Rheumatoid nodules

Rheumatoid nodules are the most common extra-articular manifestation of rheumatoid arthritis (RA), occuring in approximately 20–25% of patients with the condition. They are universally associated with a positive rheumatoid factor (RF).

Rheumatoid nodules are clinical predictors of more severe arthritis, joint erosions and rheumatoid vasculitis, and their presence often suggests a need for more aggressive treatment of the underlying RA. Rheumatoid nodules are not exclusive to RA, and histologically similar nodules can be a feature of subcutaneous granuloma annulare, necrobiosis lipoidica, systemic lupus erythematosus and foreign body granulomas.

This chapter is set out as follows:

• The exact aetiology of rheumatoid nodules is unknown. Experts speculate that a series of events beginning with local vascular trauma and pooling of rheumatoid factor immune complexes, followed by activation and mobilisation of local monocytes or macrophages; fibrinoid deposition by procoagulants; tissue necrosis by cytotoxins, proteinases and collagenase secretion from macrophages; and chemotactic attraction of macrophages to the necrotic zone is responsible for formation of rheumatoid nodules

Distribution

• Most nodules are found on bony prominences, extensor surfaces, or adjacent to joints. They are most frequently found on extensor surfaces of the proximal ulna and olecranon, metacarpophalangeal and proximal interphalangeal joints, ischial tuberosities, joints in the foot and the sacrum
• Occasionally they manifest on the sclera, pinna of the ears, heart, vocal cords, lungs, nervous system, abdominal wall and muscle

Morphology

• ​Single or multiple 
• Firm, skin-coloured, non-tender, mobile nodules within the subcutaneous tissue; however, they can also be attached to underlying structures such as the periosteum, fascia, and tendons
• Lesions range from a few mm to several cm in diameter, and can enlarge or regress, recur, or persist indefinitely

• A diagnosis of rheumatoid nodules is made in the clinical context of the disease eg a symmetric inflammatory polyarthritis, seropositivity for rheumatoid factor and other associated symptoms such as vasculitis

• Although biopsies of subcutaneous nodules can be performed, the histological features of other subcutaneous nodules are often similar to those found in rheumatoid nodules. Rheumatoid nodules tend to show homogeneous, eosinophilic necrobiosis, giant cells within palisaded foci and significant stromal fibrosis, while subcutaneous granuloma annulare (SGA) lesions demonstrate pale, oedematous necrobiosis, an absence of giant cells and lesser degrees of fibrosis. The single most useful differentiating feature in one study was alcain blue stain for mucin, which was positive in all cases of SGA but only one case of a rheumatoid nodule

• Rheumatoid nodules typically present asymptomatically as a cosmetic complaint. Indications for treatment include areas exposed to repetitive trauma, and nodules on weight-bearing prominences that might cause progressive erosions and severe pain, neuropathy, restriction of movement, deformity and damage to underlying structures. Some nodules rupture and lead to deep infections

• There are very few treatment options for rheumatoid nodules. Large nodules can be excised, but they frequently recur within scar tissue, especially if subjected to repetitive trauma. Injecting corticosteroids directly into the lesion sometimes reduces its size. While this procedure is most effective for deep lesions in the olecranon bursa, nodules on the buttocks and feet tend to ulcerate and are likely to become infected. Once they are infected, surgical excision or drainage is required. Oral corticosteroids and hydroxychloroquine can also be used, but their effects on rheumatoid nodules vary and many patients with RA already receive these medications for the underlying condition. Rheumatoid nodules occasionally resolve without medical or surgical intervention