Connective Tissue Diseases

Clinical Background

Several autoimmune connective tissue diseases may present with similar features. These include systemic lupus erythematosus (SLE), Sjögren syndrome, mixed connective tissue disease (MCTD), scleroderma (SS), inflammatory myopathies (polymyositis/dermatomyositis [PM/DM]) and undifferentiated connective tissue disease (UCTD)

Epidemiology

Incidence - ranges from 15-50/100,000 depending on disease
Age - onset 15-40 years with peak onset 20-30 years
Sex - F>M (6-10:1)

Pathophysiology

Circulating antigen-antibody complexes affect a variety of organs
Multisystem disease presentation; major blood vessels are the predominant target

Clinical Presentation

Musculoskeletal - arthralgias, arthritis, synovitis, myopathy
Dermatologic - skin rashes, Raynaud phenomena, photosensitivity
Cardiopulmonary - pleuritis, pericarditis, fibrosis
Renal - proteinuria, glomerulonephritis
Otorhinolaryngologic - Sicca syndrome, oral ulcers
Gastrointestinal - gastroesophageal reflux disease (GERD)
Neurologic - seizures, encephalopathy
Hematologic - cytopenias (involving neutrophils, erythrocytes and platelets)

Treatment

Anti-inflammatory based and includes glucocorticosteroids and other drugs such as methotrexate and mycophenolate

See Also

Inflammatory Myopathies

Mixed Connective Tissue Disease - MCTD

Rheumatoid Arthritis - RA

Scleroderma - Systemic Sclerosis

Sjögren Syndrome

Systemic Lupus Erythematosus - SLE

Tests

Tests generally appear in the order most useful for common clinical situations

Test name: Anti-Nuclear Antibodies (ANA), IgG Screen with Reflex to IFA Titer

ARUP #: 0050080

Methodology: Enzyme-Linked Immunosorbent Assay/Indirect Fluorescent Antibody

Use:

Initial screen for connective tissue diseases

Limitations:

Not disease specific

Follow-up:

Confirm specificity based on pattern and/or clinical suspicion; results are not disease specific

Test name: Connective Tissue Diseases Profile

ARUP #: 0051668

Methodology: Multi-Analyte Fluorescent Detection

Use:

Follow-up testing based on positive ANA

Components include IgG antibody testing for: Smith; RNP (U1) (Ribonucleic Protein); SSA (Ro); SSB (La); Jo-1; Ribosomal P Protein; Centromere; Scleroderma (Scl-70)

Additional Tests Available

Test name: RNP (U1) (Ribonucleic Protein) (ENA) Antibody, IgG

ARUP #: 0050470

Methodology: Multi-Analyte Fluorescent Detection

Comments:

Test name: Extractable Nuclear Antigen Antibodies (RNP, Smith, Scleroderma, SSA, & SSB)

ARUP #: 0050653

Methodology: Multi-Analyte Fluorescent Detection

Comments:

Test name: Anti-Nuclear Antibody (ANA), IgG Screen with Reflex to ANA IFA Titer, dsDNA, RNP, Smith, SSA, & SSB Antibodies

ARUP #: 0050317

Methodology: Enzyme-Linked Immunosorbent Assay/Indirect Fluorescent Antibody/Multi-Analyte Fluorescent Detection

Comments:

Test name: Extractable Nuclear Antigen Antibodies (RNP, Smith, SSA, & SSB)

ARUP #: 0050652

Methodology: Multi-Analyte Fluorescent Detection

Comments:

Test name: Jo-1 Antibody, IgG

ARUP #: 0099592

Methodology: Multi-Analyte Fluorescent Detection

Comments:

Test name: SSA (Ro) (ENA) Antibody, IgG

ARUP #: 0050691

Methodology: Multi-Analyte Fluorescent Detection

Comments:

Test name: PM-Scl Antibody, ID

ARUP #: 0099591

Methodology: Immunodiffusion

Comments:

Test name: SSB (La) (ENA) Antibody, IgG

ARUP #: 0050692

Methodology: Multi-Analyte Fluorescent Detection

Comments:

