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

Yoshimasa Hachisu; Yasuhiko Koga; Shu Kasama; Kyoichi Kaira; Masakiyo Yatomi; Haruka Aoki-Saito; Hiroaki Tsurumaki; Yosuke Kamide; Noriaki Sunaga; Toshitaka Maeno; Tamotsu Ishizuka; Takeshi Hisada

doi:10.3390/jcm9010096

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

J Clin Med. 2019 Dec 30;9(1):96. doi: 10.3390/jcm9010096.

Authors

Affiliations

¹ Department of Allergy and Respiratory Medicine, Gunma University Graduate School of Medicine, Gunma 371-8511, Japan.
² Maebashi Red Cross Hospital, Gunma 371-0813, Japan.
³ Institute for Clinical and Translational Science, Nara Medical University Hospital, Nara 634-8522, Japan.
⁴ Department of Respiratory Medicine, Comprehensive Cancer Center, International Medical Center, Saitama Medical University, Saitama 350-1298, Japan.
⁵ Clinical Research Center for Allergy and Rheumatology. Sagamihara National Hospital, Kanagawa 252-0392, Japan.
⁶ Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan.
⁷ Gunma University Graduate School of Health Sciences, Gunma 371-8514, Japan.

Abstract

Immune reconstitution inflammatory syndrome (IRIS) is an immune reaction that occurs along with the recovery of the patient's immunity. Tuberculosis-related IRIS (TB-IRIS) upon tumor necrosis factor (TNF)-α inhibitor treatment has been reported in non-human immunodeficiency virus (HIV) patients. However, the importance of biological treatment, as a risk factor of IRIS, has not yet been established. In this study, we examined TB-IRIS in non-HIV patients to explore the role of TNF-α inhibitor treatment. Out of 188 patients with pulmonary TB, seven patients had IRIS. We examined univariate logistic and multivariate analysis to elucidate risk factors of TB-IRIS. Univariate analysis indicated that usage of immunosuppressive drugs, TNF-α inhibitors, and history of food or drug allergy were significantly related with TB-IRIS. On initial treatment, the values of serological markers such as serum albumin and serum calcium were significantly related with TB-IRIS. There was a higher mortality rate in patients with TB-IRIS. Furthermore, multivariate analysis revealed that usage of TNF-α inhibitors, history of allergy, and serum hypercalcemia were related to TB-IRIS. Usage of TNF-α inhibitors, history of allergy, and serum hypercalcemia may be independent predictors of TB-IRIS in non-HIV patients. Since higher mortality has been reported for TB-IRIS, we should pay attention to TB patients with these risk factors.

Keywords: IRIS; TNF-α inhibitor; TNFI; Th1; Th2; history of allergy; hypercalcemia; immune reconstitution inflammatory syndrome; paradoxical response; tuberculosis.