Risk of Hospitalized Infection Among Patients With Sarcoidosis: A Population-Based Retrospective Cohort Study

Background/Purpose: Increased risk of infection has been observed in several autoimmune disorders.  Immune dysregulation and use of immunosuppressive agents, especially glucocorticoids, are thought to be responsible for the increased risk. It is unclear whether patients with sarcoidosis, another relatively common immune-mediated chronic inflammatory disorder characterized by the presence of non-caseating granuloma, might also be at an increased risk of infection.  

Methods: 345 patients (50% female; 90% Caucasian, 5% African-American; mean age 45.6 years) with incident sarcoidosis in 1976-2013 in a geographically well-defined population were identified based on comprehensive individual medical record review. Inclusion required physician diagnosis supported by histopathology and radiologic features of intrathoracic sarcoidosis, compatible clinical presentation, and exclusion of other granulomatous diseases. 345 sex and age-matched comparators (50% female; 95% Caucasian, 1% African-American; mean age 45.4 years) were also identified from the same underlying population. Medical records of both cases and comparators were individually reviewed for first hospitalized infection for each type of infection (and not multiple infections per patient). The cumulative incidence of hospitalized infection adjusted for the competing risk of death was estimated. Cox proportional hazards models with adjustment for age, sex, calendar year, current smoking, diabetes mellitus, hypertension, dyslipidemia and obesity were used to compare the rate of development of hospitalized infection between patients with sarcoidosis and the non-sarcoidosis comparison cohort.

Results: Hospitalized infection after index date occurred in 84 cases and 47 comparators. After adjusting for age, sex and calendar year, the risk of at least one hospitalized infection after index date was significantly increased among patients with sarcoidosis with adjusted hazard ratio (HR) of 2.00 (95% CI, 1.41 – 2.84). Further adjustment for current smoking, diabetes mellitus, hypertension, dyslipidemia and obesity yielded adjusted HR of 2.09 (95% CI, 1.33 – 3.28).  Sensitivity analysis including only hospitalized infection that occurred at least 6 months after index date to reduce the likelihood of detection bias was also performed.  When only these cases were considered, the adjusted HR was essentially unchanged (HR 1.97; 95% CI, 1.38 – 2.82). Patients in this cohort were at significantly increased risk especially for some types of infections including pneumonia, gastrointestinal and soft tissue infections as shown in table 1.

Conclusion: Risk of hospitalized infection is increased among patients with sarcoidosis. How this risk should be addressed in clinical practice requires further investigations.