Improved Management of Harlequin Ichthyosis With Advances in Neonatal Intensive Care Jaimie B Glick, MD,a Brittany G Craiglow, MD,b, c Keith A Choate, MD, PhD,b, d, e Hugo Kato, MD,f Robert E Fleming, MD, f Elaine Siegfried, MD, f, g Sharon A Glick, MDa

Harlequin ichthyosis (HI) is the most severe phenotype of the autosomal abstract recessive congenital ichthyoses. HI is caused by mutations in the lipid transporter adenosine triphosphate binding cassette A 12 (ABCA12). Neonates are born with a distinct clinical appearance, encased in a dense, platelike keratotic scale separated by deep erythematous fissures. Facial features are distorted by severe ectropion, eclabium, flattened nose, and a rudimentary ears. Skin barrier function is markedly impaired, which can Department of Dermatology, State University of New York Downstate Medical Center, Brooklyn, New York; lead to hypernatremic dehydration, impaired thermoregulation, increased Departments of bDermatology, cPediatrics, dGenetics, metabolic demands, and increased risk of respiratory dysfunction and and ePathology, Yale University School of Medicine, New Haven, Connecticut; and Departments of fPediatrics and infection. Historically, infants with HI did not survive beyond the neonatal gDermatology, Saint Louis University School of Medicine, period; however, recent advances in neonatal intensive care and coordinated St Louis, Missouri multidisciplinary management have greatly improved survival. In this Dr J. Glick drafted the initial manuscript; review, the authors combine the growing HI literature with their collective Drs Craiglow, Choate, and Fleming critically experiences to provide a comprehensive review of the management of reviewed and revised the manuscript; Mr Kato contributed critical sections to the manuscript and neonates with HI. revised the manuscript; Drs Siegfried and S. A. Glick conceptualized the article and critically reviewed and revised the manuscript; and all authors Harlequin ichthyosis (HI) is the most improved long-term survival. This approved the fi nal manuscript as submitted and agree to be accountable for all aspects of the work. severe phenotype of the autosomal review incorporates the growing recessive congenital ichthyoses. 1 HI literature with the collective DOI: 10.1542/peds.2016-1003 Neonates have a striking appearance, experience of the authors to provide Accepted for publication Jul 5, 2016 encased in a cream-colored, dense, an update on practical management Address correspondence to Sharon A Glick, MD, platelike keratotic scale punctuated of HI. Department of Dermatology, State University of New York Downstate Medical Center, 450 Clarkson by deep red fissures. Facial features Ave, Brooklyn, NY 11203. E-mail: sharon.glick@ are distorted by the presence of dense downstate.edu PATHOPHYSIOLOGY opaque scale on the face resulting PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, in severe ectropion (outturning of 1098-4275). HI is caused by mutations in the lipid the eyelids), eclabium (eversion of transporter adenosine triphosphate Copyright © 2017 by the American Academy of the lips), and flattened nose and ear Pediatrics binding cassette A12 (ABCA12). 3, 4 cartilage. Skin barrier function is FINANCIAL DISCLOSURE: ABCA12 is a member of the subfamily The authors have markedly impaired with associated indicated they have no fi nancial relationships of adenosine triphosphate–binding relevant to this article to disclose. hypernatremic dehydration, impaired cassette protein transporters. FUNDING: No external funding. thermoregulation, increased Its function in the epidermis is metabolic demands, and increased to facilitate the delivery of lipid POTENTIAL CONFLICT OF INTEREST: The authors have no potential confl icts of interest to disclose. risk of respiratory failure and glucosylceramides into lamellar sepsis.2 Historically, HI was viewed granules, which then deliver them into as a fatal disease; however, recent the extracellular space. 3, 5– 7 Electron To cite: Glick JB, Craiglow BG, Choate KA, et al. advances in neonatal intensive care microscopy of lamellar granules in HI Improved Management of Harlequin Ichthyosis and coordinated multidisciplinary are abnormally shaped, reduced in With Advances in Neonatal Intensive Care. Pediatrics. 2017;139(1):e20161003 management have dramatically number, and in some cases absent. 8

