Paradoxical exacerbation of sclerouveitis following Rituximab infusion.

PURPOSE: To report on an unexpected side effect of Rituximab (RTX), a B-cell targeting monoclonal agent, in a patient with severe sclerouveitis, leading to severe visual loss. METHODS: Observational case report. RESULTS: A 61-year-old female was treated with RTX for a severe sclerouveitis occurring with granulomatosis with polyangiitis. Initially it responded partly to high dose of oral corticosteroids, however, her sclerouveitis recurred after two months during tapering below 20mg daily. The days following the RTX infusions, aggravation of the intraocular inflammation was seen, endangering visual acuity. No evidence for an infection or other cause were found. High doses of oral corticosteroids were started within one week, where after the ocular inflammation resolved. For persisting hypotony and chorioretinal detachment a combined pars plana vitrectomy with phacoemulsification and silicone oil tamponade was performed. The retina remained attached under oil tamponade with partial improvement of the BCVA to finger counting. CONCLUSION: Ophthalmologist should be aware of the possibility of this paradoxical local reaction to RTX infusion, particularly in bilateral and/or severe cases, which carry a risk of a poor outcome.

Cutaneous Lesions of Mastocytosis: Mast Cell Count, Morphology, and Immunomolecular Phenotype.

ABSTRACT: Mastocytosis is a condition characterized by accumulation of clonal mast cells (MCs) that often involves the skin. Pathologists are often challenged with skin biopsies with a question of cutaneous lesions of mastocytosis (CLM) including cutaneous mastocytosis, mastocytosis in the skin, or systemic mastocytosis. The histopathological criteria for CLM remain poorly defined due to heterogeneity of the published literature and the lack of comparative prospective studies. MC count is greatly influenced by detection and counting techniques, criteria for viable MCs used, anatomical location biopsied, and the dermal level that is analyzed. Although MC numbers in CLM can be significantly higher compared with healthy controls and a patient with other inflammatory skin diseases, in some instances, considerable overlap exists. Based on the largest studies published, it is suggested that a number of MCs between 75 and 250 MCs/mm 2 are a range in which CLM should be considered and, above 250 MC/mm 2 , a diagnosis of CLM can be made. A recent study showed a high specificity of >95% of a MC count >139 MC/mm 2 compared with patients with other inflammatory skin diseases. Noteworthy, the total number and percentage of MCs is significantly higher in children compared with adults, particularly in polymorphic maculopapular cutaneous mastocytosis. In difficult cases, ancillary techniques such as D816V mutation analysis on formalin-fixed paraffin-embedded tissue have a high sensitivity and specificity. There is no enough evidence that immunohistochemistry of CD25, CD2, or CD30 has any additional value in the diagnosis, subtyping, or clinical course of mastocytosis.

COVID-19 Incidence and Disease Course Among Patients at an Allergy Department.

Background: Since the coronavirus pandemic in 2020, there is not much reported about the disease course of COVID-19 in patients with allergic diseases. Objectives: The aim of this study was to investigate the cumulative incidence and severity of COVID-19 among patients from the allergy department compared with the general Dutch population and people from their household. Design: We conducted a comparative longitudinal cohort study. Methods: In this study patients of the allergy department were included with their household members as a control group. Data from the beginning of the pandemic were systematically obtained through questionnaires by telephonic interviews and retrieved from electronic patient files between October 15, 2020 and January 29, 2021. Main outcomes were confirmed SARS-CoV-2 infection, disease duration, hospitalization, intensive care admission, and mortality. Questions regarding applied social distancing measures were inventoried as well. Results: Three hundred and eighty nine patients (median age 39.1 (18.7-84.7) years, 69.9% female) and 441 household members (median age 42.0 (18.0-91.5), 44.1% female) were included. The cumulative COVID-19 incidence in patients was higher compared with the general population (10.5% vs 5.6%, P < .001). In total, 41 (10.5%) patients attending the allergy clinic compared to 38 (8.6%) household members were infected with SARS-CoV-2 (P = .407). Median disease duration was 11.0 (0.0-61.0) days in patients compared to 10.5(1.0-232.0) days in household members (P = .996). Conclusion: The cumulative COVID-19 incidence in patients from the allergy cohort was higher compared with the general Dutch population, but similar compared with household members. There was no difference in symptoms, disease duration, or hospitalization rate between the allergy cohort and their household members.

