Scleroderma (sklere-o-DER-muh) is a rare, progressive disease that leads to hardening and tightening of the skin and connective tissues the fibers that provide the framework and support for your body. Scleroderma usually starts with a few dry patches of skin on the hands or face that begin getting thicker and harder. These patches then spread to other areas of the skin. In fact, scleroderma literally means “hard skin.”
Scleroderma is a chronic disease characterized by excessive deposits of collagen in the skin or other organs. The localized type of the disease, while disabling, tends not to be fatal. The systemic type or systemic sclerosis, the generalized type of the disease, can be fatal as a result of heart, kidney, lung or intestinal damage
In some cases, scleroderma also affects the blood vessels and internal organs. Scleroderma is one of a group of arthritic conditions called connective tissue disorders. In these disorders, a person’s antibodies are directed against his or her own tissues.
Researchers haven’t established a definitive cause for scleroderma. It’s more common in women than in men and more common in adults than in children. Scleroderma can run in families, but in most cases it occurs without any known family tendency for the disease. Scleroderma isn’t considered contagious or cancerous, but this chronic condition can greatly affect self-esteem and the ability to accomplish everyday tasks.
Scleroderma affects the skin, and in more serious cases it can affect the blood vessels and internal organs. The most evident symptom is usually the hardening of the skin and associated scarring. The skin may appear tight, reddish or scaly. Blood vessels may also be more visible. Where large areas are affected, fat and muscle wastage may weaken limbs and affect appearance.
The seriousness of the disease varies hugely between cases. The two most important factors to consider are the level of internal involvement (beneath the skin) and the total area covered by the disease. In general, the more skin that is involved, the more severe the case of scleroderma.
For the systemic form of the disease, almost all patients(over 80%) have vascular symptoms and Raynaud’s phenomenon. During an attack, there is discoloration of the hands and feet in response to cold. Raynaud’s normally affects the fingers and toes.
Systemic scleroderma and Raynaud’s can cause painful ulcers on the fingers or toes which are known as digital ulcers.
Calcinosis is also common in systemic scleroderma, and is often seen near the elbows, knees or other joints.
Diffuse scleroderma can cause musculoskeletal, pulmonary, gastrointestinal, renal and other complications.Patients with larger amounts of cutaneous involvement are more likely to have involvement of the internal tissues and organs.
The first joint symptoms that patients with scleroderma have are typically non specific joint pains, which can lead to arthritis, or cause discomfort in tendons or muscles. Joint mobility, especially of the small joints of the hand, may be restricted by calcinosis or skin thickening. Patients may develop muscle weakness, or myopathy, either from the disease, or its treatments.
Some impairment in lung function is almost universally seen in patients with diffuse scleroderma on pulmonary function testing; however, it does not necessarily cause symptoms, such as shortness of breath. Some patients can develop pulmonary hypertension, or elevation in the pressures of the pulmonary arteries. This can be progressive, and lead to right sided heart failure. The earliest manifestation of this may be a decreased diffusion capacity on pulmonary function testing.
Other pulmonary complications in more advanced disease include aspiration pneumonia, pulmonary hemorrhage and pneumothorax.
Diffuse scleroderma can affect any part of the gastrointestinal tract. The most common manifestation in the esophagus is reflux esophagitis, which may be complicated by peptic stricturing, or benign narrowing of the esophagus. This is best initially treated with proton pump inhibitors for acid suppression, but may require bougie dilatation in the case of stricture.
click to see…..(2)
Scleroderma can decrease motility anywhere in the gastrointestinal tract. The most common source of decreased motility involvement is the esophagus and the lower esophageal sphincter, leading to dysphagia and chest pain. As Scleroderma progresses, esophageal involvement from abnormalities in decreased motility may worsen due to progressive fibrosis (scarring). If this is left untreated, acid from the stomach can back up into the esophagus causing esophagitis, and GERD. Further scarring from acid damage to the lower esophagus many times leads to the development of fibrotic narrowing, also known as strictures which can be treated by dilitation, and Barrett’s esophagus. The small intestine can also become involved, leading to bacterial overgrowth and malabsorption, of bile salts, fats, carbohydrates, proteins, and vitamins. The colon can be involved, and can cause pseudo-obstruction or ischemic colitis.
Rarer complications include pneumatosis cystoides intestinalis, or gas pockets in the bowel wall, wide mouthed diverticula in the colon and esophagus, and liver fibrosis. Patients with severe gastrointestinal involvement can become profoundly malnourished.
Scleroderma may also be associated with gastric antral vascular ectasia (GAVE), also known as watermelon stomach. This is a condition where atypical blood vessels proliferate usually in a radially symmetric pattern around the pylorus of the stomach. GAVE can be a cause of upper gastrointestinal bleeding or iron deficiency anemia in patients with scleroderma.
