What is Scleroderma? (AKA "The Big S")

Scleroderma (sklere-o-DUR-muh) is a group of rare, progressive diseases characterized by fibrosis (or hardening), vascular alterations, and autoantibodies. Scleroderma is a chronic, degenerative, autoimmune disorder that leads to the over-production of collagen in the body's connective tissue. The word "scleroderma" means "hardening of the skin" and refers the hardening and tightening of the skin and connective tissues (the fibers that provide the framework and support for your body) which is one of the possible physical effects of the disease.

Approximately 300,000 people in the U.S. have scleroderma. Women are affected three times as often as men. Although the disease can develop at any age, it most frequently appears in the third to fifth decades of life. It is most frequently a chronic and often progressive illness.

Collagen, a protein manufactured by the connective tissues of the body, is produced in excess in someone suffering with scleroderma. This over-production of collagen can be likened to the process of "scarring," which is the way the body heals a wound. For persons with scleroderma, the production of collagen is abnormal, depositing it in various organs and/or tissues of the body, especially in layers of the skin.

There are two forms of scleroderma: localized and generalized (also called systemic sclerosis).


Localized Scleroderma affects mainly the skin in different areas of the body, may affect muscles and bone but does not affect internal organs and is not usually as severe as generalized scleroderma

Generalized Scleroderma (otherwise known as Systemic Sclerosis) affects the skin and/or internal body parts, such as blood vessels, the digestive system (esophagus, stomach, and bowel), the heart, lungs, kidneys, muscles, and joints. Systemic Sclerosis Scleroderma most often presents as either Limited or diffuse scleroderma.

Limited scleroderma mainly affect the hands, arms and face. Previously called CREST syndrome in reference to the following complications: Calcinosis, Raynaud's phenomenon, Esophageal dysfunction, Sclerodactyly, and Telangiectasias. Additionally, pulmonary arterial hypertension may occur in up to one third of patients and is the most serious complication for this form of scleroderma.

Diffuse systemic sclerosis/scleroderma is rapidly progressing and affects a large area of the skin and one or more internal organs, frequently the kidneys, esophagus, heart and lungs. This form of scleroderma can be quite disabling. There are no treatments for scleroderma itself, but individual organ system complications are treated

Other forms of scleroderma include;  Systemic sine scleroderma, which lacks skin changes, but has systemic manifestations, chemically induced localized scleroderma, eosinophilic myalgia syndrome (a disorder caused by the ingestion of L-tryptophan), toxic oil syndrome (associated with contaminated oil), and graft-versus-host disease.


The cause is unknown. Scleroderma runs in families, but the genes have not been identified. It affects the small blood vessels known as arterioles, in all organs. First, the endothelial cells of the arteriole die off, along with smooth muscle cells, by a process of apoptosis. They are replaced by collagen and other fibrous material. Inflammatory cells, particularly CD4+ helper T cells, infiltrate the arteriole, and cause further damage. Many of the inflammatory and destructive protein signals have been identified, and they are potential targets for drugs that could interrupt the process

Effects Of Scleroderma On The Body:


Scleroderma in the skin may cause the cessation of hair growth and sweating; and the tightening and thinning of skin over the knuckles or finger joints, resulting in ulcers (open sores) and curving of the digits.
Scleroderma in the kidney may cause severe hypertension (high blood pressure) and kidney failure.

Scleroderma in the gastrointestinal tract hampers the action of the smooth muscle that lines the esophagus, small intestine, and colon; resulting in swallowing difficulties, malabsorption of digested food into the circulation, severe constipation and/or possible intestinal obstruction.

Scleroderma in the lung makes the lungs less flexible and reduces their blood supply resulting in shortness of breath, susceptibility to bronchial problems, and pulmonary fibrosis (scarring and thickening of lung tissue).

Scleroderma in the heart and pericardium (fibrous sac that lines the heart) restricts the normal pulsation and pumping of the blood by encasing the heart in a shell of sclerosed tissue. This may lead to heart failure.

Scleroderma in the joints causes arthritic symptoms such as inflammation, pain, swelling, stiffness, redness, and, in some cases, joint deformity.
 
Symptoms and Complications:


Raynauds

Raynaud's phenomenon is often the first sign of the scleroderma disease process. With this condition, small blood vessels narrow in the fingers, toes, ears, and even the nose.

Attacks of Raynaud's phenomenon can occur several times a day, and are often brought on or worsened by exposure to cold. Warmth relieves these attacks. In severe cases, attacks can develop regardless of the temperature. Severe cases may also cause open sores or damage to the skin and bones, if the circulation is cut off for too long. Stress also can trigger the syndrome.

Typically, the fingers go through three color changes:
•First, they become very pale.

•As the blood flow is cut off, they turn a bluish color, usually in the top two sections of the second and third fingers.

