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Systemic Lupus Erythematosus Systemic lupus Angelfire

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Systemic Lupus Erythematosus Systemic lupus Angelfire Powered By Docstoc
					                                                       Etiology / Risk factors
                                                Environment:
     Systemic Lupus Erythematosus               • Sunlight, UV exposure
                                                • Chemicals
             Joy S. Boresi, Pharm.D.            • Foods
                December 2, 2003                • Infectious agent




Systemic lupus erythematosus (SLE)                     Etiology / Risk factors
 •   2-8 / 100,000 cases / year                 Drugs:
 •   Prevalence: 1/1000                         • Induce lupus-like symptoms
 •   Females > Males                            • Does not induce true lupus
 •   Younger age                                • Does not activate dz in pts with SLE
 •   African Americans > Caucasians             • Reversible
                                                • Do not rechallenge




          Etiology / Risk factors                          Pathophysiology
 Genetics:               Hormonal:              • External antigens processed by antigen
 • MHC genes             • Androgens: inhibit     presenting cells → death of host cells
 • Complement receptor     autoimmunity
                                                • Self antigen released, processed by B cells,
   genes                 • Estrogens: promote     antigen presenting cells
 • Immunoglobulin          autoimmunity
   receptor genes        • ↑ prolactin levels
                                                • T cells, B cells stimulated → immune
                                                  complexes, targeting glomeruli, endothelial
                                                  cells, platelets
                  Symptoms

• Fatigue, fever, weight loss
• Arthritis, arthralgia, myositis
• Dermatologic
• Renal
• GI: N/V, abdominal pain




                  Symptoms                                    Differential diagnosis

• Pulmonary: pleurisy, pulmonary HTN               •   Undifferentiated connective tissue disease
                                                   •   Sjogren’s syndrome
• Cardiac: pericarditis, endocarditis
                                                   •   Antiphospholipid antibody syndrome
• Reticuloendothelial
                                                   •   Fibromyalgia
• Neuropsychiatric: psychosis, seizures            •   Idiopathic thrombocytopenic purpura
                                                   •   Rheumatoid arthritis
                                                   •   Vasculitis




        Laboratory abnormalities                                       Diagnosis
•   Anemia                  •   Anti-Sm            •   Malar rash              •   Renal
•   Thrombocytopenia        •   Anti-RNP           •   Discoid rash            •   Neurologic
•   Leukopenia              •   Anti-Ro            •   Photosensitivity        •   Hematologic
•   (+) ANA – rim pattern   •   Anti-La            •   Oral ulcers             •   Immunologic
•   dsDNA                   •   Antiphospholipid   •   Non-erosive arthritis   •   Antinuclear
                                antibodies         •   Pulmonary
                                                   Non-pharmacologic therapy
                                              •   Education
                                              •   Balanced routine of exercise / rest
                                              •   Diet
                                              •   Avoid smoking / second-hand smoke
                                              •   Limit sunlight exposure / sunscreens




                  Prognosis                                      Mild SLE
•   Renal disease                             • Clinically stable
•   Hgb < 12.4 at time of diagnosis           • Not life threatening
•   Hypoalbuminemia                           • Normal, stable function of organ systems
•   Hypocomplementemia
•   Low socioeconomic status
•   Antiphospholipid antibody




                     SLE                               Treatment – mild SLE
Goals:                                        NSAIDs / COX-2s:
• Management of sx / induction of remission   • First line for mild arthritis sx
  during disease flares                       • Cautions:
• Maintenance of remission between disease        – Renal involvement
  flares                                          – Increased risk of GI bleeding
                                                  – Hepatotoxicity
         Treatment – mild SLE                          Topical glucocorticoids
Antimalarials: (HCQ, chloroquine)             Adverse Effects:
• Second line for arthritis                   • Skin atrophy
• Dermatitis, photosensitivity, oral ulcers   • Depigmentation
• Inhibits T lymphocyte activation and        • Skin fragility
  cytokines                                   • Telangiectasia




