Clinical presentation and management practice of systemic mastocytosis. A survey on 460 Italian patients.

Systemic mastocytosis is a rare heterogeneous myeloproliferative neoplasm characterized by abnormal proliferation and activation of mast cells. We describe a large multicentre series of 460 adult patients with systemic mastocytosis, with a diagnosis based on WHO 2008 criteria, in a "real-life" setting of ten Italian centers with dedicated multidisciplinary programs. We included indolent forms with (n = 255) and without (n = 165) skin lesions, smouldering (n = 20), aggressive (n = 28), associated with other hematological diseases mastocytosis (n = 21) and mast cell leukemia (n = 1). This series was uniquely characterized by a substantial proportion of patients with low burden of neoplastic mast cells; notably, 38% of cases were diagnosed using only minor diagnostic criteria according to WHO 2008 classification, underlying the feasibility of early diagnosis where all diagnostic approaches are made available. This has particular clinical relevance for prevention of anaphylaxis manifestations, that were typically associated with indolent forms. In multivariate analysis, the most important features associated with shortened overall survival were disease subtype and age at diagnosis >60 years. Disease progression was correlated with mastocytosis subtype and thrombocytopenia. As many as 32% of patients with aggressive mastocytosis suffered from early evolution into acute leukemia. Overall, this study provides novel information about diagnostic approaches and current presentation of patients with SM and underlines the importance of networks and specialized centers to facilitate early diagnosis and prevent disease-associated manifestations. Am. J. Hematol. 91:692-699, 2016. © 2016 Wiley Periodicals, Inc.

Can periodontal disease affect conception? A literature review.

Today periodontal health is considered as an integral part of systemic health itself and no longer as a single factor. The literature recognizes that the presence of periodontal disease can represent a risk factor for numerous systemic conditions such as heart disease and diabetes. In recent years, we have witnessed a progressive interest regarding the influence exerted by this condition on reproduction, as well as the possible repercussions on conception possibilities. Upon analyzing a limited number of studies available for the correlation between periodontal disease and female infertility, it could be inferred that this condition can be equated to the presence of a real outbreak of infection and therefore exert its influence, not only through bacterial translocation in the bloodstream, causing the systemic dissemination of pathogens, but also through the production of cytokines and immunoglobulins by inflammatory mediators. This situation limits bacterial growth, but it could cause damage to the fetus, to the reproductive system, and could hinder conception attempts. Although further research is needed to better clarify the mechanism underlying the possible correlation between periodontal disease and female infertility, the present article aims to review all the available literature on this topic. LAY SUMMARY: In recent years, interest regarding the influence of gum disease on conception has increased. Since serious gum disease (periodontitis) can be compared to an outbreak of infection, studies suggest that the bacteria that mediate inflammation do not remain confined only to the gum tissue, but can enter the bloodstream and spread, thus spreading the infection and having a whole-body effect. This situation could cause damage to the developing baby, to the reproductive system and could hinder conception attempts. Constant maintenance of oral health is definitely necessary. It is important for the professionals involved (gynecologists, obstetricians, dentists, etc.) to communicate and collaborate on these issues. Dentists could advise on the correct hygienic maintenance not only to pregnant women, but also to those who are planning a pregnancy in order to avoid the occurrence of unfavorable conditions.

Primary role of multiparametric flow cytometry in the diagnostic work-up of indolent clonal mast cell disorders.

BACKGROUND: According to the World Health Organization (WHO) classification the diagnosis of systemic mastocytosis (SM) relies on bone marrow (BM) examination and is based on one major and four minor criteria. Herein, we used WHO criteria to compare flow cytometry (FC) with other available techniques in the diagnosis of SM after BM examination. METHODS: We analyzed a cohort of 95 patients with suspect SM. All patients underwent comprehensive BM examination by using cytology, immunohistochemistry, FC and molecular study for mutation of c-Kit and serum tryptase dosage. FC evaluation was based on a combination of monoclonal antibodies, specifically CD25/CD2/CD45/CD34/CD117. RESULTS: Seventy-four out of ninety-five patients were diagnosed with indolent SM (n = 59) or monoclonal mast cell activation syndrome (n = 15) because satisfying less than 3 minor criteria. Thirty-nine out of these seventy-four patients fulfilled the major histological criterion, whereas the presence of a minor criterion was assessed by FC, molecular study, cytology, and tryptase level in 70/74, 52/67, 56/74, and 42/74 patients, respectively. FC showed higher sensitivity than IHC in detection of CD25+ mast cells (MC) (92.9% vs. 73.8%; P = 0.019), especially in the absence of the major histological criterion (90.5% vs. 47.6%; P = 0.003). Moreover, CD2 expression was documented by FC and IHC in 97.1% and 35.3% of cases, respectively (P < 0.001). CONCLUSIONS: FC showed the best sensitivity for identifying abnormal MC compared to other techniques, especially in cases with low MC burden. Therefore, we hope for a major role of FC in the diagnostic work-up of clonal MC disorders.

Bone mineral density, bone turnover markers and fractures in patients with indolent systemic mastocytosis.

OBJECTIVE: We systematically assessed bone mineral density (BMD), bone turnover markers (BTM), and fractures in a large cohort of patients with Indolent Systemic Mastocytosis (ISM). METHODS: Eighty-two patients (mean age 48 years, 37 women) with ISM were studied. BMD was measured by dual X-ray absorptiometry at the lumbar spine and proximal hip. The serum markers of bone turnover included bone-specific alkaline phosphatase, C-telopeptides of type I collagen, and serum osteocalcin. Previous clinical fractures were registered and spine X-ray was obtained from all patients. RESULTS: Three women were excluded for concomitant diseases associated to osteoporosis. Osteoporosis according with the WHO classification (T-score<-2.5) was found in 16 patients (20.0%) (7 females and 9 men). Mastocytosis-related low BMD (Z-score at either the spine or the hip<-2) was found in 3 women (9%) and 13 men (28%). The BMD was generally lower at the spine than at the hip. No significant correlation was observed between serum tryptase levels and T or Z-score BMD. One or more moderate or severe vertebral fractures were found in 17 patients (12 men); in 11 of them Z-score values were>-2 or not valuable at the spine. No significant difference was found in the prevalence of mastocytosis-related low BMD and/or vertebral fractures between patients with or without skin involvement. Two patients had radiographic and densitometric osteosclerosis-like characteristics. In osteoporotic patients higher, normal or lower serum BTM were found, without correlations with serum tryptase levels, while in patients with osteosclerosis both BTM and serum tryptase values were particularly increased. CONCLUSIONS: Vertebral osteoporosis and fractures are frequent in patients with ISM. Spine X-ray and densitometric examination are warranted in all patients, also without skin involvement and particularly in males; Z-score other than T-score BMD must be evaluated. Patients with idiopathic osteoporosis should be evaluated for mast cell disease. Both high than low BTM can be observed in patients with osteoporosis while osteosclerosis is characterized by high bone turnover and serum tryptase levels.