6.1.10.2Clinical Manifestations

Pulmonary inÞltrates and sinusitis are the two most common presenting signs of GPA [337]. Arthralgias or arthritis, fever, otitis (usually related to eustachian tube obstruction), cough, and (less frequently) functional renal impairment also may be presenting manifestations. Malaise, fatigue, fever, and weight loss are characteristic of the onset of active or generalized GPA.

Over the course of GPA, lower respiratory tract or upper airway abnormalities (sinusitis, hemorrhagic rhinitis, nasal mucosal ulcerations, and otitis media) are the most common manifestations. Characteristic lower respiratory tract symptoms are cough, hemoptysis, dyspnea, and (less often) pleuritic pain. Chest X-ray Þndings show multiple, bilateral nodal inÞltrates with a tendency toward cavitation, as well as evanescent areas of atelectasis. Pleural effusions and subglottal stenosis of the airway also may occur, but hilar adenopathy is rare [337]. Nasal septal perforation and loss of supporting nasal structures may lead to the characteristic saddle nose deformity. Secondary infections, almost invariably caused by Staphylococcus aureus, often complicate upper airway abnormalities.

Renal disease, the second most common manifestation, usually occurs after upper and lower airway manifestations. It may range from mild, focal, and segmental glomerulonephritis, with minimal urinary sediment Þnding or functional impairment, to fulminant, diffuse, necrotizing glomerulonephritis, with proliferative and crescentic changes. Renal disease, once present, may progress rapidly and is associated with poor prognosis [341].

Other manifestations include arthralgias and nondeforming arthritis; skin lesions, such as papules, vesicles, palpable purpura, ulcers, and subcutaneous nodules; neurological abnormalities, such as peripheral neuropathy (mononeuritis multiplex) or cranial nerve palsies; and cardiac involvement, such as acute pericarditis and dilated congestive cardiomyopathy [337].

6.1.10.3Ocular Manifestations

Ocular manifestations occur in 29Ð58% of GPA patients [337, 342Ð344]. They can be divided into two categories: contiguous and focal [344].

Contiguous ocular manifestations, such as severe orbital pseudotumor, orbital abcess or cellulitis, or nasolacrimal duct obstruction, occur as a result of the extension of contiguous granulomatous sinusitis of long duration. Orbital inßammation with proptosis is the most common ocular manifestation in GPA [342Ð344]. Focal ocular disease in GPA is unrelated to any upper airway disease; it is characterized by a focal vasculitis of the anterior and/or posterior segments of the eye and possibly the orbit. Of the focal ocular manifestations of GPA, conjunctivitis, scleritis, episcleritis, and keratitis are the most common [342Ð344]. Ischemic optic neuropathy and retinal artery occlusion are other types of focal eye involvement that can occur in GPA. Uveitis [342Ð344], chorioretinal ischemia and infarction [345], and KCS [346] may occasionally occur. Although most patients with complete or limited GPA present with upper and lower airway symptoms, ocular involvement also may be the Þrst sign prompting patients to seek medical attention [203, 337, 342, 343, 347]. In the highly limited form of GPA, ocular or orbital involvement is the only objective Þnding of the condition [338]. The ophthalmologist may be the Þrst to diagnose GPA.

Scleritis

The reported incidence of GPA in patients with scleritis ranges from 3.79 to 8% [123, 124]. Conversely, the reported incidence of scleritis in patients with GPA ranges from 7 to 11% [341Ð 343]. The scleritis may be diffuse, nodular, or necrotizing. Necrotizing scleritis and PUK are the most malignant ocular manifestations of GPA; they can result in ocular perforation, leading to blindness, and possibly loss of the eye [242]. Corneal ulceration, exactly like that seen in RA or PAN, develops after breakdown of the peripheral corneal epithelium and progresses centrally and circumferentially, producing an overhanging lip of the cornea; the biomicroscopic appearance is similar to that of MoorenÕs ulcer, except that sclera is never involved in the latter. Patients with complete, limited, or highly limited forms of GPA may have scleritis at the time of the initial medical examination [203, 334, 338, 343, 344, 348Ð350].. Scleritis often parallels systemic