Definition and diagnosis of mixed connective tissue disease
- Robert M Bennett, MD, FRCP, MACR
Robert M Bennett, MD, FRCP, MACR
- Professor of Medicine
- Oregon Health & Science University
Mixed connective tissue disease (MCTD) was originally defined in 1972 as a connective tissue disorder characterized by the presence of high titers of a distinctive autoantibody, now called anti-U1 ribonucleoprotein (RNP) (previously termed antibody to extractable nuclear antigens [anti-ENA]) . The central premise of the MCTD concept is that of an overlap syndrome associated with anti-U1 RNP antibodies that incorporates selected clinical features of systemic lupus erythematosus (SLE), systemic sclerosis (scleroderma [SSc]), and polymyositis (PM) .
The definitive diagnosis of MCTD is often complicated by the fact that the overlapping features tend to occur sequentially . This confusion arises due to the overlap of the various diffuse connective tissue diseases (DCTD), as well as to changes in the underlying pathology of the illnesses.
The definition and diagnosis of mixed connective tissue disease are reviewed here. The clinical manifestations, prognosis, and treatment of the illness, as well as a detailed discussion of anti-U1 RNP antibodies, are presented separately. (See "Clinical manifestations of mixed connective tissue disease" and "Prognosis and treatment of mixed connective tissue disease" and "Anti-U1 RNP antibodies in mixed connective tissue disease".)
Five major diffuse connective tissue diseases (DCTD) exist according to classification schema: systemic lupus erythematosus (SLE); systemic sclerosis (scleroderma [SSc]); polymyositis (PM); dermatomyositis (DM); and rheumatoid arthritis (RA). A sixth disorder, Sjögren’s syndrome, is commonly associated with each of these diseases but is called primary Sjögren’s syndrome when it occurs alone.
The classical clinical descriptions of these disorders are well known, and most patients with well-differentiated disease are easily recognized. However, the definitive diagnosis of each of these disorders is based upon criteria derived from expert opinion; as such, the diagnostic criteria are updated from time to time, depending upon the relevance of contemporary research. Clinicians experienced in the clinical presentations of the connective tissue disorder often note that one autoimmune rheumatic disease seems to evolve into another over the course of several years . This occurs in about 25 percent of patients, who are then said to have an overlap syndrome . (See "Undifferentiated systemic rheumatic (connective tissue) diseases and overlap syndromes".)
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