Mast cell leukemia: clinical and molecular features and survival outcomes of patients in the ECNM Registry.

Mast cell leukemia (MCL) is a rare subtype of systemic mastocytosis defined by ≥20% mast cells (MC) on a bone marrow aspirate. We evaluated 92 patients with MCL from the European Competence Network on Mastocytosis registry. Thirty-one (34%) patients had a diagnosis of MCL with an associated hematologic neoplasm (MCL-AHN). Chronic MCL (lack of C-findings) comprised 14% of patients, and only 4.5% had "leukemic MCL" (≥10% circulating MCs). KIT D816V was found in 62/85 (73%) evaluable patients; 9 (11%) individuals exhibited alternative KIT mutations, and no KIT variants were detected in 14 (17%) subjects. Ten evaluable patients (17%) had an abnormal karyotype and the poor-risk SRSF2, ASXL1, and RUNX1 (S/A/R) mutations were identified in 16/36 (44%) patients who underwent next-generation sequencing. Midostaurin was the most common therapy administered to 65% of patients and 45% as first-line therapy. The median overall survival (OS) was 1.6 years. In multivariate analysis (S/A/R mutations excluded owing to low event rates), a diagnosis of MCL-AHN (hazard ratio [HR], 4.7; 95% confidence interval [CI], 1.7-13.0; P = .001) and abnormal karyotype (HR, 5.6; 95% CI, 1.4-13.3; P = .02) were associated with inferior OS; KIT D816V positivity (HR, 0.33; 95% CI, 0.11-0.98; P = .04) and midostaurin treatment (HR, 0.32; 95% CI, 0.08-0.72; P = .008) were associated with superior OS. These data provide the most comprehensive snapshot of the clinicopathologic, molecular, and treatment landscape of MCL to date, and should help further inform subtyping and prognostication of MCL.

The Number of MRGPRX2-Expressing Cells Is Increased in Skin Lesions of Patients With Indolent Systemic Mastocytosis, But Is Not Linked to Symptom Severity.

Background: Recently, the expression of the mast cell (MC) receptor Mas-related G protein-coupled receptor X2 (MRGPRX2) has been detected in lesional skin of adult patients with cutaneous mastocytosis. As of yet, little is known about the clinical relevance of MRGPRX2 and its agonists in patients with mastocytosis, including indolent systemic mastocytosis (ISM). Methods: MRGPRX2 and MRGPRX2 agonists, cortistatin (CST), and major basic protein (MBP) were analyzed in lesional and non-lesional skin of patients with ISM and skin of healthy controls by immunohistochemistry. Co-localization of MRGPRX2 and MRGPRX2-mRNA with the MC marker tryptase was assessed by immunofluorescence microscopy and in situ hybridization, respectively. We assessed clinical, demographic, and laboratory data, including mastocytosis activity score (MAS), serum tryptase, and KIT D816V allele burden. Results: The number of MRGPRX2-expressing (MRGPRX2+) cells, MRGPRX2-mRNA+ MCs, and CST-expressing (CST+) and MBP-expressing (MBP+) cells was significantly higher in lesional skin as compared to non-lesional skin and/or skin of healthy controls (all p < 0.05). Increased numbers of MRGPRX2+ cells, MRGPRX2-mRNA+ MCs, and CST+ and MBP+ cells were not associated with clinical and laboratory features of ISM, including disease burden, symptom severity, evidence of anaphylaxis, and tryptase levels. Conclusions: Skin lesions of patients with ISM showed high numbers of MRGPRX2+ cells, although they were not linked to symptom severity. Clinical relevance of the MRGPRX2-mediated pathway of MC activation in ISM remains unclear and should be investigated in further studies.

