Acrodermatitis Enteropathica

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Acrodermatitis Enteropathica

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Acrodermatitis enteropathica is a rare inherited form of zinc deficiency, characterized by periorificial and acral dermatitis, alopecia, and diarrhea.

Zinc is an essential trace nutrient required for the proper function of more than 100 enzymes and plays a crucial role in nucleic acid metabolism. [1, 2]

Acrodermatitis enteropathica is an autosomal recessive disorder postulated to occur as a result of mutations in the SLC39A4 gene located on band 8q24.3. [3, 4, 5] The SLC39A4 gene encodes a transmembrane protein that is part of the zinc/iron-regulated transporter–like protein (ZIP) family required for zinc uptake. [6, 7] This protein is highly expressed in the enterocytes in the duodenum and jejunum [8, 9] ; therefore, affected individuals have a decreased ability to absorb zinc from dietary sources. Absence of a binding ligand needed to transport zinc may further contribute to zinc malabsorption. [10]

Differentiating acquired zinc deficiency disorders from acrodermatitis enteropathica is difficult because they have similar clinical presentations. Acquired zinc deficiency can occur as a result of low nutritional intake, malabsorption, excessive loss of zinc, or a combination of these factors. [11] Acrodermatitis enteropathica can only be accurately diagnosed after attempts to remove zinc supplementation have failed. [12] Importantly, transient acquired zinc deficiencies can occur in premature infants secondary to their greater physiological demand for zinc and lower body stores. [13, 14] Additionally, zinc deficiency can present in full-term breastfed infants as a result of low maternal serum zinc levels or a defect in mammary zinc secretion. [1, 15] Thus, not all infants who have an acrodermatitis enteropathica–like presentation have the genetic disorder. In 2018, a case was also reported of acrodermatitis enteropathica due to total parenteral nutrition devoid of zinc as there was a recent shortage; the condition resolved upon addition of zinc into the total parenteral nutrition. [16]

The etiopathogenesis of the zinc deficiency is postulated to occur as a result of a mutation in a zinc transport protein encoded by the SLC39A4 gene and perhaps alteration in a zinc transport ligand. [17] However, a case was reported of a patient with a new mutation of SLC39A4 who had normal zinc levels and a milder phenotype. [18]

United States

The frequency of acrodermatitis enteropathica is unknown.

International

An estimated 1 in 500,000 people in Denmark are affected by acrodermatitis enteropathica. [19]

Acrodermatitis enteropathica has no racial predilection.

Acrodermatitis enteropathica has no sexual predilection.

Acrodermatitis enteropathica typically appears in the first few weeks after birth if the child is fed bovine milk or shortly after cessation of breastfeeding. [9] Acrodermatitis enteropathica can occur in children who are still breastfeeding if the levels of zinc are low in the breast milk. [20]

With zinc supplementation, the response rate is 100%; however, without appropriate zinc supplementation, acrodermatitis enteropathica usually is lethal within the first few years of life. Untreated infants exhibit severe growth retardation, dermatitis, alopecia, secondary bacterial and fungal infections, and neurologic and behavioral changes; however, all symptoms are reversible with therapy.

In the future, genetic counseling with genetic testing may be available for siblings at risk for acrodermatitis enteropathica.

Perafan-Riveros C, Franca LF, Alves AC, Sanches JA Jr. Acrodermatitis enteropathica: case report and review of the literature. Pediatr Dermatol. 2002 Sep-Oct. 19(5):426-31. [Medline].

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

Kury S, Dreno B, Bezieau S, et al. Identification of SLC39A4, a gene involved in acrodermatitis enteropathica. Nat Genet. 2002 Jul. 31(3):239-40. [Medline].

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

Wang K, Pugh EW, Griffen S, Doheny KF, Mostafa WZ, al-Aboosi MM. Homozygosity mapping places the acrodermatitis enteropathica gene on chromosomal region 8q24.3. Am J Hum Genet. 2001 Apr. 68(4):1055-60. [Medline].

Schmitt S, Kury S, Giraud M, Dreno B, Kharfi M, Bezieau S. An update on mutations of the SLC39A4 gene in acrodermatitis enteropathica. Hum Mutat. 2009 Jun. 30(6):926-33. [Medline].

Kilic M, Taskesen M, Coskun T, Gürakan F, Tokatli A, Sivri HS, et al. A Zinc Sulphate-Resistant Acrodermatitis Enteropathica Patient with a Novel Mutation in SLC39A4 Gene. JIMD Rep. 2012. 2:25-8. [Medline]. [Full Text].

Wang K, Zhou B, Kuo YM, Zemansky J, Gitschier J. A novel member of a zinc transporter family is defective in acrodermatitis enteropathica. Am J Hum Genet. 2002 Jul. 71(1):66-73. [Medline]. [Full Text].

