Mixed Connective Tissue Disease: Still Crazy After All These Years

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Diagnostic criteria

Four sets of diagnostic criteria have been published, those of Sharp [6], Kasukawa [7], Alarcon-Segovia [8], and Kahn [9], summarized in a review by Smolen and Steiner [10]. These four diagnostic criteria have been evaluated [11] alongside ACR criteria for other well-defined ARDs, and Alarcon-Segovia's [8] and Kahn's [9] criteria were concluded to be comparable to the highest sensitivity (62.5% [increased to 81.3% if “myositis” is replaced with “myalgia”]) and specificity (86.3%) when tested in

A benign disease course?

Studies have shown that MCTD is not a benign disease, and vital organs, such as the lungs, can be involved. It has a mortality rate that exceeds that of SLE, according to one report [4]. The clinical course of MCTD was observed in a retrospective study of 47 patients who fulfilled the Kasukawa criteria [7] and did not evolve into another ARD [14]. Their clinical and serologic information had been collected from presentation, diagnosis, and follow-up for more than 3 years (mean 15 years). Mean

A disease entity or part of autoimmune rheumatic disease evolution?

A number of studies have been undertaken to answer this question but have produced conflicting results. Selection criteria and length of follow-up differ between groups, and many patients were selected on serologic rather than clinical grounds. Furthermore, many of the studies are retrospective.

Gendi and colleagues [4], using a prospective study of patients with the greatest disease duration, concluded that only 36% of patients presenting with high titers of anti-RNP and clinical features of

Autoantibodies

Sharp [1] described MCTD around the presence of anti–U1-RNP antibodies; however, they are not diagnostic because they occur in other ARDs, including PM/DM, RA, lupus, and scleroderma. In addition, they are not always found in patients with typical MCTD symptoms. Here we summarize the nature of these antinuclear antibodies.

Eukaryotic cells contain small nuclear RNAs complexed with several proteins to make small nuclear ribonucleoproteins. The most commonly described snRNPs are U1, U2, U3, U4/6,

Human leukocyte antigen association

There are variable associations between ARD and major histocompatibility complexes (MHC). RA, for example, has been strongly associated with an epitope found on DR4 subtypes DRB1*0401, 0404, 0405, and DR1 subtype DRB1*0101 [50].

A few studies have demonstrated an association with MCTD and human leukocyte antigen (HLA) DR4 [51], [52]. A study comparing haplotypes of patients with SLE (fulfilling the ARA criteria) and MCTD (fulfilling the Alarcon-Segovia criteria) showed that there was a DR4

Summary

The controversy about the existence of MCTD challenges us to reflect upon the question of disease nomenclature and its utility. We identify individual diseases and give them labels as a matter of convenience and because we believe they may provide a guide to outcome and thus help us to decide what we can tell our patients about future possible complications. For patients in whom problems are straightforward (eg, an attack of measles or mumps), this approach is useful because the outcome is

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