Patients with Rheumatoid Arthritis (RA) may develop nodules at several parts of their bodies. These are called rheumatoid nodules. The condition may be termed as rheumatoid nodulosis.
How many people do rheumatoid arthritis nodules affect?
Classic rheumatoid nodules are seen in nearly 20% to 25% of patients who test positive for Rheumatoid factor and have classic symptoms of RA. These are in fact one of the commonest features of RA affecting sites other than the joints.
Around 90% of all patients with RA and rheumatoid nodules test positive for rheumatoid factor. Furthermore nearly 40% of all patients testing positive for rheumatoid factor have subcutaneous nodules whereas only 6% among those who are rheumatoid factor negative develop rheumatoid nodules.
In patients with RA-associated Felty syndrome, rheumatoid nodules are seen in around 75% patients. These nodules are more common in the white population and affect men more commonly than women.
The severity of the nodule is directly related to joint erosions and other severe features of RA as well as the levels of the rheumatoid factor titre. Rheumatoid nodules have also been seen in 5% to 10% of children with juvenile RA.
Genes and rheumatoid nodules
Genes seem to play a role in the appearance of these nodules. The HLA-DR4 haplotype including the heterogeneous group of DRB1 alleles can predict the risk of subcutaneous nodules in RA.
RA patients who have heterozygosity for HLADRB1 alleles, specifically *0401 with B1*0404/8 or *0101 have a greater risk of rheumatoid nodules.
Homozygosity for HLA-DRB1*0401 also raises the risk of subcutaneous rheumatoid nodules.
Symptoms
The nodules typically develop as a later manifestation of RA. However, nearly 11% of RA patients may present with these nodules at the time of initial diagnosis. These nodules may be seen even before joint involvement is detected.
The nodules are skin colored and may be single or clustered. They may range in size from 2 milimeters to more than 5 cm in diameter. Majority are circular but some may be longitudinal.
The nodules are painless and may feel firm to touch. They may be movable under the skin or may be fixed to underlying structures including bones, tendons etc.
Where do Rheumatoid arthritis nodules appear?
The most commont sites for these nodules are areas that are injured commonly. This includes bony prominences like elbows or sites near the joints, back, heel, scalp, hip prominences, and joints in the foot, the Achilles tendons, ears, penis, and vulva.
Bedbound patients or those in wheelchairs may develop the nodules over the low back or buttocks and those wearing spectacles may develop the nodules on the bridge of the nose.
Rare sites include lungs, pleura (covering of the lungs), pericardium (covering of the heart), peritoneum, tendons, bones, sclera (whites of the eyes), heart, vocal cords, trachea, liver, pancreas, kidney, breast central nervous system, muscles etc.
Appearance under the microscope
The rheumatoid nodules appear in three different stages under the microscope. The initial stage is the acute inflammatory stage followed by the granulomatous stage and a necrotic stage.
In the acute inflammatory stage there is presence of cells of acute inflammation. The features of this stage are similar to that of an evolving scar. As the condition progresses the necrosis or death of the tissues in the central core of the nodules.
Diagnosis and management
Diagnosis of rheumatoid nodules is made clinically. Occasionally laboratory testing are useful to diagnose the condition.
These rheumatoid nodules need to be differentiated from:
- gouty tophi
- subcutaneous granuloma annulare
- fibromas
- xanthomas
- nodular or keloidal scleroderma
- metastatic tumors
- foreign body granulomas
- basal cell carcinoma
- synovial cysts etc.
The rheumatoid nodules are generally benign and cause few complications. However, there is a risk of infections and ulcerations and even gangrene over the nodules leading to their rupture.
These lesions may require surgical removal. It is recommended that nodules are not drained, injected, or excised surgically for cosmetic purposes alone for the risk of infections and recurrence.
The nodules usually improve or resolve with conventional treatment for RA. Reviewed by April Cashin-Garbutt, BA Hons (Cantab)
Further Reading
Machine learning identifies key genes linking rheumatoid arthritis and osteoporosis