EXTRA-ARTICULAR MANIFESTATIONS

Rheumatoid arthritis is a systemic illness, not just a disease of the joints, and thus has a variety of nonarticular, or extra-articular, manifestations (see Plates 5-6 and 5-7). Some of these features are occult, with little clinical importance, but others are clinically significant. In some cases, extra-articular features are the dominant clinical signs.

Rheumatoid inflammation may be nodular or diffuse and may occur in parenchyma and connective tissues throughout the body. It therefore produces a variety of pathologic lesions in many locations. The inflammation of the nonarticular connective tissue has the same characteristics as the synovitis: it is a proliferative inflammatory reaction containing lymphocytes, macrophages, and plasma cells. The lymphocytes often cluster in a follicular pattern.

Rheumatoid Nodules. In about 15% of cases, nodules develop in connective tissue along tendons, at tendon sheaths, in bursa and joint capsules, and in the subcutaneous connective tissue around bony prominences (see Plate 5-6). A common place for nodules to occur is a few centimeters distal to the olecranon process of the ulna. The nodules in subcutaneous tissue are freely movable, whereas those that originate in the periosteum are firmly attached to the underlying bone. Rheumatoid nodules occur singly or in aggregate in clusters, and they vary from 1 mm to more than 2 cm in diameter.

When surrounded by soft tissue, rheumatoid nodules are painless, but nodules located over bony prominences are often painful when pressure is exerted on them. For example, nodules around the ischial tuberosity cause pain when the patient sits on a firm seat and nodules over spinous processes or the occipital protuberance make lying supine on a firm surface painful. Similarly, those occurring on the plantar surface of the foot cause discomfort when standing or walking. Nodules located over the knuckles, toes, or knees may restrict motion in the underlying joint.

The presence of rheumatoid nodules greatly aids in the diagnosis of rheumatoid arthritis because they occur with no other form of chronic arthritis. However, nodular swellings near joints and along the border of the ulna are associated with other illnesses (e.g., urate deposits, or tophi, in gout). If the nature of the nodular swelling and the diagnosis of rheumatoid arthritis is not clear, excision and microscopic study of the tissue is advised. Characteristic histopathologic features of rheumatoid nodules are (1) a central zone of fibrinoid degeneration surrounded by (2) an intermediate zone of palisading epithelioid cells and (3) an outer coat of granulation tissue infiltrated with lymphocytes and plasma cells.

Pulmonary Involvement. Rheumatoid nodules may develop in the parenchyma of the lung (see Plate 5-6). On radiographs, a solitary nodule often cannot be differentiated from a neoplasm, nodules are generally located in subpleural areas or in association with interlobular septa, but histologic study of the lesion reveals the pathologic features of a rheumatoid nodule. Medications such as methotrexate can cause pulmonary nodules, which are usually located in the middle zones of the lungs. TNF-α inhibitors, used to treat rheumatoid arthritis, can rarely cause lung nodules. Other parenchymal lung diseases (e.g., interstitial fibrosis, pulmonary nodules, and bronchiolitis obliterans/organizing pneumonia) can occur. Caplan syndrome is a unique form of pneumoconiosis that may be a granulomatous response to chronic exposure to silica dust. It is especially prevalent in coal miners. Widely distributed and particularly prevalent in the periphery, the nodules usually appear abruptly, with little or no evidence of prior pneumoconiosis. They may occur before, during, or after the onset of arthritis. Patients with Caplan syndrome usually have a high serum titer of rheumatoid factor. Progressive interstitial fibrosis and pleurisy with or without effusion are other pulmonary manifestations of rheumatic disease.