Discussion:
Harlequin ichthyosis, also called as keratosis diffusa foetalis or
ichthyosis congenital, is a rare disorder found equally in both
sexes1 with an overall incidence of 1:300,000 births.
Currently, more than 100 cases have been described in the
literature.2 The first case was reported by Oliver
Hart in 1750.3 This condition is usually seen in
premature babies, early pregnancies, preterm delivery, and more often in
consanguineous marriages.4,5 In such cases, vaginal
delivery is generally the norm while in high-risk pregnancies, caesarean
delivery is performed. In our case, the young mother presented with
obstetric pain and preterm premature rupture of membrane as an obstetric
emergency and caesarean delivery was performed. The recurrence of this
condition in the subsequent pregnancy is estimated to be
25%.6 Hence, it is crucially important to counsel the
parents regarding the genetic disorder and its probability in their next
conception.
HI is clinically diagnosed at birth with the typical presentation of
large, coarse, shiny, yellowish brown, generalized hyper-keratinized
sticky plates resulting in constricted mobility in upper and lower limbs
with clasped fists and incurved toes. Later, deep fissures or cracks
occur on these hard plates that spread to the dermis. Neonates with HI
have growth retardation, eclabium, edema, microcephaly, and
ectropion.7 Ear appendages, nostrils look undeveloped
and immature.8 Additionally, neonates have
hypothermia, hypoglycemia, water and electrolytes imbalance,
dehydration, infections, sepsis, inadequate feeding habits, renal
failure, and more often respiratory complications as a result of limited
chest expansion and skeletal abnormalities, eventually leading to death
in the early days of life.9,10
Later in surviving patients, the hyperkeratotic scales fall off in the
first few months, leaving an overlying persistent erythematous skin. In
our patient, all these features were present suggestive of HI. Several
studies have reported the presence of mutations in the ABCA12
(Adenosine-triphosphate-Binding Cassette A12) gene encoding a protein
for lipid transport in the skin are involved in the pathophysiology of
the disease. The ABCA12 gene on chromosome 2 translates a protein
involved in keratinocyte lipid transport across the epidermis of the
skin which helps in the physiological development of skin and controls
the progression of desquamation. The lack of normal ABCA12 function of
transportation of lipids from the cytosol to the lamellar granules
results in defective skin permeability and accumulation of
scales.11,12
Prenatal diagnosis is important and helps in early detection of the
disease. Chorionic villous sampling and microscopic analysis of the
amniotic fluid cells and USG especially 3D USG for assessment of the
shape of the fetal mouth particularly during the early third trimester
of pregnancy have been useful for early detection.13Akiyama et al. specified the first DNA-based prenatal diagnosis of HI by
direct sequential analysis of ABCA12 gene mutation from amniotic fluid
cells and established the efficiency of early DNA-based prenatal
diagnosis.14
In addition to this, obtaining a detailed account of family history,
previous obstetric history, consanguinity between the parents, and the
presence of other dermatological disorders in other offspring is equally
important.15 Postnatal diagnosis includes a skin
biopsy that probably shows structural abnormalities of lamellar granules
and epidermal keratin expression and is confirmed by testing for ABCA12
gene mutation. Generally, the late phenotypic expression of this
condition possesses a challenge and leads to missed or delayed diagnosis
on prenatal scans.12 Similarly in our case, there was
no remarkable complication noted in the last ultrasound examination at
28 weeks of pregnancy. Hence, the gross appearance of the fetus is
usually insufficient for diagnosis. To prevent complications and tackle
its associated comorbidities multi-disciplinary team management is
required.
Initial management necessitates monitoring in Neonatal intensive care
unit settings (NICU) including supportive therapy to maintain quality of
life by use of humidified incubator for monitoring temperature
regulation. Intubation helps with the airway and breathing. Maintenance
of fluids, electrolytes, and nutritional support through umbilical
cannulation as access to peripheral veins becomes difficult. Limb
contracture leads to amputation due to the presence of tissue necrosis
and gangrene. Hence, it should be a reminder for surgical intervention
using autologous skin grafts with the utmost care, physiotherapy,
analgesia for painful deep fissures and proper infection
control.16 Eye care by artificial tears lubrication
and frequent evaluation by ophthalmologists is recommended. Repeated
blockage of the ear canal may occur and debridement is often required.
Mild ointments should be applied to make skin soft and soaking with
saline compressions helps in desquamation. Further repeated skin culture
would be crucial to detect harmful microorganisms.8
A comprehensive case series comprising 45 patients assessed by Rajpot
et al. suggested early oral retinoids, aid in the shedding of
hyperkeratotic scales, with an overall survival rate of more than
50%.17 Some studies have shown systemic retinoids can
improve survival rates but have both acute and chronic
toxicity.18 In addition, genetic counselling and
molecular investigation of the ABCA12 gene should be considered in
subsequent pregnancies as an autosomal recessive disease has been
recognized. Studies should further investigate the possible use of
immunotherapy.
Critical factors in this patient’s management include cooperation and
educating the family about the outcomes and options because HI has a
social disgrace in our country linked with lack of Knowledge and
awareness of the disease and to avoid further endangering the child. Our
patient was discharged on request after birth due to non-compliance by
her father.