Mesia, D

Rossi, G

English

MSF Field Research

Management of harlequin ichthyosis in low-income
countries
G. ROSSI & D. MESIA*
Me ´de ´cins sans Frontie `res, Rome, Italy and *Me ´de ´cins sans Frontie `res, Brussels, Belgium
(Accepted March 2011)
Abstract Harlequin ichthyosis (HI) is a very rare severe form of autosomal recessive congenital ichthyosis,
usually associated with stillbirth and early neonatal death. A newborn girl with HI is described. She presented in a
critical condition with severe universalis hyperkeratosis, diffuse scales and deep erythematous fissures. She received
preventive systemic antibiotics and hygienic nursing with skin and eye care, feeding and appropriate hydration. She
was discharged at 28 days in good general condition.
Introduction
Severe types of congenital ichthyosis present-
ing in the newborn with intense hyperker-
atosis over the whole body are rare and
characterised bya variable phenotypeexpres-
sion which mirrors the complexity of the
underlying genotype determinants. The birth
of an infant affected by congenital ichthyosis
is a challenge both for parents and clinicians.
In poor medical settings typical of low-
income countries, the lack of proper diag-
nostic laboratory and therapeutic facilities
are major constraints in managing severe
dermatological conditions.
An infant with congenital ichthyosiform
erythroderma is presented.
Case Report
A female infant was delivered in the Me ´de ´-
cins sans Frontie `res (MSF)-supported Pae-
diatric Clinic in Dakoro Hospital in the
Maradi Region of Niger. She was born at
term (birthweight 3170 g), without compli-
cations, to consanguineous parents. Her
mother was primiparous. There was no
family history of skin disorder or mention of
previous neonatal deaths.
On examination, the patient was in a
critical condition with severe ichthyosis with
hyperkeratosis, scales and deep erythema-
tous fissures over a large part of the body
surface and severe bilateral ectropion. The
face was expressionless with an open mouth
and eclabium (Fig. 1).
1 The hands and feet
were swollen because of circumferential skin
constriction. The fingers and toes were
ischaemic (Fig. 2). A diagnosis of harlequin
ichthyosis (HI) was made. Systemic anti-
biotics (ceftriaxone 60 mg/kg/day i.v. and
cloxacillin 75 mg/kg/day BID i.v) and
tetracycline eye ointment were prescribed.
Intensive skin care was undertaken, mainly
by daily moisturising and greasing with a
topical preparation made of vaseline oil
(70%), zinc oxide (20%) and aureomicine
pomate (10%). Over the next few days, her
general condition improved and complete
desquamation of the hypercheratotic skin,
accompanied by bloody secretions, occurred
Corresponding author: Dr Gabriele Rossi, Me ´de ´cins
sans Frontie `res, via Como 17, 20095 Cusano Milanino,
Italy. Fax: z39 2 619 3038; email gab.rossi@tiscali.it
Annals of Tropical Paediatrics (2011) 31, 247–249
# W. S. Maney & Son Ltd 2011
DOI: 10.1179/1465328111Y.0000000020(Figs 3 & 4). Clinical management included (i)
regular observations (temperature, heart rate,
activity level, feeding); (ii) avoidance of
hypothermia by ensuring regular wrapping,
especially at night-time, and an overhead
heater if necessary; (iii) encouraging early and
frequent (3–4 hours initially) breastfeeding
(comprising a total fluid input of 60 ml/kg/
day the 1st day, increasing to 180 ml/kg/day
within 1 week); (iv) continuous monitoring for
and timely treatment of hypoglycaemia (possi-
bly associated with hypothermia and sepsis);
and (v) asepsis and hygienic care were closely
monitored and adhered to by the nursing staff.
The following was given to the mother in
preparation for discharge: (a) soap and
explanation of the rules of hand hygiene;
(b) the importance of regular medical follow-
up was stressed; (c) use of insecticide-
impregnated bed nets to decrease the risk of
malaria was advised and three bed nets were
provided for thefamily; (d)theimportanceof
boiling water to decrease the risk of gastro-
enteritis was stated; and (e) information and
education on timely recognition of four main
dangersignsinthechild (lethargy,notable to
feed, vomiting and seizures).
The infant was discharged on day 28
weighing 4110 g and in good general con-
dition, and the mother was given a supply of
topical moisturising cream. At that time, the
skin showed some signs of hyperkeratosis.
The family lived in a distant rural area and
did not return for follow-up.
Discussion
HI is a severe and usually fatal form of
congenital ichthyosis; it belongs to the family
of genodermatoses and has an autosomal
FIG. 2. Day 1: Several hyperkeratotic plaques with a
diamond-like configuration, resembling a harlequin
clown’s costume. Limbs are in a rigid fixed position.
FIG. 1. Day1:Classicalfacialpresentationofharlequin
