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Elevated CRP Levels Linked to Worse Outcomes in Patients with Fibromyalgia

C-reactive protein (CRP), an acute phase protein produced mainly by liver hepatocytes in response to interleukin-6 (IL-6), is a non-specific marker of inflammation.

Although some patients with fibromyalgia (FM) have elevated high-sensitivity C-reactive protein (hsCRP) levels due to physical inactivity and being overweight, affected patients tended to have worse symptoms and exhibited an impaired ability to work. Measuring hsCRP may be beneficial in identifying patients with FM who are at a greater need of interventions supporting working ability, according to a study published in Advances in Rheumatology.1

“Fibromyalgia, a common pain syndrome, is thought to be a non-inflammatory, nociplastic condition, but evidence implicating neuroinflammation has been increasing,” investigators stated. “Systemic inflammation may be associated with more severe symptoms in some FM patients…CRP is an acute phase protein produced mainly by liver hepatocytes in response to interleukin-6 (IL-6) and is a non-specific marker of inflammation.”

Investigators measured hsCRP levels (elevated levels were considered >3 mg/l) and gathered clinical and questionnaire data, including the 10-item Fibromyalgia Impact Questionnaire (FIQ), which evaluates the severity of symptoms and how that impacts daily function, from female patients with FM and gender- and age-matched healthy controls. Participants also completed the Pain Catastrophizing Scale (PCS) and the State-Trait Anxiety Inventory B (STAI-B), which measured anxiety tendencies. A cognitive stress test with surface electromyography and electrocardiography was performed and data regarding medical history, lifestyle, body mass index (BMI), education, employment status, and smoking status was collected. An oral glucose tolerance test was offered to all participants.

Leisure-time physical activity (LTPA) was rated for both frequency and intensity. Participants subjectively rated their physical fitness compared with healthy peers as worse, average, or better (on a scale of 1-3, respectively). Those with an overall score of ≥8 were considered active.

Patients with FM had significantly higher mean hsCRP levels when compared with controls (mean 2.33 mg/l [SD 2.43] vs 1.17 [SD 1.11], P = 0.013), especially in those who were overweight and who had lower LTPA. However, there was no significant difference in the rate of elevated hsCRP compared with controls (21.6% vs 10.3%, P = 0.323).

A total of 21.6% (n = 8/37) with FM had elevated hsCRP levels and 29 exhibited normal levels (78.4%). Those with higher hsCRP were significantly associated with higher FIQ scores (64.8 [SD 17.2] vs 45.5 [SD 17.4], P = 0.017), worse physical functioning (4.33 [SD 2.15] vs 2.40 [SD 2.09], P = 0.045), greater pain levels (7.85 [SD 1.50] vs 5.10 [SD 2.52], P = 0.001), and were less likely to be employed when compared with those with normal hsCRP. Patient groups were similar regarding clinical characteristics such as blood count, lipid profiles, and liver function, as well as education, sleep disturbances, comorbidities, smoking status, and psychological measures.

Although the study had an adequately sized sample of patients with FM, generalizability was limited as investigators did not include male patients. Additionally, there was a delay between the collection of the questionnaire data and the blood samples due to protocol demands (median time gap 86 days), which may have led to potential changes in scores and samples and ultimately affected subgroup comparisons and correlation analyses.

“The role of pharmacotherapy targeting the inflammatory system in FM warrants further research,” investigators concluded. “Physical activity and normal weight are recommended for all FM patients, but hsCRP may help identify those at the greatest risk who would benefit most from lifestyle interventions. The importance of lifestyle factors is supported by the positive correlation between BMI and hsCRP and changes indicative of metabolic syndrome seen in FM patients with elevated hsCRP.”


Zetterman T, Markkula R, Kalso E. Elevated highly sensitive C-reactive protein in fibromyalgia associates with symptom severity. Rheumatol Adv Pract. 2022;6(2):rkac053. Published 2022 Jun 25. doi:10.1093/rap/rkac053