Systemic Sclerosis (Scleroderma)

What is Systemic Sclerosis (Scleroderma)?

Scleroderma, also known as systemic sclerosis, is a rare disease that affects the connective tissue (tissues that support, bind, or separate other tissues or organs). Its cause is not well understood, and it can have complex effects on the body. There are two main types of scleroderma: localized scleroderma, which includes morphea and linear scleroderma, and systemic sclerosis. Systemic sclerosis is further divided into two categories, each with its own unique set of symptoms. Limited systemic sclerosis, once known as CREST syndrome, is identified by symptoms which include skin that hardens or thickens, a condition called Raynaud’s phenomenon that affects blood flow to the fingers and toes, difficulty moving the esophagus, tightening of the skin on the fingers, and widening of small blood vessels on visible areas of the skin. The second category of systemic sclerosis is referred to as diffuse systemic sclerosis.

While we’ve made great strides in understanding scleroderma over the years, it still places a significant burden on patients’ health and quality of life. Localized scleroderma mainly affects the skin and tissue just below the skin, leading to patches of thickened skin. If these patches are examined under a microscope, the skin changes resemble those seen in systemic sclerosis. However, localized scleroderma doesn’t cause Raynaud’s phenomenon, restricted blood flow resulting in tissue damage, or problems in internal organs. While 50% of those with localized scleroderma may have a positive antinuclear antibody (substances produced by the immune system) test, the antibodies specifically related to systemic sclerosis are usually not present. Most importantly, localized scleroderma does not lead to increased rates of death. Systemic sclerosis, on the other hand, leads to numerous symptoms and can affect the internal organs, causing increased mortality rates.

Limited cutaneous systemic sclerosis, or CREST syndrome, is marked by skin thickening, but this thickening is typically seen near the ends of the arms and legs, or on the face, and doesn’t affect the trunk. Diffuse cutaneous systemic sclerosis, however, can involve skin thickening across a larger area of the body. Both types are associated with numerous symptoms and positive antibody tests. More than 90% of cases of systemic sclerosis may show antinuclear antibodies in blood tests, and up to 70% have at least one specific antibody. People with scleroderma frequently show signs affecting their skin, gastrointestinal tract, lungs, kidneys, skeletal muscles, and the lining of the heart. The symptoms of scleroderma can look very similar to those of other diseases related to the immune system. The severity of the disease varies and is influenced by when it is diagnosed.

What Causes Systemic Sclerosis (Scleroderma)?

The exact cause of systemic sclerosis, an autoimmune disease, isn’t entirely known but is thought to be due to both genetic and environmental factors.

Genetic Factors

Systemic sclerosis often occurs within families, suggesting that it is partly passed down through genes. It also shares some genetic traits with other autoimmune conditions like lupus and rheumatoid arthritis. Identified genes related to systemic sclerosis include: HLA DRB1*1104, DQA1*0501, and DQB1*0301. Other genes like PTPN22, NLRP1, STAT4, and IRF5 have also been linked to the disease.

Environmental Factors

Besides genes, our environment also plays a role. Certain infectious agents like Cytomegalovirus (CMV), Epstein-Barr virus, and parvovirus B19 have been tied to systemic sclerosis. Environmental factors including silica dust, organic solvents, toluene, xylene, trichloroethylene, and polyvinyl chloride are known triggers. However, strangely enough, cigarette smoke, despite being harmful, is not a proven risk factor for this disease.

There are also diseases similar to systemic sclerosis that are triggered by environmental exposure. For example, contaminated cooking oil can cause toxic oil syndrome, and a substance called L-tryptophan can cause the eosinophilia-myalgia syndrome. Plus, certain drugs have been linked with triggering systemic sclerosis-like illnesses. These include bleomycin, a cancer treatment, and illegal drugs such as cocaine.

Risk Factors and Frequency for Systemic Sclerosis (Scleroderma)

Systemic sclerosis is a rare condition, and due to this, there’s not a lot of data about how many people it affects. However, we do know that its occurrence can be influenced by factors like where someone lives, how it’s defined, and how the diagnosis was confirmed. Generally, there are between 38 to 341 cases per million people, and every year there are about 8 to 56 new cases per million people globally.

One study in the US found that there were about 19.3 new cases per million adults each year, and there were 242 cases per million adults in the Detroit area between 1989 to 1991. Another study in Quebec in 2003 reported 443 cases per million adults. It’s interesting to note that there are more cases in the US and Australia compared to Europe and Asia, particularly Japan and Taiwan. The highest occurrence of systemic sclerosis was found among the Choctaw Native Americans from Oklahoma, with 660 cases per million adults. This points out that this condition can vary depending on where you live.

