Systemic Autoimmune Rheumatic Diseases – Connective Tissue Diseases

Systemic autoimmune rheumatic diseases (SARDs) are characterized by autoantibodies that may affect many tissues and organs throughout the body. Laboratory testing for antinuclear antibodies (ANA) and specific autoantibodies associated with the presence of ANA may be useful in the evaluation of these diseases. The SARDS include systemic lupus erythematosus (SLE), Sjögren syndrome, mixed connective tissue disease/undifferentiated connective tissue disease, systemic sclerosis (scleroderma), idiopathic inflammatory myopathies (including polymyositis, dermatomyositis, and necrotizing autoimmune), and overlap syndromes.

ANA and related autoantibodies may also be useful in evaluating autoimmune liver diseases such as autoimmune hepatitis and primary biliary cholangitis.

Tabs Content

Clinical Overview

Diagnosis

Indications for Testing

Common indications for testing for SARDs (Petri, 2012; van den Hoogen, American College of Rheumatology [ACR]/European League against Rheumatism [EULAR], 2013; Pope, ACR/EULAR, 2015; Lundberg, EULAR/ACR, 2017); see Clinical Presentation for additional information
- SLE
  - Rash, photosensitivity, oral ulcers, polyarticular arthritis, proteinurea or cellular casts, pleuritis, pericarditis, interstitial nephritis, fatigue, cytopenia, seizures or psychosis
- Sjögren syndrome
  - Dry mouth, dry eyes
- Mixed or undifferentiated connective tissue disease
  - Raynaud syndrome, joint aches, puffy fingers, low-grade myositis
- Systemic sclerosis
  - Raynaud syndrome, sclerodactyly, interstitial lung disease/pulmonary hypertension, gastroesophageal reflux
- Inflammatory myopathies
  - Progressive muscle weakness (usually proximal) with or without rashes

Laboratory Testing

Antinuclear autoantibody (ANA) testing for autoantibodies
- Test description
  - Antibodies in systemic rheumatological diseases are against any element of the cell – nucleus, cytoplasmic elements, etc.
  - Best used for individuals with high pretest probability (Pisetsky, 2017; Satoh, 2012)
    - ANA reactivity may be present in nonrheumatic or healthy patients
  - Reporting should include
    - Positive or negative result
    - Level of dilution (titration)
- ANA testing methodologies
  - Gold standard is indirect fluorescent antibody (IFA) assay using HEp-2 (HEp-2000) cells in an experienced lab
  - Enzyme-linked immunosorbent assay (ELISA) – not recommended; variable diagnostic accuracies reported
  - Test interpretation is based on common ANA patterns with consistent correlation with SARDs
    - ARUP patterns reported include homogeneous, speckled, centromere, nucleolar, nuclear dots, or cytoplasmic (see table below)
    - International Consensus on ANA Patterns has comprehensive information on patterns, targets, and clinical associations
Specific autoantibodies testing
- In cases of high clinical suspicion for autoimmune connective tissue diseases, specific autoantibody testing should be performed, even if ANA testing is negative (Agmon-Levin, 2014)
- Patterns, autoantibody targets, and clinical associations

