Transcript Ocular Cicatrial Pemphigoid - University of Louisville Department of

Grand Rounds
Shivani V. Reddy, M.D.
University of Louisville
Department of Ophthalmology and Visual Sciences
History

CC: “eyelashes turned in”

HPI: 72 y/o WM referred to oculoplastics clinic for a
progressive trichiasis over 3-4 years. Patient states that
growth is much more pronounced in the left eye . Also
c/o chronic tearing, irritation and yellowish-white
discharge in both eyes, worse on the left. States that
overall symptoms have been progressing over about a 5
year span
History
POHx: Retinal detachment OS 1997, CE + IOL OU
PMHx: Bullous Pemphigoid, Peripheral neuropathy, Asthma,
Hypothyroidism, HTN
FAMHx: noncontributory
ROS: joint pain, muscle aches and difficulty swallowing
intermittently
MEDS: dapsone, zioptan, avodart, bystolic, cymbalta,
nexium, b12, synthroid,
NKDA
Exam
4→3
20/20-1
VA
P
20/100+1 (PH: NI)
4→3
+ RAPD OS
EOM: full OU
CVF: superior field limitation OU
Anterior Segment
OD
Lids/Lashes
Conj
Cornea
mild entropion
few trichiatic lashes
mild injection
multiple SPE
OS
UL+LL entropian
trichiasis
symblepharon
2+ injection
multiple SPE
inferonasal corneal erosion
Iris
WNL
WNL
Lens
PCIOL
PCIOL
Physical Exam
HENT: single tense vesicular lesion on soft palate
Thorax: 2 vesicular lesions on upper back
Extremities: single vesiculo-bullous lesion on right
leg
Skin Lesion
erupted bullous lesion on the right lower extremity
Summary
72 y/o WM presents with trichiasis OU 2/2 entropion, decreased
visual acuity OS, symblepharon OS , 2+ conjunctival injection OS
with an inferonasal corneal erosion. Dermatologic exam reveals
vesicular lesions on the soft palate, upper back and lower extremity
DDx:
o Autoimmune Cicatricial Conjunctivitis
o MMP, Sarcoidosis , SLE, Lichen Planus, IgA dermatosis
o Atopic Keratoconjunctivitis
o Ocular Rosacea
o Chronic Infectious Conjunctivitis
o Adenovirus , streptococcus
o Pseudopemphigoid (drug-induced )
o Conjunctival Trauma
Treatment
o Same day: UL + LL epilation OS, aggressive
lubrication
o OS cicatricial entropion repair + MMG of Upper and
lower lid
o Pathology results
o Acutely inflamed tissue infiltrated with
histiocytes, lymphocytes and neutrophils. Subepithelial fibrosis lacking elastic fibers indicative
of scarring
o Immunofixation not performed
One Month Post-Op Visit
Grafts healing well, significant inflammation persistent,
no residual trichiasis
Mucous Membrane Pemphigoid
• Group of heterogeneous diseases characterized by
inflammatory blistering of the oral, ocular,
pharyngeal, laryngeal and genital mucosa
• Main pathological feature: linear deposits of IgG,
IgA and C3 in the epithelial basement membrane
zone
• When MMP presents as a chronic scarring
conjunctivitis, it is known as Ocular Cicatricial
Pemphigoid
Ocular Cicatricial Pemphigoid
Clinical features
o Early on, signs of chronic or relapsing conjunctivitis with
vesicles detected on the conjunctiva
o Tearing , burning, mucous drainage
o Loss of goblet cells
o As the disease progresses, conjunctival shrinkage can cause
impaired eye movements and lagophthalmos
o Lid margin inflammation and scarring  trichiasis
o Eventually trichiasis and gland loss lead to progressive
corneal keratinization and scarring
Ocular Cicatricial Pemphigoid
Epidemiology
o Incidence: 1/8000 – 1/46000 ophthalmic
patients
o Average age of diagnosis: 60 – 70 years
o Female:Male: 1.5:1 – 3:1
o No geographic or racial predilection
Ocular Cicatricial Pemphigoid
Pathogenesis
o Binding of circulating autoantibodies (IgG, IgA, C3 and other
complement factors) to the BMZ (lamina lucida of the dermalepidermal junction)
o 205 kd β4 peptide of α6β4 integrin most frequent target
Why scarring instead of bullae formation?
o Autoantibody binding to BMZ  secretion of cytokines (TNFa, IL-1, migration inhibiting factor)  recruitment of
