ocular cicatricial pemphigoid [1] 4th year pco rotation
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Ocular Cicatricial PemphigoidA Rare Chronic Conjunctivitis and more
Salus UniversityApril 27th, 2012
Is NOT:INFECTIOUSISCHEMICIATROGENICINJURIOUS
IS:INFLAMMATORYINFILTRATIVE/Non-NEOPLASTICINHERITED/AUTOIMMUNE
Ocular Cicatricial Pemphigoidin Older F>M
http://friendlydoc.blogspot.com/2011/03/lacrimal-syringing-how-and-why-its-done.html
Ocular Cicatricial Pemphigoid
STAGE 1
STAGE 2
STAGE 3
STAGE 4
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 RashidOcular Cicatricial Pemphigoid: atypical presentation as pseudopterygium and limbal stem cell deficiency
Matthew S. Ward, MD, Nasreen A. Syed, MD, Kenneth M. Goins, MDSeptember 27, 2010
Dr. Wing
Dr. Wing
OCP Antibody binding site
• LAMINA LUCIDA OF BASAL LAMINA• Protein: integrin• Integrins: transmembrane
proteins• binds to extracellular matrix
(collagen, laminin, fibronectin).
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.)
Eye (1994) 8, 196–199; doi: 10.1038/eye.1994.45The 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.
Eye (1994) 8, 196–199; doi: 10.1038/eye.1994.45The 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 aboveSome a little below the level of OCP, but all these occur mostly away from the eye
Dr. Wing: Leukocytes AGRANULOCYTES
GRANULES GRANULOCYTES
MPO
MPO
MPO MPO
MPO
D E S T R U C T I V E
P R O T E C T I V E
Goal of treatment
Stop progression as early as possibleMostly using medical therapy,
surgeries have a poor prognosisOften dx by biopsy at stage III when
patient is older and may not be able to tolerate the meds well
http://www.rndsystems.com/resources/images/6295.gifhttp://3.bp.blogspot.com/-1svMw42HKxo/T3KyBCXi7vI/AAAAAAAAADw/K7D2M9o20po/s1600/vasodilation.jpg
Foster: 8 Steps in pathogenesis
1. Unknown 1st step: basement membrane becomes antigen
2. Complement system and mast cells cause
http://www.rndsystems.com/resources/images/6295.gifhttp://3.bp.blogspot.com/-1svMw42HKxo/T3KyBCXi7vI/AAAAAAAAADw/K7D2M9o20po/s1600/vasodilation.jpg
Foster: 8 Steps in pathogenesis
3. Leukocytes in the bone marrow
Leukocyte production, itself, inhibited by following cytotoxic immunosuppr. meds:– Cyclophosphamide-
alkylating agent– Methotrexate,
azathioprine, mycophenolate mofetil-antimetabolites
http://www.daviddarling.info/images/bone_marrow.gifhttp://photo-dictionary.com/photofiles/list/644/1052DNA.jpg
CentrallyActing Agents
3. Leukocytes in peripheral tissues• Leukocyte recruitment cascade with effects
on tissue architecture.
http://www.daviddarling.info/images/bone_marrow.gif
Inflammation:Where Immune Cells and Blood Vessels CollideCCR Connections Vol. 3 , no. 2, 2009
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
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
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=2k3XefDJCIz0cM:&tbnh=125&tbnw=119&ei=H-WZT8WGFsnlrAf304CgDQ&prev=/search%3Fq%3DTNF%2Balpha%2Beffects%26hl%3Den%26lr%3D%26tbm%3Disch&itbs=1
Individuality: the barrier to optimal immunosuppressionBarry D. Kahan
Nature Reviews Immunology 3, 831-838 (October 2003)
Macrophage
T cellCalcineurin
5. Macrophage as APC to agranulocyteproinflam.
Individuality: the barrier to optimal immunosuppressionBarry D. Kahan
Nature Reviews Immunology 3, 831-838 (October 2003)
Macrophage
T cellCalcineurin
6. T cell and autocrine IL-2proinflam.
IL-2
Individuality: the barrier to optimal immunosuppressionBarry D. Kahan
Nature Reviews Immunology 3, 831-838 (October 2003)
CsAtacrolimus
IL-2
Macrophage
T cellCalcineurin
6. T cell and autocrine IL-2 inhibited by cytostatics:a. cyclosporin and b. Tacrolimus-Calc. inhib
Individuality: the barrier to optimal immunosuppressionBarry D. Kahan
Nature Reviews Immunology 3, 831-838 (October 2003)
CsAtacrolimus
IL-2
Macrophage
T cellCalcineurin
6. T cell and autocrine IL-2 inhibited by cytostatics:a. cyclosporin and b. Tacrolimus-Calc. inhib(c. daclizumab-biologic)
Effects of IL-4 on Conjunctival Fibroblasts: Possible Role in Ocular Cicatricial PemphigoidMohammed 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
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
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
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
A patient on my rotation with OCP
70’s CF, suspected to have OCP about 1 yr agoCC: 1) ocular irritation 2) loss of vision
• 10/11 Cleveland Clinic performed biopsy, recommended Dapsone
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
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
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
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
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