Abstract
Purpose: To describe IgG4-positive sclerosing orbital inflammation with prominent conjunctival and scleral involvement.
Design: Case report.
Methods: Clinical, radiologic, and pathologic correlation.
Results: A 66-year-old man presented with right eye redness and irritation. Examination revealed unilateral scleritis and nongranulomatous anterior uveitis with elevated p-ANCA and CRP. Orbital CT scan showed inferotemporal scleral thickening. Biopsy revealed sclerosis and IgG4-positive plasma cells in the conjunctiva and inferior rectus.
Conclusions: IgG4-mediated sclerosing inflammation is well-recognized in the orbit and adnexa, particularly the lacrimal gland. Scleritis with anterior uveitis should be recognized as a possible presentation for this entity, which has important systemic associations.
IgG4-related sclerosing inflammation involves numerous sites systemicallyCitation1 and is well described in the lacrimal gland and orbit but not the conjunctiva. We present a case of IgG4-related orbital sclerosis involving the conjunctiva, sclera, anterior chamber, and inferior rectus muscle.
CASE SUMMARY
A 66-year-old man with ectropion presented with right eye redness and irritation for 2 weeks, without discharge or constitutional symptoms. Visual acuity was 20/50 bilaterally. Slit-lamp biomicroscopy of the right eye showed moderate scleritis, fine keratic precipitates, anterior chamber inflammation, and synechiae. The left anterior segment, orbit, motility, and fundus examinations were normal. Inflammation of the right eye worsened despite therapy with prednisolone acetate 1% qid and cyclopentolate 1% qhs (). ANCA and CRP were mildly elevated initially, and 2 months later revealed ANCA titers of 1:80 (normal <1:20) and CRP of 2.61 (normal < 0.61). Values for proteinase-3 (pANCA), ACE, syphilis ELISA, HLA-B27, rheumatoid factor, ESR, complete blood count, TSH, urinalysis, and PPD were normal. Chest radiography demonstrated atelectasis and scarring. General physical exam was unremarkable. Orbital CT showed thickening of the right inferotemporal sclera, with normal extraocular muscles and fat ().
FIGURE 1 (A) External photo of the cornea and conjunctiva showing inferotemporal injection, keratic precipitates, anterior chamber cell and flare, and nasal synechiae. (B) External photo of the inferotemporal bulbar conjunctiva with injection and chemosis.
FIGURE 2 Coronal CT scan of the orbit demonstrating asymmetric thickening of right inferotemporal sclera.
During orbitotomy, significant inflammation of the inferior conjunctiva, sclera, and inferior rectus muscle was noted; the lacrimal gland appeared normal. Histology revealed dense lymphoplasmacytic infiltrates with sclerosis of the conjunctiva and inferior rectus muscle (). There was no histologic evidence of MALT lymphoma, and plasma cells were polytypic by immunohistochemistry (3:1 kappa:lambda ratio). There was a marked excess of IgG4+ plasma cells, with an average of 89.7 IgG4+ plasma cells per 40×, 0.24 mm2 high-power field (n = 3; expected <10) and an increased IgG4/IgG+ plasma cell ratio of 50.3% (n = 3; expected <6%). Serum IgG4 was elevated (143 mg/dL, normal <86). Serum IgG1 was also mildly elevated (1300 mg/dL, normal < 929) in association with a lambda monoclonal gammopathy of uncertain significance (MGUS).
FIGURE 3 Histopathology of conjunctival and inferior rectus muscle biopsies. (A) Conjunctival lymphoplasmacytic inflammation and sclerosis (40×). (B) Higher magnification reveals predominance of cytologically bland plasma cells (100×). (C) Conjunctival IgG4+ plasma cells (brown) are markedly increased (40×). (D) The inferior rectus biopsy reveals dense fibrosis of striated skeletal muscle with a predominantly plasmacytic infiltrate (100×).
Depot triamcinolone was injected into the inferior orbit. Rheumatology initiated oral prednisone 1 mg/kg daily and methotrexate 15 mg weekly but noted no signs of systemic sclerosis. The patient’s symptoms and redness improved over 1 month. Prednisone was continued for 3 weeks followed by a 1-month taper, methotrexate was discontinued after 2 months, and visual acuity improved to 20/30 bilaterally. The patient has been stable for 2 years.
DISCUSSION
Nonspecific orbital inflammation (NSOI), or orbital pseudotumor, accounts for 5–8% of all orbital biopsies.Citation2 The histologic and clinical features of NSOI overlap with those of IgG4-related sclerosing disorders of the orbit. In the largest study to date of 112 patients with NSOI, 19% were IgG4-related.Citation3 The lacrimal gland was involved in 81% of IgG4 cases, 71% bilaterally, but the conjunctiva was not involved. Another study reported on 10 cases of IgG4+ NSOI involving ocular adnexa (6), lacrimal gland (5), and extraocular muscles (1), but not conjunctiva.Citation4 A variant has been described called sclerosing NSOI in which patients report atypical pain and have limited inflammation with extensive fibrosis from the start.Citation6
Proper identification of IgG4-related NSOI is important due to associated systemic sclerosis.Citation4 Differential diagnostic considerations include MALT lymphoma and non-IgG4-related NSOI; in rare cases MALT lymphoma and IgG4-related NSOI may coexist.Citation5 IgG4-related NSOI should be considered in the differential diagnosis of atypical scleritis unresponsive to conventional therapy, and histopathology can show conjunctival involvement.
ACKNOWLEDGMENT
The authors would like to thank Paul Helgerson, MD, at the Veterans Administration Palo Alto Health Care System Internal Medicine Department for assistance with laboratory workup and patient management. The views expressed in this article are those of the authors and do not necessarily reflect the position or policies of the Department of Veterans Affairs or the United States government.
Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
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