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.

25. THANK YOU