Necrotizing Scleritis as a Manifestation of Eosinophilic Granulomatosis With Polyangiitis: A Case Report

Abstract

Eosinophilic granulomatosis with polyangiitis (EGPA) is an ANCA-associated vasculitis characterized by the development of necrotizing granulomas rich in eosinophils and vasculitis of small and medium vessels, with compromise of the respiratory tract, peripheral nervous system, and least frequent ocular involvement. We report the case of a 54-year-old Caucasian man with a history of EGPA who presented ocular pain, red eye, vision loss, and evidence of scleral slimming compatible with necrotizing scleritis. The patient was treated with systemic steroids and cyclophosphamide, which reduced the ocular pain but did not improve visual acuity, needing surgical treatment of the scleral coverage defect. While necrotizing scleritis is an unusual manifestation of EGPA, it should be part of the differential diagnosis in patients with red eye or ocular pain as an accurate diagnosis and prompt treatment could reduce local complications.

Introduction

Eosinophilic granulomatosis with polyangiitis (EGPA) is the least common form of ANCA-associated vasculitis, with an estimated incidence of 0.9 to 2.4 cases per million people. This disease is characterized by necrotizing granulomas rich in eosinophils and vasculitis of small and medium vessels.^1,2

The most frequently involved organs are the lungs, superior respiratory tract, and peripheral nervous system, meanwhile ocular compromise is described in 5% to 20% of patients.^3,4 This damage is divided into orbital inflammation, characterized by the tissular injury caused by the inflammatory response on the orbit cavity, eyeball, and nervous structures; and ischemic phenomena with vascular occlusion and thrombosis as manifestations. The clinical forms of ocular damage are listed in Table 1.

Table 1.

Types of ocular involvement on patients with eosinophilic granulomatosis with polyangiitis (EGPA).

Type of compromise	Clinical manifestation
Orbital inflammation	Diffuse orbital inflammation, dacryoadenitis, myositis, nodular infiltration of conjunctiva, periescleritis, scleritis or perineuritis
Ischemic vasculitis phenomena	Amaurosis fugax, optic ischemic neuropathy, occlusion of branches of central artery of the retina

While scleritis is a common manifestation of other types of ANCA-associated vasculitis, there are few reports of isolated compromise of an eyeball layer in EGPA patients.^{2 -4} We present the case of a patient with necrotizing scleritis as a severe manifestation of eosinophilic granulomatosis with polyangiitis.

Case Presentation

A Caucasian 54-year-old man presented to the emergency room with 2 years of burning pain in the left eye associated with vision loss and red eye. Given the unavailability of Ophthalmology at his residence place, was not evaluated by this specialty, and only received topical management for symptom control.

Three years before, he had 2 months of dyspnea, cough, weight loss, hypoesthesia, dysesthesia, and myalgias in the distal extremities. A thorax computed tomography scan documented a nodule in the apical segment of the inferior lobule of the right lung, followed by a percutaneous biopsy with histopathology that showed eosinophilic granulomatosis, capillaritis, and lung necrosis.

Also, due to the neuropathic symptoms a 4-extremities electromyography was performed, with evidence of sensitive, asymmetric, and distal axonal mononeuropathy compatible with multiplex mononeuritis. ANCA antibodies by indirect immunofluorescence showed PR3 positive, supporting the diagnosis of EGPA with the organ compromise and laboratory findings.

After the diagnosis, prednisolone was started at 25 mg per day and methotrexate at 2.5 mg up to 2 weeks before the visit to the emergency room. At this point, the patient denied respiratory symptoms and reported a slight improvement in extremity hypoesthesia without other symptoms besides the ocular ones.

On physical examination, the superior and temporal margins of the left eye presented severe scleral slimming, with visualization of the uvea, fibrinoid tissue, and mucous secretion, without perforation of the eyeball, compatible with necrotizing scleritis at high risk of perforation. The diagnosis of scleritis was made from the physical examination findings (Figure 1).

Figure 1.

Ocular compromise of the patient: Left eye, quadrant superior and temporal, red arrow: slimming of the sclera. Blue arrow: uvea. Green arrow: pupil.

