Extra-pulmonary tuberculosis: towards an integrated diagnostic and management pathway: a narrative review

Extrapulmonary tuberculosis (EPTB) accounts for a substantial and increasing share of global tuberculosis (TB) notifications, yet remains disproportionately difficult to diagnose because of its paucibacillary nature, heterogeneous organ involvement, and the fragmented way in which clinical, radiological, histopathological, and microbiological data are typically interpreted. To synthesize current evidence on EPTB diagnosis and management within a single pathway-based framework, with attention to organ specific diagnostic yield, special populations, and unresolved controversies. This narrative review synthesizes evidence from World Health Organization (WHO) consolidated guidelines, Cochrane systematic reviews, landmark randomized trials and recent diagnostic accuracy studies to provide an updated overview of the diagnosis and management of EPTB. Evidence suggests that no single test reliably excludes EPTB, diagnostic yield varies markedly by disease site and specimen type, with Xpert MTB/RIF Ultra outperforming Xpert MTB/RIF and smear microscopy across most extrapulmonary specimens but still leaving important gaps, particularly in cerebrospinal and pleural fluid. Children and people living with HIV are disproportionately affected and pose distinct diagnostic challenges. Management increasingly requires site-specific tailoring, especially for drug-resistant disease, where current WHO shorter regimens explicitly exclude central nervous system, osteoarticular, and disseminated forms. An integrated, multidisciplinary diagnostic pathway rather than test by test or organ by organ, evaluation offers the most practical framework for reducing diagnostic delay in EPTB.