Mixed connective tissue disease
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Transcript of Mixed connective tissue disease
Global Critical Carehttps://www.facebook.com/groups/1451610115129555/#!/groups/1451610115129555/
Wellcome in our new group ..... Dr.SAMIR EL ANSARY
History• 1972 Sharp and colleagues– Identified patients with high levels of antibodies
against a ribonucleic protein (RNP)– These patients shared several clinical features
including Raynaud’s phenomenom, arthralgias, mild arthritis, puffy hands, abnormal esophageal mobility, and myositis
– Additional findings – hypergammaglobulinemia (80%), anemia and leukopenia (50%); pulmonary, renal and CNS involvement was “rare”
History• 1980 Nimelstein and colleagues– Doubts after reviewing 22/25 original patients– Many patients evolved into scleroderma– High mortality rate (8/22)– Not everyone had antibodies to RNP– Some patients had antibodies without clear
clinical features of the syndrome• Then, 20 years of contradictory views
regarding the existence and nature of MCTD
Diagnostic Criteria
• Features of SLE, systemic sclerosis, RA, and polymyositis
• Four different diagnostic criteria have been proposed– Sharp– Kasukawa– Alarcon-Segovia– Kahn
• Highest sensitivity (62%) and specificity (86%) with Alarcon-Segovia and Kahn in 45 patients
Diagnostic Criteria – Sharp• Major Criteria– Myositis– Pulmonary
Involvement– Raynaud
phenomenom or esophageal dysmobility
– Swollen hands or sclerodactyly
– High anti-U1-RNP with negative anti-Sm
• Definite – 4 major plus serology• Probable – 3 major or 2 major
(1st 3 listed) and 2 minor; and serology
• Minor Criteria– Alopecia– Leukopenia– Anemia– Pleuritis– Pericarditis– Arthritis– Trigeminal Neuralgia– Malar Rash– Thrombocytopenia– Mild Myositis– h/o swollen hands
Diagnostic CriteriaAlarcon-Segovia
–Clinical Criteria 3/5 (must have synovitis or myositis)• Edema of the hands• Synovitis•Myositis• Raynaud’s phenomenon• Acrosclerosis
Serologic: high titers of anti-U1 RNP
Diagnostic Criteria
• “The crux of the MCTD diagnosis is the presence of high titers of antibodies to U1-RNP.”
• Many patients who satisfy criteria for MCTD also satisfy ACR criteria for RA or SLE, and many had symptoms of systemic sclerosis.
• “With serology superseding the clinical symptoms in the diagnosis, there is a risk of fitting the clinical symptoms to the antibody signs”
Clinical Presentation
• Early Clinical Findings– Malaise, easy
fatiguability– Arthralgias– Myalgias– Raynaud’s
phenomenom– Low-grade fevers
• Unusual Presentations– FUO Fever of unknown origin
– Serositis– Trigeminal neuropathy– Severe polymyositis– Acute arthritis– Aseptic meningitis– Digital gangrene
Characteristic At Diagnosis Cumulative at 5 years
Raynaud’s Phenomenom
89% 96%
Arthralgia/Arthritis 85% 96%
Swollen Hands 60% 66%
Esophageal Dysmotility
47% 66%
Pulmonary Dysfunction
43% 66%
Serositis 34% 43%
Hematologic 30% 53%
Erythematous Skin Rash
30% 53%
Muscle Myositis 28% 51%
Pulmonary Hypertension
9% 23%
Sclerodermatous Changes
4% 19%
CNS (or peripheral) 0% 17%
Renal 2% 11%
Pulmonary Manifestations
• Pleural Effusions• Pulmonary Hypertension• Pleuritic Pain• Intersitial Lung Disease (30-50%)• Thromboembolic Disease• Obstructive Disease• Pulmonary Vasculitis
• 75% of patients• Early Symptoms– Dry cough– Dyspnea– Pleuritic Chest Pain
Pericardial Disease
• Pericardial Involvement– Scleroderma59%– SLE 44%– MCTD 30%– RA 24%
• MCTD– At autopsy – 56% had pericardial disease– Asymptomatic pericardial effusion – 24-38%
Laboratory Findings
• High titer, speckled ANA pattern• Leukopenia, anemia, thrombocytopenia• Elevated ESR• Very high serum immunoglobulins• Complement levels usually normal or high• Rheumatoid Factors increased in 70% of patients• Negative findings include anti-dsDNA and anti-Sm
antibodies (if positive, some argue that it represents exclusion criteria for MCTD)
Antibody Findings
Disease
ANA RF dsDNA
Sm Scl-70
RNP
SLE 95-99 20 50-70 30 0 30-50
RA 15-35 85 <5 0 0 10
DiffuseSSc
>90 30 0 0 40 30
MCTD 95-99 50 0 <5 0 100
Follow-Up
• 39 MCTD patients at 10 year follow-up– 64% “differentiated” into another syndrome– 11 systemic sclerosis, 10 SLE, 2 RA, 2 overlap
syndrome• Other studies have found similar results• About 40% of patients with anti-U1RNP
antibodies retain the diagnosis of MCTD and others are “reclassified” within 5 years of presentation
Undifferentiated and Overlap Syndromes
• MCTD– SLE, SSc, PM, RA
• Undifferentiated Systemic Rheumatic Disease–Undifferentiated connective tissue,
collagen, vascular, or autoimmune disease• Nonclassical SLE• “Atypical” rheumatic disease• Undiiferentiated Polyarthritis Syndrome• Undifferentiated Spondyloarthritis
Undifferentiated and Overlap Syndromes
Overlap Syndromes• RA-lupus– Rhupus
• Scleroderma-PM/DM• Scleroderma-lupus• Scleroderma-PBC-Sjogren’s• Scleroderma-RA
JRA-lupus Psoriatic arthritis-lupus
Psupus Sjogren’s overlaps PM overlaps Raynaud’s phenomenom overlaps
SLE Criteria• Malar Rash• Discoid Rash• Photosensitivity• Oral Ulcers• Arthritis• Serositis• Renal Disease• Neurologic Disease
• Hematologic Disease– Hemolytic anemia– Leukopenia, lymphopenia
• Immunologic– Anti-dsDNA– Anti-Sm
• ANA
• 4/11 Criteria
Global Critical Carehttps://www.facebook.com/groups/1451610115129555/#!/groups/1451610115129555/
Wellcome in our new group ..... Dr.SAMIR EL ANSARY