Recalcitrant Atopic Keratoconjunctivitis

in Children: A Case Report

and Literature Review
Jing Li, MD, Xiaohui Luo, MD, Hongmin Ke, MD, Lingyi Liang, MD, PhD

abstract Atopic keratoconjunctivitis (AKC) is the most severe type of allergic

conjunctivitis and may eventually lead to blindness. Although AKC is
reported to be more prevalent in adults, we report a child with AKC whose
clinical characteristics were not inconsistent with those typically seen
State Key Laboratory of Ophthalmology, Zhongshan
in adult patients with AKC, and who was refractory to traditional topical
Ophthalmic Center, Ocular Surface Center, Sun Yat-sen
University, Guangzhou, China anti-inflammatory and immunosuppressant therapies. An 11-year-old
boy presented with a 3-month history of ocular redness and itching and
Dr Li designed the case report, collected data,
drafted the initial manuscript, and revised the decreased vision for a week in both eyes. Slit-lamp examination revealed
manuscript; Drs Luo and Ke collected data and typical signs of vernal keratoconjunctivitis, including cobblestone papillae
revised the manuscript; Dr Liang conceptualized in both upper conjunctiva, superficial punctate keratopathy on the right
and designed the study and reviewed and revised
the manuscript; and all authors approved the cornea, and a sterile shield-shaped ulcer on the left cornea. Physical
final manuscript as submitted and agree to be examination revealed eczematous lid changes and a generalized body
accountable for all aspects of the work. rash, particularly on the face, neck, and flexor surfaces of the limbs.
DOI: https://​doi.​org/​10.​1542/​peds.​2016-​2069 He was diagnosed to have AKC in both eyes and atopic dermatitis. The
Accepted for publication Aug 4, 2017 patient did not respond well to conventional topical antihistamine, mast
Address correspondence to Lingyi Liang, MD, PhD, cell stabilizers, corticosteroids, or tacrolimus, even in combination with
State Key Laboratory of Ophthalmology, Zhongshan amniotic membrane transplant. After using systemic immunosuppressants,
Ophthalmic Center, 54S Xianlie Nan Rd, Guangzhou
510060, China. E-mail: [email protected]
the symptoms were relieved; the inflammation on the skin and ocular
surface subsided, the cobblestone papillae disappeared, and the corneal
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online,
1098-4275). ulcer healed gradually within 8 weeks. This case reveals that pediatric AKC
Copyright © 2018 by the American Academy of should be differentiated from vernal keratoconjunctivitis because both
Pediatrics disorders include upper cobblestone papillae, but the former is accompanied
FINANCIAL DISCLOSURE: The authors have by atopic dermatitis. Pediatric AKC requires appropriate and aggressive
indicated they have no financial relationships treatment to prevent sight-threatening corneal complications. Systemic
relevant to this article to disclose.
immunosuppressant should be considered when traditional topical anti-
FUNDING: Supported by a grant (81300739) from inflammatory therapies have failed.
the National Natural Science Foundation of China,
a grant (2014B020226003) from the Technological
Project Foundation of Guangdong Province, and a
grant from the Technological Project Foundation
of Guangzhou (201510010219). The sponsors or Allergic conjunctivitis is one of the atopic dermatitis (AD), conjunctival
funding organizations had no role in the design or
most common ocular conditions cicatrization, symblepharon, and
conduct of this research; collection, management,
analysis, and interpretation of the data; and and its incidence has increased various corneal disorders that may
preparation, review, or approval of the manuscript. dramatically in recent decades. It can eventually lead to blindness.‍1 Atopy
POTENTIAL CONFLICT OF INTEREST: The authors be classified into 5 types, including affects 5% to 20% of the general
have indicated they have no potential conflicts of seasonal allergic conjunctivitis, population, and AKC occurs in 20% to
interest to disclose. perennial allergic conjunctivitis, 43% of individuals with AD.‍2,​3‍
giant papillary conjunctivitis, vernal According to the literature, AKC is
To cite: Li J, Luo X, Ke H, et al. Recalcitrant Atopic keratoconjunctivitis (VKC), and atopic prevalent in adults and uncommon in
Keratoconjunctivitis in Children: A Case Report keratoconjunctivitis (AKC). Of these, children.‍4 Here, we report a child with
and Literature Review. Pediatrics. 2018;141(s5): AKC is considered to be the most AKC whose clinical characteristics
e20162069
severe form and is characterized by were not inconsistent with traits

