Aruoriwo Oboh-Weilke , MD Florian Weilke , MD Georgetown University Hospital, Washington, D.C.

1. Anterior Segment Inflammation as a Presenting Sign of Wegener’s Granulomatosisin a 15-Year-Old Boy AruoriwoOboh-Weilke, MD FlorianWeilke, MD Georgetown University Hospital, Washington, D.C. Consulting Ophthalmologists, LLC, Hollywood, M.D. The authors have no financial interest in this subject matter

2. Purpose • We report a case of a 15 year old boy who presented with a two week history of left ocular irritation. He was noted to have some inflammation in the anterior segment. A persistent and extensive review of systems revealed other systemic symptoms which led to the workup and early diagnosis of Wegener’s Granulomatosis.

3. Introduction • Wegener’s Granulomatosis is a multisystem granulomatousvasculitisthat affects small to medium-sized blood vessels. It is believed to be of an autoimmune origin (2). • This is a potentially lethal disorder and several organ systems are affected especially the respiratory tracts and the renal system (5). • Ophthalmic manifestations are observed in about 50% of adults (1). There is no precise statistical data about ocular involvement in Wegener’s granulomatosis in children (3). • The disease is rare in the pediatric age group although it may initially present with some ocular manifestations (1). The most common form of systemic vasculitis in children is Henoch-Schonleinpurpura(3).

4. Introduction • Ocular involvement in Wegener’s Granulomatosis has many variable presentations. There have been reports that include scleritis, proptosis, nasolacrimal duct obstruction, altered motility, orbital inflammation, uveitis and vasculitis of the retina, choroid and optic nerve (1,2,3) . • Patients with Wegener’s Granulomatosis are typically cANCA positive (ie have cytoplasmic staining to antineutrophiliccytoplasmic antibodies. Up to 5% are however pANCA positive (i.e. have a perinuclear staining) (4) • Classic pathologic diagnostic criteria include necrotic tissue, vasculitis and granulomatous inflammation (4). • Glucocorticoids in addition to cytotoxic agents have decreased the mortality and morbidity of the disease (3)

5. Case Report • A 15 year old boy was referred for a cornea evaluation by his ophthalmologist. He had presented with a two week history of ocular irritation in the left eye. He had been treated with topical steroids and some systemic steroids. However, his Ophthalmologist referred him when he did not appear to be improving and had an atypical anterior segment inflammation.

6. Case Report • On initial review of systems the patient and his parents denied any systemic symptoms. The patient admitted to some ocular redness and occasional pain on motion in the left eye. • On physical examination, the patient’s VA OD was 20/20 and OS 20/40 • EOM were full, without any pain on motion. • Pupils were normal. The IOP in the left eye was elevated due to a steroid response • Slit Lamp Exam revealed on the right: superior nasal corneal opacification. On the left there was diffuse 3+ superior bulbar injection with chemosis. There was also opacificationof the cornea superiorly and pannus.

7. Case Report • Dilated fundus exam was normal and did not reveal any choroidal folds or posterior segment inflammation. • The patient improved with topical lubricants, and oral NSAIDS. Due to his symptoms of ocular irritation and history of not improving on systemic steroids, SLK in addition to an atypical scleritis was on the list of differential. A resection of the superior bulbar conjunctiva was performed when it appeared necrotic on exam. • Persistent questioning on ROS, led to the discovery that the patient had suffered from chronic ear infections within the past 8 months leading to the placement of ear tubes. On further questioning the parents admitted to a recent history of sinusitis, athralgias and some lesions on the patients tongue. A workup was then undertaken to look for possible underlying causes of his anterior segment inflammation.

8. Results • A CBC was within normal • ESR was elevated at 51mm/hr • CRP was elevated at 4.2mg/dl • Serum uric acid was normal • Rheumatoid factor was positive • C-ANCA was positive at 1:64 • P-ANCA was negative • The conjunctival resection revealed marked chronic inflammation with reactive changes

9. Results • After the initial results were obtained, a staff Rheumatologist was contacted. He suggested obtaining antibodies to proteinase 3 (PR3, a major target antigen for ANCA). That was highly positive at 89.4 (normal range <3.0) • Based on the above findings and systemic signs and symptoms, a diagnosis of Wegener’s granulomatosis was made. A CT of the sinuses revealed diffuse inflammatory mucosal thickening in the paranasal sinuses, opacificationof a large portion of the right middle ear but no bony destruction. • The patient was referred to a rheumatologist and was treated with high does of systemic steroids and cytoxan. He was given a good prognosis by his rheumatologist due to the early detection and treatment of his disease.

10. Results

11. Discussion • Wegener’s Granulomatosisis a rare, systemic, granulomatousvasculitis. It has a strong preponderance for Caucasians, especially of northern European descent. Women and men are equally affected (2). • The annual incidence is estimated to be about 10 per 1 million people with an average age at diagnosis of 50 years (2) • It is described as having a triad of pulmonary, renal and head (eyes/ENT) manifestations. However, its diagnosis is not easily made due to its varied presentations. The diagnosis of this condition is further complicated in children as the triad of disease defining features is not always present.

12. Discussion • Very few cases of the occurrence of Wegener’s Granulomatosis in children exist in the literature (1). • Ophthalmic complications of this disease may result from focal vasculitis, granulomatous inflammation, vascular thrombosis or from chronic inflammation and ischemia (2) • Ocular inflammation can occur with or without obvious systemic manifestations of the disease (4). • The use of cytotoxic therapy in combination with corticosteroids has greatly improved the survival rates of patients with Wegener’s Granulomatosis(4)

13. Conclusion • This report draws attention to a systemic disease with many variable presentations and it should be included in the differential diagnosis of a patient with atypical anterior segment inflammation or symptoms. • These patients are best managed by a team of doctors which includes rheumatologists, internists, ophthalmologists and otorhinolaryngologists • A high index of suspicion in addition to an extensive and vigilant review of systems can aid in making an early diagnosis and lead to early treatment of this potentially fatal disease.

14. References 1. Levi M, Kodsi S, Rubin S (2008) Ocular involvement as the initial manifestation of Wegener’s granulomatosis in children. J AAPOS 12: 94-96 2. Vischio J, McCrary C (2008) Orbital Wegener’s granulomatosis: a case report and review of the literature. ClinRheumatol 27: 1333-1336 3. Wardyn K, Zycinska K, Matuszkiewicz-Rowinska M (2003) Pseudotumororbitae as the initial manifestation Wegener’s granulomatosis in a 7-year-old girl. ClinRheumatol 22: 472-474

15. References 4.Harper S, Letko E, Samson, M (2001) Wegener’s Granulomatosis: The Relationship Between Ocular and Systemic Disease. The J of Rheumatol 28: 1025-1032 5. Fortney A, chodosh J (2002) Conjunctival Ulceration in Recurrent Wegener’s Granulomatosis. Cornea 21(6): 623-624 6. Samuelson T, Margo C (1990) Protracted Uveitis as the Initial Manifestation of Wegener’s Granulomatosis. Arch Ophthalmol (108)

16. Special thanks to Doug Litchfield, MD and Joseph Sleckman, MD