               Antimalarials                              Oral glucocorticoids
Time to benefit:                              • Arthritis, myalgias, skin lesions
• HCQ: 3-6 months                               unresponsive to first line therapy
• Chloroquine: 1 month                        • Rapid benefits
Dose:                                         • Limit dose
• HCQ: 200-400 mg/day                         • Caution due to adverse effects
• Chloroquine 250-500 mg/day
• Quinacrine 100 mg/day




        Topical glucocorticoids                                Severe disease
• Dermatitis, skin lesions                    •   Vasculitis              • Myelopathies
• Rapid benefits                              •   Severe dermatitis       • Peripheral
• Intensity depends on location:              •   Polyarthritis             neuropathies
  –   Face: low-medium                        •   Pericarditis,pleurisy   • Lupus crisis
  –   Trunk/arm: medium                       •   Myocarditis             • Thrombocytopenia
  –   Scalp: medium                           •   Lupus pneumonitis       • Hemolytic anemia
  –   Palms/ soles: high                      •   Glomerulonephritis
  –   Hypertrophic: high
     High-dose glucocorticoids                               Cytotoxic agents
• Prednisone 40-60mg/day po x 6 weeks             MOA:
                                                  • Cyclophosphamide: alkalates DNA
• Prednisone, prednisolone,                       • Azathioprine: inhibits purine synthesis
  methylprednisolone: 1-2mg/kg/day po
                                                  Time to benefit:
• Methylprednisolone 500-1000mg IV x 3-5          • Cyclophosphamide: 2-16 weeks
  days, then 1-1.5 mg/kg/day po                   • AZA: 6-12 months




         Tapering strategies                                 Cytotoxic agents
• ↓ dose by 5-15% q week until 30mg QD, then      Dose: cyclophosphamide
  ↓ by 2.5mg/ week until 15mg qd, then ↓ by       • 1-3 mg/kg/day po or 8-20mg/kg IV q month
  1mg/week                                        • 0.5-2 mg/kg/day po or 8-20mg/kg IV q 4-12
• Taper QOD                                         weeks
• Use glucocorticoid sparing agents               • CrCl 25-50mls/min: ↓ by 25%
• Disease flares during taper: increase to most   • CrCl < 25 mls/min: ↓ by 30-50%
  effective dose x weeks                          • Mesna




           Cytotoxic agents                                  Cytotoxic agents
• Combination w/ steroids – lupus nephritis       Dose: azathioprine
• Non-renal manifestations not responding to      • Initial: 1-3 mg/kg/day po
  steroids, pts unable to take steroids           • Maintenance: 1-2 mg/kg/day po
• Cyclophosphamide more effective, toxic
• Combination > steroids in prevention of
  kidney scarring
             Adverse effects                              Antiphospholipid antibody
Cyclophosphamide        Azathioprine                             syndrome
• Bone marrow           • Bone marrow
                                                    • Lupus anticoagulant, anticardiolipin
  suppression             suppression
                        • Immunosuppression         • Diagnosis by clinical event + lab finding
• Infertility
• Immunosuppression     • Malignancies              • Treatment not well established, depends on
• Leukopenia            • Infertility                 clinical situation
• Malignancy            • Hepatotoxicity
• Cystitis              • Nausea
• N/V
• Alopecia




      Decreasing adverse effects                                        Pregnancy
•   Reserve use of steroids / cytotoxic drugs       •   Fertility rate unchanged
•   Monitoring                                      •   Higher rate of miscarriages / stillborns
•   Lowest possible doses                           •   Disease controlled at conception
•   Infection prophylaxis / treatment               •   Glucocorticoids, HCQ to suppress disease
•   Control HTN, hypokalemia, hyperglycemia             during pregnancy
•   Exercise
•   Osteoporosis prevention / tx




            Alternative agents                                   Summary - SLE
• Plasmapheresis        •   UV A1 irradiation       • Variable course of disease / symptoms
• Cyclosporine          •   Monoclonal antibodies   • NSAIDs / HCQ – mild disease
• Immune globulin       •   DHEA
                                                    • Steroids – mild / severe disease
• TXA2 synthetase       •   Bromocriptine
                                                        – Caution: AE
  inhibitor             •   Danazol
• PGE1                                              • Cytotoxic drugs: severe disease
                                                    • Numerous future therapies

				
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