systemic lupus erythematosus (sle) is an autoimmune disease in which organs and cells undergo damage...
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• Systemic lupus erythematosus (SLE) is an autoimmune disease in which organs and cells undergo damage mediated by tissue-binding autoantibodies and immune complexes.
• Female : male 9 : 1 young women• 15–50 per 100,000
Definition & Prevalence
Abnormal immune response
1. activation of innate immunity 2. lowered thresholds of adaptive immunity
cells (antigen-specific T and B lymphocytes)3. ineffective regulatory mechanism4. reduced clearance of apoptotic cells and of
immune complexes (Self-antigens: nucleosomal DNA, RNA in Sm, Ro,
La; phospholipids) 5. Activation of complement system
Multigenic factors
• C1q, MBL - clearance of apoptic cells
• FcR 2A &3A - clearance of immune complexes
• HLA-DR2,3,8 - antigen presentation
• PTPN22 – T - cell activation
• MCP-1 – chemotaxis
• IL – 10 - B cell activation
Environmental factors
• Exposure to U/V radiation
• Infections – EBV virus
• Gender – estradiol increases survival of
Lymphocytes
• Drugs – procainamide, hydralazine, D-
Pencilamaine
Environmental Triggers
Genetically Susceptible Individual
Nuleasomal proteins & Self
antigens
Activation of Th&B cells
Ig G Auto Ab
Clinical Manifestations
Clinical ManifestationsMusculoskeletalCutaneous Renal Neurological Vascular Occlusions Pulmonary Cardiac Hematologic Gastrointestinal Ocular
Musculoskeletal Manifestations
• Intermitent Polyarthritis nondeforming and nonerosive
• Myositis with muscle weakness & myalgias,
Jaccoud’s Arthopathy: Nonerosive, Reducible Deformities
Cutaneous Manifestations discoid lupus erythematosus
• Lupus dermatitis systemic rash subacute cutaneous lupus
erythematosus (SCLE)• SLE rash is photosensitive, common on
the face (particularly the cheeks and nose—the "butterfly" rash), ears, chin, V region of the neck, upper back, and extensor surfaces of the arms
Renal Manifestations
• 50-70% of all lupus patients experience renal developments.
• ISN & RPS Classification of Lupus Nephritis
Minimal Lupus nephritis class – I Mesangial Lupus nephritis class – II Focal Lupus nephritis class – III Diffuse Proliferative Lupus nephritis class –IV Membranous Lupus nephritis class –V
• Class III & IV present with hematuria & proteinuria (>500mg / day)
• Nearly ½ end up in nephrotic syndrome
• ESRD occurs in DPGN after 2Yrs of disease manifestation. Leading cause of death in SLE
Neurological Manifestations • cognitive dysfunction (memory & reasoning
diffic.)
• Headache• Seizures• Psychosis• Myelopathy
• Important to exclude other etiologies • If SLE then determine
DiffuseVascular occlusion
Vascular Occlusions• TIA• Strokes• MI
• Those with aPL Ab have hypercoagulable state & acute thrombotic events
• Accelerated atherosclerosis
Pulmonary Manifestations
• Pleuritis & pleural effusions
• Life-threatening – interstitial inflammation leading to fibrosis, shrinking lung syndrome, and intraalveolar hemorrhage
Cardiac Manifestations
• Pericarditis• Myocarditis• Endocarditis
(Libman – Sacks)• MI• Valvular
insufficiencies
Gastrointestinal Manifestations• Nausea,vomiting, and diarrhea• abdominal pain -autoimmune
peritonitis• Increases (AST) and (ALT)• Vasculitis involving the intestine may be
life-threatening; perforations, ischemia, bleeding, and sepsis
Laboratory Tests
Tests for Autoantibodies a) ANA antibodies ,DNA (dsDNA) are
specific for SLE
b) Antibodies to Sm are also specific for SLE
c) aPL their presence identify patients at increased risk for venous or arterial clotting, thrombocytopenia, and fetal loss
d) anti-Ro - neonatal lupus, sicca syndrome, and SCLE
Tests for Diagnosis
• blood count• platelet count• Urinalysis• serum levels of creatinine or albumin
Conservative Therapies for Non-Life-Threatening Disease
fatigue, pain, and autoAb of SLE, but without major organ involvement
• NSAID`S { adv effects specific for SLE:
aseptic meningitis, elevated serum transaminases, hypertension, & renal dysfunction }
ASPIRIN is da D.O.C
• Antimalarials (hydroxychloroquine, chloroquine, and quinacrine) often reduce dermatitis, arthritis, and fatigue
{Adv eff. – retinal toxicity}
• low doses of systemic glucocorticoids may be necessary
Life-Threatening SLE – Rx high-dose i.v glucocorticoid (1000mg for
3 days followed by 0.5–1 mg/kg of daily prednisone ) -standard practice
(or)
systemic glucocorticoids (0.5–2 mg/kg per day)
{ Adv eff. - infection, hyperglycemia, hypertension, osteoporosis, etc}
• maintenance dose 5 to 10 mg/ day for many years
• Cytotoxic/immunosuppressive agents
Cyclophosphamide { Adv eff. – ovarian failure}
(500–750 mg/m2 i.v, monthly for 3–6 months)
mycophenolate mofetil - safer
Azathioprine – slow acting
used in combination with GC`s
Special Conditions 1)Pregnancy Fetal demise higher in mothers with high
disease activity, aPL & Ro Ab`s . Maternal flares
• GC`s induced low birth weight, developmental abnormalities, and adult metabolic syndrome.