Scleroderma, also known as systemic sclerosis, is a chronic autoimmune rheumatic disease characterized by the immune system mistakenly attacking its own connective tissues. This involves the excessive production and accumulation of collagen, leading to the hardening and tightening of the skin and internal organs, including blood vessels, the digestive tract, lungs, heart, and kidneys. Because symptoms overlap with other conditions, there is no single definitive test for scleroderma. Instead, diagnosis is established by a comprehensive collection of clinical evidence, specific laboratory results, and specialized organ function assessments, requiring careful evaluation by a rheumatologist.
Recognizing the Need for Testing
The diagnostic process begins with a physical examination and a review of the patient’s medical history. Doctors look for specific physical indicators, such as Raynaud’s phenomenon, where fingers and toes turn white, blue, or red in response to cold or stress. This vascular symptom is often the first noticeable change, sometimes preceding other symptoms by years.
Puffy or swollen fingers, often worse in the morning, are also common early signs before the skin hardens. The examination assesses the degree of skin thickening and tightness, particularly sclerodactyly (on the hands). Skin involvement is classified as either limited (typically below the elbows and knees) or diffuse (involving skin above these joints and the torso). Joint pain, stiffness, and digestive issues like persistent heartburn or difficulty swallowing also raise suspicion, prompting the need for laboratory investigation.
Blood Tests and Autoantibody Markers
Specialized blood tests search for specific markers of autoimmune activity. The Antinuclear Antibody (ANA) test is a primary screening tool, positive in 85% to 95% of individuals with systemic sclerosis. Since a positive ANA is not specific enough to confirm scleroderma, the process looks for more specific autoantibodies highly correlated with the disease. These markers help predict the likely course and potential organ complications.
The Anti-Centromere Antibody (ACA) is associated with the limited form of systemic sclerosis, and patients generally have a lower risk of severe internal organ involvement. Conversely, the Anti-Scl-70 (Topoisomerase I) Antibody is strongly linked to the diffuse form and carries an increased risk for pulmonary fibrosis and more widespread disease.
The Anti-RNA Polymerase III antibody is found in 11% to 23% of patients. Individuals positive for this marker are at a higher risk of developing diffuse skin involvement and scleroderma renal crisis (rapid kidney failure). These autoantibody profiles are mutually exclusive, meaning a patient typically has only one major scleroderma-specific antibody, which aids in classifying the disease subtype and guiding monitoring strategies.
Evaluating Internal Organ Involvement
Extensive testing is required to determine if the disease has damaged major internal organs. These tests stage disease severity and assess the risk of serious complications, rather than establishing the initial diagnosis. Interstitial lung disease (ILD) is a major concern and a leading cause of death related to scleroderma. Pulmonary Function Tests (PFTs) measure lung capacity, including Forced Vital Capacity (FVC) and diffusing capacity (DLCO). However, the gold standard for diagnosing ILD is the High-Resolution CT (HRCT) scan of the chest, which provides detailed images to detect subtle fibrosis or inflammation.
The heart requires careful screening for issues like pulmonary arterial hypertension (PAH) or direct muscle involvement. This evaluation includes an Echocardiogram (Echo) to assess structure and function, and an Electrocardiogram (ECG) to monitor electrical activity. For the kidneys, a basic metabolic panel monitors function. Patients with the diffuse subtype are often instructed to regularly monitor blood pressure to detect scleroderma renal crisis. Additional studies, such as a barium swallow, may be ordered to evaluate the gastrointestinal tract if severe acid reflux or dysmotility symptoms are present.
Confirming the Diagnosis and Next Steps
The final diagnosis of systemic sclerosis is a clinical judgment made by a rheumatologist. This involves synthesizing physical findings (like Raynaud’s phenomenon and skin thickening) with objective data from autoantibody tests and organ staging assessments. The presence of specific autoantibodies and characteristic clinical symptoms confirms the diagnosis and classifies the disease as limited or diffuse systemic sclerosis.
Once confirmed, the physician determines the severity and the organs at greatest risk, transitioning the patient to the treatment planning phase. Patients are referred to relevant specialists, such as cardiologists or pulmonologists, for ongoing monitoring and management tailored to their specific organ involvement. Regular follow-up testing, including repeat PFTs and Echos, is scheduled to track disease progression and ensure timely intervention.