Nefritis Lúpica

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Por: Dr. Graham Hughes
XIII Congreso Colombiano de Reumatologia 2011 Barranquilla

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  • Biologically false-positive WR (Reinhart 1909) L.E. Cell (Hargraves 1948) Antinuclear antibodies (Miescher 1954, Friou 1959, Beck 1961) DNA (Tan, Koffler, Kunkel, Pincus, Christian 1966-71) ENA (Reichlin 1976) Anti-phospholipid antibodies (Harris, Gharavi, Hughes 1983)
  • Reference 9. David O'Hair D.P et al. Inhibition of chronic vascular rejection in primate cardiac xenografts using mycophenolate mofetil. Ann Thorac Surg 1994; 58: 1311-1315.
  • Nefritis Lúpica

    1. 1. Professor Graham Hughes The London Lupus Centre The London Bridge Hospital
    2. 2. Lupus and the kidney
    3. 5. History
    4. 6. 1970 <ul><li>Introduction of the (Farr) </li></ul><ul><li>anti-DNA test </li></ul>
    5. 8. July 1969 <ul><li>Geigy Scholarship. </li></ul><ul><li>New York </li></ul>
    6. 10. Serological Changes 1909 1948 1959 1966-70 1976 1983 WR LE Cell ANA DNA ENA aPL
    7. 11. Antibodies predicting disease Anti-Topo1 …………… Scleroderma…………… 11 yrs Rh factor/ccp ………… RA ……………………… 14 yrs Anti-Ro & La ………… Sjogrens ………………. 5 yrs Anti-DNA …………….. SLE ……………………. 11 yrs Anti-cardiolipin ………. Hughes Syndrome ….… 32 yrs ---------------------- Anti-thyroid ………….. Thyroid ………………… 10 yrs Anti-mitochondrial ….. PBC ……………………. 25 yrs
    8. 12. Explosion of Lupus
    9. 15. Lupus Diagnosis Professor Hughes’ “alternative” criteria ● Childhood migraine ● Childhood ‘growing pains’ ● Teenage prolonged ‘glandular fever’ ● Agoraphobia ● Septrin allergy ● Chronic fatigue ( ‘fibromyalgia’) ● Intermittent alopecia ● Lupus patients don’t catch colds
    10. 16. <ul><li>FAILURE </li></ul><ul><li>SUCCESS </li></ul>
    11. 17. Failure
    12. 18. Failure
    13. 19. Failure
    14. 20. Sticky Blood and Headache
    15. 22. LUPUS “- the new diabetes”
    16. 23. Failure
    17. 24. Lupus Nephritis <ul><li>Aspects of treatment </li></ul><ul><li>Failure?..... </li></ul>
    18. 25. What’s still bad in Lupus? <ul><li>Long time to diagnosis </li></ul><ul><li>Worldwide fluctuation in severity </li></ul><ul><li>No drugs licensed for Lupus </li></ul><ul><li>Poor recognition of “sticky blood” </li></ul><ul><li>Lupus awareness still poor </li></ul><ul><li>COMPLIANCE? </li></ul>
    19. 26. Compliance? Plaquenil blood levels Ann Rheum Dis: 66,621, 2007
    20. 28. Lupus pregnancy and the kidney
    21. 29. Flares in pregnancy? <ul><li>Only 15% of L.N. flared in pregnancy </li></ul><ul><li>Only 2% suffered progressive fall in GFR </li></ul>
    22. 30. Treatment options 2011
    23. 31. Antimalarials
    24. 33. Anti-malarial treatment and lupus survival <ul><li>Anti-malarial use was associated with a 38% reduction in the mortality rate. </li></ul><ul><li>Shirijo SK et al </li></ul><ul><li>A & R 2010 62 855 </li></ul>
    25. 35. Thalidomide analogues?
    26. 36. Steroids
    27. 37. The Case for Conservative Management <ul><li>Steroids </li></ul><ul><li>Low-dose steroids in SLE </li></ul><ul><li>Hughes GRV. Clin Rheum Dis 1972 </li></ul><ul><li>Low-dose methylprednisolone: equally effective, less infection </li></ul><ul><li>Badsha H et al. Semin Arthritis Rheum 2003 </li></ul>
    28. 38. Cyclophosphamide
    29. 39. NIH Regime <ul><li>Used worldwide </li></ul><ul><li>Improved renal outlook </li></ul><ul><li>Toxic: infections 25% </li></ul><ul><li> up to 30% infertility </li></ul>
    30. 41. The St Thomas’ Hospital Regime (1985) <ul><li>500mg cyclo I.V. weekly x 3 </li></ul><ul><li>500mg cyclo monthly x 3-6 </li></ul><ul><li>AZA (or MMF) </li></ul>
    31. 43. Euro-Lupus Nephritis Trial Conclusion <ul><li>“… achieves clinical results comparable to those obtained with the high dose regimen” </li></ul>Houssiau et al. A&R 2011