Patterns, Autoantibody Targets, and Clinical Associations
Patterns	Primary Autoantibody Targets	Clinical Associations
Centromere	Centromere A/B(C)	SSc, PBC
Homogeneous	dsDNA, histones or chromatin (nucleosomes)	SLE, drug-induced SLE or JIA
Nuclear dots	NXP-2, Sp100	PBC, DM, SjS, SLE, SSc, PM
Nucleolar	PM/Scl, RNA polymerase, URNP, U3-RNP (fibrillarin), Th/To, NOR-90	SSc, SSc/PM overlap, SjS
Speckled	SSA-52 (Ro52), SSA-60 (Ro60), SSB/LA, Topo-1 (Scl-70), Smith, U1-RNP, U2-RNP, Mi-2, TIF1g, Ku, RNA polymerase, DFS70/LEDGF-P75	SLE, SSc, SjS, DM, PM, MCTD, UCTD (may also be found in healthy individuals)
Cytoplasmic	Ribosomal P, tRNA synthetase (Jo-1, PL-7, PL-12, EJ, OJ), SRP or mitochondria (AMA)	ARS, ILD, IM,^a SLE, SSc, SjS, RA, MCTD, PBC, AIH, infectious, neurologic, and other inflammatory conditions
^aIM includes DM, PM, and NAM ARS, antisynthetase syndrome; AIH, autoimmune hepatitis; DM, dermatomyositis; ILD, interstitial lung disease; IM, inflammatory myopathies; JIA, juvenile idiopathic arthritis; MCTD, mixed connective tissue disease; NAM, necrotizing autoimmune myopathy; PBC, primary biliary cholangitis; PM, polymyositis; RA, rheumatoid arthritis; SjS, Sjögren syndrome; SLE, systemic lupus erythematosus; SRP, signal recognition particle; SSc, systemic sclerosis; UCTD, undifferentiated connective tissue disease Sources: Tebo, 2017; Agmon-Levin, 2014

Differential Diagnosis

Arthritis/arthralgia
- Rheumatoid arthritis
- Psoriatic arthritis
- Reactive arthritis
- Ankylosing spondylitis
- Crystalline arthritis
- Sarcoidosis
- Behçet disease
- Osteoarthritis
- Septic arthritis
- Avascular necrosis
- Bursitis or other soft tissue inflammation
- Diffuse idiopathic skeletal hyperostosis
- Spinal stenosis
- Heritable connective tissue disorder
- Lyme disease
- Hemochromatosis
Myositis/myalgia
- Polymyalgia rheumatica
- Cushing syndrome
- Demyelinating disease (multiple sclerosis, etc)
- Guillain-Barré syndrome
- Paraneoplastic syndromes
- Peripheral neuropathy
- Fibromyalgia
- Drug-induced myositis
- Inclusion body myositis
- Vasculitis
- Metabolic myopathy
- Hypothyroidism
Multiorgan presentation
- IgG4
- Antiphospholipid syndrome (APS)
- Malignancy
- Vasculitis
- Endocarditis
- Hemochromatosis
Acute renal failure
- Thrombotic thrombocytopenic purpura (TTP)
- Hemolytic uremic syndrome (HUS)
- HELLP
- Multiple myeloma
- Wegener Granulomatosis
- Microscopic polyangiitis
- Contrast agent exposure
- Acute tubular necrosis (ATN)
- Acute interstitial nephritis
- Rhabdomyolysis
- Acute glomerulonephritis
- Vasculitis
Central nervous system
- Brain tumor
- Infectious meningitis/encephalitis
- Malignancy
  - Leukemia (most commonly acute lymphoblastic leukemia [ALL])
  - Lymphoma
- Migraine
- Stroke
- Vasculitis (temporal arteritis)
- Psychiatric disease
Cytopenias
- Autoimmune hemolytic diseases
- Malignancy
  - Infiltrative metastatic tumor
  - Leukemia (ALL and acute myeloid leukemia [AML])
  - Myelodysplastic syndromes
  - Myeloproliferative neoplasms

Monitoring

Once diagnosis has been made, use monitoring tests based on organ involvement
- If cytopenias present, follow with sequential CBCs
- Certain treatment drugs require liver function testing
Monitor for malignancy
- Dermatomyositis – increased risk for malignancy
- Mixed connective tissue disorder (MCTD) – increased risk for malignancy
- Sjögren syndrome – increased risk for hematological malignancy

Background

Epidemiology

Refer to individual topics below for epidemiology information
- SLE
- Sjögren syndrome
- MCTD
- Systemic sclerosis
- Inflammatory myopathies (for polymyositis/dermatomyositis)

