2014 Article 33
2014 Article 33
2014 Article 33
BRIEF REPORT
Open Access
Abstract
Background: The purpose of this study is to describe a patient who was diagnosed with granulomatosis with
polyangiitis based on conjunctival biopsy. This study is a case report and review of the literature.
Findings: A 48-year-old Caucasian woman presented with a 2-week history of a left eye peripheral corneal ulcer
with adjacent conjunctivitis and a 4-month history of a non-resolving productive cough. Given her elevated serum
perinuclear antineutrophil cytoplasmic antibody (P-ANCA) and erythrocyte sedimentation rate (ESR) levels as well as
a chest computed topography (CT) that showed bilateral patchy infiltrates, suspicion of limited granulomatosis with
polyangiitis with lung and ocular involvement was high. Because bronchoalveolar lavage was nondiagnostic for
granulomatous disease, conjunctival biopsy was initially attempted in order to avoid a more invasive lung biopsy.
The conjunctival biopsy revealed mixed subacute inflammatory mediators and vasculitis consistent with granulomatosis
with polyangiitis.
Conclusions: Conjunctival biopsy may be a valuable, minimally invasive method for diagnosing systemic granulomatosis
with polyangiitis.
Keywords: Conjunctivitis; Cornea; Ulceration; Biopsy; Granulomatosis with polyangiitis
Findings
Background
87%) of cases of generalized granulomatosis with polyangiitis [11,12]. Furthermore, ophthalmic disease may be
the presenting symptom in 8% to 16% of patients
[12,13]. Almost any ocular or adnexal tissue can be affected. According to Harman and Margo [14], the most
common findings are proptosis, described in nearly one
fifth of patients, as well as keratoscleritis. Proptosis can
result either from primary orbital involvement or secondarily from extensive sinusitis. Other common ocular
manifestations of granulomatosis with polyangiitis include conjunctivitis (4% to 15%) [4,13], episcleritis, scleritis, retinal and optic nerve vasculitis, nasolacrimal duct
obstruction, uveitis, and dacryocystitis.
The diagnostic workup of granulomatosis with polyangiitis includes laboratory tests, imaging studies, and biopsy of affected tissues. Testing for serum antineutrophil
cytoplasmic antibodies (ANCAs) has significant value in
the diagnosis of Wegener's as well as other systemic vasculitides. Although cytoplasmic antineutrophil cytoplasmic antibody (C-ANCA) testing in Wegener's has a
sensitivity of 85%, perinuclear antineutrophil cytoplasmic antibody (P-ANCA) testing has a much lower sensitivity of 10% [15].
2015 Ursea et al.; licensee Springer. This is an Open Access article distributed under the terms of the Creative Commons
Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction
in any medium, provided the original work is properly credited.
While biopsy is an integral component of the diagnostic workup, the classic pathologic triad of parenchymal
necrosis, vasculitis, and granulomatous inflammation is
not commonly seen in extrapulmonary sites, with 91%
of open lung biopsies yielding positive results [4] compared to 54% of orbital biopsies [16]. Only a few case reports have been published in the literature on the role of
conjunctival biopsy in the diagnosis of systemic granulomatosis with polyangiitis [17-20]. Furthermore, to date,
there have been no publications regarding the diagnosis
of Wegener's based on conjunctival biopsy in the setting
of elevated P-ANCA titers.
Methods and results
Case report
A 48-year-old Caucasian woman presented with a 2week history of left eye redness and pain. She had initially been treated by a local emergency room physician
with ciprofloxacin 0.3% ophthalmic solution twice daily,
which after 4 days did not alleviate her symptoms. Her
primary care physician subsequently diagnosed her with
allergic conjunctivitis and instructed her to stop the
antibiotic drops and start topical allergy medications.
When her symptoms worsened, the patient was placed
on erythromycin ophthalmic ointment three times daily
and referred to a cornea specialist in the community.
This specialist diagnosed her with a left eye peripheral
corneal ulcer and immediately referred her to the authors for further evaluation and treatment.
This patient's past medical history was significant for
symptomatic cholelithiasis, mild hypertension, and a 4month history of recurrent left lower lobe pneumonia
for which her primary care physician had been treating
her with multiple courses of cephalexin 500 mg orally
three times daily as well as oral montelukast, a fluticasone inhaler, and an albuterol inhaler. Despite mild improvement in response to this regimen, her symptoms
persisted. Computed topography (CT) imaging of the
thorax with contrast was consequently performed, which
was significant for left lower lobe lateral and posteromedial basilar segment patchy infiltrates that were suggestive of primary granulomatous disease, and she was
referred to a pulmonologist. Bronchoalveolar lavage was
negative for acid-fast bacilli and fungi and was nondiagnostic with regard to granulomatous disease.