Renal involvement, in scleroderma, is considered a poor prognostic factor and not infrequently a cause of death in patients with scleroderma…..click & see
The most important clinical complication of scleroderma involving the kidney is scleroderma renal crisis. Symptoms of scleroderma renal crisis are malignant hypertension (high blood pressure with evidence of acute organ damage), hyperreninemia (high renin levels), azotemia (kidney failure with accumulation of waste products in the blood) and microangiopathic hemolytic anemia (destruction of red blood cells). Apart from the high blood pressure, hematuria (blood in the urine) and proteinuria (protein loss in the urine) may be indicative.
In the past scleroderma renal crisis was almost uniformily fatal. While outcomes have improved significantly with the use of ACE inhibitors the prognosis is often guarded, as a significant number of patients are refractory to treatment and develop renal failure. Approximately 10% of all scleroderma patients develop renal crisis at some point in the course of their disease.Patients that have rapid skin involvement have the highest risk of renal complications.
Treatments for scleroderma renal crisis include ACE inhibitors, which are also used for prophylaxis, and renal transplantation. Transplanted kidneys are known to be affected by scleroderma and patients with early onset renal disease (within one year of the scleroderma diagnosis) are thought to have the highest risk for recurrence.
There are three major forms of scleroderma: diffuse, limited (CREST syndrome) and morphea/linear. Diffuse and limited scleroderma are both a systemic disease, whereas the linear/morphea form is localized to the skin. (Some physicians consider CREST and limited scleroderma one and the same, others treat them as two separate forms of scleroderma.) There is also a subset of the systemic form known as “systemic scleroderma sine scleroderma”, meaning the usual skin involvement is not present.
Diffuse scleroderma…..click & see
Diffuse scleroderma (progressive systemic sclerosis) is the most severe form – it has a rapid onset, involves more widespread skin hardening, will generally cause much internal organ damage (specifically the lungs and gastrointestinal tract), and is generally more life threatening.
Limited scleroderma/CREST syndrome……click & see
The limited form is much milder: it has a slow onset and progression, skin hardening is usually confined to the hands and face, internal organ involvement is less severe, and a much better prognosis is expected.
In typical cases of limited scleroderma, Raynaud’s phenom…striction of the small arteries of exposed peripheries – particularly the hands and feet – in the cold. It is classically characterised by a triphasic colour change – first white, then blue and finally red on rewarming. The scleroderma may be limited to the fingers – known as sclerodactyly.
The limited form is often referred to as CREST syndrome. “CREST” is an acronym for the five main features:
CREST is a limited form associated with antibodies against centromeres and usually spares the lungs and kidneys.
Morphea/linear scleroderma….…click & see
Morphea/linear scleroderma involves isolated patches of hardened skin – there generally is no internal organ involvement.
Diagnosis is by clinical suspicion, presence of autoantibodies (specifically anti-centromere and anti-scl70/anti-topoisomerase antibodies) and occasionally by biopsy. Of the antibodies, 90% have a detectable anti-nuclear antibody. Anti-centromere antibody is more common in the limited form (80-90%) than in the systemic form (10%), and anti-scl70 is more common in the diffuse form (30-40%) and in African-American patients (who are more susceptible to the systemic form).
In 1980 the American College of Rheumatology agreed upon diagnostic criteria for scleroderma
There is no clear obvious cause for scleroderma and systemic sclerosis. Genetic predisposition appears to be limited: genetic concordance is small; still, there often is a familial predisposition for autoimmune disease. Polymorphisms in COL1A2 and TGF-Î²1 may influence severity and development of the disease. There is limited evidence implicating cytomegalovirus (CMV) as the original epitope of the immune reaction, and organic solvents and other chemical agents have been linked with scleroderma.
Click to see>Gene clue to fatal skin disease
One of the suspected mechanisms behind the autoimmune phenomenon is the existence of microchimerism, i.e. fetal cells circulating in maternal blood, triggering an immune reaction to what is perceived as “foreign” material.
A distinct form of scleroderma and systemic sclerosis may develop in patients with chronic renal failure. This entity, nephrogenic fibrosing dermopathy or nephrogenic systemic fibrosis, has been linked to the exposure to gadolinium-containing radiocontrast.
Bleomycin (a chemotherapeutic agent) and possibly taxane chemotherapy may cause scleroderma, and occupational exposure to solvents has been linked with an increased risk of systemic sclerosis.
The overproduction of collagen is thought to result from an autoimmune dysfunction, in which the immune system would start to attack the kinetochore of the chromosomes. This would lead to genetic malfunction of nearby genes. T cells accumulate in the skin; these are thought to secrete cytokines and other proteins that stimulate collagen deposition. Stimulation of the fibroblast, in particular, seems to be crucial to the disease process, and studies have converged on the potential factors that produce this effect.