Clinical Presentation

Disease	Organ System and Signs/Symptoms
SLE	Skin/mucosa – malar rash, discoid lupus rash, photosensitivity, oral or nasopharyngeal ulcers
	Joints – polyarticular arthritis, primarily hands, wrists, knees, stiffness; rarely, avascular necrosis
	Renal – proteinuria or cellular casts
	Pulmonary – pleuritis
	Vascular/cardiac – Raynaud syndrome, pericarditis
	CNS – seizures or psychosis, confusion, headaches
	Reproductive – recurrent miscarriages
	Muscle – rarely, myalgias or low-grade myositis
Sjögren syndrome	Skin/mucosa – dry mouth
	Ocular – dry eyes
	Pulmonary – pleuritis
MCTD, UCTD	Joints – joint pain with or without synovitis
	Muscle – myalgias, low-grade myositis
	Pulmonary – pulmonary hypertension
	Vascular/cardiac – Raynaud syndrome
Systemic sclerosis	Skin/mucosa – sclerodactyly
	Renal - renal artery hypertension
	Pulmonary – pulmonary fibrosis, pulmonary hypertension
	Vascular/cardiac – Raynaud syndrome
	Gastrointestinal – dysphagia/reflux
Inflammatory myopathies^a	Muscle – myalgias, myositis, progressive symmetric proximal muscle weakness
Inflammatory myopathies^a	Skin/mucosa – rashes, including Heliotrope rash, Gottron papules
^aInflammatory myopathies include polymyositis, dermatomyositis, and necrotizing autoimmune myopathies CNS, central nervous system; MCTD, mixed connective tissue disease; SLE, systemic lupus erythematosus; UCTD, undifferentiated connective tissue disease Sources: Lundberg, EULAR/ACR, 2017; Petri, 2012; Pope, ACR/EULAR, 2015; van den Hoogen, ACR/EULAR, 2013

Pediatrics

Epidemiology

Different in children than in adults, though disorders are the same
Incidence – varies by disease but lower than in adults
Sex – M<F for most disorders
Age – presents more often >10 years

Clinical Presentation

Presentations and indications are similar for adults and can be used for children – see Background

Diagnosis

Growth and development issues associated with SARDs in children make diagnosis important
ANA testing is used for diagnosis in children as in adults – see Diagnosis for adults
- Standard cutoffs may not be validated for children

Differential Diagnosis

Polyarthritis
- Juvenile rheumatoid arthritis
- Juvenile ankylosing spondylitis
- Infectious arthritis
- Psoriatic arthritis
- Vasculitis
- Growing pains
- Reactive arthritis (Campylobacter spp, Salmonella, Shigella, group A streptococcus)
Renal
- Acute glomerulonephritis
- Vasculitis
Central nervous system
- Vasculitis
- Migraine
- Brain tumor
Rash
- Kawasaki disease
- Scarlet fever
- Parvovirus
Multiorgan
- Vasculitis
- Malignancy
- Endocarditis
- Acute rheumatic fever
- Sarcoidosis
Myositis/weakness
- Muscular dystrophies
- Guillain-Barré syndrome
- Cushing disease
- Mitochondrial diseases
- Metabolic disease
- Infections
  - Toxoplasma gondii
  - Enterovirus (polio)
  - Trichinella spiralis (trichinosis)
Hematologic
- Autoimmune hemolytic diseases
- Malignancy
  - Infiltrative metastatic tumors
  - Leukemia
  - Myeloproliferative neoplasms
  - Myelodysplastic syndromes

ARUP Lab Tests

Tests generally appear in the order most useful for common clinical situations. Click on number for test-specific information in the ARUP Laboratory Test Directory.

