Scleroderma

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.

The Different Types of Scleroderma

The group of diseases known as scleroderma fall into 2 main classes: localized and systemic

• Localized Scleroderma affect only certain parts of the body.

• Systemic Scleroderma, or Systemic Sclerosis, can affect the whole body.

• Both groups include subgroups which may be broken down or referred to in different ways.

Common Classifications of Scleroderma

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.

Localized SclerodermaMorphea

• First signs of this form of the disease are reddish patches of skin that thicken into firm, oval-shaped areas.

• The center of each patch becomes ivory colored with violet borders, and they sweat very little and have little hair growth.

• Patches appear most often on the chest, stomach, and back, and sometimes, appear on the face, arms, and legs.

Localized SclerodermaLinear Scleroderma

• Signs of this condition are characterized by a single line or bands of thickened or abnormally colored skin.

• Usually, the line runs down an arm or leg, but in some people it runs down the forehead, and may also involve muscle or bone.

• The French term en coup de sabre, or “sword stroke” is sometimes used to describe this highly visible line.

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 Cutaneous Scleroderma

• Typically comes on gradually and affects the skin only in certain areas: the fingers, hands, face, lower arms, and legs.

• People with this form often have all or some of the symptoms that some doctors call CREST. Because of the predominance of CREST symptoms in people with limited systemic scleroderma, many use the term CREST syndrome to refer to this form of the disease.

• CREST syndrome is an acronym for a collection of symptoms that occur to some degree in all people with systemic sclerosis.

• Symptoms include: Calcinosis, Raynaud’s phenomenon, Esophageal dysfunction, Sclerodactyly, and Telangiectasia.

• Most people experience Raynaud’s phenomenon for years before skin thickening starts, followed by Telangiectasia and Calcinosis.

• Gastrointestinal involvement also commonly occurs, as well as severe lung problems, even if the skin thickening remains limited.

Systemic Scleroderma Limited Scleroderma/CREST Syndrome

CalcinosisCalcinosis: 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.

Raynaud’s PhenomenonRaynaud’s 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.

Systemic Scleroderma Diffuse Cutaneous Scleroderma

• Typically comes on suddenly and begins with skin thickening on hands that spreads quickly and over much of the body, affecting the hands, face, upper arms, upper legs, chest, and stomach in a symmetrical fashion.

• Diffuse form may also cause damage to internal organs such as the intestines, lungs, heart, and kidneys. This can become severe and even life-threatening.

• After the first 3-5 years, people often enter a stable phase lasting for varying lengths of time, and during this phase, many of the symptoms will subside.

• Diffuse scleroderma can overlap with other autoimmune diseases, including systemic lupus erythematosus and polymyositis. In such cases, this is referred to as mixed connective disease.

What Causes Scleroderma?

• The exact cause of scleroderma is still unknown, but evidence shows that the disease may be caused by a number of genetic abnormalities which are triggered by environmental factors. Factors can lead to immunological disturbances and vascular changes.

• Microchimerism has also been proposed as a cause of scleroderma in which fetal cells are left in the mother’s body after giving birth. This theory arose from the fact that the disease occurs mostly in women of child-bearing age, and symptoms resemble those of graft-versus-host disease (GVHD) which occurs in bone marrow transplant patients who have received cells from another person.

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 sclerosis–related deaths. Lung fibrosis and heart changes are responsible for 9% of systemic sclerosis–related 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.