Treatment of SLE H Michael Belmont Hospital for

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-A 1, B 8, Dr 3 - C 4 A 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, Antineuronal 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) • C 3 • C 4

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 (C 3, C 4, ds. DNA) • 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-C 5, soluble CR 1) • Adhesion molecule inhibitors (anti-ICAM 1 anti. CD 11 b/CD 18) • Co-stimulatory pathway inhibitors (anti. CTLA-4, anti-CD 40 ligand)