eMedicine Specialties > Ophthalmology > Dermatologic Disorders

Acrodermatitis Enteropathica

Author: John D Sheppard Jr, MD, MMSc, Professor of Ophthalmology, Microbiology and Molecular Biology, Clinical Director, Thomas R Lee Center for Ocular Pharmacology, Program Director, Ophthalmology Residency Training, Eastern Virginia Medical School; President, Virginia Eye Consultants
Coauthor(s): Timothy G Woodall, MD, Dermatology, Carolinas Medical Center - Pineville
Contributor Information and Disclosures

Updated: Jun 8, 2009

Introduction

Background

Acrodermatitis enteropathica (AE) is a rare autosomal recessive disorder characterized by periorificial and acral dermatitis, alopecia, growth failure, gastrointestinal disturbance, and diarrhea. Symptoms of AE occur within the first few months after birth and tend to appear in nonbreastfed infants or in infants shortly after discontinuation of breastfeeding. Ocular complications include lid and surface involvement as well as secondary infections.1

Pathophysiology

The nature of the metabolic defect is currently attributed to zinc absorption. The AE mutation creates reduced zinc uptake and abnormal zinc metabolism in human fibroblasts. The gene defect is located on chromosome 8, characterized as the intestinal zinc transporter gene, or SLC39A4 gene, at locus 8q24.3.2,3

Frequency

United States

Unknown

International

It is estimated that 1 in 500,000 people in Denmark are affected.

Mortality/Morbidity

AE is lethal, usually within the first few years of life, if left untreated. However, an untreated adult survivor was reported.

Race

No racial predilection exists.

Sex

No sexual preference exists.

Age

AE appears in the first few months after birth or after cessation of breastfeeding.

Clinical

History

  • Symptoms of AE occur within the first few months after birth in nonbreastfed infants or tend to appear in infants shortly after discontinuation of breastfeeding.
  • Ocular disease is a byproduct of lid, conjunctival, and ocular surface deficits.
  • Infants display photophobia and blepharospasm, which may threaten deprivation amblyopia in severe cases.
  • Lid sloughing and secondary infections can be significant. Alopecia of the scalp, eyebrows, and cilia is common.
  • Chronic conjunctivitis, blepharitis, punctate keratopathy, and even keratomalacia further complicate the ocular picture.

Physical

  • Physical examination is significant for erythematous patches and plaques of dry, scaly, eczematous skin, which may evolve into crusted, vesiculobullous, erosive, and pustular lesions. Lesions are distributed in a periorificial and acral pattern, on the face, scalp, lids, hands, feet, and anogenital areas.4
  • Paronychia and alopecia with loss of scalp hair, eyebrows, and eyelashes may occur.
  • Ocular manifestations may also include punctal stenosis, corneal changes, and keratomalacia.
  • The cutaneous lesions may become secondarily infected with Staphylococcus aureus and Candida albicans.
  • Infants also may experience withdrawal, growth failure, photophobia, and loss of appetite, leading to failure to thrive.

Causes

The appearance of AE shortly after the cessation of breastfeeding has led many to believe that human milk has a beneficial ligand, which bovine milk lacks. Evans and Johnson postulated picolinate as the ligand5 ; Lonnerdal suggested citric acid6 ; Cousins and Smith proposed that the protein concentration of human milk affects zinc bioavailability.7

The nature of the metabolic defect has been debated and clarified with the identification of the 8q24.3 locus. Fibroblast proteins that are absent in the fibroblasts of patients with AE have recently been discovered, suggesting that these proteins may be responsible for decreased zinc uptake and abnormal zinc metabolism.

More on Acrodermatitis Enteropathica

Overview: Acrodermatitis Enteropathica
Differential Diagnoses & Workup: Acrodermatitis Enteropathica
Treatment & Medication: Acrodermatitis Enteropathica
Follow-up: Acrodermatitis Enteropathica
References
Further Reading
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References

  1. Tabanlioglu D, Ersoy-Evans S, Karaduman A. Acrodermatitis enteropathica-like eruption in metabolic disorders: acrodermatitis dysmetabolica is proposed as a better term. Pediatr Dermatol. Mar-Apr 2009;26(2):150-4. [Medline].

  2. Andrews GK. Regulation and function of Zip4, the acrodermatitis enteropathica gene. Biochem Soc Trans. Dec 2008;36:1242-6. [Medline].

  3. Kambe T, Andrews GK. Novel proteolytic processing of the ectodomain of the zinc transporter ZIP4 (SLC39A4) during zinc deficiency is inhibited by acrodermatitis enteropathica mutations. Mol Cell Biol. Jan 2009;29(1):129-39. [Medline].

