Detection of clonal mast cell disease in wasp venom allergic patients with normal tryptase.

Background: Clonal mast cell disease (CMD) is an underlying aggravating condition in wasp venom allergy (WVA) which requires a different treatment strategy. CMD is increasingly recognized in patients with normal basal serum tryptase (bsT). However, methods to identify at risk patients have not yet been assessed in large cohorts of WVA patients with normal bsT. Methods: This retrospective study evaluated the reliability of the REMA score in detecting CMD in a cohort of grade IV WVA patients with normal bsT and assessed the added value of other clinical parameters, KIT D816V mutation analysis in peripheral blood (PB) and the diagnosis of hereditary alpha tryptasemia (HAT). All patients had a conclusive bone marrow evaluation that demonstrated or excluded underlying CMD. Results: In total 35 CMD and 96 non-CMD patients were included. REMA score had a sensitivity of 72% (95% CI 56%-88%) and specificity of 79% (95% CI 70%-87%) in this cohort. Loss of consciousness during systemic reaction and bsT between 6.3 and 11.4 ng/ml were additional parameters independently associated with CMD. Sensitivity of KIT in PB was relatively low, 56% (95% CI 36%-75%), but had added value as screening method in patients with a low REMA score due to 100% specificity. Conclusion: The REMA score is a relatively reliable method to detect patients at risk of CMD among WVA patients with normal bsT. KIT mutation analysis in PB could serve as additional screening method in patients with low REMA scores.

Fracture Risk Reduction by Bisphosphonates in Mastocytosis?

BACKGROUND: Fragility fractures (FFxs) and osteoporosis are frequent manifestations of indolent systemic mastocytosis (ISM). So far, the effect of antiosteoporotic therapy on FFxs has scarcely been investigated. OBJECTIVE: This study evaluates the long-term effect of bisphosphonate treatment on FFxs, bone mineral density (BMD), and bone resorption in patients with ISM in daily clinical practice. METHODS: Patients with ISM who received bisphosphonates because of osteoporosis and/or FFxs were retrospectively analyzed (n = 58). Fractures were recorded by vertebral fracture assessment, X-rays of the thoracolumbar spine, medical records, and a questionnaire. Five-year analysis (n = 30) was made by comparing observed 5-year FFx risk with MastFx-predicted FFx risk for patients with ISM not treated with antiosteoporotic drugs and analyzing 5-year change in BMD and serum collagen C telopeptide (sCTx) Z-scores. RESULTS: During the median follow-up of 7.3 years, 14 of 58 patients suffered 40 FFxs. Five- and 10-year FFx-free survival were 81.9% (standard error [SE], 5.5%) and 67.0% (SE, 7.7%), respectively. FFx risk was significantly higher in patients with previous vertebral FFxs (P = .004), lower femoral BMD at baseline (P = .042), and history of anaphylaxis (P = .028). No 5-year FFx risk reduction could be proven, possibly due to the small sample size. The lumbar BMD Z-score significantly increased from median (interquartile range [IQR]) -2.20 (-2.80 to -1.50) to -1.50 (-2.30 to -0.60) (P < .001, n = 27). The sCTx Z-score decreased from median 0.71 (IQR, -0.59 to 2.39) to -0.95 (-1.30 to -0.16) (P = .008, n = 15). CONCLUSION: Bisphosphonates significantly increase BMD and decrease sCTx in patients with ISM. However, FFxs still frequently occur. Especially patients with previous FFxs remain at high risk of new FFxs.

Mast Cell Clonal Disorders: Classification, Diagnosis and Management.

Mast cell clonal disorders are characterized by the clonal proliferation of pathological mast cells as a result of somatic mutations in the KIT gene, most commonly the D816V mutation. Accumulation and degranulation of these cells causes a wide variety of symptoms. Mast cell clonal disorders can be divided into mastocytosis and monoclonal mast cell activation syndrome, depending of the level of clonality. The severity of mastocytosis varies from an indolent variant with a good prognosis, to an aggressive condition with short life expectancy. Diagnosis is based on demonstration of clonality and accumulation in the skin and in extracutaneous tissues. Treatment is highly individualized, and is based on the severity of the condition. Treatment of patients with indolent systemic mastocytosis is aimed at reducing symptoms, using histamine H1 and H2 receptor antagonists as a starting point. In addition, associated conditions such as osteoporosis must be treated. Treatment of advanced systemic mastocytosis is aimed at reducing mast cell load through cytoreductive therapy. The choice of such therapy depends on the KIT mutational status. Though currently there is no curative treatment available, promising new therapies such as midostaurin are emerging that have demonstrated success in reducing symptoms and improving quality of life.