Nuclear Antibody (ANA) by IFA, IgG 0050639
Method: Semi-Quantitative Indirect Fluorescent Antibody

Recommended Use

Preferred ANA screening test for connective tissue diseases

If positive, patterns reported include homogeneous, speckled, centromere, nucleolar, nuclear dots, or cytoplasmic; all positive results are reported with endpoint titers

Limitations

A negative ANA by IFA test does not rule out the presence of connective tissue disease

Anti-Nuclear Antibody (ANA), IgG by IFA with Reflex by IFA Pattern 2008467
Method: Semi-Quantitative Indirect Fluorescent Antibody/Qualitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Multiplex Bead Assay/Qualitative Immunoblot

Recommended Use

Initial screen for autoimmune connective tissue diseases

One or more reflexive tests may be added, depending on the ANA pattern detected

Limitations

Only cytoplasmic, nuclear mitotic apparatus (NuMA), and/or nuclear dot pattern will be reported if observed

Titers are not performed

Dual or mixed patterns will not be reflexed; additional testing for dual or mixed patterns should be determined by the ordering physician

A negative ANA by IFA test does not rule out the presence of connective tissue disease

Anti-Nuclear Antibodies (ANA), IgG by ELISA with Reflex to ANA, IgG by IFA 0050080
Method: Qualitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Indirect Fluorescent Antibody

Recommended Use

Aid in initial diagnosis of connective tissue disease

Detects antibodies against dsDNA, histone, SS-A (Ro), SS-B (La), Smith, snRNP/Sm, Scl-70, Jo-1, centromere, and an extract of lysed HEp-2 cells

Reflex pattern – if ANA are detected by ELISA, then ANA by IFA titer will be added

Limitations

Results are not disease specific

ANA ELISA assays have been reported to have lower sensitivities than ANA IFA for SARDs

Connective Tissue Diseases Profile 0051668
Method: Semi-Quantitative Multiplex Bead Assay

Recommended Use

Confirmatory tests for specific and more common connective tissue disease

Components include Sm (ENA) antibody; RNP (U1) (ribonucleic protein); SSA (Ro); SSB (La); Jo-1; ribosomal P protein; centromere; and scleroderma (Scl-70)

Systemic Sclerosis Comprehensive Panel 2013325
Method: Qualitative Immunoblot/Semi-Quantitative Indirect Fluorescent Antibody/Semi-Quantitative Multiplex Bead Assay/Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Recommended Use

Comprehensive evaluation of systemic sclerosis (SSc)

Indicated when suspicion for SSc is high and patient presents with features of overlap syndrome

Panel includes ANA titer, ANA pattern, anti-Scl-70, anti-RNA polymerase III antibody, anti-U1 RNP antibody, antifibrillarin (U3 RNP), anti-PM/Scl antibody

Limitations

Negative antibody test result does not exclude SSc; 5-10% of SSc patients are ANA IFA negative

Panel does not include Th/To

Systemic Sclerosis Panel 2012057
Method: Semi-Quantitative Indirect Fluorescent Antibody/Semi-Quantitative Multiplex Bead Assay/ Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Recommended Use

Indicated for patients with distinct features of SSc

Reflex pattern – if ANA IFA is positive and SSc-specific markers are negative, testing for other markers associated with SSc or connective tissue disease based on observed ANA IFA pattern(s) is performed (ethnicity or clinical presentation may be clinically useful)

Components include ANA by IFA, IgG; scleroderma (Scl-70) antibody, IgG; and RNA polymerase III antibody, IgG

Limitations

Negative antibody test result does not exclude SSc

Panel does not include Th/To

Polymyositis and Dermatomyositis Panel (Temporary Delay as of 04/17/18 - no referral available) 2013992
Method: Qualitative Immunoprecipitation/Semi-Quantitative Multiplex Bead Assay/Qualitative Immunoblot

Recommended Use

May be useful for evaluation of patients with progressive proximal muscle weakness and/or cutaneous manifestations suggestive of dermatomyositis and/or associated connective tissue disease

Components include Jo-1, PL-7, PL-12, EJ, SRP, OJ, Mi-2, P155/140, SAE1, MDA5, NXP-2, and TIF1-γ antibodies

Limitations

Results by themselves are not diagnostic; strong clinical correlation is recommended

