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OUTLINE
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
Etiology
Genetic (HLA DR3 association)
Abnormal immune response Environmental
UV
Viruses Hormones (Estrogen)
1. Genetic factor
Many studies have described familial aggregation of SLE. 5-13% of lupus have at least one first or second degree relative with lupus 24-58% concordance in monozygotic twins. 2-5% concordance in dizygotic twins or siblings The risk of a child developing lupus born from a mother (or father) with lupus is calculated to be 3-4% at worst.
2. Environmental factors
UV light, especially UVB, flares SLE in most patients. There is good evidence that exposure of skin to UV light alters the location and chemistry of DNA
3. Allergy. Does it induce lupus flare? No direct evidence. 4. Infection. the possibility that infectious agents might initiate or flare SLE. Mechanism might include molecular mimicry between external Ag and a self-Ag, epitope spreading, nonspecific activation of T or B cells. There has been recent interest in EB, CMV and other virus.
3. Sex hormones
Female : Male=10:1 The sex difference is most prominent during the female reproductive years. In mice, castrating females and /or providing androgens or antiestrogens protects from disease,whereas castrating males and providing estrogens accelerates and worsens SLE.
The metabolish of sex hormone is abnormal in some lupus patients. Men and women with lupus metabolized testosterone more rapidly than normal, and estrogenic metabolites of estradial persist longer in women.
Neuroendocrine system.
Hyperprolactinemia, abnormalities in hypothalamic and/or pituitary function.
Autoantibodies to DNA, RNA, and a host of other cell nucleus antigens. Circulating immune complexes are frequently deposit in the kidney, skin, brain, lung, and other tissues. It causes inflammation and tissue damage
Self Ag
Skin cell
External Ag
APC
B cell
Ab
Target
Defective IC clearance
CLINICAL FEATURES
General symptoms
The most common symptoms listed as initial complaints are fatigue, fever, and weight loss. Fever: fever secondary to active disease was recorded from 50% to 86%. No fever curve or pattern is characteristic. It can be difficult, but very important to distinguish the fever of SLE from that caused by complicating infections.
Fatigue is common in patients with SLE, especially during periods of disease activity. It is also often the only symptom that remains after treatment of acute flares. Low grade fever, anemia, or any source of inflammation can result in fatigue.
Vasculitic ulceration Oral ulceration Nasal septal perforation Nailfold capillary changes
MALAR RASH
Fixed erythema, flat or raised, over the malar eminences
DISCOID RASH
Erythematous raised patches with adherent keratotic scaling and follicular plugging; Atrophic scarring may occur in older lesions
Alopecia
Follicular Plugging
Livedo Reticularis
ACR
ORAL ULCERS
Oral ulcer: Painless sores in the nose or mouth need to be observed and documented by a doctor.
SLE - VASCULOPATHY
Small vessel vasculitis
Raynauds phenomenon
Antiphospholipid antibody syndrome
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
Cardiac failure
Cardiac Arrythmias-common Valvular heart disease
Lupus - Endocarditis
Noninfective thrombotic endocarditis involving mitral valve in SLE. Note nodular vegetations along line of closure and extending onto chordae tendineae.
D)
Develops in up to 50% of patients 10% SLE patients go to dialysis or transplant Hallmark clinical finding is proteinuria
50% of all lupus patients will have kidney involvement during their life
Circulating immune complexes bind to the basement membrane of the glomeruli (the sieve)
These result in inflammation of the glomeruli (glomerulonephritis)
Usually asymptomatic Gross hematuria Nephrotic syndrome Acute renal failure Hypertension End stage renal failure
Class I Class II
Normal Mesangial
Class VI
Minimal alteration Mesangial glomerulitis Focal and segmental proliferative glomerulonephritis Diffuse proliferative glomerulonephritis Membranous glomerulonephritis Glomerular sclerosis
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
Laboratory Findings
Complete blood count
Anemia Leukopenia Lymphopenia Thrombocytopenia
Urine Analysis
Hematuria Proteinuria Granular casts
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
Biologic false + RPR Lupus anticoagulant-antibodies tocoagulation factors. risk factor for venous and arterial thrombosis and miscarriage. Prolonged aPTT Anti-cardiolipin
Antiphospholipid antibody
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%
DIFFERENTIAL DIAGNOSIS
Rheumatic: RA, Sjogrens syndrome, systemic sclerosis, dermatomyositis
Nonrheumatic: HIV, endocarditis, viral infections, hematologic malignancies, vasculitis, ITP, other causes of nephritis Overlap Syndrome (UCTD, MCTD)
Deep venous thrombosis (blood clot). Notice the contrast between the involved left leg and the normal right leg. Redness, swelling, and warmth combined with discomfort in the involved leg are cardinal manifestations of a deep venous thrombosis.
Raynauds Syndrome: -Not part of the diagnostic criteria for SLE - Does NOT warrant ANA if no other clinical evidence to suggest autoimmune disease
Treatment
THERAPEUTIC MODALITIES
STEROIDS ANTI-MALARIAL DRUGS CYCLOPHOSPHAMIDE AZATHIOPRINE
CYCLOSPORIN
Plasmapheresis IV Ig
Biological therapy
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
TREATMENT
Antiphospholipid Syndrome
Anticoagulation with warfarin (teratogenic) subcutaneous heparin and aspirin is usual approach in pregnancy
PROGNOSIS
PROGNOSIS
Unpredictable course 10 year survival rates exceed 85% With good managemen Most SLE patients die from infection, probably related to therapy which suppresses immune system Typically the course of the disease is a series of remissions and exacerbations.