Harlequin Ichthyosis Treatment & Management
- Author: Julie Prendiville, MBBCh; Chief Editor: Dirk M Elston, MD more...
Newborns with harlequin ichthyosis require management in a neonatal intensive care unit.
Ensure that the patient's airway, breathing, and circulation are stable after delivery. Early intubation may be required. Babies require intravenous access. Peripheral access may be difficult and umbilical cannulation may be necessary. Place infants in a humidified incubator. Monitor temperature, respiratory rate, heart rate, and oxygen saturation. Once stabilized, transfer newborn with harlequin ichthyosis to a NICU.
Exposure keratitis results from ectropion of the eyelids. Apply ophthalmic lubricants frequently to protect the conjunctivae.
Bathe infants twice daily and use frequent wet sodium chloride compresses followed by application of bland lubricants to soften hard skin. Dilute bleach baths may reduce the risk of skin infection.
Topical keratolytics (eg, salicylic acid) are not recommended in newborns because of potential systemic toxicity.
According to Rajpopat et al, early retinoid treatment (by day 7) may require prompt consideration, as these medications can take some days to obtain. See Medication.
Tazarotene, a topical retinoid, has been reported to be beneficial.[21, 22]
Intravenous fluids are almost always required. Consider excess cutaneous water losses in daily fluid requirement calculations. Monitor serum electrolyte levels. A risk of hypernatremic dehydration exists.
Neonates with harlequin ichthyosis initially do not feed well and may require tube feeding.
Maintain a sterile environment to avoid infection. Take frequent cultures of the skin. Growth of pathogenic organisms (eg, Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella) indicates risk of sepsis. Draw blood cultures because sepsis can occur quickly in affected infants.
Further inpatient care
Continue careful attention to skin care and use of emollients during retinoid therapy.
Infants with harlequin ichthyosis can be successfully breastfed or bottle-fed as the eclabium improves. Involving occupational therapy to aid in feeding strategies is advised. Carefully monitor weight gain and intake. Affected infants are at risk of failure to thrive.
Physical bonding between the parents and the baby should be encouraged.
Early formation of a multidisciplinary team is recommended and may include the following:
Hyperkeratosis causing constriction of limbs, digits, or nasal obstruction may need to be treated surgically.[19, 21, 24]
Complications in the neonatal period include the following:
Dehydration, hypernatremia, hypocalcemia, hypoglycemia
Limb or digital constriction, ischemia
Infants who survive the newborn period have a lifelong, severe ichthyosiform erythroderma.
Recurrent skin infections may continue after the newborn period.
Contractures and painful fissuring of the hands and the feet may occur. Rajpopat et al reported palmoplantar keratoderma in 52% of survivors, causing pain and delay in walking.
Pruritus was reported in 44% of patients, heat and cold intolerance was found in 36%, reduced sweating was found in 28%, and photosensitivity and pigmented macules were found in one patient each. Poor hair growth and nail deformities were common. Hearing impairment may result from obstruction of the ear canals by skin debris.
Developmental delay and normal intellectual development are described. Rajpopat et al reported that most school-aged survivors were attending mainstream schools, although many needed additional help.
Growth must be closely monitored. Short stature is common and weight below average. Nutritional rickets due to vitamin D deficiency is reported. This is likely due to defective vitamin D synthesis in the abnormal skin, calcium loss, and reduced exposure to sunlight.
Infants are discharged from the hospital when their cutaneous symptoms are improving, feeding and weight gain are established, and they are free of infection.
Social and psychological support should be provided for the parents/caregivers.
The primary care physician should closely monitor the infants for growth, development, social issues, and skin surveillance. A dermatologist should monitor affected infants for ongoing assessment and for monitoring of retinoid therapy.
Adverse effects of retinoid therapy (eg, mucocutaneous dryness, aberrant liver function tests, hypertriglyceridemia, benign intracranial hypertension) should be noted. Serum AST, ALT, total cholesterol, and triglyceride levels should initially be obtained on a monthly basis initially. The clinician should be cognizant of the musculoskeletal abnormalities that can occur with long-term retinoid therapy, if treatment is continued.
Follow-up with an ophthalmologist is required. Recurrent exposure keratitis can be a problem as a result of persistent ectropion.
Oji V, Tadini G, Akiyama M, Blanchet Bardon C, Bodemer C, Bourrat E. Revised nomenclature and classification of inherited ichthyoses: results of the First Ichthyosis Consensus Conference in Sorèze 2009. J Am Acad Dermatol. 2010 Oct. 63(4):607-41. [Medline].
Lawlor F. Progress of a harlequin fetus to nonbullous ichthyosiform erythroderma. Pediatrics. 1988 Dec. 82(6):870-3. [Medline].
Ahmed H, O'Toole EA. Recent advances in the genetics and management of harlequin ichthyosis. Pediatr Dermatol. 2014 Sep-Oct. 31 (5):539-46. [Medline].
