1. Treatment of SLE H. Michael Belmont Hospital for Joint Diseases NYU 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 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)