Downloaded from www.aappublications.org/news by guest on September 24, 2021 PEDIATRICS Volume 139 , number 1 , January 2017 :e 20161003 STATE-OF-THE-ART REVIEW ARTICLE Less damaging mutations in ABCA12 carrier status allows for DNA-based greatly improved analysis of facial cause milder forms of congenital prenatal or preimplantation genetic morphology and may aid in prenatal ichthyosis phenotypes that fall on diagnosis in future pregnancies. Next diagnosis; however, detection of the lamellar ichthyosis–congenital generation sequencing is replacing these unusual features requires ichthyosiform erythroderma Sanger sequencing for diagnosis of HI tertiary expertise, and they are not spectrum. 9 –11 as a less expensive and more efficient detectable until the second trimester, alternative. Resources for gene excluding the option of early The compromised skin barrier is testing for HI in the United States are termination. 16 likely related to abnormal lamellar listed in Table 1. granule maturation and secretion resulting in inadequate delivery of CLINICAL CHARACTERISTICS lipids, antimicrobial peptides, and PRENATAL DIAGNOSIS Affected neonates are often born enzymes necessary for keratinocyte Advances in fetal DNA analysis and prematurely. 15 The thickened desquamation into the extracellular ultrasound technology have replaced armorlike skin can cause space. As a result, transepidermal the more invasive techniques of fetal pseudocontractures that restrict water loss (TEWL) is increased, skin biopsy. 1 Fetal DNA analysis movement, and impaired perfusion leading to increased metabolic can be offered to parents who had a can result in digital necrosis. Skin of demand, 12 risk for hypernatremic previous child with HI. Fetal genomic surviving infants gradually adapts dehydration, temperature DNA is obtained from amniotic fluid from the aqueous intrauterine dysregulation, and increased via amniocentesis or chorionic villus to the extrauterine environment, accumulation of stratum corneum. sampling. 13 New research has shown with skin phenotype evolving to that messenger RNA analysis using generalized erythema and scaling, EPIDEMIOLOGY, RECOGNITION, AND hair samples can also more easily often with associated palmoplantar GENETIC TESTING and less invasively be used to identify keratoderma. 15, 17 ABCA12 mutations. 14 HI is recognized at birth by the HI can usually be differentiated typical clinical appearance ( Fig 1A). In some cases, prenatal from the less severe collodion baby Reverend Oliver Hart reported ultrasonography may allow phenotype (CBP) on the basis of the first case in 1750, and disease detection of signs suggestive of clinical appearance. HI features incidence has been estimated to be HI, including eclabium, ectropion, generalized armorlike yellow scale, ∼1 in 300 000 births.1 HI is inherited rudimentary ears, contractures, and whereas the classic skin changes in an autosomal recessive fashion. dense floating particles in amniotic of CBP are more translucent and Single-nucleotide polymorphism fluid (“snowflake sign”). 15 The waxy. Ectropion and eclabium are array technology for homozygosity application of three-dimensional often present in patients with CBP, mapping identified the HI locus ultrasound theoretically offers a but are generally far less severe. at chromosome 2q25. 4 Multiple mutations have been reported, including premature termination, insertion, deletion, and frameshift mutations, resulting in an absent or truncated ABCA12 protein. 1,3, 4 Mutations that permit residual ABCA12 function appear to have a survival advantage over those with early termination mutations.

