SUCCESFUL TREATMENT OF SURGICALLY INDUCEDNECROTIZING SCLEROKERATITIS (SINS) WITHSYSTEMIC IMMUNOSUPPRESIVE AGENTS AND

AMNIOTIC MEMBRANE GRAFTING

TRATAMIENTO INMUNOSUPRESOR SISTÉMICO Y TRASPLANTEDE MEMBRANA AMNIÓTICA EN ESCLERITIS NECROTIZANTE

INDUCIDA POR CIRUGÍA (ENIC)

CORDERO-COMA M1, FRANCO-BENITO M1, GARCÍA-RUIZ-DE-MORALES JM2, ALONSO-ORCAJO N3, DEL BARRIO-MANSO I4

Received: 10/1/08. Accepted: 4/11/09.Hospital of León. León. Spain.1 Graduate in Medicine. Ophthalmology Service. Uveitis Unit. 2 Ph.D. in Medicine. Immunology Section. Uveitis Unit. 3 Graduate in Medicine. Pathological Anatomy Service. 4 Graduate in Medicine. Ophthalmology Service. Communication presented at the LXXXI Congress of S.E.O. (Zaragoza 2005).

Correspondence:Miguel Cordero-ComaHospital de LeónC/. Altos de Nava, s/n24080 León SpainE-mail: miguelcorderocoma@gmail.com

ABSTRACT

Clinical case: We report the case of a 74-year-oldfemale who developed a necrotizing sclerokeratitisaffecting her left eye after uncomplicated cataractsurgery. She had no previous history of systemicautoimmune disease. Histopathology of the lesionrevealed necrotic granulomatosis with an increasednumber of plasma cells.Discussion: Surgically induced necrotizing scleroke-ratitis (SINS) is a serious entity which requiresprompt and aggressive therapy to prevent its poten-tial devastating ocular consequences. Conjunctivalresection and amniotic membrane grafting may benecessary to temporarily interrupt local immunologicevents in severe cases. However, associated systemicimmunomodulatory therapy seems to be mandatory(Arch Soc Esp Oftalmol 2009; 84: 577-580).

RESUMEN

Caso clínico: Presentamos el caso de una mujer de74 años que desarrolló una escleroqueratitis necro-tizante en su ojo izquierdo tras cirugía de cataratano complicada. No tenía antecedentes de enferme-dad autoinmune sistémica. El análisis histopatoló-gico de la lesión mostró granulomatosis necrotizan-te con abundantes células plasmáticas.Discusión: La escleroqueratitis necrotizante indu-cida por cirugía (ENIC) es una grave afección querequiere tratamiento precoz y agresivo tratando deprevenir sus potencialmente devastadoras conse-cuencias. La resección conjuntival junto conimplante de membrana amniótica pueden ser nece-sarias para interrumpir temporalmente el procesoinmunológico local. No obstante, es esencial aso-ciar un tratamiento inmunosupresor sistémico.

ARCH SOC ESP OFTALMOL 2009; 84: 577-580 SHORT COMMUNICATION

INTRODUCTION

Surgically induced Necrotizing scleritis (SINS) isa rare local self-immune condition which appearsclose to previous surgical incisions. It has been rela-ted with virtually all kinds of ocular surgeries (1-5).SINS develops after a latency period ranging from afew weeks to several years and could be the firstexpression of a self-immune vasculitis. It may alsoindicate the onset of vasculitis in a patient who hasbeen already diagnoses with a self-immune entity(2). Post-surgery infections and the use of specificsuture materials have been identified as potentiallycontributing factors for the development of SINS (3).

CLINICAL CASE

A healthy 74-year old female visits the practicereferred by her ophthalmologist for evaluation andtreatment of painful red eye with approximately onemonth of evolution. She had no antecedents of inte-rest excepting a non-complicated cataracts surgery

(phacoemulsification) in the same eye four monthsearlier. The ophthalmological exploration revealedan elevated injury at the level of the superonasallimbus in her left eye (close to the surgical incision)associated to multiple corneal micro-infiltrates aswell as vascular ingurgitation in the conjunctiva anddeep scleral plexus (fig. 1). Treatment was establis-hed with broad range antibiotic eye drops, addingautologous serum eye drops and medroxiprogeste-rone.

Due to the poor response to treatment, severalserological tests were requested (including bioche-mistry, hemogram, acute phase reactants and self-immunity markers). At the same time, treatmentwas initiated with systemic corticoids at dosages of1 mg/kg. In addition, we decided to take a sclero-conjunctival sample with prior resection of the adja-cent conjunctiva, with subsequent implant ofamniotic membrane (inlay technique) joined to theapplication of biological adhesive (Fibrin Glue®)over the injury area (fig. 2). The biopsy (figs. 3a and3b) was diagnosed as necrotizing granulomatosisassociated to hyperplasia of plasmatic cells without

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CORDERO-COMA M, et al.

Key words: Surgically induced necrotizing scleri-tis, amniotic membrane grafting, immunosuppressi-ve agents, immunomodulation, complications aftercataract surgery, uveitis.