ichthyosis with severe ectropion and eclabium.
FIG. 3. Day 22: Desquamation of facial lesions.
Improvement of the ectropium and resolution of the
eclabium.
FIG. 4. Day 22: Almost complete desquamation of the
whole body. Partial resolution of the postural fixed
position of the limbs and fingers.
248 G. Rossi & D. Mesiarecessive inheritance pattern.
1 This is the
most severe form of congenital ichthyosis
with an incidence of 1:300,000 births. The
name of the skin disorder derives from the
typical presentation at birth, characterised by
thick, whitish, armour-like skin, crossed by
deep reddish fissures which often create
diamond-shaped cutaneous forms resem-
bling a harlequin costume (there are rhom-
boid scales, typical of the harlequin costume
ofacarnivalclown).Facialanomaliesinclude
bilateral ectropion and eclabion (eversion of
the lips), and usually there is malformation of
the external ears and nasal hypoplasia. The
limbs are short and surrounded by a rigid
sheath with hypoplastic fingers, toes and
nails.
2 The newborn appears to be encased in
a tight membrane that holds the limbs in a
semi-flexed position. The mouth remains
permanently open, rendering the infant at
times unable to suckle.
The gene underlying HI was identified in
2005.
1 It is responsible for production of
the protein ABCA12, a transporter which
belongs to the ATP-binding cassette (ABC)
transporter superfamily.
3 ABCA12 protein,
physiologically, transfers lipids from the
cytosol of the keratinocyte into lamellar
granules and discharges their contents into
the intracellular space, forming lipid lamellae
in the stratum corneum. Mutations of the
gene ABCA12 cause loss of function of the
protein, thus leading to a defective barrier in
the stratum corneum and HI phenotype.
1,3
The diagnosis is mainly clinical. Where there
is a family history of HI, prenatal diagnosis is
now possible through direct sequence analysis
and restriction enzyme digestion analysis using
the fetal genomic DNA from amniotic fluid
cells at 16 weeks gestation.
4
Before 2005, prenatal diagnosis by fetal
skin biopsy histological analysis, although
technically difficult and with low reliability,
was the only available method. Skin biopsies
were characterised by abnormalities, includ-
ing a large number of lipid droplets in the
keratinised cells and abnormal or absent
lamellar granules. Prenatal diagnosis by
ultrasound 2D and 3D imaging can detect
features suggestive of a harlequin fetus in
the 1st to 2nd trimester of pregnancy.
5
There is no standard, accepted therapy
for this disease. HI is usually associated with
stillbirth and early neonatal death owing to
respiratory compromise, infection, dehydra-
tion and hyponatraemia. Since Lawlor and
Peiris’s report in 1985 of a patient who
survived,
6 a few other survivors have been
reported. Outcome is variable with most
cases evolving to severe, non-bullous ichthyo-
siform erythroderma. Interestingly, all the
cases who have survived beyond the 1st year
of life (including Lawlor and Peiris’s) have
received oral retinoids for a short period or
intermittently.
7
This case demonstrates that, with the use
of essential hygienic nursing care along with
prevention of infection and appropriate
feeding, a regimen for skin and eye care
and hydration, infants with conditions as
severe as HI can be managed in low-income
countries with basic medical facilities.
References
1 Akiyama M, Sugiyama-Nakagiri Y, Sakai K, et al.
Mutations in lipid transporter ABCA12 in harlequin
ichthyosis and functional recovery by corrective
gene transfer. J Clin Invest 2005; 115:1777–84.
2 Kouskoukis C, Minas A, Tousimis D. Ichthyosis
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3 Kelsell DP, Norgett EE, Unsworth H, et al.
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Genet 2005; 76:794–803.
4 Akiyama M, Titeux M, Sakai K, et al. DNA-based
prenatal diagnosis of harlequin ichthyosis and
characterization of ABCA12 mutation conse-
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5 Bongain A, Benoit B, Ejnes J, et al. Harlequin fetus:
three-dimensional sonographic findings and new
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Harlequin ichthyosis 249

DNA-based prenatal diagnosis of harlequin ichthyosis and characterization of ABCA12 mutation consequences.

Harlequin fetus successfully treated with etretinate.

Harlequin fetus: three-dimensional sonographic findings and new diagnostic approach. Ultrasound Obstet Gynecol

Ichthyosis congenital fetalis (Harlequin fetus).

Mutations in ABCA12 underlie the severe congenital skin disease harlequin ichthyosis.

Mutations in lipid transporter ABCA12 in harlequin ichthyosis and functional recovery by corrective gene transfer.

Management of harlequin ichthyosis in low-income countries

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