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Systemic Sclerosis - Scleroderma

Last Literature Review: May 2026 Last Update:

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Systemic sclerosis (SSc), also called scleroderma, is a chronic autoimmune disorder characterized by fibrosis of the skin and various organs. ,  Early diagnosis and classification are important so that patients can be evaluated for organ involvement and/or damage.  However, because SSc is a heterogeneous disease, clinical presentation and disease course vary, and manifestations may overlap with those of other rheumatic disorders, all of which can complicate diagnosis.cite , ,  Clinical subsets of SSc include limited and diffuse cutaneous disease; in addition, some individuals have SSc overlap syndromes, which involve features of different systemic autoimmune rheumatic diseases (SARDs) as well as those of SSc.cite  Autoantibody formation is characteristic of SSc, and laboratory testing involves assessment for SSc-specific autoantibodies.  Criteria antibody tests for SSc include tests for anti-Scl-70 (also known as antitopoisomerase 1), anticentromere antibody (ACA), and anti-RNA polymerase III.  Testing for other antibodies associated with SSc may be indicated if criteria test results are negative. Refer to the Laboratory Testing section for more information on testing for SSC.

Quick Answers for Clinicians

What role do laboratory testing and clinical findings play in the diagnosis of systemic sclerosis?

The diagnosis of systemic sclerosis (SSc) involves a combination of clinical findings and autoantibody test results. SSc has a variable disease presentation and prognosis, but many patients will have skin thickening, which is commonly observed in the fingers. ,  Skin thickening extending to the metacarpophalangeal joint is sufficient to classify a patient as having SSc.  Refer to the Classification Criteria section for more detail on the classification of SSc. Approximately 95% of patients with SSc have antinuclear antibodies (ANAs),  so testing for ANAs is an initial step in disease assessment. Subsequent testing for SSc is determined by the ANA patterns observed (e.g., homogeneous, centromere, nucleolar, and speckled nuclear patterns or reticular/AMA cytoplasmic patterns). Refer to the Laboratory Testing section and the ARUP Consult Antinuclear Antibody Disease Testing Algorithm for more information.

Which tests are recommended for monitoring patients with systemic sclerosis?

Because systemic sclerosis (SSc) is a chronic illness, regular monitoring is needed to assess disease activity and progression. Laboratory tests for monitoring may include erythrocyte sedimentation rate (ESR) and/or C-reactive protein (CRP), CBC, liver function, creatinine, urea, and urinary protein tests. 

Autoantibody tests, although important for diagnosis, are not necessary for monitoring. Refer to the Monitoring section for more detail.

Indications for Testing

Individuals with skin thickening of the fingers that extends proximal to the metacarpophalangeal joints should be tested for SSc. Patients with puffy fingers or sclerodactyly, fingertip ulcers or pitting scars, abnormal nailfold capillaries, and/or signs of Raynaud phenomenon should also be tested, particularly if these signs are accompanied by pulmonary changes, telangiectasia, or arthritis/arthralgia. , 

Laboratory Testing

Diagnosis

Classification Criteria

ACR/EULAR Criteria for the Classification of Systemic Sclerodermaa
CategorySubitemsScoreb
Skin thickeningc of the fingers of both hands extending proximal to MCP joints (single criterion sufficient for classification of SSc)n/a9
Other skin thickeningc,dPuffy fingers2
Sclerodactyly of the fingers (distal to MCP, proximal to PIP joints)4
Fingertip lesionsdUlcers on digital tips2
Pitting scars3
Telangiectasian/a2
Abnormal nailfold capillariesn/a2
Pulmonary arterial hypertension and/or interstitial lung diseasen/a2
Raynaud phenomenonn/a3
Scleroderma-related antibodies (any ACA, anti-Scl-70, or anti-RNA polymerase III antibodies)n/a3

aThese criteria do not apply to patients with an SSc-like disorder that better explains their signs/symptoms.

bA total score of ≥9 is diagnostic for SSc.

cPatients with no skin thickening of the fingers cannot be classified as having SSc.

dThe highest score from this category should be used to calculate the total score.