Systemic sclerosis is more common in women than in men, with a ratio of about 5:1. Women usually get this condition at a younger age than men do. The most common age for this condition to start is between 45 to 54 for African-American women and between 55 to 64 for European-American women. However, it is rare for children and teenagers 15 years old or younger to have systemic sclerosis. It’s also rare for individuals between the ages of 15 to 24 to have this condition, with 21.2 cases per million among African-American females and 11.16 cases per million among European-American females. Individuals of African descent have a higher chance of developing systemic sclerosis, tend to have it start earlier, and often have more severe symptoms.

Signs and Symptoms of Systemic Sclerosis (Scleroderma)

Systemic sclerosis is a complex disorder that can affect various parts of the body differently. Typically, it’s more serious in males, African Americans, and those who develop it later in life.

One common symptom that over 95% of people with systemic sclerosis have is known as Raynaud phenomenon. It’s a condition where exposure to cold causes spasms in the blood vessels. When this happens, there can be color changes in the digits, and sometimes in areas such as the ears, nose, or tongue. The color changes can start with a white discoloration, move to a bluish appearance, and end with red discoloration. Not everyone experiences all three color changes, and some people might experience Raynaud phenomenon for years before other symptoms appear.

Other symptoms of systemic sclerosis can involve the skin. Almost all patients with systemic sclerosis have some sort of skin involvement, but the severity of symptoms can vary. Symptoms can include a tightening and thickening of the skin, skin ulcers, and lost skin appendages, which can lead to dry and uncomfortable skin. Some people could also get complications such as perioral skin tightening, reduced oral aperture, periodontitis, and gingivitis.

Cardiac and pulmonary manifestations, like pericarditis, pericardial effusion, and lung diseases are also common in patients with systemic sclerosis. It’s also common to see gastrointestinal symptoms like dry mouth, dysphagia, heartburn, nausea, vomiting, diarrhea, constipation, intestinal bacterial overgrowth, and a reduced anal sphincter tone.

Other common symptoms include liver damage, muscular symptoms like arthralgia and myalgia, which are similar to rheumatoid arthritis, and renal manifestations. There might also be musculoskeletal issues, including arthralgia and myalgia, or symptoms resembling rheumatoid arthritis. Renal symptoms could include new-onset hypertension or malignant hypertension, often with renal insufficiency.

Here are some of the key symptoms of systemic sclerosis to look out for:

• Raynaud phenomenon (color changes in the digits due to blood vessel spasms)
• Skin tightening and thickening
• Skin ulcers
• Dry and uncomfortable skin
• Oropharyngeal involvement like perioral skin tightening, reduced oral aperture, periodontitis, and gingivitis
• Cardiac and pulmonary issues
• Untypical gastrointestinal issues
• Possible liver damage
• Muscular issues like arthralgia and myalgia
• Renal issues with hypertension and renal insufficiency

One key aspect of dealing with systemic sclerosis is diagnosis and classification. The American College of Rheumatology has a classification criteria for systemic sclerosis, which uses a scoring system. A score of 9 or more on this scale suggests systemic sclerosis.

Testing for Systemic Sclerosis (Scleroderma)

Systemic sclerosis, or a disease affecting your body’s connective tissue, is diagnosed by a doctor examining you. The goal is to catch the disease early, determine how far it has spread, and check for signs that it has affected internal organs. All of these steps are crucial in managing the disease effectively.

During a doctor’s visit, your skin thickness will be tested using something called the modified Rodnan skin score. With this test, scores from 0 to 3 are given – a score of 0 means the skin is unaffected whereas a 3 means the skin is severely thickened. Changes in this score over time can help doctors predict how the disease will progress. Furthermore, if you present symptoms like cold fingers or toes (Raynaud’s phenomenon) your doctor will likely examine the tiny blood vessels in your fingertips. Regular blood pressure monitoring is also highly recommended for certain individuals, as abnormalities could be a sign of worsening disease.

Another key diagnostic tool involves testing for autoantibodies – proteins created by the immune system that mistakenly attack the body’s own tissues instead of foreign substances. Certain autoantibodies can provide insight into how your disease might progress. One such test detects antinuclear antibodies (ANAs), which are found in over 90% of systemic sclerosis cases.

Specific autoantibodies are often examined as well. These include anti-centromere antibodies, associated with limited skin involvement and better survival rates; antibodies against topoisomerase I (often called Scl-70), which are linked to more severe manifestations including lung and heart damage; and many others that can help doctors predict outcomes and manage your disease effectively.

