Algorithm(s)
PDF algorithm(s) available at www.arupconsult.com.
Connective Tissue Disease Testing Algorithm
Immunodeficiency Evaluation for Chronic Infections in Adults and Older Children Testing Algorithm
Immunodeficiency Evaluation for Chronic Infections in Infants and Children Testing Algorithm
Clinical Background
Systemic sclerosis is a chronic multisystem autoimmune disorder characterized by thickening of the skin and accumulation of connective tissue in various organs.
Epidemiology
- Incidence - 3-20/1,000,000
- Age - peak onset 20-40 years
- Gender - F>M
| Classification of Scleroderma (Systemic Sclerosis) and Scleroderma-like Disorders |
- Systemic sclerosis
- Limited cutaneous disease
- Diffuse cutaneous disease
- Sine scleroderma
- Undifferentiated connective tissue disease
- Overlap syndromes
- Localized scleroderma
- Morphea
- Linear scleroderma
- En coup de sabre
- Chemical-induced scleroderma-like disorders
- Toxic-oil syndrome
- Vinyl chloride-induced disease
- Bleomycin-induced fibrosis
- Pentazocine-induced fibrosis
- Epoxy- and aromatic hydrocarbons-induced fibrosis
- Eosinophilia-myalgia syndrome
- Other scleroderma-like disorders
- Scleredema adultorum of Buschke
- Scleromyxedema
- Chronic graft-vs-host disease
- Eosinophilic fascitis
- Digital sclerosis in diabetes
- Primary amyloidosis and amyloidosis associated with multiple myeloma
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Pathophysiology
- Pathologic remodeling of connective tissues
- Typified by 3 cardinal features
- Excess collagen production
- Vascular damage
- Inflammation or autoimmune processes
Clinical Presentation
- Dermatologic - thickening of skin
- Gastrointestinal - Raynaud phenomenon, esophageal dysmotility, reflux, gastroparesis, malabsorption, constipation
- Pulmonary - interstitial fibrosis, pulmonary hypertension
- Musculoskeletal - arthritis, myopathy, weakness
- Cardiovascular - fibrosis, pericarditis
- Renal - glomerulonephritis
- Head and neck - Sicca syndrome, hypothyroidism, Sjögren syndrome
- Central nervous system - cranial neuropathies, peripheral neuropathies
Treatment
- Remittive agents - cyclophosphamide
- May alter the course of the disease; however as yet no definitive studies
See Also
Algorithm(s)
PDF algorithm(s) available at www.arupconsult.com.
Connective Tissue Disease Testing Algorithm
Immunodeficiency Evaluation for Chronic Infections in Adults and Older Children Testing Algorithm
Immunodeficiency Evaluation for Chronic Infections in Infants and Children Testing Algorithm
Diagnosis
Diagnosis
- Clinical presentation is characteristic of disease
- Laboratory testing
- Antibody testing
- Scl-70 is a specific marker of scleroderma when it is the only autoantibody present
- Scl-70 seen in only 20-60% of patients with scleroderma
- Marker not useful in prognostication
| Distribution of Antibodies in Connective Tissue Disease Types |
| | Systemic Lupus Erythematosus (SLE) | Sjögren Syndrome | Mixed Connective Tissue Disease (MCTD) | Progressive Systemic Sclerosis (PSS) | Scleroderma |
| dsDNA abs | 50-60% | 20-30% | 20-25% | <5% | |
| Histone abs | Idiopathic 18-53%
Drug-induced 80-95% | | <20% | <20% | <20% |
| RNP | 20-30% | | 95-100% | 15-25% | 5-10% |
| Scl-70 | | | | 25% | 20-60% |
| SSA | ANA positive patients
30-40% | 70-75% | | 5-10% | |
| SSB | 15-25% | 50-60% | | 5-10% | |
| Jo-1 abs | Found in polymyositis, dermatomyositis, myositis associated with rheumatic disease |
Differential Diagnosis - Thyroid disorders
- Amyloidosis
- POEMS syndrome
- Diabetes
- Porphyria
- Neoplasm
- Raynaud phenomenon
Algorithm(s)
PDF algorithm(s) available at www.arupconsult.com.