Palabras clave: Escleritis necrotizante inducidapor cirugía (ENIC), trasplante de membrana amnió-tica, agentes inmunosupresores, inmunomodula-ción, complicaciones tras cirugía de catarata, uveí-tis.

Fig. 1: Slit lamp view of LE in first visit. Notice the ele-vated lesion at the level of the superonasal limbus withsuperficial and deep vascular ingurgitation, as well ascorneal microinfiltrates.

Fig. 2: Appearance of the same eye after resection ofadjacent conjunctiva and amniotic membrane implant.Notice the improvement in the previously inflamed areaafter surgery and the worsening of the annex superotem-poral tissue where the inflammatory reaction continues.

traces of vasculitis. The results of the serologicaltests were normal.

Considering the possibility of SINS, it was deci-ded to initiate treatment with Cyclosporin A (3mg/kg/day) together with oral corticosteroids (1mg/kg/day). Notwithstanding the treatment, eightweeks later the inflammation persisted and, due toits severity, it was decided to substitute cyclosporinfor Azatioprin (100 mg/day) maintaining the oralcorticosteroids.

This therapeutic regime was able to graduallycontrol the inflammatory process (figs. 4a and 4b).Seven months after onset, the patient remains freeof symptoms and continues with the treatment.

DISCUSSION

The diagnostic of SINS in the instant case wasmainly based on the following findings:

1) Ocular surgery antecedents.

2) Absence of clinical or serological signs ofsystemic self-immune disease.

3) Development of necrotizing scleritis close tothe previous surgical injury.

We believe that the surgical treatment, althoughpalliative and temporary, is an important adjuvantfor treating these patients. The resection of the con-junctiva adjacent to the injury area has been descri-bed as an efficient technique for diminishing theconcentration of proteases (such as collagenase), aswell as for the temporary interruption of the localinflammatory process, reducing the input of pro-inflammatory cytokines (4). In the instant case, theamniotic membrane contributed to controlling the

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Inmunosupresión e implante de membrana amniótica en ENIC

Fig. 3: (A) Biopsy of resected tissue (Stain with hemato-xiline/eosine, 2X amplification) showing areas of necro-tizing granulomatosis, which can be seen better in image(B) with 10X amplification.

Fig. 4: Slit lamp vision at month 1 and month 3 (figuresA and B respectively) after the introduction of Azatio-prin. Notice the absence of vascular ingurgitation andcorneal infiltrates, as well as the residual thinning of theinvolved sclera.

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inflammation in the area of the implant, althoughthe adjacent areas began to be affected as surgery onits own is unable to halt the underlying systemicimmunological process. Accordingly, it was deci-ded to begin an immunomodulator treatment in anattempt to achieve optimum control over the disea-se and prevent recurrences.

It has been postulated that SINS could be relatedto a localized relative ischemia associated to thesurgical wound (1). In approximately 60% of casesit was possible to identify a pathology causing thecondition, mostly being a connective tissue disease.However, little is known about the immunologicalmechanism inducing its appearance. It has beenspeculated that it could be a T-dependent delayedhyper-sensitivity reaction against certain unidenti-fied tissue antigens (arising out of the surgical trau-ma and/or the temporary ischemia) (1). In thisregard, some authors (5) have obtained encouragingresults utilizing specific T-cell response inhibitingagents such as Tacrolimus. Paradoxically, in ourcase the patient responded positively to Azatioprine(that inhibits T- and B-dependent immunologicalresponses) and not to Cyclosporine A (T-inhibitor).In fact, the biopsy of our patient tissue exhibitedplasmatic cell hyperplasia around the injury area,suggesting a preferential involvement of the B-dependent cellular response. In this sense, although

self-antibodies have not been identified, the presen-ce of immunocomplexes has been identified insome cases (1), reinforcing the hypothesis of aninvolvement of the B-cell response. The fact thatSINS may or may not be a defined clinical entity oronly the first expression or trigger of a self-immuneprocess in some susceptible individuals is still acontroversial topic.

REFERENCES

1. O’Donoghue S, Lightman S, Tuft S, Watson P. Surgicallyinduced necrotising sclerokeratitis (SINS)—precipitatingfactors and response to treatment. Br J Ophthalmol 1992;76: 17-21.

2. Sainz de la Maza M. Scleritis. In: Foster CS, Azar DT,Dohlman CH. Smolin and Thoft´s: The Cornea, ScientificFoundations and Clinical Practice (4th Edition). Philadel-phia: Lippincott Williams & Wilkins, 2005; 559-569.

3. Beatty S, Chawdhary S. Necrotizing sclerokeratitis follo-wing uncomplicated cataract surgery. Acta OphthalmolScand 1998; 76: 382-383.

4. Lambiase A, Sacchetti M, Sgrulletta R, Coassin M, BoniniS. Amniotic membrane transplantation associated withconjunctival peritomy in the management of Mooren’sulcer: a case report. Eur J Ophthalmol 2005; 15: 274-276.

5. Young AL, Wong SM, Leung AT, Leung GY, Cheng LL,Lam DS. Successful treatment of surgically induced necro-tizing scleritis with tacrolimus. Clin Exp Ophthalmol2005; 33: 98-99.