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Infliximab for management of severe refractory posterior scleritis in a 9-year-old boy

Published:December 22, 2020DOI:https://doi.org/10.1016/j.jcjo.2020.11.013
      Posterior scleritis (PS) is a chronic inflammatory condition of the sclera posterior to the rectus muscle insertions. PS predominantly affects adult women and is rare in children.
      • Farooq O
      • Buccilli A
      • Varma C
      • Reidy JJ
      • Faden H.
      Posterior scleritis: a rare pediatric disorder.
      ,
      • Cheung CM
      • Chee SP.
      Posterior scleritis in children: clinical features and treatment.
      Adult form of PS is typically associated with autoimmune systemic diseases; however, pediatric PS is mostly idiopathic with no known underlying conditions.
      • Cheung CM
      • Chee SP.
      Posterior scleritis in children: clinical features and treatment.
      • Majumder PD
      • Ali S
      • George A
      • Ganesh S
      • Biswas J.
      Clinical profile of scleritis in children.
      • Woon WH
      • Stanford MR
      • Graham EM.
      Severe idiopathic posterior scleritis in children.
      The initial presentation of PS in children is nonspecific with painful red eye, potential vision loss, light sensitivity, and eye movement restriction, which make the diagnosis difficult.
      • Cheung CM
      • Chee SP.
      Posterior scleritis in children: clinical features and treatment.
      • Majumder PD
      • Ali S
      • George A
      • Ganesh S
      • Biswas J.
      Clinical profile of scleritis in children.
      • Woon WH
      • Stanford MR
      • Graham EM.
      Severe idiopathic posterior scleritis in children.
      The current recommended treatment for mild PS is oral nonsteroidal anti-inflammatory drugs (NSAIDs); however, steroids and steroid-sparing immunosuppressive treatment are required for more severe cases.
      • Jabs DA
      • Mudun A
      • Dunn JP
      • Marsh MJ.
      Episcleritis and scleritis: clinical features and treatment results.
      ,
      • Thadani SM
      • Foster CS.
      Treatment of ocular inflammation in children.
      In adult PS refractory to standard immunomodulatory agent, antitumour necrosis factor agents such as infliximab have shown good disease control.
      • Doctor P
      • Sultan A
      • Syed S
      • Christen W
      • Bhat P
      • Foster CS.
      Infliximab for the treatment of refractory scleritis.
      ,
      • Murphy CC
      • Ayliffe WH
      • Booth A
      • Makanjuola D
      • Andrews PA
      • Jayne D
      Tumor necrosis factor alpha blockade with infliximab for refractory uveitis and scleritis.
      There are few case reports of pediatric PS, most of which have resolved using 2 or more immunosuppressive agents.
      • Cheung CM
      • Chee SP.
      Posterior scleritis in children: clinical features and treatment.
      ,
      • Majumder PD
      • Ali S
      • George A
      • Ganesh S
      • Biswas J.
      Clinical profile of scleritis in children.
      Here, we present a 9-year follow-up study of a patient with pediatric PS with a history of multiple flare-ups while on oral steroids, methotrexate, and mycophenolate, who achieved resolution using infliximab and maintained remission after cessation of treatment. Our case represents only the second case report of infliximab use in paediatric PS.
      We present a patient with childhood-onset PS. Written consent was obtained from the patient guardian. The data on patient's electronic chart, including history, systemic and ocular findings, laboratory results, investigations, and treatment, were reviewed.
      A 9-year-old boy with a history of asthma, sickle cell trait, and no significant birth history presented with a 4-day history of fever, left eye pain and swelling, foreign body sensation, and tearing. Eye examination showed unilateral decreased visual acuity (right and left eyes 0.1 and 0.7 logMAR, respectively) with equal, round, and reactive pupils to light. There was pain with restriction of ocular motility in the left eye and 3 mm of proptosis, periorbital swelling and injected conjunctiva. Dilated fundus examination showed left optic nerve edema (Fig. 1A). The laboratory results showed leukocytosis with increased neutrophils. After a diagnosis of presumptive orbital cellulitis, he was started on intravenous (IV) cefotaxime, cloxacillin, and clindamycin. Computerized tomography (CT) scan showed diffuse scleral thickening of the left eye associated with swelling of the lateral pre- and postseptal soft tissues extending into retrobulbar fat and surrounding the distal optic nerve. Three days of treatment did not achieve clinical improvement, and a new finding of anterior uveitis was noted. Repeat CT scan showed worsening of the orbital signs more indicative of inflammatory disease rather than orbital cellulitis. An ultrasound B-scan confirmed the characteristic T sign of scleritis (Fig. 1B), and a diagnosis of unilateral severe PS was made. He received 2 weeks of IV methylprednisolone 900 mg/day, which controlled the inflammation and improved his vision to 0.0 logMAR.
      Fig 1
      Fig. 1Ophthalmic findings in a 9-year-old boy at the initial examination. (A) Dilated fundus examination revealing left optic nerve edema. (B) Ultrasound B scan showing characteristic T sign of scleritis.
