INTRODUCTION
shortening, characterized by abnormal
Ichthyosis describes a condition in which
the skin is thick, dry, and scaly. The
condition is persistent and usually affects
the whole body including scalp. Most
types are congenital, meaning that they
are present at birth, and inherited,
meaning that they result from genetic
changes, so they may run in families.
Other types are acquired during
adulthood. Acquired ichthyosis usually
associated with another condition, such
as: an underactive thyroid, kidney disease,
sarcoidosis, swollen tissue to develop in
the body's organs, Hodgkin lymphoma, or
HIV infection. Certain medications can
also trigger ichthyosis, including some
medicines used in targeted cancer
therapy.1
Harlequin ichthyosis (HI) is one of
congenital ichthyosis and is the most
severe form that occurs within the
developing fetus.2,3 The incidence is
relatively low, occurring in 1 of 300,000
live births.2-4 Its underlying mechanisms
are not well understood, but a recent
report by Akiyama et al, said that HI was
found to be a lipid metabolism disorder,
caused by mutation in the adenosine
triphosphate (ATP)-binding cassette
(ABC) transporter, ABCA12.3
Fetuses born with HI are
characterized by severe erythrodermic
ichthyosis, epidermal desquamation, and
some ocular complications; ectropion is
one of the most common ocular
complications due to excessive dryness of
skin and subsequent contracture
eversion of the eyelids.4-6
There is currently no specific
standard for ectropion treatment, even
surgical interventions have varied results,
with frequent recurrence of ectropion or
unsatisfactory cosmetic outcomes.
Frequent lubrication drops and eye
ointments, antibiotics, and frequent eyelid
skin massage with lubrication can be
other options for treatment. 5-6
CASE REPORT
A 10-day-old boy was consulted from the
pediatric department with bilateral
ectropion and harlequin ichthyosis. The
boy was born spontaneously, low birth
weight (2100 grams), preterm (35 weeks),
without any history of infectious disease
or other abnormalities during pregnancy.
Family history and consanguinity
between parents were denied. When
consulted, his weight was 1960 grams,
treated in an incubator, and using oxygen
through nasal cannula. Systemic
evaluations revealed generalized skin
desquamation, hyperkeratosis, xerosis,
and erosion in whole body.
External ophthalmology examination
was performed. There was a remarkable
abnormal eversion in both upper eyelids
with scaly skin surface surrounding it, the
cilia were absent, the palpebral
conjunctiva was hyperemic with notable
discharge (Figure 1). Initial anterior
segment evaluation was difficult to
obtain.
 Figure 1. Day-1 assessment, 11 days old. Bilateral upper eyelids eversion, scaly skin,
hyperemic palpebral conjunctiva, and notable conjunctival discharge on both eyes.

Antibiotic eye ointment containing desquamation and minimal discharge was

combination of Polymyxin B Sulphate,
Neomycin Sulphate, and Gramicidin was
given every 8 hour for 1 month for
supportive treatment. Follow-up
assessments after 6 days of therapy
showed dramatically change; eye
eversion was disappearing, although skin
still persist. In week two, we found that
both eyes can be opened properly and
neither hyperkeratinization nor discharge
was evaluated. Unfortunately, a thorough
anterior and posterior segment evaluation
was unable to be done because the patient
stays in incubator for quite long period.

R L

Figure 2. Day-6 assessment, 16 days old. There were no bilateral upper eyelids
eversion anymore, skin desquamation and minimal discharge still persist.
 R
R L

Figure 3. Day-13 assessment, 23 days old. Both eyes can be opened properly, neither
hyperkeratinization nor discharge was evaluated.

