RESUMO
OBJECTIVES: Giant cell arteritis (GCA) may be confirmed by temporal artery biopsy (TAB) but false negatives can occur. GCA may be overdiagnosed in TAB-negative cases, or if neither TAB nor imaging is done. We used Human Leucocyte Antigen (HLA) genetic association of TAB-positive GCA as an "unbiased umpire" test to estimate historic overdiagnosis of GCA. METHODS: Patients diagnosed with GCA between 1990-2014 were genotyped. During this era, vascular imaging alone was rarely used to diagnose GCA. HLA region variants were jointly imputed from genome-wide genotypic data of cases and controls. Per-allele frequencies across all HLA variants with p< 1.0x1 0 -5 were compared with population control data to estimate overdiagnosis rates in cases without a positive TAB. RESULTS: Genetic data from 663 GCA patients were compared with data from 2619 population controls. TAB-negative GCA (n = 147) and GCA without TAB result (n = 160) had variant frequencies intermediate between TAB-positive GCA (n = 356) and population controls. For example, the allele frequency of HLA-DRB1*04 was 32% for TAB-positive GCA, 29% for GCA without TAB result, 27% for TAB-negative GCA and 20% in population controls. Making several strong assumptions, we estimated that around two-thirds of TAB-negative cases and one-third of cases without TAB result may have been overdiagnosed. From these data, TAB sensitivity is estimated as 88%. CONCLUSIONS: Conservatively assuming 95% specificity, TAB has a negative likelihood ratio of around 0.12. Our method for utilising standard genotyping data as an "unbiased umpire" might be used as a way of comparing the accuracy of different diagnostic pathways.
RESUMO
Objective: The aim was to determine prevalent co-morbidities in cases with PMR or GCA compared with matched controls. Methods: This was a nested, cross-sectional case-control study within the UK Biobank, which recruited participants aged 40-69 years. Case status was defined as self-reported prior diagnosis of PMR or GCA. Ten controls per case were matched for age, sex, ethnicity and assessment centre. Associations with selected self-reported co-morbidities 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 years. At the time of the assessment visit, compared with controls, PMR/GCA cases were more likely to report poor general health and at least several days of low mood in the past 2 weeks. PMR was associated with hypothyroidism [odds ratio (OR) = 1.34; 95% CI = 1.07, 1.67] and ever-use of HRT (OR = 1.26; 95% CI = 1.07, 1.47). Regarding common co-morbidities, PMR and GCA were both associated with hypertension (PMR: OR = 1.21; 95% CI = 1.06, 1.39; GCA: OR = 1.86; 95% CI = 1.23, 2.81) and cataract (PMR: OR = 1.51; 95% CI = 1.19, 1.93; GCA: OR = 3.84; 95% CI = 2.23, 6.60). Additionally, GCA was associated with depression (OR = 3.05; 95% CI = 1.59, 5.85). Neither condition was 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, both of which can be exacerbated by long-term glucocorticoid therapy, were over-represented in both diseases, particularly GCA.
