Recurrent pericarditis with normal C-reactive protein: Clinical and laboratory features, biomarkers and outcome in a non-inflammatory phenotype

Background: Differences in recurrent pericarditis with normal vs. elevated C-reactive protein (CRP) are unknown. Materials and methods: We studied 448 patients with recurrent or incessant pericarditis. CRP levels <10 mg/L were considered normal. Forty-one patients with normal CRP were tested for interleukin 6 (IL-6), serum amyloid A (SAA) and soluble urokinase plasminogen activator receptor (suPAR). Results: Among the cohort (median age 43 years, 48.4% females), 336 patients (75%) had elevated CRP, while 112 (25%) had normal levels. CRP-negative patients were younger (38.6 vs. 43.5 years, p=0.007) and predominantly female (67.9% vs. 42.0%, p<0.001). They presented less often with fever (23.2% vs. 74.1%, p<0.001), pleural involvement (7.1% vs. 61.6% p<0.001), and neutrophilic leucocytosis (WBC 6760 vs. 12315/µL, p<0.001). Pericardiocentesis was performed rarely in CRP-negative patients (2.7% vs. 13.4%, p=0.001). Recurrence rates were similar (5.4 vs. 5.5/100 months-patient, p=0.918). Among CRP-negative patients, 53 (47.3%) had an incessant course characterized by persistent symptoms (pain and tachycardia); abnormal instrumental findings included ECG changes (28.6%), mild pericardial effusion (86.6%), and cardiac magnetic resonance evidence of effusion/oedema/late gadolinium enhancement (43.7%). Anakinra was administered to 48 CRP-positive (14.3%) and 10 CRP-negative patients (8.9%), leading to good responses with discontinuation of NSAIDs and corticosteroids in 39/48 (81.2%) and 5/10 (50.0%), respectively. Among the 41 CRP-negative patients tested, IL-6 and suPAR levels were always normal, while SAA was elevated in 17.1%. Conclusions: Pericarditis with normal CRP exhibits distinct clinical and laboratory features, often presenting with an incessant course. Although rarely elevated, SAA may help to identify inflammation beyond CRP.