MIXED CONNECTIVE TISSUE DISORDER

DR.Y.SASIKUMAR

 Mixed connective tissue disease (MCTD) is defined as a 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, scleroderma, and polymyositis.

Mixed connective tissue disease (MCTD) was first recognized by Dr.Sharp and colleagues in 1972

People with MCTD are 1st diagnosed as SLE.

As the disease progress and other signs and symptoms become apparent the diagnosis is corrected

MCTD is much more common in women than in men (ratio of 16 : 1)

The onset of MCTD can occur at any age but typically occurs in people aged 15-25 years.

Alarcon-Segovia's criteria A. Serologic criteria High titer Anti-RNP antibodies( ≥1:1600)

B. Clinical criteria

1. Swollen fingers 2. Synovitis 3. Myositis 4. Raynaud's phenomenon 5. Acrosclerosis MCTD is present if: Criterion A is accompanied by 3 or more clinical criteria

- one of which must include synovitis or myositis.

General features — In the early phases of the MCTD easy fatigability,myalgias,

arthralgias.Fever — Fever of unknown origin may be the presenting feature of

MCTD

Skin —The most common skin change is the Raynaud phenomenon.

Swollen digits and total hand edema.

sclerodactyly and calcinosis cutis .

Discoid plaques and malar rash.

Mucous membrane involvement - orogenital and buccal ulcerations, nasal septal perforation.

Arthritis — joint involvement in MCTD is more common

and frequently more severe than in classic SLE.

Approximately 60 percent of patients with MCTD develop an obvious arthritis, often with deformities .

Myositis — Myalgia is a common symptom in patients

with the MCTD syndrome.

Cardiac disease —  All three layers of the heart may be involved in MCTD. Pericarditis is the commonest clinical manifestation of cardiac involvement

being reported in 10 to 30% of patients;

The presence of pulmonary hypertension may be suspected when the patient is having -

 • Exertional dyspnea

 • Systolic pulsation at the left sternal border

 • An accentuated second pulmonary sound

 • Dilation of the pulmonary artery on x-ray

 • Right ventricular hypertrophy on electrocardiogram

 

Two-dimensional echocardiography with Doppler flow studies is the most useful screening test .

Definitive diagnosis is requiring cardiac catheterization,will show a mean resting pulmonary artery pressure greater than 25mm Hg at rest.

Pulmonary involvement — The lungs are commonly affected in MCTD with involvement in about 75

percent of patients.

 • Pleural effusions

 • Pleuritic pain

 • Pulmonary hypertension

 • Interstitial lung disease

  • Alveolar hemorrhage

 • Diaphragmatic dysfunction

 • Aspiration pneumonitis/pneumonia

 • Obstructive airways disease

 • Pulmonary vasculitis

High resolution computed tomography (HRCT) is a sensitive test to determine the presence of ILD.

Renal disease —

 The absence of severe renal disease is a hallmark of MCTD.

Some degree of renal involvement occurs in about 25 percent of patients.

Membranous nephropathy is the most

common finding.

Gastrointestinal disease —

Occurrs in about 60 % of patients.

Disordered motility in the upper gastrointestinal tract is the commonest problem.

Other involments are hemoperitoneum,

duodenal bleeding,pancreatitis, ascites, and protein loosing enteropathy, primary biliary cirrhosis, hepatitis.

.

Central nervous system disease 

Aapproximately 25 % of patients have some mild form of CNS disease .

The most frequent CNS manifestation is a trigeminal (fifth cranial) nerve neuropathy.

Hematologic abnormalities —

 • Approximately 75% of patients have a low-grade anemia.

 •Leukopenia, mainly affecting the lymphocyte series, is a common finding.

 •The majority of patients have hypergammaglobulinemia.

.Less common problems include thrombocytopenia, hemolytic anemia.

Pregnancy — 40% prevalence of flares during pregnancy

Small for gestational age infants occurred in 50% of pregnancies.

The mechanism for pregnancy complications is probably an autoimmune reaction against placental tissues.

Treatment

The overall goal of therapy is to control symptoms and to maintain function.

Monitoring for development of complications, such as pulmonary hypertension or infection, is important.

ActivityConvincing data support the value of an

active lifestyle and an exercise programme in patients with arthritis in MCTD.

Medication The goals of pharmacotherapy are to reduce

morbidity and to prevent complications.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

These agents reduce pain and inflammation and allow for improvement in mobility and function.

Proton pump inhibitors Esophageal reflux symptoms can be

controlled effectively with these agents.

Corticosteroids These agents are reserved for more active

or severe disease.

Calcium channel blocking agents Avoiding exposure to cold temperatures and

using long-acting calcium channel blocking agents may control Raynaud phenomenon.

Phosphodiesterase (type 5) Enzyme Inhibitor

Eg-sildenafil

Phosphodiesterase inhibitors can relief symptoms of pulmonary hypertension and Raynaud phenomenon in patients with MCTD.

Endothelin Receptor Antagonist Eg- Ambrisentan These agents may be helpful for managing

pulmonary hypertension in patients with MCTD.

This leads to significant increase in cardiac index associated with significant reduction in pulmonary artery pressure, pulmonary vascular resistance.

Improves exercise ability..

Prostaglandins Eg-Epoprostenol These agents may be useful for managing

pulmonary hypertension in patients with MCTD.

Strong vasodilator of all vascular beds.

Decrease platelet clumping in the lungs by inhibiting platelet aggregation.

Cytotoxic agents Major organ involvement may require

moderate-to-high divided daily doses of cytotoxic agents.

Recent reports suggest that, in contrast to primary or scleroderma-associated pulmonary hypertension, a subset of MCTD patients with pulmonary hypertension may respond well to aggressive immunosuppression with cytotoxic agents.

PROGNOSIS  Overall mortality is apparently lower in

patients with MCTD than in those with classic SLE.

The major disease related causes of death is Progressive pulmonary hypertension and its cardiac complications.

 The patients with MCTD emphasized the relatively good prognosis and excellent response to corticosteroids.

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