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

Barr, D.A., Coussens, A.K., Irvine, S., Ritchie, N.D., Herbert, K., Choo-Kang, B., Raeside, D., Bell, D.J. and Seaton, R.A. (2017) Paradoxical upgrading reaction in extra-pulmonary tuberculosis: association with vitamin D therapy. International Journal of Tuberculosis and Lung Disease, 21(6), pp. 677-683. (doi: 10.5588/ijtld.16.0927) (PMID:28482963)

Abstract

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.

• Item Type: Articles
• Additional Information: DAB is funded through the Wellcome Trust, London, UK (doctoral studentship grant reference 105165/Z/14/A). AKC is supported by the Medical Research Council of South Africa, Cape Town, South Africa (SHIP-02-2013).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Seaton, Dr Andrew and Ritchie, Dr Neil and Irvine, Dr Sharon and Choo-Kang, Dr Brian
• Authors: Barr, D.A., Coussens, A.K., Irvine, S., Ritchie, N.D., Herbert, K., Choo-Kang, B., Raeside, D., Bell, D.J., and Seaton, R.A.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: International Journal of Tuberculosis and Lung Disease
• Publisher: International Union Against Tuberculosis and Lung Disease
• ISSN: 1027-3719
• ISSN (Online): 1815-7920
• Copyright Holders: Copyright © 2017 Barr et al.
• First Published: First published in International Journal of Tuberculosis and Lung Disease 21(6): 677-683
• Publisher Policy: Reproduced under a Creative Commons License