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International Journal of Case Reports and Images (IJCRI)International Journal of Case Reports and Images (IJCRI) is an international, peer reviewed, monthly, open access, online journal, publishing high-quality, articles in all areas of basic medical sciences and clinical specialties.

Aim of IJCRI is to encourage the publication of new information by providing a platform for reporting of unique, unusual and rare cases which enhance understanding of disease process, its diagnosis, management and clinico-pathologic correlations.

IJCRI publishes Review Articles, Case Series, Case Reports, Case in Images, Clinical Images and Letters to Editor.

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Bilateral necrotizing scleritis isolated in patients with granulomatosis with polyangiitis and p-ANCA positivity

Anita Syla Lokaj, Blerta Rama, Ylfete Retkoceri

ABSTRACT

Introduction: Granulomatosis with polyangiitis (GPA) is a rare systemic disease of unknown etiology characterized with tissue granulomatous inflammation and vasculitis. The affected sites are the upper and lower respiratory system, skin, eyes, nervous system, kidney and rarely other organs. The disease exists in two forms; milder, regional located form (limited) and severe, progressive with renal involvement form (generalized). Case Report: In this study, we represent a case of bilateral necrotizing isolated scleritis, where we had difficulties to diagnose GPA with only p-ANCA positive titrate and negative c-ANCA titrate. His c-ANCA was negative whereas p-ANCA (seen in 5% of cases) was positive. The scleral biopsy revealed histology suggestive of granulomatosis with polyangiitis. He responded well with steroid and cyclophosphamide therapy with great caution because he had diabetes mellitus. Conclusion: In cases with few organ involvements or no active disease as showed in our case, where only scleritis is present and high suspicion of 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.

(This page in not part of the published article.)

International Journal of Case Reports and Images, Vol. 7 No. 8, August 2016. ISSN – [0976-3198]

Int J Case Rep Images 2016;7(8):559–562. www.ijcasereportsandimages.com

Lokaj et al. 559

CASE REPORT OPEN ACCESS

Bilateral necrotizing scleritis isolated in patients with granulomatosis with polyangiitis and p-ANCA positivity

Anita Syla Lokaj, Blerta Rama, Ylfete Retkoceri

AbstrAct

Introduction: Granulomatosis with polyangiitis (GPA) is a rare systemic disease of unknown etiology characterized with tissue granulomatous inflammation and vasculitis. the affected sites are the upper and lower respiratory system, skin, eyes, nervous system, kidney and rarely other organs. the disease exists in two forms; milder, regional located form (limited) and severe, progressive with renal involvement form (generalized). case report: In this study, we represent a case of bilateral necrotizing isolated scleritis, where we had difficulties to diagnose GPA with only p-ANcA positive titrate and negative c-ANcA titrate. His c-ANcA was negative whereas p-ANcA (seen in 5% of cases) was positive. the scleral biopsy revealed histology suggestive of granulomatosis with polyangiitis. He responded well with steroid and cyclophosphamide therapy with great caution because he had diabetes mellitus. conclusion: In cases with few organ involvements or no active disease as showed in our case, where only scleritis is present and high suspicion of 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.

Anita Syla Lokaj1, Blerta Rama1, Ylfete Retkoceri1

Affiliations: 1Eye Clinic, University Clinical Center of Kosovo, Pristina.Corresponding Author: Anita Syla Lokaj, Prishtina, Postal Code: 10000, Republic of Kosovo; Email: anitasylaj@live.com

Received: 15 April 2016Accepted: 08 June 2016Published: 01 August 2016

Keywords: bilateral necrotizing scleritis, Granu-lomatosis, p-ANcA, Polyangiitis

How to cite this article

Lokaj AS, Rama B, Retkoceri Y. Bilateral necrotizing scleritis isolated in patients with granulomatosis with polyangiitis and p-ANCA positivity. Int J Case Rep Images 2016;7(8):559–562.

Article ID: Z01201608CR10688AL

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doi:10.5348/ijcri-2016100-CR-10688

INtrODUctION

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].

CASE REPORT PEER REviEwEd | OPEN ACCESS

International Journal of Case Reports and Images, Vol. 7 No. 8, August 2016. ISSN – [0976-3198]

Int J Case Rep Images 2016;7(8):559–562. www.ijcasereportsandimages.com

Lokaj et al. 560

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.

cAsE rEPOrt

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.

DIscUssION

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.

cONcLUsION

In cases with fewer organ involvements or no active disease as is in our case where only scleritis is present

Figure 1: Right eye showing sclera thinning in upper quadrant with visible uveal tissue and without peripheral corneal thinning. Note the avascular area of sclera.

