We read with great interest the article by Dias et al.(1) on the prevalence of latent tuberculosis infection (LTBI) among patients with interstitial lung diseases (ILDs) requiring immunosuppression. We would like to share some comments on using the tuberculin skin test (TST) as the only screening strategy.
 
There is no gold standard for LTBI detection, and both TST and interferon-gamma release assays (IGRAs) are approved for use in all settings.(2) Dias et al.(1) reported positive TST reactions in only 9.1% of patients, while the estimated prevalence of LTBI for Brazil (a country with intermediate tuberculosis incidence) is 19-20%.(1,3) Possibly, the low infection rate reflects the fact that the participants did not belong to high-risk groups for tuberculosis or that tuberculin reaction may have waned over time. It remains unclear if IGRAs would be a better option. Although IGRAs yield fewer false-negative results than does TST in immunosuppressed and elderly patients, they are less sensitive in detecting remote infections.(4) It is also possible that the disease itself may have suppressed the reaction. In a country with high tuberculosis incidence, most patients with sarcoidosis showed negative TST response, but most patients and controls also tested positive on IGRAs.(5)
 
Interestingly, a large diameter of tuberculin reaction was noted in TST-positive patients, suggesting recent infection (the main risk factor for active tuberculosis). However, the authors did not include information on risk factors for tuberculosis in the study group.(1) Perhaps tuberculosis preventive treatment (TPT) was required because of a recent contact with a patient with pulmonary tuberculosis. It would be interesting to know IGRA results of TST-positive patients. None of the current diagnostic tests for LTBI have a sufficient predictive value for progression to active tuberculosis, although IGRAs might better identify candidates for TPT among BCG vaccine recipients. Thus, IGRAs might have provided additional data on the actual LTBI prevalence among ILD patients. Moreover, 63 patients were excluded because they either failed to schedule the test or did not return for the reading. This might have been avoided with IGRAs, which require only one visit.(4)
 
Another important question is whether all ILD patients with LTBI need TPT. Identifying target groups is essential. Glucocorticoids and other immunosuppressants may increase the risk of progression to active tuberculosis. However, screening for LTBI is recommended by the WHO only before anti-TNF therapy.(2) The risk-benefit ratio must be carefully considered.(4) Additional research is needed to evaluate whether patients on specific immunosuppressive drugs would benefit more from TPT than from watchful waiting.
 
Before TPT, it may be insufficient to exclude active tuberculosis solely based on clinical and radiological signs in patients with ILDs due to abnormalities such as fibrosis or nodules. Histopathologic features may mimic tuberculosis in sarcoidosis and hypersensitivity pneumonia. Thus, microbiological analysis should be performed in all candidates for TPT to avoid misdiagnosis.
 
Finally, screening for LTBI (preferably with TST) in treatment-naïve ILD patients might provide valuable information. In conclusion, further studies are needed to assess the actual prevalence of LTBI in ILD patients and to identify candidates for TPT.
 
CONFLICTS OF INTEREST
None declared.
 
AUTHOR CONTRIBUTIONS
AK: conceptualization and drafting of the manuscript. MKK: drafting, editing, and reviewing of the manuscript. Both authors approved the final version of the manuscript.
 
REFERENCES
 
1.            Dias VL, Storrer KM. Prevalence of latent tuberculosis infection among patients with interstitial lung disease requiring immunosuppression. J Bras Pneumol. 2022;48(2):e20210382. https://doi.org/10.36416/1806-3756/e20210382
2.            World Health Organization. WHO consolidated guidelines on tuberculosis: tuberculosis preventive treatment: Module 1: prevention. [monograph on the Internet]. Geneva: World Health Organization; 2020 [cited 2022 Apr 28]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK554956/
3.            Cohen A, Mathiasen VD, Schön T, Wejse C. The global prevalence of latent tuberculosis: a systematic review and meta-analysis. Eur Respir J. 2019;54(3):1900655. https://doi.org/10.1183/13993003.00655-2019