Beyond these tests, a variety of other assessments may be used. These include complete blood counts to check for anemia, monitoring of kidney function, x-rays, and musculoskeletal ultrasound to identify any inflammation of tendons. If there are signs of muscle involvement, your doctor may recommend additional tests like nerve velocity testing or perhaps a muscle biopsy. High-resolution CT scans are the preferred method for assessing lung disease.

When it comes to lung function, additional tests may be required to detect any restrictions in your breathing. Heart tests may be done to assess any heart abnormalities. If your doctor suspects involvement of the upper digestive tract, they might recommend tests such as an upper gastrointestinal endoscopy or a barium swallow study. If your esophagus appears dilated or filled with air on a CT scan, this is a typical sign of esophageal dysfunction.

Treatment Options for Systemic Sclerosis (Scleroderma)

Currently, there’s no definitive treatment that can change the natural course of systemic sclerosis, a chronic disease affecting the body’s connective tissue. Even so, effectively managing the affected areas has shown promise. Early diagnosis is crucial for the best possible outcomes. Getting a handle on which organs are affected and how far the disease has progressed is vital for successful treatment. In terms of treatment goals, the whole person should be taken into account. The aim is to improve quality of life for affected patients and prevent further organ damage. Educating patients about the disease, encouraging regular exercise and a healthy diet, and fostering emotional support can also be beneficial for individuals with systemic sclerosis.

Various medications have been investigated for managing different symptoms of systemic sclerosis, but the lack of large-scale scientific trials has left questions about their effectiveness. Several immune-suppressing agents, including Cyclophosphamide, Mycophenolate Mofetil, Methotrexate, Azathioprine, and Hydroxychloroquine, are commonly used. However, steroids generally should be avoided due to the risk of triggering a severe kidney issue called scleroderma renal crisis.

Different therapies are used depending on the symptoms. For example, patients with Raynaud phenomenon, a condition affecting blood flow to the fingers and toes, are advised to keep warm and avoid smoking, stress, and certain medications. Vasodilator therapy, which helps to widen blood vessels, has been effective in treating Raynaud syndrome.

When it comes to skin disease, several immune-suppressing agents have been used. Antihistamines and moisturizing agents can help with itching. For musculoskeletal involvement, mild aches and pains often don’t require treatment or respond well to anti-inflammatory drugs. Physical and occupational therapy are crucial in preventing stiffness and loss of mobility.

Pulmonary involvement from systemic sclerosis is now the leading cause of death, and early detection of lung involvement is crucial. Specific medications have been shown to be beneficial for this aspect of the disease, and lung transplantation may be necessary in some cases. Living healthily while having pulmonary involvement includes getting supplemental oxygen if needed, avoiding certain medications, and leading a healthy lifestyle with exercise as tolerated. Various vasodilating therapies are recommended, all of which can improve blood flow and quality of life.

In terms of gastrointestinal involvement, exercise can help improve symptoms while maintaining good dental hygiene is essential to prevent tooth decay and cavities due to dryness symptoms. Avoiding spicy foods, opting for small, frequent meals and avoiding certain medications are recommended for those suffering from heartburn and acid reflux.

Treatment for a severe kidney issue called scleroderma renal crisis primarily involves the use of a group of drugs called ACE inhibitors which can help improve kidney function, although full recovery may take a considerable amount of time.

What else can Systemic Sclerosis (Scleroderma) be?

When examining a case of systemic sclerosis, it’s crucial to also consider other ailments that might have similar symptoms. These could include:

• Eosinophilic Fasciitis: This disease thickens and hardens the skin on your arms and legs (but doesn’t affect hands and feet) and isn’t connected to Raynaud’s syndrome, a common symptom in systemic sclerosis. Other bodies’ reactions, non-cancerous in nature, may look like systemic sclerosis. The possibility of cancer must not be ignored. A skin biopsy usually shows specific eosinophilic infiltrates.
• Scleromyxedema: Usually found in patients with monoclonal gammopathy or multiple myeloma, and demonstrates papular waxy lesions on various parts of the body, including the face, neck, and fingers. There may be other symptoms too, like seizures and dementia. Raynaud’s phenomenon isn’t present, and specific autoantibodies that are key to diagnosis are usually negative. The skin biopsy of scleromyxedema typically shows dermal fibrosis, inflammation, and the deposition of mucin and fibrocytes.
• Scleredema This condition is associated with a range of diseases and conditions such as diabetes, fatigue, infections, and cancer, and results in a doughy skin appearance. Raynaud’s phenomenon isn’t present and a skin biopsy typically shows dermal fibrosis without inflammation, and the deposition of mucin.
• Nephrogenic Systemic Fibrosis: This rare condition typically occurs in patients with severe kidney disease who’ve been exposed to a specific type of contrast dye used in some medical tests. Symptoms include a distinctive cobblestone-like skin texture. Raynaud’s phenomenon isn’t present and a skin biopsy typically shows both dermal and epidermal fibrosis without inflammation, plus the deposition of mucin and fibrocytes.
• Eosinophilia Myalgia Syndrome: This syndrome, related to the use of L-tryptophan, often presents with severe muscle pain, visceral damage, and increased CK levels.
• Toxic Oil Syndrome: This syndrome was an outbreak in Spain connected with the use of adulterated rapeseed oil, and leads to a condition similar to systemic sclerosis, skin changes , lung infiltrates and high levels of creatine kinase.

