Background/Purpose: Traditionally, elevated erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) had been considered a hallmark of GCA and both are included in the 2022 ACR/EULAR GCA classification criteria. However, emerging evidence indicates that a subset of patients even with biopsy-proven GCA may present with normal or low ESR levels. The identification and characterization of this subgroup of patients is essential to improve diagnostic accuracy and optimize the therapeutic management of GCA. The main objective of this study was to determine the prevalence of low ESR and CRP in GCA, and to investigate whether there are differences in clinical manifestations between patients with and without elevation of these acute phase reactants.

Methods: This is a retrospective population-based analysis including consecutive unselected GCA cases from a cohort diagnosed since 2017 with basal data of ESR or CRP. All patients underwent standardized bilateral ultrasound (US) of cranial arteries (common temporal artery and branches) and extra-cranial arteries (carotid, subclavian and axillary). Subtypes were classified as cranial, extra-cranial, or mixed based on vascular involvement identified by US and/or positron emission tomography (PET-CT). Demographic and clinical variables were extracted from clinical records and diagnosis required at least six months of clinical follow-up. Constitutional syndrome included weight loss, malaise, and fever. Patients included were without treatment or with less of two weeks of oral corticosteroid therapy.

Results: A total of 228 cases were included (Table 1). 85/211 GCA patients had ESR below 50 mm/h (40.3%), 27/213 (12.7%) CRP below 10mg/L and 27/228 (11.8%) CRP or ESR below these ranges. Therefore, the sensitivity of acute phase reactants as isolated value for the diagnosis of GCA in our cohort was 59.7% for patients with ESR≥ 50 mm/h, 87.3% for patients with CRP≥ 10 mg/L, and 88.2% for patients with at least one of them elevated. Headache, stroke and fever were less frequent in patients with ESR< 50 (p< 0.05) and in patients with constitutional syndrome (p< 0.01), however polymyalgia rheumatica (PMR) was more frequent with ESR< 50 (p< 0.01). CRP ≥10 mg/L was significantly more frequent in patients with jaw claudication and constitutional syndrome (p< 0.05) and the presence of at least one acute phase reactant was significantly more frequent in patients with constitutional syndrome. Regarding the vascular subtype, a statistically significant difference was observed in the large vessel subtype, which was more frequent in patients with ESR < 50 mm/h (p< 0.01).

Conclusion: An ESR ≥50 mm/h showed lower sensitivity for the diagnosis of GCA (57.3%) compared to CRP ≥10 mg/L (87.3%) or the combination of elevated ESR or CRP (88.2%). Patients with low ESR values had a lower prevalence of headache, stroke, fever, and constitutional symptoms, but a higher frequency of polymyalgia rheumatica and the large-vessel vasculitis subtype. Similarly, lower CRP levels were associated with fewer ischemic and systemic symptoms, with significant differences observed in the frequency of jaw claudication and constitutional syndrome.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/prevalence-and-clinical-significance-of-low-esr-and-crp-in-giant-cell-arteritis-a-population-based-study/