By Michael Rubin, MD
Professor of Clinical Neurology, Weill Cornell Medical College
SYNOPSIS: In this observational study from an area with a high rate of endemic tuberculosis (TB), prophylactic treatment of TB was appropriate in those treated with high doses of prednisone and evidence of prior TB infection.
SOURCE: Steyn EC, Naidoo TM, Marais S, Heckmann JM. Tuberculosis in myasthenia gravis patients on immunosuppressive therapy in a high-risk area: Implications for preventative therapy. J Neurol Sci 2021;425:117447.
Treatment of myasthenia gravis (MG) often requires long-term corticosteroid therapy, resulting in a host of systemic side effects, including weight gain, diabetes, hypertension, cataracts, glaucoma, accelerated bone demineralization, and neuropsychiatric disturbances. QuantiFERON-TB Gold or tuberculin skin testing has been recommended before initiating corticosteroid therapy, with prophylactic tuberculosis (TB) therapy indicated for those who test positive from prior exposure. Although TB prophylaxis has shown benefit in human immunodeficiency virus (HIV)-infected persons, potential side effects and the additional pill burden may give one pause before offering it in a more general manner. Accurate knowledge of the risk of developing TB in endemic areas would be useful in informing the judicious use of TB prophylaxis in immunosuppressed MG patients. To address this question, investigation of the incidence of, and risk factors for, TB in a South African cohort of MG patients receiving immunosuppressive therapy was undertaken.
Observational data collected between Jan. 1, 2010, and April 1, 2020, on MG patients followed at the MG Clinic at Groote Schuur Hospital in Cape Town, South Africa, who received immunosuppressive medication were reviewed. Patients were included if they were seen at least twice and followed for longer than six months. Data included age of MG onset, disease severity, immune therapies and duration, comorbidities (such as diabetes and HIV), and prior TB or opportunistic infections. Screening for TB was comprised of questioning for TB symptoms and chest radiograph prior to initiating immunosuppressive therapy. In the presence of a productive cough, sputum testing, microscopy, and culture also were performed. Statistical analysis included univariate analysis, the Chi-square and Fisher-exact tests, the Mann-Whitney U test/unpaired t-test, and rare events multiple logistic regression.
Among 539 MG patients seen in the clinic during the study period, 59 were excluded because of lack of inclusionary criteria, leaving 480 patients with a mean age of 43 years, of which 70% were women.
Following initiation of immunosuppressive therapy, 13 patients (3%) developed TB, 11 of which were proven by sputum analysis, and two proven by lymph-node biopsy. Among these 13 patients, five (38%) developed TB within six to 12 months of initiation of immunosuppressive therapy, and eight (62%) did so after five years. Of the five early cases, three were possibly new infections, with patients either having had a TB contact or normal chest radiographs. In two patients, a review of prior chest radiographs revealed findings suspicious for TB. Compared to those who did not develop TB, the TB group was more likely to have received higher maximum doses of prednisone (> 0.5 mg/kg/d), for longer durations (> six months), and manifested severe/refractory MG requiring two steroid-sparing agents in addition to prednisone. Overall, without receiving TB prophylaxis, more than 96% of patients did not develop TB. The incidence of TB in this cohort was similar to that of the general Cape Town population, suggesting that TB prophylaxis is not indicated in all MG patients initiating immunosuppressive therapy. In those with healed/fibrotic TB on chest radiographs, in whom higher doses (> 0.3 mg/kg/d) of prednisone are envisaged, TB prophylaxis for at least six months is justified.
COMMENTARY
As the authors noted, Cape Town has a high burden of TB, which may explain why the incidence of TB in their cohort was similar to that of the general population. Hence, the findings might not be generalizable to low TB areas. Yet, prior to initiating prednisone therapy, careful scrutiny of the chest radiograph is an excellent screen. In the United States, where MG patients generally undergo thymoma screening by chest computed tomography or magnetic resonance imaging, it is reassuring that TB likely will be identified early. Although low doses of prednisone do not mandate TB prophylaxis, its consideration is warranted when higher doses will be used in patients with evidence of prior TB on chest imaging.
