Algorithm(s)
PDF algorithm(s) available at www.arupconsult.com.
Immunodeficiency Evaluation for Chronic Infections in Adults and Older Children Testing Algorithm
Immunodeficiency Evaluation for Chronic Infections in Infants and Children Testing Algorithm
Connective Tissue Disease Testing Algorithm
Clinical Background
Sjögren syndrome, a slowly progressive autoimmune disease, is characterized by lymphocytic infiltration of exocrine glands which results in dry eyes and dry mouth.
Epidemiology
- Incidence - 2-4 million persons in U.S.
- Second most common autoimmune disease
- Age - peak 40-60 years
- Gender - M:F; 1:9
Pathophysiology
- Mononuclear infiltrate with loss of ductal cells and relative preservation of acinar cells in secretory glands
- Leads to loss of secretory capacity of the gland
Clinical Presentation
- Dry eye (xerophthalmia, keratoconjunctivitis sicca)
- Dry mouth (xerostomia)
- Enlargement of salivary glands
- Arthritis
- Raynaud phenomenon
- Increased risk of lymphoma associated with Sjögren syndrome - mostly mucosally associated lymphoid tumors (MALT)
- Often associated with other connective tissue diseases termed secondary Sjögren disease
- Rheumatoid arthritis
- Systemic lupus erythematous (SLE)
- Primary biliary cirrhosis
- Autoimmune thyroid disease
Treatment
See Also
Algorithm(s)
PDF algorithm(s) available at www.arupconsult.com.
Immunodeficiency Evaluation for Chronic Infections in Adults and Older Children Testing Algorithm
Immunodeficiency Evaluation for Chronic Infections in Infants and Children Testing Algorithm
Connective Tissue Disease Testing Algorithm
Diagnosis
Diagnosis
- Clinical features of connective tissue diseases overlap considerably. A systematic approach to laboratory diagnosis is recommended
- Laboratory testing
- ANA with followup ENA
- SS antibodies - although not specific for Sjögren syndrome, antibodies are relatively sensitive
- Strong association between SSA antibodies and vasculitis in Sjögren syndrome
- Several studies identify SSB antibodies as serological marker for SS-sicca complex
- SSB antibodies detected in approximately 60% of SS-sicca complex patients
| 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 |
- Histology
- May require labial gland biopsy
Differential Diagnosis
- Hepatitis C
- HIV
- Sarcoidosis
- Lymphoma
Algorithm(s)
PDF algorithm(s) available at www.arupconsult.com.
Immunodeficiency Evaluation for Chronic Infections in Adults and Older Children Testing Algorithm
Immunodeficiency Evaluation for Chronic Infections in Infants and Children Testing Algorithm
Connective Tissue Disease Testing Algorithm
Tests generally appear in the order most useful for common clinical situations
| 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
|
| Use: Recommended for high suspicion of SLE or Sjögren disease |
| Limitations: Low titer ANAs common with advancing ageCertain drugs may also cause low titer ANAs |
| Follow-up:
Recommend cutaneous direct immunofluorescence testing of active edge of new lesion (lesional biopsy) if dermatologic manifestations are present
|
| 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 |
Limitations: Low titer ANAs common with advancing age Certain drugs may also cause low titer ANAs |
| Follow-up:
Recommend cutaneous direct immunofluorescence testing of active edge of new lesion (lesional biopsy) if dermatologic manifestations are present
|
| Test name: Extractable Nuclear Antigen Antibodies (RNP, Smith, Scleroderma, SSA, & SSB)
|
| ARUP #: 0050653 |
| Methodology: Multi-Analyte Fluorescent Detection
|
| Use: Clarify pattern result from ANA. This assay may help to differentiate among mixed connective tissue disease, rheumatoid arthritis, scleroderma, Sjögren syndrome and systemic lupus erythematosus |
| Limitations: |
| Follow-up:
Recommend cutaneous direct immunofluorescence testing of active edge of new lesion (lesional biopsy) if dermatologic manifestations are present
|
| Test name: SSA (Ro) (ENA) Antibody, IgG
|
| ARUP #: 0050691 |
| Methodology: Multi-Analyte Fluorescent Detection
|
| Use: Order as secondary screen based on results of ANA test |
| Limitations: |
| Follow-up: Recommend cutaneous direct immunofluorescence testing of active edge of new lesion (lesional biopsy) if dermatologic manifestations are present |
| Test name: SSB (La) (ENA) Antibody, IgG
|
| ARUP #: 0050692 |
| Methodology: Multi-Analyte Fluorescent Detection
|
| Use: Order as secondary screen based on results of ANA test |
| Limitations: |
| Follow-up: Recommend cutaneous direct immunofluorescence testing of active edge of new lesion (lesional biopsy) if dermatologic manifestations are present |
Additional Tests Available
| Test name: Scleroderma (Scl-70) (ENA) Antibody, IgG
|
| ARUP #: 0050599 |
| Methodology: Multi-Analyte Fluorescent Detection
|
| Comments: |
| Test name: Extractable Nuclear Antigen Antibodies (RNP, Smith, SSA, & SSB)
|
| ARUP #: 0050652 |
| Methodology: Multi-Analyte Fluorescent Detection
|
| Comments: |
References
General References
Amarasena R, Bowman S. Sjogren's syndrome. Clin Med.
2007;
7(
1):
53-56.
Fox PC. Autoimmune diseases and Sjogren's syndrome: an autoimmune exocrinopathy. Ann N Y Acad Sci.
2007;
1098:
15-21.
Fox RI. Sjogren's syndrome. Lancet.
2005;
366(
9482):
321-331.
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.
Kassan SS, Moutsopoulos HM. Clinical manifestations and early diagnosis of Sjogren syndrome. Arch Intern Med.
2004;
164(
12):
1275-1284.
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.
Nakamura H, Kawakami A, Eguchi K. Mechanisms of autoantibody production and the relationship between autoantibodies and the clinical manifestations in Sjogren's syndrome. Transl Res.
2006;
148(
6):
281-288.
Ramos-Casals M, Tzioufas AG, Font J. Primary Sjogren's syndrome: new clinical and therapeutic concepts. Ann Rheum Dis.
2005;
64(
3):
347-354.
Soliotis FC, Moutsopoulos HM. Sjogren's syndrome. Autoimmunity.
2004;
37(
4):
305-307.
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
