Mixed Connective-Tissue Disease (MCTD) Differential Diagnoses

Updated: Dec 22, 2022
  • Author: Eric L Greidinger, MD; Chief Editor: Herbert S Diamond, MD  more...
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Diagnostic Considerations

Overlapping criteria for diagnosis of mixed connective tissue disease (MCTD) have been published by Sharp, Alarcón-Segovia, Kasukawa, and Kahn. A 1996 comparison study determined that MCTD was best identified with the Alarcón-Segovia criteria, which have 62.5% sensitivity and 86.2% specificity, and the Kahn criteria. [34]  

The Alarcón-Segovia diagnostic criteria consist of a positive anti–U1 RNP titer (>1:1600) and at least three of the following five clinical findings [7, 8] :

  • Hand edema
  • Synovitis
  • Biologically or histologically proven myositis
  • Raynaud phenomenon
  • Acrosclerosis with or without proximal systemic sclerosis

A consensus panel in Japan in 2019 offered a revised set of diagnostic criteria for MCTD, which divides the features of the disease into the following four categories [9] :

  1. Common manifestations: Raynaud phenomenon, Puffy fingers and/or swollen hands
  2. Immunologic manifestation: Anti–U1-RNP antibody positivity
  3. Characteristic organ involvement: Pulmonary arterial hypertension, aseptic meningitis, trigeminal neuropathy
  4. Overlapping manifestations: (A) SLE-like, (B) systemic sclerosis–like, (C) polymyositis/dermatomyositis-like 

SLE-like manifestations include the following:

  • Polyarthritis
  • Lymphadenopathy
  • Malar rash
  • Pericarditis or pleuritis
  • Leukopenia (4,000/μL or less) or thrombocytopenia (100,000/μL or less)

Systemic sclerosis–like manifestations include the following:

  • Sclerodactyly
  • Interstitial lung disease
  • Esophageal dysmotility or dilatation

Polymyositis/dermatomyositis-like manifestations include the following:

  • Muscle weakness
  • Elevated levels of myogenic enzymes
  • Myogenic abnormalities on electromyogram

For diagnosis of MCTD, the patient must have the following:

  • At least one common manifestation
  • Anti–U1-RNP antibodies
  • At least one characteristic organ involvement,  or at least one feature of at least two of the three disorders in the overlapping manifestations category (A, B, and C) 

Other conditions to consider in the differential diagnosis of MCTD include the following:

  • Pleuritis
  • Respiratory distress syndrome
  • Stroke

Differential Diagnoses