eMedicine Specialties > Pediatrics: General Medicine > Dermatology

Acrodermatitis Enteropathica: Differential Diagnoses & Workup

Author: KN Siva Subramanian, MD, Professor of Pediatrics and Obstetrics/Gynecology, Chief of Neonatology, Director of Nurseries, Georgetown University Medical Center
Coauthor(s): Robert A Silverman, MD, Clinical Associate Professor, Department of Pediatrics, Georgetown University; Clinical Associate Professor, Departments of Pediatrics and Dermatology, University of Virginia at Charlottesville; Aimee M Barton, MD, Fellow in Neonatal-Perinatal Medicine, Department of Pediatrics, Division of Neonatology, Georgetown University Medical Center; Sepideh Montazami, MD, Assistant Professor, Department of Pediatrics, Section of Neonatal-Perinatal Medicine, Georgetown University School of Medicine
Contributor Information and Disclosures

Updated: Sep 29, 2008

Differential Diagnoses

Atopic Dermatitis
Biotin Deficiency
Candidiasis
Epidermolysis Bullosa

Other Problems to Be Considered

Other than acquired zinc deficiency, most differential diagnoses are easily excluded. A successful trial of zinc supplementation confirms the diagnosis. The following should also be considered:

  • Acquired zinc deficiency of any cause
  • Infants receiving inadequate supplementation in parenteral alimentation
  • Infants who were born prematurely
  • Full-term or premature breastfed infants
  • Infants with malabsorption due to cystic fibrosis or small-bowel resection (especially those undergoing nasogastric decompression)
  • Human immunodeficiency virus (HIV) disease
  • Atypical epidermolysis bulbosa
  • Generalized or localized candidiasis
  • Abnormal metabolism of essential fatty acids
  • Seborrheic dermatitis
  • Kwashiorkor disease
  • Iatrogenic deficiency of branched chain amino acids (isoleucine) in restrictive diets for maple syrup urine disease or methylmalonic aciduria

Workup

Laboratory Studies

  • In patients with acrodermatitis enteropathica (AE), the zinc concentration of plasma is measured. Specimens are collected in plastic syringes or acid-washed Vacutainer tubes to prevent exogenous contamination that could lead to spuriously normal measurements.
    • In most patients with AE, plasma zinc concentrations are low (<50 mcg/dL) but are not diagnostic.
    • Zinc concentrations within the reference range have been reported in patients with AE, and low zinc concentrations have been reported in patients without AE.
    • Most of the zinc accretion in a fetus occurs during the third trimester (at a rate of 850 mcg/kg/d). Therefore, in premature infants, a lack of stored zinc may precipitate symptoms early, especially if they are fed with formula.
  • Hair, saliva, or urine zinc levels are rarely needed.
  • Production of serum alkaline phosphatase depends on zinc; therefore, a low level of alkaline phosphatase may support a diagnosis of AE.
  • Secondary infections may require cultures and additional therapy.

Procedures

  • Skin or intestinal mucosal biopsy is rarely needed.

Histologic Findings

  • Intestinal mucosal biopsy reveals a loss of villous architecture with increased cell infiltration in the lamina propria in patients with AE. The nuclei are enlarged with an open chromatin distribution.
  • Complete normalization of the intestinal mucosa is observed in mucosal biopsy samples after zinc sulphate treatment.
  • Histopathology of cutaneous lesions reveals intracellular edema and pallor of the upper third of the epidermis. This finding is not pathognomonic and may be observed in other states of nutritional deficiency.

More on Acrodermatitis Enteropathica

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

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  2. Eide DJ. The SLC39 family of metal ion transporters. Pflugers Arch. Feb 2004;447(5):796-800. [Medline].

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  4. Prasad AS. Zinc: an overview. Nutrition. Jan-Feb 1995;11(1 Suppl):93-9. [Medline].

  5. Kiechl-Kohlendorfer U, Fink FM, Steichen-Gersdorf E. Transient symptomatic zinc deficiency in a breast-fed preterm infant. Pediatr Dermatol. Sep-Oct 2007;24(5):536-40. [Medline].

  6. Wells BT, Winkelmann RD. Acrodermatitis enteropathica. Report of 6 cases. Arch Dermatol. Jul 1961;84:40-52. [Medline].

  7. Arakawa T, Tamura T, Igarashi Y, et al. Zinc deficiency in two infants during total parenteral alimentation for diarrhea. Am J Clin Nutr. Feb 1976;29(2):197-204. [Medline].

  8. Barnes PM, Moynahan EJ. Zinc deficiency in acrodermatitis enteropathica: multiple dietary intolerance treated with synthetic diet. Proc R Soc Med. Apr 1973;66(4):327-9. [Medline].

