Ocular cicatricial pemphigoid [1] 4th year pco rotation

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Ocular cicatricial pemphigoid [1] 4th year pco rotation

  1. 1. Ocular Cicatricial Pemphigoid A Rare Chronic Conjunctivitis and more Salus University April 27th, 2012
  2. 2. Is NOT: INFECTIOUS ISCHEMIC IATROGENIC INJURIOUS IS: INFLAMMATORY INFILTRATIVE/Non-NEOPLASTIC INHERITED/AUTOIMMUNE Ocular Cicatricial Pemphigoid in Older F>M
  3. 3. http://friendlydoc.blogspot.com/2011/03/lacrimal-syringing-how-and-why-its-done.html Ocular Cicatricial Pemphigoid
  4. 4. STAGE 1
  5. 5. STAGE 2
  6. 6. STAGE 3
  7. 7. STAGE 4
  8. 8. STAGE 1 STAGE 2 STAGE 3 STAGE 4 STAGE 4 Keratoprosthesis Ocular Cicatricial Pemphigoid A Patient Education Monograph prepared for the American Uveitis Society January 2003 by C. Stephen Foster, M.D., F.A.C.S. and Saadia Rashid Ocular Cicatricial Pemphigoid: atypical presentation as pseudopterygium and limbal stem cell deficiency Matthew S. Ward, MD, Nasreen A. Syed, MD, Kenneth M. Goins, MD September 27, 2010
  9. 9. Dr. Wing
  10. 10. Dr. Wing
  11. 11. Dr. Wing
  12. 12. Dr. Wing
  13. 13. Dr. Wing
  14. 14. OCP Antibody binding site • LAMINA LUCIDA OF BASAL LAMINA • Protein: integrin • Integrins: transmembrane proteins • binds to extracellular matrix (collagen, laminin, fibronectin).
  15. 15. Fig. 4. Transmission electron micrograph (10,000×) of a basal epithelial cell showing the adhesion complexes (arrowheads) that anchor it in place onto the Bowman's layer and summary inset. B, basal epithelial cell. Bar = 1 μm. (Inset from Albert and Jakobiec: Principles and practice of ophthalmology. Philadelphia, WB Saunders, 2000.)
  16. 16. Eye (1994) 8, 196–199; doi: 10.1038/eye.1994.45 The immunological features and pathophysiology of ocular cicatricial pemphigoid Mark J Elder1,2 and Susan Lightman1,2 BLISTERING Cond. Antibody binding site OCP Lamina lucida of BMZ Dermatitis herpetiformis Sublamina densa region of BMZ Epidermolysis bullosa Type VII procollagen in BMZ Pemphigus vulgarus Intercellular cement substance Bullous pemphigoid 220kDa glycoprotein in BMZ Stevens-Johnson Syndrome Blood vessel wall • The disease from above with the most serious ocular consequence is OCP.
  17. 17. Eye (1994) 8, 196–199; doi: 10.1038/eye.1994.45 The immunological features and pathophysiology of ocular cicatricial pemphigoid Mark J Elder1,2 and Susan Lightman1,2 BLISTERING Cond. Antibody binding site OCP Lamina lucida of BMZ Dermatitis herpetiformis Sublamina densa region of BMZ Epidermolysis bullosa Type VII procollagen in BMZ Pemphigus vulgarus Intercellular cement substance Bullous pemphigoid 220kDa glycoprotein in BMZ Stevens-Johnson Syndrome Blood vessel wall • The disease from above with the most serious ocular consequence is OCP. Some a little above Some a little below the level of OCP, but all these occur mostly away from the eye
  18. 18. Dr. Wing: Leukocytes AGRANULOCYTES GRANULES GRANULOCYTES D E S T R U C T I V E P R O T E C T I V E
  19. 19. Goal of treatment Stop progression as early as possible Mostly using medical therapy, surgeries have a poor prognosis Often dx by biopsy at stage III when patient is older and may not be able to tolerate the meds well
  20. 20. http://www.rndsystems.com/resources/images/6295.gif http://3.bp.blogspot.com/-1svMw42HKxo/T3KyBCXi7vI/AAAAAAAAADw/K7D2M9o20po/s1600/vasodilation.jpg Foster: 8 Steps in pathogenesis 1. Unknown 1st step: basement membrane becomes antigen
  21. 21. 2. Complement system and mast cells cause http://www.rndsystems.com/resources/images/6295.gif http://3.bp.blogspot.com/-1svMw42HKxo/T3KyBCXi7vI/AAAAAAAAADw/K7D2M9o20po/s1600/vasodilation.jpg Foster: 8 Steps in pathogenesis
  22. 22. 3. Leukocytes in the Leukocyte production, itself, inhibited by following cytotoxic immunosuppr. meds: – Cyclophosphamide- alkylating agent – Methotrexate, azathioprine, mycophenolate mofetil- antimetabolites http://www.daviddarling.info/images/bone_marrow.gif http://photo-dictionary.com/photofiles/list/644/1052DNA.jpg
  23. 23. 3. Leukocytes in tissues • Leukocyte recruitment cascade with effects on tissue architecture. http://www.daviddarling.info/images/bone_marrow.gif Inflammation:Where Immune Cells and Blood Vessels Collide CCR Connections Vol. 3 , no. 2, 2009
  24. 24. 4. Pro-inflam. activity including: a. myeloperoxidase (along with leukocyte recruitment inhib by Dapsone- antibiotic), http://ars.els-cdn.com/content/image/1-s2.0-S1286457903002417-fx3.jpg