A significant player in the process is transforming growth factor (TGFÎ²). This protein appears to be overproduced, and the fibroblast (possibly in response to other stimuli) also overexpresses the receptor for this mediator. An intracellular pathway (consisting of SMAD2/SMAD3, SMAD4 and the inhibitor SMAD7) is responsible for the secondary messenger system that induces transcription of the proteins and enzymes responsible for collagen deposition. Sp1 is a transcription factor most closely studied in this context. Apart from TGFÎ², connective tissue growth factor (CTGF) has a possible role.
Damage to endothelium is an early abnormality in the development of scleroderma, and this too seems to be due to collagen accumulation by fibroblasts, although direct alterations by cytokines, platelet adhesion and a type II hypersensitivity reaction have similarly been implicated. Increased endothelin and decreased vasodilation has been documented.
Jimenez & Derk describe three theories about the development of scleroderma:
The abnormalities are primarily due to a physical agent, and all other changes are secondary or reactive to this direct insult.
The initial event is fetomaternal cell transfer causing microchimerism, with a second summative cause (e.g. environmental) leading to the actual development of the disease.
Physical causes lead to phenotypic alterations in susceptible cells (e.g. due to genetic makeup), which then effectuate DNA changes which alter the cell’s behavior.
There is no cure for every patient with scleroderma, though there is treatment for some of the symptoms, including drugs that soften the skin and reduce inflammation. Some patients may benefit from exposure to heat.
A range of NSAIDs (nonsteroidal anti-inflammatory drugs) can be used to ease symptoms, such as naproxen. If there is esophageal dysmotility (in CREST or systemic sclerosis), care must be taken with NSAIDs as they are gastric irritants, and so a proton pump inhibitor (PPI) such as omeprazole can be given in conjunction.
Immunosuppressant drugs, such as mycophenolate mofetil (Cellcept), cyclophosphamide or methotrexate are sometimes used to slow the progress. Digital ulcerations and pulmonary hypertension can be helped by prostacyclin (iloprost) infusion. Iloprost being a drug which increases blood flow by relaxing the arterial wall.
While still experimental (given its high rate of complications), hematopoietic stem cell transplantation is being studied in patients with severe systemic sclerosis; improvement in life expectancy and severity of skin changes has been noted.
Scleroderma has no known cure there’s no treatment to stop the overproduction of collagen. Your doctor may recommend a number of medications to make it easier for you to live with scleroderma by treating its symptoms. Your doctor may also suggest medications to prevent complications of scleroderma that may affect various organs. Here are some of the many treatments prescribed for the symptoms and complications of this condition.
If you have localized scleroderma, your doctor may recommend a topical treatment, such as a moisturizer or corticosteroid medication that you apply to your skin. Corticosteroid medications impede your body’s ability to make substances that can cause inflammation.
If your condition involves a large area of skin, your doctor may recommend additional treatments. Doctors sometimes prescribe minocycline (Minocin, Dynacin) to control the skin-related (cutaneous) symptoms of scleroderma, although no studies have addressed its long-term effectiveness. In preliminary studies, light therapy (phototherapy) also has proved effective in treating the lesions that are associated with scleroderma, but more research is needed.
Cosmetic treatments are another consideration. Some people with scleroderma are discouraged or embarrassed by lesions and marks on the skin, including tiny dilated blood vessels that often appear on the face (telangiectasia). Specialized brands of foundation makeup and pulsed dye laser surgery can help camouflage or eliminate these lesions. Consult a dermatologist about treatments for skin changes.
Your doctor may also prescribe medications to dilate blood vessels and promote circulation. These medications can prevent high blood pressure and kidney problems and help treat Raynaud’s phenomenon.
Medications that help with blood circulation include:
- Calcium channel blockers.
- Alpha blockers
- Angiotensin-converting enzyme (ACE) inhibitors
- Angiotensin II receptor blockers
- Low-dose enteric-coated aspirin
Creams containing nitroglycerin also may help promote circulation.
Joint stiffness, pain and inflammation
Your doctor may prescribe anti-inflammatory medications such as aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs) or low-dose corticosteroids to relieve joint pain and stiffness.
Often, along with NSAIDs, doctors prescribe certain medications called disease-modifying antirheumatic drugs (DMARDs). These medications seem to do their job by having an effect on immune systems that have gone out of control, but doctors don’t understand exactly how DMARDs work. Common DMARDs include:
- Hydroxychloroquine (Plaquenil). This drug has relatively few side effects, and it’s also effective for the arthritis that can be associated with scleroderma. Apart from hydroxychloroquine’s apparent ability to affect the way immune cells work, scientists don’t completely understand how it helps tame the disease process.