Maverakis E, Fung MA, Lynch PJ, et al. Acrodermatitis enteropathica and an overview of zinc metabolism. J Am Acad Dermatol. 2007 Jan. 56(1):116-24. [Medline].

Evans GW, Johnson PE. Zinc-binding factor in acrodermatitis enteropathica. Lancet. 1976 Dec 11. 2(7998):1310. [Medline].

Samady JA, Schwartz RA, Shih LY, Piela Z, Lambert WC, Janniger CK. Acrodermatitis enteropathica-like eruption in an infant with nonketotic hyperglycinemia. J Dermatol. 2000 Sep. 27(9):604-8. [Medline].

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

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

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

Corbo MD, Lam J. Zinc deficiency and its management in the pediatric population: a literature review and proposed etiologic classification. J Am Acad Dermatol. 2013 Oct. 69(4):616-624.e1. [Medline].

Baruch D, Naga L, Driscoll M, Kao G. Acrodermatitis enteropathica from zinc-deficient total parenteral nutrition. Cutis. 2018 Jun. 101 (6):450-453. [Medline].

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

Garza-Rodríguez V, de la Fuente-García A, Liy-Wong C, Küry S, Schmitt S, Jamall IS, et al. Acrodermatitis Enteropathica: A Novel SLC39A4 Gene Mutation in a Patient with Normal Zinc Levels. Pediatr Dermatol. 2015 May-Jun. 32 (3):e124-5. [Medline].

Champion RH, Burton JL, Ebling FJG. Textbook of Dermatology. London: Blackwell Science; 1998. 3: 2668.

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].

Willis MS, Monaghan SA, Miller ML, et al. Zinc-induced copper deficiency: a report of three cases initially recognized on bone marrow examination. Am J Clin Pathol. 2005 Jan. 123(1):125-31. [Medline].

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

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].

Niiyama S, Koelker S, Degen I, Hoffmann GF, Happle R, Hoffmann R. Acrodermatitis acidemica secondary to malnutrition in glutaric aciduria type I. Eur J Dermatol. 2001 May-Jun. 11(3):244-6. [Medline].

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

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].

Gonzalez JR, Botet MV, Sanchez JL. The histopathology of acrodermatitis enteropathica. Am J Dermatopathol. 1982 Aug. 4(4):303-11. [Medline].

Mori H, Matsumoto Y, Tamada Y, Ohashi M. Apoptotic cell death in formation of vesicular skin lesions in patients with acquired zinc deficiency. J Cutan Pathol. 1996 Aug. 23(4):359-63. [Medline].

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].

Welsmann K, Kvist N, Kobayasi T. Bullous acrodermatitis due to zinc deficiency during total parenteral nutrition: an ultrastructural study of the epidermal changes. Acta Derm Venereol. 1983. 63(2):143-6. [Medline].

Perez-Maldonado A, Kurban AK. Metabolic Diseases and Pregnancy. Clinics in Dermatology. Elsevier; 2006. 24: 88-90.

National Institutes of Health Office of Dietary Supplements. Zinc Fact Sheet for Health Professionals. Available at https://ods.od.nih.gov/factsheets/Zinc-HealthProfessional/. February 11, 2016; Accessed: October 3, 2017.

Kristina Marie Dela Rosa, MD Dermatologist, Insight Dermatology, San Diego, CA

Kristina Marie Dela Rosa, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association

Disclosure: Nothing to disclose.

Elizabeth K Satter, MD, MPH Dermatologist and Dermatopathologist

Elizabeth K Satter, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Medical Womens Association

Disclosure: Nothing to disclose.

Michael J Wells, MD, FAAD Dermatologic/Mohs Surgeon, The Surgery Center at Plano Dermatology

Michael J Wells, MD, FAAD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, Texas Medical Association

Disclosure: Nothing to disclose.

Edward F Chan, MD Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania School of Medicine

Edward F Chan, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American Academy of Dermatology, Society for Investigative Dermatology

Disclosure: Received income in an amount equal to or greater than $250 from: Elsevier; WebMD.

Eleanor E Sahn, MD Director, Division of Pediatric Dermatology, Associate Professor, Departments of Dermatology and Pediatrics, Medical University of South Carolina

Eleanor E Sahn, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, Southern Medical Association

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.

The view(s) expressed herein are those of the authors and do not reflect the official policy or position of Naval Special Warfare Center, the U.S. Navy Medical Department, the U.S. Navy Office of the Surgeon General, the Department of the Navy, Department of Defense, or the U.S. Government.

Acrodermatitis Enteropathica

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