Estimating overdiagnosis in giant cell arteritis diagnostic pathways using genetic data: genetic association study
Charikleia Chatzigeorgiou1, Jennifer H Barrett1, Javier Martin2
1School of Medicine, University of Leeds, Leeds, UK.
Rheumatology (Oxford, England)
|December 4, 2023
Summary
Temporal artery biopsy (TAB) can miss cases of giant cell arteritis (GCA), leading to overdiagnosis. Genetic analysis suggests two-thirds of TAB-negative GCA cases may be overdiagnosed, impacting diagnostic accuracy.
Area of Science:
- Immunogenetics
- Rheumatology
- Diagnostic Accuracy
Background:
- Giant cell arteritis (GCA) diagnosis relies on temporal artery biopsy (TAB), but false negatives can lead to overdiagnosis.
- Accurate diagnosis is crucial for effective GCA management and preventing complications.
Purpose of the Study:
- To estimate the historic overdiagnosis rate of GCA using HLA genetic associations as an unbiased method.
- To evaluate the sensitivity and specificity of TAB in GCA diagnosis.
Main Methods:
- Genotyping of 663 GCA patients and 2619 population controls diagnosed between 1990-2014.
- Imputation of HLA region variants and comparison of allele frequencies between GCA cases and controls.
- Utilizing HLA genetic associations of TAB-positive GCA as a reference to estimate overdiagnosis in TAB-negative or unbiopsied cases.
Main Results:
- TAB-negative GCA and GCA without TAB results showed intermediate HLA variant frequencies between TAB-positive GCA and controls.
- Estimated overdiagnosis rates were approximately two-thirds for TAB-negative GCA and one-third for GCA without TAB.
- Estimated TAB sensitivity was 88%, with a negative likelihood ratio of 0.12 at 95% specificity.
Conclusions:
- Genetic analysis provides a method to assess diagnostic accuracy in GCA.
- A significant proportion of GCA cases may be overdiagnosed, particularly those without a positive TAB.
- The findings highlight the need for careful interpretation of diagnostic tests in GCA.
