Download Reena Agarwal - American Academy of Optometry

Ocular Cicatricial Pemphigoid
Abstract:
A 53 year old white male presents with a history of chronic conjunctivitis. Exam findings
reveal symblepharon and conjunctival granulomas. Biopsies of the eyelid growths lead to
a diagnosis of ocular cicatricial pemphigoid.
I. Case History
-Patient demographics
53 year old white male with a history of chronic conjunctivitis
-Chief complaint
Patient reports ocular irritation especially in the lateral canthus and a feeling of dryness
bilaterally for eight months. The patient also complains of a “blister” like sensation
underneath his eyelids. The eyes are also reported to be crusted shut every morning. The
patient reports currently using artificial tears every ten minutes.
-Ocular and Medical history
Medical History:
(+) Osteoarthrosis
(+) Asthma
(+) Allergic Rhinitis
(+) Bipolar Disorder
(+) Hepatitis C
(+) Cocaine Dependence
(+) Alcohol Dependence
Ocular History:
(+) history of chronic conjunctivitis in both eyes (OU)
(+) dry eye
-Medications
Albuterol
Divalproex
Docusate
Flunisolide
Fluocinolone
Loratadine
Naphazoline
Omeprazole
Sennosides
Trazodone
-Other salient information
(+) Antinuclear Antibodies (ANA)
II. Pertinent findings
-Clinical
Visual Acuity right eye (OD) 20/25+1 left eye (OS) 20/40Slit lamp:
Lids/lashes: flaking, crusting OU
mild symblepharon temporally of the inferior palpebral
conjunctiva OU
Conjunctiva: bulbar conjunctiva 1+ injection OU
palpebral conjunctiva 2+ injection with 2 distinct
growths upon lid eversion of superior palpebral conjunctiva OD
greater than OS without ulceration, smooth surface, feels firm
OU
Cornea:
superficial punctate keratitis OU with central scar OS
Iris:
flat (-) NVI
Lens:
Anterior Cortical cataracts 2+ inferiorly OU,
Nuclear Sclerotic cataracts trace OU
Goldman Tonometry: OD 15mmhg OS 10mmhg at 9:50 AM
Pachymetry:
OD 591 OS 576
Dilated Fundus Exam: cup to disk ratio: 0.3 healthy, pink, distinct OU
Macula: clear OU
Posterior pole and Periphery: unremarkable
-Physical
Patient reports negative skin or oral lesion/ulcerations during initial optometry
examination. However the dermatology consult indicated that the patient reported
previous episodes of developing blisters on his face, arms, back, legs, and buttocks. At
the time of the exam, scars and post-inflammatory hyperpigmentation were found on
areas of the body.
-Laboratory Studies
Upon subsequent visits, a biopsy of conjunctival tissue revealed deposits of
immunoglobulin A (IgA), fibrin and weak complement 3 (C3) in focal areas of the
basement membrane zone region, and deposits of IgA in the cystoid bodies in the
epithelial layer. Results indicate linear IgA bullous dermatosis (LABD) a form of ocular
mucous membrane pemphigoid (also known as cicatricial pemphigoid).
-Radiology Studies were not needed
III. Differential diagnosis
Atopic keratoconjunctivitis, Trachoma, Ocular Cicatricial Pemphigoid, Pseudo-ocular
Cicatricial Pemphigoid, Bullous Pemphius, Ocular Rosacea, Trauma, Chemical Burn,
Squamous Cell Carcinoma, Scleroderma, Pemphigoid, Stevens-Johnson Syndrome, and
Sarcoidosis .
-Primary/leading
Ocular cicatricial pemphigoid
IV. Diagnosis and discussion
Ocular cicatricial pemphigoid (OCP) is a systemic autoimmune inflammatory
disease that is part of a range of disorders termed mucous membrane pemphigoid. This
disease not only affects the conjunctiva of the eye, but also the skin, and mucous
membrane linings of the mouth, esophagus, trachea, nose, vagina, and rectum (5). The
most common site affected is the membrane linings of the mouth (3). Of the patients with
oral involvement it is estimated that 15-20% will develop ocular involvement within five
years of onset (4).
