Paradoxical tuberculous reaction to anti-tnfα discontinuation: a complex case of miliary tuberculosis and macrophagic activation syndrome with hepatic manifestations

Tuberculosis reactivation during anti-TNF-alpha therapy paradoxically worsened following reconstitution of pathogen-specific immune responses after cessation of TNFα antagonist treatment and initiation of anti-bacillary therapy. We report the case of a 46-year-old woman who was prescribed a tumor necrosis factor blocker (anti-TNF) for a relapse of Behçet's disease. The patient developed pulmonary miliary tuberculosis following the reactivation of latent tuberculosis, despite a normal pre-therapeutic work-up. Discontinuation of anti-TNF and initiation of anti-bacillary drugs triggered a paradoxical tubercular reaction (PTR). The diagnosis of paradoxical reaction to anti-tuberculosis drugs was evoked by the clinical and biological deterioration and the appearance of miliary cerebral tuberculosis and cerebral venous thrombosis after a period of clinical improvement. Although this phenomenon has been documented, it represents a major challenge for clinicians. The peculiarity of this case lies in its association with a macrophagic activation syndrome (MAS) with hepatic involvement, retained on clinical-biological and histological criteria. The overlap between MAS and PTR makes it difficult to diagnose these two entities with certainty. The patient responded favorably to moderate-dose systemic corticosteroid therapy with progressive degression, and the reintroduction of anti-tuberculosis drugs.This work aims to highlight the importance of close monitoring of TB patients on anti-TNFα therapy for early diagnosis and management of complications to improve the prognosis of these complex patients.