INTRODUCTION

Ichthyosis fetalis, otherwise known as harlequin ich-thyosis (HI) is a devastating, extremely rare form of con-genital ichthyosis with an autosomal recessive inheritancepattern. It is a severe keratinizing disorder that carries amortality rate of 44% [1].

The affected babies are frequently born prematurelyand small for gestational age [2]. They harbor a charac-teristic armor-like skin consisting of thick white scalingplates separated by deep red grooves that resemble a har-lequin costume. Clinical findings include bilateral ectro-pion, eclabium, constricting bands that could disruptvascular flow to the extremities and deformed nose andears. The defective skin barrier puts the baby at risk forsevere dehydration, electrolyte disturbances, thermalimbalance and sepsis whereas the restricted movementprohibits appropriate feeding and breathing [1-3].

HI is caused by a homozygous mutation in the geneencoding a protein adenosine triphosphate binding cas-sette subfamily A member 12 (ABCA12) which acts as akeratinocyte lipid transporter. The mutation results indefective lipid transport in epidermal keratinocytes andsubsequent abnormal desquamation of the skin [4,5].Advancements in neonatal intensive care managementhave led to improvement in prognosis allowing for sur-vival of some patients with HI.

We report a case of HI in one of two dizygotic twinsfollowing in vitro fecundation.

CASE REPORT

A 29-year-old woman, gravida 2, para 0, aborta 1 witha dichorionic diamnionic twin pregnancy at 30 weeks ofgestational age presented to the Labor and Delivery Unitcomplaining of abdominal pain and frequent loose stools.

Her pregnancy was uneventful. She denied any histo-ry of illicit drug use or radiation exposure. There wasneither consanguinity nor any family history of ichthyo-sis or other congenital anomalies. Her obstetrical historyconsisted of a first trimester spontaneous abortion thatwas followed by secondary infertility. A successful invitro fertilization cycle resulted in the current twin dizy-gotic pregnancy.

On physical examination, the patient was afebrilewith stable vital signs but diffuse abdominal tendernesswas noted. Monitoring revealed reassuring fetal heartrates with regular preterm contractions. The laboratoryworkup revealed a C reactive protein of 33 mg/L andWBC value of 48/mm3 on urinalysis.

The patient was admitted to the hospital and amoxi-cilline-clavulanate was initiated. Tocolysis was attempted,however preterm labor progressed and the patient wasrushed to the operating room for a primary cesareansection.

She delivered dizygotic twins: a healthy girl of 1.7 kgwith APGAR scores of 10 at 1 and 5 minutes and a har-lequin boy of 1.6 kg with APGAR scores of 8 and 10 at1 and 5 minutes respectively. The amniotic fluid wasclear and the cesarean section was uncomplicated.

The boy’s entire body was covered with thick hyper-keratotic plates separated by deep erythematous fissures(Figure 1). His ears were malformed and adherent tothe scalp (Figure 1). He had eclabium (eversion of thelips) and severe bilateral ectropion (complete eversionof the eyelids with occlusion of the eyes) (Figure 1).

Lebanese Medical Journal 2017 • Volume 65 (1) 49

CCAASS CCLLIINNIIQQUUEE//CCAASSEE RREEPPOORRTTMULTIDISCIPLINARY TEAM APPROACH IN HARLEQUIN BABYA Case Reporthttp://www.lebanesemedicaljournal.org/articles/65-1/case1.pdf

Marwan NASR1, Samer JABBOUR1, Elio KECHICHIAN2, Farid STEPHAN2, Imad MELKI3

Nasr M, Jabbour S, Kechichian E, Stephan F, Melki I. Multi-disciplinary team approach in Harlequin baby: A case report.J Med Liban 2017 ; 65 (1) : 49-51.

Nasr M, Jabbour S, Kechichian E, Stephan F, Melki I. Approchemultidisciplinaire dans la prise en charge du syndrome d’Arle-quin. Étude d’un cas. J Med Liban 2017; 65 (1) : 49-51.

