Extrapulmonary tuberculosis

ABSTRACT

Introduction: Tuberculosis (TB) is a major cause of morbidity and mortality globally. Extrapulmonary TB (EPTB) constitutes about 15%–20% of all TB patients, but accounts for 50% among HIV-coinfected. Confirmation of microbial diagnosis of EPTB is usually challenging.

Areas covered: Availability of newer imaging modalities like ¹⁸FDG-PET-CT and PET-MRI has facilitated precise anatomical localization of the lesions and mapping the extent of EPTB. The use of image- and endoscopy-guided invasive diagnostic methods has made procurement of tissue/body fluids for diagnostic testing possible. With the advent of universal drug-susceptibility testing, a rapid diagnosis of drug-resistance is now possible in EPTB. Drug-susceptible EPTB usually responds well to first-line anti-TB treatment; TB meningitis, bone and joint TB and lymph node TB requires longer durations of treatment.

Expert opinion: Adjunctive use of corticosteroids in the initial period is recommended in the central nervous system and pericardial TB. Surgical intervention is helpful to obtain tissue samples for diagnosis. Adjunctive surgical treatment along with medical treatment is useful in treating complications like hydrocephalus, Pott’s spine. Follow-up of EPTB patients is crucial as treatment period is usually prolonged, requires recognition of development of immune reconstitution and inflammatory syndrome (IRIS), monitoring of adverse events, serious adverse events like anti-TB drug-induced hepatotoxicity, organ-related complications, and treatment adherence.

KEYWORDS:

• Tuberculosis
• extrapulmonary
• diagnosis
• CBNAAT
• treatment
• disseminated
• miliary
• PET-CT

Article highlights

• Extrapulmonary tuberculosis (EPTB) poses a diagnostic challenge because of its paucibacillary nature and location, which is often obscure. The diagnosis is often missed or made at an advanced stage of the disease when complications have already set in.

• With recent technological advances, the diagnostic yield from various tissue specimens has immensely increased and the diagnosis is being made at an early stage. Currently, several rapid diagnostic tests such as molecular tests CBNAAT ([GeneXpert -cartridge-based or chip-based TrueNat)], line probe assays (LPAs) for the first-line and second-line anti-TB drugs, and liquid culture system [(Bactec 960)] for M. tuberculosis (Mtb) along with drug susceptibility testing (DST) for the first-line and second-line anti-TB drugs are available. Diagnostic yield from cold abscess, various fluids such as cerebrospinal fluid (CSF), pleural, ascitic, pericardial fluids, and endometrial aspirates has tremendously increased in recent years.

• Widespread dissemination of Indian guidelines on extrapulmonary tuberculosis (INDEX TB) has immensely contributed to increased awareness, early diagnosis, and management of the disease. EPTB care is primarily a domain of tertiary care centers and medical schools equipped with adequate laboratory and imaging facilities. In this context, the Central TB Division of the Ministry of Health and Family Welfare, Govt. of India has provided a state-of -the-art network of centers for diagnosis and treatment of both pulmonary and extrapulmonary TB.

• It is important to determine the extent of EPTB by both careful clinical examination and imaging, which includes ultrasonography, computed tomography (CT) with contrast (intravenous and oral), CT-enterography, plain or contrast-enhanced magnetic resonance imaging (CE MRI) and positron emission tomography - CT (PET-CT) or PET-MRI.

• EPTB diagnosis must be reviewed and alternative diagnosis such as Nocardia, nontuberculous mycobacterial (NTM) disease, fungal diseases and malignancy must be kept in mind and ruled out during follow-up if the disease progresses or treatment response is not satisfactory. NTM and Nocardia must be considered if smear for acid-fast bacilli is positive and Xpert MTB/RIF is negative.

• All efforts must be directed to establish early microbial diagnosis along with phenotypic and genotypic DST. Rapid molecular tests can facilitate early diagnosis of both drug sensitive and drug-resistant TB (DR-TB) in EPTB. However, in EPTB, it is difficult to access adequate tissue specimens and do biopsies because of proximity to vascular structures.

• Follow-up of EPTB patients is crucial as treatment is usually longer and requires monitoring of treatment adherence, adverse events, and serious adverse events, development of immune reconstitution and inflammatory syndrome (IRIS) usually during the initial 3 mo of treatment initiation, and complications. End points to monitor treatment response are not easy as one cannot access tissue and clinical evaluation along with organ imaging is of immense value in monitoring treatment response during follow-up.

Declaration of interest

The author(s) have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or material discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Acknowledgments

The authors would like to acknowledge Dr Y.S. Raju, Professor, Department of General Medicine,  Nizam's Institute of Medical Sciences, Hyderabad, Telangana, India, who  provided accuracy data of Xpert MTB/RIF in various EPTB specimens documented in his unit, at his institute that were used for analysis.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Authors’ contribution

SKS: The conception and design of the manuscript, key messages to be conveyed in the manuscript, revising it critically for important intellectual content, final approval of the version to be submitted.

AM: Design and drafting of the manuscript, revising it critically for important intellectual content, final approval of the version to be submitted.

MK: Drafting the manuscript, statistical analysis, revising it critically for important intellectual content, final approval of the version to be submitted.

Supplementary material

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Additional information

Funding

This paper was not funded.