BRIEF REPORT Pediatric Dermatology Vol. 31 No. 2 e63–e64, 2014
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Harlequin Ichthyosis: Neonatal Management and Identification of a New ABCA12 Mutation Abstract: A case of harlequin ichthyosis with compound heterozygous mutations in ABCA12 was successfully managed with intensive neonatal care and endotracheal intubation and without oral retinoids. The individual’s appearance improved dramatically during hospitalization and at discharge resembled congenital ichthyosiform erythroderma.
CASE REPORT The high neonatal mortality of harlequin ichthyosis (HI) remains unexplained and the usefulness of early oral retinoids is debatable (1). The severe HI phenotype has never been reported to persist beyond the neonatal period, and spontaneous improvement may be a characteristic of the disease (2). Because of the rarity of this disease, all new reports of successful early outcomes help in developing a consensus for better management. A boy in whom the HI diagnosis was made 2 days before birth by ultrasonography was delivered by cesarean section because of premature rupture of membranes and breech presentation at 31 weeks gestation. Apgar scores were 2 and 7, and birthweight was 848 g. A thick opaque scale covered the head, face, and intertriginous areas and a more translucent scale covered the trunk and extremities. There was severe ectropion and eclabium; the nares and ears were totally encased in scale (Fig. 1A). Poor respiratory effort and lack of patent nares prompted immediate intubation. He was placed in a humidified, heated isolette on contact isolation in a private room. Serum electrolytes were monitored closely and intravenous fluid administration was adjusted accordingly. Nutrition through an orogastric tube was based on an estimate that he would
DOI: 10.1111/pde.12263
© 2013 Wiley Periodicals, Inc.
Figure 1. A patient with harlequin ichthyosis at (A) 1 day old and (B) 1 year old.
require 30% to 50% more caloric intake than the usual neonate his size. He received daily (0.01% hypochlorite) bleach baths, and liberal amounts of petroleum ointment were applied to his skin and lubricant eye ointment to his eyes. Administration of acitretin (0.5 mg/kg) through an orogastric tube was abandoned after three attempts induced immediate vomiting. Duskiness of the fingertips was noted on the third day of life; circulatory compromise caused by constricting scale was the likely cause. Tazarotene cream 0.1% was started on the face, scalp, hands, and feet (3). Thick bands of stratum corneum on the digits were debrided using a 2-mm curette and constrictions were relieved by introducing linear fissures in the stratum corneum using a scalpel until underlying tissue began to bulge through, resulting in rapid resolution of digital duskiness, as previously described for collodion babies (4). Milestones during hospitalization included replacement of the orogastric tube with a nasogastric tube on day 6 when the nares became patent, extubation on day 11, shedding of the thick translucent scale from the trunk and extremities by week 7 and most of the opaque scale from the face by week 8, inguinal herniorrhaphy at week 7, and discharge home on day 59 with the appearance of congenital ichthyosiform erythroderma (Fig. 1B). He is currently 2.5 years old. At home he gets one or two 30-minute baths and four to five applications of petroleum ointment per day. He has delays in cognitive and motor development. This patient has compound heterozygous mutations in exon 51 of ABCA12: a previously reported C?T mutation in codon 2482 (5) and a previously unreported C?A mutation in codon 2512. Each mutation predicts truncation at the C-terminal end of
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TABLE 1. Management Considerations Affecting Neonatal Outcome in Harlequin Ichthyosis Medical Admission to neonatal intensive care unit and low threshold for early intubation Attention to greater-than-normal fluid and calorie needs Recognition that most of the hyperkeratosis resolves spontaneously Removal of clinically significant constricting or obstructing hyperkeratosis Skin care focused on improving pliability, limiting insensible water loss, and preventing infection Prevention of corneal drying Social Dedicated team of nurses Education of the family and care team about expected phenotypic improvement Regular communication between nurses, dermatologists, and intensivists Early interaction of the child with the family
the protein; compound heterozygous mutations are associated with a milder phenotype (1). Critical factors in this patient’s management include educating the family and care team about the favorable outcome in other HI patients; coordinated intensive care, including early intubation, careful attention to metabolic needs, and skin care; and mechanical removal of constricting scale that interfered with circulation (Table 1). ACKNOWLEDGMENT The authors commend the outstanding care given this patient by the staff of the Newborn Intensive Care Unit of the Yale–New Haven Hospital, New Haven, CT.
REFEERENCES 1. Rajpopat S, Moss C, Mellerio J et al. Harlequin ichthyosis: a review of clinical and molecular findings in 45 cases. Arch Dermatol 2011;147:681–686. 2. Yanagi T, Akiyama M, Nishihara H et al. Selfimprovement of keratinocyte differentiation defects during skin maturation in ABCA12-deficient harlequin ichthyosis model mice. Am J Pathol 2010;177:106–118. 3. Liu RH, Becker B, Gunkel J et al. Rapid improvement in digital ischemia and acral contracture in a collodion baby treated with topical tazarotene. J Drugs Dermatol 2010;9:713–716. 4. Roberts JB, Adelson D. Case report: prolonged collodion membrane causing constrictive bands of the digits and treatment. Dermatol Online J 2010;16:15. 5. Sakai K, Akiyama M, Yanagi T et al. ABCA12 is a major causative gene for non-bullous congenital ichthyosiform erythroderma. J Invest Dermatol 2009;129:2306–2309. Arash Koochek, M.D. Keith A. Choate, M.D., Ph.D. Leonard M. Milstone, M.D. Department of Dermatology, School of Medicine, Yale University, New Haven, Connecticut Address correspondence to Leonard M. Milstone, M.D., Department of Dermatology, Yale University School of Medicine, HRT604C, 15 York Street, New Haven, CT 06520, or e-mail: [email protected].
