Treatment of SLE H. Michael Belmont Hospital for Joint Diseases NYU School of Medicine

SLE SUBSETS Discoid lupus erythematosus (DLE) Systemic lupus erythematosus (SLE) Drug-induced SLE (DANA vs DILE) ANA negative lupus/Ro lupus/SCLE Antiphospholipid antibody syndrome Neonatal lupus

SLE:Demographics Affects .5 million (.2%) vs 1.5 million (.6%) of US population (epidemiologic vs LFA random digit dialing telephone survey) Female:Male ratio of 10:1 70% of SLE: females between ages 15-45 African American to Caucasian ratio 3:1 Highest prevalence in Afro-Caribbean females 1:250 Genetic factors HLA-A1, B8, Dr3 - C4A null genes - Fc receptor polymorphisms -gene linked to chromosome 1

SLE:Demographics Environmental factors - Concordance for monozygotic twins is 30% (70% of genetically identical twins will not share the disease) Child of SLE mother risk of SLE 1:15 (7%) ANA positive in 5-20% of population. 10 times more likely to have false positive ANA than disease

SLE:ETIOLOGY AUTOANTIBODY PRODUCTION GENERATION OF CIRCULATING IMMUNE COMPLEXES EPISODIC COMPLEMENT ACTIVATION

SLE:Pathobiology Autoantibodies (AIHA, AITP, Anti-neuronal antibody, APS) Immune complex disease (microangiitis and vasculitis) Neutrophil and endothelial cell adhesive interaction with leukoaggregation Thrombophilia (Antibody mediated thrombosis in secondary antiphospholipid antibody syndrome with micro and macrovascular noninflammatory occlusion

SEROLOGY ANA (Titer and pattern: diffuse, speckled, rim, nucleolar, centromere) double stranded-DNA Sm RNP Ro (SS-A)/La (SS-B) C3 C4

POSITIVE ANA SLE Non SLE CTD (RA, SS, PSS, CREST, DM/PM) DRUG-INDUCED NORMALS (FALSE POSTIVE) LYMPHOPROLIFERATIVE DISORDER CHRONIC INFECTION (HIV, Leprosy)

PITFALLS ANA POSITIVE FIBROMYALGIA STEROIDS FOR MUSCULOSKELETAL SYMPTOMS EXCESSIVE DURATION OF STEROIDS INADEQUATE MONITORING (C3, C4, dsDNA) DIAGNOSTIC OR THERAPEUTIC DELAYS (RENAL BIOPSY, CYTOTOXICS)

SLE:Health Status Disease activity (SLEDAI, SLAM. BILAG) Damage Index (SLICC DI) (disease, treatment or co-morbidity) Treatment/iatrogenic induced illness (e.g. avascular necrosis of bone, accelerated atherosclerosis, cataracts, striae, immunosupression, etc.) Infection

TREATMENT SUNSCREEN TOPICAL STERIODS NSAIDs ANTIMALARIALS STEROIDS CYTOTOXICS CALCIUM, VITAMIN D, FOLATE SUPPLEMENTATION INFLUENZA VACCINE (annual) PNEUMOCCOCAL VACCINE (decade)

CLINICAL FEATURES CONSITUTIONAL CUTANEOUS JOINTS SEROSAL CYTOPENIAS RENAL NEUROLOGIC ANTIPHOSPHOLIPID ANTIBODY SYNDROME

STEROID THERAPY ACUTE LUPUS CRISIS ACTIVE NEPHRITIS ACUTE ACTIVE CNS ACUTE CYTOPENIAS (AIHA,AITP) REFRACTORY SEROSITIS VASCULITIS SEVERE CONSTITUTIONAL (fever, fatigue, wgt loss, synovitis, anemia)

CYTOTOXIC THERAPY Azathioprine, Methotrexate, Leflunomide Steroid sparing (constitutional, serositis, immune cytopenias) Articular Mycophenolate mofetil, Cyclophosphamide Nephritis, CNS, immune cytopenias, vasculitis

ANTIPHOSPHOLIPID ANTIBODY SYNDROME (APS) ASYMPTOMATIC No Treatment Antiplatelet (ASA 81 mg, Ticlid, Plavix) THROMBOTIC EVENT (DVT, PE, CVA) Coumadin INR > 3 PREGNANCY ASA 81 mg, Prednisone 40-20 mg, sc Heparin, sc LMWH (IVIG) CAPS (Catastrophic APS) Heparin, steroids, pheresis, IVIG, cytoxan

NOVEL THERAPY Immunoablative chemotherapy with or without autologous stem cell transplant B-cell toleragen (Single signal anergy) Complement inhibitors (anti-C5, soluble CR1) Adhesion molecule inhibitors (anti-ICAM 1 antiCD11b/CD18) Co-stimulatory pathway inhibitors (anti-CTLA-4, anti-CD40ligand)