medwireNews: Classifying individuals with musculoskeletal symptoms and no clinical synovitis using anti-cyclic citrullinated peptide (CCP) antibody levels and self-reported hand or foot pain may be useful to prioritize rheumatology referrals, study findings indicate.
Paul Emery and colleagues, from the University of Leeds in the UK, explain that musculoskeletal complaints make up around 30% of general practice consultations in England and it can be difficult to manage the large number of referrals to rheumatology services.
“Considering this, there is need for prioritisation, and this study provides practical guidance for primary care physicians to easily assess the urgency of referral to rheumatology using widely available tests,” they write in Arthritis Research & Therapy.
Emery and team recruited 6780 individuals aged 16 years and older with new nonspecific musculoskeletal symptoms and no clinical synovitis from 312 primary care practices in the UK between 2007 and 2019. Of these, 2.8% were positive for anti-CCP antibodies (anti-CCP+).
Among the 151 anti-CCP+ participants with complete data, 65% had a high anti-CCP level (≥3 times the upper normal limit) and 35% had a low level. Overall, 45% of anti-CCP+ participants progressed to inflammatory arthritis, 84% of whom did so in less than 12 months (mean 45 weeks). The progression rates were significantly higher among individuals with high anti-CCP levels than among those with low levels, at 62% versus 13%, and the researchers note that rheumatoid arthritis was the most commonly diagnosed inflammatory disease, occurring in 93% of progressors.
Almost two-thirds (62%) of anti-CCP+ individuals reported hand pain and 44% reported foot pain, with the proportions increasing to 81% and 62%, respectively, among anti-CCP+ progressors.
After adjustment for factors including age, sex, family history of RA, and smoking, the researchers found that high anti-CCP levels, hand pain, and foot pain were each associated with a significantly increased likelihood of disease progression, at odds ratios (ORs) of 9.42, 2.74, and 4.10, respectively.
Furthermore, the absence of hand and foot pain in combination with a low anti-CCP level resulted in a negative predictive value for disease progression of 95.8%.
Emery et al say that this “should reassure clinicians that such an individual is unlikely to develop [inflammatory arthritis] at that point, and therefore, referral to rheumatology is not a priority.” Nonetheless, they recommend that “this should not discourage referral if a rheumatic disease is suspected.”
The investigators also analyzed 1-year follow-up data for 5640 anti-CCP negative (anti-CCP−) individuals, of whom 0.93% were subsequently diagnosed with general practitioner-confirmed inflammatory arthritis.
In these participants, hand pain was associated with a 2.51-fold increased odds of developing inflammatory arthritis within 12 months, while knee pain was associated with a 3.03-fold increased odds.
This suggests that although the risk for progression in anti-CCP− individuals is low overall, “hand and knee pain may be seen as a red flag that requires follow-up,” the researchers remark.
They conclude that their study “demonstrates that routinely available tests and joint symptoms provide useful discrimination that may be used to prioritise referrals to rheumatology and avoid a delayed diagnosis.”
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