symptoms and may be the initial manifestation of a systemic disease exacerbation [342, 351]. Necrotizing scleritis may appear after surgical trauma of the sclera.

In our series of 500 patients with scleritis, 14 patients had GPA (2.8%). Two patients had complete GPA, ten patients had limited GPA, and two patients had highly limited GPA. The mean age of our patients was 55 years (range, 31Ð86 years) and the scleritis was more common in females than in males (nine females and Þve males). In seven patients, the presence of scleritis was the Þrst manifestation whose study led to the diagnosis of GPA; the mean time between the onset of scleritis and diagnosis of GPA was 8.5 months. The scleritis attacks were persistent or recurrent, and often related to episodes of active disease. Necrotizing anterior scleritis was present in three patients and diffuse anterior scleritis was present in 11 patients. PUK was present in 5 of 14 patients (36%) with scleritis; three patients had necrotizing anterior scleritis and two patients had diffuse anterior scleritis. Anterior uveitis was present in 3 of 14 patients (21.4%) with scleritis. Keratitis, uveitis, glaucoma, cataract, and disk edema caused by scleral inßammation may affect visual acuity. A decrease in visual acuity (equal to or greater than two Snellen lines at the end of the follow-up period or vision equal to or worse than 20/80 at the Þrst examination) occurred in 36% of the patients.

Episcleritis

Episcleritis may occur in GPA but is less frequent than scleritis [342, 344]. It may be simple or nodular and often is recurrent. Episcleritis in GPA may be the Þrst manifestation that prompts the patient to seek medical advice [342]. In our series of 85 patients with episcleritis, there was one patient with GPA (1.18%). The patient was a 50-year-old man with complete GPA who developed recurrent simple episcleritis soon after the diagnosis of GPA.

6.1.10.4 Laboratory Findings

Normochromic normocytic anemia, leukocytosis, thrombocytosis, an elevated ESR, mild hypergammaglobulinemia (particularly of the IgA class), mildly elevated rheumatoid factor, elevated CRP, and CICs are common nonspeciÞc

abnormalities found in patients with GPA. Thrombocytosis may be seen as an acute-phase reactant. It was in 1985 that the presence of ANCA in serum was found to be speciÞc for WG and to correlate with disease activity [352]. Subsequent studies conÞrmed that ANCA is indeed speciÞc for GPA [340, 353, 354], with speciÞcity as high as 99% by indirect immunoßuorescence techniques and 98% by ELISA detection [340]. The sensitivity of ANCA depends on disease activity and extent: sensitivity is 32% for GPA patients in full remission after limited disease, 67% for GPA patients with active limited disease, and 96% for GPA patients with active generalized disease. These Þndings indicate that a negative ANCA test does not rule out a diagnosis of GPA. ÒFalse-positiveÓ ANCA titers have been found in only 0.6% of patients, all of whom have glomerulonephritis, pulmonaryÐrenal syndrome, or vasculitis [340]. Although still pending conÞrmation, relapses of GPA seem to be preceded by elevation of ANCA titers.

At least two types of ANCA staining of neutrophils may occur. The classic granular cytoplasmic staining pattern (C-ANCA) is speciÞc for myeloblastin, a neutrophil serine protease referred to as PR-3 [355, 356]. C-ANCA is highly speciÞc for GPA [338, 339], but not all patients positive for C-ANCA fullÞl the classic criteria for GPA [357]. A perinuclear staining pattern (P-ANCA) is speciÞc for various lysosomal enzymes, such as myeloperoxidase, cathepsin G, human leukocyte elastase, or lactoferrin. P-ANCA is a speciÞc marker of idiopathic necrotizing and crescentic glomerulonephritis, a disease frequently associated with microscopic polyarteritis and occasionally with GPA [355]. The absence of granulomata helps to distinguish microscopic polyarteritis from GPA, athough the clinical picture is similar. It would seem that GPA, microscopic polyarteritis, and idiopathic necrotizing and crescentic glomerulonephritis are part of the spectrum of one disease process. Although C-ANCA is typically the ANCA associated with GPA [357, 358], there are cases that fullÞl the classic criteria for GPA and show the P-ANCA pattern of staining [359].

The ANCA test must be included in the diagnostic evaluation of patients with ophthalmic