eMedicine Specialties > Ophthalmology > Dermatologic Disorders

Acrodermatitis Enteropathica: Differential Diagnoses & Workup

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

Differential Diagnoses

Blepharitis, Adult
Ichthyosis
Cellulitis, Preseptal
Kawasaki Disease
Chlamydia
Keratoconjunctivitis, Atopic
Conjunctivitis, Allergic
Keratoconjunctivitis, Sicca
Conjunctivitis, Neonatal
Keratopathy, Neurotrophic
Dermatitis, Atopic
Red Eye Evaluation
Dry Eye Syndrome
Stevens-Johnson Syndrome
Entropion
Trichiasis

Other Problems to Be Considered

Acquired zinc deficiency
Alopecia
Atopic dermatitis
Biotin and multiple decarboxylase deficiencies
Candidiasis (cutaneous)
Candidiasis (mucosal)
Cystic fibrosis
Essential fatty acid deficiencies
Epidermolysis bullosa
Glucagonoma syndrome
Histiocytosis X
Kwashiorkor
Seborrheic dermatitis
Glutaric aciduria type 1
Leucinosis
Nonketotic hyperglycinemia
Food allergy

Workup

Laboratory Studies

  • 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

  • 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.8 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.

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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