Mixed Connective Tissue DiseaseDz

Synonyms: Undifferentiated connective tissue disease or overlap syndrome.

ICD-9 Code: 710.8.

ICD-10 Code: M35.1

Definition: As initially described, MCTD is defined as having (a) a combination or overlap of clinical symptoms that are characteristic of systemic sclerosis, SLE, and inflammatory myositis (i.e., DM or PM) and (b) high titers of serum antibodies that react with nuclear ribonuclear proteins (or U1-RNP). Although MCTD was originally considered a unique disease state, that concept has come under question. Although such patients may have similar symptoms early in their disease, when followed over time, patients with MCTD evolve into a single identifiable rheumatic condition, most commonly scleroderma. Thus, the reason for designating these patients as having undifferentiated connective tissue disease. In addition, patients with MCTD do not seem to have a unique prognosis or disease course, and antibodies to ribonuclear proteins are not unique to MCTD; they are detectable in more than half of patients with SLE and in those with other autoimmune diseases. Few patients with MCTD will meet ACR criteria for more than one disorder.

Cardinal Findings: Probably more useful than the concept of a single MCTD is the appreciation that many patients have an overlap of signs and symptoms resembling several rheumatic diseases. Overlapping symptoms common to classically described MCTD and several rheumatic diseases include arthritis, dactylitis (sausage digits), Raynaud’s phenomenon, sclerodactyly, dysphagia, inflammatory myositis, pleuritis/pericarditis, and interstitial lung disease.

Diagnostic Tests: Although such patients are uniformly positive for ANA and often have very high titers of U1-RNP antibodies, neither is specific for MCTD or other connective tissue diseases. Complement levels are normal, and no antibodies to native, double-stranded DNA are detected. Blood counts may reveal leukopenia or thrombocytopenia.

Keys to Diagnosis: Overlap in symptoms among the various rheumatologic conditions may lead to diagnostic uncertainty, particularly early in the disease course. It has been estimated that one-third of patients initially presenting with clear rheumatologic complaints cannot be diagnosed with a definitive rheumatologic disease. Such patients may initially be designated as having undifferentiated connective tissue disease (the term preferred to MCTD). Careful observation over time usually discloses whether the dominant disorder is scleroderma, SLE, or an inflammatory myopathy.

Therapy: Patients with an undifferentiated disease should be treated according to the symptoms or features present. Thus, many patients may be managed with NSAIDs or analgesic agents for their musculoskeletal complaints. In some, therapy is guided by more serious end-organ involvement. For example, patients with severe myositis may require high-dose corticosteroids, whereas those with chronic polyarticular synovitis may be treated according to a paradigm similar to that used for RA.

BIBLIOGRAPHY

Hoffman RW, Greidinger EL. Mixed connective tissue disease. Curr Opin Rheumatol 2000; 12:386–390.PMID:10990174

Sharp GC, Irwin WS, Tan EM, et al. Mixed connective tissue disease—an apparently distinct rheumatic disease syndrome associated with a specific antibody to extractable nuclear antigen (ENA). Am J Med 1972;52:148–159.PMID:4621694