The optimal time for obtaining FIGURE 1 a biological sample for genetic A neonate with HI. A, A neonate with HI on day 1 of life. B, The same neonate at 4 months of age after testing is shortly after birth to receiving intensive neonatal care and acitretin at 0.5 mg/kg per day. Responses among neonates will vary. confirm the clinical diagnosis, assist with assessing prognosis, and enable genetic counseling. TABLE 1 Resources for Genetic Testing for HI in the United States Access to insurance coverage for Organization Name Web Site the costs of genetic testing may also Genetic Testing Registry www.ncbi. nlm. nih. gov/ gtr/ be easier when performed during GeneTests www.genetests. org/ hospitalization. Identifying parental Ichthyosis Registry at Yale www.dermatology. yale. edu/ research/ ichthyosis. aspx

Downloaded from www.aappublications.org/news by guest on September 24, 2021 2 GLICK et al TABLE 2 Management of HI During the Neonatal Period TABLE 3 Monitoring Parameters in HI Admission to a NICU. Complete blood count 18 Placement in a humidifi ed isolette at 50%–70% humidifi cation. Electrolytes: Na, K, Cl, Mg, P, CO2, glucose, Monitoring of body temperature to prevent TEWL and associated temperature dysregulation. calcium Monitoring of daily body weight and fl uid status; daily monitoring of electrolytes to prevent Kidney function: blood urea nitrogen, creatinine, hypernatremic dehydration during the fi rst week and thereafter based on patient’s condition. urine output Meeting high caloric demands and nutrition supplementation. Liver functiona Skin care with daily bathing (± antiseptics) followed by application of bland emollient every 4–6 h. Lipid levelsa Vigilant monitoring for respiratory compromise with a low threshold for intubation. Total protein, albumin and prealbumin Vigilant monitoring for infection with surveillance cultures from selected skin sites and folds with a low Daily weights threshold for antibiotics based on cultured microbes. Skin surface cultures daily × 1 wk and weekly Eye care with application of bland lubricant every 6–12 h; reserve topical antibiotics for conjunctivitis or while in intensive care corneal abscesses. Blood culturesb Monitoring of limb and digit perfusion. Consider surgical intervention, splinting, and physical therapy as Vitamin D levela needed. a Particularly important if retinoid therapy is instituted. Controlling pain with acetaminophen, nonsteroidal antiinfl ammatory agents and/or narcotics as needed. b Low threshold to perform especially with temperature or hemodynamic instability, decreased oral intake, or irritability Rarely, patients present with an as individualized for the patient. 19 “incomplete” harlequin phenotype, Serum electrolytes, urine output, baths. 11 This can be accomplished by with more severe findings at daily weights, prealbumin, and dampening roll gauze with warmed localized body sites, particularly the kidney and liver function should 0.125% sodium hypochlorite mixed head, in the setting of an otherwise be monitored closely ( Table 3). 1:10 with warmed sterile water. The collodion presentation. Patients Prevention of infection is particularly optimal pH is 8 to 8.5. The gauze can with both phenotypes benefit from important. Deep fissuring of the thick be applied as a wet wrap, occluded ichthyosis gene panel testing and scale can penetrate the epidermis with a plastic wrap layer for 10 to intensive neonatal management. and become a source of pain. It 20 minutes. 23 A bland emollient is important to provide adequate should be applied immediately after pain control (see section below). wet wrap removal. Products, such NEONATAL MANAGEMENT Many neonates will initially require as petrolatum jelly, extra virgin Admission to a tertiary care center narcotics. Infants with milder coconut oil, and sunflower seed oil, with a level III NICU is desirable. phenotypes may have adequate are considered safe and may even Intensive care management is pain control with acetaminophen possess antimicrobial properties.24, 25 largely supportive and involves a or nonsteroidal antiinflammatory The authors recommend handling multidisciplinary team, including agents. 20, 21 infants with sterile, latex-free gloves neonatology, dermatology, genetics, and using single use packets of ophthalmology, otolaryngology, Securing Lines emollient to minimize colonization orthopedic and plastic surgery, with pathogenic microbes. 