Rajpopat S, Moss C, Mellerio J, et al. Harlequin ichthyosis: a review of clinical and molecular findings in 45 cases. Arch Dermatol. 2011 Jun. 147(6):681-6. [Medline].
Shibata A, Akiyama M. Epidemiology, medical genetics, diagnosis and treatment of harlequin ichthyosis in Japan. Pediatr Int. 2015 Aug. 57 (4):516-22. [Medline].
Lefevre C, Audebert S, Jobard F, et al. Mutations in the transporter ABCA12 are associated with lamellar ichthyosis type 2. Hum Mol Genet. 2003 Sep 15. 12(18):2369-78. [Medline].
Akiyama M. ABCA12 mutations and autosomal recessive congenital ichthyosis: a review of genotype/phenotype correlations and of pathogenetic concepts. Hum Mutat. 2010 Oct. 31(10):1090-6. [Medline].
Akiyama M. The roles of ABCA12 in epidermal lipid barrier formation and keratinocyte differentiation. Biochim Biophys Acta. 2014 Mar. 1841(3):435-440. [Medline].
Elias PM, Williams ML, Holleran WM, Jiang YJ, Schmuth M. Pathogenesis of permeability barrier abnormalities in the ichthyoses: inherited disorders of lipid metabolism. J Lipid Res. 2008 Apr. 49(4):697-714. [Medline]. [Full Text].
Scott CA, Rajpopat S, Di WL. Harlequin ichthyosis: ABCA12 mutations underlie defective lipid transport, reduced protease regulation and skin-barrier dysfunction. Cell Tissue Res. 2013 Feb. 351(2):281-8. [Medline].
Akiyama M, Sugiyama-Nakagiri Y, Sakai K, McMillan JR, Goto M, Arita K, et al. Mutations in lipid transporter ABCA12 in harlequin ichthyosis and functional recovery by corrective gene transfer. J Clin Invest. 2005 Jul. 115(7):1777-84. [Medline]. [Full Text].
Stewart H, Smith PT, Gaunt L, Moore L, Tarpey P, Andrew S, et al. De novo deletion of chromosome 18q in a baby with harlequin ichthyosis. Am J Med Genet. 2001 Sep 1. 102(4):342-5. [Medline].
Thomas AC, Tattersall D, Norgett EE, O'Toole EA, Kelsell DP. Premature terminal differentiation and a reduction in specific proteases associated with loss of ABCA12 in Harlequin ichthyosis. Am J Pathol. 2009 Mar. 174(3):970-8. [Medline].
Berg C, Geipel A, Kohl M, Krokowski M, Baschat AA, Germer U, et al. Prenatal sonographic features of Harlequin ichthyosis. Arch Gynecol Obstet. 2003 Apr. 268(1):48-51. [Medline].
Bongain A, Benoit B, Ejnes L, Lambert JC, Gillet JY. Harlequin fetus: three-dimensional sonographic findings and new diagnostic approach. Ultrasound Obstet Gynecol. 2002 Jul. 20(1):82-5. [Medline].
Watson WJ, Mabee LM Jr. Prenatal diagnosis of severe congenital ichthyosis (harlequin fetus) by ultrasonography. J Ultrasound Med. 1995 Mar. 14(3):241-3. [Medline].
Chan YC, Tay YK, Tan LK, Happle R, Giam YC. Harlequin ichthyosis in association with hypothyroidism and juvenile rheumatoid arthritis. Pediatr Dermatol. 2003 Sep-Oct. 20(5):421-6. [Medline].
Milstone LM, Choate KA. Improving outcomes for harlequin ichthyosis. J Am Acad Dermatol. 2013 Nov. 69(5):808-9. [Medline].
Chua CN, Ainsworth J. Ocular management of harlequin syndrome. Arch Ophthalmol. 2001 Mar. 119(3):454-5. [Medline].
Koochek A, Choate KA, Milstone LM. Harlequin Ichthyosis: Neonatal Management and Identification of a New ABCA12 Mutation. Pediatr Dermatol. 2014 Mar. 31(2):e63-4. [Medline].
Liu RH, Becker B, Gunkel J, Teng J. Rapid improvement in digital ischemia and acral contracture in a collodion baby treated with topical tazarotene. J Drugs Dermatol. 2010 Jun. 9(6):713-6. [Medline].
Ripmeester P, Dunn S. Against all odds: breastfeeding a baby with harlequin ichthyosis. J Obstet Gynecol Neonatal Nurs. 2002 Sep-Oct. 31(5):521-5. [Medline].
Tontchev G, Silverberg NB, Shlasko E, Henry C, Roberts JL, Roth MZ. Techniques for toddlers: linear band incision for harlequin ichthyosis with associated compartment syndrome. Pediatr Dermatol. 2014 Sep-Oct. 31 (5):625-9. [Medline].
Harvey HB, Shaw MG, Morrell DS. Perinatal management of harlequin ichthyosis: a case report and literature review. J Perinatol. 2010 Jan. 30(1):66-72. [Medline].