Novel RAB27A Variant Associated with Late-Onset Hemophagocytic Lymphohistiocytosis Alters Effector Protein Binding.

Autosomal recessive mutations in RAB27A are associated with Griscelli syndrome type 2 (GS2), characterized by hypopigmentation and development of early-onset, potentially fatal hemophagocytic lymphohistiocytosis (HLH). We describe a 35-year old male who presented with recurrent fever, was diagnosed with Epstein-Barr virus-driven chronic lymphoproliferation, fulfilled clinical HLH criteria, and who carried a novel homozygous RAB27A c.551G > A p.(R184Q) variant. We aimed to evaluate the contribution of the identified RAB27A variant in regard to the clinical phenotype as well as cellular and biochemical function. The patient displayed normal pigmentation as well as RAB27A expression in blood-derived cells. However, patient NK and CD8+ T cell exocytosis was low. Ectopic expression of the RAB27A p.R184Q variant rescued melanosome distribution in mouse Rab27a-deficient melanocytes, but failed to increase exocytosis upon reconstitution of human RAB27A-deficient CD8+ T cells. Mechanistically, the RAB27A p.R184Q variant displayed reduced binding to SLP2A but augmented binding to MUNC13-4, two key effector proteins in immune cells. MUNC13-4 binding was particularly strong to an inactive RAB27A p.T23N/p.R184Q double mutant. RAB27A p.R184Q was expressed and could facilitate melanosome trafficking, but did not support lymphocyte exocytosis. The HLH-associated RAB27A variant increased Munc13-4 binding, potentially representing a novel mode of impairing RAB27A function selectively in hematopoietic cells.

Histopathological characteristics are instrumental to distinguish monomorphic from polymorphic maculopapular cutaneous mastocytosis in children.

BACKGROUND: Mastocytosis is characterized by the accumulation of mast cells (MCs) in the skin or other organs, and can manifest at any age. A significant number of paediatric mastocytosis cases persist after puberty. In particular, monomorphic maculopapular cutaneous mastocytosis (mMPCM) is often persistent and associated with systemic mastocytosis. However, clinical differentiation of MPCM from polymorphic (p)MPCM can be difficult. AIM: To identify histopathological features that can help to distinguish mMPCM from other subtypes of paediatric mastocytosis. METHODS: This was a retrospective study using skin biopsies from patients with any subtype of mastocytosis. The localization and density of the MC infiltrate, MC morphology and expression of aberrant markers were evaluated and correlated with clinical characteristics. RESULTS: In total, 33 biopsies were available for evaluation from 26 children [(10 with mMPCM, 5 with mastocytoma, 3 with diffuse cutaneous mastocytosis (DCM), 8 with pMPCM)] and 7 adults with MPCM. The MC number was increased in all patients, but was higher in children than adults (P < 0.01). The presence of mMPCM was associated with sparing of the papillary dermis from MC infiltration, whereas MC density in the papillary dermis was highest in pMPCM and DCM (P < 0.01). The positive predictive value of the presence of a reticular MC infiltrate for mMPCM was 72.7% (95% CI 51.4-87.0), and the negative predictive value was 83.3% (95% CI 42.2-97.2). There were no relevant differences in the expression of CD2, CD25 or CD30 between the different subtypes. CONCLUSION: Skin histopathology might enhance the phenotypical differentiation of mMPCM from other subtypes in children, thereby increasing the accuracy of one's prognosis.

[Idiopathic mast cell activation syndrome]. / Het idiopathisch mestcelactivatiesyndroom.

