Infliximab is effective as a third-line therapeutic for severe sarcoidosis; however, long-term efficacy is unknown. The aim of this study was to assess the relapse rate after discontinuation of infliximab in sarcoidosis patients and predict relapse by analysis of the activity marker soluble interleukin (IL)-2 receptor (sIL-2R) and maximum standardised uptake value (SUV_max) of¹⁸F-fluorodeoxyglucose positron emission tomography (FDG PET).In this retrospective cohort study, the proportion of relapse was analysed using the Kaplan–Meier method and predicting factors were studied using Cox regression.47 sarcoidosis patients who started infliximab therapy were included in the risk analysis. Kaplan–Meier analysis revealed a median time to relapse of 11.1 months and showed that 25% of the cohort relapsed within 4 months. Both mediastinal SUV_max≥6.0 on FDG PET (hazard ratio 3.77, p<0.001) and serum sIL-2R ≥4000 pg·mL⁻¹(hazard ratio 2.24, p=0.033) at start of therapy predicted relapse. In multivariate analysis, a mediastinal SUV_max≥6.0 at initiation of therapy was an independent predictor of relapse (hazard ratio 4.33, p<0.001).The majority of patients that discontinued infliximab therapy relapsed. High serum sIL-2R and high SUV_maxon FDG PET at initiation of therapy were significant predictors of relapse. These results suggest close monitoring of patients in this category when they discontinue infliximab treatment.

Phenotypic Characterization of Human Intermediate Monocytes

Background: Three subpopulations of monocytes can be distinguished in human blood: classical (CD14⁺⁺CD16⁻), intermediate (CD14⁺⁺CD16⁺), and nonclassical (CD14⁺CD16⁺⁺). CD16 expressing monocytes are expanded in patients with sarcoidosis and in various other inflammatory diseases. In sarcoidosis, it is unclear whether either intermediate, nonclassical or both CD16 expressing monocytes are responsible for this increase. Data relating to the monocyte subpopulations is receiving increasing attention, but the expression of TNF receptors on these subpopulations has not been studied thus far. The aim of this study was to determine frequencies of monocyte subpopulations and their expression of TNFR1 and TNFR2 in both sarcoidosis patients and healthy controls.Methods: Peripheral blood cells of sarcoidosis patients and healthy controls were stained for the markers HLA-DR, CD14, CD16, CD120a and CD120b. Cells were measured on a FACSCalibur and analyzed with FlowJo. We used Student’st-test and a parametric One-way ANOVA for statistical analysis.Results: Sarcoidosis patients had a significant higher frequency of intermediate monocytes than healthy controls. Significant differences in TNF receptor expression were found between the monocyte subpopulations, both in sarcoidosis patients as well as in healthy controls: intermediates expressed more TNFR1 than classicals and nonclassicals and nonclassicals expressed more TNFR2 than intermediates, whereas intermediates showed higher expression than classicals.Conclusions: In both sarcoidosis patients and healthy controls intermediate monocytes show the highest expression level of TNFR1 among monocyte subpopulations and nonclassical monocytes show the highest expression level of TNFR2. These findings, as wells as the higher frequency of intermediate monocytes in sarcoidosis patients, provide evidence for the existence of two functionally-distinct CD16 expressing monocyte subpopulations.

Purpose of review: The treatment of sarcoidosis remains uncertain, despite 70 years of study. The conventional approach is to initiate corticosteroids in individuals who require treatment. The position of more aggressive regimes is unknown. Recent findings: Recent recognition that many patients will require prolonged therapy, and the observation that corticosteroids lead to overt and insidious toxicities, have led to suggestions that steroid-sparing medications be used earlier in the management of sarcoidosis. Individuals with poor prognostic features, designated as ‘high-risk’ sarcoidosis may, especially benefit from a broader palette of therapeutic options in the initial treatment regimen. An even more aggressive approach, known as ‘top-down’ or ‘hit-hard and early’ therapy has emerged in the fields of gastroenterology and rheumatology in the past 15 years, on the premise that highly effective early control of inflammation leads to better outcomes. These regimens typically involve early initiation of biologic therapies. Summary: For certain subpopulations of sarcoidosis patients, ‘top-down’ therapy could be helpful. Severe pulmonary sarcoidosis, neurosarcoidosis, cardiac sarcoidosis and multiorgan sarcoidosis are phenotypes that may be most relevant for revised therapeutic algorithms. Precision medicine approaches and randomized trials will be necessary to confirm a role for top-down therapy in the routine management of sarcoidosis.