Systemic Scleroderma
Systemic scleroderma is a rare autoimmune disease that causes the body to produce too much collagen, leading to hardening and thickening of the skin and internal organs. This chronic condition affects multiple parts of the body and requires careful, ongoing management to control symptoms and prevent serious complications.
Table of contents
- What is systemic scleroderma?
- Other names for this condition
- Types of systemic scleroderma
- How common is it?
- What causes systemic scleroderma?
- Signs and symptoms
- How is it diagnosed?
- Treatment options
- Living with systemic scleroderma
- Outlook and prognosis
What is systemic scleroderma?
Systemic scleroderma, also known as systemic sclerosis, is a rare autoimmune disorder that affects the skin and internal organs[1]. An autoimmune disorder happens when the immune system, which normally protects the body from infections, makes a mistake and begins to attack the body’s own tissues[2].
The word “scleroderma” comes from Greek words meaning “hard skin,” and the condition is characterized by the buildup of scar tissue, called fibrosis, in the skin and other organs[4]. This hardening occurs because the body produces too much collagen, a protein that normally helps strengthen and support tissues throughout the body. When too much collagen is produced, the skin and other tissues become thicker and more fibrous than they should be[2].
Systemic scleroderma is different from localized scleroderma. The localized form primarily affects only the skin and the tissue just beneath it, while systemic sclerosis can affect blood vessels, internal organs including the heart, lungs, kidneys, and digestive system, leading to more serious health problems[3].
systemic sclerosis, progressive systemic sclerosis, scleroderma syndrome
ORPHA:90291
4A42
Other names for this condition
Systemic scleroderma is known by several other names in medical practice. The most common alternative name is systemic sclerosis[1]. Healthcare providers may also refer to it as progressive systemic sclerosis or scleroderma syndrome[5]. When the condition is limited to certain areas, doctors sometimes use the term CREST syndrome[3].
Types of systemic scleroderma
Healthcare providers classify systemic scleroderma into different subtypes based on how much of the skin is affected and which organs are involved[6].
Limited cutaneous systemic sclerosis is the most common type. In this form, skin thickening usually affects only the hands, arms below the elbows, feet, legs below the knees, and face[7]. This type was previously known as CREST syndrome, named after five common features: Calcinosis (calcium deposits in the skin), Raynaud’s phenomenon (color changes in fingers and toes), Esophageal dysfunction (difficulty swallowing), Sclerodactyly (tight skin on the fingers), and Telangiectasias (red spots on the skin)[3]. Limited systemic sclerosis tends to progress more slowly and is generally less severe than the diffuse form[7].
Diffuse cutaneous systemic sclerosis is a more extensive form where skin thickening can affect larger areas of the body, including the chest, abdomen, thighs, upper arms, upper legs, and face[2]. This type is more likely to affect multiple internal organs at once, including the digestive system, kidneys, heart, and lungs[2]. People with diffuse scleroderma have a higher risk of developing serious complications, and the condition tends to worsen more quickly than the limited form[6].
Systemic sclerosis sine scleroderma (where “sine” means “without” in Latin) is an uncommon type that affects one or more internal organs but does not cause skin thickening[4]. Despite having no visible skin changes, people with this type can still experience symptoms related to organ involvement[2].
How common is it?
Systemic scleroderma is a rare disease. The number of people affected is estimated to range from 50 to 300 cases per 1 million people[4]. For reasons that are not fully understood, women are four times more likely to develop the condition than men[4]. The disease most commonly appears in adults between the ages of 30 and 50, though it can occur at other ages[7]. Children are rarely affected[7].
What causes systemic scleroderma?
The exact cause of systemic scleroderma is currently unknown. Researchers believe the disease develops from a combination of factors[1].
Genetic factors appear to play a role, as the risk of developing systemic scleroderma is higher in people who have a close family member with the condition[4]. Certain genes, particularly those in the human leukocyte antigen (HLA) complex, which helps the immune system distinguish the body’s own proteins from foreign invaders, have been associated with an increased risk[4].
Environmental factors may also contribute to the development of the disease. Exposure to certain substances such as silica, solvents, and spirits has been linked to an increased risk of systemic scleroderma[22]. Certain medications and having an underlying cancer may also trigger the disease process in some people[22].
The disease process begins with inflammation, which appears to start in the blood vessels and causes damage to them. This damage leads to more inflammation, which results in additional tissue damage and the formation of autoantibodies—immune proteins that mistakenly target the body’s own tissues[22]. The combination of inflammation, damaged blood vessels, and autoantibodies leads to the characteristic scarring and thickening seen in the skin, organs, and blood vessels of people with systemic scleroderma[22].
Signs and symptoms
The signs and symptoms of systemic scleroderma vary greatly from person to person, depending on which parts of the body are affected[1]. The type and severity of symptoms can differ between individuals, and some symptoms may be mild while others can be life-threatening[5].
