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SYSTEMIC LUPUS ERYTHEMATOSUS
OUTLINE
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Definition
Epidemiology
Pathophysiology
Classification and diagnosis
Clinical Features
Lupus related syndromes
Treatment
Prognosis
DEFINITION
• Inflammatory autoimmune disorder affecting
multiple organ systems characterized by the
production of autoantibodies directed against
cell nuclei”
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
Etiology
• Genetic (HLA DR3 association)
• Abnormal immune response
• Environmental
• UV
• Viruses
• Hormones (Estrogen)
PATHOPHYSIOLOGY
CLINICAL FEATURES: Mucocutaneous
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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
MALAR RASH
• Fixed erythema, flat or raised, over the
malar eminences
• Tending to spare the nasolabial folds
DISCOID RASH
• Erythematous raised
patches with adherent
keratotic scaling and
follicular plugging;
• Atrophic scarring may
occur in older lesions
Alopecia
Subacute Cutaneous Lupus
Acute Cutaneous: Malar Rash
Note Sparing of Nasolabial Folds
Chronic Cutaneous:Discoid
Note Scarring, Hyperpigmentation
Follicular Plugging
ACR
Livedo Reticularis
ORAL ULCERS
• Oral or nasopharyngeal
ulceration
• Usually painless,
observed by a physician
SLE - VASCULOPATHY
• Small vessel
vasculitis
• Raynaud’s
phenomenon
• Antiphospholipid
antibody syndrome
CLINICAL FEATURES: Musculoskeletal
• Arthritis is NONEROSIVE, transient,
symmetrical, affecting small joints, seldom
deforming, less severe than RA
• Most common presenting feature of SLE
Jaccoud’s Arthopathy: Nonerosive, Reducible Deformities
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
CLINICAL FEATURES: Ocular
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Conjunctivitis
Photophobia
Monocular blindness-transient or permanent
Blurred vision
Cotton-Wool spots on retina-degeneration nerves
fibers due to occlusion retinal blood vessels
CLINICAL FEATURES: PLEUROPULMONAR
• Pleuritis/Pleural effusion
• Infiltrates/ Discoid Atelectasis
• Acute lupus pneumonitis
• Pulmonary hemorrhage
• “Shrinking lung” - diaphragm dysfunction
• Restrictive lung disease
CLINICAL FEATURES: Cardiac
• Pericarditis –in majority of patients
• Libman Sacks endocarditis
• Cardiac failure
• Cardiac Arrythmias-common
• Valvular heart disease
• Coronary Artery Disease
Lupus - Endocarditis
Noninfective thrombotic endocarditis involving mitral valve in SLE.
Note nodular vegetations along line of closure and extending onto chordae tendineae.
CLINICAL FEATURES: HEMATOLOGIC
DISORDER
A)
B)
C)
D)
Hemolytic anemia - with reticulocytosis
OR
Leukopenia - less than 4,000/mm3 total on 2 or more
occasions
OR
Lymphopenia - less than 1,500/mm3 on 2 or more
occasions
OR
Thrombocytopenia - less than 100,000/mm3 in the
absence of offending drugs
CLINICAL FEATURES: Neurologic
Behavior/Personality changes, depression
Cognitive dysfunction
Psychosis
Seizures
Stroke
Chorea
Pseudotumor cerebri
Transverse myelitis
Peripheral neuropathy
Total of 19 manifestations described
May be difficult to distinguish from steroid psychosis
or primary psychiatric disease
CLINICAL FEATURES: Renal (Lupus Nephritis)
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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.
CLINICAL FEATURES: Renal (Lupus Nephritis)
• Usually asymptomatic
• Gross hematuria
• Nephrotic syndrome
• Acute renal failure
• Hypertension
• End stage renal failure
WHO CLASSIFICATION OF LUPUS NEPHRITIS
Class I
Class II
IIA
Normal
Mesangial
Minimal alteration
IIB
Class III
Mesangial glomerulitis
Focal and segmental proliferative
glomerulonephritis
Class IV
Class V
Diffuse proliferative
glomerulonephritis
Membranous glomerulonephritis
Class VI
Glomerular sclerosis
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
Laboratory Findings
• Complete blood count
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Anemia
Leukopenia
Lymphopenia
Thrombocytopenia
• Urine Analysis
• Hematuria
• Proteinuria
• Granular casts
Immunological findings
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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
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Antiphospholipid antibody
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Anti-Sm (Smith)
Anti Ro/SSA-antibody
Anti La/SSB-antibody
Anti-RNP
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
CLASSIFICATION
THE 1982 REVISED CRITERIA FOR CLASSIFICATION OF SLE
1. Malar rash
2. Discoid rash
3. Photosensitivity
4. Oral ulcers
5. Arthritis
6. Serositis
7. Renal disease.
> 0.5 g/d proteinuria
≥ 3+ dipstick proteinuria
Cellular casts
8. Neurologic disease.
Seizures
Psychosis (without other cause)
9. Hematologic disorders.
Hemolytic anemia
Leukopenia (< 4000/uL)
Lymphopenia (< 1500/uL)
Thrombocytopenia
(< 100,000/uL)
10. Immunologic abnormalities.
Positive LE cell
Anti-ds- DNA
Anti- Sm
Any antiphospholipid
11. Positive ANA ( 95-100% )
CLASSIFICATION CRITERIA
• Must have 4 of 11 for Classification
• Sensitivity 96%
• Specificity 96%
• Like RA, diagnosis is ultimately clinical
• Not all “Lupus” is SLE
• Discoid Lupus
• Overlap syndrome
• Drug induced lupus
• Subacute Cutaneous Lupus
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)
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
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
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
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
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
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
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
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