Systemic Lupus Erythematosus

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

Systemic lupus erythematosus (SLE) is an autoimmune disease in which autoantibodies and immune complexes damage organs.

Epidemiology

Incidence - 1/2000
Age - peak onset teens to 40 year olds
Gender - F>M
Ethnicity - Blacks:Caucasians; 3:1

Risk Factors

Genetics
- Maybe associated with the deletion of the long arm of chromosome 1
Sunlight
Drugs
Epstein-Barr virus
Occupational exposures
- Silica
- Pesticides
- Mercury

Pathophysiology

Apoptosis (programmed cell death appears to play a role in development of autoantibodies)
B-cells are overactive
T-cell regulation is disrupted

Clinical Presentation

Dermatologic - malar or discoid rash
Musculoskeletal - arthritis, myositis, myalgias
Serositis - pleuritis, pericarditis
Renal - nephritis
Neurologic - seizures, psychosis
Hematologic - hemolytic anemia, leukopenia, thrombocytopenia, anti-phospholipid syndrome
Vascular - vasculitis, transient ischemic attack
Ocular - Sicca syndrome

Treatment

Immunosuppressives have been the mainstay of therapy
Newer biologics hold promise

See Also

Cryoglobulinemia - Cryoglobulin

Inflammatory Myopathies

Mixed Connective Tissue Disease - MCTD

Scleroderma - Systemic Sclerosis

Sjögren Syndrome

Vasculitis - ANCA

Algorithm(s)

PDF algorithm(s) available at www.arupconsult.com.

Diagnosis

Laboratory testing
- Antibodies to native DNA found in most patients with SLE
- While anti-nuclear antibody (ANA) test is useful as initial screen for SLE, follow-up of ANA-positive samples are necessary to identify antibodies to nuclear antigens such as:
  - DNA
    - Double stranded DNA (dsDNA) antibodies (1:10 or greater) are found in 50-60% of SLE
    - High antibody titers to native dsDNA are specific for SLE
  - Histones
  - Saline-extractable nuclear antigens
    - Smith (Sm) antibodies are highly specific for SLE, but occur in only 30-35% of cases
    - Patients with only antibodies to Sm have high incidence of renal and central nervous system (CNS) involvement
    - Sm antibodies also predict disease relapse in 50% of patients
- Ribonucleic protein (RNP) antibodies in SLE are associated with a relatively benign disease course and lower incidence of renal disease
- Nephritis in patients with RNP antibodies is usually associated with antibodies against antigens other than RNP, most notably DNA
- SSA and SSB antibodies occur in some patients with clinical features of SLE, including prominent cutaneous features, but who fail to demonstrate a positive ANA

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

Other connective tissue disease
Fibromyalgia
Vasculitides

Algorithm(s)

PDF algorithm(s) available at www.arupconsult.com.

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 autoimmune disease screening

Limitations:

Low titer ANAs common with advancing age; certain drugs may also cause low titer ANA

ssDNA antibody test detects ssDNA and some dsDNA antibodies; therefore, to more accurately determine level of anti-ssDNA antibodies, patients should also be tested for dsDNA antibodies Anti-Nuclear Antibodies (ANA)

Follow-up:

For low positive titer and continued clinical suspicion of connective tissue disease, repeat in 1-2 weeks

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 patients with high suspicion for SLE of Sjögren disease

Limitations:

Low titer ANAs common with advancing age; certain drugs may also cause low titer ANA

Follow-up:

For low positive titer and continued clinical suspicion of connective tissue disease, repeat in 1-2 weeks
Recommend cutaneous direct immunofluorescence testing of active edge of new lesions (lesional biopsy) if dermatologic manifestations are present

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

ARUP #: 0050215

Methodology: Enzyme-Linked Immunosorbent Assay/Indirect Fluorescent Antibody

Use:

Order as secondary screen based on results of ANA testing

Limitations:

Follow-up:

For low positive titer and continued clinical suspicion of connective tissue disease, repeat in 1-2 weeks

Recommend cutaneous direct immunofluorescence testing of active edge of new lesions (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 differentiate among mixed connective tissue disease, rheumatoid arthritis, scleroderma, Sjögren and systemic lupus erythematosus

Limitations:

Follow-up:

Test name: Smith (ENA) Antibody, IgG

ARUP #: 0050085

Methodology: Multi-Analyte Fluorescent Detection

Use:

Order as secondary screen based on results of ANA (0050080)

Limitations:

Follow-up:

For low positive titer and continued clinical suspicion of connective tissue disease, repeat in 1-2 weeks
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 (0050080)

Limitations:

Follow-up:

Inconclusive results should be repeated in 1-2 weeks

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 (0050080)

Limitations:

Follow-up:

For low positive titer and continued clinical suspicion of connective tissue disease, repeat in 1-2 weeks
Recommend cutaneous direct immunofluorescence testing of active edge of new lesion (lesional biopsy) if dermatologic manifestations are present

Test name: Ribosomal P Protein Antibody

ARUP #: 0099249

Methodology: Multi-Analyte Fluorescent Detection

Use:

Helpful in detecting the somewhat rare instances of central nervous system systemic lupus erythematosus

Test name: ssDNA Antibody, IgG

ARUP #: 0099528

Methodology: Enzyme-Linked Immunosorbent Assay

Use:

Order as secondary screen based on results of ANA testing

Limitations:

Not as useful of a marker as dsDNA

Follow-up:

For low positive titer and continued clinical suspicion of connective tissue disease, repeat in 1-2 weeks
Recommend cutaneous direct immunofluorescence testing of active edge of new lesion (lesional biopsy) if dermatologic manifestations are present

Test name: Histone Antibody, IgG

ARUP #: 0050860

Methodology: Enzyme-Linked Immunosorbent Assay

Use:

Order as secondary screen based on results of ANA testing

Limitations:

Follow-up:

For low positive titer and continued clinical suspicion of connective tissue disease, repeat in 1-2 weeks
Recommend cutaneous direct immunofluorescence testing of active edge of new lesion (lesional biopsy) if dermatologic manifestations are present

Additional Tests Available

Test name: Connective Tissue Diseases Profile

ARUP #: 0051668

Methodology: Multi-Analyte Fluorescent Detection

Comments: Panel test

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

ARUP #: 0050652

Methodology: Multi-Analyte Fluorescent Detection

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: Extractable Nuclear Antigen Antibodies (SSA & SSB)

ARUP #: 0050791

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