Latent tuberculosis infection (LTBI) is a status of persistent immune response to Mycobacterium tuberculosis infection that does not manifest clinically as active tuberculosis (TB). More than a quarter of the world's population is estimated to have LTBI, with a 5–10% chance of reactivation over their lifetime (Sterling et al., 2020). Diagnosis of LTBI is made by proving prior TB infection and ruling out active TB disease (Lewinsohn et al., 2017; WHO, 2022). The tuberculin skin test (TST) or interferon-gamma release assay (IGRA) is available to demonstrate prior exposure to TB, and recent guidelines favor IGRA over TST (Lewinsohn et al., 2017).

Given that some immunotherapies cause lymphopenia that may increase the risk of LTBI-reactivation, patients with multiple sclerosis (pwMS) require LTBI screening before starting certain disease-modifying therapies (DMTs) (Epstein et al., 2018). Decisions about whether or not to treat LTBI are based on the risk of adverse effects from anti-TB medication weighed against the risk of developing active TB (Denholm and McBryde, 2010). However, there is limited data on the true risk of TB reactivation for most immunotherapies; hence, current recommendations or guidelines were based on published case series, cases reported during clinical trials, or post-marketing surveillance that provide insufficient evidence (Dantas et al., 2021; Epstein et al., 2018; Navas et al., 2018). Moreover, these guidelines mainly focus on the theoretical risk of severe morbidity rather than the absolute reactivation chance of LTBI. Another issue with anti-TB drugs is hepatotoxic risk (Jeong et al., 2015). As most of immunotherapies may cause hepatotoxicity, it is difficult to identify the causal drug in cases of abnormal liver function. Therefore, it is advised to begin or resume immunotherapies after several weeks of anti-TB treatments for patients with MS or rheumatologic diseases who are at risk of LTBI (Cantini et al., 2015; Navas et al., 2018). However, given that delaying immunotherapies even for a few weeks can lead to devastating consequences for patients with neuromyelitis optica spectrum disorder (pwNMOSD) or pwMS with high disease activity, this is a difficult decision in actual clinical practice. In fact, the majority of our pwMS and pwNMOSD with LTBI are more concerned about their neuroinflammatory disease than LTBI, resulting in the denial of anti-TB treatment.

It is crucial to balance the risks and benefits of anti-TB drugs when caring for pwMS or pwNMOSD with LTBI. Although the clinical implications of LTBI have been reviewed in pwMS (Fragoso et al., 2014; Navas et al., 2018), there is a paucity of real-world data regarding the risk of LTBI-reactivation. This study investigates the LTBI prevalence and long-term outcome for untreated LTBI among pwMS and pwNMOSD in South Korea, where the TB burden is disproportionately high, even with the country's high socioeconomic status (Hmwe Hmwe Kyu et al., 2018).