What are the typical locations of rheumatoid nodules and methotrexate-induced nodulosis?

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From the Guidelines

Rheumatoid nodules and methotrexate-induced nodulosis typically occur over pressure points or extensor surfaces, particularly on the elbows, fingers, knuckles, forearms, heels, and Achilles tendons, with methotrexate-induced nodulosis also appearing in atypical sites such as the hands, ears, and face. The locations of these nodules are crucial for diagnosis and management, as they can indicate the severity of the underlying disease or the need for medication adjustment, as suggested by the 2021 American College of Rheumatology guideline for the treatment of rheumatoid arthritis 1. Some key points to consider include:

  • Rheumatoid nodules are found in approximately 20-25% of patients with rheumatoid arthritis, especially those with more severe disease and positive rheumatoid factor.
  • Methotrexate-induced nodulosis can be more numerous, smaller, and develop more rapidly than traditional rheumatoid nodules.
  • The pathophysiology of both conditions involves a local inflammatory response with central fibrinoid necrosis surrounded by palisading fibroblasts and inflammatory cells, though methotrexate nodules may show more pronounced vascular changes.
  • Distinguishing between these conditions is important for management decisions, as methotrexate nodulosis may require medication adjustment, such as switching to a non-methotrexate DMARD for patients with progressive subcutaneous nodules, while rheumatoid nodules often indicate more aggressive underlying disease 1. It is essential to note that the management of these conditions should be based on the most recent and highest-quality evidence, and the 2021 American College of Rheumatology guideline provides conditional recommendations for the treatment of patients with subcutaneous nodules, including the use of methotrexate and the consideration of switching to alternative DMARDs 1.

From the Research

Typical Locations of Rheumatoid Nodules and Methotrexate-Induced Nodulosis

The typical locations of rheumatoid nodules and methotrexate-induced nodulosis can be summarized as follows:

  • Rheumatoid nodulosis is characterized by multiple small subcutaneous granulomatous nodules typically located on the elbows in approximately 20% of patients with rheumatoid arthritis 2.
  • Accelerated rheumatoid nodulosis, especially involving the hands and feet, has been reported in patients receiving methotrexate therapy for rheumatoid arthritis 2, 3.
  • Methotrexate nodulosis has been described in patients with rheumatoid arthritis, with nodules located on the hands, feet, and other areas 4, 5.
  • In some cases, methotrexate-induced nodulosis has been reported to occur on the fingers, anterior chest, axillary areas, and medial sides of the upper arms and thighs 4, 5.

Graphic Representation of Nodulosis Sites

A graphic representation of the sites of nodulosis would typically include:

  • Elbows: a common location for rheumatoid nodules 2.
  • Hands and feet: areas where accelerated rheumatoid nodulosis may occur, especially in patients receiving methotrexate therapy 2, 3.
  • Fingers: a location where methotrexate-induced nodulosis has been reported to occur 5.
  • Anterior chest, axillary areas, and medial sides of the upper arms and thighs: areas where methotrexate-induced nodulosis has been described in some cases 4.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Accelerated cutaneous nodulosis during infliximab therapy in a patient with rheumatoid arthritis.

Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases, 2004

Research

Methotrexate nodulosis.

The Journal of dermatology, 1999

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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