Tuberculosis associated with tumor necrosis factor-α antagonists, case description and analysis of reported cases in Colombia

Abstract

Tumor necrosis factor-α (TNF-α) is an important fundamental cytokine during the immune response against cancer and infections such as tuberculosis. This molecule also plays a key pathogenic role in complex and difficult-to-treat diseases such as rheumatoid arthritis, ankylosing spondylitis, Crohn's disease, psoriasis and ulcerative colitis. The treatment of these diseases frequently needs TNF-α antagonists, which has been related to an increased risk of developing tuberculosis, mycoses, and other severe infections.We report the case of a 68-year-old man with Crohn's disease, who developed disseminated tuberculosis due to anti-TNF-α immunosuppressive therapy. The diagnosis was based on the histopathological findings and molecular biology assays.We discuss the clinical presentation and workup of this case, and we present a comparative analysis of tuberculosis cases associated with anti-TNF-α reported in Colombia during the last 10 years emphasizing on the diagnosis and treatment of latent tuberculosis.

Tuberculosis: A Risk Factor Approach

“…People with immune-mediated inflammatory diseases, such as rheumatoid arthritis, systemic erythematous lupus, ankylosing spondylitis, inflammatory bowel disease, etc., also represent a high-risk group for developing TB, and this risk is even higher when they are treated with tumor necrosis factor α (TNF α) -antagonist [66,67].…”

“…Different cells produce TNF, including macrophages, T cells, fibroblast, and keratinocytes. TNF is a molecule with a wide functional spectrum, plays a key role in immune response to infections, cancer etiology, and the physiopathology of many immune-mediated disorders [67]. It is also known that is important in the immune response against intracellular bacteria, and the physiology and integrity of granulomatous (Figure 1) TB-related response during LTBI, therefore its antagonism associates with TB progression [6].…”

“…During the past two decades, TNF antagonists have been successfully used for the treatment of inflammatory diseases, when patients do not respond to conventional therapy [67]. In the United States, using national surveillance data, found that TB incidence in AR patients increased from 6.2 per 100,000 people to 144 per 100,000 in who received infliximab and 35 per 100,000 for etanercept-treated individuals [69].…”

“…Most of the active TB cases in individuals treated with TNF antagonist correspond to reactivation from LTBI, when this occurs, generally happen concomitantly with the initiation of the TNF antagonist, nevertheless, also cases with long treatment periods, have been reported [67]. Therefore, screening for LTBI before any TNF inhibitor treatment initiation is mandatory, here, as in the case of other immunosuppressive conditions, such as HIV infection, both TST and IGRAs assays could be used, nowadays, there is not sufficient evidence to recommend one method over another, and considering this, an expert consensus, suggest using IGRAs or TST in people without history of BCG vaccination [71].…”

“…Among the preventive therapy options, two of the most accepted are: daily isoniazid 5 mg/kg (maximum 300 mg) for 9 months plus pyridoxine supplementation or a combined regimen with isoniazid and rifampicin for 3 months [69]. Multiple recommendations on delay periods between LTBI preventive chemotherapy and TNF antagonist have been proposed, ranging from starting both concurrently, to waiting even a month after finishing LTBI prophylaxis [67,68], these decisions must always consider the patients clinical status. In the cases when active TB is diagnosed during TNF antagonist treatment, there is no evidence that the length of anti-TB therapy needs to be prolonged, and evidence regarding the time for restarting TNF antagonist therapy is limited [72]; however, some international guidelines recommends starting TNF inhibitor at least when initial anti-TB phase is completed, while others recommend waiting until completing all TB treatment [68].…”