Primary extrapulmonary tuberculosis diagnosis warrants extra-precautious pulmonary tuberculosis exclusion workup

Abstract

This editorial article takes an opportunity to apprehend the diagnostic challenges of primary gastrointestinal tuberculosis (an uncommon extrapulmonary tuberculosis condition) utilizing the recently published case report of a young male with prolonged gastrointestinal symptoms and weight loss who received intermittent anti-tubercular treatment and underwent operative interventions to relieve gastric outlet obstruction. The diagnosis chiefly relied on high-end examinations, like computed tomography scans and histopathological evaluation of post-operatively resected bowel tissue, which wasn't preceded by an all-inclusive stepwise primary pulmonary tuberculosis exclusion approach that usually begins with a detailed tuberculosis-pertinent history acquisition. Given the geographic locations where the patient had been (and/or treated), pivotal consideration of tuberculosis-associated endemicities in those regions, like human immunodeficiency virus (HIV) infection, might have improved the case description. The obtainment of HIV-relevant histories, like intravenous drug use and sexual practice, are good places to start. The sputum bacteriology also seems imperative to rule out atypical Mycobacterium species infection because of its clinico-radio-histopathological resemblance with pulmonary Mycobacterium tuberculosis. Altogether, this editorial aims to underscore that primary extrapulmonary tuberculosis diagnosis should comprise an elaborative, comprehensive, systematic, and stepwise primary pulmonary Mycobacterium tuberculosis exclusion workup.

Key Words: Extrapulmonary tuberculosis; Tuberculosis; Gastrointestinal; Diagnosis; Human immunodeficiency virus

Core Tip: The diagnosis of primary gastrointestinal tuberculosis due to Mycobacterium tuberculosis infection requires an overarchingly holistic stepwise case evaluation approach to exclude primary pulmonary tuberculosis rather than exclusively depending on high-end radiation-intensive expensive methods. Moreover, tuberculosis-relevant history-obtainment may not be limited to the disease-specific constitutional symptoms and signs. Instead, it may consider relevant factors like countries where the patient had been, tuberculosis contacts, nutrition, smoking and drinking habits, and weight loss. Additional primary pulmonary tuberculosis workup considerations can include important caveats in its diagnostic interpretations, like latent tuberculosis, atypical tuberculosis, and immunocompromised status.

INTRODUCTION

This letter is in response to the case report published by Ali et al[1] reporting a case of a young male with yearlong gastrointestinal symptoms, weight loss, and a history of incomplete antitubercular treatment undergoing operative interventions to relieve gastric outlet obstruction. Post-operatively, the patient was diagnosed with primary gastrointestinal tuberculosis based on histopathological examination of resected bowel segments. While I admire the authors for enlightening us with the findings of this relatively uncommon disease condition (gastrointestinal tuberculosis representing 1%-3% of all tuberculosis cases globally)[2,3]. I would prefer to consider this primary extra-pulmonary (gastrointestinal) tuberculosis diagnosis presumptive as the exclusion of primary pulmonary tuberculosis diagnosis appears inadequately supported with a conceivable rationalized (evaluation) approach. These ambiguities in the workup of this case are discussed below to draw the attention of future researchers reporting identical cases.

First, the diagnosis of gastrointestinal tuberculosis presented in the report builds on the characteristic tuberculosis suggestive histopathologic findings like caseous changes. The stated limitations that acid-fast bacteria staining and Gene Xpert were not possible due to lack of peritoneal ascites may be identified as a major weakness because histopathologic findings like caseous granulomas are suggestive but not pathognomonic of tuberculosis. The sensitivity of histopathology in different extrapulmonary tissues can be between 69%-100%[4]. Therefore, the bacteriological proof is critical for a definitive diagnosis of extrapulmonary Mycobacterium tuberculosis.

Next, for the sake of this discussion, even if I consider that the case was a microbiologically confirmed extrapulmonary Mycobacterium tuberculosis, the debate remains on whether the case was primary or secondary extrapulmonary tuberculosis as the case handling doesn’t seem to have conformed with the ideal primary pulmonary tuberculosis diagnosis exclusion approaches exhaustively. For instance, the high-end radiation-intensive imaging-based primary pulmonary tuberculosis exclusion appears non-concordant with the usual way of pulmonary tuberculosis diagnosis protocols followed universally. Given the chronic nature of the presented case and tuberculosis as a possible underlying etiology for which the patient received intermittent antitubercular treatment (discontinued due to gastrointestinal symptoms), a thoracic computed tomography (CT) scan should ideally be preceded by a detailed tuberculosis-pertinent history obtainment, a chest x-ray, and/or sputum test (e.g., acid-fast bacilli (AFB) smear, AFB culture, or molecular nucleic acid amplification test). A detailed history of poverty, country of birth, countries traveled, history of tuberculosis contacts, smoking and drinking habits, weight loss pattern (e.g., when, how much), and nutrition history are key when tuberculosis is suspected. Chest x-ray and sputum AFB are much more simplistic, economical, and safer than CT thorax. When these simplistic tests fail to diagnose pulmonary tuberculosis in the milieu of clinical tuberculosis suspicion, the role of a CT thorax seems realistic. Furthermore, when a CT scan is under consideration, from the point of patient safety, the tradeoff of using low-dose CT over traditional CT should be judged, as the former has shown to have satisfactory sensitivity (100%) and positive predictive value (86%) in pulmonary tuberculosis diagnosis[5].

Additionally, concern remains if the case was due to an atypical Mycobacterium species (i.e., non- Mycobacterium tuberculosis, e.g., Mycobacterium intracellulare) as these can mimic Mycobacterium tuberculosis clinically, radiologically, and histopathologically. Without sputum bacteriology, one can’t definitively rule out different tuberculosis causing bacterial species.

Besides atypical tuberculosis, another vital consideration in this case could have been latent tuberculosis, where common pulmonary tuberculosis symptoms like cough, hemoptysis, fever, chest pain, and night sweats are absent[6]. Notably, the case report discussed here didn’t have the majority of such symptoms and signs except weight loss. Perhaps, before tagging primary extrapulmonary tuberculosis, latent tuberculosis evaluation using simple tests like tuberculin skin test could have got space in this case investigation plan as latent tuberculosis is often associated with diagnostic challenges clinically and radiologically[7].

Finally, this editorial would remain incomplete if I don’t extend the discourse on possible immunosuppression due to human immunodeficiency virus (HIV) infection and its impact on tuberculosis workup as the patient had been in regions known for HIV endemicity (e.g., Somalia and South Africa)[8]. So, the workup of this patient should ideally include a detailed HIV-pertinent history obtainment (including intravenous drug use, sexual history, and blood transfusion history) and testing for HIV status. The intricacies of tuberculosis workup in people living with HIV pose additional challenges. For instance, in HIV patients, the tuberculin skin test might be of limited value, the chest x-ray in latent tuberculosis cases might be within normal limits if CD4 cell count < 200 cells/mm³, and extrapulmonary tuberculosis in young people can be due to non-Mycobacterium tuberculosis species[7,9].

CONCLUSION

Altogether, this letter takes the opportunity to cynosure that primary extrapulmonary Mycobacterium tuberculosis diagnosis needs an extra-cautious stepwise exclusion-diagnosis approach (to exclude primary pulmonary Mycobacterium tuberculosis). Consideration of intricate intertwining factors like latent tuberculosis in HIV is needed, which might unknowingly remain embedded in between the layers of a extrapulmonary tuberculosis workup plan.