•Finally, when blood flow returns, the fingers become red.

Tingling and pain can occur in the affected regions.

Raynaud's is very common and occurs in 3 - 5% of the general population. It's important to note that more than 80% of patients with Raynaud's phenomenon do not have scleroderma, lupus, rheumatoid arthritis, or other serious illnesses. Raynaud's is more likely to be a symptom of scleroderma or some other connective tissue disease if it develops after age 30, if it is severe, and if it is accompanied by other symptoms (such as skin changes and arthritis).

Skin Changes

Course of Typical Skin Changes. The primary symptoms of scleroderma occur in the skin. They often take the following course:

•Typically, pitted scars appear first on the hands. The skin begins to thicken and harden on the hands, feet, and face. The fingers may swell. This condition is called sclerodactylia or acrosclerosis. Patients with diffuse scleroderma may have swelling of the whole hand before the skin significantly thickens.

•Thickened or hardened patches may also develop on other areas of the body. (Their appearance on the trunk and near the elbows or knees tends to be a sign of a more severe condition.)

•For the first 2 or 3 years, the skin continues to thicken and feel puffy.

•This process then stops, and can even get better. The skin may soften.

•As the disease progresses further, however, the skin loses its ability to stretch, and becomes shiny as it tightens across the underlying bone, particularly in the fingers, toes, and around the mouth.

•Eventually, in severe cases, the fingers may lose the ability to move, and can be difficult to bend. The hands and feet may curl from the tightness of the skin. It may be difficult to open the mouth widely.

•Flat red marks, known as telangiectasis, may appear in various locations, usually the face, palms, lips, or the inside of the mouth.

•In calcinosis, small white lumps form beneath the skin, sometimes oozing a white substance that looks like toothpaste. Calcinosis can lead to infections.

•Small blood vessels at the base of the fingernails may be severely narrowed in some places, and may widen in other places. This is an indication that internal organs might be involved.

•The entire surface of the skin may get darker over time, and contain patches of abnormally pale skin.

•Hair loss may occur.

•About 1% of patients have Sj√∂gren syndrome, a group of symptoms that include dry eyes and dry mucus membranes (such as those in the mouth).

•Inside the mouth, scleroderma can also cause changes that impair gum healing.

Sclerodactly


Bone and Muscle Symptoms

Changes in bones, joints, and muscles can cause the following symptoms:

•Mild arthritis. The condition is usually distributed equally on both sides of the body.

•Bone loss in the fingers. The destruction is not as severe as it is in rheumatoid arthritis, although the fingers may shorten over time.

•Trouble bending the fingers, if the disease has affected the tendons and joints.

•Muscle weakness may occur, especially near the shoulder and hip.

Digestive Tract Symptoms and Complications

Complications in the Upper Digestive Tract.

•Esophageal motility disorder develops when scarring in the muscles of the esophagus causes them to lose the ability to contract normally, resulting in trouble swallowing, heartburn, and gastroesophageal reflux (also known as GERD). Some experts believe that patients with severe GERD may aspirate (breathe in) tiny amounts of stomach acid, which in turn may be a major cause of lung scarring.

•About 80% of patients also experience impaired stomach activity. A delay in stomach emptying is very common.

•Some patients develop "watermelon stomach" (medically referred to as CAVE syndrome), in which the stomach develops red-streaked areas from widened blood vessels. This causes a slow bleeding that can lead to anemia (low red blood cell counts) over time.

•There may be a higher risk for stomach cancer.

•Problems with movement of the food (motility) through the intestines also develop. Patients may experience an increase in bacteria levels in their intestines as a result, and have trouble absorbing nutrients from foods through their intestines.

Complications in the Lower Digestive Tract. Complications in the lower digestive tract are uncommon. If they do occur, they can include the following:
•Scarring can cause blockages and constipation. In rare cases, constipation can become so severe that the bowel develops holes or tears, conditions that can be life threatening.

•Scarring can also interfere with the absorption of fats in the intestines. This can lead to an increase in the number of bacteria in the lower intestines, which can cause watery diarrhea.

•Fecal incontinence (the inability to control bowel movements) may be more common than studies indicate, because patients are reluctant to report it.

Many patients, however, have few or even no lower gastrointestinal symptoms.

Lung Symptoms and Complications

In severe cases, the lungs may be affected, causing shortness of breath or difficulty in taking deep breaths. Shortness of breath may be a symptom of pulmonary hypertension, an uncommon but life-threatening complication of systemic scleroderma.

Respiratory system
Lung problems are usually the most serious complications of systemic scleroderma. They are now the leading cause of death in scleroderma patients. Two major lung conditions associated with scleroderma, pulmonary fibrosis and pulmonary hypertension, can occur either together or independently.

