Undifferentiated Connective-Tissue Disease Workup

  • Author: Bernard Hildebrand, MD; Chief Editor: Herbert S Diamond, MD   more...
 
Updated: Jan 19, 2012
 

Laboratory Studies

Laboratory test screening is helpful to identify markers that may suggest autoimmune inflammatory disease. Routine screening tests for undifferentiated connective-tissue disease (UCTD) should include the following:

  • Complete blood count
  • Erythrocyte sedimentation rate (ESR)
  • C-reactive protein (CRP)
  • Urinalysis with microscopic analysis
  • Serum creatinine
  • Rheumatoid factor (RF)
  • Antinuclear antibodies (ANA): The American College of Rheumatology Antinuclear Antibody Task Force recommends ANA screening be performed using an immunofluorescence assay (IFA).[43] Any ANA detected by an enzyme immunoassay (EIA) or enzyme-linked immunosorbent assay (ELISA) should be confirmed with IFA testing.[44]

Other studies to consider on a case-by-case basis include the following:

  • Creatine kinase and aldolase
  • Complement components (C3, C4, CH50)
  • Thyroid-stimulating hormone
  • Anti-cyclic citrullinated peptide (CCP)
  • Anti-Ro/SSA
  • Anti-La/SSB
  • Anti-Smith
  • Anti-U1-RNP
  • Anti-Jo1
  • Anti-Mi2
  • Anti-Scl70 (topoisomerase antibody)
  • Anti-cardiolipins
  • Anti-beta-2 glycoprotein 1
  • Lupus anticoagulant
  • Anti-Ku
  • RPR
  • Vitamin D - 25(OH)D3

Anti-U1-RNP and Anti-Ro/SSA antibodies represent the antinuclear specificities most frequently detected in UCTD. Anti-Ro/SSA immunoglobulin G (IgG) antibodies are very common in UCTD.[45] A 2008 study by Zold et al suggested that vitamin D deficiency in patients with UCTD may play a role in progression to a defined CTD.[46]

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Imaging Studies

  • Chest radiography findings may be normal or may show signs of pleural effusion, pericardial effusion, enlarged cardiac silhouette, longstanding pulmonary hypertension, or interstitial lung disease. Kinder et al (2007) suggested that idiopathic nonspecific interstitial pneumonia is an autoimmune pneumonitis and a lung manifestation of UCTD.[32]
  • CT scanning of the chest, particularly high-resolution CT scanning, may better characterize pulmonary disease associated with CTD.
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Other Tests

  • Pulmonary function studies, including spirometry, lung volumes, and carbon monoxide–diffusing capacity assists in identifying interstitial lung disease or reactive airway disease.
  • Electrocardiography may be useful in patients with cardiopulmonary signs and symptoms. Nonspecific ischemic changes, axis deviation, or findings consistent with chamber enlargement may direct further evaluation.
  • Echocardiography can best clarify chamber sizes and function, estimate physiologic pressures (including pulmonary arterial pressures), and identify or quantitate the size of a pericardial effusion.
  • The Schirmer test is a useful screen for dry eyes and may be used to detect decreased tearing associated with primary or secondary SS. This test is very sensitive, but the results may be abnormal in patients taking anticholinergic medications.
  • Rose Bengal staining of the cornea can reveal keratitis associated with diminished tearing in SS.
  • Nailfold capillary microscopy may be used to identify dilated tortuous capillary loops, irregular capillary loops, and areas of avascularity or "dropout" in patients with Raynaud phenomenon. These findings indicate an underlying CTD, including UCTD.[47]
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Contributor Information and Disclosures
Author

Bernard Hildebrand, MD  Chief of Rheumatology, Mike O'Callaghan Federal Hospital, Nellis Air Force Base

Bernard Hildebrand, MD is a member of the following medical societies: American College of Physicians, American College of Rheumatology, and American Society for Bioethics and Humanities

Disclosure: Nothing to disclose.

Coauthor(s)

Daniel F Battafarano, DO, FACP, FACR  Clinical Professor of Medicine, University of Texas Health Science Center at San Antonio; Associate Professor of Medicine, Uniformed Services University of the Health Sciences, F Edward Hebert School of Medicine; Chief of Rheumatology Service, San Antonio Military Medical Center

Daniel F Battafarano, DO, FACP, FACR is a member of the following medical societies: American College of Physicians, American College of Rheumatology, and Association of Military Surgeons of the US

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Elliot Goldberg, MD  Dean of the Western Pennsylvania Clinical Campus, Professor, Department of Medicine, Temple University School of Medicine

Elliot Goldberg, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, and American College of Rheumatology

Disclosure: Nothing to disclose.

Alex J Mechaber, MD, FACP  Senior Associate Dean for Undergraduate Medical Education, Associate Professor of Medicine, University of Miami Miller School of Medicine

Alex J Mechaber, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, and Society of General Internal Medicine

Disclosure: Nothing to disclose.

Chief Editor

Herbert S Diamond, MD  Adjunct Professor of Medicine, Division of Rheumatology, University of Pittsburgh School of Medicine; Chairman Emeritus, Department of Internal Medicine, Western Pennsylvania Hospital

Herbert S Diamond, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American College of Rheumatology, American Medical Association, and Phi Beta Kappa

Disclosure: Merck Ownership interest Other; Smith Kline Ownership interest Other; Zimmer Ownership interest Other

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Table 1. Preliminary Classification Criteria for Undifferentiated Connective-Tissue Disease
Inclusion CriteriaClinical



Exclusion Criteriaa



Laboratory Exclusion Criteriaa
1. Signs and symptoms suggestive of a CTD but not fulfilling the diagnostic or classification criteria for any of the defined CTDs b for at least 3 years c



2. Presence of antinuclear antibodies determined on two different occasions



Malar rash



Subacute cutaneous lupus



Discoid lupus



Cutaneous sclerosis



Heliotrope rash



Gottron papules



Erosive arthritis



Anti-dsDNA



Anti-Smith



Anti-U1-RNP



Anti-Scl70



Anticentromere



Anti-La/SSB



Anti-Jo1



Anti-Mi2



Table 2. Predictors of Progression to Definite Connective-Tissue Disease
Connective-Tissue Disease AssociationSigns or SymptomsLaboratory Data
Systemic lupus erythematosusAge, fever, photosensitivity, serositis, alopeciaANA, Anti-dsDNA, Anti-Smith, Anti-cardiolipin antibodies, Coombs positivity, leukopenia
Systemic sclerosisSclerodactyly, Raynaud phenomenon, sicca symptoms, esophageal dysfunctionANA with nucleolar pattern
Sjögren syndromeXerostomia, xerophthalmia, Raynaud phenomenonAnti-SSA, Anti-SSB
Rheumatoid arthritisSymmetric polyarthritisRF, elevated ESR (>70 mm/h)
Mixed connective-tissue diseaseEsophageal reflux, polyarthritis, Raynaud phenomenonANA, Anti-U1-RNP
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