ABSTRACT • Harlequin ichthyosis (HI) is an autosomalrecessive disorder with a mortality rate of 44%. HI iscaused by a homozygous mutation in a protein adenosinetriphosphate binding cassette subfamily A member 12.We present a case of HI in one of two dizygotic twinssuccessfully managed using a multidisciplinary approachand discharged from the hospital at day 65 of life.Keywords : harlequin, ichthyosis, congenital diseases

RÉSUMÉ • Le syndrome d’Arlequin est une maladie autoso-male récessive avec un taux de mortalité de 44%. Elle estcausée par une mutation homozygote du membre 12 d’une cas-sette de liaison d’une protéine adénosine triphosphate de lasous-famille A. Nous présentons un cas de syndrome d’Arlequintraité avec succès par une approche multidisciplinaire jusqu’à sasortie de l’hôpital à l’âge de 65 jours.Mots-clés : syndrome d’Arlequin, ichthyosis, maladies congénitales

From Hôtel-Dieu de France University Hospital, Beirut, Lebanon1Department of Plastic and Reconstructive Surgery 2Department of Dermatology3Department of Pediatrics

Correspondence : Marwan Nasr, MD.e-mail: mnasr.hdf@usj.edu.lbFax: +961 1 615295

The scaling formed restrictive bands on all extremitiesresulting in edematous hands and feet and subsequentrestricted movements of the limbs (Figure 1).

He was admitted to the neonatal intensive care unitand placed on parenteral nutrition, systemic weightadjusted doses of ampicilline-cephotaxime and anal-gesics. Petroleum ointment was used every 2 hours tocover the scale plates. Topical Vitamin A was applied onthe eyes six times a day.

Starting day 1, the baby boy received systemic acitre-tine at a dose of 1.6 mg/kg/24h.

The neonatal intensive care unit stay was overalluneventful and the boy was discharged at 65 days ofage.

DISCUSSION

HI is the most severe ichthyotic genodermatosis. Itaffects both genders equally with a mean gestational ageat birth of 35 weeks. The survival rate is 56% and themajor causes of death include fulminant sepsis (25%),respiratory failure (25%) or both (25%). Fifty percent ofdeaths occur within three days of life. Despite this poorprognosis, the reported age of the survivors ranges from10 months to 25 years [1]. Sepsis is the product of HI’sdefective skin barrier whereas the respiratory failure isdue to restrictive chest movements caused by adherentscales on the thorax or a possible involvement of ABCA12in lung physiology [1,6].

50 Lebanese Medical Journal 2017 • Volume 65 (1) M. NASR et al. – Multidisciplinary team approach in Harlequin baby

FIGURE 1. Photographs of the Harlequin baby with the entire body covered with thick hyperkeratotic plates separated by deep erythematous fissures.Malformed ears adherent to the scalp (Above left) Severe bilateral ectropion and eclabium (Above right)Edematous hands and feet caused by the restricting bands of scaling (Below left and right)

Since it was first described in Charleston, SouthCarolina, in 1750 by Reverend Oliver Hart, HI hasknown many advances notably in 2005 when ABCA12was identified as the underlying causative gene. Thisgene encodes a protein that transports the glucosylce-ramide into the lamellar granules of the upper epidermalkeratinocytes to be processed and secreted into the stra-tum corneum [4,5]. When mutated, skin development isaltered in utero. Homozygous mutations in the ABCA12gene have been shown to cause the harlequin phenotypewhereas heterozygous mutations result in collodion ba-bies, congenital ichthyosiform erythroderma and lamel-lar ichthyosis [1,5]). Nowadays, a prenatal diagnosis canbe established using direct ABCA12 sequence analysisof fetal DNA obtained from amniocentesis fluid or cho-rionic villus sampling material in pregnancies at risk. Inaddition, there are two-dimensional ultrasound featuressuggestive of HI such as a large persistently open mouth,atypical nasal and ear dysmorphism, minimal fetal move-ment with semiflexed extremities and a hyperechogenicamniotic fluid. Three- and four-dimensional sonographyare essential to confirm the diagnosis in these cases [7].

At birth, the neonate is covered with thick plate-likedesquamation, separated by deep fissures. The defectivecutaneous barrier leads to an increased vulnerability toinfections. Other clinical findings caused by the thickepidermal plates include ectropion and eclabium. Lateron, the thick stratum corneum sheds revealing a diffuseerythema with fine scaling [1,3].

