Granulomatosis with polyangiitis (Wegener’s) is a multiorgan system disease of unknown etiology characterized by granulomatous inflammation, tissue necrosis, and variable degrees of vasculitis in small- and medium-sized blood vessels. Although initially described by Klinger in 1931 [6], it was recognized as a definitive entity after Friedrich Wegener reported three patients in 1939 [7].

GPA is a disease of unknown etiology primarily involving the upper and lower respiratory tracts and the kidneys, which, if untreated, has major organ- and life-threatening consequences. The incidence is estimated to be four to eight per million population [8] with prevalence estimated to be 30 per million population in the United States [9]. Typically seen in Caucasian men in the fourth to fifth decade, without any specific gender predilection, it may present as a classic disseminated or rarely in the limited form. The limited form of the disease is more commonly seen in women [10] and in Asians. Less than 15 % of the disease is seen in children. It may present either to the general physician or to the ophthalmologist with acute to subacute symptoms either partially or completely unresponsive to conventional and symptomatic management. In most cases, antineutrophil cytoplasmic antibodies (ANCAs) against proteinase-3 (PR-3) [11] are thought to result in neutrophilic and eosinophilic vascular and perivascular infiltration with resultant narrowing, ischemia, and damage of the organs affected [12]. The clinical spectrum of organ systems involved in GPA is summarized in Fig. 6.4. Classic disseminated GPA, characterized by a triad of upper and lower respiratory tract involvement and glomerulonephritis, may present either as an acute rapidly progressive disease or rarely a chronic disease. Upper respiratory tract involvement is manifested by sinusitis, epistaxis, and nasal bone destruction with adjacent orbital involvement. Lower respiratory tract involvement is manifested by respiratory tract ulceration and pneumonitis. Renal failure from rapidly progressive glomerulonephritis is not uncommon in untreated cases. Extrapulmonary lesions may affect the skin, joint, heart, and the eyes.

A limited form is commonly seen in females with a less severe clinical course associated with upper and lower respiratory system involved, thus resulting in delayed or missed diagnosis [13]. Significant differences between the acute, systemic form and an insidious limited form of the disease are shown in Table 6.1.

Ophthalmic involvement is seen in about 50 % of all cases. Ocular manifestations are frequently bilateral and may be protean, thus making diagnosis difficult with delayed and resultant morbidity, especially when clinical suspicion is low. Left untreated, potential blinding complications include severe necrotizing scleritis (Fig. 6.5), peripheral ulcerative keratitis with corneal perforation [14], retinal vasculitis resulting in retinal arterial occlusion, and orbital inflammatory mass with optic nerve ischemia. Orbital involvement may be either primary [15–21] or more commonly as a result of disease spread from the adjacent paranasal sinuses (Fig. 6.6a,b) or nasopharynx. Rarely fibrotic changes as a result of chronic inflammation may result in socket contracture and enophthalmos (Fig. 6.7) [22]. In fact, owing to the involvement of the nasolacrimal duct drainage pathway secondary to nasal obstruction, it is one of the very few orbital inflammatory diseases that may present as a wet, rather than a dry eye. Common ocular and ocular adnexal manifestations are summarized in Table 6.2 (see also Fig. 6.8). Owing to the severe nature of the disease, the clinical morbidity, and potential mortality, every ophthalmologist should be aware of both the typical and atypical presentations of the disease. Given the protean manifestations, a high degree of suspicion should be maintained in all patients with any of the clinical presentations shown above especially when bilateral and in the right age group. These include prior or concomitant history of nose/sinus/ENT disorder, upper or lower respiratory ailment (Fig. 6.9), partial response to conventional management, and rapidly progressive and debilitating disease [26].

Appropriate laboratory testing (Table 6.3) should be ordered when the clinical suspicion is present, and when possible, a definitive tissue biopsy should be performed. The presence of two or more of the following criteria is associated with a sensitivity of 88.2 % and a specificity of 92 % [27]: