Mixed connective tissue disease

Mixed connective tissue disease (MCTD), also known as Sharp syndrome, is a systemic autoimmune disorder characterized by overlapping features of systemic lupus erythematosus (SLE), systemic sclerosis (scleroderma), polymyositis, and sometimes rheumatoid arthritis, combined with the presence of high titers of anti-U1 ribonucleoprotein (anti-U1 RNP) antibodies. The disease was first described by Gordon Sharp in 1972 and is considered a distinct clinical entity, though some debate exists about whether it represents a separate condition or an overlap syndrome. MCTD affects multiple body systems. The most common early feature is Raynaud's phenomenon, which occurs in the vast majority of patients. Other key clinical features include swollen or "puffy" hands, polyarthralgia or arthritis, myositis with muscle weakness, esophageal dysmotility, sclerodactyly, and pulmonary involvement. Pulmonary arterial hypertension (PAH) is one of the most serious complications and a leading cause of mortality. Patients may also develop serositis (pleuritis or pericarditis), lymphadenopathy, skin rashes, cytopenias, and renal disease, though severe kidney involvement is less common than in SLE. The disease predominantly affects women, with a female-to-male ratio of approximately 9:1. There is no cure for MCTD, and treatment is tailored to the specific organ manifestations present. Mild disease with arthralgia and Raynaud's phenomenon may be managed with nonsteroidal anti-inflammatory drugs (NSAIDs), calcium channel blockers, and hydroxychloroquine. More severe manifestations such as myositis, serositis, or significant organ involvement typically require corticosteroids and immunosuppressive agents such as methotrexate, azathioprine, or mycophenolate mofetil. Pulmonary arterial hypertension requires targeted therapies including endothelin receptor antagonists, phosphodiesterase-5 inhibitors, or prostacyclin analogs. The prognosis is variable; some patients have a relatively benign course, while others may evolve toward a more defined connective tissue disease, particularly systemic sclerosis, or develop life-threatening complications.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about Mixed connective tissue disease