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

  10. Chimenti F, Aouffen M, Favier A. Zinc homeostasis-proteins: new drug targets for triggering cell fate. Curr Drug Targets. 2003;4:323-8.

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  13. Food and Nutrition Board, Institute of Medicine. Dietary reference intakes for vitamin A, vitamin K, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. Washington, DC: National Academy Press; 2001:442-501. [Full Text].

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  17. Hurley LS, Eckhert CD, Duncan JR, et al. [Acrodermatitis enteropathica and human breast milk]. Lancet. Jan 22 1977;1(8004):195. [Medline].

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  23. Moynahan EJ, Barnes PM. Zinc deficiency and a synthetic diet for lactose intolerance. Lancet. Mar 24 1973;1(7804):676-7. [Medline].

  24. Piela Z, Szuber M, Mach B, et al. Zinc deficiency in exclusively breast-fed infants. Cutis. Apr 1998;61(4):197-200. [Medline].

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  26. Samady JA, Schwartz RA, Shih LY, et al. Acrodermatitis enteropathica-like eruption in an infant with nonketotic hyperglycinemia. J Dermatol. Sep 2000;27(9):604-8. [Medline].

  27. Sivasubramanian KN, Henkin RI. Behavioral and dermatologic changes and low serum zinc and copper concentrations in two premature infants after parenteral alimentation. J Pediatr. Nov 1978;93(5):847-51. [Medline].

  28. Sivasubramanian KN, Hoy G, Davitt MK, et al. Zinc and copper changes after neonatal parenteral alimentation. Lancet. Mar 4 1978;1(8062):508. [Medline].

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Further Reading

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Keywords

acrodermatitis enteropathica, AE, skin inflammation, periorificial dermatitis, acral dermatitis, alopecia, error of zinc metabolism, zinc deficiency, periorificial dermatitis, acral dermatitis, diarrhea, failure to thrive, anorexia, alopecia, nail dystrophy, malabsorption, geophagia, food allergy, growth retardation, photophobia, paronychia

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Contributor Information and Disclosures

Author

KN Siva Subramanian, MD, Professor of Pediatrics and Obstetrics/Gynecology, Chief of Neonatology, Director of Nurseries, Georgetown University Medical Center
KN Siva Subramanian, MD is a member of the following medical societies: American Academy of Pediatrics, American Association for the Advancement of Science, American College of Nutrition, American Society for Parenteral and Enteral Nutrition, American Society of Law Medicine and Ethics, New York Academy of Sciences, and Southern Society for Pediatric Research
Disclosure: Nothing to disclose.

Coauthor(s)

Robert A Silverman, MD, Clinical Associate Professor, Department of Pediatrics, Georgetown University; Clinical Associate Professor, Departments of Pediatrics and Dermatology, University of Virginia at Charlottesville
Robert A Silverman, MD is a member of the following medical societies: American Academy of Dermatology and American Academy of Pediatrics
Disclosure: Nothing to disclose.

Aimee M Barton, MD, Fellow in Neonatal-Perinatal Medicine, Department of Pediatrics, Division of Neonatology, Georgetown University Medical Center
Aimee M Barton, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, and Medical Society of Virginia
Disclosure: Nothing to disclose.

Sepideh Montazami, MD, Assistant Professor, Department of Pediatrics, Section of Neonatal-Perinatal Medicine, Georgetown University School of Medicine
Sepideh Montazami, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, British Medical Association, and Royal College of Physicians
Disclosure: Nothing to disclose.

Medical Editor

Kevin P Connelly, DO, Clinical Assistant Professor, Department of Pediatrics, Division of General Pediatrics and Emergency Care, Virginia Commonwealth University; Medical Director, Paws for Health Pet Visitation Program of the Richmond SPCA; Pediatric Emergency Physician, Emergency Consultants Inc, Chippenham Medical Center
Kevin P Connelly, DO is a member of the following medical societies: American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from broker recommendation; Avanir Pharma Stock Investment from broker recommendation

Managing Editor

Robert A Schwartz, MD, MPH, Professor and Head of Dermatology, Professor of Medicine, Professor of Pediatrics, Professor of Pathology, Professor of Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi
Disclosure: Nothing to disclose.

CME Editor

Merrily P M Poth, MD, Professor, Department of Pediatrics and Neuroscience, Uniformed Services University of the Health Sciences
Merrily P M Poth, MD is a member of the following medical societies: American Academy of Pediatrics, Endocrine Society, and Lawson-Wilkins Pediatric Endocrine Society
Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

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