Invasive fungal disease in systemic lupus erythematosus: a systematic review of disease characteristics, risk factors, and prognosis.

OBJECTIVES Invasive fungal disease (IFD) is a life-threatening complication of systemic lupus erythematosus (SLE) and/or its treatment. We conducted a systematic review to characterize IFD in SLE and identify risk factors and outcomes. METHODS MEDLINE, Embase, and Web of Science were searched up to June 2013 using MeSH terms and keywords pertaining to SLE and IFD. Two independent reviewers selected adult cohort studies and case series/reports on IFD in SLE based on the established classification criteria for both diseases. RESULTS In total, 393 cases from 182 studies met the criteria for inclusion. Cryptococcus spp., Aspergillus spp., and Candida spp. were the most common fungal pathogens. Cohorts described IFD in 0.6-3.2% of SLE inpatients and 0.28% of SLE outpatients. IFD occurred at a median of 2 years of disease duration (IQR: 0.5-7.1), and 39% of cases occurred within the first year of SLE. Disease activity and corticosteroid dose >60mg/day emerged as risk factors for IFD. IFD was associated with a mortality rate of 53% (161/316 cases), and worse in the absence of antifungal therapy (n = 43). Overall, 44 cases of IFD were only diagnosed on autopsy. CONCLUSIONS Our systematic review confirms the severe sequelae of IFD in SLE. Cases occurred in patients with active SLE, who were on high daily corticosteroids doses and at early stages of disease. This highlights the role of poor disease control and a high "net state of immunosuppression" in risk. IFD in SLE should be prospectively examined in the modern era.