eMedicine Specialties > Rheumatology > Systemic Rheumatic Disease

Undifferentiated Connective-Tissue Disease: Differential Diagnoses & Workup

Author: Bernard A Hildebrand Jr, MD, Staff Rheumatologist, Department of Rheumatology, San Antonio Military Medical Center, San Antonio, Texas
Coauthor(s): Daniel F Battafarano, DO, FACP, FACR, Clinical Professor of Medicine, University of Texas Health Science Center, San Antonio, Texas; Associate Professor, Department of Medicine, Uniformed Services University of Health Sciences, F Edward Hebert School of Medicine; Chief of Rheumatology Service, San Antonio Military Medical Center, San Antonio, Texas.
Contributor Information and Disclosures

Updated: Jul 24, 2009

Differential Diagnoses

Antiphospholipid Syndrome
Polymyositis
Dermatomyositis
Raynaud Phenomenon
Fibromyalgia
Rheumatoid Arthritis
Localized Fibrosing Disorders: Linear Scleroderma, Morphea, Regional Fibrosis
Scleroderma
Mixed Connective-Tissue Disease
Sjogren Syndrome
Overlap syndromes
Systemic Lupus Erythematosus

Other Problems to Be Considered

Undifferentiated connective-tissue disease (UCTD) is a diagnosis of exclusion. Therefore, a diagnosis of UCTD should not be applied until an appropriate exhaustive workup has been pursued based on the patient's signs and symptoms. Definite CTDs should be considered in the evaluation of any patient who presents with features of UCTD. Despite the overlapping features of specific CTDs, early differentiation is necessary for initiation of appropriate therapy, monitoring, and prognosis determination.35 Heinlen et al (2007) report that 80% of patients with SLE have at least one defined clinical criterion 4-5 months prior to the diagnosis being established.36

A thorough history and physical examination can identify many signs and symptoms that may differentiate the diagnosis, and appropriate laboratory studies and testing may also help delineate a specific diagnosis. Data suggest that particular signs and symptoms may predict the evolution of UCTD to specific defined CTDs, as shown in Table 2.10,11,15,34,35,37

Table 2. Predictors of Progression to Definite Connective-Tissue Disease

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Table

Connective-Tissue Disease Association

Signs or Symptoms

Laboratory Data

Systemic lupus erythematosus
Age, fever, photosensitivity, serositis, alopecia
ANA, Anti-dsDNA, Anti-Smith, Anti-cardiolipin antibodies, Coombs positivity, leukopenia
Systemic sclerosis
Sclerodactyly, Raynaud phenomenon, sicca symptoms, esophageal dysfunction
ANA with nucleolar pattern
Sjögren syndrome
Xerostomia, xerophthalmia, Raynaud phenomenon
Anti-SSA, Anti-SSB
Rheumatoid arthritis
Symmetric polyarthritis
RF, elevated ESR (>70 mm/h)
Mixed connective-tissue disease
Esophageal reflux, polyarthritis, Raynaud phenomenon
ANA, Anti-U1-RNP

Connective-Tissue Disease Association

Signs or Symptoms

Laboratory Data

Systemic lupus erythematosus
Age, fever, photosensitivity, serositis, alopecia
ANA, Anti-dsDNA, Anti-Smith, Anti-cardiolipin antibodies, Coombs positivity, leukopenia
Systemic sclerosis
Sclerodactyly, Raynaud phenomenon, sicca symptoms, esophageal dysfunction
ANA with nucleolar pattern
Sjögren syndrome
Xerostomia, xerophthalmia, Raynaud phenomenon
Anti-SSA, Anti-SSB
Rheumatoid arthritis
Symmetric polyarthritis
RF, elevated ESR (>70 mm/h)
Mixed connective-tissue disease
Esophageal reflux, polyarthritis, Raynaud phenomenon
ANA, Anti-U1-RNP

Workup

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)

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.38 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.39

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.27
  • CT scanning of the chest, particularly high-resolution CT scanning, may better characterize pulmonary disease associated with CTD.

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.40

More on Undifferentiated Connective-Tissue Disease

Overview: Undifferentiated Connective-Tissue Disease
Differential Diagnoses & Workup: Undifferentiated Connective-Tissue Disease
Treatment & Medication: Undifferentiated Connective-Tissue Disease
Follow-up: Undifferentiated Connective-Tissue Disease
References
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Further Reading

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Keywords

undifferentiated connective-tissue disease, UCTD, undifferentiated connective-tissue syndromes, UCTS, early connective-tissue disease, rheumatoid arthritis, RA, systemic lupus erythematosus, SLE, systemic sclerosis, SSc, polymyositis, PM, dermatomyositis, DM, mixed connective-tissue disease, MCTD, Sjögren's syndrome, Sjögren syndrome, SS

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Contributor Information and Disclosures

Author

Bernard A Hildebrand Jr, MD, Staff Rheumatologist, Department of Rheumatology, San Antonio Military Medical Center, San Antonio, Texas
Bernard A Hildebrand Jr, MD is a member of the following medical societies: American College of Physicians and American College of Rheumatology
Disclosure: Nothing to disclose.

Coauthor(s)

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

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

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.

CME Editor

Alex J Mechaber, MD, FACP, 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, Professor of Medicine, Temple University 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: medifocus Honoraria Review panel membership; health dialogs Honoraria Consulting; West Penn Allegheny Health System None Board membership

 
 
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