Who Should Be Suspected?
SSc patients typically present with fatigue, weakness, arthralgias, and thickening and tightness of the skin, either restricted or diffuse. They can also have Raynaud phenomena and signs of multiple internal organ involvement.
Extracutaneous organ involvement can lead to dysfunction or failure of almost any internal organ including the musculoskeletal system (e.g., arthralgia, myalgia), lungs (e.g., pulmonary fibrosis, interstitial lung disease), kidneys (e.g., proteinuria, decreased GFR, scleroderma renal crisis, hypertension), heart (e.g., ventricular dysfunction), gastrointestinal tract (e.g., dysphagia, heartburn), and the nervous system (e.g., headache, seizures). Lung involvement is the leading cause of death in SSc patients.
Women are at much higher risk for scleroderma than are men, with a ratio of ≥3:1.
Laboratory Findings
Diagnosis of SSc is based on clinical findings, and can be confirmed (but not excluded) by serology.
Autoantibody levels correlate with the severity of disease, and titers fluctuate with disease activity. More than 95% of SSc patients have at least one autoantibody.
ANA test, with low titers and a nucleolar or speckled pattern by IFA, is positive in 60–90% of patients. CREST syndrome is usually associated with the centromere pattern.
Anti–topoisomerase I (anti-Scl-70) antibodies are present in 30–70% of patients with dcSSc, and they are highly specific, but occur late in the disease. When positive, they suggest higher risk of severe interstitial lung disease, cardiac, or renal involvement.
Anticentromere antibodies in moderate titers are highly specific but have only moderate sensitivity. They are typically associated with lcSSc and found in the majority of patients with CREST syndrome.
Anti-RNA polymerase III antibodies are specific for SSc and have moderate sensitivity. They are associated with extensive skin involvement and scleroderma renal crisis.
Anti-β2-glycoprotein 1 and anticardiolipin antibodies may be positive. Anti-β2-glycoprotein 1 antibodies have been found to be independently associated with macrovascular disease and mortality in SSc patients.
Antibodies to U3-RNP (antifibrillarin) are detected in dcSSc patients and associated with increased risk of pulmonary hypertension, scleroderma renal disease, and skeletal muscle involvement.