BACKGROUND: Idiopathic mast cell activation syndrome (MCAS) is one of the causes for recurrent complaints. The diagnosis is sometimes delayed but also often made incorrectly. CASE: Our patient presented with recurrent attacks of itching, redness of the skin, diarrhea and near collapse. During an attack his serum tryptase level rose significantly. We could not identify an underlying trigger. A diagnosis of idiopathic mast cell activation syndrome was made. He was successfully treated with a combination of H1 and H2 blockade. CONCLUSION: MCAS is characterized by recurrent complaints. To make the diagnosis a significant rise in mast cell mediators is required. Given the diversity of symptoms many patients with somatically unexplained symptoms wrongfully believe to be suffering from MCAS.

Altered leukocyte subsets and immune proteome indicate proinflammatory mechanisms in mastocytosis.

BACKGROUND: Indolent systemic mastocytosis (ISM) is characterized by pathologic accumulation of mast cells. The mechanism behind its phenotypic heterogeneity is not well understood. Interaction of mast cells with other immune cells might cause systemic inflammation and thereby associated symptoms. OBJECTIVE: We investigated peripheral leukocyte compartments and serum immune proteome in ISM. METHODS: Peripheral blood leukocyte phenotyping using flow cytometry in a cohort of 18 adults with ISM and 12 healthy controls. Targeted proteomics was performed to measure 169 proteins associated with inflammation on serum of another 20 ISM patients and 20 healthy controls. RESULTS: Proportions of plasmacytoid dendritic cells and monocytes were significantly decreased while TH2 cells were increased in peripheral blood of ISM patients. Furthermore, a shift from naive to memory T cells was observed. Hierarchical clustering of the serum proteome revealed 2 distinct subgroups within ISM patients. In subgroup A (n = 8), 62 proteins were significantly overexpressed, whereas those of subgroup B (n = 12) were comparable to healthy controls. Patients in subgroup A displayed upregulated signaling pathways downstream of Toll-like receptor 4, TNF-α, and IFN-γ. Fatigue was more often present in subgroup A compared to B (75% vs 33% respectively, P = .06). CONCLUSIONS: Altered distribution of leukocyte subsets and a proinflammatory proteome were observed in subsequent 2 cohorts of ISM patients. We hypothesize that neoplastic mast cells recruit and activate plasmacytoid dendritic cells, monocytes, and T cells, leading to a vicious cycle of inflammation.

Human Mast Cell Line HMC1 Expresses Functional Mas-Related G-Protein Coupled Receptor 2.

The Mas-related G-protein-coupled receptor X2 (MRGPRX2) is prominently expressed by mast cells and induces degranulation upon binding by different ligands. Its activation has been linked to various mast cell-related diseases, such as chronic spontaneous urticaria, atopic dermatitis and asthma. Therefore, inhibition of MRGPRX2 activity represents a therapeutic target for these conditions. However, the exact pathophysiology of this receptor is still unknown. In vitro research with mast cells is often hampered by the technical limitations of available cell lines. The human mast cell types LAD2 and HuMC (human mast cells cultured from CD34+ progenitor cells) most closely resemble mature human mast cells, yet have a very slow growth rate. A fast proliferating alternative is the human mast cell line HMC1, but they are considered unsuitable for degranulation assays due to their immature phenotype. Moreover, the expression and functionality of MRGPRX2 on HMC1 is controversial. Here, we describe the MRGPRX2 expression and functionality in HMC1 cells, and compare these with LAD2 and HuMC. We also propose a model to render HMC1 suitable for degranulation assays by pre-incubating them with latrunculin-B (Lat-B). Expression of MRGPRX2 by HMC1 was proven by RQ-PCR and flowcytometry, although at lower levels compared with LAD2 and HuMC. Pre-incubation of HMC1 cells with Lat-B significantly increased the overall degranulation capacity, without significantly changing their MRGPRX2 expression, phenotype or morphology. The MRGPRX2 specific compound 48/80 (C48/80) effectively induced degranulation of HMC1 as measured by CD63 membrane expression and ß-hexosaminidase release, albeit in lower levels than for LAD2 or HuMC. HMC1, LAD2 and HuMC each had different degranulation kinetics upon stimulation with C48/80. Incubation with the MRGPRX2 specific inhibitor QWF inhibited C48/80-induced degranulation, confirming the functionality of MRGPRX2 on HMC1. In conclusion, HMC1 cells have lower levels of MRGPRX2 expression than LAD2 or HuMC, but are attractive for in vitro research because of their high growth rate and stable phenotype. HMC1 can be used to study MRGPRX2-mediated degranulation after pre-incubation with Lat-B, which provides the opportunity to explore MPRGRX2 biology in mast cells in a feasible way.

