Abstract
Acquired Anti-interferon (IFN)-γ Autoantibody Syndrome (AAS) is an emerging immunodeficiency predisposing to disseminated nontuberculous mycobacterial infections. We report a 51-year-old woman with AAS presenting with Sweet's syndrome, disseminated Mycobacterium abscessus subsp. bolletii infection, and central nervous system (CNS) involvement manifested as leptomeningeal enhancement despite sterile cerebrospinal fluid. Diagnosis was confirmed by serum anti-IFN-γ autoantibody titer >1:10,000 and lymph node culture. The patient achieved sustained remission through a staged approach: 26 months of tailored antibiotics (imipenem/ceftazidime/amikacin/clarithromycin-based regimen) followed by delayed cyclophosphamide immunotherapy. This case highlights the importance of anti-IFN-γ autoantibody screening in disseminated infections and demonstrates that CNS involvement may occur without typical cerebrospinal fluid abnormalities. Our management strategy-prioritizing infection control before immunosuppression-provides a pragmatic framework for resource-limited settings.