Qualitative Immunoblot/Semi-Quantitative Indirect Fluorescent Antibody/Semi-Quantitative Multiplex Bead Assay/Semi-Quantitative Enzyme-Linked Immunosorbent Assay
- Indicated when suspicion for SSc is high and patient presents with features of overlap syndrome
- Individual tests in panel may be ordered separately. (See Related Tests.)
Semi-Quantitative Indirect Fluorescent Antibody/Semi-Quantitative Multiplex Bead Assay/Semi-Quantitative Enzyme-Linked Immunosorbent Assay
- Indicated for patients with distinct features of SSc
- Negative results do not rule out SSc; if test is negative and suspicion for SSc is high, consider testing for U3 RNP (fibrillarin), PM/Scl-100, U1RNP, Th/Tho, or other connective tissue disease autoantibodies based on patient’s clinical presentation
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. The initial testing strategy includes CBC with platelet count and automated differential and nuclear antibody (ANA) by IFA, IgG. Confirmatory or secondary testing should be performed based on ANA IFA patterns (centromere, nucleolar, and speckled patterns), clinical presentation, and/or ethnicity.
Age of Onset
Autoimmune connective tissue diseases may present with similar features, particularly early in disease, making diagnosis difficult. The following considerations may assist in determining a diagnosis of SSc:
- ANA IFA patterns may help define diagnostic pathways
- The presence of SSc-specific antibodies may help predict disease phenotypes, which include:
- Antibody patterns may differ by ethnicity
- Antibodies against U3-RNP are more common in African Americans
- Th/To autoantibodies are more common in White individuals with limited cutaneous SSc
- ANA by IFA for SSc: 90-95%
- Individual SSc-specific marker: may vary based on ethnicity
- ANA patterns (including centromere) are reported
- If positive, pattern and titers are reported
Knobler R, Moinzadeh P, Hunzelmann N, et al. European Dermatology Forum S1-guideline on the diagnosis and treatment of sclerosing diseases of the skin, Part 1: localized scleroderma, systemic sclerosis and overlap syndromes. J Eur Acad Dermatol Venereol. 2017;31(9):1401-1424.
Salazar GA, Assassi S, Wigley F, et al. Antinuclear antibody-negative systemic sclerosis. Semin Arthritis Rheum. 2015;44(6):680-686.
Tartar DM, Chung L, Fiorentino DF. Clinical significance of autoantibodies in dermatomyositis and systemic sclerosis. Clin Dermatol. 2018;36(4):508-524.
van den Hoogen F, Khanna D, Fransen J, et al. 2013 classification criteria for systemic sclerosis: an American college of rheumatology/European league against rheumatism collaborative initiative. Ann Rheum Dis. 2013;72(11):1747‐1755.
Alba MA, Velasco C, Simeón CP, et al. Early- versus late-onset systemic sclerosis: differences in clinical presentation and outcome in 1037 patients. Medicine (Baltimore). 2014;93(2):73-81.
Nandiwada SL, Peterson LK, Mayes MD, et al. Ethnic differences in autoantibody diversity and hierarchy: more clues from a US cohort of patients with systemic sclerosis. J Rheumatol. 2016;43(10):1816-1824.