Scleroderma

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General Information

Scleroderma Week

What is scleroderma?

Scleroderma was first described in 1752 as skin that is "hard to the touch".  It is an autoimmune connective tissue disease of unknown cause that can involve multiple organ systems and frequently involves the lung.

Who is at risk?

The true incidence and prevalence of scleroderma is unknown.  However, the incidence of scleroderma is generally estimated at 10 to 20 per million individuals per year, while the prevalence rates are approximately 200 cases per million individuals. There is a genetic predisposition to scleroderma and prevalence is greatest in the Choctaw Native Americans. Systemic sclerosis is more common in adults, while localized scleroderma is more common in children.  In general, the age of onset is between 25 and 55 years.  There is a female to male predominance of approximately 5:1.  There is also some association with environmental triggers including silica and organic solvent exposure.

What are the types of Scleroderma?

The two major classifications of scleroderma include localized scleroderma and systemic sclerosis (SSc).  Localized scleroderma involves the skin and occasionally muscles, but typically does not progress to systemic disease. 

Systemic sclerosis affects the skin as well as blood vessels and the major organ systems.  A subset of patients with systemic sclerosis, known as systemic sclerosis sine scleroderma, can have internal organ involvement without obvious skin thickening.  Systemic sclerosis is otherwise divided into limited cutaneous systemic sclerosis and diffuse cutaneous systemic sclerosis. 

Limited cutaneous systemic sclerosis is characterized by skin disease that does not progress above the elbows or knees, while diffuse cutaneous systemic sclerosis also involves skin proximal to the elbows and knees as well as the chest and trunk. The face and neck can be involved in both limited and diffuse forms of scleroderma.   Limited cutaneous systemic sclerosis was formerly called CREST syndrome, which stands for: Calcinosis, Raynaud's phenomenon, Esophageal dysmotility, Sclerodactyly, and Telangiectasia (dilated skin capillaries).

Symptoms

Raynaud's phenomenon is nearly always present and is typically the first symptom; it can precede other symptoms by years and may be accompanied by digital ulcers/pits.  It is characterized by a triphasic (blue/white/red) color change of the fingers with exposure to cold, stress or vibrations.  Gastroesophageal reflux is also very common and is another early symptom. Skin involvement is the hallmark of scleroderma and includes sclerodactyly (thickening of the fingers) to more proximal skin involvement.  Skin manifestations can also include discoloration, pain, itching, telangiectasias, ulcers and calcinosis.  Most patients experience fatigue, joint and muscle pain.  These may progress to disabling arthritis and muscle weakness. Symptoms of scleroderma will also depend on the organ involved.  The most common pulmonary manifestations include shortness of breath with exertion, diminished exercise tolerance, and a nonproductive cough.

Diagnosis

A joint committee of the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) established a 2013 Classification Criteria system for the diagnosis of scleroderma.  The diagnosis of scleroderma involves a careful history and physical examination, revealing the classic skin findings and a history for Raynaud's phenomenon. Systemic sclerosis related autoantibodies are also included in this classification system and include anti-Scl-70 antibodies (anti-topoisomerase I), anti-centromere and anti-RNA polymerase III antibodies. Because of the high prevalence of pulmonary involvement, the presence of interstitial lung disease and/or pulmonary arterial hypertension are included in this most recent classification scheme.  

Interstitial lung disease typically occurs within the first 5 years of the onset of scleroderma. Pulmonary arterial hypertension more often occurs later in the disease (>10 years from onset).  It is recommended that all patients get yearly, or more frequent, pulmonary function testing and echocardiograms to screen for pulmonary involvement. A chest CT scan is the most sensitive test to evaluate for the presence of ILD and will show features consistent with "nonspecific interstitial pneumonia" including peripheral and lower lobe predominant reticulations with ground glass opacities.  A right heart catheterization is essential to diagnosis pulmonary arterial hypertension.  Risk factors for interstitial lung disease in scleroderma include male gender, African American race, early disease, primary cardiac involvement, ground glass attenuation noted on high resolution CT scan, neutrophilia and/or eosinophilia on bronchoalveolar lavage and the presence of anti-Scl-70 (anti-topoisomerase I) antibodies. Risk factors for pulmonary arterial hypertension in scleroderma include current or past telangiectasias, positive anti-centromere antibody, elevated Nt-pro BNP/BNP, decreased diffusion capacity, and elevated % forced vital capacity to % diffusion ratio.

Management

There are currently no disease-modifying therapies for scleroderma, thus treatment focuses on the individual organ system involved.  Therapies directed towards ameliorating pulmonary arterial hypertension include the following classes of medications: endothelin-1 receptor antagonists, phosphodiesterase inhibitors, soluable guanylate cyclase stimulators, prostanoids and selective prostacyclin receptor agonists.  These medications have been shown to improve exercise capacity and/or delay disease progression. Drugs are being tested that also target metabolic and inflammatory pathways.

Lung transplantation remains an option for carefully selected scleroderma patients who do not respond to medical therapy, and outcomes have been shown to be similar to those with non-scleroderma lung disease. Hematopoetic stem cell transplantation is also an option for carefully selected patients.


Four Facts About Scleroderma

  1. Approximately 300,000 Americans are diagnosed with scleroderma.

  2. Approximately three to four times more women develop scleroderma. It affects every age group, but the onset is most frequent between 25 and 55.

  3. There are no known causes or treatments for scleroderma.

  4. Lung disease is a major cause of scleroderma-related deaths.