Peripheral neuropathy is a common extra-articular manifestation of rheumatoid arthritis (RA) and represents a significant source of morbidity in affected patients. While subclinical nerve involvement has been reported in up to 85% of individuals with RA, only about one-fifth develop clinically evident neuropathic symptoms. A recent retrospective study published in Medicine (Baltimore) has identified age and anti–cyclic citrullinated peptide (anti-CCP) antibody levels as significant predictors for the development of peripheral neuropathy in RA.
The analysis included data from 183 patients with established RA and evaluated the prevalence, clinical features, and risk factors associated with peripheral nerve involvement. Among the cohort, 32 patients demonstrated neuropathic complications, with 8 patients exhibiting multiple mononeuropathy and 24 patients showing single-nerve involvement. Patients with peripheral neuropathy were significantly older than those without neurological involvement, particularly in the subgroup with multiple mononeuropathy, suggesting an association between age-related vulnerability and cumulative inflammatory burden.
Peripheral neuropathy most commonly presented with pain and numbness, reported in 53.13% and 46.88% of affected patients, respectively. Other manifestations included fatigue (15.63%) and burning sensations (12.50%). Electrophysiological assessment using electromyography revealed that 84.38% of patients with neuropathy had combined sensory and motor impairment, while 12.50% had isolated sensory involvement and 3.13% had isolated motor involvement. Notably, carpal tunnel syndrome was identified in 34.38% of patients with peripheral neuropathy, underscoring the high prevalence of entrapment neuropathies in RA.
Risk factor analysis using binary logistic regression demonstrated that both increasing age (P = .044) and higher anti-CCP antibody levels (P = .049) were independently associated with the presence of peripheral neuropathy. Anti-CCP antibodies, which are well recognized markers of disease severity and poor prognosis in RA, may also reflect a broader systemic and neuro-immunological impact of the disease.
These findings are consistent with earlier studies. A landmark electrophysiological study by Nadkarni et al. showed that subclinical neuropathy is highly prevalent in RA and often precedes overt symptoms. Similarly, Agarwal et al. reported that vasculitic and entrapment neuropathies are among the most frequent neurological complications in RA, with carpal tunnel syndrome being the most common focal neuropathy. Other investigators have demonstrated that high inflammatory burden, long disease duration, and seropositivity for anti-CCP and rheumatoid factor are associated with a higher risk of extra-articular involvement, including peripheral nerve damage. Immune-mediated vasculitis of the vasa nervorum and chronic synovial inflammation causing nerve compression are believed to be key pathogenic mechanisms.
These findings highlight the importance of early recognition and systematic evaluation of neuropathic symptoms in RA patients, particularly in older individuals and those with elevated anti-CCP titers. Incorporating neurological assessment into routine rheumatology care may facilitate earlier diagnosis, timely intervention, and improved patient outcomes. Further research is warranted to clarify the mechanisms linking immune-mediated joint disease and peripheral nerve injury and to develop targeted strategies to prevent and manage neuropathy in RA.
Reference
He S, Hu SS, Xie J, Zhang J, Geng H, Jia E. Clinical characteristics of peripheral neuropathy and risk factors in rheumatoid arthritis patients: A retrospective study. Medicine (Baltimore). 2026 Jan 16;105(3):e47156.