A polymorphism in C-C Chemokine Receptor 5 (CCR5) associates with Lofgren's syndrome and alters receptor expression as well as functional response

C-C chemokine receptor 5 (CCR5) and polymorphisms in CCR5 gene are associated with sarcoidosis and Lofgren's syndrome. Lofgren's syndrome is an acute and usually self-remitting phenotype of sarcoidosis. We investigated whether the single nucleotide polymorphism (SNP) rs1799987 is associated with susceptibility for Lofgren's syndrome and has an effect on CCR5 expression on monocytes and function of CCR5. A total of 106 patients with Lofgren's syndrome and 257 controls were genotyped for rs1799987. Expression of CCR5 on monocytes was measured by flowcytometry. We evaluated calcium influx kinetics following stimulation upon N-formylmethionyl-leucyl-phenylalanine (fMLP) and macrophage inflammatory protein-1 alpha (MIP-1 alpha) on monocytes by measuring the median fluorescence intensity (MFI). The frequency of the G allele of rs1799987 was significantly higher in Lofgren's syndrome than in healthy controls (p = 0.0015, confidence interval (CI) 1.22-2.32, odds ratio (OR) 1.680). Patients with a GG genotype showed higher CCR5 expression on monocytes than patients with the AA genotype (p = 0.026). A significantly (p = 0.027) lower count of patients with the GG genotype showed a calcium influx reaction to simulation upon MIP-1 alpha, compared with patients with the AA genotype. The rs1799987 G allele in CCR5 gene is associated with susceptibility to Lofgren's syndrome and with quantitative and qualitative changes in CCR5, potentially effecting the inflammatory response.Pathophysiology and treatment of rheumatic disease

Design of a randomized controlled trial to evaluate effectiveness of methotrexate versus prednisone as first-line treatment for pulmonary sarcoidosis: the PREDMETH study

Background: Treatment of pulmonary sarcoidosis is recommended in case of significant symptoms, impaired or deteriorating lung function. Evidence-based treatment recommendations are limited and largely based on expert opinion. Prednisone is currently the first-choice therapy and leads to short-term improvement of lung function. Unfortunately, prednisone often has side-effects and may be associated with impaired quality of life. Methotrexate is presently considered second-line therapy, and appears to have fewer side-effects. Objective: The primary objective of this trial is to investigate the effectiveness and tolerability of methotrexate as first-line therapy in patients with pulmonary sarcoidosis compared with prednisone. The primary endpoint of this study will be the change in hospital-measured Forced Vital Capacity (FVC) between baseline and 24 weeks. Secondary objectives are to gain more insights in response to therapy in individual patients by home spirometry and patient-reported outcomes. Blood biomarkers will be examined to find predictors of response to therapy, disease progression and chronicity, and to improve our understanding of the underlying disease mechanism. Methods/design: In this prospective, randomized, non-blinded, multi-center, non-inferiority trial, we plan to randomize 138 treatment-naïve patients with pulmonary sarcoidosis who are about to start treatment. Patients will be randomized in a 1:1 ratio to receive either prednisone or methotrexate in a predefined schedule for 24 weeks, after which they will be followed up in regular care for up to 2 years. Regular hospital visits will include pulmonary function assessment, completion of patient-reported outcomes, and blood withdrawal. Additionally, patients will be asked to perform weekly home spirometry, and record symptoms and side-effects via a home monitoring application for 24 weeks. Discussion: This study will be the first randomized controlled trial comparing first-line treatment of prednisone and methotrexate and provide valuable data on efficacy, safety, quality of life and biomarkers. If this study confirms the hypothesis that methotrexate is as effective as prednisone as first-line treatment for sarcoidosis but with fewer sideeffects, this will lead to improvement in care and initiate a change in practice. Furthermore, insights into the immunological mechanisms underlying sarcoidosis pathology might reveal new therapeutic targets

Results of the standard set forpulmonary sarcoidosis: Feasibility and multicentre outcomes

