From the Guidelines
Rheumatoid nodules and methotrexate nodulosis are distinct manifestations that occur in rheumatoid arthritis patients, though they appear similar, with methotrexate nodulosis being a paradoxical reaction to methotrexate treatment. Rheumatoid nodules are firm, subcutaneous granulomatous lesions that develop in about 20-30% of rheumatoid arthritis patients, typically occurring over pressure points or extensor surfaces like elbows, fingers, and heels. They are associated with more severe, seropositive disease and represent a classic extra-articular manifestation of rheumatoid arthritis. In contrast, methotrexate nodulosis is a reaction where patients develop new nodules or experience worsening of existing nodules while taking methotrexate, despite the medication effectively controlling their joint inflammation. These methotrexate-induced nodules can develop in unusual locations like the hands and feet, may appear more rapidly, and can be more numerous than typical rheumatoid nodules. Histologically, both types of nodules look similar with central fibrinoid necrosis surrounded by palisading fibroblasts.
Key Differences
- Location: Rheumatoid nodules typically occur over pressure points or extensor surfaces, while methotrexate nodulosis can occur in unusual locations.
- Onset: Methotrexate nodulosis may appear more rapidly than rheumatoid nodules.
- Management: While rheumatoid nodules often improve with effective rheumatoid arthritis treatment, methotrexate nodulosis may require discontinuation of methotrexate and switching to an alternative DMARD to resolve the nodules, as conditionally recommended by the 2021 American College of Rheumatology guideline for the treatment of rheumatoid arthritis 1.
Clinical Considerations
- Patient preferences and clinician preferences are expected to vary, and the decision to switch from methotrexate to an alternative DMARD should be made on a case-by-case basis.
- The recommendation to switch is based on the premise that methotrexate is a contributing factor to progressive nodulosis, as noted in the 2021 American College of Rheumatology guideline for the treatment of rheumatoid arthritis 1.
From the Research
Rheumatoid Nodules vs Methotrexate Nodulosis
- Rheumatoid nodules are a common manifestation of rheumatoid arthritis, characterized by multiple small subcutaneous granulomatous nodules typically located on the elbows in approximately 20% of patients with rheumatoid arthritis 2.
- Methotrexate nodulosis, on the other hand, is a phenomenon that occurs in patients with rheumatoid arthritis treated with methotrexate, where accelerated nodulosis develops during methotrexate therapy 3, 4, 5.
Key Differences
- Location: Rheumatoid nodules are typically located on the elbows, while methotrexate nodulosis can occur in various locations, including the fingers, hands, and feet 4, 5.
- Time of onset: Rheumatoid nodules can occur at any time during the course of rheumatoid arthritis, while methotrexate nodulosis typically develops 1-24 months after initiating methotrexate therapy 5.
- Treatment response: Methotrexate can actually increase the development of rheumatoid nodules, while the combination of hydroxychloroquine and methotrexate may have a beneficial effect on nodulosis 2, 5.