A rheumatoid nodule is a lump of tissue, or an area of swelling, that appears on the exterior of the skin usually around the olecranon (tip of the elbow) or the interphalangeal joints (finger knuckles), but can appear in other areas. There are four different types of rheumatoid nodules: subcutaneous rheumatoid nodules, cardiac nodules, pulmonary nodules, and central nervous systems nodules. These nodules occur almost exclusively in association with rheumatoid arthritis. Very rarely do rheumatoid nodules occur as rheumatoid nodulosis (multiple nodules on the hands or other areas) in the absence of rheumatoid arthritis. Rheumatoid nodules can also appear in areas of the body other than the skin. Less commonly they occur in the lining of the lungs or other internal organs. The occurrence of nodules in the lungs of miners exposed to silica dust was known as Caplan’s syndrome. Rarely, the nodules occur at diverse sites on body (e.g., upper eyelid, distal region of the soles of the feet, vulva, and internally in the gallbladder, lung, heart valves, larynx, and spine). Rheumatoid nodules can vary in size from 2 mm to 5 cm and are usually rather firm to the touch. Quite often they are associated with synovial pockets or bursae. About 5% of people with rheumatoid arthritis have such nodules within two years of disease onset, and the cumulative prevalence is about 20–30%. Risk factors of developing rheumatoid nodules include as smoking and trauma to small vessels. In the majority of the time, nodules are not painful or disabling in any way. They are usually more of an unsightly nuisance. However, rheumatoid nodules can become painful when infection or ulcers occur on the skin of the nodule. Some nodules may disappear over time, but other may grow larger, making nodular size difficult to predict. Treatment of rheumatoid nodules can be quite difficult, but both surgical removal and injection of corticosteroids have shown good results.
Pathophysiology Although the exact process is unknown, there are a few hypotheses for the generation of rheumatoid nodules. It has been observed that rheumatoid nodules frequently form over extensor sites and areas vulnerable to trauma. The trauma causes inflammatory particles to build up and leads to a secondary inflammatory response which ultimately causes fibrin release and necrosis. Another hypothesis suggests that the inflammation of blood vessels activates complement components, which leads to the deposit of rheumatoid factors and fibrin. The rheumatoid nodule is the most common cutaneous manifestation of rheumatoid arthritis. Rheumatoid arthritis involves chronic inflammation of synovial membranes, which leads to degradation of articular cartilage and the juxta-articular bone. Inflammation is caused by T cells, B cells, and monocytes when endothelial cells are activated. Neovascularization, the growth of new blood vessels, serves as an additional marker for rheumatoid arthritis. A hyperplastic synovial lining layer can be caused by the expansion of synovial fibroblast and macrophage cells. This expansion of the synovial membrane, sometimes referred to as "pannus", can lead to bony erosions and cartilage degradation at the site of the cartilage-bone junction in the periarticular bone. The cause of rheumatoid arthritis is unknown. It is speculated that both genetic and environmental factors contribute to the development of rheumatoid arthritis. Gene loci and antigens, such as HLA class II antigens, have been seen as closely associated with rheumatoid arthritis. Environmental risk factors include smoking, periodontitis, viral infections, and gut, mouth, and lung microbiomes. Researchers have noted that Prevotella species, which are expanded in the gastrointestinal tract in early RA, and Porphyromonas gingivalis, which is associated with periodontitis, may have a role in pathogenesis.
Pathology Histological examination of nodules shows that they consist of a shell of fibrous tissue surrounding a center of fibrinoid necrosis. Pea-sized nodules have one center. Larger nodules tend to be multilocular, with many separate shells or with connections between the necrotic centers. Individual necrotic centers may contain a cleft or several centers of necrosis may all open on to a large bursal pocket containing synovial fluid. The boundary between the necrotic center and the outer fibrous shell is made up of the characteristic feature of the nodule, which is known as a cellular palisade. The palisade is a densely packed layer of macrophages and fibroblasts which tend to be arranged radially, like the seeds of a kiwifruit or fig. Further out into the fibrous shell there is a zone that contains T cells and plasma cells in association with blood vessels. The histology of pulmonary nodules are similar to that of subcutaneous nodules, with central necrosis surrounded by palisading macrophages and inflammatory infiltrate.
Risk factors Rheumatoid nodules develop if a person currently has rheumatoid arthritis. However, not all people with rheumatoid arthritis develop rheumatoid nodules. Some risk factors for rheumatoid nodules for people with rheumatoid arthritis may include:
Smoking (strong association) Elevated levels of serum rheumatoid factors HLA-DRB1 gene (weak association) Trauma to small vessels Having severe rheumatoid arthritis Taking Methotrexate over other arthritis drugs
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