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

Genes Abnormal Interaction & immune b/w Environmental response factors

1.activation of innate immunity 2.lowered thresholds of adaptive immunity cells (antigen-specific T and B lymphocytes) 3.ineffective regulatory mechanism 4.reduced clearance of apoptotic cells and of immune complexes (Self-antigens: nucleosomal DNA, RNA in Sm, Ro, La; phospholipids) 5. Activation of complement system

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

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

Musculoskeletal Cutaneous 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

Butterfly rash Subacute Cutaneous Lupus

painful ulcerations on the oral or nasal mucosa

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

Lupus Nephritis normal

Neurological Manifestations cognitive dysfunction (memory & reasoning diffic.) Headache Seizures Psychosis Myelopathy Important to exclude other etiologies If SLE then determine Diffuse Vascular 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

Hematologic Manifestations Anemia Leukopenia Thrombocytopenia

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

Ocular Manifestations Sicca syndrome Conjunctivitis retinal vasculitis and optic neuritis

AMERICAN RHEUMATISM ASS. criteria based on clinical features. ≥ 4 of these must be present

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

Lupus band test

Tests for Diagnosis blood count platelet count Urinalysis serum levels of creatinine or albumin

No Cure Aim: -to control acute flare - ↓ symptoms -prevent organ failure

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/m 2 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.

2)Lupus Dermatitis prevent UV radiation Topical GC`s & Anti malarials Retinoic acid