Medscape is available in 5 Language Editions – Choose your Edition here.


Acrodermatitis Enteropathica in Ophthalmology Workup

  • Author: John D Sheppard, Jr, MD, MMSc; Chief Editor: Hampton Roy, Sr, MD  more...
Updated: Dec 17, 2014

Laboratory Studies

See the list below:

  • Plasma zinc levels are low and characteristic histopathologic findings are seen on skin biopsy.
  • Hair, urine, and parotid saliva zinc levels, as well as serum alkaline phosphatase activity (which lowers later in the disease) may be helpful.
  • Maternal breast milk zinc concentrations also may help differentiate AE from acquired zinc deficiency.

Other Tests

See the list below:

  • The gene for AE is localized to chromosomal region 8q24.3 and the SLC39A4 gene, thereby identified as the gene for AE. SLC39A4 mutations have been demonstrated in several families with AE, and, in the initial Nakano study, 2 Japanese families with AE and with SLC39A4 mutations were described.[10] Their mutation detection strategy consisted of polymerase chain reaction amplification of all 12 exons and flanking intronic sequences, followed by direct nucleotide sequencing. It revealed 3 novel mutations, 1017ins53, which creates a premature termination codon, and 2 mis-sense mutations, R95C and Q303H. These techniques can be used to identify carriers, newborns, or fetuses by amniocentesis.

Histologic Findings

Histopathologic examination of the skin and eyelids reveals parakeratosis of the stratum corneum with occasional neutrophils and intracellular edema. The granular cell layer is diminished, and the upper epidermis demonstrates pallor and edema. Focal dyskeratosis is seen. The epidermis may be psoriasiform or atrophic. Occasionally, subcorneal (cutaneous) pustules are seen.

One case report details the ocular histopathology of a child who died before efficacious treatment was available. The findings include corneal epithelial thinning and loss of polarity of corneal epithelial cells, anterior corneal scarring and loss of Bowman membrane, cataract formation, ciliary body atrophy, retinal degeneration, retinal pigment epithelium (RPE) depigmentation, and optic atrophy.

Contributor Information and Disclosures

John D Sheppard, Jr, MD, MMSc Professor of Ophthalmology, Microbiology and Molecular Biology, Clinical Director, Thomas R Lee Center for Ocular Pharmacology, Ophthalmology Residency Research Program Director, 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, Association for Research in Vision and Ophthalmology, American Uveitis Society

Disclosure: Nothing to disclose.


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, South Carolina Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Simon K Law, MD, PharmD Clinical Professor of Health Sciences, Department of Ophthalmology, Jules Stein Eye Institute, University of California, Los Angeles, David Geffen School of Medicine

Simon K Law, MD, PharmD is a member of the following medical societies: American Academy of Ophthalmology, Association for Research in Vision and Ophthalmology, American Glaucoma Society

Disclosure: Nothing to disclose.

Christopher J Rapuano, MD Professor, Department of Ophthalmology, Jefferson Medical College of Thomas Jefferson University; Director of the Cornea Service, Co-Director of Refractive Surgery Department, Wills Eye Hospital

Christopher J Rapuano, MD is a member of the following medical societies: American Academy of Ophthalmology, American Ophthalmological Society, American Society of Cataract and Refractive Surgery, Contact Lens Association of Ophthalmologists, International Society of Refractive Surgery, Cornea Society, Eye Bank Association of America

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Cornea Society, Allergan, Bausch & Lomb, Bio-Tissue, Shire, TearScience, TearLab<br/>Serve(d) as a speaker or a member of a speakers bureau for: Allergan, Bausch & Lomb, Bio-Tissue, TearScience.

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, Pan-American Association of Ophthalmology

Disclosure: Nothing to disclose.

Additional Contributors

Andrew A Dahl, MD, FACS Assistant Professor of Surgery (Ophthalmology), New York College of Medicine (NYCOM); Director of Residency Ophthalmology Training, The Institute for Family Health and Mid-Hudson Family Practice Residency Program; Staff Ophthalmologist, Telluride Medical Center

Andrew A Dahl, MD, FACS is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, American Intraocular Lens Society, American Medical Association, American Society of Cataract and Refractive Surgery, Contact Lens Association of Ophthalmologists, Medical Society of the State of New York, New York State Ophthalmological Society, Outpatient Ophthalmic Surgery Society

Disclosure: Nothing to disclose.

  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. 2009 Mar-Apr. 26(2):150-4. [Medline].

  2. Andrews GK. Regulation and function of Zip4, the acrodermatitis enteropathica gene. Biochem Soc Trans. 2008 Dec. 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. 2009 Jan. 29(1):129-39. [Medline].

  4. Coromilas A, Brandling-Bennett HA, Morel KD, Chung WK. Novel SLC39A4 mutation in acrodermatitis enteropathica. Pediatr Dermatol. 2011 Nov-Dec. 28(6):697-700. [Medline].

  5. Wessells KR, King JC, Brown KH. Development of a plasma zinc concentration cutoff to identify individuals with severe zinc deficiency based on results from adults undergoing experimental severe dietary zinc restriction and individuals with acrodermatitis enteropathica. J Nutr. 2014 Aug. 144(8):1204-10. [Medline].

  6. 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. 2008 Oct. 35 Suppl 1:1-13. [Medline].

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

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

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

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

  11. Gupta M, Mahajan VK, Mehta KS, Chauhan PS. Zinc therapy in dermatology: a review. Dermatol Res Pract. 2014. 2014:709152. [Medline]. [Full Text].

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

  31. 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. 2009 Jan 29. [Medline].

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

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

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

Sharply demarcated, brightly erythematous periorificial plaque in an infant with acrodermatitis enteropathica.
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.