Mixed connective tissue disease (MCTD) is defined as a generalized connective tissue disorder characterized by the presence of high titer anti-U1 ribonucleoprotein (RNP) antibodies in combination with clinical features commonly seen in systemic lupus erythematosus (SLE), scleroderma (Scl), and polymyositis (PM) [1,2]. It often takes several years before enough overlapping features have appeared to be confident that MCTD is the most appropriate diagnosis . The distinctive overlap features of SLE, Scl, and PM commonly appear sequentially over time. Thus, in its early stages, MCTD is often referred to as an undifferentiated connective tissue disease (UCTD) [4,5]. (See "Undifferentiated systemic rheumatic (connective tissue) diseases and overlap syndromes".)
This topic will review the major clinical manifestations that can occur in patients with MCTD. The pathogenesis and diagnosis of this disorder are discussed separately. (See "Definition and diagnosis of mixed connective tissue disease".)
There is very little information available regarding the prevalence and incidence of MCTD. In a 2011 nation-wide study in Norway, the prevalence of MCTD was 3.8 per 100,000 adults, with an incidence of 2.1 per million per year . MCTD is much more common in women than in men, although estimates of the difference range widely (from a ratio of 3.3:1 to up to 16:1) [6-9].
The early clinical features of MCTD are nonspecific and may consist of general malaise, arthralgias, myalgias, and low-grade fever [10,11]. A specific clue that these symptoms are caused by a connective tissue disease is the discovery of a positive antinuclear antibody (ANA) in association with the Raynaud phenomenon .
As will be described below, almost any organ system can be involved in MCTD. There are, however, four clinical features that suggest the presence of MCTD rather than another connective tissue disorder such as SLE or Scl: