eMedicine Specialties > Dermatology > Pediatric Diseases

Ichthyosis Fetalis: Treatment & Medication

Author: Julie Prendiville, MB, BCh, Clinical Professor in Pediatrics, University of British Columbia; Head, Division of Pediatric Dermatology, British Columbia's Children's Hospital, Canada
Contributor Information and Disclosures

Updated: Oct 21, 2008

Treatment

Medical Care

  • Ensure that the ichthyosis fetalis patient's airway, breathing, and circulation are stable after delivery. Babies require intravenous access. Peripheral access may be difficult. Umbilical cannulation may be necessary.
  • Place infants in a humidified incubator. Monitor temperature, respiratory rate, heart rate, and oxygen saturation. Once stabilized, transfer newborns with HI to a level 3 neonatal nursery.
  • Exposure keratitis results from ectropion of the eyelids. Apply ophthalmic lubricants frequently to protect the conjunctivae.14 Bathe infants twice daily. Use frequent applications of wet sodium chloride compresses followed by bland lubricants to soften hard skin and to facilitate desquamation. Topical keratolytics (eg, salicylic acid) are not recommended in newborns because of potential systemic toxicity.
  • Intravenous fluids are almost always required; neonates with ichthyosis fetalis initially do not feed well. Consider excess cutaneous water losses in daily fluid requirement calculations. Monitor serum electrolyte levels. A risk of hypernatremic dehydration exists.
  • Maintain a sterile environment to avoid infection. Take frequent cultures of the skin. Growth of pathogenic organisms (eg, Staphylococcus aureus, Pseudomonas aeruginosa) indicates risk of sepsis. Draw blood cultures because sepsis can occur quickly in affected infants. A consensus does not exist regarding the use of prophylactic antibiotics in ichthyosis fetalis patients.

Consultations

  • Neonatologist
  • Dermatologist
  • Medical geneticist
  • Social worker

Medication

Enhanced survival and decreased morbidity is reported with the use of systemic retinoids for HI. Retinoids bind to specific retinoic acid receptors and regulate gene transcription. They influence keratinocyte differentiation, normalize abnormal keratinocyte proliferation, and mediate desquamation of hyperkeratotic scale.

Etretinate was first used for the treatment of this disorder in 1985. An effective dose of 1 mg/kg/d was established. Etretinate is no longer available, but it has been replaced by other retinoids with improved safety profiles.15

Isotretinoin is a retinoid that has been used in ichthyosis fetalis. The reported dose is 0.5 mg/kg/d. Treatment is usually initiated within the first few days of life and given orally. Case reports have documented improvement in pliability of the skin, limb movements, sucking, and eyelid closing within a week of starting therapy. Treatment has been continued for several years in some patients, and it may be required indefinitely to prevent relapse.

Acitretin, a carboxylic acid derivative of etretinate, has also been used in neonates with HI.16,17 Initial doses of 1 mg/kg/d have been used with success. Improvement in hyperkeratosis, ectropion, and eclabium is reported. The duration of therapy is variable, and continuous, long-term, daily therapy may be required. The daily dose can be titrated to the degree of ichthyosis.

Liver function and serum lipid levels should be monitored during retinoid therapy. Clinical monitoring for skeletal adverse effects should be done periodically. Before retinoid therapy is considered, discuss the expected outcome and the potential adverse effects with the parents.

Retinoids

These agents decrease the cohesiveness of abnormal hyperproliferative keratinocytes. They modulate keratinocyte differentiation.


Isotretinoin (Accutane)

Synthetic 13-cis isomer of naturally occurring tretinoin (trans -retinoic acid). Both agents structurally related to vitamin A.

Adult

None; HI is a pediatric condition

Pediatric

0.5 mg/kg/d PO

Toxicity may occur with vitamin A coadministration; pseudotumor cerebri or papilledema may occur when coadministered with tetracyclines; acitretin may reduce plasma levels of carbamazepine

Documented hypersensitivity; pregnancy

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

May decrease night vision; may be associated with hepatitis; occasional exaggerated healing response of acne lesions (excessive granulation with crusting); diabetic patients may have problems controlling their blood glucose level during therapy; patients should use UV protection until tolerance achieved; radiographic findings suggestive of premature closure of epiphyses reported


Acitretin (Soriatane)

Metabolite of etretinate and related to retinoic acid and retinol (vitamin A). Mechanism of action unknown but thought to exert therapeutic effect by modulating keratinocyte differentiation, keratinocyte hyperproliferation, and tissue infiltration by inflammatory cells.

Adult

None; HI is a pediatric condition

Pediatric

1 mg/kg/d initially; duration of therapy variable and continuous; long-term daily therapy may be required; titrate daily dose to degree of ichthyosis

Increases toxicity of methotrexate (avoid concomitant use); coadministration with alcohol may result in formation of etretinate, which has long half-life (>120 d)

Absolute: Pregnancy or woman likely to become pregnant or intends to become pregnant within 3 y of treatment or who cannot use reliable contraception during treatment and for at least 3 y afterward; noncompliance with contraception; nursing mothers; concurrent use of methotrexate (increased liver toxicity) or tetracyclines (pseudotumor cerebri); hypersensitivity
Relative: obesity, leukopenia; moderate-to-severe cholesterol or triglyceride elevation; clinically hepatic or renal dysfunction

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

Women of childbearing age must be able to comply with effective contraception; contraception should be continued for at least 3 y after treatment; etretinate may form and takes about 2-3 y to clear from body; caution in impaired renal or liver function; test aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) before therapy, q1-2wk until stable, and then at intervals as clinically indicated

More on Ichthyosis Fetalis

Overview: Ichthyosis Fetalis
Differential Diagnoses & Workup: Ichthyosis Fetalis
Treatment & Medication: Ichthyosis Fetalis
Follow-up: Ichthyosis Fetalis
Multimedia: Ichthyosis Fetalis
References
[ CLOSE WINDOW ]

References

  1. Haftek M, Cambazard F, Dhouailly D, Réano A, Simon M, Lachaux A, et al. A longitudinal study of a harlequin infant presenting clinically as non-bullous congenital ichthyosiform erythroderma. Br J Dermatol. Sep 1996;135(3):448-53. [Medline].

  2. Lawlor F. Progress of a harlequin fetus to nonbullous ichthyosiform erythroderma. Pediatrics. Dec 1988;82(6):870-3. [Medline].

  3. Kelsell DP, Norgett EE, Unsworth H, Teh MT, Cullup T, Mein CA, et al. Mutations in ABCA12 underlie the severe congenital skin disease harlequin ichthyosis. Am J Hum Genet. May 2005;76(5):794-803. [Medline].

  4. Lefévre C, Audebert S, Jobard F, Bouadjar B, Lakhdar H, Boughdene-Stambouli O, et al. Mutations in the transporter ABCA12 are associated with lamellar ichthyosis type 2. Hum Mol Genet. Sep 15 2003;12(18):2369-78. [Medline].

  5. Uitto J. The gene family of ABC transporters--novel mutations, new phenotypes. Trends Mol Med. Aug 2005;11(8):341-3. [Medline].

  6. Michel M, Fleckman P, Smith LT, Dale BA. The calcium-activated neutral protease calpain I is present in normal foetal skin and is decreased in neonatal harlequin ichthyosis. Br J Dermatol. Dec 1999;141(6):1017-26. [Medline].

  7. 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. Jul 2005;115(7):1777-84. [Medline].

  8. 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. Sep 1 2001;102(4):342-5. [Medline].

  9. Akiyama M, Dale BA, Smith LT, Shimizu H, Holbrook KA. Regional difference in expression of characteristic abnormality of harlequin ichthyosis in affected fetuses. Prenat Diagn. May 1998;18(5):425-36. [Medline].

  10. Akiyama M, Suzumori K, Shimizu H. Prenatal diagnosis of harlequin ichthyosis by the examination of keratinized hair canals and amniotic fluid cells at 19 weeks' estimated gestational age. Prenat Diagn. Feb 1999;19(2):167-71. [Medline].

  11. Berg C, Geipel A, Kohl M, Krokowski M, Baschat AA, Germer U, et al. Prenatal sonographic features of Harlequin ichthyosis. Arch Gynecol Obstet. Apr 2003;268(1):48-51. [Medline].

