Rheumatoid nodules are common cutaneous manifestations of rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA). The characteristic rheumatoid nodule occurs in 20% of patients with RA and may be an indication of RA disease severity. The pathogenesis of rheumatoid nodules remains unclear, but vascular trauma and external trauma combined with accumulation of immune complexes likely lead to rheumatoid nodule formation. Rheumatoid nodules may also occur within internal organs such as the muscle, heart (including pericardial and endocardial tissues), and lungs. Visceral nodules may clinically mimic infections, malignancies, or other autoimmune / inflammatory processes. Pulmonary rheumatoid nodules can present with cavitations. Large pulmonary rheumatoid nodules can cause pneumothoraces, pleural effusions, and hemoptysis.

Patients affected with rheumatoid nodules will often have a high titer of rheumatoid factor. In addition, patients with RA who are positive for rheumatoid factor and anti-cyclic citrullinated peptide (CCP) antibodies are more likely to develop rheumatoid nodules. However, patients with mild RA may also develop rheumatoid nodules, as may patients who have rheumatoid disease without significant joint involvement. Nodules can also precede the onset of clinically significant arthritis by a number of years.

Rheumatoid nodules may persist, enlarge, or spontaneously regress over time. Nodules on areas subject to pressure or trauma, such as the sacrum, have a greater tendency to ulcerate. Secondary infections of ulcerated rheumatoid nodules can lead to septic arthritis. Additional complications of rheumatoid nodules include pain, reduced joint mobility, and peripheral neuropathy.

In a poorly understood phenomenon, patients with RA treated with methotrexate and TNF-alpha inhibitors can experience an increase in the number and size of rheumatoid nodules.