19 Initial placement of a central venous nutrition, physical therapy, and umbilical line is standard for high- Application of keratolytic-containing nursing. risk neonates and useful in patients emollients should be avoided in the Because of the significant morbidity with HI for hydration, parenteral neonatal period due to the risk of associated with HI, the high risk nutrition, and laboratory sampling. percutaneous toxicity. Respiratory of respiratory failure requiring Alternative access is via peripheral distress has been reported after use intubation, and potential risk of scalp vein or a peripherally inserted of topical salicylic acid. 26 Reports neonatal demise, discussion regarding central catheter line. A protocol to on the use of topical ceramide- aggressivity of support should be held secure lines in infants with fragile containing emollients have been with parents and documented early in skin has been developed ( Fig 2). conflicting. Although ceramides the course (see Ethical Considerations can stimulate ABCA12 expression section below). Beyond complications Skin Care through the peroxisome proliferator- of prematurity, minimizing TEWL, δ27 Skin barrier dysfunction in neonates activated receptor PPAR , topical preventing electrolyte imbalance, is especially problematic, given application has not been shown to temperature dysregulation, 28 the large body surface-to-weight improve barrier function. respiratory distress, malnutrition, and ratio.22 Skin care should include Digital necrosis is a common infection are key to survival and best once to twice daily cleansing to complication in HI, related to a performed in the NICU (Table 2). hydrate and promote shedding of the compartmentlike syndrome from Neonates should be maintained in stratum corneum. 21 Some suggest epithelial constriction. Surgical an incubator with added humidity, daily buffered dilute hypochlorite intervention can be digit or limb

Downloaded from www.aappublications.org/news by guest on September 24, 2021 PEDIATRICS Volume 139 , number 1 , January 2017 3 FIGURE 2 A protocol to secure lines in infants with fragile skin. Gently dab skin with Chloraprep (BD, Franklin Lakes, NJ) or Betadine (Purdue Products LP, Stamford, CT). Then apply Cavilon skin prep (3M, St. Paul, MN). Place Mepiform (Mölnlycke, Göteborg, Sweden) as bottom layer. Ensure that the cover dressing and steri-strips do not come in contact with skin. Leave at least a 1-cm border of Mepiform extending beyond cover dressing to ease removal. Mepitac (Mölnlycke, Göteborg, Sweden); Tegaderm (3M, St. Paul, Minnesota); Biopatch (Ethicon, Someville, NJ); Silvasorb (Medline, Mundelein, IL). (Fragile skin dressing image courtesy of a collaboration between the Aurora Children's Hospital [Denver, CO] and the Epidermolysis Bullosa Center at Cincinnati Children's Hospital Medical Center [Cincinnati, OH].) saving ( Figs 3, 4, and 5). Several fasciotomy techniques have been described, including a linear band incision technique. 29 Daily application of a topical retinoid (eg, 0.1% tazarotene cream) and soft splinting of the hands and feet may be an alternative to or augment surgical intervention.21

Nutrition Increased TEWL and skin turnover increases caloric demands in HI FIGURE 3 neonates. 12, 20 Furthermore, eclabium Digital pallor and pseudocontractures resulting and jaw constriction may interfere from cutaneous constriction on day 1 of life. FIGURE 4 with oral feeding. Often, neonates Evidence of compromised perfusion and require supplemental oropharyngeal maintain caloric needs has been impending digital necrosis on day 3 of life. or nasogastric tube feeds. Fluid noted in infants with HI, and long- balance, serum protein, albumin, term supplemental tube feeding may ichthyosis.15, 30 There is conflicting and electrolytes must be monitored be required. Frequent emesis has also evidence regarding whether this carefully. Once an adequate suck been observed, but the possibility of deficiency is associated with the use and swallow has been established, associated gastroenteral dysmotility of oral retinoids. 31, 32 Lower vitamin D breastfeeding should be encouraged has not been studied. levels have also been associated with to enhance bonding between mother Vitamin D deficiency and rickets increased risk of neonatal sepsis.33 and child. 19, 21 Inadequate suck to have been reported in neonates with Monitoring vitamin D levels and

Downloaded from www.aappublications.org/news by guest on September 24, 2021 4 GLICK et al and exposure keratitis. 1 Lubricant antimicrobial peptides cathelicidin ophthalmic ointment should be (LL-37) and human β defensin 2.41 applied to lid margins a minimum There is limited evidence for the of every 6 to 12 hours. Surgical benefits of antimicrobial prophylaxis correction of ectropion has been in neonates with HI. The authors reported with full-thickness recommend serial surveillance swabs autografts from the thigh and for bacterial and fungal cultures posterior auricular skin as well as from selected sites (eg, skin folds, from engineered human skin. 34 – 36 nares, ear canals, perianal area) daily There is no evidence that early for the first week of life and once surgery results in less ectropion at 6 weekly for the remainder of the NICU to 12 months of age than would occur stay. Early recognition of infection as part of the natural history of HI. FIGURE 5 in infants with HI is important, but Enhanced perfusion of digits immediately after Because retinoids promote stratum can be challenging. Many of the releasing incisions on day 4 of life. corneum desquamation, both findings associated with infection in oral37 and topical retinoids 38 may supplementation as necessary may infants (eg, tachypnea, tachycardia, be effective in reducing ectropion. be useful for the care of the HI infant. poor intake) are even less specific Early ophthalmology evaluation is in infants with HI. Tachypnea may recommended. Pain Control be due to restricted tidal volumes or to pain. Tachycardia may be a Deep fissures and skin sloughing can Otologic Management be a source of pain in neonates. 