  12. Bongain A, Benoit B, Ejnes L, Lambert JC, Gillet JY. Harlequin fetus: three-dimensional sonographic findings and new diagnostic approach. Ultrasound Obstet Gynecol. Jul 2002;20(1):82-5. [Medline].

  13. Watson WJ, Mabee LM Jr. Prenatal diagnosis of severe congenital ichthyosis (harlequin fetus) by ultrasonography. J Ultrasound Med. Mar 1995;14(3):241-3. [Medline].

  14. Chua CN, Ainsworth J. Ocular management of harlequin syndrome. Arch Ophthalmol. Mar 2001;119(3):454-5. [Medline].

  15. Haftek M, Cambazard F, Reano A. Harlequin foetus: a histological, ultrastructural and biochemical study of an etretinate-treated patient. Clin Exp Dermatol. 1989;14:393.

  16. Lacour M, Mehta-Nikhar B, Atherton DJ, Harper JI. An appraisal of acitretin therapy in children with inherited disorders of keratinization. Br J Dermatol. Jun 1996;134(6):1023-9. [Medline].

  17. Singh S, Bhura M, Maheshwari A, Kumar A, Singh CP, Pandey SS. Successful treatment of harlequin ichthyosis with acitretin. Int J Dermatol. Jul 2001;40(7):472-3. [Medline].

  18. Ripmeester P, Dunn S. Against all odds: breastfeeding a baby with harlequin ichthyosis. J Obstet Gynecol Neonatal Nurs. Sep-Oct 2002;31(5):521-5. [Medline].

  19. Thacher TD, Fischer PR, Pettifor JM, Darmstadt GL. Nutritional rickets in ichthyosis and response to calcipotriene. Pediatrics. Jul 2004;114(1):e119-23. [Medline].

  20. Chan YC, Tay YK, Tan LK, Happle R, Giam YC. Harlequin ichthyosis in association with hypothyroidism and juvenile rheumatoid arthritis. Pediatr Dermatol. Sep-Oct 2003;20(5):421-6. [Medline].

  21. Suzumori K, Kanzaki T. Prenatal diagnosis of harlequin ichthyosis by fetal skin biopsy; report of two cases. Prenat Diagn. Jul 1991;11(7):451-7. [Medline].

  22. Suresh S, Vijayalakshmi R, Indrani S, Lata M. Short foot length: a diagnostic pointer for harlequin ichthyosis. J Ultrasound Med. Dec 2004;23(12):1653-7. [Medline].

  23. Akiyama M. The pathogenesis of severe congenital ichthyosis of the neonate. J Dermatol Sci. Sep 1999;21(2):96-104. [Medline].

  24. Allen DM, Esterly NB. Significant systemic absorption of tacrolimus after topical application in a patient with lamellar ichthyosis. Arch Dermatol. Sep 2002;138(9):1259-60. [Medline].

  25. Ammirati CT, Mallory SB. The major inherited disorders of cornification. New advances in pathogenesis. Dermatol Clin. Jul 1998;16(3):497-508. [Medline].

  26. Dale BA, Holbrook KA, Fleckman P, Kimball JR, Brumbaugh S, Sybert VP. Heterogeneity in harlequin ichthyosis, an inborn error of epidermal keratinization: variable morphology and structural protein expression and a defect in lamellar granules. J Invest Dermatol. Jan 1990;94(1):6-18. [Medline].

  27. Dale BA, Kam E. Harlequin ichthyosis. Variability in expression and hypothesis for disease mechanism. Arch Dermatol. Nov 1993;129(11):1471-7. [Medline].

  28. DiGiovanna JJ. Ichthyosiform dermatoses. In: Fitzpatrick's Dermatology in General Medicine. 5th ed. New York, NY: McGraw-Hill; 1999:581-601.

  29. Fleck RM, Barnadas M, Schulz WW, Roberts LJ, Freeman RG. Harlequin ichthyosis: an ultrastructural study. J Am Acad Dermatol. Nov 1989;21(5 Pt 1):999-1006. [Medline].

  30. Gunes T, Akcakus M, Kurtoglu S, Cetin N, Karakükçü M. Harlequin baby with ecthyma gangrenosum. Pediatr Dermatol. Nov-Dec 2003;20(6):529-30. [Medline].

  31. Gånemo A, Sjöden PO, Johansson E, Vahlquist A, Lindberg M. Health-related quality of life among patients with ichthyosis. Eur J Dermatol. Jan-Feb 2004;14(1):61-6. [Medline].

  32. Haake AR, Holbrook K. The structure and development of skin. In: Fitzpatrick's Dermatology in General Medicine. New York, NY: McGraw-Hill; 1999:70-86.

  33. Hofmann B, Stege H, Ruzicka T, Lehmann P. Effect of topical tazarotene in the treatment of congenital ichthyoses. Br J Dermatol. Oct 1999;141(4):642-6. [Medline].

  34. Hovnanian A. Harlequin ichthyosis unmasked: a defect of lipid transport. J Clin Invest. Jul 2005;115(7):1708-10. [Medline].

  35. Prasad RS, Pejaver RK, Hassan A, al Dusari S, Wooldridge MA. Management and follow-up of harlequin siblings. Br J Dermatol. May 1994;130(5):650-3. [Medline].

  36. Roberts LJ. Long-term survival of a harlequin fetus. J Am Acad Dermatol. Aug 1989;21(2 Pt 2):335-9. [Medline].

  37. Unamuno P, Pierola JM, Fernandez E, Roman C, Velasco JA. Harlequin foetus in four siblings. Br J Dermatol. Apr 1987;116(4):569-72. [Medline].

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

ichthyosis fetalis, harlequin ichthyosis, HI, harlequin baby, ichthyosis congenita, keratosis diffusa fetalis, harlequin fetus

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

Julie Prendiville, MB, BCh, Clinical Professor in Pediatrics, University of British Columbia; Head, Division of Pediatric Dermatology, British Columbia's Children's Hospital, Canada
Julie Prendiville, MB, BCh is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

Medical Editor

Abby S Van Voorhees, MD, Assistant Professor, Director of Psoriasis Services and Phototherapy Units, Department of Dermatology, University of Pennsylvania School of Medicine, Hospital of the University of Pennsylvania
Abby S Van Voorhees, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, National Psoriasis Foundation, Phi Beta Kappa, Sigma Xi, and Women's Dermatologic Society
Disclosure: Amgen Honoraria Consulting; Astellas Grant/research funds Other; Abbott Honoraria Consulting; Genentech Honoraria Consulting; Incyte Grant/research funds Other; Centocor Honoraria Consulting; Warner Chilcott  Consulting; Merck Salary Review panel membership

Pharmacy Editor

Richard P Vinson, MD, Assistant Clinical Professor, Department of Dermatology, Texas Tech University School of Medicine; Consulting Staff, Mountain View Dermatology, PA
Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Association of Military Dermatologists, Texas Dermatological Society, and Texas Medical Association
Disclosure: Nothing to disclose.

Managing Editor

Van Perry, MD, Assistant Professor, Department of Medicine, Division of Dermatology, University of Texas Health Science Center
Van Perry, MD is a member of the following medical societies: American Academy of Dermatology and American Society for Laser Medicine and Surgery
Disclosure: Nothing to disclose.

CME Editor

Joel M Gelfand, MD, MSCE, Medical Director, Clinical Studies Unit, Assistant Professor, Department of Dermatology, Associate Scholar, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania
Joel M Gelfand, MD, MSCE is a member of the following medical societies: Society for Investigative Dermatology
Disclosure: AMGEN Consulting fee Consulting; AMGEN Grant/research funds None; Genentech Consulting fee Consulting; Centocor Consulting fee Consulting; Centocor Grant/research funds None; Covance Consulting fee Consulting; Shire  Consulting

Chief Editor

William D James, MD, Paul R Gross Professor of Dermatology, University of Pennsylvania School of Medicine; Vice-Chair, Program Director, Department of Dermatology, University of Pennsylvania Health System
William D James, MD is a member of the following medical societies: American Academy of Dermatology and Society for Investigative Dermatology
Disclosure: elsevier Royalty Other; american college of physicians Honoraria Other

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.