Therefore, when diagnosing systemic sclerosis, it’s essential to look out for these other conditions and cross-check the signs and symptoms properly, to confirm an accurate diagnosis.

What to expect with Systemic Sclerosis (Scleroderma)

Systemic sclerosis, also known as scleroderma, is linked to high mortality rates. It holds the record for the highest mortality rate among all connective tissue diseases. In the past, the leading cause of death from this disease was a severe kidney problem called scleroderma renal crisis. However, with the introduction of ACE inhibitors (medication used to treat high blood pressure and heart failure) and greater disease awareness, death rates from scleroderma renal crisis have significantly dropped. Now, lung disease is the most common cause of death for patients with systemic sclerosis.

The overall prognosis for systemic sclerosis has improved over the past three decades, with the 5-year survival rate now reaching up to 80%. However, patients with severe pulmonary arterial hypertension (high blood pressure in the lung’s arteries) generally have a less optimistic outlook, with less than 50% surviving for two years.

Before the use of ACE inhibitors, the 1-year survival rate for patients suffering from scleroderma renal crisis was under 15%. These days, thanks to more awareness about the disease and the benefit of ACE inhibitors, the 1-year survival rate has significantly improved to over 85%. However, patients with systemic sclerosis also have an increased risk of developing cancer, particularly lung cancer. Furthermore, gastroesophageal reflux (acid reflux) linked to systemic sclerosis can lead to a condition called Barrett’s esophagus, which raises the risk for a type of cancer known as esophageal adenocarcinoma.

There are certain factors associated with the disease and its outcomes:

– Being of African-American descent, early onset of the disease (scleroderma), and severe illness are associated with lung disease and kidney problems.
– Diagnosing the disease at an older age is linked with poor outcomes if the patient experiences the kidney complication or develops pulmonary arterial hypertension.
– If the disease affects the skin extensively or sparsely, different complications can arise, including skin conditions, arthritis, kidney issues, and heart disease.
– The presence of multiple skin conditions, heart complications, and kidney issues are linked with poor prognosis.
– New anemia (lack of red blood cells), use of corticosteroids (a type of medication), and certain antibodies in the body could indicate a more severe form of the disease.

Possible Complications When Diagnosed with Systemic Sclerosis (Scleroderma)

Systemic sclerosis, a condition related to fibrosis or tissue scarring, can lead to various complications. For instance, reduced blood flow to the fingers or toes could become severe enough to result in gangrene, a condition which often requires amputation.

The disease can also affect the digestive system, making it difficult for patients to obtain proper nutrition. One of the main problems associated with systemic sclerosis is its impact on the lungs, causing irreversible fibrosis or scarring.

Furthermore, patients can suffer from a condition known as scleroderma renal crisis, which can cause permanent damage to the kidneys. Luckily, the use of a type of medication called ACE inhibitors has been shown to restore kidney function in most cases.

Common complications:

• Digital ischemia (limited blood flow to fingers or toes)
• Gangrene, potentially necessitating amputation
• Gastrointestinal complications causing malnutrition
• Pulmonary fibrosis (lung scarring)
• Scleroderma renal crisis leading to kidney damage
• Potential renal damage
• ACE inhibitors can restore kidney function

Preventing Systemic Sclerosis (Scleroderma)

Teaching patients about their conditions is essential in managing diseases and making necessary lifestyle changes. For example, if you have a medical condition called Raynaud’s phenomenon, it’s crucial that you know how to keep your body and hands and feet warm. You should avoid exposure to extreme cold, substances that narrow your blood vessels (vasoconstrictive agents), and injuring your fingers and toes.

If, on the other hand, you have a disease called systemic sclerosis (scleroderma), it’s advisable to stop smoking and try to stay away from secondhand smoke. Monitoring your blood pressure regularly at home can help catch a potential scleroderma kidney crisis early. Knowing these steps can help you manage your condition effectively.