On presentation to the authors, the patient reported
redness and itchiness of the left eye with severe photophobia but no discharge. Her uncorrected vision was 20/
20 right eye and 20/25 left eye. Her pupils were equally
round and reactive to light with no afferent pupillary defect. Intraocular pressure measured 14 mmHg right eye
and 11 mmHg left eye. Slit lamp examination of the
right eye was within normal limits, and that of the left
eye revealed 2+ left upper lid edema and a 2.2 0.8 mm
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Figure 1 External and slit lamp photos of the left eye showing corneal ulceration.
Figure 2 Anterior segment optical coherence tomography (Visante) of the affected left cornea showing significant peripheral thinning.
Top: anterior segment scan; bottom: angle view.
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Figure 3 Histopathology and immunopathology of the conjunctival biopsy. (a) Severe conjunctival inflammation with prominent vasculitis
in the deep substantia propria (hematoxylin & eosin, original magnifications: upper left 100, upper right 200, lower 400). (b-d) Strong
immunoreactivities to T cells (CD3), B cells (CD20), macrophages (CD68), M2 macrophages (CD163), and costimulatory signal (CD80) (avidin-biotin
complex immunohistochemistry, original magnification: 400).
With regard to cases that were diagnosed based on biopsy of the conjunctiva in particular, there are only a
few case reports in the literature. Karakousis et al. [17]
described an 18-year-old boy with scleritis, refractory sinusitis, and an elevated C-ANCA titer. He was diagnosed with granulomatosis with polyangiitis after his
conjunctival biopsy revealed perivascular inflammation
with areas of necrosis. In addition, Toh et al. [18] reported a 61-year-old woman who presented with mild
proptosis, bulbar conjunctival ulceration adjacent to the
limbus, and central retinal artery occlusion, along with
marked nasal turbinate hypertrophy. Biopsy obtained
during her turbinectomy demonstrated non-specific acute
inflammation only, but when the margins of the conjunctival ulcer were biopsied, the histopathology showed
pauci-immune granulomatous inflammation consistent
with Wegener's. In another report [19], conjunctival biopsy in two patients with palpebral conjunctivitis revealed
granulomatous infiltration with focal vasculitis in one patient and mixed inflammatory cellular reaction in the
other. Finally, a 70-year-old man with cicatricial palpebral
conjunctival inflammation and secondary trichiasis and
marginal ectropion underwent palpebral conjunctival biopsy in order to rule out malignancy. The biopsy was significant for chronic granulomatous inflammation with
multinucleated giant cells and areas of perivascular inflammation consistent with Wegener's [20]. In general,
given the possible risk of surgically induced scleritis in
patients with serological and/or clinical evidence of collagen vascular disease, performing a biopsy should be a
well-thought-after decision. In our patient's case, given
her nondiagnostic CT and BAL, a definitive diagnosis
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Conclusions
Conjunctival biopsy is a relatively simple, minimally invasive means of supporting the diagnosis of granulomatosis
with polyangiitis. It can be considered as a possibility in
patients who present with conjunctivitis and in which biopsy of other involved organs such as the nasal passages,
lungs, or kidneys is contraindicated. Results of this type of
biopsy will likely not include the full classic histopathological triad but, when considered in combination with the
clinical presentation and other diagnostic findings, can be
strongly supportive of the diagnosis. Larger studies are
needed in order to more fully elucidate the diagnostic utility of conjunctival biopsy in patients with conjunctival involvement and suspected granulomatosis with polyangiitis.
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Consent
The patient presented in this case report agreed and gave
her consent for the report to be published.
Competing interests
The authors declare that they have no competing interests.
17.
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19.
Authors' contributions
RU participated in the conception and design of this work, as well as the
writing of the manuscript. DDC participated in the writing of the manuscript.
CCC participated in the design of this work, the writing of the manuscript, and
the histopathologic preparation of the tissue and its evaluation. TJB participated
in the critical review. All authors read and approved the final manuscript.
20.
Acknowledgements
This brief report was an unfunded project.
22.
Author details
1
Department of Ophthalmology and Vision Science, College of Medicine,
University of Arizona, Tucson, AZ 85711, USA. 2Oculoplastics Service,
Massachusetts Eye and Ear Infirmary, Boston, MA 02114, USA. 3College of
Medicine, University of Arizona, Tucson, AZ 85711, USA. 4Immunopathology
Section, National Eye Institute, Bethesda, MD 20892, USA.
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