Objectives We aimed to conduct a systematic review and meta-analysis on the incidence and prevalence of SSc covering the entire literature. Methods This study followed the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement of 2009. We conducted a systematic search in MEDLINE, Web Of Science, and EMBASE to identify articles reporting incidence and/or prevalence of SSc. Two authors conducted the search, reviewed articles for inclusion and extracted relevant data. We used random-effects models to estimate the pooled prevalence and incidence of SSc and performed subgroup analyses by sex, case definition, and region to investigate heterogeneity. We explored the association between calendar period and reported estimates using meta-regression. Results Among 6983 unique records identified, we included 61 studies of prevalence and 39 studies of incidence in the systematic review. The overall pooled prevalence of SSc was 17.6 (95% CI 15.1-20.5) per 100000 and the overall pooled incidence rate of SSc was 1.4 (95% CI 1.1-1.9) per 100000 person-years. We observed significant regional variations in reported estimates; studies conducted in North America reported considerably higher estimates than other regions. The pooled incidence and prevalence in women were 5 times higher than in men. More recent studies reported higher estimates than older ones. Conclusion In this comprehensive review of the incidence and prevalence of SSc across the world, there was large heterogeneity among estimates, which should be taken into consideration when interpreting the results.

We aimed to investigate sarcoidosis mortality in a large, population-based cohort, taking into account disease heterogeneity.Individuals with incident sarcoidosis (n=8207) were identified from the Swedish National Patient Register using International Classification of Disease codes (2003‒2013). In a subset, cases receiving treatment ±3 months from diagnosis were identified from the Prescribed Drug Register. Nonsarcoidosis comparators from the general population were matched to cases 10:1 on birth year, sex and county. Individuals were followed for all-cause death in the Cause of Death Register. Adjusted mortality rates, rate differences and hazard ratios (HRs) were estimated, stratifying by age, sex and treatment status.The mortality rate was 11.0 per 1000 person-years in sarcoidosis versus 6.7 in comparators (rate difference 2.7 per 1000 person-years). The HR for death was 1.61 (95% CI 1.47‒1.76), with no large variation by age or sex. For cases not receiving treatment within the first 3 months, the HR was 1.13 (95% CI 0.94‒1.35). The HR was 2.34 (95% CI 1.99‒2.75) for those receiving treatment.Individuals with sarcoidosis are at a higher risk of death compared to the general population. For the majority, the increased risk is small. However, patients whose disease leads to treatment around diagnosis have a two-fold increased risk of death. Future interventions should focus on this vulnerable group.

Sarcoidosis is believed to be caused by both genetic and environmental risk factors, but the proportion of the susceptibility to sarcoidosis that is mediated by genetics remains unknown. We aimed to estimate the familial aggregation and heritability of sarcoidosis using a case-control-family study design and population-based Swedish registers.We identified 23 880 individuals with visits for sarcoidosis in the Swedish National Patient Register using International Classification of Diseases codes (1964‒2013). Information on Löfgren's syndrome was available for a subset diagnosed at Karolinska University Hospital (Stockholm, Sweden). General population controls were matched to cases (10:1). Relatives of cases and controls were identified from the Swedish Multi-Generation Register and ascertained for sarcoidosis in the National Patient Register. We estimated familial relative risks for sarcoidosis using conditional logistic regression and heritability using biometric models.Having at least one first-degree relative with sarcoidosis was associated with a 3.7-fold increase in the risk of sarcoidosis (95% CI 3.4-4.1). The relative risk increased in those with two or more relatives (relative risk 4.7) and in Löfgren's syndrome (relative risk 4.1). The heritability was 39% (95% CI 12-65%).This large investigation showed that having a relative with sarcoidosis is a very strong risk factor for the disease. Genetic variation is an important, albeit partial, contributing factor to the risk for sarcoidosis.

Sarcoidosis is characterized by noncaseating granulomas which form in almost any part of the body, primarily in the lungs and/or thoracic lymph nodes. Environmental exposures in genetically susceptible individuals are believed to cause sarcoidosis. There is variation in incidence and prevalence by region and race. Males and females are almost equally affected, although disease peaks at a later age in females than in males. The heterogeneity of presentation and disease course can make diagnosis and treatment challenging. Diagnosis is suggestive in a patient if one or more of the following is present: radiologic signs of sarcoidosis, evidence of systemic involvement, histologically confirmed noncaseating granulomas, sarcoidosis signs in bronchoalveolar lavage fluid (BALF), and low probability or exclusion of other causes of granulomatous inflammation. No sensitive or specific biomarkers for diagnosis and prognosis exist, but there are several that can be used to support clinical decisions, such as serum angiotensin‐converting enzyme levels, human leukocyte antigen types, and CD4 Vα2.3+ T cells in BALF. Corticosteroids remain the mainstay of treatment for symptomatic patients with severely affected or declining organ function. Sarcoidosis is associated with a range of adverse long‐term outcomes and complications, and with great variation in prognosis between populations. New data and technologies have moved sarcoidosis research forward, increasing our understanding of the disease. However, there is still much left to be discovered. The pervading challenge is how to account for patient variability. Future studies should focus on how to optimize current tools and develop new approaches so that treatment and follow‐up can be targeted to individuals with more precision.