The earliest and most common symptom is Raynaud’s phenomenon, which can occur weeks to years before other signs appear[4]. In Raynaud’s phenomenon, the fingers and toes turn white, blue, or red in response to cold temperatures or stress. This happens because the small blood vessels that carry blood to the extremities narrow excessively[1]. The affected areas may also feel numb, tingle, or become painful. While Raynaud’s most commonly affects the fingers and toes, it can also occur in the nose and ears[5]. In severe cases, repeated episodes can lead to painful open sores called ulcers on the fingertips[8].
Skin changes are another hallmark of the disease. Nearly everyone with systemic scleroderma experiences hardening and tightening of the skin[1]. Early signs often include puffy or swollen hands before the skin begins to thicken and harden due to fibrosis[4]. The first areas to be affected are usually the fingers, hands, feet, and face[1]. The skin may become shiny because of the tightness, and its color can become lighter or darker. Some people develop small red spots called telangiectasias, which are visible clusters of small blood vessels just under the skin[4]. Hard lumps can form under the skin, particularly at the fingertips, caused by calcium deposits known as calcinosis[1].
Many people with systemic scleroderma experience problems with their digestive system. Heartburn is very common and occurs because the muscle connecting the esophagus to the stomach stops working properly, allowing stomach acid to flow back into the esophagus[4]. This can lead to difficulty swallowing, a condition called dysphagia[22]. Other digestive symptoms may include bloating, increased belching and gas, constipation, diarrhea, and cramping[22]. In severe cases, problems with intestinal movement can develop[1].
Joint and muscle symptoms are also common. People may experience joint pain, stiffness, and swelling[5]. The thickening of skin around joints can limit movement, making it difficult to open the mouth fully or move the fingers freely[9]. Some people develop muscle weakness, pain, and fatigue due to muscle inflammation called myositis[22].
Internal organ involvement can cause serious complications. When the lungs are affected, people may develop shortness of breath and reduced ability to exercise[1]. Lung complications include interstitial lung disease (scarring of lung tissue) and pulmonary arterial hypertension (high blood pressure in the blood vessels of the lungs)[22]. Heart problems can include irregular heartbeats, heart failure, and inflammation of the heart’s outer lining[8]. Kidney involvement can lead to high blood pressure and kidney failure, particularly in a condition called scleroderma renal crisis[1].
Other symptoms may include dry mouth, dental problems, fatigue, and weight loss[5]. Some people also experience itching of affected skin areas[8].
How is it diagnosed?
Diagnosing systemic scleroderma can be challenging because the condition can take many forms and affect different areas of the body[9]. Early diagnosis is important for starting treatment promptly and monitoring disease progression[3].
The diagnostic process typically begins with a thorough physical examination. A healthcare provider will look for characteristic signs such as skin thickening, especially on the fingers and hands, and ask about symptoms like Raynaud’s phenomenon and digestive problems[9].
Blood tests are an important part of the diagnosis. Healthcare providers will check for elevated levels of certain antibodies produced by the immune system[9]. People with systemic scleroderma often have positive antinuclear antibodies (ANA), which are proteins that attack the body’s own cell nuclei[22]. More specific antibodies can help determine the subtype of the disease. For example, anti-centromere antibodies are more common in limited cutaneous systemic sclerosis, while anti-topoisomerase antibodies (also called Scl-70 antibodies) or anti-RNA polymerase antibodies are more often found in diffuse cutaneous systemic sclerosis[22].
Additional tests may be needed to check for internal organ involvement. These can include imaging tests and organ function studies[9]. For the lungs, pulmonary function tests measure how well the lungs are working, and chest imaging can detect lung disease[3]. An echocardiogram (ultrasound of the heart) can check for heart problems and pulmonary hypertension[3]. Blood tests and urine tests can assess kidney function[3]. Tests to evaluate the digestive system may include studies of how food moves through the esophagus and intestines[9].
A technique called nail-fold capillary microscopy can be used to examine the tiny blood vessels at the base of the fingernails. Changes in these vessels are characteristic of systemic scleroderma[16].
Treatment options
While there is no cure for systemic scleroderma and no treatment can stop the overproduction of collagen, a variety of treatments can help control symptoms, slow disease progression, and prevent complications[1]. Treatment plans are personalized based on which symptoms and organs are affected[10].
For Raynaud’s phenomenon, medications that dilate blood vessels are the main treatment. Calcium channel blockers, which are blood pressure medications like nifedipine and amlodipine, can improve blood flow to the fingers and toes[10]. Phosphodiesterase-5 (PDE-5) inhibitors such as sildenafil and tadalafil can also help improve circulation and are particularly useful for treating severe Raynaud’s and digital ulcers[10]. Topical creams may help with mild symptoms[10].
For digestive problems, several types of medications can provide relief. Antacids and proton pump inhibitors such as omeprazole can reduce stomach acid and help with heartburn[9]. Antibiotics and medications that help move food through the intestines may reduce bloating, diarrhea, and constipation[9].
For skin and lung involvement, medications that suppress the immune system are often used, especially early in the disease. Methotrexate and mycophenolate mofetil are commonly prescribed[10]. These medications can help slow the progression of skin thickening and lung disease[14]. Cyclophosphamide, another immunosuppressive drug, has been shown to improve lung disease in some patients[16].