  4. Jensen SL, McCuaig C, Zembowicz A, Hurt MA. Bullous lesions in acrodermatitis enteropathica delaying diagnosis of zinc deficiency: a report of two cases and review of the literature. J Cutan Pathol. Oct 2008;35 Suppl 1:1-13. [Medline].

  5. Evans GW, Johnson PE. Characterization and quantitation of a zinc-binding ligand in human milk. Pediatr Res. Jul 1980;14(7):876-80. [Medline].

  6. Lonnerdal B, Stanislowski AG, Hurley LS. Isolation of a low molecular weight zinc binding ligand from human milk. J Inorg Biochem. Jan 1980;12(1):71-8. [Medline].

  7. Cousins RJ, Smith KT. Zinc-binding properties of bovine and human milk in vitro: influence of changes in zinc content. Am J Clin Nutr. May 1980;33(5):1083-7. [Medline].

  8. Nakano A, Nakano H, Nomura K. Novel SLC39A4 mutations in acrodermatitis enteropathica. J Invest Dermatol. 2003;Jun;120(6):963-6. [Medline]. [Full Text].

  9. Aggett PJ, Atherton DJ, More J, et al. Symptomatic zinc deficiency in a breast-fed preterm infant. Arch Dis Child. Jul 1980;55(7):547-50. [Medline].

  10. Bilinski DL, Ehrenkranz RA, Cooley-Jacobs J, McGuire J. Symptomatic zinc deficiency in a breast-fed, premature infant. Arch Dermatol. Sep 1987;123(9):1221-4. [Medline].

  11. Bye AM, Goodfellow A, Atherton DJ. Transient zinc deficiency in a full-term breast-fed infant of normal birth weight. Pediatr Dermatol. Jul 1985;2(4):308-11. [Medline].

  12. Cameron JD, McClain CJ. Ocular histopathology of acrodermatitis enteropathica. Br J Ophthalmol. Sep 1986;70(9):662-7. [Medline].

  13. Camille S. Matta, MD; Gary V. Felker, MD; Carl H. Ide, MD. Eye Manifestations in Acrodermatitis Enteropathica. Arch Ophthalmol. 93(2):140-142.

  14. Champion RH, et al, eds. Rook/Wilkinson/Ebling Textbook of Dermatology. Vol. 3. 1998: 2668.

  15. Connors TJ, Czarnecki DB, Haskett MI. Acquired zinc deficiency in a breast-fed premature infant. Arch Dermatol. Apr 1983;119(4):319-21. [Medline].

  16. Elder D, Elenitsas R, Jawarsky C, et al, eds. Lever's Histopathology of the Skin. 8th ed. Philadelphia: Lippincott-Raven;1998:356.

  17. Feldberg R, Yassur Y, Ben-Sira I, et al. Keratomalacia in acrodermatitis enteropathica (AE). Metab Pediatr Ophthalmol. 1981;5(3-4):207-11. [Medline].

  18. Fraker PJ, King LE, Laakko T, Vollmer TL. The dynamic link between the integrity of the immune system and zinc status. J Nutr. May 2000;130(5S Suppl):1399S-406S. [Medline]. [Full Text].

  19. Glover MT, Atherton DJ. Transient zinc deficiency in two full-term breast-fed siblings associated with low maternal breast milk zinc concentration. Pediatr Dermatol. Feb 1988;5(1):10-3. [Medline].

  20. Graves K, Kestenbaum T, Kalivas J. Hereditary acrodermatitis enteropathica in an adult. Arch Dermatol. May 1980;116(5):562-4. [Medline].

  21. Grider A, Mouat MF. The acrodermatitis enteropathica mutation affects protein expression in human fibroblasts: analysis by two-dimensional gel electrophoresis. J Nutr. Aug 1998;128(8):1311-4. [Medline].

  22. Hambridge KM. The role of zinc and other trace metals in pediatric nutrition and health. Pediatr Clin N Amer. Feb 1977;1:95-106.

  23. Matta CS, Felker GV, Ide CH. Eye manifestations in acrodermatitis enteropathica. Arch Ophthalmol. Feb 1975;93(2):140-2. [Medline].

  24. Ozturkcan S, Icagasioglu D, Akyol M, Cevit O. A case of acrodermatitis enteropathica. J Dermatol. Jul 2000;27(7):475-7. [Medline].

  25. Roberts LJ, Shadwick CF, Bergstresser PR. Zinc deficiency in two full-term breast-fed infants. J Am Acad Dermatol. Feb 1987;16(2 Pt 1):301-4. [Medline].

