Recalcitrant Atopic Keratoconjunctivitis in Children: A

Recalcitrant Atopic Keratoconjunctivitis inJing Li, MD,Children: Xiaohui Luo, MD, Hongmin AKe, MD, Case Lingyi Liang, MD,Report PhD and Literatureabstract Review

Atopic keratoconjunctivitis (AKC) is the most severe type of allergic conjunctivitis and may eventually lead to blindness. Although AKC is State Key Laboratory of Ophthalmology, Zhongshan reported to be more prevalent in adults, we report a child with AKC whose Ophthalmic Center, Ocular Surface Center, Sun Yat-sen clinical characteristics were not inconsistent with those typically seen University, Guangzhou, China in adult patients with AKC, and who was refractory to traditional topical Dr Li designed the case report, collected data, anti-inflammatory and immunosuppressant therapies. An 11-year-old drafted the initial manuscript, and revised the manuscript; Drs Luo and Ke collected data and boy presented with a 3-month history of ocular redness and itching and revised the manuscript; Dr Liang conceptualized decreased vision for a week in both eyes. Slit-lamp examination revealed and designed the study and reviewed and revised typical signs of vernal keratoconjunctivitis, including cobblestone papillae the manuscript; and all authors approved the final manuscript as submitted and agree to be in both upper conjunctiva, superficial punctate keratopathy on the right accountable for all aspects of the work. cornea, and a sterile shield-shaped ulcer on the left cornea. Physical DOI: https://​doi.​org/​10.​1542/​peds.​2016-​2069 examination revealed eczematous lid changes and a generalized body Accepted for publication Aug 4, 2017 rash, particularly on the face, neck, and flexor surfaces of the limbs. Address correspondence to Lingyi Liang, MD, PhD, He was diagnosed to have AKC in both eyes and atopic dermatitis. The State Key Laboratory of Ophthalmology, Zhongshan patient did not respond well to conventional topical antihistamine, mast Ophthalmic Center, 54S Xianlie Nan Rd, Guangzhou cell stabilizers, corticosteroids, or tacrolimus, even in combination with 510060, China. E-mail: [email protected] amniotic membrane transplant. After using systemic immunosuppressants, PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, the symptoms were relieved; the inflammation on the skin and ocular 1098-4275). surface subsided, the cobblestone papillae disappeared, and the corneal Copyright © 2018 by the American Academy of Pediatrics ulcer healed gradually within 8 weeks. This case reveals that pediatric AKC should be differentiated from vernal keratoconjunctivitis because both FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships disorders include upper cobblestone papillae, but the former is accompanied relevant to this article to disclose. by atopic dermatitis. Pediatric AKC requires appropriate and aggressive FUNDING: Supported by a grant (81300739) from treatment to prevent sight-threatening corneal complications. Systemic the National Natural Science Foundation of China, immunosuppressant should be considered when traditional topical anti- a grant (2014B020226003) from the Technological Project Foundation of Guangdong Province, and a inflammatory therapies have failed. grant from the Technological Project Foundation of Guangzhou (201510010219). The sponsors or funding organizations had no role in the design or conduct of this research; collection, management, Allergic conjunctivitis is one of the atopic dermatitis (AD), conjunctival analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. most common ocular conditions cicatrization, symblepharon, and and its incidence has increased various corneal disorders that may POTENTIAL CONFLICT OF INTEREST: The authors 1 have indicated they have no potential conflicts of dramatically in recent decades. It can eventually lead to blindness. Atopy interest to disclose. be classified into 5 types, including affects 5% to 20% of the general seasonal allergic conjunctivitis, population, and AKC occurs 2,in3​ 20% to To cite: Li J, Luo X, Ke H, et al. Recalcitrant Atopic perennial allergic conjunctivitis, 43% of individuals with AD. ‍ Keratoconjunctivitis in Children: A Case Report giant papillary conjunctivitis, vernal According to the literature, AKC is and Literature Review. Pediatrics. 