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Infections and the risk of incident giant cell arteritis: a population-based, case-control study
  1. Rennie L Rhee1,
  2. Peter C Grayson2,
  3. Peter A Merkel1,3,
  4. Gunnar Tomasson4
  1. 1Division of Rheumatology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
  2. 2Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA
  3. 3Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
  4. 4Department of Public Health Sciences, University of Iceland, Reykjavik, Iceland
  1. Correspondence to Dr Rennie L Rhee, Department of Rheumatology, Perelman School of Medicine at the University of Pennsylvania, 3400 Spruce Street, White Building 5th Floor, Philadelphia, PA 19104, USA; Rennie.rhee{at}


Objectives Alterations in the immune system and infections are suspected to increase susceptibility to giant cell arteritis (GCA). Recently herpes zoster has been directly implicated in the pathogenesis of GCA. We examined the association between prior infections, in particular herpes zoster, and incident GCA in a population-based cohort.

Methods A nested case-control study was performed using an electronic database from the UK. Cases with newly diagnosed GCA were identified using a validated algorithm and compared with age-matched, sex-matched and practice-matched controls. Conditional logistic regression was used to examine the relationship between any infection or herpes zoster infection on the development of GCA after adjusting for potential confounders; results were expressed as incidence rate ratios (IRRs).

Results There were 4559 cases of GCA and 22 795 controls. Any prior infection and herpes zoster were associated with incident GCA (IRR 1.26 (95% CI 1.16 to 1.36), p<0.01; and 1.17 (95% CI 1.04 to 1.32), p<0.01, respectively). A greater number of infections was associated with a higher risk of developing GCA (IRR for 1, 2–4 and ≥5 infections was 1.28, 1.60 and 2.18, respectively).

Conclusions Antecedent infections and, to a lesser extent, herpes zoster infections are modestly associated with incident GCA. These data provide population-level support for the hypothesis that long-standing alterations of the immune system are associated with susceptibility to GCA and suggest that herpes zoster is unlikely to play a major causal role in the pathogenesis of GCA.

  • Giant Cell Arteritis
  • Infections
  • Epidemiology

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  • Handling editor Tore K Kvien

  • Contributors All authors were involved in the conception and design of study, analysis and interpretation of data, and drafting of manuscript.

  • Funding RLR receives support from the Rheumatology Research Foundation (Scientist Development Award) and the Vasculitis Foundation (Fellowship Award).

  • Competing interests Intercontinental Marketing Services (IMS) Health Real World Evidence Solutions is an UK-based expert in anonymous patient data for the healthcare industry. IMS Health is a commercial organisation that supplies data and trains and supports researchers in the use of primary care patient data. Data are available for us in medical research in the academic setting as well as in industry for a fee which varies depending on the type of data requested. Aside from undergoing ethical review by The Health Improvement Network (THIN) Scientific Review Committee, independent academic groups who voluntarily act as an ethical review body, this protocol was not in any way discussed with IMS Health nor were any changes made by the company. We did not receive financial support or other forms of computational or analytical support from IMS/THIN. The data were collected by IMS and the general practitioners without knowledge of the study objectives and hypotheses.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement Unpublished data are available to anyone after request. Please contact