systemic lupus erythematosus. outline definition epidemiology pathophysiology classification and...
TRANSCRIPT
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SYSTEMIC LUPUS ERYTHEMATOSUS
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OUTLINE
• Definition
• Epidemiology
• Pathophysiology
• Classification and diagnosis
• Clinical Features
• Lupus related syndromes
• Treatment
• Prognosis
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DEFINITION
• Inflammatory autoimmune disorder affecting multiple organ systems characterized by the production of autoantibodies directed against cell nuclei”
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EPIDEMIOLOGY
• Prevalence influenced by age, gender, race, and genetics• Prevalence: 1:2000
• Peak incidence 14-45 years
• Black > White (1:250 vs. 1:1000)
• Female predominance 10:1
• HLA DR3 association, Family History
• Severity is equal in male and female
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Etiology
• Genetic (HLA DR3 association)• Abnormal immune response
• Environmental• UV
• Viruses
• Hormones (Estrogen)
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PATHOPHYSIOLOGY
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CLINICAL FEATURES: Mucocutaneous
• Malar Rash (butterfly erythema)
• Discoid rash
• Photosensitive rash
• Subacute cutaneous LE
• Livedo reticularis
• Alopecia
• Raynaud’s
• Vasculitic ulceration
• Oral ulceration
• Nasal septal perforation
• Nailfold capillary changes
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MALAR RASH
• Fixed erythema, flat or raised, over the malar eminences
• Tending to spare the nasolabial folds
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DISCOID RASH
• Erythematous raised patches with adherent keratotic scaling and follicular plugging;
• Atrophic scarring may occur in older lesions
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Alopecia
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Subacute Cutaneous Lupus
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Acute Cutaneous: Malar RashNote Sparing of Nasolabial Folds
Chronic Cutaneous:DiscoidNote Scarring, Hyperpigmentation
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Follicular Plugging Livedo Reticularis
ACR
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ORAL ULCERS
• Oral or nasopharyngeal ulceration
• Usually painless, observed by a physician
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SLE - VASCULOPATHY
• Small vessel vasculitis
• Raynaud’s phenomenon
• Antiphospholipid antibody syndrome
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CLINICAL FEATURES: Musculoskeletal
• Arthritis is NONEROSIVE, transient, symmetrical, affecting small joints, seldom deforming, less severe than RA
• Most common presenting feature of SLE
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Jaccoud’s Arthopathy: Nonerosive, Reducible Deformities
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CLINICAL FEATURES: Musculoskeletal
• Synovitis-90% patients, often the earliest sign
• Osteoporosis
• From SLE itself and therapy (usually steroids)
• Osteonecrosis (avascular necrosis)
• Can occur with & without history of steroid therapy
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CLINICAL FEATURES: Ocular
• Conjunctivitis
• Photophobia
• Monocular blindness-transient or permanent
• Blurred vision
• Cotton-Wool spots on retina-degeneration nerves fibers due to occlusion retinal blood vessels
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CLINICAL FEATURES: PLEUROPULMONAR
• Pleuritis/Pleural effusion
• Infiltrates/ Discoid Atelectasis
• Acute lupus pneumonitis
• Pulmonary hemorrhage
• “Shrinking lung” - diaphragm dysfunction
• Restrictive lung disease
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CLINICAL FEATURES: Cardiac
• Pericarditis –in majority of patients
• Libman Sacks endocarditis
• Cardiac failure
• Cardiac Arrythmias-common
• Valvular heart disease
• Coronary Artery Disease
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Lupus - Endocarditis
Noninfective thrombotic endocarditis involving mitral valve in SLE.
Note nodular vegetations along line of closure and extending onto chordae tendineae.
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CLINICAL FEATURES: HEMATOLOGIC DISORDER
A) Hemolytic anemia - with reticulocytosisOR
B) Leukopenia - less than 4,000/mm3 total on 2 or more occasions
ORC) Lymphopenia - less than 1,500/mm3 on 2 or more
occasionsOR
D) Thrombocytopenia - less than 100,000/mm3 in the absence of offending drugs
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Behavior/Personality changes, depressionCognitive dysfunctionPsychosisSeizuresStrokeChoreaPseudotumor cerebriTransverse myelitisPeripheral neuropathyTotal of 19 manifestations describedTotal of 19 manifestations described
May be difficult to distinguish from steroid psychosis or primary psychiatric disease
CLINICAL FEATURES: Neurologic
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CLINICAL FEATURES: Renal (Lupus Nephritis)
• Develops in up to 50% of patients• 10% SLE patients go to dialysis or transplant• Hallmark clinical finding is proteinuria• Advancing renal failure complicates assessment
of SLE disease activity
Nephritis remains the most frequent cause of disease-related death.
