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We report a young patient with a variant of juvenile idiopathic arthritis, who, after 4 years of infliximab treatment, developed miliary tuberculosis (TB) with central nervous system involvement (meningitis and multiple tuberculomas). After anti-TB treatment, clinical and radiologic responses were observed, but severe cerebrospinal fluid and brain inflammatory reaction, nonresponsive to corticosteroids, persisted. It was considered a life-threatening paradoxical reaction based on initial cerebrospinal fluid isolation of Mycobacterium tuberculosis fully sensitive to primary anti-TB drugs. After 4 months in the hospital, infliximab was administered considering that infliximab is a potent tumor necrosis factor α inhibiting agent that participates in the formation and preservation of granulomas and may help to modulate the exaggerated cell-mediated immune response against mycobacterial antigens. Clinical complications associated to brain inflammation resolved, and after 3 years of follow-up, the patient remains self-sufficient without neurologic sequels.