Infections and the Risk of Incident Giant Cell Arteritis: A Population-Based, Case-Control Study

Rennie L. Rhee¹, Peter C. Grayson², Peter A. Merkel³ and Gunnar Tomasson⁴, ¹Rheumatology, University of Pennsylvania, Philadelphia, PA, ²National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, ³Division of Rheumatology, Univ of Pennsylvania; Perelman School of Med, Philadelphia, PA, ⁴Dept of Public Health Sciences, University of Iceland, Reykjavik, IS

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: Giant cell arteritis and infection

Session Information

Date: Sunday, November 13, 2016

Title: Vasculitis - Poster I: Large Vessel Vasculitis and Polymyalgia Rheumatica

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose : Alterations in the immune system and infections are suspected to increase susceptibility to giant cell arteritis (GCA). Recently herpes zoster has been raised as a potential candidate pathogen for 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 The Health Improvement Network (THIN) database, an electronic database originating from general practices in the United Kingdom. Cases with newly-diagnosed GCA were identified using a validated algorithm and compared to age-, sex-, and practice-matched controls using incidence density sampling. Patients with a prior diagnosis of polymyalgia rheumatica were excluded. Infections, including herpes zoster, that occurred prior to the onset of GCA were identified using diagnostic codes. Conditional logistic regression was used to examine the relationship between any infection or herpes zoster infection on the development of GCA and expressed as incidence rate ratios (IRR). All analyses were adjusted for prior use of glucocorticoid and non-glucocorticoid immunosuppressive therapies, alcohol use, smoking history, and the Charlson Comorbidity Index. Patients were analyzed according to the time period prior to index date in which the infection occurred to determine if recent infections were more strongly associated with GCA compared to earlier infections. A sensitivity analysis excluding patients who previously received at least 1 prescription for an oral glucocorticoid or immunosuppressive medication was performed.

Results : There were 4,559 cases of GCA and 22,795 controls. Any prior infection and herpes zoster was associated with incident GCA (IRR 1.26 [1.16, 1.36] and 1.17 [1.04, 1.32], respectively) (Table 1). A greater number of infections was associated with a higher risk of developing GCA. A sensitivity analysis excluding patients who received immunosuppressive medications produced similar results. The risk of developing GCA was greatest among those who experienced an infection within a year of the index date but was also significantly associated with infections that occurred in earlier time periods (Table 2).

Conclusion : 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 longstanding 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.

Table 1: The Association of Infections with Incident Giant Cell Arteritis

Exposure	Unadjusted IRR (95% CI)	P-value	Adjusted IRR (95% CI)*	P-value
Herpes zoster infection	1.24 (1.10, 1.39)	< 0.01	1.17 (1.04, 1.32)	< 0.01
Herpes zoster infection AND antiviral therapy	1.16 (0.99, 1.36)	0.05	1.09 (0.93, 1.28)	0.27
Any infection	1.44 (1.34, 1.56)	< 0.01	1.26 (1.16, 1.36)	< 0.01
Number of infections 0 1 2-4 5 or more	1 (reference) 1.38 (1.27, 1.50) 1.88 (1.71, 2.08) 2.94 (2.58, 3.36)	— < 0.01 < 0.01 < 0.01	1 (reference) 1.28 (1.18, 1.40) 1.60 (1.44, 1.77) 2.18 (1.90, 2.51)	— < 0.01 < 0.01 < 0.01
	Test for trend	< 0.01	Test for trend	< 0.01

*Adjusted for Charlson Comorbidity Index, alcohol use, smoking history, prior use of immunosuppressive therapies, and prior use of oral glucocorticoids if applicable.

IRR = incident rate ratio; CI = confidence interval.

Table 2: The Association of Any Infection and Herpes Zoster Infection with Incident Giant Cell Arteritis Stratified by Time Period Prior to Index Date

	Any Infection		Herpes Zoster Infection
	Adjusted IRR (95% CI)*	P-value	Adjusted IRR (95% CI)*	P-value
<1 year	1.66 (1.54, 1.79)	< 0.01	1.32 (0.95, 1.82)	0.10
1-2 years	1.32 (1.22, 1.43)	< 0.01	1.11 (0.79, 1.56)	0.55
2-3 years	1.19 (1.09, 1.29)	< 0.01	1.00 (0.70, 1.43)	0.99
3-4 years	1.19 (1.09, 1.30)	< 0.01	0.92 (0.63, 1.36)	0.69
4-5 years	1.14 (1.05, 1.25)	< 0.01	1.15 (0.77, 1.70)	0.49
5-10 years	1.26 (1.17, 1.35)	< 0.01	1.36 (1.14, 1.64)	< 0.01
> 10 years	1.22 (1.13, 1.32)	< 0.01	1.18 (0.99, 1.42)	0.07

* Adjusted for Charlson Comorbidity Index, alcohol use, smoking history, prior use of immunosuppressive therapies, and prior use of oral glucocorticoids.

IRR = incident rate ratio; CI = confidence interval.

Disclosure: R. L. Rhee, None; P. C. Grayson, None; P. A. Merkel, None; G. Tomasson, None.

To cite this abstract in AMA style:

Rhee RL, Grayson PC, Merkel PA, Tomasson G. Infections and the Risk of Incident Giant Cell Arteritis: A Population-Based, Case-Control Study [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/infections-and-the-risk-of-incident-giant-cell-arteritis-a-population-based-case-control-study/. Accessed .

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