Clinical and Imaging Features Predictive of Orbital Granulomatosis with Polyangiitis and the Risk of Systemic Involvement

doi:10.1016/j.ophtha.2013.12.003

Ophthalmology

Volume 121, Issue 6, June 2014, Pages 1304-1309

https://doi.org/10.1016/j.ophtha.2013.12.003 Get rights and content

Objective

Granulomatosis with polyangiitis (GPA), previously Wegener's granulomatosis, requires prompt diagnosis and systemic review to exclude life-threatening disease. However, early diagnosis of orbital GPA may be difficult because anti–neutrophil cytoplasmic antibody (ANCA) and anti-PR3 antibody screening can be negative at presentation and orbital biopsies taken for diagnosis may not show the classic features of GPA. This study was designed to compare GPA with other causes of orbital inflammation and to identify the presenting clinical and imaging features most likely to predict GPA and its systemic spread.

Design

Retrospective noninterventional comparative case series.

Participants

A total of 247 patients who had undergone orbital biopsies for clinical presentations with orbital inflammation were identified from the Institute of Ophthalmology pathology database.

Methods

Patients were divided into GPA and non-GPA groups on the basis of their final clinical diagnosis. Clinical and imaging features of these 2 groups were compared to determine those predictive of GPA, and patients with GPA also had long-term evaluation for systemic involvement.

Main Outcome Measures

A diagnosis of orbital GPA and development of systemic GPA were the main outcome measures.

Results

Features highly suggestive of GPA were sinonasal symptoms, sinonasal changes, or paranasal bone erosion on imaging (P < 0.001). Bony erosion was independent of ANCA status or systemic involvement. Twenty-two percent of patients (8/37) with GPA had evidence of systemic involvement at presentation, and no patient presenting with solely orbital GPA developed later systemic disease over a median follow-up of 2.7 years.

Conclusions

A high index of suspicion should be maintained for GPA when a patient presents with an orbital mass and sinonasal symptoms or imaging shows sinonasal involvement or paranasal bone erosion. No patient with solely orbital GPA involvement at presentation developed systemic disease, suggesting that orbital GPA can remain localized in the long-term.

Section snippets

Methods

Ethical approval was obtained from the Moorfields and Whittington Research Ethics Committee for a retrospective noninterventional study of patients who had an orbital biopsy for orbital inflammatory disease at Moorfields Eye Hospital over a 21-year period.

Patient demographics and clinical data were gathered from clinical records, including the presenting signs and symptoms, imaging features, ANCA status, final orbital diagnosis, evidence of systemic involvement, treatment, and follow-up

Results

Complete clinical and pathologic records were available for 247 patients undergoing biopsy for orbital inflammation, for whom imaging was available in 165 (67%). Thirty-seven patients (15%) had a final diagnosis of GPA; of the 210 patients without GPA, the final diagnosis was idiopathic orbital inflammatory disease (n = 70; 33%), dacryoadenitis (n = 33; 16%), sarcoidosis (n = 19; 9%), lymphoid hyperplasia (n = 11; 5%), atypical thyroid eye disease (n = 11; 5%), lymphoma (n = 7; 3%), and various

Discussion

Granulomatosis with polyangiitis often is a multisystem disorder that can affect almost any organ, although localized disease without renal involvement has been recognized as a distinct subtype, and, more recently, there has been recognition of disease restricted to the eye and periocular tissues.13, 15, 20, 21 Orbital involvement is uncommon but can lead to devastating complications with reduced orbital functions, visual loss, and facial deformity. The clinical features of orbital disease are

