Central Nervous System Manifestations of Tuberculosis-associated Immune Reconstitution Inflammatory Syndrome during Adalimumab Therapy: A Case Report and Review of the Literature

Abstract

A 64-year-old neurologically asymptomatic woman with rheumatoid arthritis who was treated with the tumor necrosis factor (TNF)-α antagonist adalimumab developed disseminated tuberculosis (TB). After receiving anti-TB therapy and discontinuing adalimumab, she exhibited paradoxical worsening due to immune reconstitution inflammatory syndrome (IRIS) with the appearance of meningitis and brain tuberculomas. This case indicates that continuing anti-TNF therapy may be necessary to prevent IRIS in patients who develop TB, particularly disseminated TB, during the course of anti-TNF therapy. In addition, careful screening for central nervous system (CNS) TB should be performed prior to the initiation of therapy, as even neurologically asymptomatic patients can develop CNS manifestations of IRIS.

Protective effects of tumor necrosis factor alpha inhibitors on methotrexate-induced pancreatic toxicity

“…5,6,24,25 Methotrexate is used for the treatment of pancreatic cancer, but has been shown to destroy the beta cells of the pancreas, primarily through oxidative stress. 5,6,[24][25][26] A decrease in islets of Langerhans insulin and somatostatin-immunopositive cells was shown in this study following the administration of MTX (Fig. 2B, 3B).…”

“…4,5,10,11,19,27 It has been experimentally proven that TNF inhibitors prohibit organ tissue damage by suppressing the formation of TNF-α, proinflammatory cytokines, and nitric oxide. 5,26,27 A decrease in edema, acinar cell edema, and necrotic cells was observed in Group 3 (p < 0.05) ( Table 2) after the administration of ADA. An increase in islets of Langerhans insulin and somatostatin-positive cells was also demonstrated following the application of ADA treatment to Group 3 (Fig.…”

Treatment with Tumor Necrosis Factor-α Inhibitors, History of Allergy, and Hypercalcemia Are Risk Factors of Immune Reconstitution Inflammatory Syndrome in HIV-Negative Pulmonary Tuberculosis Patients

“…Risk factors of IRIS in a patient undergoing treatment with tumor necrosis factor (TNF)-α inhibitors (TNFIs) are disseminated TB, history of TB, and use of steroids at diagnosis [9,10]. In the TB patient without HIV infection it has been reported that IRIS is not related to the immunosuppressed state [11].…”

Bacteriologically Determined <i>De Novo</i> Tuberculosis during Tumor Necrosis Factor-α Inhibitor Therapy

“…In our patient, IRIS was recognized as lymphadenopathy and the appearance of a new polyp-like lesion in the trachea after discontinuing adalimumab and receiving anti-tuberculosis treatment. As with IRIS in HIV-infected pa-tients (11), corticosteroid therapy is usually required to treat IRIS that develops after discontinuing anti-TNFα therapy, although there is a lack of good supporting evidence (12). Controversy also exists concerning the continuation of anti-TNFα therapy in patients who develop tuberculosis (13,14).…”