  25. 25. 4. Pro-inflam. activity including: b. IL-1 (inhibited by Anakinra- biologic), http://www.google.com/imgres?imgurl=http://www.kineretrx.com/professional/images/il- 1.gif&imgrefurl=http://www.kineretrx.com/professional/about/mechanism_action.jsp&usg=__jPm6A52fMdKCPyjKqO0yirlWmD4=&h=281&w=300&sz=25&hl=en&start=1&zoom=1&tbnid=PGZXS_SZllkI7M:&tbnh=109&tbnw=116&ei=Gd- ZT8LPC4bkrAfRjOGMDQ&prev=/search%3Fq%3DIL-1%26hl%3Den%26lr%3D%26tbm%3Disch&itbs=1
  26. 26. 4. Pro-inflam. activity including: c. TNF-alpha (inhibited by Infliximab and etanercept – biologic- cytostatic?)http://www.google.com/imgres?imgurl=http://pharmacologycorner.com/wp- content/uploads/2009/05/tnfmacrophage.png&imgrefurl=http:/ /pharmacologycorner.com/mechanism-of-action-indications- and-adverse-effects-of-etanercept-infliximab-and- adalimumab/&usg=__nrZn4hcVPyipE_il5X83WYuBdhw=&h=411 &w=392&sz=20&hl=en&start=9&zoom=1&tbnid=2k3XefDJCIz0c M:&tbnh=125&tbnw=119&ei=H- WZT8WGFsnlrAf304CgDQ&prev=/search%3Fq%3DTNF%2Balpha %2Beffects%26hl%3Den%26lr%3D%26tbm%3Disch&itbs=1
  27. 27. Individuality: the barrier to optimal immunosuppression Barry D. Kahan Nature Reviews Immunology 3, 831-838 (October 2003) Macrophage T cell Calcineurin 5. Macrophage as APC to agranulocyte proinflam.
  28. 28. Individuality: the barrier to optimal immunosuppression Barry D. Kahan Nature Reviews Immunology 3, 831-838 (October 2003) Macrophage T cell Calcineurin 6. T cell and autocrine IL-2 proinflam. IL-2
  29. 29. Individuality: the barrier to optimal immunosuppression Barry D. Kahan Nature Reviews Immunology 3, 831-838 (October 2003) CsA tacrolimus IL-2 Macrophage T cell Calcineurin 6. T cell and autocrine IL-2 inhibited by cytostatics: a. cyclosporin and b. Tacrolimus-Calc. inhib
  30. 30. Individuality: the barrier to optimal immunosuppression Barry D. Kahan Nature Reviews Immunology 3, 831-838 (October 2003) CsA tacrolimus IL-2 Macrophage T cell Calcineurin 6. T cell and autocrine IL-2 inhibited by cytostatics: a. cyclosporin and b. Tacrolimus-Calc. inhib (c. daclizumab-biologic)
  31. 31. Effects of IL-4 on Conjunctival Fibroblasts: Possible Role in Ocular Cicatricial Pemphigoid Mohammed S. Razzaque 1 , Babar S. Ahmed 1 , C. Stephen Foster 2 and A. Razzaque Ahmed 1 7. Macrophage anti-inflam. production of TGF-beta and IL-4, ↑fibroblast, ↓MMP, ↑ECM, ↓fibroblast locomotion, myofibroblast contraction, scarring
  32. 32. http://friendlydoc.blogspot.com/2011/03/lacrimal-syringing-how-and-why-its-done.html 8. Possible antigen presentation by conjunctival epithelial cells, self-destruction Last step in pathogenesis
  33. 33. http://friendlydoc.blogspot.com/2011/03/lacrimal-syringing-how-and-why-its-done.html 8. Possible antigen presentation by conjunctival epithelial cells, self-destruction Last step in pathogenesis
  34. 34. OCP Patient Education • OCP is a systemic autoimmune condition best treated with systemic immunosuppressive agents for a few years or more by a specialist/oncologist/hematologist • Specialist will do a biopsy, rate of positive biopsy 20 to 67% (Jacobiec in Ocular Cicatricial Pemphigoid: A Review of Clinical Features, Immunopathology, Differential Diagnosis, and Current Management Seminars in Ophthalmology July-September 2011) • Trouble swallowing? you must seek medical attention, might have to get an endoscopy • Prognosis: Guarded
  35. 35. A patient on my rotation with OCP 70’s CF, suspected to have OCP about 1 yr ago CC: 1) ocular irritation 2) loss of vision • 10/11 Cleveland Clinic performed biopsy, recommended Dapsone
  36. 36. A patient on my rotation with OCP Last December –VA’s ~20/40 in worse eye –Glaucoma on 2 meds d/c’ed 1 med, –severe dry eyes –using Preserved Theratears >4times a day, d/c’ed –start Oasys PF AT’s, –Durezol bid OU, d/c’ed due to high IOP –hx of Restasis, Punctal Plugs, and bandage Cl’s
  37. 37. A patient on my rotation with OCP Appearance of ocular surface: –shortened inferior fornices, –staining across entire ocular surface in both eyes, greatest in conjunctival area, red, painful, burning
  38. 38. A patient on my rotation with OCP almost 2 months later –VA’s ~20/100 in worse eye; –same appearance + difficulty elevating eyelid above line of sight due to fibrosis, –restart Travatan, Combigan, –pt asked about immunosuppressives, was already on azathioprine, pt edu to f/u with PCP and obtain a rheumatologist
  39. 39. A patient on my rotation with OCP ISSUES • Patient can’t afford to drive to specialist every time has a worsening of symptoms • Patient does not fully understand why the medicine she is taking is important and why regular check ups and blood work are necessary
  40. 40. Credits • Dr. DeGaulle Chigbu • Dr. C. Stephen Foster and Dr. Frederick Jakobiec • Dr. Joan Wing • Robbins Pathology text • Dr. Paul Lobby and Dr. Kara Shirley

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