Given the severity of ocular involvement and the risk of flap loss in the case of surgical intervention, in medical board with Rheumatology and Ophthalmology management with systemic steroids was decided, first with 3 days of pulsed methylprednisolone (500 mg/day) and then oral prednisone 0.5 mg/kg/day with 6 cycles of 750 mg cyclophosphamide every 28 days. The patient responded well to this therapy, which resolved ocular pain but did not improve visual acuity. After 6 cycles of cyclophosphamide, he underwent scleral coverage defect closure surgery. After the procedure, contact with the patient was lost, and we are unaware of the current evolution and visual recovery after several months of the intervention.

Discussion

We presented the case of a patient with EGPA, with lung and peripheral nervous system compromise at the time of diagnosis, who developed necrotizing scleritis of the left eye as a manifestation of severe activity, being the ocular damage, an underreported complication of this disease.^3,4

The EGPA does not have an elucidated physiopathology and is a product of a complex interaction between the host and the inflammatory response mediated by eosinophils and lymphocytes. The compromise is divided into the one made by the eosinophils and the one dependent of Anti-Neutrophil Cytoplasmic Antibodies (ANCA).^5,6

The chronic proliferation of eosinophils leads to the release of IL-4, 5, 9, 12, 25, and eotaxin-3, which polarize the lymphocytes to TH2 and induce the formation of necrotizing granulomas with eosinophils, fibroblast, and palisade cells that destroy the adjacent tissue.⁶ At the same time, the eosinophilic activity is related to hypercoagulability, local thrombosis, and ischemic-type manifestations in the eye, as enunciated in Table 1.³

Between 30% and 40% of patients with EGPA have positive ANCA, which correlates with antibody-mediated vasculitis. Of this group of patients, 90% have MPO type antibodies that join surface antigens of neutrophils, penetrate the vascular wall, and release oxygen free radicals that induce necrosis of endothelial cells and damage to the extracellular matrix, which explains the involvement of small vessels like renal or nervous beds.^{5 -7} Nevertheless, a mechanism of predilection to the damage of a specific vascular bed is not described, and it is not clear if there is some element that facilitates the susceptibility of the eye to vascular injury.

Our patient’s case draws attention to the fact that he had PR3 positive, which occurs in less than 5% of patients with EGPA, so we cannot rule out the association between this finding and the atypical ocular manifestation. Especially since scleritis is more common in patients with granulomatosis with polyangiitis (GPA), a condition characterized by the presence of ANCA PR3 type.^1,8

In cohort descriptions of patients with EGPA, ocular involvement is reported in up to 20% of cases, and this compromise is divided into orbital inflammation and ischemic vasculitis phenomena (Table 1).^7,9,10

The orbital inflammatory compromise represents 80% of the eye manifestations, with conjunctival nodules (40%), orbital myositis (25%), and dacryoadenitis (10%) as the more frequent forms, while scleritis occurs in less than 4% of cases.^3,4,11 For this reason, the occlusive compromise of retinal vessels, optic neuropathy, and especially pseudotumors or granulomas of the orbit are common in the reported cases.^3,4,12

Takanashi et al⁹ reported the isolated compromise of an eyeball layer in a patient with EGPA and periescleritis, whose main complaint was conjunctival hyperemia. At the same time, Cury et al¹² documented a patient with uveoscleritis and papilledema who responded well to steroids. In all the reported cases patients received topical or systemic steroids, with appropriate responses in up to 90% of cases.⁸ In our patient, while the oral steroids led to the control of symptoms and stopped the progression of visual compromise, surgical treatment was needed to cover the scleral surface defect; this severe manifestation could be related to the late consultation and the time since the beginning of symptoms.

Conclusions

Even with the infrequent ocular involvement in patients with EGPA, the active search for ischemic or inflammatory injuries should be made in patients with ocular symptoms due to potential permanent complications like blindness or need of surgical treatment.

More studies are necessary on the pathophysiological mechanisms that lead to the clinical manifestations of EGPA and the elements that favor the selective compromise in different vascular beds, including the ocular one.