Figure 1. Clinical photograph and magnetic resonance images. A, Clinical photograph shows hypertropia and lower eyelid ectropion of the left eye. Coronal (B) and axial (C) T1-weighted magnetic resonance imaging with fat suppression demonstrates a left inferomedial orbital mass involving the orbital floor and inferior rectus, with extension into the area of the nasolacrimal fossae.
Figure 2. Histologic analysis shows granulomatous inflammation (hematoxylin-eosin, original magnification ×20) (A), necrosis (hematoxylin-eosin, original magnification ×40) (B), and vasculitis (hematoxylin-eosin, original magnification ×40) (C and D), which are consistent with Wegener granulomatosis, with striking tissue eosinophilia (A and C). E, Immunohistochemistry demonstrates strongly positive IgE plasma cells (original magnification ×40).
Customize your JAMA Network experience by selecting one or more topics from the list below.
Chan ASY, Yu DL, Rao NA. Eosinophilic Variant of Wegener Granulomatosis in the Orbit. Arch Ophthalmol. 2011;129(9):1238–1240. doi:10.1001/archophthalmol.2011.259
Author Affiliations: Singapore National Eye Centre, Singapore (Dr Chan); Doheny Eye Institute, Department of Ophthalmology, Keck School of Medicine, University of Southern California, Los Angeles (Drs Chan and Rao); and Plastic and Reconstructive Surgery, Department of Ophthalmology, University of Kansas Medical Center, Kansas City (Dr Lu).
Wegener granulomatosis (WG) is a multisystem vasculitis of unknown etiology that preferentially involves small to medium-sized vessels, with a peak incidence in the fifth decade of life.1,2 The typical histologic triad described in WG consists of tissue necrosis, vasculitis, and granulomatous inflammation. Although mild eosinophilia has been reported in WG, significant eosinophilia is rare. The eosinophilic variant is a clinical and histologic variant characterized by significant tissue eosinophilia that is clinically consistent with WG in the absence of asthma or atopy.3-6 We describe an eosinophilic variant of WG occurring in the orbit in association with local IgE production.
An 84-year-old woman had a 2-month history of left ptosis, painless proptosis, and binocular vertical diplopia. Magnetic resonance imaging identified a 2.5 × 2.5 × 1.5-cm left inferomedial orbital mass. An incisional biopsy suggested the diagnosis of eosinophilic angiocentric fibrosis, and she was referred for further management.
Clinically, her visual acuity was 20/40 OU. Orbital examination revealed a left ptosis with 2.5 mm of relative proptosis, 15 prism diopters of left hypertropia with decreased depression, and a left lower eyelid ectropion (Figure 1A).
She had no history of atopy or asthma, sinonasal disease, respiratory disease, or renal disease. Antineutrophil cytoplasmic antigen antibodies were negative.
Follow-up magnetic resonance imaging demonstrated interval recurrence (Figure 1B and C), and another incisional biopsy was performed. Histologic analysis revealed granulomatous inflammation (Figure 2A), with areas of vasculitis and a prominent perivascular hyalinization (Figure 2D). Significant eosinophilia was also seen (Figure 2A and C). Serial sections revealed a focal area of necrosis (Figure 2B). Acid-fast bacteria and Gomori methenamine silver stains were negative. Immunohistochemistry revealed a striking IgE staining of the plasma cells (Figure 2E). The diagnosis of an eosinophilic variant of WG was made based on clinical history and histologic findings.
Eosinophilic WG is characterized by systemic WG with lung and renal disease and histologic findings consistent with WG but with additional peripheral and/or tissue eosinophilia in the absence of asthma or atopy.3-6 This variant is rare, and no ophthalmic involvement has been reported to our knowledge. However, other causes of eosinophilia must be excluded before this diagnosis is made.3-6 Wegener granulomatosis and Churg-Strauss syndrome are closely related antineutrophil cytoplasmic antigen–positive vasculitides.3-6 Churg-Strauss syndrome is typically associated with tissue eosinophilia and vasculitis but is differentiated from eosinophilic WG by the clinical history of atopy or asthma. Asthma and atopy are rare in WG, occurring no more frequently than in the general population.6 Eosinophilic angiocentric fibrosis is a rare inflammatory disease involving the sinonasal tract with tissue eosinophilia and distinctive perivascular fibrosis. It is differentiated from eosinophilic WG by the absence of necrosis. Fungal and parasitic infections can be excluded by histopathologic analysis and tissue cultures.6 Management of eosinophilic WG does not differ from that of systemic or limited WG, although the prognosis is variable.3-5
Our case revealed the typical features seen in WG: focal necrosis, granulomatous inflammation, and vasculitis. In addition, marked infiltration of eosinophils was seen. Limited ophthalmic WG occurs in 50% of patients and may represent the first sign of systemic WG in 16% of cases.1,2 Ophthalmic manifestations include conjunctivitis, uveitis, and orbital inflammation.1 Results of serological testing for antineutrophil cytoplasmic antigen are positive in 96% of patients with systemic WG; however, in limited WG, this decreases to 32% to 67%.1,2 Hence, a negative result for antineutrophil cytoplasmic antigen does not exclude the diagnosis.1,2
Elevated local IgE is unusual in WG.3,4 The role of eosinophilia and IgE in WG is unknown, and both are traditionally associated with atopy. However, in the absence of atopy, this striking presence of local IgE production and eosinophilia may represent a local hypersensitivity reaction toward an unrecognized extrinsic allergen as the underlying pathogenesis of this disease.
Correspondence: Dr Rao, Doheny Eye Institute, 1355 San Pablo St, DVRC 211, Los Angeles, CA 90033 (firstname.lastname@example.org).
Financial Disclosure: None reported.