Highly sensitive assays are mandatory for the differential diagnosis of patients presenting with symptoms of mast cell activation: diagnostic work-up of 38 patients.

Mastocytosis is a heterogeneous disease caused by excessive mast cell (MC) proliferation. Diagnosis of systemic mastocytosis (SM) is based on the presence of major and minor criteria defined by the World Health Organization. Symptoms of MC activation can also occur in patients without SM or without allergic or inflammatory disease. These MC activation syndromes (MCAS) can be divided into primary (monoclonal) MCAS (MMAS) vs. secondary and idiopathic MCAS. In this single center study, the diagnostic work-up of 38 patients with a clinical suspicion of SM and/or with elevated basic tryptase levels is presented. Clinical symptoms, biochemical parameters, results of bone marrow investigation, flow cytometric immunophenotyping, and molecular analysis were retrospectively reviewed. Twenty-three patients were found to have a monoclonal MC disorder of which 19 were diagnosed with SM and 4 with MMAS. In 13/19 SM patients, multifocal MC infiltrates in the bone marrow were found (major criterion), while in 6 the diagnosis was based on the presence of ≥3 minor criteria. Flow cytometric analysis of bone marrow showed CD25 expression of MCs in all patients with SM and MMAS (range: 0.002-0.3% of cells). In bone marrow, the KIT D816V mutation was detected in all SM patients but in only 2 patients with MMAS (range: 0.007-9% mutated cells). Basic tryptase elevation was demonstrated in 16/19 patients with SM but also in 9/19 patients without SM. Our study reveals the heterogeneity of primary MC disorders and the importance of sensitive assays in patients suspected of having SM.

Chronic urticaria is associated with mast cell infiltration in the gastroduodenal mucosa.

Chronic urticaria (CU) is characterized by recurrent itching skin eruptions caused by mast cell degranulation. Relapses can be provoked by food intake. The aim of this study was to investigate if the mast cell number in the gastroduodenal mucosa is increased in CU patients, and whether mast cell counting by pathologists is clinically useful. We defined two study groups: 50 disease controls (16 Belgians and 34 Italians) and 43 Belgian CU patients. Mast cells were detected using immunohistochemistry for tryptase and CD117. The mast cell number in the disease controls was 20.2/high-power filed (HPF; 133.3/mm2) in the stomach and 32.5/HPF (209.2/mm2) in the duodenum. There was no difference between Belgian and Italian controls, indicating that dietary habits have no influence on the normal gastroduodenal mast cell number. In CU patients, mast cell numbers were significantly higher: 32.4/HPF (186.0/mm2) in the stomach (P<0.0001) and 44.8/HPF (246.0/mm2) in the duodenum (P=0.0002). CU is thus associated with mast cell infiltration in the gastroduodenal mucosa, even if patients do not have gastrointestinal symptoms. Mast cell counting in gastroduodenal biopsies of CU patients can be useful in selecting patients who may respond to a therapy with intestinal mast-cell-stabilizing agents.

Detection of basophil-activating IgG autoantibodies in chronic idiopathic urticaria by induction of CD 63.

BACKGROUND: Approximately 40% to 50% of patients with chronic idiopathic urticaria (CIU) have functional IgG autoantibodies against FcepsilonRIalpha or IgE, which induce histamine release from basophils and cutaneous mast cells. A positive autologous serum skin test response is believed to reflect the presence of these autoantibodies. OBJECTIVE: We sought to further define the functional properties of and develop a sensitive functional assay for detection of autoantibodies in patients with CIU. METHODS: Sera from patients with CIU (n=61) and sera from healthy control subjects (n=23) were incubated with donor basophils. Activation of basophils was determined on the basis of CD 63 surface expression, as analyzed on a FACScan flow cytometer. RESULTS: A positive basophil activation test result was found in 51% of patients with CIU, and basophil-activating properties were present in the IgG fractions of sera. When both the in vitro test and the autologous serum skin test were considered, basophil/mast cell-activating autoantibodies were present in 62% of the patients. Patients with a positive basophil activation test result had a significantly higher prevalence of other autoantibodies, had more severe urticaria, and were more likely to have angioedema. CONCLUSION: The results demonstrate the presence of basophil-activating autoantibodies in about 50% of patients with CIU. The data support the autoimmune cause of the disease and provide a simple test for detection of these autoantibodies.