This is a rare condition generally found within the population of individuals aged
between sixty and eighty; however a few cases have been reported in young children (3).
The disease has been known to affect more women then men (5). No racial or geographic
predilection has been found (5).
Patients with undiagnosed OCP will present with complaints of burning, redness,
tearing, decreased vision, and foreign body sensation (7). These patients also generally
have a history of chronic conjunctivitis (7). The disease is best described in four stages.
Stage one is described as conjunctival injection and scarring. Stage two begins with the
foreshortening of the inferior conjunctival cul-de-sac. This leads to the formation of a
symblepharon which is described as stage three. Stage three also includes such signs as
corneal neovascularization, keratopathy, trichiasis, entropion, dystichiasis and decreased
tear production, which eventually lead to corneal damage. Stage four is considered the
end stage of OCP and results in ankyloblepharon and ocular surface keratinization (7, 6).
The clinical signs and symptoms of OCP are further confirmed with laboratory testing.
Once a patient is suspected of having OCP, a biopsy of the conjunctiva is ordered
using the immunofluorescent or immunoperoxidase technique (7). For a definitive
diagnosis of OCP a linear deposition of immunoreactants at the basement membrane of
inflamed conjunctiva is necessary. A negative result does not exclude a diagnosis of OCP
but a positive result confirms the clinical diagnosis (7). Immunofluorescent testing is
both sensitive and specific for the diagnosis of mucous membrane pemphigoid and is
considered the gold standard method of diagnosing the condition (4). The disease may
take anywhere from ten to twenty years to progress through each stage. An untreated eye
or even a treated eye can lead to blindness due to the severe corneal scarring and due to
the likelihood of recurrences (6).
V. Treatment, management
-Treatment and response to treatment
The goal of treatment is to prevent inflammation and scarring, reduce recurrences,
and decrease symptoms (7). Treatment today consists of oral and or intravenous
medications. Topical and subconjunctival treatment with corticosteroids, mitomycin-C,
cyclosporine, and retinoids have been shown to be in effective in controlling ocular
inflammation (1). First line therapy commonly used today, consists of
immunosuppressive medications with or without corticosteroids. However, studies have
also shown the use of intravenous immunoglobulin therapies (IVIg) and anti-tumor
necrosis factor agents (TNF-a) for treating OCP.
The immunosuppressive medications that are routinely used are Dapsone
(Jacobus, diamino-diphenyl sulfone), methotrexate, mycophenolate mofetil, azathioprine,
cyclophophamide, and systemic prednisone. High doses of corticosteroids alone were
found to control scarring, but did not fully control the disease. Patients generally have to
remain on the medication for a long period of time and due to the long term
complications of steroid use, it may be an undesirable treatment option. Patients were
also found to have recurrences during the tapering period of the steroid (1). Ahmed et al.,
reported that of the immunosuppressive medications, Dapsone was most commonly used,
followed by methotrexate, axathioprine, and cyclophophamide, and prednisone was
commonly used as adjunctive treatment (1). The medications were found to control
ocular inflammation in 90% of the sixty-one patients studied even when medications
were discontinued, but 46% needed to remain on a maintenance dose to prevent
recurrences, and 10% progressed regardless of different drugs used. It was also reported,
that some patients in this study were required to take more then one drug to control ocular
inflammation. Some patients needed anywhere from two to six different medications to
control the disease. Common side effects of the medications included hematologic,
gastrointestinal, cardiovascular, and urinary complications. Dapsone was found to cause
the greatest number of side effects while methotrexate was found to cause the least
number of side effects.
