ABSTRACT
PURPOSE: To investigate the phenotype of sarcoidosis according to the time when a malignancy is diagnosed (preexisting to the diagnosis of sarcoidosis, concomitant, or sequential) and to identify prognostic factors associated with malignancies in a large cohort of patients with sarcoidosis. METHODS: We searched for malignancies in the SARCOGEAS cohort, a multicenter nationwide database of consecutive patients diagnosed with sarcoidosis according to the ATS/ESC/WASOG criteria. Solid malignancies were classified using the International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) nomenclature, and hematological malignancies using the 2016 WHO classification. We excluded patients with a biopsy-proven diagnosis of sarcoidosis based exclusively on demonstrating granulomas in tissues also involved by malignant cells. RESULTS: Out of 1942 patients with sarcoidosis, 233 (12%) developed 250 malignancies, including solid (n = 173), hematological (n = 57), and both types of malignancies (n = 3). Concerning the time interval between the diagnoses of both conditions, 83 (36%) patients were diagnosed with malignancy at least 1 year before sarcoidosis diagnosis, 22 (9%) had s synchronous diagnosis of both diseases, and 118 (51%) developed malignancies at least 1 year after the diagnosis of sarcoidosis (the remaining cases developed malignancies in different time intervals). The multivariate-adjusted model showed that individuals with sarcoidosis who developed a malignancy had an hazard ratio (HR) of 2.27 [95% confidence interval (CI), 1.62-3.17] for having an asymptomatic clinical phenotype at diagnosis of sarcoidosis and that spleen (presence vs. absence: HR = 2.06; 95% CI, 1.21-3.51) and bone marrow (presence vs. absence: HR = 3.04; 95% CI, 1.77-5.24) involvements were independent predictors for the development of all-type malignancies. No predictive factors were identified when the analysis was restricted to the development of solid malignancies. The analysis limited to the development of hematological malignancies confirmed the presence of involvement in the spleen (HR = 3.73; 95% CI, 1.38-10.06) and bone marrow (presence vs. absence: HR = 8.00; 95% CI, 3.15-20.35) at the time of sarcoidosis diagnosis as predictive factors. CONCLUSION: It is essential to consider the synchronous or metachronous timing of the diagnosis of malignancies in people with sarcoidosis. We found that half of the malignancies were diagnosed after a diagnosis of sarcoidosis, with spleen and bone marrow involvement associated with a four to eight times higher risk of developing hematological malignancies. Key messages What is already known on this topic Malignancies are one of the comorbidities more frequently encountered in people with sarcoidosis What this study adds Malignancies occur in 12% of patients with sarcoidosis Malignancy may precede, coincide with, or follow the diagnosis of sarcoidosis One-third were identified before sarcoidosis, and half were diagnosed after Spleen and bone marrow involvement are risk factors for developing hematological malignancies How this study might affect research, practice or policy Patients with sarcoidosis should be regularly monitored for neoplasms, informed of the increased risk, and educated on early detection. Those with spleen or bone marrow involvement must be closely followed.
ABSTRACT
OBJECTIVE: To analyze whether immune-mediated diseases (IMDs) occurs in sarcoidosis more commonly than expected in the general population, and how concomitant IMDs influence the clinical presentation of the disease. METHODS: We searched for coexisting IMDs in patients included in the SARCOGEAS-cohort, a multicenter nationwide database of consecutive patients diagnosed according to the ATS/ESC/WASOG criteria. Comparisons were made considering the presence or absence of IMD clustering, and odds ratios (OR) and their 95% confidence intervals (CI) were calculated as the ratio of observed cases of every IMD in the sarcoidosis cohort to the observed cases in the general population. RESULTS: Among 1737 patients with sarcoidosis, 283 (16%) patients presented at least one associated IMD. These patients were more commonly female (OR: 1.98, 95% CI: 1.49-2.62) and were diagnosed with sarcoidosis at an older age (49.6 vs. 47.5years, P<0.05). The frequency of IMDs in patients with sarcoidosis was nearly 2-fold higher than the frequency observed in the general population (OR: 1.64, 95% CI: 1.44-1.86). Significant associations were identified in 17 individual IMDs. In comparison with the general population, the IMDs with the strongest strength of association with sarcoidosis (OR>5) were common variable immunodeficiency (CVID) (OR: 431.8), familial Mediterranean fever (OR 33.9), primary biliary cholangitis (OR: 16.57), haemolytic anemia (OR: 12.17), autoimmune hepatitis (OR: 9.01), antiphospholipid syndrome (OR: 8.70), immune thrombocytopenia (OR: 8.43), Sjögren syndrome (OR: 6.98), systemic sclerosis (OR: 5.71), ankylosing spondylitis (OR: 5.49), IgA deficiency (OR: 5.07) and psoriatic arthritis (OR: 5.06). Sex-adjusted ORs were considerably higher than crude ORs for eosinophilic digestive disease in women, and for immune thrombocytopenia, systemic sclerosis and autoimmune hepatitis in men. CONCLUSION: We found coexisting IMDs in 1 out of 6 patients with sarcoidosis. The strongest associations were found for immunodeficiencies and some systemic, rheumatic, hepatic and hematological autoimmune diseases.
