"Systemic Sclerosis: Introduction and Overview"

by John Varga, M.D., Professor of Medicine, University of Illinois/Chicago College of Medicine, (originally published in "Scleroderma Voice," 2004 #2)

Systemic sclerosis (SSc) is an autoimmune connective tissue disease with multi-organ involvement and unpredictable course.

While still considered incurable, SSc is now viewed as a chronic treatable disease.

Scleroderma affects the circulation and blood vessels; causes inflammation and autoimmunity; and results in fibrosis (scarring) on the skin, lungs, and other organs.

SSc affects 1 in 4,000 adults in the United States. It is more frequent in women than men and in African-Americans than whites. The highest prevalence rates (1 in 1,500) are reported in Choctaw Native Americans.

What Causes Scleroderma?

The cause of SSc is still unknown. Some evidence links SSc with environmental or occupational exposures to silica, vinyl chloride and organic solvents. Cells of maternal origin (maternal microchimerism) can be detected in the circulation of 22% of healthy individuals and 72% of women with SSc. In SSc, these microchimeric cells may infiltrate the skin and other affected tissues, and play some role in the disease.

The Key Role of Vascular Injury

The application of powerful new research tools, such as DNA microarrays, population-based genetic studies and gene targeting in animals has brought the pathophysiology of SSc into sharper focus during the past decade. It is now generally accepted that vascular injury is an early event that leads to inflammation in the skin, the lungs, and other target tissues. Something then happens in the context of the lesional tissue that allows injury and scarring to persist even after resolution of the local inflammation. Damage to circulation is prominent in the small and medium-size blood vessels of the fingers, lungs, heart, and gastrointestinal tract.

Raynaud Phenomenon and Renal Crisis

Raynaud phenomenon is a prominent early vascular feature, and in some patients may progress to severe digital ischemia. However, many newer treatments are now available, and in most patients can successfully reduce the frequency and severity of Raynaud attacks, and prevent the progression of this complication.

In the kidneys, injury to the medium-sized arteries can precipitate scleroderma renal crisis (SRC), an acute syndrome with malignant hypertension and progressive renal failure.

Pulmonary Hypertension: A Major Complication of Scleroderma

Pulmonary hypertension (PH) is a major underrecognized complication in systemic scleroderma (SSc). It develops in 40% of SSc patients, and occurs more frequently in limited cutaneous scleroderma (lcSSc, also known as CREST).

Risk factors include older age of disease onset and the presence of antibodies to fibrillarin. While early PH is asymptomatic, with progression increasing heart failure develops.

Because patients may have no specific respiratory complaints, all patients should be screened. Tests for PH include pulmonary function testing, echocardiogram and CT of the chest. The gold standard for the diagnosis of PH remains cardiac catheterization. Many patients with SSc also develop scarring/fibrosis in the lungs, which is frequently progressive, ultimately leading to limitation in exercise tolerance. Screening for this complication is also essential at time of diagnosis and on an ongoing basis to detect its presence. Screenings include pulmonary funtion tests, chest X-ray and High Resolution CT scan. In addition, many centers perform bronchoscopic lavage of the lung, in order to look for early evidence of lung fibrosis.

Scleroderma Treatment

Until recently, therapeutic options for patients with SSc were few. The relative rarity of SSc, its variable presentation, and absence of interest from the pharmaceutical industry all contributed to a dearth of studies of new treatments. In contrast, many potential treatments are now becoming available, and the therapeutic pipeline is rich.

Furthermore, an international group of collaborating centers is working together to standardize treatments and their evaluation. SSc should be approached as a chronic treatable disease, much like diabetes.

Because SSc is a complex and heterogeneous disease with an unpredictable course and highly variable prognosis, treatment must be individualized. Patients should be referred to specialized centers where they can receive coordinated multispecialty care, and access to investigational treatments.

Print This Page