ACR, American College of Rheumatology; EULAR, European League Against Rheumatism; MCP, metacarpophalangeal; n/a, not applicable; PIP, proximal interphalangeal

Source: van den Hoogen, 2013 

Initial Tests

Testing for SSc typically starts with a CBC with platelet count and an automated differential, followed by antinuclear antibody (ANA) immunoglobulin G (IgG) testing by immunofluorescence assay (IFA). ANAs are observed in the majority of patients with SSc (approximately 95%),  although a small subset of patients will be negative for ANAs. 

Because ANAs can be found in many conditions, ANA testing is best used when suspicion for SSc or another SARD is high.  Subsequent testing is based on the ANA patterns observed (e.g., homogeneous, centromere, nucleolar, and speckled nuclear patterns or reticular/AMA cytoplasmic pattern). For comprehensive information about ANA patterns and clinical associations, refer to the International Consensus on ANA Patterns. 

Criteria Antibody Tests

Criteria antibodies for SSc include the following :

  • Anti-Scl-70 (also known as antitopoisomerase 1)
  • ACA
  • Anti-RNA polymerase III

More than 50% of patients with SSc will have one of these three antibodies, which are generally exclusive of each other. ,  The presence of SSc-specific antibodies may help predict disease phenotype. For example, ACAs are generally associated with limited cutaneous SSc, including CREST (calcinosis, Raynaud syndrome, esophageal dysmotility, sclerodactyly, and telangiectasia) syndrome.  Anti-Scl -70 and anti-RNA polymerase III antibodies are more common in diffuse disease.

Noncriteria Antibody Tests
 

Testing for other antibodies may be indicated in patients with negative criteria antibody tests in whom SSc is still strongly suspected. These additional antibodies include the following:

  • Antifibrillarin or anti-u3 ribonucleoprotein (anti-U3 RNP)
  • Anti-PM/Scl (anti-PM/Scl-100)
  • Anti-Th/To

The following antibodies have also been reported in some studies as associated with SSc, ,  but the clinical utility of testing for these antibodies in the workup for SSc continues to be explored:

  • Anti-Smith/RNP
  • Anti-Ro
  • Anti-La
  • Anti-Ku
  • Antimitochondrial antigen M2 (AMAs)
  • Antiphospholipid
  • Cyclic citrullinated peptide (CCP)

Monitoring

Because SSc is chronic, patients with the disease require annual follow-up, and those with progressive disease may need more frequent follow-up. Some studies associate particular antibodies with clinical manifestations; therefore, detection of particular antibodies early in the disease course may be useful to assess risks for specific clinical manifestations, ,  including organ involvement and cancer. Other laboratory tests to monitor disease activity include erythrocyte sedimentation rate (ESR) and/or C-reactive protein (CRP), CBC, liver function, creatinine, urea, and urine protein tests. 

ARUP Laboratory Tests

SSc Panel Tests
Criteria Antibody Tests
Noncriteria/Other Antibody Tests and Panels
3018867
Extended Myositis Panel 3018867
Method

Qualitative Immunoprecipitation / Semi-Quantitative Multiplex Bead Assay / Qualitative Immunoblot / Semi-Quantitative Indirect Fluorescent Antibody (IFA) / Qualitative Particle-Based Multianalyte Technology (PMAT)

Components: ANA titer, ANA pattern, anti-Scl-70, anti-RNP III antibody, anti-Smith/RNP antibody, antifibrillarin (U3 RNP), anti-PM/Scl antibody

3018869
Interstitial Lung Disease Autoantibody Panel 3018869
Method

Qualitative Immunoprecipitation / Semi-Quantitative Multiplex Bead Assay / Qualitative Immunoblot / Semi-Quantitative Enzyme-Linked Immunosorbent Assay (ELISA) / Quantitative Immunoturbidimetry / Semi-Quantitative Indirect Fluorescent Antibody (IFA) / Qualitative Particle-Based Multianalyte Technology (PMAT)

References