This document discusses mixed connective tissue disease (MCTD), including its definition, key diagnostic criteria, common symptoms and organ involvement, treatment approaches, and prognosis. MCTD is characterized by features of lupus, scleroderma, and polymyositis combined with high levels of anti-U1 RNP antibodies. Common symptoms include Raynaud's phenomenon, joint and muscle issues, lung and heart involvement. Treatment focuses on managing symptoms with medications like NSAIDs, corticosteroids, calcium channel blockers, and pulmonary hypertension drugs. Overall mortality is lower than lupus, but progressive pulmonary hypertension can be a major cause of death.

1. DR.Y.SASIKUMAR

2.  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.

3.  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

4.  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.

5. 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.

6.  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.

7. 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.

8.  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

9.  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.

10. 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.

11.  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.

12.  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.
.

13.  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.

14.  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.

15.  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.

16. 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.

17. Activity
Convincing data support the value of an active
lifestyle and an exercise programme in
patients with arthritis in MCTD.

18. 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.

19. 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.

20. Phosphodiesterase (type 5) Enzyme Inhibitor
Eg-sildenafil
 Phosphodiesterase inhibitors can relief
symptoms of pulmonary hypertension and
Raynaud phenomenon in patients with MCTD.

21. 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..

22. 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.

23. 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.

24. 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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