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. See Classification Criteria below.
ACR/EULAR Criteria for the Classification of Systemic Sclerodermaa
|Skin thickeningb of the fingers of both hands extending proximal to MCP joints (single criterion sufficient for classification of SSc)
|Other skin thickeningbc
|Sclerodactyly of the fingers (distal to MCP, proximal to PIP joints)
||Ulcers on digital tips
|Abnormal nailfold capillaries
|Pulmonary arterial hypertension and/or interstitial lung disease
|Scleroderma-related antibodies (any ACA, anti-Scl-70, or anti-RNA polymerase III antibodies)
|aThese criteria do not apply to patients with an SSc-like disorder that better explains their signs/symptoms.
bPatients with no skin thickening of the fingers cannot be classified as having SSc.
cThe highest score from this category should be used to calculate the total score.
dA total score of ≥9 is diagnostic for SSc.
ACR, American College of Rheumatology; EULAR, European League Against Rheumatism; MCP, metacarpophalangeal; n/a, not applicable; PIP, proximal interphalangeal
Source: Adapted from van den Hoogen, 2013
Testing for SSc typically starts with a CBC with platelet count and an automated differential, followed by antinuclear antibody (ANA) IgG testing by immunofluorescence assay (IFA). ANAs are seen in the majority of patients with SSc (approximately 95%), although a small subset of patients will be negative for ANAs.
Since 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 (eg, centromere, nucleolar, and speckled patterns). For comprehensive information about ANA patterns and clinical associations, refer to the International Consensus on ANA Patterns website.
Criteria Antibody Tests
Criteria antibodies for SSc include the following :
- Anti-Scl-70 (also known as antitopoisomerase 1)
- 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 and anti-RNA polymerase III antibodies are more common in diffuse disease.
Noncriteria Antibody Tests
Testing for additional antibodies (such as the following) may be indicated in patients with negative criteria antibody tests in whom SSc is still strongly suspected:
- Anti-fibrillarin or anti-u3 ribonucleoprotein (anti-U3 RNP) antibodies
- Anti-PM/Scl (anti-PM/Scl-100) antibodies
- Anti-Th/To antibodies
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-U1 RNP antibodies
- Anti-Ku antibodies
- Antimitochondrial antigen M2 antibodies (AMAs)
- Antiphospholipid antibodies
- Cyclic citrullinated peptide (CCP)
Because SSc is chronic, patients with the disease require annual follow-up, and those with progressive disease may have need of 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 in assessing 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 tests, creatinine, and urea; and urine protein tests.