Adult mastocytosis is an incurable clonal disease associated with c-KIT mutations, mostly in exon 17 (D816V). In contrast, pediatric mastocytosis often spontaneously regresses and is considered a reactive disease. Previous studies on childhood mastocytosis assessed only a few patients and focused primarily on codon 816 mutations, with various results. In this study, we analyzed the entire c-KIT sequence from cutaneous biopsies of 50 children with mastocytosis (ages 0-16 years). A mutation of codon 816 (exon 17) was found in 42% of cases, and mutations outside exon 17 were observed in 44%. Unexpectedly, half of the mutations were located in the fifth Ig loop of c-KIT's extracellular domain, which is encoded by exons 8 and 9. All mutations identified in this study were somatic and caused a constitutive activation of c-KIT. There was no clear phenotype-genotype correlation, no clear relationship between the mutations and familial versus spontaneous disease, and no significant change in the relative expression of the c-KIT GNNK+ and GNNK isoforms. These findings strongly support the idea that, although pediatric mastocytosis can spontaneously regress, it is a clonal disease most commonly associated with activating mutations in c-KIT.

Background: Dupilumab is the first biologic available to treat atopic dermatitis (AD). Its effectiveness and safety were demonstrated in clinical trials. Objective:We sought to assess the effectiveness and safety of dupilumab in adults with AD in a real-life French multicenter retrospective cohort.Methods: Patients were included between March 2017 and April 2018. Efficacy outcomes were collected both at baseline and three months (M3), when available, including SCORAD (Scoring Atopic Dermatitis) and EASI (Eczema Area and Severity Index) scores. Adverse events (AE) were recorded at the follow-up. Results:We included 241 patients. The median follow-up time was 3.8±3.7 months. SCORAD75 and EASI75 were achieved in 27/163 (16.6%) and 40/82 (48.8%) patients, respectively. The median SCORAD and EASI at M3 were significantly lower compared with baseline (25±21 vs 56±27.4, p<10 -9 and 4.1±6.8 vs 17.9±15.4, p<10 -9 , respectively).Conjunctivitis was reported in 84/241 (38.2%) patients. The proportion of eosinophilia (>500/mm 3 ) during follow-up (57%) was higher than at baseline (33.7%) (n=172, p<10 -6 ).Dupilumab was stopped in 42 cases, 27 of which were due to an AE. Limitations:No control group, missing data. Conclusion:This real-life study demonstrated results similar to clinical trials, with regard to dupilumab effectiveness, but revealed a higher frequency of conjunctivitis and eosinophilia.

We here distinguish three different clinical presentations of BPDCN. A nodular pattern is a more common feature than the originally reported 'bruise-like' pattern. Despite the fact that BPDCN may initially appear as a localized skin tumour, aggressive management including allogeneic bone marrow transplantation should be considered immediately, as it is currently the only option associated with long-term survival.

Vemurafenib has an objective and sustained efficacy in BRAF(V600E)-mutated ECD as second-line therapy. In contrast to melanoma, no resistance has emerged to date after 6 to 16 months.

Key Points• The association of both Langerhans cell histiocytosis and Erdheim-Chester disease is not exceptional. • This association is linked to BRAF V600E mutation.Histiocytoses are a group of heterogeneous diseases that mostly comprise Langerhans cell histiocytosis (LCH) and non-LCH. The association of LCH with non-LCH is exceptional. We report 23 patients with biopsy-proven LCH associated with Erdheim-Chester disease (ECD) (mixed histiocytosis) and discuss the significance of this association. We compare the clinical phenotypes of these patients with those of 56 patients with isolated LCH and 53 patients with isolated ECD. The average age at diagnosis was 43 years. ECD followed (n 5 12) or was diagnosed simultaneously with (n 5 11) but never preceded LCH. Although heterogeneous, the phenotype of patients with mixed histiocytosis was closer to that of isolated ECD than to that of isolated LCH (principal component analysis). LCH and ECD improved in response to interferon alpha-2a treatment in only 50% of patients (8 of 16). We found the BRAF V600E mutation in 11 (69%) of 16 LCH lesions and in 9 (82%) of 11 ECD lesions. Eight patients had mutations in both ECD and LCH biopsies. Our findings indicate that the association of LCH and ECD is not fortuitous and suggest a link between these diseases involving the BRAF V600E mutation. (Blood.

Background Blastic plasmacytoid dendritic cell neoplasm (BPDCN) represents the malignant counterpart derived from plasmacytoid dendritic cells. This rare entity is usually revealed and diagnosed on cutaneous lesions associated or not with a leukaemic component. The prognosis associated with BPDCN is very poor. Objectives To perform a retrospective review of BPDCN cases registered in the French Study Group on Cutaneous Lymphoma database from June 1995 to May 2008. Methods Forty-seven patients were included. Demographic data, initial staging, therapeutic management and outcome were recorded. Results The mean survival was 16.7 months (95% confidence interval 12.6-20.8). Only eight (17%) and one (2%) patients reached respectively 2 and 5 years of survival. Initial spreading of the disease did not represent, in this cohort, a reliable prognosis factor. The outcome was overall influenced by treatment provided. While radiation therapy, monochemotherapy or even polychemotherapy regimens did not significantly affect the course of the disease, the survival of bone marrow transplanted patients was significantly higher. Conclusions Despite the fact that BPDCN is often initially limited to the skin, only an aggressive initial therapy may improve the patients' prognosis. Local treatments, such radiation therapy, are definitively useless. Regardless of the initial extension of the disease, in our experience only bone marrow transplantation significantly improved the outcome.

Our study reports new insights into the therapeutic management of EF: (i) CS treatment remains the standard therapy for EF, taken alone or in association with an ISD; (ii) MPPs at initiation of treatment are associated with a better outcome and a lower need of ISD use; (iii) an ISD, usually MTX, might be useful as a second-line therapy, mainly in patients with morphoea-like lesions. Naturally, these practical conclusions should be confirmed by a prospective and multicentre study.

BackgroundIndolent forms of mastocytosis account for more than 90% of all cases, but the types and type and severity of symptoms and their impact on the quality of life have not been well studied. We therefore performed a case-control cohort study to examine self-reported disability and impact of symptoms on the quality of life in patients with mastocytosis.Methodology/Principal FindingsIn 2004, 363 mastocytosis patients and 90 controls in France were asked to rate to their overall disability (OPA score) and the severity of 38 individual symptoms. The latter was used to calculate a composite score (AFIRMM score). Of the 363 respondents, 262 were part of an ongoing pathophysiological study so that the following data were available: World Health Organization classification, standard measures of physical and psychological disability, existence of the D816V KIT mutation, and serum tryptase level. The mean OPA and AFIRMM scores and the standard measures of disability indicated that most mastocytosis patients suffer from disabilities due to the disease. Surprisingly, the patient's measurable and perceived disabilities did not differ according to disease classification or presence or absence of the D816V KIT mutation or an elevated (≥20 ng/mL) serum tryptase level. Also, 32 of the 38 AFIRMM symptoms were more common in patients than controls, but there were not substantial differences according to disease classification, presence of the D816V mutation, or the serum tryptase level.ConclusionsOn the basis of these results and for the purposes of treatment, we propose that mastocytosis be first classified as aggressive or indolent and that indolent mastocytosis then be categorized according to the severity of patients' perceived symptoms and their impact on the quality of life. In addition, it appears that mastocytosis patients suffer from more symptoms and greater disability than previously thought, that mastocytosis may therefore be under-diagnosed, and that the symptoms of the indolent forms of mastocytosis might be due more to systemic release of mediators than mast cell burden.