Neurosarcoidosis-like reaction under TNF-α inhibitors: a case report and literature review of a paradoxical immune phenomenon

BACKGROUND: Neurosarcoidosis (NS) is a rare manifestation of sarcoidosis that oftenrequires long-term immunosuppressive treatment (IST), including tumor necrosis factor-α (TNF-α) inhibitors in refractory cases. Paradoxically, TNF-α blockade has also been associated withsarcoidosis-like reactions (SLRs), granulomatous inflammatory conditions that mimic idiopathicsarcoidosis. Case presentation: We report a case of NS occurring in the context of a TNF-αinhibitor–associated SLR and review previously reported cases during TNF-α inhibitor therapy. DISCUSSION: A 25- year-old man with HLA-B27–negative ankylosing spondylitis developed anacute central nervous system (CNS) inflammatory syndrome during prolonged adalimumabtherapy. The diagnosis was supported by inflammatory cerebrospinal fluid (CSF) findings,including an elevated CD4+/CD8+ ratio, histologically confirmed pulmonary SLR, and sustainedradiological and neurological remission after adalimumab withdrawal. A review of the literatureidentified only seven reported cases of NS during anti-TNF-α therapy across heterogeneousimmune-mediated inflammatory diseases. Clinical and neuroimaging features were variable,whereas CSF analysis consistently showed inflammatory changes. Exposure duration prior toneurological onset and follow-up strategies were inconsistently reported, and acute IST wasfrequently required because of CNS involvement. CONCLUSIONS: This case expands the clinicalspectrum of anti-TNF-α– associated SLRs and underscores the importance of considering aniatrogenic etiology in paradoxical neuroinflammatory presentations. Recognition of a“neurosarcoidosis-like reaction” may inform long-term therapeutic decisions, including carefulconsideration of TNF-α inhibitor re-exposure and selection of alternative ISTs for the underlyingdisease.