Paradoxical upgrading reaction in extra-pulmonary tuberculosis: association with vitamin D therapy

• Published in: The international journal of tuberculosis and lung disease Vol. 21; no. 6; pp. 677 - 683
• Main Authors: Barr, D. A., Coussens, A. K., Irvine, S., Ritchie, N. D., Herbert, K., Choo-Kang, B., Raeside, D., Bell, D. J., Seaton, R. A.
• Format: Journal Article
• Language: English
• Published: France International Union Against Tuberculosis and Lung Disease 01.06.2017; International Union against Tuberculosis and Lung Disease (IUATLD)
• Subjects: Adult; Age Factors; Antigens; Antitubercular Agents - therapeutic use; Bacilli; Cell number; Cohort Studies; Female; HIV; Host-Directed Therapy; Host-Pathogen Interaction; Host-Pathogen Interactions; Human immunodeficiency virus; Humans; Immune system; Inflammation; Innate Immunity; Logistic Models; Male; Middle Aged; Multivariate Analysis; Original; Patients; Retrospective Studies; Risk analysis; Risk Factors; Scotland; Signaling; Treatment Outcome; Tuberculosis; Tuberculosis - drug therapy; Tuberculosis - microbiology; Tuberculosis, Lymph Node - drug therapy; Tuberculosis, Lymph Node - microbiology; Viruses; Vitamin D; Vitamin D - administration & dosage
• ISSN: 1027-3719; 1815-7920
• DOI: 10.5588/ijtld.16.0927

SETTING: Glasgow, Scotland, UK.BACKGROUND: Paradoxical reactions in tuberculosis (TB) are a notable example of our incomplete understanding of host-pathogen interactions during anti-tuberculosis treatment.OBJECTIVES: To determine risk factors for a TB paradoxical reaction, and specifically to assess for an independent association with vitamin D use.DESIGN: Consecutive human immunodeficiency virus (HIV) negative adult patients treated for extra-pulmonary TB were identified from an Extended Surveillance of Mycobacterial Infections database. In our setting, vitamin D was variably prescribed for newly diagnosed TB patients. A previously published definition of paradoxical TB reaction was retrospectively applied to, and data on all previously described risk factors were extracted from, centralised electronic patient records. The association with vitamin D use was assessed using multivariate logistic regression.RESULTS: Of the 249 patients included, most had TB adenopathy; 222/249 had microbiologically and/or histologically confirmed TB. Vitamin D was prescribed for 57/249 (23%) patients; 37/249 (15%) were classified as having paradoxical reactions. Younger age, acid-fast bacilli-positive invasive samples, multiple disease sites, lower lymphocyte count and vitamin D use were found to be independent risk factors.CONCLUSION: We speculate that vitamin D-mediated signalling of pro-inflammatory innate immune cells, along with high antigenic load, may mediate paradoxical reactions in anti-tuberculosis treatment.