The subcutaneous nodule: Its significance in the diagnosis of rheumatic disease

Summary A wide variety of cutaneous and subcutaneous nodules are seen clinically. By far the most common of these is the rheumatoid granuloma, occurring at pressure points in patients with rheumatoid arthritis. These nodules are often of long duration and generally imply severe disease. In contrast, the now uncommon rheumatic nodule is transient and does not manifest the typical trizonal architecture of central necrosis, palisading histiocytes, and surrounding fibrosis, so typical of the rheumatoid nodules. The rheumatic nodule does not correlate with severity of arthritis in rheumatic fever but is strongly associated with cardiac involvement. The rheumatoid variant arthritides are not associated with nodules, although rare patients with nodules have been reported. Patients with systemic lupus erythematosus and Jaccoud arthritis may develop typical rheumatoid nodules. It is claimed that the nodules of juvenile rheumatoid arthritis more closely resemble the rheumatic nodule than the rheumatoid nodule. Numerous reports of children without arthritis describe subcutaneous nodules with histology identical to the rheumatoid nodule. These are known as pseudorheumatoid nodules. They do not precede the onset of arthritis and are probably part of the spectrum of granuloma annulare. Necrobiosis lipoidica diabeticorum likewise shares a very similar histology with the rheumatoid nodule. The subcutaneous adiposa is the site of numerous inflammatory nodules that can be grouped together under panniculitis. In erythema nodosum, nodular panniculitis (Weber-Christian disease), lupus profundus, and the nonsystemic cutaneous vasculitides, angiitis plays a prominent role in the pathogenesis. Pancreatic disease in which direct enzymatic cytolysis occurs is an exception to this rule. The skin manifestations of the systemic angiitides are diverse, and nodules are among the least common of the dermal manifestations, with the exception of the frequent eruptions in Behcet disease. Gout, amyloidosis, and hypercholesterolemia represent metabolic disorders in which normal body materials accumulate in excess, with resultant nodular deposition in cutaneous tissue and in or around joints (tendons). The tophus can closely mimic the rheumatoid nodule clinically. Likewise, the nodules and arthropathy of amyloidosis have been confused with rheumatoid disease. Only two storage diseases, multicentric reticulohistiocytosis and Farber disease, cause both subcutaneous nodules and arthritis. The bacterial pathogens producing nodules and arthritis include the treponemal organisms, syphilis, yaws, and pinta, as well as leprosy. Erythema nodosum leprosum is probably an immune complex-mediated reaction. Among the fungi, coccidioidomycosis is a well-described cause of erythema nodosum and arthritis. Disseminated sporotricosis rarely produces juxtaarticular nodules and arthritis. Of the viruses associated with arthritis only the hepatitis B virus has been documented to produce both arthritis and subcutaneous nodules. This uncommon association may also represent an immune complex-mediated phenomenon. Finally, such miscellaneous conditions as osteoarthritis and Dupuytren contracture are common causes of nodular disease which can be clinically confusing to the uninitiated.