Mixed connective tissue disease (Sharp syndrome)

Definition

Mixed connective tissue disease (MCTD, Sharp syndrome) is an uncommon, specifically defined syndrome with overlapping features of systemic lupus erythematosus, systemic sclerosis, and polymyositis. It is characterized by very high titers of antinuclear antibodies against U1 ribonucleoprotein (U1 RNP).

Occurrence & epidemiology

MCTD occurs worldwide and in all ethnic groups. Incidence peaks in adolescence; females are affected more often.

Aetiopathogenesis

It is an autoimmune disease within the spectrum of connective tissue diseases. Many patients initially have an undifferentiated connective tissue disease; the clinical pattern changes over time. A significant minority evolve into a well-defined disease such as systemic sclerosis, systemic lupus erythematosus, or an inflammatory myopathy a few years after diagnosis.

Clinical features

• Raynaud syndrome, often years before other symptoms
• Diffuse swelling of the hands typical at onset but not universal
• Skin: chilblains, discoid lesions, lupus-like malar rash; scleroderma-like skin changes, ischemic necrosis or ulceration of the fingertips
• Joints: polyarthralgias in almost all, arthritis in 75 %, usually nondeforming; erosive changes and deformities as in rheumatoid arthritis also possible
• Muscles: proximal muscle weakness with elevated muscle enzymes
• Gastrointestinal: dysmotility similar to systemic sclerosis
• Lungs: affected in up to 75 %, mainly pleural effusions and interstitial lung disease; pulmonary hypertension in up to 13 %
• Kidney: in about 25 %, usually mild (mostly membranous nephropathy)
• Heart: pericarditis common, myocarditis uncommon; secondary Sjögren syndrome possible

Diagnosis

• ANA on indirect immunofluorescence in almost all, high titer with a speckled pattern.
• Anti-U1 RNP antibodies, usually at very high titers; not sufficient alone, typical clinical findings are required.
• Anti-Sm and anti-dsDNA are measured to exclude SLE; anti-dsDNA is negative in MCTD by definition.
• Rheumatoid factor frequently positive, sometimes high titer; ESR and CRP often elevated.
• Organ assessment: pulmonary function tests and echocardiography to look for pulmonary hypertension; creatine kinase, MRI, electromyography, or muscle biopsy when myositis is suspected; further tests depending on renal or pulmonary involvement.

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Further reading (open access)

1. MSD Manual Professional: Mixed Connective Tissue Disease (MCTD)

Cross-references