20 sign of pain or of dehydration. Poor Assessing the severity of pain in Reports on the otologic oral intake may be indicative of neonates with HI, however, can manifestations of HI have noted that restricted jaw movement and tiring be challenging. Newborn pain patients have signs or symptoms with feedings. As such, a high index scales include facial expression of ear discomfort.39 Possible of suspicion for infection needs to be as a parameter; most also include causes include excessive ear canal maintained, as well as a low threshold extremity tone and respiratory rate. debris, dysbiosis, or secondary for laboratory workup, blood, Interpreting each of these can be contact dermatitis. Vigorous ear spinal fluid, and urine cultures, and problematic in infants with HI. The debridement and skin manipulation initiation of systemic antimicrobial characteristic eclabium results in a should be avoided to minimize therapy in infants with HI. fixed facial appearance as if in pain. the risks of infection. Professional Respiratory Function The respiratory rate can be increased microsuctioning to remove skin due to restricted tidal volumes. The debris may help prevent early Respiratory failure and sepsis are fingers and toes may remain fixed conductive hearing loss. 15, 21 Ear the leading causes of early demise due to encasement. As such, other drops have also been used to in HI. 15 Several mechanisms other parameters, such as heart rate, blood soften keratin plugs in the ear than infection can contribute to pressure, crying, and state of arousal, canal. Options include 0.25% acetic respiratory failure in these infants. become relatively more useful. It is acid or 2% aluminum acetate. Restricting bands of thickened imperative that pain is well managed, Avoid the potential percutaneous epidermis and painful fissures may and that parents are reassured toxicity of salicylic acid and the compromise chest expansion, and that this issue has been addressed. risk of Malassezia overgrowth excessive keratotic debris may block Adequate pain control might associated with olive oil. 40 Early nasal respiration in these obligate require the use of narcotics, even otolaryngology26 and audiology nose breathers. Pulmonary defects if such treatment contributes to a intervention is recommended. of surfactant secretion have been requirement for assisted ventilation. reported in one mouse model of HI, 42 The severity of pain dissipates after Infection but not in another. 43 A low threshold the surface layer has been shed, and HI neonates are particularly prone for intubation and mechanical the underlying skin epithelialized. to sepsis. Although the impaired ventilation should be considered for 44 skin barrier is a likely portal, 20 these neonates. Ocular Management there may be a cellular basis for The thick stratum corneum on decreased innate immune function the eyelids results in bilateral related to impaired lamellar granule RETINOID THERAPY ectropion, placing infants at high transport and secretion of various The use of systemic retinoids has risk for conjunctivitis, squinting, antimicrobial peptides, including the become standard-of-care in the

Downloaded from www.aappublications.org/news by guest on September 24, 2021 PEDIATRICS Volume 139 , number 1 , January 2017 5 management of HI, following a Bronx, NY), an aqueous-based vehicle with application of 0.1% tazarotene reported 83% survival among 25 with a slightly acidic pH to help cream to the face, scalp, hands, treated infants compared with 24% reduce oxidative degradation (Table 4). and feet. 11 One report documented survival of 21 infants who did not application of a topical retinoid as The current literature suggests that receive an oral retinoid. 15 However, an effective alternative to systemic the acitretin dose be between 0.5 and these results must be interpreted therapy with improvement in limb 1 mg/kg per day. 21, 46 A 2-day half- with some caution, because half of contractures 50 and another for life suggests that once daily dosing the untreated infants died within 3 ectropion management. 38 Topical is sufficient. Surveillance laboratory days after birth, which is earlier than retinoid therapy has also been used data includes a complete blood when retinoid therapy is usually successfully in older infants as oral count, comprehensive metabolic available for administration. Another retinoid therapy was tapered. 