Mixed connective tissue disease
Mixed connective tissue disease is an overlap syndrome defined by a high-titer anti-U1-ribonucleoprotein antibody together with clinical features of systemic lupus erythematosus, systemic sclerosis, and inflammatory myositis, with Raynaud phenomenon and puffy fingers as near-universal early findings. Treatment is organ-directed, built on hydroxychloroquine and glucocorticoids with methotrexate, azathioprine, or mycophenolate mofetil escalation guided by the dominant manifestation.
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What this article covers
- Overview
Definition: mixed connective tissue disease (MCTD) is a distinct overlap syndrome, serologically defined by a high titer of anti-U1-ribonucleoprotein (RNP) antibody, with manifestations meeting a…
- Epidemiology
Rare disease: an uncommon diagnosis within the connective tissue disease spectrum.
- Risk factors
Female sex: the strongest demographic risk factor.
- Pathophysiology
Anti-U1-RNP antibody: the defining serologic feature; it binds the 70-kD epitope of the ribonucleoprotein complex, but how it contributes to tissue injury is not established.
- Clinical features
Raynaud phenomenon: bi- or tricolor color change of the digits with cold or stress, present in nearly all patients and often the presenting symptom.
- Differential diagnosis
Systemic lupus erythematosus: shares ANA positivity, arthritis, and serositis, but anti-double-stranded DNA, anti-Smith, or anti-Ro, or severe kidney or neurologic disease, favor primary SLE over MCTD.
- Diagnosis
The diagnosis is established by a high titer of anti-U1-RNP antibody with clinical features fulfilling criteria for at least two of systemic sclerosis, autoimmune myositis, and SLE; antibody titer…
- Management
First, treat by the dominant organ manifestation, mirroring the management of whichever parent disease the presentation most resembles; no single approach covers all of MCTD.
- Complications
Pulmonary arterial hypertension: the leading cause of death in MCTD; once established it carries a poor prognosis.
- Prognosis
Prognosis tracks organ involvement: outcome depends on the spectrum and severity of organs affected.
- Prevention
Screen proactively for PAH: pulmonary function testing with DLCO and transthoracic echocardiography at baseline and annually, and for new cardiopulmonary symptoms, using an FVC/DLCO ratio of 1.6 or greater as a clue to underlying PAH.
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