Rheumatoid nodules are the most common dermatologic manifestation of rheumatoid arthritis (RA), occurring in approximately 20-30% of RA patients. RA is a chronic, systemic autoimmune disease characterized by inflammation in the synovial joints, leading to progressive joint destruction, morning stiffness, and multi-joint arthritis. The presence of rheumatoid nodules can indicate a more severe form of the disease, often correlating with more extensive joint damage and higher disease activity. 

Pathophysiology

Rheumatoid nodules are subcutaneous masses that develop as a result of inflammation triggered by the autoimmune response in RA. In RA, the immune system produces antibodies against the body’s own tissues, particularly targeting the synovial lining of joints.. Rheumatoid nodules are typically associated with seropositive RA, meaning that they occur predominantly in patients who test positive for rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA).

The exact cause of rheumatoid nodules remains unclear, but they are thought to form in response to prolonged inflammation and localized immune reactions. 

Clinical Presentation

Rheumatoid nodules are typically well-demarcated, flesh-colored, subcutaneous lumps or masses. They are usually freely movable but may become attached to underlying tissues in some cases. The size of the nodules can range from small pea-sized lesions to larger masses the size of a lemon. These nodules most commonly develop on extensor surfaces such as the elbows, fingers, and forearms, but can also occur in areas of prolonged pressure in bedridden patients, such as the heel, sacrum, and posterior scalp.

Nodules may not be tender unless there is underlying inflammation, ulceration, or nerve impingement. In severe cases, nodules may lead to functional impairment, such as restricted movement due to their location or irritation of peripheral nerves. In some cases, the nodules may ulcerate, becoming painful and prone to infection.

Interestingly, although external nodules are more common, rheumatoid nodules can also develop internally, affecting sites such as the lungs, sclera of the eyes, or vocal cords. However, diagnosis at these locations is often challenging due to the difficulty of detecting them without specialized imaging or biopsy.

Diagnosis

The diagnosis of rheumatoid nodules is typically clinical, based on a history of RA and the characteristic presentation of painless, slow-growing, movable subcutaneous nodules, especially in areas prone to pressure or trauma. The diagnosis is most straightforward when the rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) levels are elevated, which are highly specific markers for RA. In approximately two-thirds of RA patients, arthritis symptoms precede the development of nodules, although a small subset may present with nodules at the time of initial diagnosis .

While biopsy of mature nodules is not typically required, it may be performed in ambiguous cases. 

Treatment Options

The treatment of rheumatoid nodules is often tailored to the severity of the disease and the presence of associated symptoms. For many patients, rheumatoid nodules are asymptomatic and primarily a cosmetic concern. In these cases, no treatment may be necessary. However, when the nodules cause symptoms such as pain, ulceration, or functional impairment, more aggressive treatment may be warranted.

• Conservative Management
  For patients with asymptomatic nodules, conservative management, including monitoring, is generally sufficient. In cases where nodules are tender or ulcerated, topical treatments, including corticosteroid creams, may provide some relief. The primary focus of treatment for RA itself—disease-modifying antirheumatic drugs (DMARDs), including methotrexate, biologic agents (TNF inhibitors, IL-6 inhibitors), and nonsteroidal anti-inflammatory drugs (NSAIDs)—can also help reduce inflammation and, in some cases, slow the growth of nodules.
• Corticosteroid Injections
  For symptomatic nodules, corticosteroid injections such as methylprednisolone may help reduce their size and alleviate pain. However, these injections carry the risk of infection and ulceration, particularly in immunosuppressed patients.
• Surgical Excision
  In cases where nodules are causing significant discomfort, impinging on nerves, or located in areas subject to repeated trauma (e.g., the foot), surgical excision may be considered. However, nodules often recur after excision, and surgery should be performed with caution, particularly in immunosuppressed patients.
• Alternative Therapies
  Some studies have suggested that other therapies, such as the use of methotrexate alternatives (e.g., sulfasalazine) or the addition of biologics like rituximab, may help reduce the formation or growth of nodules, particularly in patients experiencing accelerated nodulosis due to methotrexate use. Collaboration with a rheumatologist is essential when adjusting medications in response to nodule formation.

Psychological Considerations

Although rheumatoid nodules are typically benign, they can lead to significant psychological distress, particularly when they affect visible areas or cause functional limitations. It is important for healthcare providers to consider the psychological impact of nodules on patients, providing support or referrals to mental health professionals when necessary to address body image concerns and quality of life issues.

Conclusion

Rheumatoid nodules are a common and distinctive manifestation of rheumatoid arthritis, affecting a significant proportion of patients. While they are generally benign, their presence can indicate more severe disease and may lead to discomfort, functional impairment, or psychological distress. Treatment is individualized based on symptom severity, and options range from conservative management to surgical intervention. Collaboration with a rheumatologist is essential to ensure that the treatment plan aligns with the patient’s broader management of RA. Further research is needed to fully understand the mechanisms driving nodule formation and to identify more effective therapies.

References

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2. López-Hoyos, M., González, L. A., & Pérez, M. (2020). Rheumatoid nodules in rheumatoid arthritis: A clinical overview. Clinical Reviews in Allergy and Immunology, 59(2), 257-264. https://doi.org/10.1007/s12016-020-08781-1
3. McInnes, I. B., & Schett, G. (2017). The pathogenesis of rheumatoid arthritis. The New England Journal of Medicine, 376(16), 1509-1520. https://doi.org/10.1056/NEJMra1616338
4. Vargas, S. L., Hernández, R. A., & López, M. (2019). Rheumatoid nodules: Pathophysiology, clinical features, and treatment strategies. Rheumatology International, 39(6), 933-940. https://doi.org/10.1007/s00296-019-04358-w
5. Yu, W., Zhang, S., & Deng, Y. (2021). Histological features of rheumatoid nodules: A review of pathogenesis and differential diagnosis. Journal of Clinical Pathology, 74(4), 246-251. https://doi.org/10.1136/jclinpath-2020-206712