Abstract Background Leprosy can mimic systemic lupus erythematosus (SLE) due to overlapping clinical, laboratory, and immunological features, frequently resulting in misdiagnosis and inappropriate immunosuppressive treatment. We report a case of leprosy initially misdiagnosed as SLE and systematically review the literature on leprosy cases mimicking SLE, emphasizing clinical, laboratory, therapeutic, and outcome characteristics, evaluated in light of the 2019 ACR/EULAR classification criteria for SLE. Methods A systematic review was conducted according to PRISMA guidelines. PubMed, SciELO, and Google Scholar were searched for articles published up to August 2025. Case reports and case series describing leprosy previously diagnosed as SLE were included. The protocol was prospectively registered in PROSPERO (CRD420261283210). Results Twenty-three patients, including the index case, were analyzed. Most were female (78.2%), with a median age of 35 years (interquartile range IQR 30–47.5). Cutaneous manifestations were present in all patients, particularly malar rash (43.4%), photosensitivity (34.7%), and cutaneous nodules (30.4%). Osteoarticular involvement occurred in 78.2% and neurological manifestations in 43.4%. Antinuclear antibodies were positive in 74% of cases, frequently at low to moderate titers. Lepromatous leprosy was the most frequent form (69.5%). Prior to the correct diagnosis, 65.2% of patients fulfilled the EULAR/ACR classification criteria for SLE, 87% received corticosteroids and 69.5% antimalarials. Diagnostic delay exceeded one year in nearly half of cases. After initiation of multidrug therapy, 47% of patients showed clinical improvement, although leprosy reactions and residual symptoms remained common (35.3%). Conclusion Leprosy should be considered in the differential diagnosis of SLE, particularly in patients presenting with cutaneous and articular manifestations accompanied by peripheral neuropathy and poor response to immunosuppressive therapy. By delineating recurring clinical patterns and diagnostic pitfalls, our findings provide practical clues for earlier recognition, helping to prevent diagnostic delay, inappropriate immunosuppression, and adverse outcomes.
Melo et al. (Fri,) studied this question.