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Objective: To assess the efficacy and risks of treatment with infliximab (anti-tumor necrosis factor alpha) in pathology-confirmed neurosarcoidosis., Methods: In a retrospective study in 2 tertiary referral centers in the Netherlands, we analyzed clinical characteristics, complications, and outcome of patients with neurosarcoidosis treated with infliximab., Results: Twenty-eight patients were identified with a mean age of 42 years. Neurosarcoidosis presented with a cerebral parenchymal localization in 16 (59%), pituitary gland/hypothalamic sarcoidosis in 15 (54%), peripheral nerve involvement in 12 (43%), and chronic meningitis in 11 patients (41%). Initial treatment response after the start of infliximab was complete remission in 6 (21%) and improvement in 14 (50%), whereas 7 patients had stable disease (25%), and 1 (4%) deteriorated and died. At the end of follow-up, with a median of 32 months, 5 patients (18%) had died, and 2 (40%) were using infliximab at the time of death. Tapering or discontinuation of corticosteroids without a relapse was achieved in 19 of 28 patients (68%). In patients with decreasing dosing or discontinuation of infliximab, a relapse occurred in 5 of 19 patients (26%). Complications of infliximab were reported in 10 of 28 patients (36%) and mainly consisted of infections in 8 (29%)., Conclusion: Infliximab is an effective treatment in neurosarcoidosis leading to remission or improvement in 70%. The mortality rate in infliximab-treated patients was substantial, indicating the severity of disease and treatment-associated complications., Classification of Evidence: This study provides Class IV evidence that in people with pathology-confirmed neurosarcoidosis, infliximab is beneficial., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Background: The soluble interleukin 2 receptor (sIL-2R) has been proposed as a marker of disease activity in patients with sarcoidosis. However, no studies have evaluated whether serum sIL-2R measurement is of use in establishing the diagnosis of sarcoidosis in patients who are suspected of sarcoidosis among other diseases., Methods: A cohort study was conducted, consisting of new patients who visited the immunology outpatient clinic and whose serum sIL-2R levels were available before a definitive diagnosis was established between February 2011 and February 2016. All patients underwent standard diagnostic testing for sarcoidosis (e.g. laboratory tests, radiographic and/or nuclear imaging and/or affected site biopsy). This resulted either in the diagnosis of sarcoidosis or the exclusion of sarcoidosis with the diagnosis of another disease. Results of sIL-2R and angiotensin-converting enzyme (ACE) levels, radiographic and nuclear imaging and histology results were collected and definitive diagnoses were recorded. Sensitivity, specificity, the concordance statistic from the receiver operating characteristic curve and Youden's Index were calculated to assess the performance of sIL-2R in the diagnosis of sarcoidosis and were compared to ACE, currently one of the most used diagnostic biomarkers in the diagnosis of sarcoidosis., Results: In total 983 patients were screened for inclusion, of which 189 patients met the inclusion criteria. A total of 101 patients were diagnosed with sarcoidosis after diagnostic workup, of whom 79 were biopsy-proven. In 88 patients a diagnosis other than sarcoidosis was made. The sensitivity and specificity of serum soluble interleukin 2 receptor levels to detect sarcoidosis were 88% and 85%. The sensitivity and specificity of ACE were 62% and 76%. Receiver operating characteristic curve analysis revealed that sIL-2R receptor is superior to ACE (p<0.0001)., Conclusion: Serum sIL-2R is a sensitive biomarker and superior to ACE in establishing the diagnosis of sarcoidosis and can be used to rule out sarcoidosis in patients suspected of sarcoidosis., Competing Interests: The authors have declared that no competing interests exist.

Background: IgG 4 -related disease (IgG 4 -RD) is a systemic fibroinflammatory condition affecting various organs and has a diverse clinical presentation. Fibrosis and accumulation of IgG 4 + plasma cells in tissue are hallmarks of the disease, and IgG 4 -RD is associated with increased IgG 4 serum levels. However, disease pathogenesis is still unclear, and these cellular and molecular parameters are neither sensitive nor specific for the diagnosis of IgG 4 -RD., Objective: Here we sought to develop a flow cytometric gating strategy to reliably identify blood IgG 4 + B cells to study their cellular and molecular characteristics and investigate their contribution in disease pathogenesis., Methods: Sixteen patients with histologically confirmed IgG 4 -RD, 11 patients with sarcoidosis, and 30 healthy subjects were included for 11-color flow cytometric analysis of peripheral blood for IgG 4 -expressing B cells and T H subsets. In addition, detailed analysis of activation markers and chemokine receptors was performed on IgG 4 -expressing B cells, and IgG 4 transcripts were analyzed for somatic hypermutations., Results: Cellular and molecular analyses revealed increased numbers of blood IgG 4 + memory B cells in patients with IgG 4 -RD, but not patients with sarcoidosis, had increased numbers of circulating plasmablasts and CD21 4 -RD, but not patients with sarcoidosis, had increased numbers of circulating plasmablasts and CD21 low 2 and regulatory T cells, indicating a common disease pathogenesis in patients with IgG H 2 and regulatory T cells, indicating a common disease pathogenesis in patients with IgG 4 -RD., Conclusion: These results provide new insights into the dysregulated IgG 4 response in patients with IgG 4 -RD. A specific "peripheral lymphocyte signature" observed in patients with IgG 4 -RD, could support diagnosis and treatment monitoring., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Rationale: Although chest radiography is currently recommended for the initial evaluation of patients with new-onset uveitis, the efficacy of this diagnostic screening modality is not known., Objectives: To evaluate the diagnostic value of chest radiographs in patients with active uveitis of recent onset in a tertiary center in Western Europe., Methods: A retrospective cross-sectional study was conducted by reviewing all chest imaging for adults with new-onset (<1 yr) uveitis of unknown origin undergoing initial evaluation in the Department of Ophthalmology at Erasmus University Medical Center (Rotterdam, the Netherlands). Radiographic findings were related to clinical and other imaging characteristics and to final diagnoses., Results: Screening chest radiographs were abnormal for 30 of 200 patients (15%) included in this study. Twenty-two of the 200 patients (11%) had biopsy-confirmed sarcoidosis, and an additional 12 patients were presumed to have sarcoidosis. The finding of chest radiographic abnormalities interpreted as typical of sarcoidosis was specific (91%; 95% confidence interval, 85.9-94.4%) but not sensitive (64%; 95% confidence interval, 43.0-80.3%) for biopsy-confirmed sarcoidosis. The combination of elevated serum angiotensin-converting enzyme level and chest radiographic findings typical of sarcoidosis increased the sensitivity to 79%. Biopsy-confirmed sarcoidosis was more common in patients with panuveitis (17 of 84; 20%) compared to patients with other anatomical locations of uveitis (5 of 116, 4%; P < 0.001). One patient was diagnosed with active pulmonary and ocular tuberculosis., Conclusions: Abnormal chest radiographs were found in 15% of patients with active uveitis of unknown origin and onset within 1 year of referral to a tertiary center in the Netherlands. A majority of the abnormal chest radiographs showed findings compatible with a diagnosis of sarcoidosis.

Sarcoidosis is a granulomatous disease of unknown etiology. Standard treatment with immune suppressants such as glucocorticoids is started when vital organ function is threatened. Biotechnology has resulted in new treatments ('biologicals'), in particular monoclonal antibodies, that may be effective in the treatment of sarcoidosis. In patients with sarcoidosis, only the use of monoclonal antibodies that block tumour necrosis factor (TNF) has been studied scientifically, other biologicals hardly at all. TNF-blockers are used at present in patients with therapy refractory sarcoidosis.