Screening for Tuberculosis in an Outpatient Population of Multiple Sclerosis.

Background: Up to 13 million people have latent tuberculosis infection (LTBI) in the USA. Patients with a compromised immune system are at risk for converting from LTBI to active tuberculosis infection. Immunomodulatory therapies for multiple sclerosis (MS) may put individuals with LTBI at higher risk of developing active tuberculosis. The QuantiFERON-TB Gold In-Tube (QFT-GIT) assay measures the release of interferon-gamma (IFNγ) to detect LTBI.

Objectives: We aimed to screen patients with MS for LTBI to stratify their risk of developing tuberculosis on immunosuppressive agents. We then used laboratory data to determine if immunosuppressive agents compromise the validity of tuberculosis screening.

Methods: Patients of the Beth Israel Deaconess Medical Center’s Multiple Sclerosis Center in Boston, MA were screened for tuberculosis as part of routine testing with the QFT-GIT assay from December 2013 to December 2017. Patients were tested either prior to initiating therapy or while on immunomodulating therapy. Data were analyzed using JMP Pro 13.0.0 (SAS, Cary, NC). Wilcoxon rank sum was used to compare non-parametric continuous data. Pearson’s χ² was used to compare categorical data; Fisher’s exact test was used when any cell contained fewer than 10 observations.

Results: 3 out of 212 (1.4%) patients were positive for LTBI; 2 of these patients had no known risk factors for tuberculosis, while the other patient had emigrated from Russia. 29 out of 212 (13.7%) patients had an indeterminate assay result. 22 of the 29 (75.9%) indeterminate results occurred in patients actively taking dimethyl fumarate. 1 patient with an indeterminate result was receiving intravenous methylprednisolone, 1 patient was taking fingolimod, and 5 patients were not on therapy. Indeterminate assay results were associated with dimethyl fumarate use, lymphocytopenia, decreased absolute lymphocyte count, decreased CD3 count, decreased CD4 count, decreased CD8 count, and increased CD4/CD8 ratio (P < 0.001).

Conclusions: In the MS clinic, LTBI may be more common than expected. Screening for LTBI prior to starting immunosuppressive agents for MS could help prevent activation of tuberculosis. Dimethyl fumarate appears to preferentially reduce both CD8 counts and CD8 function as measured by the IFNγ release via the QFT-GIT assay.