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.