Figure 2: Left eye showing sclera thinning in upper nasal (correct nasal).

International Journal of Case Reports and Images, Vol. 7 No. 8, August 2016. ISSN – [0976-3198]

Int J Case Rep Images 2016;7(8):559–562. www.ijcasereportsandimages.com

Lokaj et al. 561

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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Author contributionsAnita Syla Lokaj – Substantial contributions to conception and design, Acquisition of data, Analysis and interpretation of data, Drafting the article, Revising it critically for important intellectual content, Final approval of the version to be publishedBlerta Rama – Analysis and interpretation of data, Revising it critically for important intellectual content, Final approval of the version to be publishedYlfete Retkoceri – Analysis and interpretation of data, Revising it critically for important intellectual content, Final approval of the version to be published

GuarantorThe corresponding author is the guarantor of submission.

conflict of InterestAuthors declare no conflict of interest.

copyright© 2016 Anita Syla Lokaj et al. This article is distributed under the terms of Creative Commons Attribution License which permits unrestricted use, distribution and reproduction in any medium provided the original author(s) and original publisher are properly credited. Please see the copyright policy on the journal website for more information.

rEFErENcEs

1. Martinez F, Chung JH, Digumarthy SR, et al. Common and uncommon manifestations of Wegener granulomatosis at chest CT: radiologic-pathologic correlation. Radiographics 2012 Jan-Feb;32(1):51–69.

2. Pakrou N, Selva D, Leibovitch I. Wegener’s granulomatosis: ophthalmic manifestations and management. Semin Arthritis Rheum 2006 Apr;35(5):284–92.

3. Hattar K, Bickenbach A, Csernok E, et al. Wegener’s granulomatosis: antiproteinase 3 antibodies induce monocyte cytokine and prostanoid release-role of autocrine cell activation. J Leukoc Biol 2002 Jun;71(6):996–1004.

4. https://en.wikipedia.org/w/index.php?title=P-ANCA&oldid=688569689

5. Seo P, Stone JH. The antineutrophil cytoplasmic antibody-associated vasculitides. Am J Med 2004 Jul 1;117(1):39–50.

6. Agarwal PK, Gogia A. Limited Wegener’s granulomatosis with p-ANCA positivity. JIACM 2004;5(4):348–50.

7. Haynes BF, Fishman ML, Fauci AS, Wolff SM. The ocular manifestations of Wegener’s granulomatosis. Fifteen years experience and review of the literature. Am J Med 1977 Jul;63(1):131–41.

8. Harper SL, Letko E, Samson CM, et al. Wegener’s granulomatosis: the relationship between ocular and systemic disease. J Rheumatol 2001 May;28(5):1025–32.

9. Foster CS, Forstot SL, Wilson LA. Mortality rate in rheumatoid arthritis patients developing necrotizing scleritis or peripheral ulcerative keratitis. Effects of systemic immunosuppression. Ophthalmology 1984 Oct;91(10):1253–63.

10. Galperin C, Hoffman GS. Antineutrophil cytoplasmic antibodies in Wegener’s granulomatosis and other diseases: clinical issues. Cleve Clin J Med 1994 Nov-Dec;61(6):416–27.

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International Journal of Case Reports and Images, Vol. 7 No. 8, August 2016. ISSN – [0976-3198]

Int J Case Rep Images 2016;7(8):559–562. www.ijcasereportsandimages.com

Lokaj et al. 562

ABOuT THE AuTHORS

Article citation: Lokaj AS, Rama B, Retkoceri Y. Bilateral necrotizing scleritis isolated in patients with Granulomatosis with polyangiitis and p-ANCA positivity. Int J Case Rep Images 2016;7(8):559–562.

Anita syla Lokaj is Ophthalmologist at university Center Clinic of Kosova. She is a represantitve of young ophthalmologist from Kosova at SOE group. Her field of interests are anterior segment disease.Actually i am PhD candidate.E-mail: anitasylaj@live.com

blerta rama is resident in Ophthalmology in university Clinic Center of Kosovo in Pristina. She is an assistant in Occupational Medicine in Medical university of Pristina. She earned the degree Doctor of Medicine in Faculty of Medicine in university of Pristina. She intends to pursue fellowship in Ophthalmology after completing her residency.E-mail: b_rameka86@yahoo.com

Ylfete retkoceri, Eye Clinic, university Clinical Center of Kosovo, Pristina. She is Imonologist at university Center Clinic in Kosova.

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