Rheumatoid nodulosis M06.3-

Bywaters 1949

The term rheumatoid nodulosis is used to describe an entity characterized by subcutaneous rheumatoid nodules(see Rheumatoid Nodules below), cystic bone lesions (emphasized on the hand and foot bones), rheumatoid factor positivity, and arthralgias in patients with little or no evidence of systemic manifestations of rheumatoid arthritis or erosive joint disease. This constellation was first described in 1949

Men are preferentially affected.

30-60 years

Hands, feet, ears, but also heart, lungs and meninges. Rare is the infestation of the conjunctiva.

The criteria require multiple nodules demonstrated by biopsy, recurrent joint symptoms without chronic synovitis or radiographic findings, and no or mild systemic manifestations. A modified version of the criteria presented in 2003 included these criteria and added a positive RF and poor response to standard treatment.

In a study of 16 patients initially diagnosed with rheumatoid nodulosis, 6 of them later developed overt RA. Most (14 of 16) had large subchondral bone cysts that often had cholesterol crystals within the joint. Although early reports suggested that nonsteroidal anti-inflammatory drugs (NSAIDs) were sufficient for the treatment of rheumatoid nodulosis, the disease was successfully controlled with NSAIDs alone in only 5 of 16 patients, and only one patient experienced complete remission with NSAID therapy. Methotrexate has been associated with exacerbation of nodulosis. Therefore, methotrexate should be used with caution in patients with rheumatoid nodulosis.

In children, a benign variant of rheumatoid nodulosis, pseudorheumatoid nodules or benign rheumatoid nodules, may occur. Histologically, these skin lesions resemble rheumatoid nodules but occur in a different distribution, involving the tibia, dorsum of the foot, and scalp. They can be large, but there is no systemic disease or positive serologic result, and most regress within 2 years. In a report describing the clinical features of 174 previous cases, only 2 cases developed systemic disease.5

Accelerated rheumatoid nodulosis develops in the setting of mildly painful nodules in patients with rheumatoid arthritis who are prescribed various disease-modifying antirheumatic drugs. Originally, these lesions were observed in patients treated with methotrexate. More recently, azathioprine, leflunomide, antitumor necrosis factor agents, and tocilizumab have also been associated with accelerated rheumatoid nodulosis. The HLA-DRB1*0401 haplotype and methionine synthase reductase variants have been found to increase susceptibility to accelerated rheumatoid nodulosis; an association with EBV has also been reported. Histopathologically, these lesions show epithelioid palisade granulomas with areas of central necrobiosis. Evidence includes some cases of MTX-induced accelerated rheumatoid nodulosis in the conjunctiva.

1. Tilstra JS et al (2015) Granulomatous Disorders of Adult Skin. Dermatologic Clinics