DISCUSSION longer performed to diagnose. In

A new born infant diagnosed with HI by
performing clinical examination.
Laboratory investigations and imaging
studies used to identify complications of
HI in the newborn period. Fetal skin
biopsy as early as 19 weeks' gestation
sometimes used to detect ultrastructural
changes consistent with HI, but now no
histopathologic, we find an
extraordinarily thickened and compact
orthokeratotic stratum corneum. Cells
within the stratum corneum are
abnormally keratinized. The granular,
spinous, and basal cell layers appear
unremarkable. Inflammatory cells may
infiltrate the papillary dermis. Hair
follicles show marked, concentric
accumulation of keratotic material around
the hair shafts, which is considered a
diagnostic feature of HI and has been
used to establish the diagnosis prenatally.
Other test is using electron microscopy
that reveals absent or abnormal lamellar
granules within the granular layer
keratinocytes.7 In this case, the patient
diagnosed with HI based on his clinical
examination. We don’t perform
histopathologic and electron microscopy
examination. Correspondingly, Ashley
Khalili et al (2019) also reported an
infant diagnosed with HI based on
clinical examination without perform
histopathologic and electron microscopy
examination.8
As reported in some literature,
ectropion almost universally improves
after the neonatal period. But in some
cases, it can last a lifetime. It can even
cause medical consequences, such as:
keratitis, conjunctivitis, and epiphora.6
Regarding to minimize those serious
concequences, we treat this patient
without delay. Until now there is no
standard medical management for
ectropion. So far, ectropion treatment has
not led to significant and sustained
improvement, nor it doesn't prevent the
complications associated with chronic
corneal exposure. But, systemic retinoids,
usually isotretinoin, and topical retinoids,
usually tazarotene, have been utilized
effectively in some cases.9 Brittany G.
Craiglow et al (2013) reported the use of
topical retinoid in 77-year-old woman
with recessive ichthyosis and looking for
evaluation of bilateral long standing
lower eyelids ectropion. This showed a
significant improvement after using
Tazarotene 0.1% cream daily on both
lower eyelids for 1 year and continued to
improve during the follow-up period 30
months later.6 Retinoids are a class of
compounds derived from vitamin A or
showing structural and/or functional
similarities to vitamin A and widely
applied in cosmetology and dermatology.
10
The skin of the body consists of 2
mutually dependent layers, the epidermis
and dermis, which rest on a fatty
subcutaneous layer. Skin thickness varies
based on anatomic location, sex, and age
of the individual. Skin is thickest on the
palms and soles of the feet (1.5 mm
thick), while the thinnest is found on the
eyelids and in the post auricular region
(0.05 mm thick). Male skin is
characteristically thicker than female skin
in all anatomic locations. Children have
relatively thin skin, which progressively
thickens until the fourth or fifth decade of
life when it begins to thin. 11,12
The skin of the eyelids is the thinnest
of the body (< 1 mm). There are
transition from this thin eyelid skin to the
thicker skin of the eyebrow and the cheek
skin. The subcutaneous tissue consists of
loose connective tissue. Fat is very sparse
in preseptal and preorbital skin and is
absent from pretarsal skin. Subcutaneous
tissue is absent over the medial and
lateral palpebral ligaments, where the
skin adheres to the underlying fibrous
tissue.12
 Figure 4. Anatomy of the skin

Figure 5. Upper eyelid anatomy Figure 6. Lower eyelid anatomy

The sensitivity of the ocular tissues four general classes of ointment:

and the presence of various attributes of hydrocarbon or oleaginous bases,
physicochemical and biological barriers absorption bases, water-removable bases,
are challenges in ocular drug and water-soluble bases.14 Ocular
administration. Due to ease of access and ointment comprises of mixture of
patient compliance, topical administration semisolid and a solid hydrocarbon
is a widely accepted and preferred route (paraffin) that has a melting point at
of administration.13 Ointments are the physiological ocular temperature (34°C).
popular dosage forms in topical The choice of hydrocarbon is dependent
administration. Ointments offer on biocompatibility that help to improve
advantages over eye drops, such as ocular bioavailability and sustain the drug
increased contact time, reduced release.15
nasolacrimal drainage, minimization of
tear dilution, and higher effective In this case, we report resolution of
concentrations. As we know, there are bilateral congenital ectropion in HI
patient without using topical retinoid as
reported by Brittany G. Craiglow et al
(2013), but only using antibiotic eye
ointment. Surprisingly, the use of
antibiotic eye ointment results significant
ectropion resolution and promotes faster
desquamation of the eyelid skin in just
six days and continues to improve during
the follow-up period one month later.
Ashley Khalili et al (2019) reported
an 1-day-old girl with hyperkeratotic
plaques over her entire body, with severe
thickening of the skin around her face,
abdomen, and extremities with outward
turning of her lips (eclabium) and
ectropion. Ophthalmology examination
was notable for thickening and tightness
of the skin around her eyes, with
cicatricial ectropion of the upper eyelids.
Good lid closure was noted, with
excellent Bell’s phenomenon and limited
exposure. The conjunctivae appeared
white and quiet and the corneas were
clear in both eyes. The patient was started
on ophthalmic ointment treatment every 2
hours, alternating between petrolatum
and erythromycin. The last ophthalmic
examination at 20 months of age showed
no evidence of exposure keratopathy with
clear corneas and resolved ectropion and
she was maintained on petroleum
ointment every four hours.8 On the other
hand, Lori Vollmer et al (2019) reported
a 25-year-old female patient with
bilateral lagophthalmos and cicatricial
ectropion of both upper and lower lids.
The slit lamp examination revealed an
injected eye with corneal ulcer with
hypopyon in the right eye and quiet eye
with corneal scarring in the left eye. The
patient was treated with topical
moxifloxacin and polymyxin B technology: a case report. Medical
sulfate/trimethoprim and 5% homatropine
in the right eye. After one month,
keratitis is treated with resolution, but
there is no significant improvement for
ectropion so the patient is referred for a
consultation about eyelid repair.16
Based on several references, there
were no cases with HI that report a
recurrence after being declared improved
with ointment therapy.
CONCLUSION
This case report illustrates that ointment
therapy may be an alternative treatment
option for ectropion patient with
harlequin ichthyosis besides surgical
intervention. In addition, we assume that
eye ointment therapy must be given as
soon as possible without delay to achieve
a good outcome. However, it still requires
further research to establish a time
standard for patient follow-up and
whether there is a possibility for the
ectropion to relapse.
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