Granulomatosis with polyangiitis is a systemic disease involving granulomatous inflammation, necrosis and vasculitis that most frequently targets the upper respiratory system, the lower respiratory system and kidney [1]. As systemic disease, it can affect other systems like musculoskeletal system, skin, eyes and others. Therefore, granulomatosis with polyangiitis can cause a lot of ocular manifestation with different management approaches [2].

Determination of the specific antibodies can aid the diagnosis. Anti-neutrophil cytoplasmic antibodies (c-ANCA), which act against serine proteinase 3, are relatively sensitive and highly specific for granulomatosis with polyangiitis [3]. The perinuclear anti-neutrophilic cytoplasmic antibodies (p-ANCA), which act against myeloperoxidase, are not specific for any kind of vasculitis, but are found in some patients with GPA and other diseases [4].

ANCA associated diseases can be difficult to diagnose and treat [5], especially in cases with only p-ANCA positive titrate [6].

In this study, we represent a case of isolated bilateral necrotizing scleritis where we had difficulties to diagnose GPA with only p-ANCA positive titrate and negative c-ANCA titrate.

We report a case of 75-year-old male who presented to us with a history of episcleritis in his eyes for two months. He complained of some discomfort and pain in eyes and forehead. He gave a history of hypertension and diabetes mellitus which were controlled by medication therapy. On examination his visual acuity was nearly normal. There was mild congestion of conjunctiva in upper nasal quadrant. Sclera thinning in upper nasal quadrant with visible uveal tissue and no signs of inflammation was noted. He had very large patches of true scleritis in right eye and three small patches in left eye. Anterior chamber, iris, pupil and lens were normal. Applanation tension (intraocular pressure) was 16 mmHg. Ocular movements were normal. Dilated fundus examination was with normal limits.

Investigation revealed moderate ESR (60 mm/hr), red blood cell in normal range as well as white blood cell and platelets, negative rheumatoid factor, negative antinuclear antibodies, C3 and C4 complement were in normal value, negative cytoplasm staining pattern (c-ANCA) and positive p-ANCA. Anti-neutrophil cytoplasm antibody was performed by an enzyme-linked immunosorbent assay (ELISA) for the presence of anti-MPO antibodies. Chest X-ray was normal. Renal function was normal as assessed by urea, electrolytes and creatinine levels. At the end, we did sclera biopsy of left eye to verify the extra diagnosis and results were positive for GPA. Pathologically, scleral biopsy showed multinucleated giant cells. Perivascular was seen with epithelioid cells surrounding vessels. Blood vessels within sclera shows an intense inflammatory infiltrate with destruction of the blood vessels wall. Also in biopsy was collagen necrosis that suggested an aggressive ischemic process.

The patient was started on oral prednisolone (initial dose 40 mg/day), which were not effective to improve scleral inflammation. Therefore, we decided to start with A, oral cyclophosphamide (150 mg/day). Within 4–6 weeks, the scleral inflammation had subsided and the ANCA titers had become negative. After a follow-up of 18 months the scleritis remains on remission on a combination of cyclophosphamide (75 mg/day) and prednisolone (7.5 mg/day). So far, there was no evidence of extra ocular involvement. Serial ANCA titers remained negative.

Granulomatosis with polyangiitis (GPA) may be in classic or limited form and ocular sign as scleritis, proptosis, corneal ulceration may be the major component of GPA [7]. In cases with bilateral scleritis, in addition to GPA, rheumatoid arthritis, ANCA-associated vasculitis associated scleritis as microscopic polyangiitis, polyarteritis nodosa, relapsing polychondritis, Churg-Strauss syndrome must also be taken into consideration. This is because they are associated with scleritis but the limited form is very rare in these diseases. In our case, peripheral ulcerative thinning, keratitis, uveitis, ischemic optic neuropathy, retinal artery occlusion were not present, even though they usually accompany this diseases. Scleritis in patients with GPA has a rate between 16–38%. Necrotizing scleritis can be manifested with other systemic disease, but in GPA it may be present and it has a great mortality rate if the patient are not undergoing immunosuppressive therapy [8] [9].

The presence of cytoplasmic ANCA in a patient who is suspected to have Wegener's granulomatosis is strong circumstantial evidence in support of that diagnosis. However, it does not represent absolute proof and should be viewed with skepticism if the clinical presentation is atypical [10], because its implication was in other disease.

In cases with fewer organ involvements or no active disease as is in our case where only scleritis is present and there is high suspicion of Granulomatosis with polyangiitis (GPA) clinically, a biopsy of organ with active disease is mandatory, as diagnosis cannot be made only on the presence of ANCA and signs of scleritis.

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