Characteristics of COVID-19 infection and antibody formation in patients known at a tertiary immunology department.

BACKGROUND: Knowledge about COVID-19 infections is expanding, although knowledge about the disease course and antibody formation in patients with an auto-immune disease or immunodeficiency is not fully unraveled yet. It could be hypothesized that immunodeficient patients, due to immunosuppressive drugs or their disease, have a more severe disease course due to their immunocompromised state. However, it could also be hypothesized that some of the immunosuppressive drugs protect against a hyperinflammatory state. METHODS: We collected data on the incidence of COVID-19, disease course and SARS-CoV-2 antibody formation in COVID-19 positive patients in a cohort of patients (n â€‹= â€‹4497) known at the Clinical Immunology outpatient clinic in a tertiary care hospital in the Netherlands. RESULTS: In the first six months of the pandemic, 16 patients were identified with COVID-19, 14 by nasal swab PCR, and 2 patients by SARS-CoV-2 antibodies. Eight patients were admitted to the hospital. SARS-CoV-2 antibodies were measured in 8 patients and were detectable in all, including one patient on B-cell ablative therapy and one patient with Common Variable Immunodeficiency Disorder. CONCLUSION: This study indicates that the disease course differs among immunocompromised patients, independently of (dis)continuation of immunosuppressive drugs. Antibody production for SARS-CoV-2 in immunocompromised patients was shown. More research needs to be conducted to confirm these observations and guidelines regarding (dis)continuation of immunosuppressive drugs in COVID-19 positive immunocompromised patients should be developed.

Increased group 2 innate lymphoid cells in peripheral blood of adults with mastocytosis.

BACKGROUND: Systemic mastocytosis is a hematological disease in which aberrant mast cells accumulate because of gain-of-function mutations in the KIT receptor. Group 2 innate lymphoid cells (ILC2s) are effector cells of type 2 immune responses that also express KIT and colocalize with mast cells at barrier tissue sites. In mouse models, mast cell-ILC2 crosstalk can drive local inflammation. However, a possible role for ILC2s in the pathophysiology of mastocytosis remains unexplored. OBJECTIVE: We sought to characterize circulating ILC2s in a clinically diverse cohort of patients with mastocytosis. METHODS: We included 21 adults with systemic mastocytosis and 18 healthy controls. Peripheral blood ILC2 abundance and phenotype were analyzed by flow cytometry and correlated to clinical characteristics, including the presence of the D816V KIT mutation. RESULTS: ILC2 levels were significantly higher in D816V+ patients with mastocytosis compared with D816V- patients or healthy controls. We observed increased proportions of KIT+ ILC2s among patients with mastocytosis, regardless of D816V status. Patients with skin involvement and itch showed the highest levels of ILC2s, which was independent from atopy or serum tryptase levels. Allele-specific quantitative PCR showed that the vast majority of ILC2s did not carry the D816V mutation. CONCLUSIONS: Our findings suggest a role for ILC2s and pathogenic ILC2-mast cell crosstalk in mastocytosis. We hypothesize that a high cutaneous D816V+ mast cell burden alters the skin microenvironment to induce chronic local ILC2 activation and their dissemination into the circulation. Activated ILC2s could contribute to skin symptoms by producing inflammatory mediators and by further augmenting mast cell mediator release.