inflammatory cells  release of pro-fibrotic cytokines such as
TGF-beta and IFN-gamma  scarring
o Inciting Event unknown
Ocular Cicatricial Pemphigoid
4 Stages
Stage II – Shortening of the inferior fornix
Ocular Cicatricial Pemphigoid
4 Stages
Stage III – Symblepharon formation
Ocular Cicatricial Pemphigoid
4 Stages
Stage IV – End stage disease manifesting as ankyloblepharon,
severe sicca syndrome, severe ocular surface keratinization
Ocular Cicatricial Pemphigoid
Diagnosis
o Most cases are caught in stage 2 to 3 and beyond due to the
often insidious nature of progression
o Diagnosis is based on:
o Clinical Features
o Tissue Biopsy
o Should be performed perilesionally
o Conj biopsy best during active disease
o Specimen handling is extremely important as
using the wrong specimen fixative can lead to false
negative results
Ocular Cicatricial Pemphigoid
Hematoxylin & Eosin Staining
o inflammatory infiltrate
of variable intensity .
Contains neutrophils,
macrophages, plasma
cells, lymphocytes, and
Langerhans cells
o Essentially nonspecific
Ocular Cicatricial Pemphigoid
Direct Immunofluorescence
o Characteristic finding :
Linear deposition of
IgG, IgA, and/or C3 in
basement membrane
o However, diagnostic
sensitivity is only around
50% . Therefore a
negative result does not
rule out a disease
process
Ocular Cicatricial Pemphigoid
Immunoperoxidase Assay
o Performed if
immunofluorescence
is negative but strong
clinic suspicion
o Increases sensitivity
of testing from 5283%1
1. Power WJ, Neves RA, Rodriguez A, Dutt JE, Foster CS. Increasing the diagnostic yield of conjunctival biopsy in patients with
suspected ocular cicatricial pemphigoid. Ophthalmology. 1995;102(8):1158
Ocular Cicatricial Pemphigoid
Treatment
Mild to Moderate Disease
o Dapsone 50 – 200 mg/day for 12 weeks
o Important to check labs – hemolytic anemia risk
o MTX, mycophenolate, azathioprine can also be used, but more
serious side effect profile
Severe Disease
o Cyclophosphamide +/- Prednisone for 12 months or less
o Must beware of leukopenia
o Newer Therapies
o IVIG
o Rituximab
Ocular Cicatricial Pemphigoid
Treatment
Surgical Intervention
o Entropion repair
o Symblepharon excision
o limbal stem cell transplantation, PK, keratoprosthesis
Maintainence Measures
o Aggressive ocular lubrication
o Lid hygiene for infection prevention
o Epilation
PROGNOSIS? Current literature shows long term remission
in 1/3 of patients for an average of 34 months with IM therapy
References
1. BSCS Volume 8, External Diseases and Cornea . 2013
2. Pepose,Holland, Wilhelmus. Ocular Infection & Immunity. 1996
3. 1. Power WJ, Neves RA, Rodriguez A, Dutt JE, Foster CS. Increasing the
diagnostic yield of conjunctival biopsy in patients with suspected ocular cicatricial
pemphigoid. Ophthalmology. 1995;102(8):1158
4. Ahmed M, Zein G, Khawaja F, Foster CS. Ocular cicatricial pemphigoid:
pathogenesis, diagnosis and treatment. Prog Retin Eye Res 2004; 23:579.
5.Fleming TE, Korman NJ. Cicatricial pemphigoid. J Am Acad Dermatol 2000;
43:571.
6. Foster CS. Cicatricial pemphigoid. Trans Am Ophthalmol Soc 1986; 84:527.
7. Chan LS, Ahmed AR, Anhalt GJ, et al. The first international consensus on
mucous membrane pemphigoid: definition, diagnostic criteria, pathogenic factors,
medical treatment, and prognostic indicators. Arch Dermatol 2002; 138:370.
8.Letko E, Bhol K, Foster SC, Ahmed RA. Influence of intravenous
immunoglobulin therapy on serum levels of anti-beta 4 antibodies in ocular
cicatricial pemphigoid. A correlation with disease activity. A preliminary study. Curr
Eye Res 2000; 21:646.
9. 60.Foster CS, Chang PY, Ahmed AR. Combination of rituximab and intravenous
immunoglobulin for recalcitrant ocular cicatricial pemphigoid: a preliminary report.
Ophthalmology 2010; 117:861.
Thank You