  26. Schacner LA, Hansen RC. Pediatric Dermatology. New York, New York: Churchill Livingstone;1988:759.

  27. Schmidt CP, Tunnessen W. Cystic fibrosis presenting with periorificial dermatitis. J Am Acad Dermatol. Nov 1991;25(5 Pt 2):896-7. [Medline].

  28. Schmitt S, Küry S, Giraud M, Dréno B, Kharfi M, Bézieau S. An update on mutations of the SLC39A4 gene in acrodermatitis enteropathica. Hum Mutat. Jan 29 2009;[Medline].

  29. Van Wouwe JP. Clinical and laboratory diagnosis of acrodermatitis enteropathica. Eur J Pediatr. Oct 1989;149(1):2-8. [Medline].

  30. Vasantha K, Kannan KA. Acrodermatitis enteropathica--a case report. Indian J Ophthalmol. Oct-Dec 1989;37(4):197-8. [Medline].

  31. Zimmerman AW, Hambidge KM, Lepow ML, et al. Acrodermatitis in breast-fed premature infants: evidence for a defect of mammary zinc secretion. Pediatrics. Feb 1982;69(2):176-83. [Medline].

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Keywords

acrodermatitis enteropathica, AE, autosomal recessive zinc deficiency, ocular disease, photophobia, blepharospasm, amblyopia, lid sloughing, chronic conjunctivitis, seborrheic blepharitis, punctate keratopathy, keratomalacia, lid deficit, conjunctival deficit, ocular surface deficit, paronychia, alopecia, trichiasis, entropion, lash loss, brow loss, punctal stenosis, corneal changes, keratitis sicca, infectious keratitis

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Contributor Information and Disclosures

Author

John D Sheppard Jr, MD, MMSc, Professor of Ophthalmology, Microbiology and Molecular Biology, Clinical Director, Thomas R Lee Center for Ocular Pharmacology, Program Director, Ophthalmology Residency Training, Eastern Virginia Medical School; President, Virginia Eye Consultants
John D Sheppard Jr, MD, MMSc is a member of the following medical societies: American Academy of Ophthalmology, American Society for Microbiology, American Society of Cataract and Refractive Surgery, American Uveitis Society, and Association for Research in Vision and Ophthalmology
Disclosure: Nothing to disclose.

Coauthor(s)

Timothy G Woodall, MD, Dermatology, Carolinas Medical Center - Pineville
Timothy G Woodall, MD is a member of the following medical societies: American Academy of Dermatology, American Society for Dermatologic Surgery, and South Carolina Medical Association
Disclosure: Nothing to disclose.

Medical Editor

Andrew A Dahl, MD, Director of Ophthalmology Teaching, Mid-Hudson Family Practice Institute, The Institute for Family Health; Assistant Professor of Surgery (Ophthalmology), New York College of Medicine
Andrew A Dahl, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Ophthalmology, American College of Surgeons, American Medical Association, American Society of Cataract and Refractive Surgery, and Wilderness Medical Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Simon K Law, MD, PharmD, Assistant Professor of Ophthalmology, Jules Stein Eye Institute; Chief of Section of Ophthalmology Surgical Services, Department of Veterans Affairs Healthcare Center, West Los Angeles
Simon K Law, MD, PharmD is a member of the following medical societies: American Academy of Ophthalmology, American Glaucoma Society, and Association for Research in Vision and Ophthalmology
Disclosure: Nothing to disclose.

Managing Editor

Christopher J Rapuano, MD, Professor, Department of Ophthalmology, Jefferson Medical College of Thomas Jefferson University; Co-Chairman of the Cornea Service, Co-Chairman of Refractive Surgery Department, Wills Eye Institute
Christopher J Rapuano, MD is a member of the following medical societies: American Academy of Ophthalmology, American Society of Cataract and Refractive Surgery, Contact Lens Association of Ophthalmologists, Cornea Society, Eye Bank Association of America, International Society of Refractive Surgery, and Pan-American Association of Ophthalmology
Disclosure: Allergan Honoraria Speaking and teaching; Allergan Consulting fee Consulting; Alcon Honoraria Speaking and teaching; Inspire Honoraria Speaking and teaching; RPS Ownership interest Other; Vistakon Honoraria Speaking and teaching

CME Editor

Lance L Brown, OD, MD, Ophthalmologist, Affiliated With Freeman Hospital and St John's Hospital, Regional Eye Center, Joplin, Missouri
Disclosure: Nothing to disclose.

Chief Editor

Hampton Roy Sr, MD, Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences
Hampton Roy Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, and Pan-American Association of Ophthalmology
Disclosure: Nothing to disclose.

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