Scleroderma.
The prototypic autoimmune diseases involving skin (lupus, dermatomyositis) typically result in epithelial injury and autoantibodies to characteristic cellular antigens. Disease-specific autoantibodies are also found in scleroderma, but scleroderma is different from other cutaneous autoimmune diseases because epithelial injury does not occur. Multiple factors and combinations of factors (immune system, vascular and extracellular matrix abnormalities) are the most likely triggers in an individual with a genetic predisposition to scleroderma. These lead to increased synthesis of normal collagen in skin, lungs and gut in the systemic form of scleroderma, systemic sclerosis. The hypotheses for the pathophysiology of scleroderma are diverse and include abnormal immunologic processes such as cytokine and chemokine dysregulation, abnormal T cell signaling, B cell dysfunction, injury due to autoantibodies to endothelial cells, persistent wound healing condition due to dysregulation of matrix homeostasis, abnormalities in the fibrinolytic system, polymorphisms in critical molecules of the immune system and matrix homeostasis, and microchimerism due to fetal/maternal placental exchange of HLAcompatible cells. Systemic sclerosis/scleroderma is chronic and progressive. To date, no definitive therapy is effective for any of the scleroderma variants, although agents for the vascular dysfunction have some utility. Hematopoietic bone marrow or stem cell transplantation before significant tissue fibrosis has occurred may be the most effective treatment.
Gilliam
Anita C
AC
Department of Dermatology, Case/University Hospitals of Cleveland, Cleveland, Ohio, USA. gilliaa@pamf.org
D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D018925:Chemokines / Q000235:genetics / Q000276:immunology; D046528:Chimerism; D002908:Chronic Disease; D042783:Endothelial Cells / Q000276:immunology / Q000473:pathology; D005109:Extracellular Matrix / Q000235:genetics / Q000276:immunology / Q000473:pathology; D005260:Female; D005331:Fetomaternal Transfusion / Q000235:genetics / Q000276:immunology / Q000473:pathology; D005342:Fibrinolysis / Q000235:genetics / Q000276:immunology; D020022:Genetic Predisposition to Disease; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic / Q000276:immunology; D011247:Pregnancy; D012595:Scleroderma, Systemic / Q000235:genetics* / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D014945:Wound Healing / Q000235:genetics / Q000276:immunology
D018925:Chemokines