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• Usually asymptomatic• Gross hematuria• Nephrotic syndrome• Acute renal failure• Hypertension• End stage renal failure
CLINICAL FEATURES: Renal (Lupus Nephritis)
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WHO CLASSIFICATION OF LUPUS NEPHRITIS
Class I Normal
Class II Mesangial
IIA Minimal alteration
IIB Mesangial glomerulitis
Class III Focal and segmental proliferative glomerulonephritis
Class IV Diffuse proliferative glomerulonephritis
Class V Membranous glomerulonephritis
Class VI Glomerular sclerosis
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CLINICAL FEATURES: Gastrointestinal & Hepatic
• Uncommon SLE manifestations
• Severe abdominal pain syndromes in SLE often indicate mesenteric vasculitis, resembling medium vessel vasculitis (PAN)
• Diverticulitis may be masked by steroids
• Hepatic abnormalities more often due to therapy than to SLE itself
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Laboratory Findings
• Complete blood count• Anemia • Leukopenia• Lymphopenia• Thrombocytopenia
• Urine Analysis• Hematuria• Proteinuria• Granular casts
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Immunological findings
• ANA - 95-100%-sensitive but not specific for SLE• Anti -ds DNA-specific(60%)-specific for SLE, but positive to other non
lupus conditions• 4 RNA associated antibodies
• Anti-Sm (Smith)• Anti Ro/SSA-antibody• Anti La/SSB-antibody• Anti-RNP
• Antiphospholipid antibody• Biologic false + RPR• Lupus anticoagulant-antibodies tocoagulation factors. risk factor for venous
and arterial thrombosis and miscarriage. Prolonged aPTT• Anti-cardiolipin
• Depressed serum complement• Anti hystones antibodies
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CLASSIFICATION
1. Malar rash 2. Discoid rash3. Photosensitivity4. Oral ulcers5. Arthritis6. Serositis7. Renal disease.
> 0.5 g/d proteinuria ≥ 3+ dipstick proteinuria Cellular casts
8. Neurologic disease. SeizuresPsychosis (without other cause)
9. Hematologic disorders. Hemolytic anemiaLeukopenia (< 4000/uL) Lymphopenia (< 1500/uL) Thrombocytopenia (< 100,000/uL)
10. Immunologic abnormalities. Positive LE cell Anti-ds- DNAAnti- SmAny antiphospholipid
11. Positive ANA ( 95-100% )
THE 1982 REVISED CRITERIA FOR CLASSIFICATION OF SLE
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CLASSIFICATION CRITERIA
• Must have 4 of 11 for Classification• Sensitivity 96%Sensitivity 96%
• Specificity 96%Specificity 96%
• Like RA, diagnosis is ultimately clinical
• Not all “Lupus” is SLE• Discoid Lupus
• Overlap syndrome
• Drug induced lupus
• Subacute Cutaneous Lupus
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DIFFERENTIAL DIAGNOSIS
• Almost too broad to consider given number of clinical manifestations
• Rheumatic: RA, Sjogren’s syndrome, systemic sclerosis, dermatomyositis
• Nonrheumatic: HIV, endocarditis, viral infections, hematologic malignancies, vasculitis, ITP, other causes of nephritis
• “Overlap Syndrome” (UCTD, MCTD)
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LUPUS RELATED SYNDROMES
• Drug Induced Lupus• Classically associated with hydralazine, isoniazid,
procainamide
• Male:Female ratio is equal
• Nephritis and CNS abnormalities rare
• Normal complement and no anti-DNA antibodies
• Symptoms usually resolve with stopping drug
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LUPUS RELATED SYNDROMES
• Antiphospholipid Syndrome (APS)• Hypercoagulability with recurrent thrombosis of either venous or
arterial circulation
• Thrombocytopenia-common
• Pregnancy complication-miscarriage in first trimester
• Lifelong anticoagulation warfarin is currently recommended for patients with serious complications due to common recurrence of thrombosis
• Antiphospholipid Antibodies
• Primary when present without other SLE feature.
• Secondary when usual SLE features present
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LUPUS RELATED SYNDROMES
Raynaud’s Syndrome:
-Not part of the diagnostic criteria for SLE
- Does NOT warrant ANA if no other clinical evidence to suggest autoimmune disease
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SLE – treatment I.
• Mild cases (mild skin or joint involvement): NSAID, local treatment, hydroxy-chloroquin
• Cases of intermediate severity (serositis, cytopenia, marked skin or joint involvement): corticosteroid (12-64 mg methylprednisolon), azathioprin, methotrexat
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SLE – treatment II.
• Severe, life-threatening organ involvements (carditis, nephritis, systemic vasculitis, cerebral manifestations): high-dose intravenous corticosteroid + iv. cyclophosphamide + in some cases: plasmapheresis or iv. immunoglobulin, or, instead of cyclophosphamide: mycophenolate mofetil (not registered in the EU)
• Some cases of nephritis (especially membranous), myositis, thrombocytopenia: cyclosporine
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TREATMENT
• Antiphospholipid Syndrome• Anticoagulation with warfarin (teratogenic)
• subcutaneous heparin and aspirin is usual approach in pregnancy
• Lupus and Pregnancy• No longer “contraindicated”
• No changes in therapy other than avoiding fetal toxic drugs
• Complications related to renal failure, antiphospholipid antibodies, SSA/SSB
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TREATMENT
• ESR, CRP probably useful as general markers of disease activity
• Complement and anti-DNA antibodies may correlate to disease activity but often impractical turnaround time from lab
• Patient history
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PROGNOSIS
• Unpredictable course
• 10 year survival rates exceed 85%
• Most SLE patients die from infection, probably related to therapy which suppresses immune system
• Recommend smoking cessation, yearly flu shots, pneumovax q5years, and preventive cancer screening recommendations