A multidisciplinary approach and strong bonds withthe family are key elements in optimal management ofthe affected neonate [8]. Our team was composed of apediatric intensive care neonatologist, a dermatologist,an obstetrician, a geneticist, an ophthalmologist, a plas-tic surgeon and a psychologist as well as experiencedNICU staff. Pictures of survivors were shown to the par-ents suggesting that the neonate will not be as severelyaffected once he survives the critical period.

There is no standard approach to manage the HIpatient. Systemic retinoids have proven clinical efficacyin ichthyosis and ichthyosiform dermatosis [9,10]. In thesetting of HI, studies have shown that oral retinoids couldincrease survival from 24% to 83% by promoting peelingand thinning of the stratum corneum [1]. Parenteral nutri-tion and heated high humidity incubators compensate forthe difficulty in feeding and thermal imbalance. Support-ive measures are primordial and include: regular emol-lient application to maintain skin hydration, lubricationof the cornea to prevent dryness, adequate analgesics andfrequent blood draws and cultures to monitor for anyelectrolyte imbalances or signs of infection. Fluid bal-ance and weights should be followed closely. Surgical

release of constricting bands is an important adjunct tomanagement in case of respiratory distress or extremitycongestion [11].

CONCLUSION

In summary, a multidisciplinary approach and aggressiveneonatal intensive care are key elements in the successfulmanagement of HI babies. Evidence of improvement insurvival brings hope to burdened families. The revolution-ary use of retinoid and the continuous advances in neo-natal care strive to make harlequin ichthyosis a chroniccondition rather than a fatal disease. Nonetheless, furtherstudies are still needed to establish a standardized treat-ment protocol.

REFERENCES:

1. Rajpopat S, Moss C, Mellerio J et al. Harlequin ichthyo-sis: A review of clinical and molecular findings in 45cases. Arch Dermatol 2011 Jun 20; 147 (6): 681-6.

2. Aamir Habib WP. Harlequin ichthyosis in two siblings.J Coll Physicians Surg Pak 2011; 21 (8): 503-5.

3. Harvey HB, Shaw MG, Morrell DS. Perinatal manage-ment of harlequin ichthyosis: a case report and literaturereview. J Perinatol Off J Calif Perinat Assoc 2010 Jan; 30(1): 66-72.

4. Thomas AC, Tattersall D, Norgett EE et al. Prematureterminal differentiation and a reduction in specific pro-teases associated with loss of ABCA12 in Harlequinichthyosis. Am J Pathol. 2009; 174 (3): 970-8.

5. Kelsell DP, Norgett EE, Unsworth H et al. Mutations inABCA12 underlie the severe congenital skin disease har-lequin ichthyosis. Am J Hum Genet 2005 May; 76 (5):794-803.

6. Ying Zuo DZZ. ABCA12 maintains the epidermal lipidpermeability barrier by facilitating formation of ceramidelinoleic esters. J Biol Chem. 2008; 283 (52): 36624-35.

7. Vohra N, Rochelson B, Smith-Levitin M. Three-dimen-sional sonographic findings in congenital (harlequin) ich-thyosis. J Ultrasound Med Off J Am Inst Ultrasound Med2003 Jul; 22 (7): 737-9.

8. Milstone LM, Choate KA. Improving outcomes for harle-quin ichthyosis. J Am Acad Dermatol 2013; 69 (5): 808-9.

9. Frost P, Weinstein GD. Topical administration of vitaminA acid for ichthyosiform dermatoses and psoriasis.JAMA 1969 Mar 10; 207 (10): 1863-8.

10. Digiovanna JJ, Mauro T, Milstone LM, Schmuth M, Toro JR.Systemic retinoids in the management of ichthyoses andrelated skin types. Dermatol Ther 2013 Feb; 26 (1): 26-38.

11. Roberts JB, Adelson D. Case report: Prolonged collodionmembrane causing constrictive bands of the digits andtreatment. Dermatol Online J [Internet] 2010 Jan 1 [cited2014 Jul 29]; 16 (1). Available from: http://escholarship.org/uc/item/2zh869q7

M. NASR et al. – Multidisciplinary team approach in Harlequin baby Lebanese Medical Journal 2017 • Volume 65 (1) 51