Systemic scleroderma(also known as progressive systemic sclerosis)is chronic disease with skin involvement and visceral manifestations.
Etiology. The role of viruses, genetic factors causing disturbances in collagen synthesis cannot be
excluded. Abnormal collagen disintegrates quickly and is followed by sclerosis.
The pathogenesis of scleroderma is poorly understood, although vascular endothelial cell damage is believed to trigger the connective tissue overgrowth. Possible mechanisms of endothelial injury include serum cytotoxic factors, cellular or humoral autoimmunity, and toxins Fibroblast proliferation occurs, perhaps by the same mechanisms that cause endothelial injury. T-cell sensitization to collagen and humoral hypersensitivity have been postulated. A variety of autoantibodies are found in scleroderma patients, including antibodies to smooth muscle, rheumatoid factor, and antibodies to nucleolar components.
Pathology. The salient feature in scleroderma is the development of fibrosis in multiple organs. Vascular sclerosis with myxoid change and focal fibrinoid necrosis also are seen.
Skin. Early in the disease, there are edema, perivascular lymphoid infiltrates, and a degenerative change of the dermal collagen. Later, dense dermal sclerosis occurs, with atrophy of the epidermis and adnexal structures. Arterioles may be hyalinized. These changes account for the skin «tightness» that is characteristic of clinical scleroderma.
Castrointestinal tract involvement occurs in about 50% of patients. The lower two-thirds of the esophagus develops fibrosis of the submucosal muscularis, with associated motility dysfunction. Fibrosis also may be
seen in the small bowel and colon, with similar associated motility problems.
Kidney involvement is characterized by slowly progressive, interlobular arterial intimal proliferation and periarterial fibrosis, which may be clinically silent. However, acute collapse of renal blood flow, with consequent renal cortical ischemia and malignant hypertension, can be associated with fibrinoid necrosis of the microvasculature and result in acute renal failure (the leading cause of death in scleroderma patients). Cortical necrosis may develop when the vessels of the kidneys are involved. It manifests by acute renal failure, termed «true sclerodermic kidney».
Lung. The picture is very similar to the one for idiopathic pulmonary fibrosis with diffuse interstitial fibrosis. Variable thickening of the pufmonary vessels also is seen.
Musculoskeletal system. Joints may show a nonerosive mildly inflammatory synovitis. Tendon sheath involvement is not unusual, with carpal tunnel syndrome as a possible outcome. In skeletal muscle, edema and perivascular mononuclear inflammation appear early. In more established disease, interfascicular fibrosis has occurred.
Development of large-focus cardiosclerosis, and subpleural cavities (basal pneumosclerosis) are possible.
The complications and the causes of death depend on the visceral lesions (kidneys, heart, lungs).