Our study presents findings on a previously developed standard set of clinical outcome data for pulmonary sarcoidosis patients. We aimed to assess whether changes in outcome varied between the different centres and to evaluate the feasibility of collecting the standard set retrospectively. This retrospective observational comparative benchmark study included six interstitial lung disease expert centres based in the Netherlands, Belgium, the UK and the USA. The standard set of outcome measures included 1) mortality, 2) changes in pulmonary function (forced vital capacity (FVC), forced expiratory volume in 1 s, diffusing capacity of the lung for carbon monoxide), 3) soluble interleukin-2 receptor (sIL-2R) change, 4) weight changes, 5) quality-of-life (QoL) measures, 6) osteoporosis and 7) clinical outcome status (COS). Data collection was considered feasible if the data were collected in ⩾80% of all patients. 509 patients were included in the retrospective cohort. In total six patients died, with a mean survival of 38±23.4 months after the diagnosis. Centres varied in mean baseline FVC, ranging from 110 (95% CI 92–124)% predicted to 99 (95% CI 97–123)% pred. Mean baseline body mass index (BMI) of patients in the different centres varied between 27 (95% CI 23.6–29.4) kg·m−2 and 31.8 (95% CI 28.1–35.6) kg·m−2. 310 (60.9%) patients were still on systemic therapy 2 years after the diagnosis. It was feasible to measure mortality, changes in pulmonary function, weight changes and COS. It is not (yet) feasible to retrospectively collect sIL-2R, osteoporosis and QoL data internationally. This study shows that data collection for the standard set of outcome measures for pulmonary sarcoidosis was feasible for four out of seven outcome measures. Trends in pulmonary function and BMI were similar for different hospitals when comparing different practices

First patient-centred set of outcomes for pulmonary sarcoidosis: a multicentre initiative

Introduction Routine and international comparison of clinical outcomes enabling identification of best practices for patients with pulmonary sarcoidosis is lacking. The aim of this study was to develop a standard set of outcome measures for pulmonary sarcoidosis, using the valuebased healthcare principles. Methods Six expert clinics for interstitial lung diseases in four countries participated in a consensus-driven RANDmodified Delphi study. A mixed-method approach was applied for the identification of an outcome measures set and initial conditions for patients with pulmonary sarcoidosis. The expert team consisted of multidisciplinary professionals (n=14) from Cleveland Clinic, Cincinnati MC, Erasmus MC, Leuven UZ, Royal Brompton and St. Antonius Hospital. During a ranking process, participants were instructed to rank variables on a scale from 1 to 10 based on whether it has (1) impact of the outcome on quality of life, (2) impact of quality of care on the outcome and (3) the number of patients negatively affected by the outcome. Results An outcome measures set was defined consisting of seven outcome measures: mortality, pulmonary function, soluble interleukin-2 receptor change as an activity biomarker, weight gain, quality of life, osteoporosis and clinical outcome status. Discussion Collecting outcomes in pulmonary sarcoidosis internationally and the use of a broadly accepted set can enable international comparison. Differences in outcomes can potentially be used as a starting point for quality improvement initiatives

Caution for interstitial lung disease as a cause of CA 15-3 rise in advanced breast cancer patients treated with everolimus

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Intraocular sarcoidosis: association of clinical characteristics of uveitis with positive chest high-resolution computed tomography findings.

Item does not contain fulltextAIM: To assess specific clinical criteria in patients with uveitis that are related to signs of sarcoidosis on high-resolution computed tomography (HRCT) of the chest. METHODS: Retrospective study of 50 consecutive patients with uveitis who were referred for chest HRCT because of suspicion of sarcoidosis. Clinical characteristics, laboratory findings, chest radiographs and chest HRCT scans were retrieved. HRCT scans were reassessed for signs of sarcoidosis. Mann-Whitney and Fisher exact test were used for data analysis. RESULTS: Ten of 50 (20%) uveitis patients referred for HRCT demonstrated signs of sarcoidosis on HRCT. The median age of these patients was significantly higher than those patients with a negative HRCT (71.1 vs 44.7 years, p=0.002). The presence of peripheral chorioretinal punched out lesions and posterior synechiae were significantly related to an abnormal HRCT scan. CONCLUSION: Increasing age, presence of peripheral multifocal chorioretinitis and posterior synechiae were associated with an abnormal HRCT scan.1 februari 201