The vasculitides represent type III hypersensitivity reactions to circulating immune complexes leading to infiltration of vessel walls by inflammatory cells. Orbital involvement usually leads to significant morbidity and is typically associated with systemic vasculitis. The following discussion focuses mainly on the orbital manifestations of the vasculitides. See also BCSC Section 1, Update on General Medicine; Section 5, Neuro-Ophthalmology; and Section 9, Uveitis and Ocular Inflammation.
Giant cell arteritis
Although it is not typically thought of as an orbital disorder, giant cell arteritis (GCA; also called temporal arteritis) involves inflammation of the orbital vessels. The vasculitis affects the aorta, vertebral arteries, and branches of the external and internal carotid arteries; however, it typically spares the intracranial carotid artery branches, which lack an elastic lamina. Vision loss may occur from central retinal artery occlusion or ischemic optic neuropathy, and diplopia may result from ischemic dysfunction of associated cranial nerves. Systemic manifestations include headache, scalp tenderness, jaw claudication, and constitutional symptoms.
The combined sensitivity of erythrocyte sedimentation rate (ESR) and C-reactive protein testing may be as high as 99%, and thrombocytosis (platelet count) greater than 400 × 103 μL supports the diagnosis. However, temporal artery biopsy represents the gold standard for diagnosis (Video 4-1). Biopsies may contain intervals of normal tissue between affected segments, and discordant biopsy may occur after bilateral biopsy. For these reasons, bilateral biopsy and longer specimens have been advocated by some; however, no consensus exists.
Temporal artery biopsy. Courtesy of Julian D. Perry, MD, and Alexander D. Blandford, MD.
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Because serologic testing may be negative in some cases, and because devastating progression may occur without treatment, administration of high-dose corticosteroids should begin as soon as possible when GCA is suspected. Tocilizumab, a monoclonal interleukin-6 receptor antibody, can induce and maintain remission with a shorter corticosteroid taper. Risks associated with biopsy include scarring, hemorrhage, and cranial nerve VII frontal branch injury that produces paralytic lagophthalmos or brow ptosis, especially if nerve injury occurs proximal to its course over the zygoma.
Stone JH, Tuckwell K, Dimonaco S, et al. Trial of tocilizumab in giant-cell arteritis. N Engl J Med. 2017;377(4):317–328.
Granulomatosis with polyangiitis
Granulomatosis with polyangiitis (GPA, formerly known as Wegener granulomatosis), is a multisystem disease characterized by necrotizing granulomatous inflammation and vasculitis of small-to medium-sized vessels. Although the disease often affects the respiratory and renal systems, it can affect any body site. Orbital involvement occurs in 45%–60% of patients with GPA and represents the most common ophthalmologic manifestation of the disease.
GPA typically presents clinically as either a systemic and generalized disease or in a more limited form. The generalized form may produce sinusitis with or without bone erosion, tracheobronchial necrotic and stenotic lesions, cavitary lung lesions, and glomerulonephritis (Fig 4-14). It is unclear whether the limited form of the disease represents a distinct clinical entity or is just a subtype of the general form. Either form can extend from the surrounding sinuses to involve the orbit and nasolacrimal drainage system, but the limited form causes approximately two-thirds of orbital GPA cases.
Histologic examination, especially in cases of isolated orbital involvement, may not always show the classic triad of vasculitis, granulomatous inflammation (with or without giant cells), and tissue necrosis. Often, only 1 or 2 of these findings are present on extrapulmonary biopsies.
Although their exact pathogenic role remains unclear, antineutrophil cytoplasmic autoantibodies (ANCAs) are strongly associated with certain vasculitides, including GPA. Testing for ANCAs distinguishes 2 types of immunofluorescence patterns.
Diffuse granular fluorescence within the cytoplasm (c-ANCA) is highly specific for GPA. This pattern is caused by autoantibodies directed against proteinase-3, which can then be measured by enzyme-linked immunosorbent assay (ELISA).
Fluorescence surrounding the nucleus (p-ANCA) is an artifact of ethanol fixation and can be caused by autoantibodies against many different target antigens. This finding is therefore nonspecific and needs to be confirmed by ELISA for ANCA reacting with myeloperoxidase (MPO-ANCA). MPO-ANCA testing has moderate specificity for smallvessel vasculitis but may return a positive result in patients with nonvasculitic diseases such as rheumatoid arthritis, sarcoidosis, or systemic lupus erythematosus.
Figure 4-14 Granulomatosis with polyangiitis (GPA). A, Photograph of a patient with restrictive strabismus of the left eye due to inflammatory tissue extending into the medial aspects of the orbit. B, Coronal CT scan shows extensive destruction of the nasal and sinus cavities with inflammatory tissue extending into orbits and brain (arrow). C, CT of chest shows cavitary lung lesions (arrow).
(Courtesy of Jeffrey A. Nerad, MD.)
Although highly specific for GPA, c-ANCA tests possess less sensitivity, especially in cases of isolated sino-orbital GPA and in inactive disease. Unlike c-ANCA–positive disease, p-ANCA–positive disease rarely affects the eye and orbit. Absolute levels of ANCA do not define disease severity or activity, and the use of titers to monitor for response to therapy, remission, and relapse remains controversial.
Treatment of GPA relies on remission-induction therapy, often using cytotoxic agents (eg, cyclophosphamide) and corticosteroids, followed by remission-maintenance therapy, often using methotrexate, azathioprine, and corticosteroids. Long-term treatment with TMP-SMX appears to suppress disease activity in some patients, and rituximab may help induce remission, although relapses are common regardless of treatment. Patients require care coordination from a rheumatologist, because both GPA and its treatment can produce life-threatening effects.
Polyarteritis nodosa (PAN) is a multisystem disease in which small- and medium-sized arteries are affected by inflammation characterized by the presence of neutrophils and eosinophils, with necrosis of the muscularis layer. Although PAN may affect multiple organ systems, the disease rarely produces orbital inflammation. Ophthalmic manifestations more commonly result from retinal and choroidal infarction.
Excerpted from BCSC 2020-2021 series: Section 10 - Glaucoma. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.