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

Dr. Wing

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

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Foster: 8 Steps in pathogenesis

1. Unknown 1st step: basement membrane becomes antigen

2. Complement system and mast cells cause

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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