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

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.

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

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  1. Treatment of SLEH. Michael BelmontHospital for Joint DiseasesNYU School of Medicine

  2. 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

  3. 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

  4. 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

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

  6. 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

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

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

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

  10. 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

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

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

  13. 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)

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

  15. 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

  16. 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)

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