21 panel, and lipids at baseline and study documented a 92% survival monthly. Acitretin should be titrated rate among 12 infants treated with to the lowest dose possible for retinoids compared with 50% among FAMILY COUNSELING individual patients based on clinical those not treated. 45 The efficacy of improvement with regular skin The birth of a neonate with HI poses oral retinoids is not well understood. examinations and monitoring of side a great challenge for the family. Some authors suggest that the effects. Retinoids are typically able to During the first several days, parents reported benefit may be an overall be discontinued by 6 months of age. 18 will need to cope with the initial improvement in intensive care in shock of an affected child, grieve addition to oral retinoid therapy. 15, 44 The early introduction of retinoid the loss of the anticipated child, and therapy is likely related to hastened Several oral retinoids have been come to an understanding of the desquamation 21 (Fig 1B). Retinoids used in the management of HI as long-term medical issues that their may be especially useful for well as other congenital ichthyoses, child will face. As in other situations improving digital and thoracic including etretinate, isotretinoin, and in which dysmorphology is so constrictions, thus improving acitretin. 21, 46, 47 The first successful strongly manifested, the appearance functional movement and breathing neonatal use of acetretin in HI was of the neonate may lead parents to in HI neonates. 37 The benefits of reported in 200146 at a dose of 1 harbor feelings of guilt or resentment oral retinoid therapy outside of mg/kg per day, started on day 10 of and avoid seeing the baby after the neonatal period are unclear, life. Acitretin administration has been birth. 21 Bond formation between because there may be spontaneous the retinoid most often used by the mother and infant has been shown skin improvement in HI. 49 As genetic authors. Additionally, compounding to be delayed in the NICU setting testing expands, more information isotretinoin rapidly isomerizes the when a neonate’s appearance was on genotype/phenotype correlations 13-cis molecule to all-trans retinoic not compatible with a mother’s may provide additional information acid, which may have greater toxicity expectation. 51 There are approaches on which neonates will respond best than the aromatic acitretin.48 that can foster bonding between the to retinoid therapy. family and infant. Touch should be Treatment initiation within the In cases where oral retinoid therapy encouraged. Sharing photographs first 7 days of life is recommended cannot be tolerated, the use of topical of survivors to family members has for all infants who can tolerate the retinoids has proved beneficial. been a beneficial intervention. 44 It is medication. 15 However, neonatal A 2014 report of an infant with HI also important for healthcare teams acitretin administration has been demonstrated improvement in skin to educate and prepare families hindered by a lack of commercially available liquid formulations in the United States. The authors have TABLE 4 Product Master Formula Card found that capsular acitretin is not Product Acitretin Oral Suspension 2 mg/mL water soluble, so preparing a liquid Prescription: Acitretin 10 mg capsule 10 mg requires compounding expertise. Ora-Plus 5 mL Acitretin can be compounded by Ingredients and equipment required for preparation: extracting the powder from 10 mg (1) 1 × 10 mg Acitretin capsule capsules. The powder is weighed, and (2) 5 mL Ora-Plus (3) 1-oz glass amber bottle the appropriate dose is administered Directions for preparing: in a small aliquot of warm milk. (1) Prepare this compound under the chemotherapy hood with mask and gloves. At Maimonides Medical Center (2) Measure out 5 mL of Ora-Plus via graduated cylinder and add to 1-oz glass amber bottle. (Brooklyn, NY) acitretin is prepared (3) Empty the contents of 1 Acitretin 10 mg capsule into the same amber bottle and mix thoroughly. in an Ora-Plus solution (Perrigo, Expiration date: 5 d with refrigeration

Downloaded from www.aappublications.org/news by guest on September 24, 2021 6 GLICK et al before discharge for the prolonged their families should be addressed, Currently, infants with HI have care that will be necessary at home. including issues of socialization, self- a similar survival rate and more In some cases, transitioning care confidence, and quality of life. 1, 15, 22 favorable neurocognitive outcome to an assisted care facility may than, for example, infants born at 26 be appropriate. In selected cases, weeks gestation 56: a situation in which hospice care may be needed. Several ETHICAL CONSIDERATIONS aggressive intervention is generally Web sites are available for family and initiated where available. At the same The diagnosis of HI can present ethical patients, including the