Rheumatoid Nodules: Definition, Evaluation, and Management
What Are Rheumatoid Nodules?
Rheumatoid nodules are firm, painless subcutaneous protuberances that occur in approximately 20-30% of patients with rheumatoid arthritis and represent the most common extra-articular manifestation of the disease. 1, 2 These nodules are found on extensor surfaces at specific anatomical sites including the elbows, knees, wrists, and along the occiput and spinous processes of thoracic and lumbar vertebrae. 1
Clinical Significance and Prognostic Implications
Nodules are markers of severe, seropositive disease and strongly indicate rheumatoid arthritis rather than other forms of arthritis, specifically signaling more aggressive disease with increased risk of extra-articular manifestations, joint destruction, and cardiovascular complications. 1
The presence of nodules is associated with high swollen joint counts, progression of joint damage, serum rheumatoid factor (RF), and anti-citrullinated protein antibodies (ACPAs). 1
Nodules indicate worse long-term outcomes, including increased cardiovascular morbidity and mortality, with life expectancy shortened by 3-5 years in patients with extra-articular disease. 1
Cardiovascular disease is the primary driver of excess mortality in RA, with a 50% increase in cardiovascular morbidity and mortality compared to the general population. 1
Distinguishing Rheumatoid Nodules from Other Nodular Lesions
Key Differential Diagnoses
Heberden's nodes in osteoarthritis are bone spurs at the distal interphalangeal (DIP) joints, not inflammatory joint swelling, and represent a helpful clinical marker differentiating primary osteoarthritis from secondary osteoarthritis. 1
Patients displaying rheumatoid nodules, extra-articular involvement, and high titers of rheumatoid factor should NOT be given the diagnosis of Psoriatic Arthritis (PsA). 1 Involved joints in PsA are usually less tender and swollen and less symmetric in distribution than in RA. 1
Polyarteritis nodosa (PAN) presents with cutaneous manifestations such as nodules and livedo reticularis, but these are associated with systemic vasculitis affecting medium-sized vessels, fever, weight loss, and characteristic angiographic findings (saccular or fusiform aneurysms). 3
Histologic Features
- When biopsied, rheumatoid nodules reveal palisading granulomas and fibrinoid necrosis, with an absence of granulomas and giant cells that would suggest other diagnoses. 4, 5, 2
Evaluation of Rheumatoid Nodules
Clinical Assessment
Perform a detailed 28-joint count examination assessing proximal interphalangeal joints (PIPs), metacarpophalangeal joints (MCPs), wrists, elbows, shoulders, and knees for tenderness and swelling. 6
Document the specific location, size, and number of nodules, particularly noting whether they are on extensor surfaces or in atypical locations. 7, 8
Assess for other extra-articular manifestations including interstitial lung disease, vasculitis, and inflammatory eye disease. 6
Laboratory Monitoring
Monitoring disease activity should include tender and swollen joint count, patient's and physician's global assessments, ESR, and CRP, usually by applying a composite measure such as SDAI or CDAI. 3, 1
Arthritis activity should be assessed at 1-3 month intervals until the treatment target has been reached. 1
Patient-reported outcomes such as quality of life, fatigue, and physical function are key to evaluate outcome. 1
Imaging Considerations
Baseline imaging including bilateral hand, wrist, and foot X-rays is essential for monitoring structural damage progression. 6
When nodules have atypical localizations or concerning features (such as cortical disruption), CT-guided biopsy may be necessary to exclude malignancy. 7
Management of Rheumatoid Nodules
Medical Management
There is no evidence that systemic therapy specifically treats underlying rheumatoid nodules. 2 However, optimal control of the underlying rheumatoid arthritis is the foundation of management.
Methotrexate should be used with caution as it paradoxically can cause accelerated cutaneous nodulosis in some patients, particularly those with HLA-DRB1*0401 genetic risk factors. 5, 2 Accelerated nodulosis has been reported especially involving the hands and feet during methotrexate therapy. 5
Anti-TNF biologic therapy (infliximab, etanercept) can also cause accelerated nodulosis in some patients, even when RA is in remission. 4, 2
If accelerated nodulosis develops during methotrexate therapy, consider discontinuing methotrexate and adding colchicine, as nodules may resolve after methotrexate is stopped. 5
Surgical Management
Surgical excision is effective and indicated when nodules cause:
- Local pain
- Nerve compression
- Limited range of motion
- Erosion
- Infection 8
Treatment of rheumatoid nodules is often not necessary unless patients are experiencing pain or there is interference with mechanical function. 2
Observation
Conservative management with observation is appropriate for asymptomatic nodules that do not interfere with function. 8
Critical Pitfalls to Avoid
Do not assume all nodules in RA patients are benign rheumatoid nodules—atypical locations or rapid growth warrant biopsy to exclude malignancy. 7
Do not continue methotrexate or anti-TNF therapy without reassessment if accelerated nodulosis develops, as these medications may be the causative factor. 4, 5, 2
Do not diagnose psoriatic arthritis in patients with rheumatoid nodules and high-titer RF, as this combination strongly indicates rheumatoid arthritis. 1
Recognize that nodules indicate severe disease requiring aggressive treatment of the underlying RA to prevent cardiovascular complications and reduce mortality risk. 1