Dermatologic Manifestations of Mixed Connective Tissue Disease

Updated: Jun 06, 2017
  • Author: Robert A Schwartz, MD, MPH; Chief Editor: William D James, MD  more...
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Overview

Background

Mixed connective-tissue disease (MCTD) is a disorder with features of systemic sclerosis (SSc), lupus erythematosus, and polymyositis. U1-ribonucleoprotein (RNP) antibodies are a specific marker of the disease. [1] MCTD is considered a distinct syndrome and should not be confused with other connective-tissue disease overlap syndromes with features of various connective-tissue diseases. [2] The course of MCTD is chronic and usually milder than other connective-tissue diseases. Although MCTD is a distinct clinical entity, a subgroup of patients may evolve into having another connective-tissue disease. [3]

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Pathophysiology

A defining feature of mixed connective-tissue disease (MCTD) is the presence of antibodies against the U1-RNP complex, but other autoantibodies have also been described in MCTD. [4] Some hypotheses implicate modified self-antigens and/or infectious agents in the pathogenesis of MCTD. MCTD differs from systemic lupus erythematosus (SLE) in a number of ways; a study of major histocompatibility complex class I polypeptide-related sequence A and human leukocyte antigen (HLA) gene polymorphisms showed the allele frequency of MICA129 Val was significantly increased in MCTD patients compared with controls and with SLE patients. [5]

The U1 small nuclear ribonucleoprotein particle (snRNP) is a target of autoreactive B cells and T cells in MCTD. [6] Understanding the interactions between U1-snRNP and the immune system may prove beneficial.

The pathogenesis of MCTD is not completely known. As with other connective-tissue diseases, MCTD is considered an autoimmune disease to which individuals who express specific HLA antigens such as HLA-DR4 or HLA-DQB1 are genetically predisposed. The frequency of HLA-DR4 in patients with MCTD is estimated to be 52%. Its strong HLA association with MCTD was further shown in the significantly increased frequency of the combination of HLA-B15 with HLA-DR4. Thus, the genetic background in patients with MCTD seems to be different from that in patients SLE or systemic sclerosis. This observation could partly explain the clinical differences between these diseases. The specific nature of the HLA associations that occur in patients with MCTD may vary depending on the ethnicity of the population studied. HLA-DRB1 genotypes may have a modulating influence on MCTD in Polish patients. [7]

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Epidemiology

Frequency

Mixed connective-tissue disease (MCTD) is uncommon worldwide. The incidence of adult-onset mixed connective-tissue disease (MCTD) in Norway was found to be 2.1 per million per year. [8] It has a female predominance. Its incidence and prevalence is lower than for polymyositis, dermatomyositis, systemic sclerosis, and systemic lupus erythematosus. MCTD was documented in about two persons per 100,000 population annually in Olmsted County, Minnesota. [9]

Sex

Women are affected by mixed connective-tissue disease (MCTD) more often than men. The female-to-male ratio is 4:1.

Age

Mixed connective-tissue disease (MCTD) usually occurs in individuals aged 30-50 years.

MCTD also affects children, in whom the course is more severe because cardiac and renal involvement are more common. MCTD-related thrombocytopenia, which is unusual in adults, may be marked in children.

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Prognosis

Prognosis for patients with mixed connective-tissue disease (MCTD) is better than for patients who have only one form of overlapping disease. Many patients will later progress to scleroderma or lupus; some will remain undifferentiated. In addition, myositis of MCTD may have a better prognosis than other forms of myositis.  The prognosis for patients with MCTD is generally better than that of patients with systemic lupus erythematosus, systemic sclerosis, and dermatomyositis.

In one case series, solid tumors developed in approximately 10% of patients.

Nephritis is associated with a poor prognosis. It is considered a common cause of death.

However, pulmonary involvement is linked with the worst prognosis and high mortality. [10] Pulmonary arterial hypertension is the leading cause of death in these patients in a study of the survival rate and prognostic indicators of MCTD in a Hungarian population, although cardiovascular morbidity and mortality, cancer, and thrombotic events were enhanced during the disease course of MCTD. [11] The presence of antiphospholipid antibodies correlated with an increased risk of mortality. About 4% of patients die, usually as a result of pulmonary hypertension, nephritis, myocarditis, or widespread vasculitis.

MCTD changing to other connective-tissue diseases was uncommon, with mortality found to be unaffected, in a survey in Olmsted County, Minnesota. [9]

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Patient Education

Educate mixed connective-tissue disease (MCTD) patients regarding photoprotection. Patients should avoid sun exposure, which is a triggering and aggravating factor.

Patients with Raynaud phenomenon should be instructed to avoid exposure to cold.

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