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Dermatology > METABOLIC DISEASES
Acrodermatitis Enteropathica
Article Last Updated: Feb 28, 2007
AUTHOR AND EDITOR INFORMATION
Section 1 of 11  
Author: Timothy G Woodall, MD, Dermatology, Carolinas Medical Center - Pineville
Timothy G Woodall is a member of the following medical societies: American Academy of Dermatology, American Society for Dermatologic Surgery, and South Carolina Medical Association
Editors: Eleanor E Sahn, MD, Director, Division of Pediatric Dermatology, Associate Professor, Departments of Dermatology and Pediatrics, Medical University of South Carolina; Michael J Wells, MD, Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center; Edward F Chan, MD, Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania School of Medicine; Catherine Quirk, MD, Clinical Assistant Professor, Department of Dermatology, Brown University; William D James, MD, Paul R Gross Professor of Dermatology, University of Pennsylvania School of Medicine; Vice-Chair, Program Director, Department of Dermatology, University of Pennsylvania Health System
Author and Editor Disclosure
Synonyms and related keywords:
AE, zinc deficiency
Background
Acrodermatitis enteropathica (AE) is an autosomal recessive disorder characterized by periorificial and acral dermatitis, alopecia, and diarrhea.
Pathophysiology
The genetic mutation of SLC39A4 on 8q24.3 appears to be the cause.
AE can only be accurately diagnosed after attempts to remove zinc supplementation have failed. Therefore, patients with AE must remain on zinc supplementation for life. Differentiating AE from acquired zinc deficiencies can be difficult because both conditions present in the same manner. Some studies have shown that low zinc levels in the mother's milk may produce an acquired zinc deficiency in full-term, breastfed infants. Zimmerman et al has proposed that some acquired zinc deficiencies may be due to a defect in mammary zinc secretion. These studies tend to dispute the claim that human breast milk has a protective effect against zinc deficiency. Acquired zinc deficiency may also occur in premature infants, whether or not maternal zinc levels are low or normal, because of the infants' greater bodily demand or lower bodily stores of zinc.
Frequency
United States
The frequency is unknown.
International
An estimated 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, Graves et al reported an untreated adult survivor.
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.
History
Symptoms of AE occur within the first few months after birth and tend to appear shortly after discontinuation of breastfeeding.
Physical
- Physical examination is significant for erythematous patches and plaques of dry, scaly, eczematous skin that may evolve into crusted, vesiculobullous, erosive, and pustular lesions. Lesions are distributed in a periorificial and acral pattern on the face, the scalp, the hands, the feet, and the anogenital areas.
- Paronychia as well as loss of scalp hair, eyebrows, and eyelashes may occur.
- The lesions may become secondarily infected with Staphylococcus aureus and Candida albicans.
- Infants may also experience withdrawal, photophobia, and loss of appetite.
Causes
The genetic defect appears to involve SLC39A4 on 8q24.3. The SLC39A4 gene appears to encode a transmembrane protein that serves as a zinc uptake protein. Symptoms of AE occur within the first few months after birth and tend to appear shortly after discontinuation of breastfeeding. This phenomenon has led many to believe that human milk has a beneficial ligand, which bovine milk lacks. Evans and Johnson postulated picolinate as the ligand; Lonnerdal et al suggested citric acid. Cousins and Smith proposed that the protein concentration of human milk affects zinc bioavailability. While the genetic defect has apparently been identified, the breastfeeding link has not clearly been established.
Atopic Dermatitis
Candidiasis, Cutaneous
Candidiasis, Mucosal
Epidermolysis Bullosa
Glucagonoma Syndrome
Seborrheic Dermatitis
Other Problems to be Considered
Biotin and multiple decarboxylase deficiencies
Cystic fibrosis
Essential fatty acid deficiencies
Histiocytosis X
Kwashiorkor
Acquired zinc deficiency
Glutaric aciduria type 1
Leucinosis
Nonketotic hyperglycinemia
Food allergy
Lab Studies
- Plasma zinc levels are low (Use an acid-washed tube with no rubber stopper because they can sometimes contain zinc), and characteristic histopathologic findings are seen on skin biopsy specimens.
- Determining hair, urine, and parotid saliva zinc levels as well as serum alkaline phosphatase activity (which lowers later in the disease) may be helpful.
- Analysis of maternal breast milk zinc concentrations may also help in differentiating AE from acquired zinc deficiency.
Histologic Findings
Histopathologic examination 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 pustules are seen.
Medical Care
Treatment of AE involves greater than 1-2 mg/kg of oral zinc supplementation per day for life.
Diet
No special diet is necessary as long as zinc supplementation is continued.
Activity
No activity restrictions are necessary.
Zinc dietary supplementation of 1 mg/kg/d for life is essential. Secondary bacterial and/or candidal infections need to be addressed as necessary.
Drug Category: Mineral supplements
These agents are used to reduce morbidity and to prevent complications.
| Drug Name | Zinc gluconate (Verazinc, Zinca-Pak, Orazinc) |
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| Description | Cofactor for more than 70 types of enzymes. Plays a role in many metabolic processes. One 10-mg tab contains 1.4 mg of elemental zinc. |
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| Adult Dose | 1 mg/kg/d PO for life |
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| Pediatric Dose | 0.5-1 mg elemental zinc/kg PO qd, divided 1-3 times/d |
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| Contraindications | Documented hypersensitivity |
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| Interactions | May reduce effect of penicillamine, tetracycline, and quinolones; concomitant administration of copper or iron with zinc may decrease their gastrointestinal absorption |
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| Pregnancy | C - Safety for use during pregnancy has not been established.
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| Precautions | Caution in renal impairment; very high dosages can result in sideroblastic anemia and microcytic anemia, secondary to zinc-induced copper deficiency (latter can be associated with neurologic defects |
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In/Out Patient Meds:
- Zinc supplementation as already described (see Medical Care).
Complications:
- If untreated, the lesions may become secondarily infected with S aureus and C albicans.
- Infants may experience withdrawal, photophobia, and loss of appetite.
Prognosis:
- Further progression and even death may occur if AE is left untreated.
Patient Education:
- Genetic counseling and testing may determine persons who are at risk.
Medical/Legal Pitfalls
- Early diagnosis and treatment should preclude any medicolegal pitfalls.
| Media file 1:
Sharply demarcated, brightly erythematous periorificial plaque in an infant with acrodermatitis enteropathica. |
 |  View Full Size Image | |
Media type: Photo
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Acrodermatitis Enteropathica excerpt Article Last Updated: Feb 28, 2007
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