Psychological functioning and quality of life in patients with mastocytosis: A cross-sectional study.

BACKGROUND: Psychological symptoms appear to be frequent among patients with mastocytosis and can significantly affect patient quality of life. However, it remains unclear whether and to which extent this may be the case. OBJECTIVE: To investigate he presence and type of psychological symptoms and quality of life in patients with mastocytosis. METHODS: In this cross-sectional cohort study of adult patients with mastocytosis, all patients completed the 36-item Short Form Health Survey (SF-36) and the 90-item Symptom Checklist (SCL-90). Results were compared with those of a healthy groups of patients with other diseases (chronic pain and cancer) and healthy populations. RESULTS: Fifty patients were included in the study. Seventy percent had indolent systemic mastocytosis. Patients with mastocytosis scored significantly worse than a healthy norm group on the total SCL-90 and more specifically on the dimensions of depression, somatization, sleeping problems, and inadequacy of acting and thinking. Strikingly, patients with mastocytosis scored similarly to patients with cancer on the SF-36 subdomains of general health perception and vitality. However, no significant difference in the mental health subdomain of the SF-36 was found when compared with a healthy group. CONCLUSION: In addition to the presence of psychological symptoms, the physical symptoms that are associated with mastocytosis also have a significant impact on the quality of life of patients with this disease. Therefore, correct treatment through symptom control and psychological counseling is necessary. TRIAL REGISTRATION: EudraCT Identifier 2015-004604-37.

The JAK1/JAK2- inhibitor ruxolitinib inhibits mast cell degranulation and cytokine release.

BACKGROUND: Mastocytosis is characterized by the accumulation of aberrant mast cells (MC). Patients suffering from mastocytosis suffer from a wide range of symptoms due to increased levels of MC mediators. It would therefore be of great benefit to inhibit MC mediator release. However, to date there are few drugs available that are known to effectively lower MC mediator levels. The evidence for the involvement of the janus kinase 2 (JAK2)-signal transducer and activation of transcription 5 (STAT5) signalling pathway in MC activation is slowly accumulating. Interference with the JAK2-STAT5 pathway might inhibit MC mediator release. Ruxolitinib, a JAK1/JAK2 inhibitor, indeed decreases symptoms like pruritus and fatigue in patients with myeloproliferative neoplasms. Yet, detailed studies on how ruxolitinib affects human mast cell activity are lacking. OBJECTIVE: To investigate the effect of JAK1/2-inhibition with ruxolitinib in the human mast cell lines LAD2 and HMC1. METHODS: LAD2 and HMC1 were stimulated with substance P, codeine or the calcium ionophore A23817. The effect of ruxolitinib on mast cell degranulation (via measurement of ß-hexosaminidase, histamine release and CD63 membrane expression) and IL-6, IL-13, MCP-1 and TNF-α production was investigated. The involvement of STAT5 activation was explored using the selective STAT5 inhibitor pimozide. RESULTS: Ruxolitinib effectively inhibited codeine- and substance P-induced degranulation in a concentration-dependent manner. Ruxolitinib also significantly inhibited the production of IL-6, TNF-α and MCP-1 as induced by A23817 and substance P. Selective STAT5 inhibition with pimozide resulted in diminished degranulation and inhibition of cytokine production as induced by A23817 and substance P. CONCLUSIONS & CLINICAL RELEVANCE: This study demonstrates that the JAK1/JAK2 inhibitor ruxolitinib can inhibit MCactivity, possibly through prevention of STAT5 activation. This renders the JAK-STAT pathway as an interesting target for therapy to release symptom burden in mastocytosis and many other MC mediator-related diseases.

Management around invasive procedures in mastocytosis: An update.

