and it should be prescribed lifelong. Severe adverse reactions to hymenoptera stings or venom immunotherapy have been associated with increased serum baseline tryptase; however, presence of clonal MC has not been ruled out in most reports and thus both SM and clonal MC activation syndrome might be underdiagnosed in such patients. In fact, clonal BM MC appears to be a relevant risk factor for both HVA and severe reactions to venom immunotherapy, while the increase in serum baseline tryptase by itself should be considered as a powerful surrogate marker for anaphylaxis. The Spanish Network on Mastocytosis has developed a scoring system based on patient gender, the clinical symptoms observed during anaphylaxis and serum baseline tryptase to predict for the presence of both MC clonality and SM among individuals who suffer from anaphylaxis. © 2011 Future Medicine Ltd.Peer Reviewe

Evaluation of Basophil Activation in Mastocytosis with Hymenoptera Venom Anaphylaxis

[Background]: Basophil activation tests (BATs) have been demonstrated to be useful in detecting IgE-mediated sensitization by measuring basophil activation surface markers (CD63 and CD203c). Hymenoptera venom is one of the best known mediators-release trigger in patients with systemic mastocytosis (SM). The aim of this study was to investigate the use of BATs as an additional diagnostic tool in patients with mastocytosis suffering from hymenoptera venom anaphylaxis (HVA). [Methods]: A total of 22 patients with history of HVA and SM, together with a group of 11 patients with HVA in whom SM was ruled out after a complete bone marrow study, were analyzed. [Results]: Among 11 SM patients who had specific serum IgE (sIgE) against hymenoptera venom and an evaluable BAT, a positive BAT was found in nine. Additionally, a positive BAT was detected in three of seven patients who had no sIgE. These three patients had low levels of total IgE compared with control population (mean of 20 vs. 78 IU/mL); one had discontinued immunotherapy after 5 years, when sIgE levels had turned negative, and, in the other two patients, BAT identified the culprit insect. [Conclusions]: BAT is a useful complementary diagnostic tool to sIgE in mastocytosis patients with HVA, and it may contribute to predict or confirm these nearly fatal reactions, especially before discontinuing venom immunotherapy in patients who are negative for skin tests or sIgE or display low total IgE levels; in such cases, it also provides evidence on the culprit insect prompting HVA. (C) 2010 International Clinical Cytometry SocietySEAIC 2006; Grant sponsor: Fondo de Investigaciones Sanitarias of the Ministerio de Sanidad y Consumo; Grant number: PS 09/00032; Grant sponsor: Junta de Comunidades de Castilla La Mancha; Grant numbers: FISCAM 2007/36 and FISCAM 2008/46.Peer Reviewe

Systemic mastocytosis as a risk factor for severe Hymenoptera sting-induced anaphylaxis

Correspondence to the Editor.-- et al.Peer Reviewe

Validation of the REMA score for predicting mast cell clonality and systemic mastocytosis in patients with systemic mast cell activation symptoms

[Background]: A variable percentage of patients with systemic mast cell (MC) activation symptoms meet criteria for systemic mastocytosis (SM). We prospectively evaluated the clinical utility of the REMA score versus serum baseline tryptase (sBt) levels for predicting MC clonality and SM in 158 patients with systemic MC activation symptoms in the absence of mastocytosis in the skin (MIS). [Methods]: World Health Organization criteria for SM were applied in all cases. MC clonality was defined as the presence of KIT-mutated MC or by a clonal HUMARA test. The REMA score consisted of the assignment of positive or negative points as follows: male (+1), female (–1), sBt 25 µg/l (+2), presence (–2) or absence (+1) of pruritus, hives or angioedema and presence (+3) of presyncope or syncope. Efficiency of the REMA score for predicting MC clonality and SM was assessed by receiver operating characteristic (ROC) curve analyses and compared to those obtained by means of sBt levels alone. [Results]: Molecular studies revealed the presence of clonal MC in 68/80 SM cases and in 11/78 patients who did not meet the criteria for SM. ROC curve analyses confirmed the greater sensitivity and a similar specificity of the REMA score versus sBt levels (84 vs. 59% and 74 vs. 70% for MC clonality and 87 vs. 62% and 73 vs. 71% for SM, respectively). [Conclusions]: Our results confirm the clinical utility of the REMA score to predict MC clonality and SM in patients suffering from systemic MC activation symptoms without MIS.Peer Reviewe

Real‐life report of allergen immunotherapy management during the COVID‐19 outbreak in France and Spain

International audienceNo abstract availabl