2018;141(s5): keratoconjunctivitis (VKC), and atopic prevalent4 in adults and uncommon in e20162069 keratoconjunctivitis (AKC). Of these, children. Here, we report a child with AKC is considered to be the most AKC whose clinical characteristics severe form and is characterized by were not inconsistent with traits Downloaded from www.aappublications.org/news by guest on September 28, 2021 CASE REPORT PEDIATRICS Volume 141, number s5, April 2018:e20162069 typically seen in adults with AKC, and amniotic membrane transplant who was refractory to traditional (AMT) was performed uneventfully topical immunosuppressants. on the left eye, as reported in the treatment of a noninfectious CASE REPORT 5,6​ corneal ulcer, including AKC. ‍ Postoperatively, the membrane was covered by a bandage contact lens. An 11-year-old boy presented with The topical anti-inflammatory and a 3-month history of ocular redness immunosuppressant regimens were and itching and decreased vision in continued after AMT. The membrane both eyes for a week. He had been dissolved 10 days postoperatively, previously diagnosed as having at which time, the papillae were vernal conjunctivitis in both eyes, persisting, and the corneal ulcer but did not respond well to topical was worsening, with progressive mast cell stabilizers, antihistamines, vascularization (Fig 1C inset). or fluorometholone 0.1%. He did FIGURE 1 Because the patient did not respond not wear contact lenses. His medical External and slit-lamp photographs. A, Note to the above-mentioned conventional history was unremarkable except for the eczematous lids; B, the giant papillae on the upper lids; C (and inset), the cornea shield topical immunosuppressant AD and allergic rhinitis. His mother ulcer that worsened after AMT; and D, the facial treatment, we initiated systemic has allergic asthma. eczema. E and F, After treatment, the ocular immunosuppressant therapy, inflammation and papillae subsided; G, the comprising oral tacrolimus capsules His visual acuity was 20/100 in both cornea ulcer healed; and H, the skin became (PROGRAF; Astellas Pharmaceutical eyes. External examination revealed less inflamed. Co, Ltd, Killorglin, County Kerry, eczema, erythematous rashes on Ireland) at a dose of 4 mg per day, the eyelids, thickened lid margins in methotrexate tablets (Methotrexate; both eyes, and ptosis affecting the left The patient was started on topical Sine Pharmaceutical Co, Ltd, eye (Fig 1A). Slit-lamp examination immunosuppressant eye drops Shanghai Shi, China) 12.5 mg per revealed conjunctival injection, tacrolimus 0.1% (Talymus; Senju week, and prednisone acetate tablets cobblestone papillae, and follicles in Pharmaceutical Co, Ltd, Osaka, Japan) (Prednisone; Sine Pharmaceutical both upper tarsal conjunctiva (Fig twice daily, a combination of mast Co, Ltd), 40 mg per day, gradually 1B). Superficial punctate keratitis × cell stabilizer and antihistamine eye tapered to 10 mg per day. After was noted in the right cornea and a drops olopatadine hydrochloride systemic treatment, the eyelid (Fig 1E) shield-shaped ulcer measuring 6 7 (Patanol; Alcon Co, Ltd, Fort Worth, and ocular surface inflammation mm was noted in the left cornea (Fig TX) twice daily, corticosteroid decreased significantly, the giant 1C). Other ocular examinations were papillae gradually subsided (Fig 1F), unremarkable. Physical examination eye drops fluorometholone 0.1% and the corneal epithelial defect revealed severe periorbital erythema (Flumetholon; Santen Pharmaceutical ’ healed with faint scarring within 6 with excoriations and generalized Co, Ltd, Osaka, Japan) 4 times daily, weeks (Fig 1G). The patient s vision rashes on the body, particularly on an antibiotic levofloxacin (Cravit; improved to 20/30 in the right the face (Fig 1D), neck, and flexor Santen Pharmaceutical Co, Ltd) eye and 20/40 in the left eye. The surfaces of the limbs. 4 times daily, and artificial tears sodium hyaluronate 0.3% (Hialid; rash on the face and body was also significantly improved (Fig 1H). All In vivo confocal microscopy Santen Pharmaceutical Co, Ltd) 4 oral medications were continued revealed apoptotic cells in the times daily, with a bandage contact through the 10-month follow-up. No superficial epithelium and dendritic lens applied to the left eye. After systemic side effects or recurrence cell infiltration underneath the 3 weeks of treatment, the condition was noted during follow-up. epithelial layer in both eyes (Fig 2). in neither eye improved and the The serum immunoglobulin E level shield ulcer worsened. Delayed DISCUSSION was markedly elevated (>2500 IU/mL; healing of such lesions may result normal <120 IU/mL) and the in corneal scarring and a decrease 3 eosinophil percentage was also in vision. To protect the cornea AKC was first described by Hogan in – markedly increased to 20% (normal against the mechanical rubbing 1952 as a severe ocular complication 0.5% 5%). Skin tests showed insult from the giant papillae on of AD, but was almost forgotten by hypersensitivity to dust mite, beef, the upper lid, promote healing, the ophthalmic2 community for1 half and pollen. and suppress the inflammation, a century. Foster and Calonge then Downloaded from www.aappublications.org/news by guest on September 28, 2021 PEDIATRICS Volume 141, number s5, April 2018 S471 é

