Progressive Systemic Sclerosis Scleroderma

Scleroderma is a disease of unknown cause characterized by abnormally increased collagen deposition in the skin. The course is usually slowly progressive and chronically disabling, but it can be rapidly progressive and fatal because of involvement of internal organs. It commonly begins in the third or fourth decade of life, but children are occasionally affected. The prevalence of the disease is one case per 100,000 in the population. Women are affected twice as often as men. There is no racial predisposition.

Scleroderma has been categorized based on the nature and extent of end-organ involvement. Patients with extensive visceral involvement often have widespread skin involvement (progressive systemic sclerosis). In limited scleroderma, skin thickening usually involves the distal extremities and, sometimes, the face and neck. CREST syndrome, which is defined by the presence of soft-tissue calcinosis, Raynaud’s phenomenon, esophageal dysmotility, and telangiectasias, is the major form of limited scleroderma. Morphea is a scleroderma-like cutaneous lesion without visceral involvement.

Sclerosis Scleroderma Immunologic Pathogenesis

Little is definitively known about the pathogenesis of scleroderma. Any pathogenetic scheme must explain the vasomotor instability, microvasculature abnormalities, and accumulation of extracellular matrix that are prominent features of scleroderma. The association of scleroderma with several autoimmune disorders (primary biliary cirrhosis, syndrome, and thyroiditis), the existence of overlap syndromes that have features of both scleroderma and SLE, and the clinical similarities between scleroderma and graft-versus-host disease provide circumstantial evidence for a role for immune mechanisms in the pathogenesis of scleroderma.

Similarly, the presence of autoantibodies to nuclear components in the great majority of patients with scleroderma suggests an abnormality of the immune system. Cell-mediated immune mechanisms, antibodies, and immune complexes have the potential to injure vascular endothelium, and cytokines produced by T cells and macrophages can activate fibroblasts to produce collagen and other matrix components. At present, however, there is little hard evidence that these events are critical in the pathogenesis of scleroderma.

Sclerosis Scleroderma Pathology

Biopsy of clinically involved skin reveals thinning of the epidermis with loss of the rete pegs, atrophy of the dermal appendages, hyalinization and fibrosis of arterioles, and a striking increase of compact collagen fibers in the reticular dermis.
Synovial findings range from an acute lymphocytic infiltration to diffuse fibrosis with relatively little inflammation.

The histologic changes in muscles include interstitial and perivascular inflammatory infiltration followed by fibrosis and myofibrillar necrosis, atrophy, and degeneration.
In patients with renal involvement, the histologic appearance of the kidney is similar to that of malignant hypertensive nephropathy, with intimal proliferation of the interlobular arteries and fibrinoid changes in the intima and media of more distal interlobular arteries and of afferent arterioles.

Collagen deposition is increased in the lamina propria, submucosa, and muscularis of the gastrointestinal tract. Small-vessel changes similar to those that occur in the skin may also result. With loss of normal smooth muscle, the large bowel is subject to development of the characteristic wide-mouthed diverticula and to infiltration of air into the wall of the intestine (pneumatosis cystoides intestinalis).