High-Dose Intravenous Pulse Methotrexate in Patients With Eosinophilic Fasciitis.

Importance: Eosinophilic fasciitis (EF) is a connective tissue disorder in which conventional treatment leads to disappointing results in a proportion of patients. Therefore, we investigated high-dose intravenous (IV) pulse methotrexate (MTX) as a treatment for EF. Objective: To examine safety and effects of monthly high-dose IV pulse MTX in EF. Design, Setting, and Participants: For this prospective single-arm study, we recruited 12 patients diagnosed with biopsy specimen-proven EF between 2006 and 2009 from the Department of Dermatology and Rheumatology at the Radboud University Medical Centre. Interventions: Intravenous MTX (4 mg/kg) monthly for 5 months with folinic acid rescue 24 hours after MTX administration. Main Outcomes and Measures: The primary outcome was improvement of the modified skin score at month 5 vs baseline. Secondary outcomes were durometry, range of motion, visual analog scale scores for disease activity, and 36-Item Short Form Survey health questionnaires. Results: Overall, 12 patients (11 women between 37-69 years old) received a median (range) monthly dose of 288 (230-336) mg MTX. Median (range) modified skin score improved from 17.5 (8.0-24.0) at baseline to 8.5 (1.0-20.0) at month 5 (P = .001). Secondary outcome measures improved significantly, except for durometer scores and range of motion of the elbows. Adverse events included gastrointestinal symptoms (n = 9), mild stomatitis (n = 5), and alopecia (n = 4). Conclusions and Relevance: High-dose IV pulse MTX is a safe and effective treatment option in EF. Trial Registration: clinicaltrials.gov Identifier: NCT00441961.

Use of Mycophenolate Mofetil in Patients with Severe Localized Scleroderma Resistant or Intolerant to Methotrexate.

To assess the efficacy and safety of mycophenolate mofetil (MMF) in patients with localized scleroderma (LoS) resistant or intolerant to previous treatment with methotrexate (MTX). A case series of patients with LoS treated with MMF. Outcome was assessed through clinical examination. Adverse events were documented. Seven patients with LoS were treated with MMF. Median age at MMF initiation was 15 years (range 7-74 years). Three patients received MMF due to MTX ineffectiveness and 4 due to MTX intolerance. Disease remission was achieved in 4 patients and maintained in one patient. One patient showed a favourable response, but had to discontinue treatment due to elevated liver enzymes. The remaining patient experienced disease progression. MMF was shown to improve the clinical condition of patients with refractory LoS and may be a relatively safe alternative in patients who are intolerant to MTX.

Scleroderma-polymyositis overlap syndrome versus idiopathic polymyositis and systemic sclerosis: a descriptive study on clinical features and myopathology.

INTRODUCTION: The objective was to characterize the clinical and myopathologic features of patients with scleroderma-polymyositis (SSc-PM) overlap compared with a population of patients with systemic sclerosis (SSc) and polymyositis (PM). METHODS: A three-way comparison of patients with SSc-PM overlap (n = 25) with patients with SSc (n = 397) and PM (n = 40) on clinical and myopathologic features and causes of death. One neuropathologist blinded for the diagnosis evaluated all recent available muscle biopsies. Biopsies were scored for presence of inflammation, necrotic muscle fibers, rimmed vacuoles, fibrosis, and immunohistochemical staining. Clinical or myopathologic characteristics were compared by using the χ(2) test or one-way analysis of variance (ANOVA). RESULTS: The prevalence of SSc-PM overlap in the Nijmegen Systemic Sclerosis cohort was 5.9%. The mortality was 32% (eight of 25) in SSc-PM, of which half was related to cardiac diseases. The prevalence of pulmonary fibrosis was significantly increased in SSc-PM (83%) (P = 0.04) compared with SSc (49%) and PM (53%). SSc or myositis-specific antibodies were nearly absent in the SSc-PM group. In almost all biopsies (96%) of SSc-PM patients, necrotic muscle fibers were present, which was significantly increased compared with PM patients (P = 0.02). CONCLUSIONS: Patients with SSc-PM have increased prevalence of pulmonary fibrosis and cardiac disease as the cause of death compared with patients with SSc and PM . In addition, we found that necrotizing muscle fibers with inflammation characterize SSc-PM overlap in muscle biopsies. Further research should focus on underlying mechanisms causing necrosis, inflammation, and fibrosis and their relation to pulmonary involvement and mortality in patients with SSc-PM overlap.

Therapy for Whipple's disease.

Whipple's disease was first described in 1907, the genomic composition of the causative organism, Tropheryma whipplei, was unravelled in 2003 and its in vitro susceptibility to antibiotics started to be explored in 2004-05. Still today, this knowledge is not fully applied in the recommendations for the therapy of this disease. In this paper, we summarize the current recommendations on antimicrobial therapy for Whipple's disease and propose a shift in the maintenance therapy.