Overlapping syndromes, undifferentiated connective tissue disease, and other fibrosing conditions

Abstract

Connective tissue diseases (CTDs) frequently present with one or only a few symptoms, which does not allow prompt diagnosis. Raynaud's phenomenon is one of those symptoms. However, only a minority of patients who present with Raynaud's phenomenon develop a CTD. Prognostic factors for the future development of CTD in such patients are older age at presentation, more severe Raynaud's phenomenon, the presence of antinuclear antibodies, and abnormal patterns on nailfold capillary microscopy. Some patients have overlapping symptoms of various CTDs. Mixed connective tissue disease (MCTD) is the prototype of such an overlapping syndrome. However, during follow-up, most patients with MCTD develop a specific CTD, either scleroderma, systemic lupus erythematosus, rheumatoid arthritis, or combinations of those illnesses. Primary pulmonary hypertension is one of the leading causes of death in MCTD. Its treatment is insufficient, although continuous prostacyclin infusion may provide some relief. New therapies such as nitric oxide and combined heart-lung transplantation in an early stage should be explored. The autoimmune response to small nuclear ribonucleoproteins, which is highly characteristic for MCTD, interestingly shows cross-reactivity with retroviral antigens, and the cooccurrence of human T cell lymphotropic virus type I and HIV infection with MCTD has been reported. This suggests that those viruses, possibly by molecular mimicry, play a role in the induction of the disease. Fibrotic conditions related to silicone exposure still evoke much interest. However, most recent data do not substantiate a role for silicone gel breast implants in the development of autoimmune CTDs.