value. Br mond-Gignac reported

the largest series of pediatric12 AKC, which included 23 patients. Most clinical features in that case

series overlapped12 with those of VKC,​ as documented in our case. The presence of AKC-related clinical features but an absence of VKC-related clinical features in combination with a history of eczema and conjunctivitis and/or keratitis

may secure an accurate12 diagnosis of AKC in children. However, if a pediatric patient presents with typical clinical features of VKC, distinguishing AKC from VKC is challenging. For example, our patient had ocular redness and itching, conjunctival injection, cobblestone papillae on the conjunctiva of the upper lid, and a shield ulcer, which are the typical manifestations of VKC and explain why the patient had been previously misdiagnosed as having VKC. The poor response FIGURE 2 to topical immunosuppressants and In vivo confocal microscope examination of the left cornea. A and B, Note the lymphocyte infiltration the presence of AD prompted us to é in the epithelial and subepithelial layers; C, infiltration of dendritic cells (arrows); and D, neovas­ make a diagnosis of AKC according to cularization (arrows). 12 the criteria of Br mond-Gignac and

the Japanese13 diagnostic criteria for AKC. reported a series of 45 patients with is thought to occur predominantly severe ocular surface involvement in adults. There is no unified global Differentiating AKC from VKC in and a background of AD in 1990. diagnostic criterion for AKC, so it children is important. VKC is self- The seriousness of AKC, including is difficult to study this disease, limiting with a generally favorable the high prevalence of severe especially in children. In Japan, prognosis, but may have seasonal blepharitis, conjunctival scarring, patients with keratoconjunctivitis recurrences or exacerbation. The course14 of VKC lasts from 2 to 10 persistent corneal epithelial defects, and any history of AD are diagnosed10 and the increased risk of secondary with AKC, regardless of age. years and resolves without15 infections, which often result in However, in Europe, only patients significant loss of vision. In contrast, AKC is chronic, progressive, visual loss and even blindness, has7, 8​ beyond the age of puberty presenting not been sufficiently emphasized. with concurrent keratoconjunctivitis and perennial, and may persist into é 11 Patients often have symptoms of would be diagnosed as having AKC. the fourth and fifth decades of life. AKC tends to have a poor prognosis ocular irritation,– including itching, In 2015, Br mond-Gignac proposed because it may be complicated by redness,7 11 tearing, pain, and blurred the diagnostic criterion of pediatric vision. ‍ AKC as the presence of severe failure of the ocular surface and intraocular complications, such as allergic conjunctivitis with AD that12 is AKC has been defined as a chronic diagnosed before 16 years of age. cataract and retinal detachment. inflammation of the ocular surface Therefore, early diagnosis, treatment, that patients with atopy may suffer VKC is another rare but severe type and lifelong follow-up of AKC are – at any time during the course of their of allergic conjunctivitis that may important, especially when the 16 18 atopic disease and independent9 of involve the cornea. Severe itching condition develops in childhood. ‍ its degree of severity. Historically, and cobblestone papillae are the Similarly, an ophthalmic consultation

AKC has rarely been recognized as a most significant characteristics is needed when a patient with AD19 diagnostic entity before puberty and of VKC, and thus have diagnostic presents with ocular discomfort. Downloaded from www.aappublications.org/news by guest on September 28, 2021 S472 LI et al The key feature that helps to the cornea against mechanical complicated by loss of vision, distinguish pediatric AKC from VKC is rubbing by the giant papillae on the so early diagnosis and prompt AD. However, the cutaneous changes upper lids when blinking. Therefore, treatment are particularly important. of AD might be located in areas for patients with a corneal ulcer Careful examination of the skin that are covered by clothes, such as complicated by AKC, AMT may and identification of AD are key for “ ” flexor surfaces of the arms and legs, be highly 27,effective28​ as previously the diagnosis of AKC. For pediatric which might be overlooked by the reported. ‍ Use of a nonsecured patients with intractable AKC in ophthalmologist. AM such as ProKera (Biotissue Inc, whom topical treatment has failed, Doral, FL), which is an AM draped systemic immunosuppressants may It is worth noting that the clinical over a large plastic ring that is placed be initiated under close monitoring. features in our pediatric patient on the eye like a contact lens, has ABBREVIATIONS with AKC were not completely in been reported in the treatment of conformity with those of typical noninfectious keratitis. This is easily adult-onset AKC, which usually performed in the office, and the AM AD: atopic dermatitis manifests as subconjunctival and ring remain in place for 1 to 2 AKC: atopic keratoconjunctivitis infiltration and cicatrization in the 20 weeks until the AM dissolves, after AM: amniotic membrane lower lid rather than the upper lid,​ which the ring is removed, which AMT: amniotic membrane whereas the giant papillae were 29 can also be performed in the office. transplant concentrated on the upper lid in our Furthermore, the giant papillae can VKC: vernal keratoconjunctivitis pediatric patient. We suggest that occasionally be surgically removed the clinical characteristics and even in conjunction with an autologous REFERENCES the pathologic process involved in conjunctival graft or AMT, which can 1. Foster CS, Calonge M. Atopic childhood-onset and adult-onset AKC also accelerate the healing process keratoconjunctivitis. Ophthalmology. may be different. 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