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Jindaprasert, J.
Introduction
Introduction
1972- Dr Sharp published syndromes assosciated with autoAb to ribonucleoprotein... later U1RNP Concept: overlap syndrome or disease
systemic lupus erythematosus (SLE) Systemic sclerosis (scleroderma, Scl) polymyositis (PM)
Fact!!
Some autoantibodies can cause disease. Rheumatoid arthritis
Rheumatoid factor Anti cyclic citrullinated peptide
Diagnosis
Sharp criteria Kasukawa criteria Alarcon-Segovia and Kahn criteria
THE BEST Sensitivity 63 Specificity 86
Clinical criteria
Swollen hands Synovitis Myositis Raynauds phenomenon Acrosclerosis with or without proximal sclerosis
Clinical Presentation
Early Clinical Findings
Malaise, easy fatiguability Arthralgias Myalgias Raynauds phenomenom Low-grade fevers
Unusual Presentations
FUO Serositis Trigeminal neuropathy Severe polymyositis Acute arthritis Aseptic meningitis Digital gangrene
Clinical features
General- women>men, 20-30 yr Sun exposure: NOT precipitating factor No drug induced MCTD Associated agents: silica, vinyl chloride
Skin
Raynaud s phenomenon Swollen digits Discoid plaques Malar rash Buccal ulceration Nasal septal perforation Sicca complex
Raynaud s phenomenon
Clinical criteria
Definite RP Repeated episodes of biphasic color changes upon exposure to cold Possible RP Uniphasic color changes plus numbness or paresthesia No RP No color changes
Primary RP
Onset 15-30 years
Current criteria :
Symmetric episodic attacks No evidence of peripheral vascular disease No tissue gangrene, digital pitting, or tissue injury Negative nailfold capillary examination Negative antinuclear antibody test and normal erythrocyte sedimentation rate (ESR)
Secondary RP
connective tissue diseases (MCTD, PM, DM, RA, vasculitis) Occlusive vascular disease (arteriosclerosis, emboli, and TAO) Drug-induced Hemorrheologic (Cold agglutinin disease, cryofibrinogenemia, cryoglobulinemia, paraproteinemia, and polycythemia) Vibration-induced (pneumatic drills and hammers) Vascular trauma Frostbite
Drug-induced RP
Arthritis
More common, more severe than LE 60% obvious arthritis Deformity: boutonniere, swan neck Film: resembles Jaccoud s arthropathy
small marginal erosion
Myositis
myopathy identical to PM Myalgia, no weakness Sometimes flare
Cardiac
Pericarditis 10-30% EKG: RVH, RAE, interventricular conduction defects PHT: cause of death asso- capillary nailfold pattern in SSc antiendothelial cell Ab, anticardiolipin
Pulmonary
75% of patients Interstitial lung dz
30-50% Reduced DLCO HRCT
Renal
Absence of severe renal disease High titer U1RNP
Protect against DPGN
Some- membranous nephropathy or nephrotic-range proteinuria Very rare- scleroderma renal crisis
Gastrointestinal
Motility disorder Malabsorption
From bacterial overgrowth
CNS
MCTD patients do not develop severe CNS complications Trigeminal neuropathy Headaches- vascular, aseptic meningitis, tension
Hematological presentation
Anemia Leukopenia, mainly lymphocyte Hypergammaglobulinemia RF + 50-70% APS- correlate with thrombocytopenia, pulmonary hypertension NOT abortion/ thrombosis
Vasculopathy
Raynaud s : typical+early MCTD Patho: bland intimal proliferation and medial hypertrophy of vv Abnormal nailfold capillary Angiography: medium-sized
Autoantibodies
Autoimmunity to spliceosomal components Spliceosomes: complex nuclear particles involved in the processing of pre-mRNA into mature "spliced RNA major spliceosomal sub-units
small nuclear ribonucleoprotein protein particles (snRNP) heterogeneous nuclear RNP particles (hnRNP).
Anti-Sm antibodies precipitate 5 proteins common to the U1, U2, U4, U5, and U6 RNAs Anti-RNP antibodies precipitate 3 proteins with molecular weights of 68,000 (70K), 33,000 (A'), and 22,000 (C) associated with U1 RNA
U1RNP
Treatment
Not much evidence Original- all manifestations response to 1 mg/kg prednisolone BUT not the case for vascular involvement Organ based
Treatment
Anti inflammatory
NSAIDS Corticosteroids
Immunomodulatory
Chloroquine HQ Azathioprine MMF cyclophosphamide
Practice points