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B
Harlequin Ichthyosis: Neonatal Management and Identification of a New ABCA12 Mutation Abstract: A case of harlequin ichthyosis with compound heterozygous mutations in ABCA12 was successfully managed with intensive neonatal care and endotracheal intubation and without oral retinoids. The individual’s appearance improved dramatically during hospitalization and at discharge resembled congenital ichthyosiform erythroderma.
CASE REPORT The high neonatal mortality of harlequin ichthyosis (HI) remains unexplained and the usefulness of early oral retinoids is debatable (1). The severe HI phenotype has never been reported to persist beyond the neonatal period, and spontaneous improvement may be a characteristic of the disease (2). Because of the rarity of this disease, all new reports of successful early outcomes help in developing a consensus for better management. A boy in whom the HI diagnosis was made 2 days before birth by ultrasonography was delivered by cesarean section because of premature rupture of membranes and breech presentation at 31 weeks gestation. Apgar scores were 2 and 7, and birthweight was 848 g. A thick opaque scale covered the head, face, and intertriginous areas and a more translucent scale covered the trunk and extremities. There was severe ectropion and eclabium; the nares and ears were totally encased in scale (Fig. 1A). Poor respiratory effort and lack of patent nares prompted immediate intubation. He was placed in a humidified, heated isolette on contact isolation in a private room. Serum electrolytes were monitored closely and intravenous fluid administration was adjusted accordingly. Nutrition through an orogastric tube was based on an estimate that he would
DOI: 10.1111/pde.12263
© 2013 Wiley Periodicals, Inc.
Figure 1. A patient with harlequin ichthyosis at (A) 1 day old and (B) 1 year old.
require 30% to 50% more caloric intake than the usual neonate his size. He received daily (0.01% hypochlorite) bleach baths, and liberal amounts of petroleum ointment were applied to his skin and lubricant eye ointment to his eyes. Administration of acitretin (0.5 mg/kg) through an orogastric tube was abandoned after three attempts induced immediate vomiting. Duskiness of the fingertips was noted on the third day of life; circulatory compromise caused by constricting scale was the likely cause. Tazarotene cream 0.1% was started on the face, scalp, hands, and feet (3). Thick bands of stratum corneum on the digits were debrided using a 2-mm curette and constrictions were relieved by introducing linear fissures in the stratum corneum using a scalpel until underlying tissue began to bulge through, resulting in rapid resolution of digital duskiness, as previously described for collodion babies (4). Milestones during hospitalization included replacement of the orogastric tube with a nasogastric tube on day 6 when the nares became patent, extubation on day 11, shedding of the thick translucent scale from the trunk and extremities by week 7 and most of the opaque scale from the face by week 8, inguinal herniorrhaphy at week 7, and discharge home on day 59 with the appearance of congenital ichthyosiform erythroderma (Fig. 1B). He is currently 2.5 years old. At home he gets one or two 30-minute baths and four to five applications of petroleum ointment per day. He has delays in cognitive and motor development. This patient has compound heterozygous mutations in exon 51 of ABCA12: a previously reported C?T mutation in codon 2482 (5) and a previously unreported C?A mutation in codon 2512. Each mutation predicts truncation at the C-terminal end of
e63
e64 Pediatric Dermatology Vol. 31 No. 2 March/April 2014
TABLE 1. Management Considerations Affecting Neonatal Outcome in Harlequin Ichthyosis Medical Admission to neonatal intensive care unit and low threshold for early intubation Attention to greater-than-normal fluid and calorie needs Recognition that most of the hyperkeratosis resolves spontaneously Removal of clinically significant constricting or obstructing hyperkeratosis Skin care focused on improving pliability, limiting insensible water loss, and preventing infection Prevention of corneal drying Social Dedicated team of nurses Education of the family and care team about expected phenotypic improvement Regular communication between nurses, dermatologists, and intensivists Early interaction of the child with the family
the protein; compound heterozygous mutations are associated with a milder phenotype (1). Critical factors in this patient’s management include educating the family and care team about the favorable outcome in other HI patients; coordinated intensive care, including early intubation, careful attention to metabolic needs, and skin care; and mechanical removal of constricting scale that interfered with circulation (Table 1). ACKNOWLEDGMENT The authors commend the outstanding care given this patient by the staff of the Newborn Intensive Care Unit of the Yale–New Haven Hospital, New Haven, CT.
REFEERENCES 1. Rajpopat S, Moss C, Mellerio J et al. Harlequin ichthyosis: a review of clinical and molecular findings in 45 cases. Arch Dermatol 2011;147:681–686. 2. Yanagi T, Akiyama M, Nishihara H et al. Selfimprovement of keratinocyte differentiation defects during skin maturation in ABCA12-deficient harlequin ichthyosis model mice. Am J Pathol 2010;177:106–118. 3. Liu RH, Becker B, Gunkel J et al. Rapid improvement in digital ischemia and acral contracture in a collodion baby treated with topical tazarotene. J Drugs Dermatol 2010;9:713–716. 4. Roberts JB, Adelson D. Case report: prolonged collodion membrane causing constrictive bands of the digits and treatment. Dermatol Online J 2010;16:15. 5. Sakai K, Akiyama M, Yanagi T et al. ABCA12 is a major causative gene for non-bullous congenital ichthyosiform erythroderma. J Invest Dermatol 2009;129:2306–2309. Arash Koochek, M.D. Keith A. Choate, M.D., Ph.D. Leonard M. Milstone, M.D. Department of Dermatology, School of Medicine, Yale University, New Haven, Connecticut Address correspondence to Leonard M. Milstone, M.D., Department of Dermatology, Yale University School of Medicine, HRT604C, 15 York Street, New Haven, CT 06520, or e-mail: [email protected].
