Risk Factors for Development of Paradoxical Response During Antituberculosis Therapy in HIV-Negative Patients

The risk factors for development of paradoxical response were studied in a cohort of 104 patients with culture-documented Mycobacterium tuberculosis infection. Paradoxical deterioration occurred in 16 (15.4%) patients (case group) during antituberculosis therapy, involving lungs and pleura (n=4), spine and paraspinal tissue (n=5), intracranium (n=3), peritoneum (n=2), bone and joint (n=1), and lymph node (n=1). The median time from commencement of treatment to paradoxical deterioration was 56 days (range, 20–109 days). Compared with 53 patients without clinical deterioration after antituberculosis therapy (control group), patients with paradoxical response were more likely to have extrapulmonary involvement (62.5% vs. 17.0%; P<0.05) at initial diagnosis, to have lower baseline lymphocyte counts (672±315 cells/μl vs. 1,328±467 cells/μl; P<0.001), and to exhibit a greater surge in lymphocyte counts (627±465 cells/μl vs. 225±216 cells/μl; P<0.05) during paradoxical response. Further studies on lymphocyte subsets and cytokine levels would be useful in understanding the exact immunological mechanisms involved in immunorestitution.