From the Guidelines
Diagnosing Systemic Sclerosis (SSc) requires a comprehensive approach that includes clinical evaluation, laboratory tests, and imaging studies, with a focus on characteristic skin thickening, specific antibodies, and organ involvement, as outlined in the most recent study from 2025 1. The diagnostic criteria for SSc involve a combination of clinical findings, laboratory results, and imaging studies. Key features include:
- Characteristic skin thickening and hardening, particularly affecting the fingers, hands, and face
- Presence of specific antibodies, such as anti-Scl-70 (associated with diffuse scleroderma) and anti-centromere antibodies (linked to limited scleroderma)
- Nailfold capillaroscopy to examine tiny blood vessels under the fingernails
- Pulmonary function tests to assess lung involvement
- Echocardiogram to evaluate heart function
- Gastrointestinal studies to check for digestive tract issues
- Skin biopsy to examine tissue changes microscopically According to the 2025 study 1, SSc is a rare and heterogeneous systemic autoimmune disease characterized by a triad of pathogenic factors, including vasculopathy, inflammation and autoimmunity, and fibrosis. The study highlights the importance of early intervention to limit the onset and/or progression of life-threatening manifestations, such as SSc-interstitial lung disease (SSc-ILD) and SSc-related heart involvement. The 2024 study 1 provides further insight into the diagnostic criteria, noting that SSc is an orphan disease with a heterogeneous expression, characterized by fibrosis of the skin, generalized vasculopathy, and the presence of SSc-specific antibodies. The study also emphasizes the importance of screening for ILD and pulmonary arterial hypertension (PAH) in patients with SSc. In terms of morbidity, mortality, and quality of life, early diagnosis and treatment of SSc are crucial to prevent or delay the onset of life-threatening complications, such as SSc-ILD and PAH, as highlighted in the 2023 study 1. The study notes that nearly all patients with SSc have Raynaud phenomenon, and half have digital ulcers, emphasizing the need for comprehensive management of the disease. Overall, the diagnostic criteria for SSc require a multidisciplinary approach, taking into account clinical findings, laboratory results, and imaging studies, with a focus on preventing or delaying the onset of life-threatening complications.
From the Research
Diagnostic Criteria for Systemic Sclerosis (SSc)
The diagnostic criteria for Systemic Sclerosis (SSc) include a combination of clinical features and serologic markers. Some of the key diagnostic clues in patients with SSc are:
- Raynaud phenomenon
- Skin involvement
- Clinically visible mat-like telangiectasias
- SSc-related autoantibodies 2 The sensitivity of Raynaud and proximal finger skin thickening for the diagnosis of SSc is only 57%, but the addition of clinically visible mat-like telangiectasias and SSc-related antibodies improves the sensitivity to 97% 2.
Autoantibodies in SSc
Autoantibodies play a crucial role in the diagnosis and prognosis of SSc. Some of the common autoantibodies associated with SSc include:
- Anti-centromere antibodies (ACA)
- Anti-topoisomerase I antibodies (anti-topo I)
- Anti-RNA polymerase antibodies (anti-RNAP)
- Anti-nucleolar antibodies These autoantibodies can be used to subgroup patients and predict clinical evaluation and prognosis 3, 4.
Clinical Features of SSc
The clinical features of SSc can vary widely, but some common features include:
- Sclerodactyly
- Lung fibrosis
- Pulmonary hypertension
- Gastrointestinal tract involvement
- Raynaud phenomenon
- Skin involvement above the fingers These features can be used in combination with autoantibody profiles to diagnose and manage SSc 5, 2.
Test Performance in SSc
The sensitivity and specificity of anti-centromere (ACA) and anti-Scl-70 antibodies in SSc have been studied extensively. ACA are found in 32% of SSc patients, while anti-Scl-70 antibodies are found in 34% of SSc patients 6. The specificity of each antibody is high, but varies by control group. A positive test result can be relied upon as being specific in the detection of disease, but a negative result does not exclude the diagnosis 6.