Paradoxical upgrading reaction in extra-pulmonary tuberculosis: association with vitamin D therapy
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.
Keywords: host-directed therapy; host–pathogen interaction; inflammation; innate immunity
Document Type: Research Article
Affiliations: 1: Wellcome Trust Liverpool Glasgow Centre for Global Health Research, University of Liverpool, Liverpool, UK 2: Department of Pathology, Faculty of Health Sciences, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, South Africa 3: Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow 4: Hairmyres Hospital, East Kilbride 5: Department of Respiratory Medicine, Glasgow Royal Infirmary, Glasgow 6: Department of Respiratory Medicine 7: Department of Infectious Diseases, The Queen Elizabeth University Hospital, Glasgow, Scotland, UK
Publication date: 01 June 2017
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