Polymyalgia rheumatica (PMR) is the commonest inflammatory rheumatic disease affecting older people. The current mainstay of treatment is long-term oral glucocorticoid therapy. Management of these patients in clinical practice is often complicated by the presence of comorbidity. Comorbidity might be due to shared risk factors such as age, sex, or genetic background; to the presence of the disease itself; or to adverse effects of glucocorticoid therapy. Cardiovascular disease, osteoporosis/fracture, metabolic and ocular comorbidity are of particular interest to clinicians because of their relationship to glucocorticoid therapy and the relevance to clinical treatment decisions regarding glucocorticoid tapering. Patients at high risk of exacerbation of comorbidity by glucocorticoid therapy may be considered for adjunctive steroid-sparing therapies and thus may need specialist management. From a public health perspective, with the ageing population the prevalence of PMR is predicted to increase; accurate data on comorbidity will be needed for planning and delivery of healthcare services.

Objective. To determine prevalent comorbidities in cases with polymyalgia rheumatica (PMR) or giant cell arteritis (GCA) compared to matched controls. Methods. Nested, cross sectional case-control study within UK Biobank. Case status was defined as self-reported prior diagnosis of PMR or GCA. 10 controls per case were matched for age, sex, ethnicity and assessment centre. Associations with selected self-reported comorbidities were studied using conditional logistic regression. Results. Of PMR (n=1036) or GCA (n=102) cases, 72% were female, 98% white and 58% reported current use of glucocorticoids. Mean age was 63. At the time of the assessment visit, compared to controls, PMR/GCA cases were more likely to report poor general health and at least several days of low mood in the two past weeks. PMR was associated with hypothyroidism (odds ratio (OR) 1.34, 95% confidence interval (CI) 1.07-1.67) and ever-use of hormone replacement therapy (OR 1.26, CI 1.07-1.47). Regarding common comorbidities, PMR and GCA were both associated with hypertension (PMR: OR 1.21, CI 1.06-1.39; GCA: OR 1.86, CI 1.23-2.81) and cataract (PMR: OR 1.51, CI 1.19-1.93; GCA: OR 3.84, CI 2.23-6.60). Additionally GCA was associated with depression (OR 3.05, CI 1.59-5.85). Neither were associated with diabetes. Conclusion. Participants with a history of PMR/GCA, including those not currently taking glucocorticoids, rated their health as poorer than matched controls,. Some previously-described disease associations (hypothyroidism and early menopause) were replicated. Hypertension and cataract, which can both be exacerbated by long-term glucocorticoid therapy, were over-represented in both diseases, particularly GCA.

Objectives: Prompt diagnosis of giant cell arteritis (GCA) is important to avert visual loss. False-negative temporal artery biopsy (TAB) can occur. Without vascular imaging, GCA may be overdiagnosed in TAB-negative cases, but it is unclear how often this occurs. An unbiased test is a way to address an imperfect reference standard. We used the known Human Leukocyte Antigen (HLA) region genetic association of TAB-positive GCA to estimate the extent of overdiagnosis before widespread adoption of temporal artery ultrasound as a first-line test. Methods: Patients diagnosed with GCA between 1990-2014 consented to the UKGCA Consortium study. HLA region variants were jointly imputed from genome-wide genotypic data of cases and controls. Per-allele frequencies across all variants with p<1.0x10-5 were compared with population control data to estimate overdiagnosis rates in cases without a positive TAB. Results: Genetic data from 663 patients diagnosed with GCA were compared with data from 2619 population controls. TAB-negative GCA (n=147) and GCA without a TAB result (n=160) had variant frequencies intermediate between those of TAB-positive GCA and population controls. Making several strong assumptions, we estimated that around two-thirds of TAB-negative cases and around one-third of cases without TAB result may have been overdiagnosed. From these data, TAB sensitivity is estimated at around 88%. Conclusions: Conservatively assuming 95% specificity, TAB has a negative likelihood ratio of around 0.12. Genotyping alone cannot diagnose GCA at the individual level. Group-level HLA variant genotyping might be used to compare the overall accuracy of different diagnostic pathways or different classification criteria sets.

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