mixed connective tissue disease
TRANSCRIPT
Mixed Connective Tissue Disease
SAMIR EL ANSARYICU PROFESSOR
AIN SHAMSCAIRO
Global Critical Carehttps://www.facebook.com/groups/1451610115129555/#!/groups/145161011512
9555/ Wellcome in our new group ..... Dr.SAMIR EL ANSARY
“Mixed Connective Tissue Disease:
Still Crazy After All These Years”
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 phenomenomor 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’sphenomenom
– 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
– Scleroderma 59%
– 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-Smantibodies (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
Diffuse
SSc
>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/145161011512
9555/ Wellcome in our new group ..... Dr.SAMIR EL ANSARY