For people with lung scarring (interstitial lung disease), several treatment options are available. Tocilizumab, a biologic medication, has been approved for treating progressive lung disease in systemic sclerosis[16]. Nintedanib, originally developed for other lung diseases, has also been approved to slow the decline in lung function in people with systemic scleroderma-related lung disease[16]. Rituximab, which targets specific immune cells, has shown promising results in trials for both skin and lung involvement[16].
For pulmonary arterial hypertension, specialized medications that relax constricted blood vessels can help reduce high blood pressure in the lungs. These include endothelin receptor antagonists and phosphodiesterase-5 inhibitors, often used in combination[13]. Newer agents such as selexipag and riociguat have also improved outcomes for people with this complication[13].
In cases of severe, progressive disease, autologous hematopoietic stem cell transplantation (bone marrow transplant) may be considered. This intensive treatment involves using high-dose chemotherapy followed by transplanting the patient’s own stem cells back into their body. While it carries significant risks, it has shown promise in improving survival and quality of life for carefully selected patients with severe disease[15]. Emerging therapies being studied include CAR T-cell therapy, which involves modifying a patient’s immune cells to target and remove specific disease-causing cells[15].
Pain management is also an important part of treatment. Over-the-counter or prescription pain relievers may be needed for joint pain and muscle discomfort[9]. Physical therapy and occupational therapy can help maintain joint flexibility and address functional limitations[23].
Vaccinations are particularly important for people with systemic scleroderma to protect against infections. Healthcare providers recommend staying up to date with vaccines for influenza, pneumonia, shingles, HPV, COVID-19, and RSV[9].
In some cases, surgery may be necessary. Hard calcium lumps under the skin may need to be removed, and tightened muscles may require surgical release[7]. Newer approaches such as laser therapy and photodynamic therapy may also be available for certain symptoms[7].
Living with systemic scleroderma
Living with systemic scleroderma requires ongoing management and lifestyle adjustments, but many people with the condition lead long, fulfilling lives[20].
For managing Raynaud’s phenomenon, it is important to keep the body warm. Wearing layered clothing, boots, and gloves in cold weather can help prevent episodes[9]. Protecting fingers and toes from activities that could injure the skin is essential, as wounds can be slow to heal and prone to infection[9].
Skin care is important for managing the skin changes that occur with scleroderma. Keeping skin moisturized can help prevent dryness and itching and may help maintain some flexibility[9].
Diet modifications can help with digestive symptoms. Eating several smaller meals throughout the day instead of three large meals can reduce heartburn[9]. Avoiding eating right before bedtime can also help prevent acid reflux[9].
Regular exercise and physical therapy are valuable for keeping joints flexible and maintaining muscle strength[9]. However, it’s important to work with healthcare providers to develop an appropriate exercise program that doesn’t worsen symptoms[23].
Depression and mood problems are possible with any chronic illness. It’s important to seek support from family and friends, join patient support groups, or seek professional mental health treatment when needed[20]. Patient organizations and support groups can provide valuable resources, education, and connection with others who understand the challenges of living with systemic scleroderma[21].
Regular monitoring by healthcare providers is essential. People with systemic scleroderma typically need frequent check-ups and tests to watch for complications[3]. This includes regular blood pressure checks, lung function tests, heart evaluations, and kidney function monitoring[16].
Because systemic scleroderma can affect multiple organ systems, care often involves a team of specialists working together. This may include rheumatologists, pulmonologists (lung specialists), cardiologists (heart specialists), gastroenterologists (digestive system specialists), nephrologists (kidney specialists), and dermatologists (skin specialists)[3]. Treatment centers that specialize in scleroderma can provide coordinated, comprehensive care[19].
Patient education is a crucial component of successful disease management. Understanding the condition, recognizing warning signs of complications, and knowing when to seek immediate medical attention can help prevent serious problems[19].
Outlook and prognosis
The outlook for people with systemic scleroderma varies considerably depending on the type of disease and which organs are affected[8]. People with limited cutaneous systemic sclerosis generally have a better prognosis than those with the diffuse form[3].
The most serious complications and causes of death in systemic scleroderma are related to lung, heart, and kidney involvement[8]. Interstitial lung disease and pulmonary arterial hypertension are major concerns and require careful monitoring and treatment[22]. Scleroderma renal crisis, though less common than in the past due to better blood pressure control, remains a serious complication[14].
The risk of cancer is slightly increased in people with systemic scleroderma compared to the general population[8].
Importantly, survival rates have greatly improved over recent decades due to earlier diagnosis, better monitoring for complications, and more effective treatments[8]. The development of medications to control blood pressure has dramatically improved outcomes for kidney involvement[16]. Advances in treating lung disease and pulmonary hypertension have also improved quality of life and survival[13].
With appropriate medical care, many people with systemic scleroderma can manage their symptoms effectively and maintain a good quality of life[19]. The disease course is highly individual, and ongoing research continues to develop new treatment approaches that may further improve outcomes for people living with this condition[13].
