Summary

Giant Cell Arteritis (GCA) is a serious condition that causes inflammation of the blood vessels, primarily affecting older adults. If left untreated, it can lead to permanent vision loss or stroke. Doctors often rely on two blood tests - ESR (Erythrocyte Sedimentation Rate) and CRP (C-Reactive Protein) - to help diagnose GCA, as these are typically elevated in active disease. However, some patients (about 4-15%) have only ESR or CRP elevated, and 1% have both normal despite having active vasculitis [2].

This study was conducted at a specialized fast-track clinic that aims to diagnose GCA rapidly. The authors examined over 130 patients diagnosed with GCA, including 23 with normal ESR and CRP levels at the time of initial assessment. The two groups had comparable ages and previous medical histories. The patients exhibited the same symptoms as those with high inflammation markers, including headache, scalp tenderness, jaw pain, and even vision problems. Both groups had similar rates of ultrasound positivity (91% in the normal marker group and 89% in the elevated marker group), comparable numbers of halo signs on ultrasound (78% vs. 68% respectively) and rates of large vessel vasculitis on ultrasound were also similar (48% vs. 38%). The researchers found that the group with normal test results had waited longer (on average 35 days vs. 20 days) between first experiencing symptoms and getting their blood work done. When the team examined the accuracy of these tests, they found that CRP was more sensitive than ESR, i.e. it identified more people with GCA (74% vs. 48%). However, neither test was perfectly reliable.

Significantly, and as a limitation to the presented study, the diagnosis of GCA relied on the clinical presentation, ultrasound, and the clinical judgment of a rheumatologist. The patients all fulfilled the ACR criteria; however, only very few received additional imaging by MRI or PET-CT to further provide evidence for active vasculitis. Studies from VASAS researchers previously demonstrated that ultrasound findings in vasculitis can persist, despite successful treatment of the vasculitis [3]. Moreover, others have reported lower frequencies of ESR/CRP-negative GCA patients [2]. The authors related this to the fast-track clinic setting, where they see more complicated cases and tertiary referrals, suggesting a certain bias.

Impact on Patient Treatment and Future Perspectives

This study highlights a critical gap in knowledge regarding inflammation-parameter negative GCA and the diagnosis of GCA. If a doctor relies too heavily on ESR and CRP, some patients with active disease might be missed.

For patients, this means you should speak up about any concerning symptoms—such as new headaches, jaw pain while chewing, or vision changes—even if your blood tests appear normal. For doctors, it’s a reminder to evaluate the overall situation: symptoms, timeline, and imaging like ultrasound, instead of relying solely on blood test results.

Moving forward, developing sensitive biomarkers and early diagnostic techniques is essential to prevent overlooking any GCA patient.

References:

[1] Normal inflammatory markers in giant cell arteritis: a diagnostic blind spot. Currier CE et al. Rheumatol Int. 2025 Jul 19;45(8):175. doi: 10.1007/s00296-025-05930-3.

[2] Systematic review of the literature and a case report informing biopsy-proven giant cell arteritis (GCA) with normal C-reactive protein. Laria A et al. Clin Rheumatol. 2012 Sep;31(9):1389-93. doi: 10.1007/s10067-012-2031-3

[3] The clinical benefit of imaging in the diagnosis and treatment of giant cell arteritis. Berger CT et al. Swiss Med Wkly. 2018 Aug 22:148:w14661. doi: 10.4414/smw.2018.14661. eCollection 2018 Aug 13.

Composed by

Prof. Dr. Christof Berger, Leitender Arzt, Universitätsspital Basel