Negative results do not rule out a diagnosis of inflammatory myopathy or overlap syndrome

Polymyositis Panel (Temporary Delay as of 04/17/18 - no referral available) 2013990
Method: Qualitative Immunoprecipitation/Semi-Quantitative Multiplex Bead Assay

Recommended Use

May be useful for evaluation of patients with progressive proximal muscle weakness and antisynthetase syndrome

Components include Jo-1, PL-7, PL-12, EJ, SRP, and OJ antibodies

Dermatomyositis Panel (Temporary Delay as of 04/17/18 - no referral available) 2013991
Method: Qualitative Immunoprecipitation/Qualitative Immunoblot

Recommended Use

May be useful for evaluation of patients with characteristic cutaneous manifestations of dermatomyositis with or without muscle weakness

Components include Mi-2, P155/140 (TIF1-gamma), SAE1 (SUMO activating enzyme), MDA5 (CADM-140), NXP-2, and TIF1-gamma antibodies

Interstitial Lung Disease Panel (Temporary Delay as of 04/17/18 - no referral available) 2013993
Method: Qualitative Immunoprecipitation/Semi-Quantitative Multiplex Bead Assay/Qualitative Immunoblot/Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Quantitative Immunoturbidimetry

Recommended Use

May be useful for evaluation of interstitial lung disease in the context of connective tissue disease

Components include SSA 52 and 60 (Ro), Scl-70, Jo-1, PL-7, PL-12, EJ, Ku, SRP, OJ, PM/Scl-100, MDA5, NXP-2, rheumatoid factor, cyclic citrullinated peptide (CCP), and ANA antibodies

Myositis Extended Panel (Temporary Delay as of 04/17/18 - no referral available) 2013961
Method: Qualitative Immunoprecipitation/Semi-Quantitative Multiplex Bead Assay/Qualitative Immunoblot

Recommended Use

May be useful in the differential evaluation of polymyositis, dermatomyositis, necrotizing autoimmune myopathy, or overlap syndromes associated with connective tissue disease

Components include SSA 52 and 60 (Ro), RNP (U1) (ENA), Jo-1, Mi-2, PL-7, PL-12, P155/140 (TIF1-gamma), EJ, Ku, U2 sn RNP, SRP, OJ, SAE1, MDA5, NXP-2, TIF1-gamma (TIF1-γ), fibrillarin (U3 RNP), and PM/Scl-100 antibodies

Limitations

Results by themselves are not diagnostic; strong clinical correlation is recommended

Negative results do not rule out a diagnosis of inflammatory myopathy or overlap syndromes

Rheumatoid Arthritis Panel 2003277
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Immunoturbidimetry

Recommended Use

Preferred panel for the workup of suspected rheumatoid arthritis or undifferentiated inflammatory arthritides

Components include CCP antibody, IgG, and rheumatoid factor

Fibrillarin (U3 RNP) Antibody, IgG 2012173
Method: Qualitative Immunoblot

Recommended Use

Recommended for the diagnosis of SSc in patients negative for centromere, Scl-70, or RNA polymerase III antibodies

May predict skeletal muscle involvement and pulmonary arterial hypertension (PAH)

Limitations

Negative test result does not rule out the diagnosis of SSc

Test results alone are not diagnostic; results should be used in conjunction with other laboratory tests and clinical findings

Anti-Neutrophil Cytoplasmic Antibody with Reflex to Titer and MPO/PR-3 Antibodies 2002068
Method: Semi-Quantitative Indirect Fluorescent Antibody/Semi-Quantitative Multiplex Bead Assay

Recommended Use

Preferred reflex panel for managing patients with a known diagnosis of vasculitis; may be assistive in evaluating suspected vasculitis

For the workup of suspected vasculitis, the preferred panel is ANCA-associated vasculitis profile (ANCA/MPO/PR-3) with reflex to ANCA titer