Foundation time, it must be acknowledged that challenges for parents and healthcare for Ichthyosis & Related Skin Types more difficult ethical scenarios may providers. The striking physical (FIRST) at http:// firstfoundation. org present themselves; for example, appearance of the newborn with HI and the Ichthyosis Support Group at HI patients with additional or may lead to perceptions of decreased www. ichthyosis. org. uk/ . complicating medical problems, amenability to treatment and greater settings without resources for physical pain than are actually the intensive care, or long-term medical case. Such perceptions can influence BEYOND THE NEONATAL PERIOD treatment. Consideration of comfort decisions regarding agressivity of care. The severely abnormal keratotic care over intensive care management In a survey exploring the parental epithelium marking HI at birth might be appropriate in such selected perspectives regarding end-of life care gradually transitions over 4 to 6 situations. in the PICU, 31% of parents described weeks to a severe ichthyosiform the way their child looked as being a erythroderma secondary to “very important” consideration. 53 the dryness of a postuterine CONCLUSIONS The influence of appearance on environment. 15, 17 This condition ethical decision-making also extends HI is a rare form of congenital requires treatment with frequent to health care providers. 54 Specialists ichthyosis that can present many application of bland emollients and knowledgeable in HI should thus challenges throughout a lifetime, active skin care techniques. Children make particular effort to ameliorate but especially during the nenonatal remain prone to infection, although the potentially disproportionate period. An understanding of the less so than during the neonatal period. influence of the physical appearance. ABCA12 mutation and skin barrier Persistent ectropion requires frequent It is important that the family and disruption provides a basis for therapy. eye lubrication and protection. 15 As the health care team are helped Aggressive and supportive care from discussed previously, topical retinoids to understand that the initial an interdisciplinary team is required applied to the eyelids may be useful. appearance is transient, that pain can for effective management; additionally, Additionally, patients can have heat be controlled, and that the underlying in the absence of data to the contrary, and cold intolerance, pruritus, and the authors believe it is advisable to 15 skin disorder can be treated. hair and nail abnormalities. institute early retinoid therapy. At the same time, the long-term Physical and occupational therapy problems facing children with HI must is key to optimizing range of motion be given consideration. These have ACKNOWLEDGMENTS in infancy and childhood as the been outlined previously, and include hyperkeratotic skin can lead to We thank Leonard M. Milstone, MD, life-long dermatologic problems, encasement and constriction of for insightful advice and critical potential for chronic pain, increased limbs and digits, affecting fine and review of the manuscript. We also risk for neurodevelopmental delay, gross motor skills. 1, 15, 21 Some infants thank Anne W. Lucky, MD, Jean increased frequency of hospitalization, and children may display impaired Whalen, RNIII, BSN, CPN, and Susan and possible need for surgical cognitive and social functioning, Rowe, RNIII, BSN, CPN, for their interventions. 1 It is questionable, making speech and language therapy assistance in sharing the fragile skin however, whether the severity necessary.1, 11, 15 It is important to dressing technique and image ( Fig 2). of these issues rises to the level note that some children with HI that foregoing early intensive care are able to function well and attend management and retinoid therapy regular schools. 15 ABBREVIATIONS should be considered. A patient with ABCA12: adenosine triphosphate Children with HI require long-term HI is not expected to have the severe binding cassette A12 coordinated, multispecialty care. neurocognitive disabilities that have CBP: collodion baby phenotype Enhanced long-term survival may been used in other situations to justify HI: harlequin ichthyosis permit recognition of other associated nonintervention during an early TEWL: transepidermal water comorbidities, such as synovitis. 52 “window,” in which survival depends loss The mental health of patients and on intensive care management. 55

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Downloaded from www.aappublications.org/news by guest on September 24, 2021 Improved Management of Harlequin Ichthyosis With Advances in Neonatal Intensive Care Jaimie B Glick, Brittany G Craiglow, Keith A Choate, Hugo Kato, Robert E Fleming, Elaine Siegfried and Sharon A Glick Pediatrics 2017;139; DOI: 10.1542/peds.2016-1003 originally published online December 20, 2016;

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