1. Ocular Cicatricial Pemphigoid
A Rare Chronic Conjunctivitis and more
Salus University
April 27th, 2012

2. Is NOT:
INFECTIOUS
ISCHEMIC
IATROGENIC
INJURIOUS
IS:
INFLAMMATORY
INFILTRATIVE/Non-NEOPLASTIC
INHERITED/AUTOIMMUNE
Ocular
Cicatricial
Pemphigoid
in Older F>M

3. http://friendlydoc.blogspot.com/2011/03/lacrimal-syringing-how-and-why-its-done.html
Ocular
Cicatricial
Pemphigoid

4. STAGE 1

5. STAGE 2

6. STAGE 3

7. STAGE 4

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. Dr. Wing

10. Dr. Wing

11. Dr. Wing

12. Dr. Wing

13. Dr. Wing

14. OCP Antibody binding site
• LAMINA LUCIDA OF BASAL
LAMINA
• Protein: integrin
• Integrins: transmembrane
proteins
• binds to extracellular matrix
(collagen, laminin, fibronectin).

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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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