Panel includes ANCA, IgG; myeloperoxidase antibody; and serine protease 3 antibody

Reflex pattern – if screen is positive, titer and MPO/PR-3 antibodies testing will be added

Medical Reviewers

Tebo, Anne E., PhD, D(ABMLI), Medical Director, Immunology at ARUP Laboratories; Associate Professor of Clinical Pathology, University of Utah

References

Guidelines

Agmon-Levin N, Damoiseaux J, Kallenberg C, Sack U, Witte T, Herold M, Bossuyt X, Musset L, Cervera R, Plaza-Lopez A, Dias C, Sousa MJ, Radice A, Eriksson C, Hultgren O, Viander M, Khamashta M, Regenass S, Andrade LE, Wiik A, Tincani A, Rönnelid J, Bloch DB, Fritzler MJ, Chan EK, De La Torre G, Konstantinov KN, Lahita R, Wilson M, Vainio O, Fabien N, Sinico RA, Meroni P, Shoenfeld Y. International recommendations for the assessment of autoantibodies to cellular antigens referred to as anti-nuclear antibodies. Ann Rheum Dis. 2014; 73(1): 17-23. PubMed

Lundberg IE, Tjärnlund A, Bottai M, Werth VP, Pilkington C, de Visser M, Alfredsson L, Amato AA, Barohn RJ, Liang MH, Singh JA, Aggarwal R, Arnardottir S, Chinoy H, Cooper RG, Dankó K, Dimachkie MM, Feldman BM, De La Torre IG, Gordon P, Hayashi T, Katz JD, Kohsaka H, Lachenbruch PA, Lang BA, Li Y, Oddis CV, Olesinska M, Reed AM, Rutkowska-Sak L, Sanner H, Selva-O'Callaghan A, Song Y, Vencovský J, Ytterberg SR, Miller FW, Rider LG, International Myositis Classification Criteria Project consortium, The Euromyositis register and The Juvenile Dermatomyositis Cohort Biomarker Study and Repository (JDRG) (UK and Ireland). 2017 European League Against Rheumatism/American College of Rheumatology classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups. Ann Rheum Dis. 2017; 76(12): 1955-1964. PubMed

Petri M, Orbai A, Alarcón GS, Gordon C, Merrill JT, Fortin PR, Bruce IN, Isenberg D, Wallace DJ, Nived O, Sturfelt G, Ramsey-Goldman R, Bae S, Hanly JG, Sánchez-Guerrero J, Clarke A, Aranow C, Manzi S, Urowitz M, Gladman D, Kalunian K, Costner M, Werth VP, Zoma A, Bernatsky S, Ruiz-Irastorza G, Khamashta MA, Jacobsen S, Buyon JP, Maddison P, Dooley MA, van Vollenhoven RF, Ginzler E, Stoll T, Peschken C, Jorizzo JL, Callen JP, Lim S, Fessler BJ, Inanc M, Kamen DL, Rahman A, Steinsson K, Franks AG, Sigler L, Hameed S, Fang H, Pham N, Brey R, Weisman MH, McGwin G, Magder LS. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum. 2012; 64(8): 2677-86. PubMed

Pisetsky DS. Antinuclear antibody testing - misunderstood or misbegotten? Nat Rev Rheumatol. 2017; 13(8): 495-502. PubMed

Pope JE, Johnson SR. New Classification Criteria for Systemic Sclerosis (Scleroderma). Rheum Dis Clin North Am. 2015; 41(3): 383-98. PubMed