Test name: dsDNA (Double Stranded DNA) Antibody, IgG

ARUP #: 0050215

Methodology: Enzyme-Linked Immunosorbent Assay/Indirect Fluorescent Antibody

Comments:

Test name: Smith (ENA) Antibody, IgG

ARUP #: 0050085

Methodology: Multi-Analyte Fluorescent Detection

Comments:

Test name: Ribosomal P Protein Antibody

ARUP #: 0099249

Methodology: Multi-Analyte Fluorescent Detection

Comments:

Test name: ssDNA Antibody, IgG

ARUP #: 0099528

Methodology: Enzyme-Linked Immunosorbent Assay

Comments:

Test name: Histone Antibody, IgG

ARUP #: 0050860

Methodology: Enzyme-Linked Immunosorbent Assay

Comments:

Test name: Anti-Neutrophil Antibody

ARUP #: 0055506

Methodology: Flow Cytometry

Comments:

Test name: Lupus Comprehensive Reflexive Panel

ARUP #: 0050119

Methodology: Refer to individual components

Comments:

Test name: Scleroderma (Scl-70) (ENA) Antibody, IgG

ARUP #: 0050599

Methodology: Multi-Analyte Fluorescent Detection

Comments:

Test name: Centromere Antibody, IgG

ARUP #: 0050714

Methodology: Multi-Analyte Fluorescent Detection

Comments:

References

General References

Bossuyt X, Frans J, Hendrickx A, Godefridis G, Westhovens R, Marien G. Detection of anti-SSA antibodies by indirect immunofluorescence. Clin Chem. 2004;50(12):2361-2369.

Brouwer R, Hengstman GJ, Vree Egberts W, Ehrfeld H, Bozic B, Ghirardello A, Grondal G, Hietarinta M, Isenberg D, Kalden JR, Lundberg I, Moutsopoulos H, Roux-Lombard P, Vencovsky J, Wikman A, Seelig HP, van Engelen BG, van Venrooij WJ. Autoantibody profiles in the sera of European patients with myositis. Ann Rheum Dis. 2001;60(2):116-123.

Haugbro K, Nossent JC, Winkler T, Figenschau Y, Rekvig OP. Anti-dsDNA antibodies and disease classification in antinuclear antibody positive patients: the role of analytical diversity. Ann Rheum Dis. 2004;63(4):386-394.

Hoffman IE, Peene I, Meheus L, Huizinga TW, Cebecauer L, Isenberg D, De Bosschere K, Hulstaert F, Veys EM, De Keyser F. Specific antinuclear antibodies are associated with clinical features in systemic lupus erythematosus. Ann Rheum Dis. 2004;63(9):1155-1158.

Koenig M, Fritzler MJ, Targoff IN, Troyanov Y, Senecal JL. Heterogeneity of autoantibodies in 100 patients with autoimmune myositis: insights into clinical features and outcomes. Arthritis Res Ther. 2007;9(4):R78-.

McGhee JL, Kickingbird LM, Jarvis JN. Clinical utility of antinuclear antibody tests in children. BMC Pediatr. 2004;4:13-.

Peene I, Meheus L, Veys EM, De Keyser F. Diagnostic associations in a large and consecutively identified population positive for anti-SSA and/or anti-SSB: the range of associated diseases differs according to the detailed serotype. Ann Rheum Dis. 2002;61(12):1090-1094.

Tozzoli R, Bizzaro N, Tonutti E, Villalta D, Bassetti D, Manoni F, Piazza A, Pradella M, Rizzotti P. Guidelines for the laboratory use of autoantibody tests in the diagnosis and monitoring of autoimmune rheumatic diseases. Am J Clin Pathol. 2002;117(2):316-324.

Medical Reviewers

Hill, Harry R., M.D. Group Medical Director, Laboratory of Immunology, ARUP Laboratories, and Executive Director of the ARUP Institute for Clinical and Experimental Pathology; Professor and Division Head, Clinical Pathology, University of Utah

Tebo, Anne E., Ph.D. Assistant Medical Director, Immunology at ARUP Laboratories; Clinical Assistant Professor, Clinical Pathology, University of Utah

Comprehensive Review: July 2008
Last Update: July 2008