Connective Tissue Disease Testing Algorithm
Immunodeficiency Evaluation for Chronic Infections in Adults and Older Children Testing Algorithm
Immunodeficiency Evaluation for Chronic Infections in Infants and Children Testing Algorithm
| 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: First line test for connective tissue disease screening |
| Test name: Scleroderma (Scl-70) (ENA) Antibody, IgG
|
| ARUP #: 0050599 |
| Methodology: Multi-Analyte Fluorescent Detection
|
| Use: Order as secondary screen based on results of ANA testing |
| Test name: Centromere Antibody, IgG
|
| ARUP #: 0050714 |
| Methodology: Multi-Analyte Fluorescent Detection
|
| Use: Order as secondary screen based on results of ANA testing |
| Test name: RNP (U1) (Ribonucleic Protein) (ENA) Antibody, IgG
|
| ARUP #: 0050470 |
| Methodology: Multi-Analyte Fluorescent Detection
|
| Use: Order as secondary screen based on results of ANA testing |
| Limitations: RNP antigens also contain epitopes which are immunologically identical to free Smith antigens. The Smith antibody response must be considered when interpreting RNP results |
| Test name: PM-Scl Antibody, ID
|
| ARUP #: 0099591 |
| Methodology: Immunodiffusion
|
| Use: Order as secondary screen based on results of ANA testing |
Additional Tests Available
| Test name: SSA (Ro) (ENA) Antibody, IgG
|
| ARUP #: 0050691 |
| Methodology: Multi-Analyte Fluorescent Detection
|
| Comments: |
| Test name: SSB (La) (ENA) Antibody, IgG
|
| ARUP #: 0050692 |
| Methodology: 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: Centromere Antibody, IgG
|
| ARUP #: 0050714 |
| Methodology: Multi-Analyte Fluorescent Detection
|
| Comments: |
Additional Information
When cell culture substrates (Hep-2 cells) are used in ANA testing, ANA incidence is:
- >80% in SLE, Sjögren syndrome and scleroderma
- 50-80% in adult rheumatoid arthritis and mixed connective tissue disease
- About 40% in juvenile rheumatoid arthritis
References
Guidelines
Zulian F, Woo P, Athreya BH, Laxer RM, Medsger TA Jr, Lehman TJ, Cerinic MM, Martini G, Ravelli A, Russo R, Cuttica R, de Oliveira SK, Denton CP, Cozzi F, Foeldvari I, Ruperto N. The Pediatric Rheumatology European Society/American College of Rheumatology/European League against Rheumatism provisional classification criteria for juvenile systemic sclerosis. Arthritis Rheum.
2007;
57(
2):
203-212.
Cited References
Gilliland BC. Systemic Sclerosis (Scleroderma) and Related Disorders. In Kasper D et al. eds. Harrison's Principles of Internal Medicine, 16th ed. New York: McGraw-Hill, 2005. pp. 1979-1990.
General References
Basu D, Reveille JD. Anti-scl-70. Autoimmunity.
2005;
38(
1):
65-72.
Chung L, Lin J, Furst DE, Fiorentino D. Systemic and localized scleroderma. Clin Dermatol.
2006;
24(
5):
374-392.
Jaskowski TD, Schroder C, Martins TB, Mouritsen L, Hill HR. Comparison of three commercially available enzyme immunoassays for the screening of autoantibodies to extractable nuclear antigens. J Clin Lab Anal.
1995;
9(
3):
166-172.
Lyons R, Narain S, Nichols C, Satoh M, Reeves WH. Effective use of autoantibody tests in the diagnosis of systemic autoimmune disease. Ann N Y Acad Sci.
2005;
1050:
217-228.
Pope JE. Scleroderma overlap syndromes. Curr Opin Rheumatol.
2002;
14(
6):
704-710.
Scleroderma Foundation (Accessed 30 May 2008) (Linked to resource)Steen VD. Autoantibodies in systemic sclerosis. Semin Arthritis Rheum.
2005;
35(
1):
35-42.
Zulian F. Scleroderma in children. Pediatr Clin North Am.
2005;
52(
2):
521-45, vii.
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: November 2007
Last Update: July 2008