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To report a unique case of orbital inflammatory disease which was ultimately diagnosed as granulomatosis with polyangitis (GPA) and thus successfully treated.
A 47 year-old man presented with a rapidly progressive necrotic soft tissue mass within the medial antero-superior aspect of the right eyelid and orbit. He also had transient retinal vasculitis in the left. Serology, histology and imaging were atypical of, but consistent with, GPA. He was thus successfully treated with intravenous rituximab followed by reconstruction of the medial eyelid.
A high index of suspicion of GPA is required in orbital inflammatory disease, especially when typical diagnostic findings are absent.
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Orbital disorders usually manifest with a unifying constellation of symptoms and signs that include proptosis, periocular swelling, blurred vision, and double vision. The presence of proptosis distinguishes diseases of the orbit from other neuro-ophthalmic conditions with similar symptomatology. In this chapter, relevant orbital anatomy and typical signs and symptoms encountered in orbital disease are put into clinical context; the advantages and disadvantages of various orbital imaging techniques are critically examined; and the orbital entities frequently encountered in neuro-ophthalmic practice are analyzed, including thyroid-associated ophthalmopathy, orbital inflammatory disorders, orbital tumors, and the sequelae of orbital infections and trauma. The pathogenesis, evaluation, and treatment of each orbital disorder are reviewed with particular emphasis on those conditions that can be vision- or life-threatening.
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Mujer de 43 años, consulta por aumento de volumen orbitario superolateral izquierdo, doloroso, eritematoso de 2 meses de evolución. Se realiza biopsia escisional revelando vasculitis con poliangeítis de glándula lagrimal. El estudio sistémico no reveló compromiso de otros órganos.
El compromiso orbitario ocurre hasta en el 60% de los pacientes con granulomatosis con poliangeítis. La afección de la glándula lagrimal es rara, y frecuentemente unilateral. Las pruebas serológicas generalmente son negativas, tanto en etapas iniciales, como en las formas localizadas de la enfermedad.
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Citation Excerpt :
The lack of storiform fibrosis and/or obliterative fibrosis together with the relative paucity of IgG4+ lymphocytes was insufficient to render a diagnosis of IgG4-related disease, although strict criteria for orbital IgG4-related disease remain to be established.2,11 The diagnosis of granulomatosis with polyangiitis, formerly Wegener granulomatosis, was excluded due to the lack of vasculitis, necrosis, or granulomatous inflammation.28,42,63 The pathological diagnosis was IOI (idiopathic inflammatory pseudotumor) involving orbital fibroadipose tissue, bone fragments, and sinus mucosa.
Idiopathic orbital inflammation developed in the right orbit of a woman in her mid-thirties, causing tearing, photophobia, diplopia, altered depth perception, proptosis, and pain on eye movements. Computed tomography disclosed a mass involving the intraconal and extraconal nasal right orbit, extending to the orbital apex with anterior displacement of the globe, effacement of the medial rectus muscle, portions of the fat plane, and the superior oblique muscle, and bone destruction with extension of the mass through the orbital floor into the superior maxillary sinus and through the lamina papyracea into the ethmoid sinus. Orbital biopsy disclosed dense fibrous connective tissue with numerous lymphocytes and macrophages. Immunohistochemical stains supported a diagnosis of idiopathic inflammatory pseudotumor involving the orbit and sinus mucosa. Treatment with a prednisone taper and a retrobulbar injection of triamcinolone acetonide have relieved her symptoms and diminished her proptosis. This patient highlights the rare potential of idiopathic orbital inflammation to erode though bone into adjacent cranial structures.
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It is important to remember that GPA comes in 2 flavors–a systemic disease and a more localized, sino-orbital form. A positive c-ANCA is noted in only <45% of patients with sino-orbital GPA.21,24,26 Regardless of the serologic results, biopsy is required in this patient and, because the possibility of rhabdomyosarcoma still looms large, it should be obtained quickly.
A 10-year-old child presented with right eyelid swelling and a palpable orbital mass. Diagnostic evaluation with the aid of excisional biopsy revealed a pseudoencapsulated mass associated with high levels of serum perinuclear antineutrophil cytoplasmic antibodies. Family history of rheumatic diseases, response to treatment with corticosteroids and immunosuppressant drugs, and clinical and histopathologic features suggested an orbital autoimmune response in which perinuclear antineutrophil cytoplasmic antibodies were detected, and a diagnosis of probable IgG4-related disease was made.
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: Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

: Funding: G.E.R. receives some funding from the National Institute of Health Research (NIHR) Biomedical Research Centre at Moorfields Eye Hospital, NHS Foundation Trust, and UCL Institute of Ophthalmology. C.D.P. receives support from the Imperial NIHR Biomedical Research Centre. The sponsor or funding organization had no role in the design or conduct of this research.

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Original articleClinical and Imaging Features Predictive of Orbital Granulomatosis with Polyangiitis and the Risk of Systemic Involvement

Objective

Design

Participants

Methods

Main Outcome Measures

Results

Conclusions

Section snippets

Methods

Results

Discussion

Am J Med

Am J Med

Ophthalmology

Ophthalmology

Auris Nasus Larynx

Ophthalmology

2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides

Arthritis Rheum

Granulomatosis with polyangiitis (Wegener's): an alternative name for Wegener's granulomatosis

Arthritis Rheum

Wegener's granulomatosis: pathology and review of the literature

AMA Arch Pathol

Uber eine eigenartige rhinogene Granulomatose mit besonderer Beteiligung des Arteriensystems under Nieren

Beitr Pathol Anat

Prevalence and incidence of Wegener's granulomatosis in the UK general practice research database

Arthritis Rheum

Epidemiology of Wegener's granulomatosis in northern Norway

Arthritis Rheum

A staged approach to the treatment of Wegener's granulomatosis: induction of remission with glucocorticoids and daily cyclophosphamide switching to methotrexate for remission maintenance

Arthritis Rheum

Update on the treatment of granulomatosis with polyangiitis (Wegener's)

Curr Treat Options Cardiovasc Med

Classical versus non-renal Wegener's granulomatosis

Q J Med

Orbital Wegener granulomatosis without systemic findings

Ophthal Plast Reconstr Surg

Localised Wegener's granulomatosis in otolaryngology: a review of six cases

ORL J Otorhinolaryngol Relat Spec

Histopathological features predictive of a clinical diagnosis of ophthalmic granulomatosis with polyangiitis (GPA)

Int J Clin Exp Pathol

Diagnosis of limited ophthalmic Wegener granulomatosis: distinctive pathologic features with ANCA test confirmation

Int Ophthalmol

The role of antineutrophil cytoplasmic antibody (c-ANCA) testing in the diagnosis of Wegener granulomatosis: a literature review and meta-analysis

Ann Intern Med

Original article
Clinical and Imaging Features Predictive of Orbital Granulomatosis with Polyangiitis and the Risk of Systemic Involvement