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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
corneal ulcer, including AKC.‍5,​6‍
CASE REPORT 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 Because the patient did not respond
not wear contact lenses. His medical to the above-mentioned conventional
history was unremarkable except for FIGURE 1 topical immunosuppressant
AD and allergic rhinitis. His mother External and slit-lamp photographs. A, Note
the eczematous lids; B, the giant papillae on treatment, we initiated systemic
has allergic asthma. the upper lids; C (and inset), the cornea shield immunosuppressant therapy,
ulcer that worsened after AMT; and D, the facial comprising oral tacrolimus capsules
His visual acuity was 20/100 in both eczema. E and F, After treatment, the ocular
inflammation and papillae subsided; G, the
(PROGRAF; Astellas Pharmaceutical
eyes. External examination revealed
cornea ulcer healed; and H, the skin became Co, Ltd, Killorglin, County Kerry,
eczema, erythematous rashes on less inflamed. 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
eye drops fluorometholone 0.1% papillae gradually subsided (‍Fig 1F),
unremarkable. Physical examination
(Flumetholon; Santen Pharmaceutical and the corneal epithelial defect
revealed severe periorbital erythema
Co, Ltd, Osaka, Japan) 4 times daily, healed with faint scarring within 6
with excoriations and generalized
an antibiotic levofloxacin (Cravit; weeks (‍Fig 1G). The patient’s vision
rashes on the body, particularly on
Santen Pharmaceutical Co, Ltd) improved to 20/30 in the right
the face (‍Fig 1D), neck, and flexor
4 times daily, and artificial tears eye and 20/40 in the left eye. The
surfaces of the limbs.
sodium hyaluronate 0.3% (Hialid; rash on the face and body was also
Santen Pharmaceutical Co, Ltd) 4 significantly improved (‍Fig 1H). All
In vivo confocal microscopy
times daily, with a bandage contact oral medications were continued
revealed apoptotic cells in the
lens applied to the left eye. After through the 10-month follow-up. No
superficial epithelium and dendritic
3 weeks of treatment, the condition systemic side effects or recurrence
cell infiltration underneath the
in neither eye improved and the was noted during follow-up.
epithelial layer in both eyes (‍Fig 2).
The serum immunoglobulin E level shield ulcer worsened. Delayed
was markedly elevated (>2500 IU/mL; healing of such lesions may result
DISCUSSION
normal <120 IU/mL) and the in corneal scarring and a decrease
eosinophil percentage was also in vision. To protect the cornea AKC was first described by Hogan‍3 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 ophthalmic community for half
and pollen. and suppress the inflammation, a century.‍2 Foster and Calonge‍1 then

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PEDIATRICS Volume 141, number s5, April 2018 S471
 value. Brémond-Gignac reported
the largest series of pediatric AKC,
which included 23 patients.‍12
Most clinical features in that case
series overlapped with those
of VKC,​‍12 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 accurate diagnosis
of AKC in children.‍12 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
to topical immunosuppressants and
the presence of AD prompted us to
FIGURE 2 make a diagnosis of AKC according to
In vivo confocal microscope examination of the left cornea. A and B, Note the lymphocyte infiltration
the criteria of Brémond-Gignac‍12 and
in the epithelial and subepithelial layers; C, infiltration of dendritic cells (arrows); and D, neovas­
cularization (arrows). the Japanese diagnostic criteria for
AKC.13
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
persistent corneal epithelial defects, and any history of AD are diagnosed course of VKC lasts from 2 to 10
and the increased risk of secondary with AKC, regardless of age.‍10 years‍14 and resolves without
infections, which often result in However, in Europe, only patients significant loss of vision.‍15 In
visual loss and even blindness, has beyond the age of puberty presenting contrast, AKC is chronic, progressive,
not been sufficiently emphasized.‍7,​8 with concurrent keratoconjunctivitis and perennial, and may persist into
Patients often have symptoms of would be diagnosed as having AKC.‍11 the fourth and fifth decades of life.
ocular irritation, including itching, In 2015, Brémond-Gignac proposed AKC tends to have a poor prognosis
redness, tearing, pain, and blurred the diagnostic criterion of pediatric because it may be complicated by
vision.‍7–11
‍‍‍ AKC as the presence of severe failure of the ocular surface and
allergic conjunctivitis with AD that is intraocular complications, such as
AKC has been defined as a chronic diagnosed before 16 years of age.‍12 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
atopic disease and independent of involve the cornea. Severe itching condition develops in childhood.‍16–18‍
its degree of severity.‍9 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 AD
diagnostic entity before puberty and of VKC, and thus have diagnostic presents with ocular discomfort.‍19

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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 effective as previously the diagnosis of AKC. For pediatric
which might be overlooked by the ‍ Use of a “nonsecured”
reported.‍27,​28 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
with AKC were not completely in
been reported in the treatment of
conformity with those of typical ABBREVIATIONS
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
weeks until the AM dissolves, after AM: amniotic membrane
lower lid rather than the upper lid,​‍20
which the ring is removed, which AMT: amniotic membrane
whereas the giant papillae were
can also be performed in the office.29 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
the pathologic process involved in
conjunctival graft or AMT, which can
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S474 LI et al
 Recalcitrant Atopic Keratoconjunctivitis in Children: A Case Report and
Literature Review
Jing Li, Xiaohui Luo, Hongmin Ke and Lingyi Liang
Pediatrics 2018;141;S470
DOI: 10.1542/peds.2016-2069

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 Recalcitrant Atopic Keratoconjunctivitis in Children: A Case Report and
Literature Review
Jing Li, Xiaohui Luo, Hongmin Ke and Lingyi Liang
Pediatrics 2018;141;S470
DOI: 10.1542/peds.2016-2069

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