      All infective work-up including Tuberculosis, syphilis and the Herpes Simplex, Varicella-zoster, Cytomegalovirus, Epstein-Barr, Human Herpes, Human immunodeficiency, Hepatitis B and Hepatitis C viruses, as well as autoantibodies including antinuclear antibody (ANA), anti-dsDNA, antineutrophil cytoplasmic antibody, antimyeloperoxidase antibody, anti-proteinase 3 antibody, anticardiolipin antibody, and rheumatoid factor were negative. We excluded Immunoglobulin (Ig) G4 disease and the total serum levels of IgG, IgM, and IgA were also within the normal range. He was discharged on oral prednisolone 40 mg per day on a slow taper and methotrexate subcutaneous injection 25 mg per week. He re-presented with severe left scleritis 6 months later while on oral prednisolone 10 mg and methotrexate 25 mg, requiring further IV methylprednisolone treatment for 2 weeks. Mycophenolate 540 mg was also added to prednisolone 40 mg and methotrexate in order to control the scleritis. The patient exhibited 3 additional flare-ups of bilateral scleritis over the following 3 years (Fig. 2) as a consequence of tapering the oral prednisolone to 10 mg. These flare-ups were controlled by hospitalization and receiving pulse of IV methylprednisolone. The family's initial resistance to treatment with antitumour necrosis factor medication required further discussions at this stage. They agreed to infliximab 300 mg infusion every 4 weeks, and methotrexate and mycophenolate were stopped. The patient successfully weaned off oral prednisolone. He achieved sustained remission on infliximab alone for 4 years, except for one flare-up owing to treatment noncompliance, which resolved quickly on resumption of infliximab. He tapered off infliximab over a further period of 1 year. The patient had a mild flare-up of scleritis 6 months after stopping infliximab, which responded to ibuprofen 400 mg 3 times a day for a month with no further episodes. He stays in remission with 0.1 logMAR uncorrected vision and a normal eye examination 9 years after initial presentation.
      Fig 2
      Fig. 2Posterior scleritis flare-ups in the right (A) and left (B) eyes showing marked deep injection involving predominantly the posterior sclera.
      PS is rare in children, with a nonspecific, heterogeneous clinical presentation. Ocular pain, redness, lid involvement, and restriction of extraocular muscle movement are the most common early signs of pediatric PS, which are also features of other common diseases affecting children. Our case was initially managed as orbital cellulitis owing to significant pain and restricted ocular motility, proptosis, fever, and raised white cell counts. Orbital cellulitis is much more common than PS and represents a life-threatening differential diagnosis, which must be excluded when acute orbital inflammation is noted. On the other end of severity scale, Mallick et al.
      • Mallick J
      • Pujahari S
      • Maharana PK.
      Posterior scleritis presenting as conjunctivitis in a child.
      reported a case of a 14-year-old boy with eye redness, decreased vision, and conjunctival congestion who initially was managed as viral conjunctivitis. After careful clinical examinations and imaging, he was diagnosed with PS and was subsequently treated with oral NSAIDs and topical steroid for 2 weeks, resolving the eye inflammation and improving his visual acuity to 20/20.
      • Mallick J
      • Pujahari S
      • Maharana PK.
      Posterior scleritis presenting as conjunctivitis in a child.
      Oral NSAIDs are the first line of treatment for PS; however, immunosuppressive drugs are often needed to fully control the inflammation.
      • Cheung CM
      • Chee SP.
      Posterior scleritis in children: clinical features and treatment.
      ,
      • Thadani SM
      • Foster CS.
      Treatment of ocular inflammation in children.
      One study reported on 20 eyes of 13 pediatric patients with PS and reported flare-ups when tapering the oral corticosteroid to <0.5 mg/kg/day.
      • Cheung CM
      • Chee SP.
      Posterior scleritis in children: clinical features and treatment.
      Owing to exhibiting side effects or relapse on low-dose corticosteroid, at least one immunosuppressive drug was added to control the inflammation. In the current case report, the patient experienced 3 separate episodes of flare-up whilst on full dose of methotrexate and mycophenolate when oral prednisolone was reduced to 10 mg/day (0.2 mg/kg/day). Therefore, infliximab 300 mg every 4 weeks was successfully started to control his inflammation. Only one previous case report on paediatric PS used infliximab for disease resistant to methotrexate, methylprednisolone, and cyclosporine treatment.
      • Weiss K
      • Rieger R
      • Keitzer R
      • Pleyer U.
      Successful infliximab treatment of posterior scleritis in a 13-year-old child refractory to other immunosuppressive therapy.
      Weiss et al. presented the case of a 13-year-old girl diagnosed with PS who maintained remission with 10 infusions of infliximab (5 mg/kg) with no side effects over a 16-month follow-up.
      • Weiss K
      • Rieger R
      • Keitzer R
      • Pleyer U.
      Successful infliximab treatment of posterior scleritis in a 13-year-old child refractory to other immunosuppressive therapy.
      Our case likely represents a more severe case requiring much longer immunomodulation with infliximab (5 years total) to achieve long-term remission. Although there are published data on infliximab therapy for childhood refractory uveitis,
      • Ardoin SP
      • Kredich D
      • Rabinovich E
      • Schanberg LE
      • Jaffe GJ.
      Infliximab to treat chronic noninfectious uveitis in children: retrospective case series with long-term follow-up.
      • Kahn P
      • Weiss M
      • Imundo LF
      • Levy DM.
      Favorable response to high-dose infliximab for refractory childhood uveitis.
      • Rajaraman RT
      • Kimura Y
      • Li S
      • Haines K
      • Chu DS.
      Retrospective case review of pediatric patients with uveitis treated with infliximab.
      it is encouraging to report safe and effective disease control in PS as well.
      In conclusion, the majority of pediatric PS cases in literature report poor disease control with only NSAIDs or corticosteroids, with many requiring at least one immunosuppressive agent to avoid steroid side effects. We propose that infliximab can be considered an alternative treatment for severe paediatric PS resistant to treatment.

      Footnotes and Disclosure

      The authors have no proprietary or commercial interest in any materials discussed in this article.

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