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

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

• Affects .5 million (.2) vs 1.5 million (.6) of
  US population (epidemiologic vs LFA random digit
  dialing telephone survey)
• FemaleMale ratio of 101
• 70 of SLE females between ages 15-45
• African American to Caucasian ratio 31
• Highest prevalence in Afro-Caribbean females
  1250
• Genetic factors HLA-A1, B8, Dr3 - C4A null genes
  - Fc receptor polymorphisms -gene linked to
  chromosome 1

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SLEDemographics

• 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 115 (7)
• ANA positive in 5-20 of population. 10 times
  more likely to have false positive ANA than
  disease

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SLEETIOLOGY

• AUTOANTIBODY PRODUCTION
• GENERATION OF CIRCULATING IMMUNE COMPLEXES
• EPISODIC COMPLEMENT ACTIVATION

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SLEPathobiology

• 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

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SEROLOGY

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

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POSITIVE ANA

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

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PITFALLS

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

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SLEHealth 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

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TREATMENT

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

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CLINICAL FEATURES

• CONSITUTIONAL
• CUTANEOUS
• JOINTS
• SEROSAL
• CYTOPENIAS
• RENAL
• NEUROLOGIC
• ANTIPHOSPHOLIPID ANTIBODY SYNDROME

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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)

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CYTOTOXIC THERAPY

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

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ANTIPHOSPHOLIPID ANTIBODY SYNDROME (APS)

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

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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)