Mixed Connective Tissue Disease

by

Farshid MokhberiShahid beheshti University Of Medical Sciences & health

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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

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

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.

Differential Diagnoses

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

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.

Diagnostic Criteria

Diagnostic Criteria

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

Treatment•MCTD: extremely responsive to Glucocorticoids

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.

•Thanks for your attention