Systemic Sclerosis Pulmonary

Systemic sclerosis affecting the lungs is one of the leading causes of death in people with this rare autoimmune disease, occurring in approximately 35-65% of patients and accounting for 20-40% of all systemic sclerosis-related deaths.

Table of contents

• What is systemic sclerosis?
• Lung involvement in systemic sclerosis
• Symptoms of lung involvement
• Causes and risk factors
• Screening and diagnosis
• Treatment options
• Monitoring and follow-up

What is systemic sclerosis?

Systemic sclerosis, also called scleroderma, is a rare autoimmune disease where the body’s immune system mistakenly attacks its own tissues. This happens when the immune system, which normally protects you from infections and cancer, makes a mistake and begins attacking parts of your body instead.^[5]

The condition causes excessive inflammation and increased production of collagen, a protein that forms connective tissue. This leads to scarring or fibrosis, which means tissues become hardened and thickened, somewhat like scar tissue. This fibrosis can affect the skin and multiple internal organs, including the lungs, heart, kidneys, and digestive system.^[4]

Systemic sclerosis can be classified into different forms based on how much of the skin is affected. Limited cutaneous systemic sclerosis involves skin changes limited to the face, neck, and areas below the elbows and knees. Diffuse cutaneous systemic sclerosis involves more extensive skin changes, extending above the elbows and knees and sometimes affecting the trunk. Some patients have a form called systemic sclerosis sine scleroderma, where fibrosis affects internal organs without any skin changes.^[5]

Lung involvement in systemic sclerosis

Interstitial lung disease, or ILD, is one of the most common and serious complications of systemic sclerosis. It occurs when the lung tissue becomes scarred and thickened, making it harder for the lungs to work properly. Between 35% and 65% of people with systemic sclerosis develop some form of lung involvement, depending on how it is detected.^[8]

The lungs can be affected in different ways in systemic sclerosis. The most common problem is interstitial lung disease, where the tissue between the air sacs in the lungs becomes scarred. Another serious complication is pulmonary hypertension, which means increased blood pressure in the blood vessels of the lungs. Some patients may have both conditions at the same time, which makes diagnosis and treatment more complex.^[9]

The risk of developing lung disease is greatest early in the course of systemic sclerosis. Timely detection is important for monitoring how the disease progresses and making decisions about treatment.^[8]

Symptoms of lung involvement

People with systemic sclerosis who develop lung involvement may experience a cough and shortness of breath, along with other symptoms common to pulmonary fibrosis.^[4] These symptoms can make everyday activities more difficult and may worsen over time.

When pulmonary hypertension develops, additional symptoms may appear. These include a racing or fast heartbeat, chest pain, swelling of the legs, and tiredness.^[4] However, some patients may not have obvious symptoms in the early stages of lung disease, which is why regular screening is so important.^[8]

Treatment decisions are often influenced by the duration and degree of shortness of breath, changes in breathing tests, and how much the lungs are affected on imaging scans.^[8]

Causes and risk factors

The exact cause of systemic sclerosis remains unknown, but certain genetic and environmental factors appear to play a role. The risk is higher if a family member also has the condition. Environmental exposures to substances like silica, solvents, and certain medications may also increase risk. In some cases, having cancer may trigger the disease process.^[14]

The disease process begins with inflammation that seems to start in the blood vessels, damaging them. This damage causes more inflammation, which results in more tissue damage and the formation of autoantibodies, which are immune proteins that attack the body’s own tissues. The combination of inflammation, damaged blood vessels, and autoantibodies leads to the scarring seen in the skin and organs.^[14]

Certain factors increase the risk of developing or having progressive lung disease. These include being male, being African-American, having the diffuse form of systemic sclerosis, having specific antibodies in the blood (particularly anti-Scl-70 or anti-topoisomerase I antibodies), and having heart involvement.^[8]

Screening and diagnosis

Experts recommend that all patients with systemic sclerosis be screened for lung disease. Screening methods include listening to the chest with a stethoscope, breathing tests called spirometry with measurement of how well gases move from the lungs to the blood (called diffusing capacity), a specialized chest scan called high-resolution computed tomography or HRCT, and testing for specific antibodies in the blood.^[8]

The HRCT scan is considered the primary tool for diagnosing lung involvement in systemic sclerosis. This imaging test can show the extent and pattern of scarring in the lungs, which helps doctors make treatment decisions.^[8]

Breathing tests are important for tracking how the lungs are functioning over time. The most commonly used tests measure how much air the lungs can hold and how well oxygen moves from the lungs into the bloodstream. Changes in these measurements over time help doctors understand whether the lung disease is staying stable, improving, or getting worse.^[2]

Treatment options

There is currently no cure for systemic sclerosis, but treatments can help manage symptoms and slow down damage to the lungs and other organs. Because the disease involves the immune system attacking connective tissues, it is usually treated with medicines that suppress the immune system.^[4]

Among immunosuppressive medications, mycophenolate mofetil has been identified by experts as the initial treatment of choice for many patients with lung involvement. Another option is cyclophosphamide, which has also been shown to be helpful.^[8]

In 2019, a medication called nintedanib became the first treatment approved by the U.S. Food and Drug Administration specifically to slow the rate of decline in lung function in patients with systemic sclerosis-associated interstitial lung disease. This is an anti-fibrotic medication, meaning it works against the scarring process.^[10] Experts consider nintedanib a therapeutic option in patients whose lung disease continues to progress despite immunosuppressive therapy, or in patients who cannot tolerate immune-suppressing drugs. In some cases, nintedanib can be used together with mycophenolate or cyclophosphamide, particularly in patients with advanced disease when first diagnosed or those with aggressive disease progression.^[8]

In 2021, another medication called tocilizumab was approved for the same indication. This drug blocks a protein involved in inflammation. Experts consider it a therapeutic option for patients with early systemic sclerosis and lung disease who have elevated markers of inflammation in their blood.^[8][10]

If pulmonary hypertension develops, specific treatments that cause blood vessels to widen and lower pressure may be prescribed. Medications called diuretics may also be used if leg swelling occurs.^[4]

It is essential to stop smoking if you smoke, as smoking can cause narrowing of blood vessels and worsen symptoms.^[4]

Monitoring and follow-up

Regular follow-up appointments with your medical team are essential to monitor how the condition is progressing and to discuss whether treatment needs to change.^[4] Treatment success is generally defined as stabilization or improvement of signs or symptoms of lung disease and overall functional status.^[8]

Monitoring typically includes repeated breathing tests, imaging scans, and assessments of symptoms and daily functioning. The frequency of these tests depends on the severity of disease and how active it is.^[2]

Because systemic sclerosis can affect multiple organs, care often involves a team of specialists working together. This may include rheumatologists who specialize in autoimmune diseases, lung doctors, heart specialists, kidney doctors, gastroenterologists for digestive problems, and dermatologists for skin issues. This multi-disciplinary approach helps ensure all aspects of the disease are properly managed.^[8]

• Lungs
• Blood vessels
• Connective tissue

scleroderma, systemic sclerosis-associated interstitial lung disease, SSc-ILD