- Penicillamine (Cuprimine, Depen). Similar to other DMARDs, penicillamine can reduce inflammation. Its full effect may require many months to develop, but its beneficial effects may be longer lasting. However, because of a relatively high incidence of adverse reactions to this drug and studies casting doubt on its effectiveness, its use has declined in recent years.
- Methotrexate (Rheumatrex, Trexall). This drug does its job by affecting cells that are responsible for some of the pain, inflammation and joint swelling that accompany scleroderma. Trials have shown conflicting results regarding the effectiveness of methotrexate in treating scleroderma.
Immunosuppresents are another class of medications that can help manage out-of-control immune systems. Cyclophosphamide (Cytoxan) is one example. This extremely potent medication works by damaging cells’ genetic information. In particular, it kills white blood cells called lymphocytes that are part of autoimmune disease.
If you have scleroderma that affects your lungs, you may need additional medications. Cyclophosphamide (Cytoxan) is sometimes used to treat pulmonary fibrosis. A 2006 study of people with scleroderma-related lung disease found cyclophosphamide modestly improved lung function and quality of life. The long-term effects of cyclophosphamide treatment in people with scleroderma are unknown. Bosentan (Tracleer) is an oral medication that has been approved for pulmonary hypertension in people with scleroderma.
If scleroderma has affected your esophagus and you’re experiencing heartburn, your doctor may suggest prescription medications that decrease stomach acid production. These medications include H-2-receptor blockers and proton pump inhibitors. Your doctor may also suggest antibiotics, special diets and medications that improve your gut’s ability to contract.
Having systemic scleroderma may result in a number of other health conditions:
Gastrointestinal complications. In scleroderma, wasting occurs in the muscular walls of your intestine. This can reduce absorption of nutrients and movement within the intestine, resulting in weight loss and malnutrition. When scleroderma affects the muscular lining of your esophagus, heartburn can occur.
Lung complications. Scarring of lung tissue (pulmonary fibrosis) can result in reduced lung function, reduced ability to breathe and reduced tolerance for exercise. You may also develop high blood pressure in the arteries to your lungs (pulmonary hypertension).
Kidney complications. When scleroderma affects your kidneys, you can develop an elevated blood pressure and an increased level of protein in your urine. More serious effects of kidney complications may include renal crisis, which involves a sudden increase in blood pressure and rapid kidney failure.
Heart complications. Scarring of heart tissue increases your risk of heart arrhythmias and congestive heart failure, and can cause inflammation of the membranous sac surrounding your heart (pericarditis).
You can take a number of steps to help manage your symptoms of scleroderma:
- Stay active. Exercise keeps your body flexible, improves circulation and relieves stiffness. Range-of-motion exercises can help keep your skin and joints flexible.
- Don’t smoke. Nicotine causes blood vessels to contract, making Raynaud’s phenomenon worse. Smoking can also cause permanent narrowing of your blood vessels. Quitting smoking is difficult â€” ask your doctor for help.
- Manage heartburn. Avoid foods that give you heartburn or gas. Also avoid late-night meals. Elevate the head of your bed to keep stomach acid from backing up into your esophagus (reflux) as you sleep. Try over-the-counter antacids for relief of symptoms.
- Protect yourself from the cold. Wear warm mittens for protection when your hands encounter cold temperatures such as when you reach into a freezer. When you’re outside in the cold, cover your face and head and wear layers of warm clothing.
Depending on how you’re affected by scleroderma, you may benefit from physical therapy and occupational therapy. Therapists can help you manage pain, improve your strength and mobility, and work on performing essential daily tasks to maintain your independence. Ask your doctor to recommend a physical therapist or an occupational therapist.
As is true with other chronic diseases, living with scleroderma can place you on a roller coaster of emotions. Here are some suggestions to help you even out the ups and downs:
- Maintain normal daily activities as best you can.
- Pace yourself and be sure to get the rest that you need.
- Stay connected with friends and family.
- Continue to pursue hobbies that you enjoy and are able to do.
If scleroderma makes it difficult for you to do things you enjoy, ask your doctor about ways to get around the obstacles.
Keep in mind that your physical health can have a direct impact on your mental health. Denial, anger and frustration are common with chronic illnesses.
At times, you may need additional tools to deal with your emotions. Professionals, such as therapists or behavior psychologists, may be able to help you put things in perspective. They can also help you develop coping skills, including relaxation techniques.
Joining a support group, where you can share experiences and feelings with other people, is often a good approach. Ask your doctor what support groups are available in your community.
In addition, many chronic illnesses place you at an increased risk of depression. This isn’t a failure to cope but may indicate a disruption in your body’s neurochemistry that can be helped with appropriate medical treatment. Talk with your family, friends and doctor if you’re feeling depressed.
Disclaimer: This information is not meant to be a substitute for professional medical advise or help. It is always best to consult with a Physician about serious health concerns. This information is in no way intended to diagnose or prescribe remedies.This is purely for educational purpose.