Mixed connective tissue disease (MCTD) was first identified in 1972 and involves overlapping features of systemic lupus erythematosus, scleroderma, and myositis. The cause is unknown but likely involves autoimmunity against the U1-70 kD small nuclear ribonucleoprotein. Diagnosis requires high levels of anti-U1 RNP antibodies and a positive antinuclear antibody test. While prognosis can be poor if pulmonary hypertension develops, MCTD is generally very responsive to treatment with glucocorticoids.

1. Mixed Connective Tissue Disease
by
Farshid Mokhberi
Shahid beheshti University Of Medical Sciences & health services

2. Definition
• Mixed connective-tissue disease (MCTD) was first
recognized by Sharp and colleagues (1972) in a group
of patients with overlapping clinical features:
Systemic lupus erythematosus
Scleroderma
Myositis

3. Pathophysiology
• B-lymphocyte hyperactivity
• T-lymphocyte activationin
• Apoptotic modification of the U1-70 kd antigen
• Immune response against apoptotically modified
self-antigens
• Genetic association with major
histocompatibility genes human leukocyte
antigen (HLA)–DRB1*04/*15
• Vascular endothelial proliferation with
widespread lymphocytic and plasmacytic
infiltration of tissues

4. Etiology
• The fundamental cause of MCTD remains unknown.
• Autoimmunity to components of the U1-70 kd snRNP
are a hallmark of disease. Anti-RNP antibodies can
precede overt clinical manifestations of MCTD but after 1
year.
• The loss of T-lymphocyte and B-lymphocyte tolerance,
abnormalities of apoptosis, or molecular mimicry by
infectious agents, and driven by U1-RNA-induced innate
immune responses, are proposed current theories of
pathogenesis.

7. Differential Diagnoses
• Bacterial Sepsis
• Dermatomyositis
• Polymyositis
• Primary Pulmonary Hypertension
• Raynaud Phenomenon
• Rheumatoid Arthritis
• Scleroderma
• Systemic Lupus Erythematosus (SLE)

8. Diagnosis
• High titers of anti-U1-RNP antibody, of SLE,
scleroderma, and inflammatory myositis.
• High-titer speckled pattern fluorescent
antinuclear antibody (FANA) is typical of MCTD
• Anti-RNP antibodies are required for diagnosis
of MCTD.The presence of anti–U1-70 kd is
characteristic of MCTD.
• MCTD can enter sustained remission later in the
clinical course. Anti-RNP autoantibodies
typically become undetectable in patients in
remission.

9. Diagnostic Criteria

10. Diagnostic Criteria

11. Imaging Studies
• Chest radiography : infiltrates, effusion, or
cardiomegaly
• Echocardiography: effusion ,pulmonary
hypertension
• Ultrasonography/CT scanning :abdominal pain
(indicated for evidence of serositis, pancreatitis,
or visceral perforation related to vasculitis)
• MRI - Used to assess neuropsychiatric signs or
symptoms

12. Treatment
• MCTD:
extremely responsive to Glucocorticoids

14. Prognosis
 Mortality:
• Progressive pulmonary
hypertension and its cardiac
complications.
• Pulmonary hypertension due to
scleroderma-like vasculopathy
can lead to death in a few
weeks.
• Myocarditis
• Renovascular hypertension and
cerebral hemorrhage
 Morbidity:
• recurrent musculoskeletal pain
• low energy levels
• Flares of polymyositis
• glucocorticoid use:
aseptic necrosis, vertebral
compression fractures,
cataracts, weight gain,
accelerated atherosclerosis,
nosocomial infections, and
proximal myopathy.

15. •Thanks for your attention