Diagnostic Considerations

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.^[47]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.^[48]

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.^{[14, 15, 19, 46, 47, 49]}

Table 2. Predictors of Progression to Definite Connective-Tissue Disease (Open Table in a new window)

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

Differential Diagnoses

Workup

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

Inclusion Criteria

Clinical

Exclusion Criteria (Applicable to patients at disease onset)

Laboratory Exclusion Criteria (Applicable to patients at disease onset)

1. Signs and symptoms suggestive of a CTD but not fulfilling the diagnostic or classification criteria for any of the defined CTDs (using previously established classification criteria for SLE, MCTD, SSc, PM/DM, RA and SS) for at least 3 years. If the disease duration is less than 3 years, patients may be defined as having an early UCTD.

Adapted from Mosca et al^[14]and Doria et al.^[23]

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 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