Satoh M, Chan EK, Ho LA, Rose KM, Parks CG, Cohn RD, Jusko TA, Walker NJ, Germolec DR, Whitt IZ, Crockett PW, Pauley BA, Chan JY, Ross SJ, Birnbaum LS, Zeldin DC, Miller FW. Prevalence and sociodemographic correlates of antinuclear antibodies in the United States. Arthritis Rheum. 2012; 64(7): 2319-27. PubMed

van den Hoogen F, Khanna D, Fransen J, Johnson SR, Baron M, Tyndall A, Matucci-Cerinic M, Naden RP, Medsger TA, Carreira PE, Riemekasten G, Clements PJ, Denton CP, Distler O, Allanore Y, Furst DE, Gabrielli A, Mayes MD, van Laar JM, Seibold JR, Czirjak L, Steen VD, Inanc M, Kowal-Bielecka O, Müller-Ladner U, Valentini G, Veale DJ, Vonk MC, Walker UA, Chung L, Collier DH, Csuka ME, Fessler BJ, Guiducci S, Herrick A, Hsu VM, Jimenez S, Kahaleh B, Merkel PA, Sierakowski S, Silver RM, Simms RW, Varga J, Pope JE. 2013 classification criteria for systemic sclerosis: an American College of Rheumatology/European League against Rheumatism collaborative initiative. Arthritis Rheum. 2013; 65(11): 2737-47. PubMed

General References

Chan EK, Damoiseaux J, Carballo OG, Conrad K, Cruvinel Wd, Francescantonio PL, Fritzler MJ, De La Torre IG, Herold M, Mimori T, Satoh M, von Mühlen CA, Andrade LE. Report of the First International Consensus on Standardized Nomenclature of Antinuclear Antibody HEp-2 Cell Patterns 2014-2015. Front Immunol. 2015; 6: 412. PubMed

Levy DM, Kamphuis S. Systemic lupus erythematosus in children and adolescents. Pediatr Clin North Am. 2012; 59(2): 345-64. PubMed

Recommendations for Anti-Nuclear Antibody (ANA) Test System Premarket (510(k)) Submissions.. U.S. Food and Drug Administration. Silver Spring, MD [Updated: Feb 2018; Accessed: Apr 2018]

Tebo AE. Recent approaches to optimize laboratory assessment of antinuclear antibodies. Clin Vaccine Immunol. 2017; 24(12): PubMed

Testing Algorithms

Antinuclear Antibody Testing Algorithm

Read more about Antinuclear Antibody Testing Algorithm

Content Review:

April 2018

Last Update: May 2018


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Systemic Autoimmune Rheumatic Diseases – Connective Tissue Diseases

Diagnosis

Indications for Testing

Laboratory Testing

Differential Diagnosis

Monitoring

Background

Epidemiology

Clinical Presentation

SLE

Skin/mucosa – malar rash, discoid lupus rash, photosensitivity, oral or nasopharyngeal ulcers

Joints – polyarticular arthritis, primarily hands, wrists, knees, stiffness; rarely, avascular necrosis

Renal – proteinuria or cellular casts

Pulmonary – pleuritis

Vascular/cardiac – Raynaud syndrome, pericarditis

CNS – seizures or psychosis, confusion, headaches

Reproductive – recurrent miscarriages

Muscle – rarely, myalgias or low-grade myositis

Sjögren syndrome

Skin/mucosa – dry mouth

Ocular – dry eyes

Pulmonary – pleuritis

MCTD, UCTD

Joints – joint pain with or without synovitis

Muscle – myalgias, low-grade myositis

Pulmonary – pulmonary hypertension

Vascular/cardiac – Raynaud syndrome

Systemic sclerosis

Skin/mucosa – sclerodactyly

Renal - renal artery hypertension

Pulmonary – pulmonary fibrosis, pulmonary hypertension

Vascular/cardiac – Raynaud syndrome

Gastrointestinal – dysphagia/reflux

Inflammatory myopathiesa

Muscle – myalgias, myositis, progressive symmetric proximal muscle weakness

Skin/mucosa – rashes, including Heliotrope rash, Gottron papules

Pediatrics

Epidemiology

Clinical Presentation

Diagnosis

Differential Diagnosis

ARUP Lab Tests

Medical Reviewers

References

Guidelines

General References

Antinuclear Antibody Testing Algorithm

Inflammatory myopathies^a