OBJECTIVE: Mastocytosis is a chronic hematologic disorder that is characterized by the accumulation of aberrant mast cells and typically involves the skin and/or bone marrow. Patients with mastocytosis are at increased risk of anaphylaxis. Based on theoretical assumptions, medical procedures requiring general anesthesia or radiocontrast media are deemed hazardous for patients with mastocytosis. The objective of this article is to provide a comprehensive overview of the actual risk of iatrogenic anaphylaxis and provide recommendations for daily practice. DATA SOURCES: Various scientific search engines were used (eg, PubMed and Medline). STUDY SELECTIONS: Because of the paucity of high-level studies on this topic, all available evidence was considered, including case reports. RESULTS: Reliable data on the incidence of iatrogenic anaphylaxis in mastocytosis are lacking. However, although the incidence as reported in (retrospective) cohort studies is higher than in the general population, it is still lower than commonly anticipated, with an incidence of 5.4% in 1 study. Adequate premedication and avoidance of certain physical stimuli can further decrease this risk by 10-fold. The role of drugs as elicitors of anaphylaxis is perhaps overestimated, and physical stimuli are at least as important in inducing release of mast cell mediators. CONCLUSION: This article provides practical recommendations for the management of invasive procedures in patients with mastocytosis based on current knowledge of this topic.

A unique presentation of pulmonary disease in advanced systemic mastocytosis, proven by the presence of mast cells in bronchoalveolar lavage: a case report.

BACKGROUND: Systemic mastocytosis is a rare myeloproliferative disease characterized by the uncontrolled proliferation of aberrant mast cells. It has varying clinical manifestations. For unknown reasons, pulmonary localization of mastocytosis is extremely rare. CASE PRESENTATION: In this report, we describe a case of a young Caucasian female with systemic mastocytosis who had an associated hematological non-mast-cell lineage disease with pulmonary interstitial disease directly related to her mastocytosis. The diagnosis was proven by the presence of mast cells in bronchoalveolar lavage. The treatment of her associated hematological disease (myelofibrosis with myelodysplasia) was hampered by rapidly declining pulmonary function and progressive organ dysfunction due to aggressive systemic mastocytosis. She died approximately 1 year after the diagnosis. CONCLUSIONS: To our knowledge, this is the first case in which mast cells were detected in bronchoalveolar lavage. Moreover, to date, only two other cases of pulmonary interstitial disease due to mastocytosis have been published. Juggling therapies for systemic mastocytosis and myelofibrosis is very difficult; however, aggressive therapy for both diseases is essential to give these patients a chance to survive.

The Basophil Activation Test Is Not a Useful Screening Tool for Hymenoptera Venom-Related Anaphylaxis in Patients with Systemic Mastocytosis.

BACKGROUND: Systemic mastocytosis (SM) patients are at a high risk for anaphylaxis, with Hymenoptera as the main culprit. A screening instrument to identify which patients are sensitized to Hymenoptera before they experience anaphylaxis would therefore be of great value. The basophil activation test (BAT) is proposed as a possible tool for diagnosing Hymenoptera venom-related allergy (HVA), especially in patients in whom conventional allergy tests yield contradictory results. METHODS: We included outpatients with SM, according to WHO criteria, from September 2011 to January 2012. Next, to obtain various clinical data including intradermal test results, specific immunoglobulin E (sIgE) measurements and BAT were performed. RESULTS: We included 29 patients, 9 of whom had a history of HVA and 4 of whom had experienced anaphylaxis due to other triggers. Sixteen patients had no history of anaphylaxis. sIgE was detected in 6 patients with HVA and in 2 patients with anaphylaxis due to other triggers. The BAT was positive in only 1 patient, in whom the skin test and sIgE were also positive. Compared to patients with skin lesions, those without skin lesions had significantly more anaphylaxis and sIgE to Hymenoptera. During a 3-year follow-up, no one experienced new anaphylactic episodes. CONCLUSION: The BAT is not a reliable tool for randomly screening SM patients for HVA.