Reactivation of Latent Tuberculosis After Treatment With Biologic Therapy

Abstract

Anti-tumor necrosis factor (TNF) therapy is associated with increased infectious risk including reactivation of latent tuberculosis infection (LTBI). It is recommended that patients with risk factors for tuberculosis (TB) be evaluated for LTBI prior to initiation of anti-TNF therapy. Patients with evidence of LTBI undergo treatment before initiation of biologic therapy. The risk of disseminated TB after treatment and initiation of biologic therapy is not well characterized in patients with inflammatory bowel disease. We present a patient who developed disseminated TB as a complication of anti-TNF therapy after completing appropriate treatment for LTBI Case Report: A 52 yo Sri Lankan male with clinical and pathologic evidence of Crohn colitis is found to have asymptomatic LTBI. Treatment with isoniazid (INH) was initiated. After 6 weeks of therapy he was started on infliximab. The patient had a good initial response to therapy but required intermittent prednisone for control of his symptoms. After a viral URI, infliximab was discontinued and not restarted. He completed a 9-month course of INH and was feeling well on no anti-TB treatment. The patients Crohn disease flared and he was initiated on adalimumab after a colonoscopy confirmed active disease. Three months after adalimumab initiation and 4 months after completion of INH for LTBI he had a febrile illness, diarrhea and weight loss. A CT abdomen/pelvis was obtained and showed multiple lesions throughout the spleen and liver. The adalimumab was stopped and he was admitted to hospital for further work-up. After an extensive work-up including evaluation for fungal etiologies and a spleen biopsy he was initiated on empiric anti-TB treatment. After several weeks the AFB smear from both sputum and spleen were positive for pan-susceptible TB. While undergoing treatment for active TB he has been maintained on mesalamine based therapy with marginal control of his Crohn disease. Discussion: Prior to initiation of anti-TNF treatment patients with IBD should be evaluated for active and latent TB1. The risk of disseminated TB after treatment for LTBI and initiation of biologic therapy is unknown. If evidence of LTBI is found, treatment is recommended prior to starting biologic therapy2,3. Recommendations from the ATS and BTS vary from 1-9 months of treatment prior to starting anti-TNF therapy, even though chemoprophylaxis is only effective 70% of the time after 9 months. 4,5 We present the case of a patient with Crohn disease, found to have LTBI and initiated on therapy. After completion of LTBI treatment anti-TNF therapy was instituted. He became ill and was admitted to hospital where he was found to have disseminated TB. Though this patients TB presented after completion of therapy for LTBI most cases of disseminated TB are discovered early in the treatment course of anti-TNF therapy. Close monitoring for reactivation is warranted even if patients have undergone treatment, since treatment is not always effective. We present a case report of a patient with Crohn disease and treated LTBI who developed disseminated disease after completion of treatment and initiation of a biologic agent.