Presented By
Carrie Shufran
What is Scleroderma?
Derived from Greek words skleros, meaning hard, and derma, meaning skin. Literally means hard skin. A chronic autoimmune connective tissue disease that may have multi-organ involvement when systemic and has an unpredictable course that affects the circulation and blood vessels; causing inflammation and autoimmunity; and results in fibrosis (scarring) on the skin, lungs, and other organs. Characterized by alterations of the microvasculature, disturbances of the immune system and by massive deposition of collagen and other matrix substances in the connective tissue. Scleroderma is often referred to as a single disease, but really a symptom of a group of diseases involving the abnormal growth of connective tissue, which supports the skin and internal organs.
What is Scleroderma?
Scleroderma is both a rheumatic disease and a connective tissue disease: Rheumatic disease refers to a group of conditions characterized by inflammation or pain in the muscles, joints, or fibrous tissue. Connective tissue disease is one that affects tissues such as skin, tendons, and cartilage.
Localized Scleroderma
Localized Scleroderma is limited to the skin and related tissues and, in some cases, the muscle below. Internal organs are not affected, and usually, the localized form never progresses to the systemic form of the disease. Localized conditions often go away on their own over time, but damage can be permanent.
Localized Scleroderma
Generally, there are two recognized types of Localized Scleroderma: Morphea-refers to local patches of scleroderma which can be either localized, limiting itself to one or several patches, or generalized, where the skin patches spread over larger areas of the body. Linear Scleroderma-refers to a form of the condition characterized by a single line or band of thickened or abnormally colored skin.
Systemic Scleroderma
Systemic Sclerosis is the form of the disease that not only includes the skin, but also involves the tissues beneath, the blood vessels, and the major organs. Generally, this form of the disease is broken down into two major types: Limited Cutaneous Scleroderma and Diffuse Cutaneous Scleroderma. Sometimes, it is also broken down into a third subset called Systemic Sclerosis Sine in which patients do not have any overt skin thickening, but show other manifestations of the disease.
Systemic Scleroderma
Limited Scleroderma/CREST Syndrome
Calcinosis
Calcinosis: Formation of calcium deposits in the connective tissues, which can be detected by x-ray. Deposits are typically found on the fingers, hands, face, and trunk and on the skin above elbows and knees. When the deposits break through the skin, painful ulcers can result.
Raynauds Phenomenon
Raynauds phenomenon: Condition in which the small blood vessels of the hands or feet contract in response to cold or anxiety. As the vessels contract, the hands or feet turn white and cold, then blue. As blood flow returns, they become red. Fingertip tissues may suffer damage, leading to ulcers, scars, or gangrene.
Esophageal Dysfunction
Esophageal dysfunction: Impaired function of the esophagus that occurs when smooth muscles in the esophagus lose normal movement. In the upper and lower esophagus, the result can be difficulties in swallowing. In the lower esophagus, the result can be chronic heartburn and inflammation, or other symptoms of gastroesophageal reflux disorder (GERD) .
Sclerodactyly
Sclerodactyly: Thickened and tight skin on the fingers, resulting from deposits of excess collagen within skin layers. The condition makes it harder to bend or even straighten the fingers. The skin may also appear shiny and darkened, with hair loss. The abnormal build-up of fibrous tissue in the skin can cause the skin to tighten so severely that the fingers curl and lose their motility.
Telangiectasia
Telangiectasia: A condition caused by the swelling of tiny blood vessels, in which small red spots appear on the hands, face, and tongue. Although not painful, these red spots can create cosmetic problems.
Pathophysiology
As stated before, different factors, including genetic, environmental, vascular, autoimmunologic, and microchimeric factors are involved in systemic sclerosis pathogenesis. One theory states that antigens from the human leukocyte antigen (HLA) histocompatability complex, including HLA-B8, HLA-DR5, HLA-DR3, HLA-DR52, and HLA-DQB2, are involved in systemic sclerosis. Some data suggest that apoptosis and the generation of free radicals may also be involved in the pathogenesis of systemic sclerosis. Fibrosis can be caused by profibrotic cytokines, including transforming growth factor-beta (TGF-beta), interleukin-4 (IL-4), platelet-derived growth factor (PDGF), and connective-tissue growth factor. The vasculopathy may be linked to TGF-beta and PDGF, while the diminishing of lesional cutaneous blood vessels can be attributed to antiendothelial cell autoantibodies. The activation of the immune system is of great importance in the pathogenesis of systemic sclerosis. Antigen-activated T cells, activated infiltrate early, infiltrate the skin, and produce the profibrotic cytokine IL-4. B cells may also contribute to fibrosis, as deficiency of CD19, a B-cell transduction molecule, which results in decreased fibrosis in animal models.
Pathophysiology
Epidemiology
Frequency United States-Systemic sclerosis is a rare disease. Systemic sclerosis is diagnosed in approximately 67 male patients and 265 female patients per 100,000 people each year. International-Systemic sclerosis is estimated to occur in 2.3-10 people per 1 million. Systemic sclerosis is rare in the resident population of Japan and China. Mortality/Morbidity The mortality rate is increasing in the United States and Europe; as many as 3.08 persons are affected per 1 million. Generally, renal and lung changes are responsible for death in patients with systemic sclerosis. Pulmonary hypertension leads to 12% of systemic sclerosisrelated deaths. Lung fibrosis and heart changes are responsible for 9% of systemic sclerosisrelated deaths. Race No apparent racial predominance exists. However, systemic sclerosis is rare in the resident population of Japan and China. Diffuse systemic sclerosis (dSSc) occurs more often in black women than in caucasian women. Sex Overall, a substantial female predominance exists, with a female-to-male ratio of 3-6:1. However, dSSc occurs equally in males and females. The limited form of systemic sclerosis (lSSc) has a strong female predominance, with a female-to-male ratio of 10:1. Another analysis showed that men tend to have diffuse disease and women to have calcinosis. Age Systemic sclerosis usually appears in women aged 30-40 years, and it occurs in slightly older men. In approximately 85% of cases, systemic sclerosis develops in individuals aged 20-60 years. Cases also are observed in children and in the elderly population.