Undifferentiated Connective-Tissue Disease Differential Diagnoses

Updated: Jun 15, 2021
  • Author: Bernard Hildebrand, MD, MA; Chief Editor: Herbert S Diamond, MD  more...
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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