Mixed Connective Tissue Disease

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

Mixed connective tissue disease (MCTD) is an autoimmune connective tissue disease.

Exhibits varied combinations of features common to other autoimmune diseases such as:
- Systemic lupus erythematosus
- Polymyositis
- Rheumatoid arthritis
- Systemic sclerosis

Epidemiology

Incidence - uncommon autoimmune disorder
Age - mean age of onset in 2nd and 3rd decades

Clinical Presentation

Raynaud phenomenon
Musculoskeletal - arthritis, polymyositis, swollen hands
Neurologic - trigeminal neuralgias, aseptic meningitis
Pulmonary - pleuritis, fibrosis
Renal - glomerulonephritis
Gastrointestinal - esophageal dysmotility
Cardiac - pericarditis

See Also

Cryoglobulinemia - Cryoglobulin

Inflammatory Myopathies

Scleroderma - Systemic Sclerosis

Sjögren Syndrome

Systemic Lupus Erythematosus - SLE

Vasculitis - ANCA

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 connective tissue disease screening

Limitations:

Low titer ANAs common with advancing age

Certain drugs may cause low titer ANAs

Follow-up:

For low level ANAs, repeat in 2-3 weeks
Recommend cutaneous direct immunofluorescence testing of active edge of new lesions (lesional biopsy) if dermatologic manifestations are present

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

ARUP #: 0050470

Methodology: Multi-Analyte Fluorescent Detection

Use:

Secondary screening test based on results of ANA test

Limitations:

RNP antigens contain epitopes which are immunologically identical to free Smith antigens; therefore, Smith antibody response must be considered when interpreting RNP results

Follow-up:

For inconclusive testing, repeat in 2-3 weeks

Recommend cutaneous direct immunofluorescence testing of active edge of new lesion (lesional biopsy) if dermatologic manifestations are present

Test name: Connective Tissue Diseases Profile

ARUP #: 0051668

Methodology: Multi-Analyte Fluorescent Detection

Use:

Clarify pattern result from ANA

Panel consists of Smith (ENA), RNP, SSA, SSB, Jo-1, RPP, Centromere and Scl-70 antibodies

Limitations:

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 syndrome and systemic lupus erythematosus

Limitations:

RNP antigens contain epitopes which are immunologically identical to free Smith antigens; therefore, Smith antibody response must be considered when interpreting RNP results

Follow-up:

For inconclusive testing, repeat in 2-3 weeks

Recommend cutaneous direct immunofluorescence testing of active edge of new lesion (lesional biopsy) if dermatologic manifestations are present

Additional Tests Available

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: 4 panel test

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

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