Interstitial Pulmonary Fibrosis. Scleroderma involving the lung causes scarring (pulmonary fibrosis). Pulmonary fibrosis occurs in about 70% of scleroderma patients, although its progression is very slow and patients have a wide range of symptoms:

•When pulmonary fibrosis progresses, patients develop a dry cough, shortness of breath, and reduced ability to exercise.

•Severe pulmonary fibrosis occurs in about 16% of patients with diffuse scleroderma. About half of these patients experience the most profound changes within the first 3 years of diagnosis. In such cases, lung function worsens rapidly over that period, and then the progression slows down.

Pulmonary fibrosis also places the patient at higher risk for lung cancer. This condition may be due to severe dysfunction in the esophagus, which causes patients to aspirate tiny amounts of stomach acid.

The most important indication of future worsening in the lungs appears to be inflammation in the small airways (alveolitis). Doctors detect alveolitis by using a lung test called bronchoalveolar lavage.
Pulmonary hypertension is the narrowing of the pulmonary arteries in the lung. The narrowing of the arteries creates resistance and increases the workload of the heart. The heart becomes enlarged from pumping blood against the resistance. Some symptoms include chest pain, weakness, shortness of breath, and fatigue. The goal of treatment is to control the symptoms, although the disease usually develops into congestive heart failure.

Pulmonary Hypertension. Pulmonary hypertension is the narrowing of the pulmonary arteries in the lung. The narrowing of the arteries creates resistance to blood flow and increases the workload of the heart. The heart becomes enlarged from pumping blood against this resistance. Some symptoms of pulmonary hypertension include shortness of breath, chest pain, weakness, and fatigue. Shortness of breath,the primary symptom of pulmonary hypertension, worsens over time. The goal of treatment is to control the symptoms, although the disease usually develops into congestive heart failure.

Pulmonary hypertension can develop in one of two ways:
•As a complication of pulmonary fibrosis

•As a direct outcome of the scleroderma process itself. In this case, it is most likely to develop in patients with limited scleroderma after many years.

Kidney Symptoms and Complications

Signs of kidney problems, such as increased levels of protein in the urine and mild high blood pressure (hypertension), are common in scleroderma. As with pulmonary hypertension, the degree of severity depends on whether the kidney problems are acute or chronic.

Slow Progression. The typical course of kidney involvement in scleroderma is a slow progression that may produce some damage but does not usually lead to kidney failure.

Renal Crisis. The most serious kidney complication in scleroderma is renal crisis. It is a rare event that occurs in a small number of patients with diffuse scleroderma, most often early in the course of the disease. This syndrome includes a life-threatening condition called malignant hypertension, a sudden increase in blood pressure that can cause rapid kidney failure. This condition may be fatal. However, if the condition is successfully treated, it rarely recurs.

Until recently, renal crisis was the most common cause of death in scleroderma. Aggressive treatment with drugs that lower blood pressure, particularly those known as ACE inhibitors, is proving to be successful in reducing this risk.

Heart Symptoms and Complications

Many patients with even limited scleroderma have some sort of functional heart problem, although severe complications are uncommon and occur in only about 15% of patients with diffuse scleroderma. As with other serious organ complications, they are more likely to occur within 3 years after the disease begins.
Fibrosis of the Heart. The most direct effect of scleroderma on the heart is fibrosis (scarring). It may be very mild or it can cause pain, low blood pressure, or other complications. By damaging muscle tissue, the scarring increases the risk for heart rhythm problems, problems in electrical conduction, and heart failure. The membrane around the heart can become inflamed, causing a condition called pericarditis.

Pericarditis

Pulmonary hypertension and hypertension associated with kidney problems in scleroderma can also affect the heart.
Other Symptoms and Complications

•Patients with CREST may be at increased risk for biliary cirrhosis, an inflammatory autoimmune disorder of the liver.

•Nerve damage may occur in the extremities (legs and feet, arms and fingers), causing numbness and pain. This damage can progressively worsen and lead to severe open sores (ulcerations), particularly in the hands. The feet are less often affected, but when they are, the disease tends to affect the joints and cause pain.

•Bone loss (osteoporosis) can occur because of impaired blood flow.

•About half of scleroderma patients develop underactive thyroid gland (hypothyroidism).
Hypothyroidism

•Erectile dysfunction, usually due to scarring of the penis, may be one of the first complications of the disease in men.

•Systemic scleroderma does not generally affect fertility in women. Pregnant women with scleroderma, however, have a slightly increased risk of premature birth and low-birth-weight babies. Although they can carry a baby to term, because complications such as kidney crisis can occur with the disease, pregnant women with scleroderma need to be monitored closely in a high-risk obstetric facility.

•More than half of scleroderma patients are likely to experience significant depression. Researchers say it may be beneficial for scleroderma patients to be routinely screened for depression.Currently, there is no cure for scleroderma and treatment involves alleviating specific symptoms associated with scleroderma.