    32. 44. New therapies for SLE <ul><li>Kaul A, D’Cruz, Hughes GRV 2006 </li></ul><ul><li>Future Rheumatology 1 235-247 </li></ul>
    33. 45. Expenditure for drugs for lupus <ul><li>2008 …………….. …. $1.1 billion </li></ul><ul><li>2015 ………………… $1.6 billion </li></ul>
    34. 46. Mycophenolate-mofetyl (cellcept ® )
    35. 47. 24 hour Proteinuria in Class V Lupus Nephritis Ferro et al. Abstract ACR 2003
    36. 48. MMF and teratogenicity <ul><li>Hypoplastic nails </li></ul><ul><li>Short 5 th fingers </li></ul><ul><li>Diaphragmatic hernia </li></ul><ul><li>Ear deformity </li></ul><ul><li>Small jaw </li></ul><ul><li>Cleft lip and palate </li></ul><ul><li>Congenital heart defects </li></ul>
    37. 49. Could MMF play a protective role in vascular disease in SLE?
    38. 50. Primate cardiac xenografts Inhibition of chronic vascular rejection by MMF O’Hair et al. Ann Thorac Surg, 1994
    39. 51. 1988………………..................…..…BLyS 23 years 2011...Benlysta approval in U.K.
    40. 52. Belimumab BLISS 52 & 72 Results <ul><li>Reduced SLE disease activity </li></ul><ul><li>Reduced flare rates </li></ul><ul><li>Reduced prenisolone use </li></ul><ul><li>Petri et al. </li></ul><ul><li>A & R S190 2010 </li></ul>
    41. 53. Rituximab: <ul><li>Approved by FDA in 1997 for NHL </li></ul>
    42. 54. - but RTX in lupus trials has had a bumpy ride………………..
    43. 55. In defence of Rituximab ……………
    44. 56. Off-label use of RTX in lupus <ul><li>(27 studies) </li></ul><ul><li>Reduction in SLEDAI 59% </li></ul><ul><li>Reduction in BILAG 61% </li></ul><ul><li>Murray & Perry </li></ul><ul><li>Clin.Rheum 2010 </li></ul>
    45. 57. RTX may even allow a “no-steroid” regime ……………..
    46. 58. “ No-Steroid” Regime: <ul><li>Methyl-pred 500mg+RTX 1gm (Days 1 + 15) </li></ul><ul><li>  </li></ul><ul><li>followed by: MMF (2 – 3 daily) </li></ul><ul><li>No oral steroids </li></ul><ul><li>Lightstone et al 2010 </li></ul>
    47. 59. “ No-Steroid” Regime: <ul><li>Early Results. </li></ul><ul><li>  </li></ul><ul><li>29 patients </li></ul><ul><li>>2years follow-up </li></ul><ul><li>47% of patients complete remission at 1 year </li></ul><ul><li>88% of patients complete remission at 3 years </li></ul><ul><li>(No weight gain. Only 3 infections) </li></ul><ul><li>Lightstone et al 2011. </li></ul>
    48. 60. <ul><li>Words of caution………… </li></ul>
    49. 61. RTX and pregnancy <ul><li>Stop before pregnancy </li></ul><ul><ul><ul><ul><ul><li>Ostensen et al Rheumatology 2008, 3 , 28-31 </li></ul></ul></ul></ul></ul><ul><li>Crosses placenta and inhibits neonatal </li></ul><ul><li>B-lymphocyte development </li></ul><ul><ul><ul><ul><ul><li> Klink et al Clin Dev Immuno 2008 </li></ul></ul></ul></ul></ul>
    50. 62. Infections ?
    51. 63. Ocrelizumab <ul><li>Opportunistic infections so far reported: </li></ul><ul><li>  </li></ul><ul><li>Pneumocystis jiroveci pneumonia </li></ul><ul><li>Disseminated herpes zoster </li></ul><ul><li>Myco. TB and other species </li></ul><ul><li>Reactivation of hep. B. </li></ul><ul><li>Systemic candidiasis </li></ul><ul><li>CMV pneumonia and CMV retinitis </li></ul><ul><li>Histoplasmosis </li></ul>
    52. 64. JC Virus
    53. 65. <ul><li>FAILURE </li></ul><ul><li>SUCCESS </li></ul>
    54. 66. SUCCESS Eric Liddell: 1923 Olympic Gold Medallist
    55. 67. Success <ul><li>Recognition and Treatment of APS </li></ul>
    56. 68. SUCCESS Lupus and Pregnancy 50 years of progress
    57. 69. Success <ul><li>Fewer lupus patients are being overtreated </li></ul>
    58. 70. And finally …….
    59. 71. Don’t Believe the Textbooks!
    60. 73. Don’t Believe the Textbooks!
    61. 74. … eventually it usually kills the patient...
    62. 75. 40 years later...
    63. 77. Lupus street, London
    64. 78. Perseverance!

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