Letko, E. et al compared the clinical outcome of ocular involvement in patients
with OCP between conventional immunosuppressive and intravenous immunoglobulin
therapies. Sixteen people were divided into two groups of eight. One group received
IVIg therapy and the other group received immunosuppressive therapy. In the end it was
found that patients treated with IVIg had a more rapid control of ocular inflammation and
did not progress to advanced stages of OCP, where as patients treated with
immunosuppressive therapy had multiple recurrences. Side effects were also non
significant when compared to the side effects of immunosuppressive drugs.
Canizanes et al. described three cases of patients with mucous membrane
phemphigoid who were treated with the anti-tumor necrosis factor agent, Etanercept
(Enbrel). Of the three patients, all of them had oral involvement and one had ocular
involvement. All three patients were initially treated with some form of steroid,
immunosuppressive, or intravenous immunoglobulin therapies with little success in
suppressing the disease. The patients were then treated with 25 mg of Etanercept twice
weekly. In all three patients the oral mucosal disease improved and the patient with the
ocular involvement had stabilization of progression. This study shows some indication
that TNF-a may play a role in the pathogenesis of the disease, and therefore could be a
promising treatment modality in the future.
Thus, our patient was treated on initial presentation with artificial tears, punctal
plugs, Restasis (Allergan) four times a day OU, cromolyn four times a day OU, ketotifen
four times a day OU, and tobredex ointment at bedtime OU. Once diagnosed with OCP
the patient was treated with 60 mg prednisone orally per day and upon follow-up,
mycophenolate moteil 1000 mg BID orally may be added to his treatment plan.
-Bibliography, literature review encouraged
1. Ahmed, A.R. et al.“The effect of Treatment and it’s Related Side Effects in
Patients with Severe Ocular Cicatricial Pemphigoid.” Ophthalmology 2002; 109,
111-118.
2. Ahmed, M. et al., “Ocular cicatricial pemphigoid: pathogenesis, diagnosis and
treatment.” Progress in Retinal and Eye Research. 2004; 23, 579-592
3. Canizares MJ, Smith Dl, Conners MS, et al. “Successful treatment of mucous
membrane pemphigoid with Etanercept in 3 patients.” Archives of Dermatology.
2006; 142;1457-1461.
4. Danier, E., and Thorne, J.E. “Recent advances in mucous membrane Pemphigoid.”
Current Opinion in Ophthalmology. 2008, 19; 292-297.
5. Foster, C. S. “Ocular Cicatricial Pemphigoid.” American Uveitis Society. 2003.
<http:// www.uveitissociety.org/pages/diseases/ocp.htm>
6. Friedman, N. and Kaiser, P. The Massachusetts Eye and Ear Infirmary Illustrated
Manual of Ophthalmology. Pennsylvania: Elsevier, Inc, 2004. pp 132-134.
7. Letko, E. et al., “A nonrandomized comparison of the clinical outcome of ocular
Involvement in patients with mucous membrane (cicatricial) pemphigoid between
conventional immunosuppressive and intravenous immunoglobulin therapies.”
Clinical Immunology. 2004; 111, 303-310.
VI. Conclusion
-Clinical pearls, take away points if indicated
Ocular cicatricial pemphigoid is a rare disease but one that optometrists should be
aware of. Due to the difficulty of distinguishing the early signs and symptoms of
conjunctival conditions, OCP is often diagnosed in stages three or four. As a result,
aggressive treatment is sometimes necessary. As discussed in this report, different modes
of therapy are available. However due to the lack of well controlled clinical trials, a gold
standard for treatment has yet to be developed. Choice of treatment is made based on
clinical experience, recent case reports, trial and error, and cost of the treatment plan.
When treating OCP it is also important to co-manage the disease with other health care
providers such as dermatologists, primary care providers, and dentists due to the
possibility of systemic involvement. Even with the development of new therapies
recurrences are still possible; therefore frequent follow up are important. In the end, the
best thing you can do for your patient is to treat their symptoms.