Approach Considerations

The overall goals of therapy for mixed connective-tissue disease (MCTD) are to control symptoms, to maintain function, and to reduce the risk of future disease consequences. Medical therapy targets control of disease activity in general and management of specific organ involvement (see Medication), while monitoring for and mitigating the risks of complications either of the condition itself (eg, pulmonary hypertension, interstitial lung disease) or of its treatment (eg, infection) (see Follow-up).

Patients with MCTD may require hospital admission while undergoing assessment for suspected infection or complications related to disease or treatment. Admit patients to the appropriate service with rheumatology care, if available. Obtain subspecialty consultations as indicated.

Consultations

Whenever possible, a rheumatologist experienced in diagnosis and treatment of the disease should co-manage all patients with mixed connective-tissue disease (MCTD). Consultation with other specialists or subspecialists may be indicated for the evaluation and/or treatment of specific aspects of disease, such as pulmonary hypertension, interstitial lung disease, gastroesophageal reflux, or acute ischemia due to Raynaud's phenomenon.

Diet and Activity

Aggressive cold avoidance may help to reduce the risk of flares of Raynaud's Phenomenon.

Patients with hypertension, esophageal reflux, malabsorption, or other sclerodermatous-type bowel involvement may need special consideration.

Because atherosclerotic heart disease remains a major risk in all patients, advocate a heart-healthy diet. However, no specific dietary manipulations have been demonstrated to be effective in treating MCTD.

Convincing data support the value of an active lifestyle and an exercise program tailored to the needs of patients with arthritis of various types. This approach also appears to be appropriate in MCTD.

Prevention

Given that other inflammatory rheumatic diseases—including rheumatoid arthritis, lupus, and scleroderma—are reported to be independent risk factors for the development of atherosclerosis and related conditions, patients with MCTD may also be at increased risk for atherosclerosis. As in those other conditions (and modeled after recommendations developed for diabetes mellitus), more aggressive targets for blood pressure and cholesterol control may be appropriate.

Long-Term Monitoring

Patients with stable disease and no recent changes in medications should be seen approximately every 2-4 months and undergo routine laboratory evaluation, including a complete blood cell count and chemistry studies. Patients with active disease are typically seen approximately every 3-6 weeks, depending on the severity of disease.

Recommendations for screening and early detection of pulmonary artery hypertension (PAH) associated with connective tissue diseases, including MCTD, have been published.^[36] Although these guidelines do not recommend screening of asymptomatic patients with MCTD who lack features of scleroderma, the following studies are recommended for symptomatic patients:

Pulmonary function testing (spirometry with lung volumes) with single-breath diffusing capacity for carbon monoxide (DLCO)
Transthoracic echocardiogram (TTE)
N-terminal pro-B-type natriuretic peptide (NT-Pro BNP) tests

Use of 6-minute walk stress echocardiography has also been proposed as a means of predicting the development of PAH in patients with connective tissue disorders.^[37]

Abnormalities on noninvasive tests require confirmation with right heart catheterization, which remains the gold standard for diagnosis of PAH.

Medication

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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.