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]:

Common manifestations: Raynaud phenomenon, Puffy fingers and/or swollen hands
Immunologic manifestation: Anti–U1-RNP antibody positivity
Characteristic organ involvement: Pulmonary arterial hypertension, aseptic meningitis, trigeminal neuropathy
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

Workup

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Media Gallery

Raynaud phenomenon is a common feature of mixed connective tissue disease.
Chest radiograph in a patient with pulmonary hypertension reveals enlarged pulmonary arteries.

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Author

Eric L Greidinger, MD Associate Professor, Department of Medicine, Division of Rheumatology and Immunology, University of Miami, Leonard M Miller School of Medicine, Miami Veterans Affairs Medical Center

Eric L Greidinger, MD is a member of the following medical societies: American College of Physicians, American College of Rheumatology

Disclosure: Received research grant from: Corbus Pharmaceuticals; Eli Lilly & Company; Horizon Pharmaceuticals; INFLARX GBMH, Mitsubishi Pharmaceuticals, Reatta Pharmaceuticals, Swedish Orphan Biovitrum AB.

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: Received salary from Medscape for employment. for: Medscape.

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

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

Disclosure: Nothing to disclose.

Chief Editor

Herbert S Diamond, MD Visiting Professor of Medicine, Division of Rheumatology, State University of New York Downstate Medical Center; 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, Phi Beta Kappa

Disclosure: Nothing to disclose.

Additional Contributors

Bryan L Martin, DO Associate Dean for Graduate Medical Education, Designated Institutional Official, Associate Medical Director, Director, Allergy Immunology Program, Professor of Medicine and Pediatrics, Ohio State University College of Medicine

Bryan L Martin, DO is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American College of Allergy, Asthma and Immunology, American College of Osteopathic Internists, American College of Physicians, American Medical Association, American Osteopathic Association

Disclosure: Nothing to disclose.

Acknowledgements

Robert W Hoffman, DO, FACP, FACR Chief, Division of Rheumatology and Immunology, Professor, Departments of Medicine and Microbiology & Immunology, University of Miami, Leonard M Miller School of Medicine

Robert W Hoffman, DO, FACP, FACR is a member of the following medical societies: American Association for the Advancement of Science, American Association of Immunologists, American College of Physicians, American College of Rheumatology, and Clinical Immunology Society

Disclosure: Nothing to disclose.