Acrodermatitis Enteropathica 

Updated: Aug 21, 2019
Author: Kristina Marie Dela Rosa, MD; Chief Editor: William D James, MD 

Overview

Background

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

Pathophysiology

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 occurring 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]

Etiology of Acrodermatitis Enteropathica

The etiopathogenesis of the zinc deficiency occurs as a result of a mutation in a zinc transport protein encoded by the SLC39A4 gene.[17] A case has been reported of a patient with a mutation of SLC39A4 who had normal zinc levels and a mild phenotype.[18]

Epidemiology

Frequency

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]

Race

Acrodermatitis enteropathica has no racial predilection.

Sex

Acrodermatitis enteropathica has no sexual predilection.

Age

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]

Prognosis

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.

Patient Education

Genetic counseling is recommended for family members of parents with the congenital form of acrodermatitis enteropathica.

 

Presentation

History

Patients have a history of refractory diarrhea, failure to thrive, irritability, dermatitis, and alopecia that gradually appeared shortly after weaning from breast milk. Occasionally, patients have a history of siblings or other family members with similar symptoms in infancy.[1] Only 20% of cases have all the components of the triad of dermatitis, alopecia, and diarrhea.[1]

Physical Examination

Physical signs and symptoms are as follows:

  • General: Infants are typically irritable and often inconsolable, and they show a slowing or cessation of growth and development.

  • Skin: Erythematous, dry, and scaly patches and plaques are present and may evolve into crusted, vesiculobullous, erosive, psoriasiform, and pustular lesions. Lesions are predominantly distributed in a periorificial and acral pattern and may become secondarily infected with Staphylococcus aureus or Candida albicans.

  • Mucosa: Findings include angular cheilitis, glossitis, conjunctivitis, blepharitis, punctate keratopathy, and photophobia.

  • Nails: Paronychia and nail dystrophy are typical.

  • Hair: Patients have loss of scalp hair, eyebrows, and eyelashes.

See the image below.

Sharply demarcated, brightly erythematous periorif Sharply demarcated, brightly erythematous periorificial plaque in an infant with acrodermatitis enteropathica.

Complications

If untreated, the lesions of acrodermatitis enteropathica may become secondarily infected with Staphylococcus aureus and Candida albicans. Additionally, high-dose zinc supplementation occasionally causes gastric upset and can adversely affect copper metabolism.[21]

 

DDx

Diagnostic Considerations

Other considerations include the following:

  • Biotin and multiple decarboxylase deficiencies

  • Malabsorption syndromes secondary to cystic fibrosis or intestinal disease[22]

  • Essential fatty acid deficiencies

  • Kwashiorkor

  • Human immunodeficiency virus (HIV) disease

  • Iatrogenic deficiency of branched chain amino acids (isoleucine) in restrictive diets for maple syrup urine disease or methylmalonic aciduria[23]

  • Glutaric aciduria type 1[24]

  • Leucinosis

  • Nonketotic hyperglycinemia[11]

Differential Diagnoses

 

Workup

Laboratory Studies

Plasma zinc levels should be tested. Specimens should be collected in plastic syringes or acid-washed Vacutainer tubes with no rubber stopper to prevent exogenous contamination that could lead to spuriously normal measurements. Plasma zinc concentrations of less than 50 mcg/dL are suggestive, but not diagnostic, of acrodermatitis enteropathica.[9]

Hair, saliva, or urine zinc levels can be obtained but are rarely needed.[25]

Because alkaline phosphatase is a zinc-dependent enzyme, reduced serum levels of alkaline phosphatase in the context of normal zinc levels can indicate a zinc deficiency.[26] However, alkaline phosphatase levels are typically not decreased unless the individual has advanced disease.

Analysis of maternal breast milk zinc concentrations may help in differentiating acrodermatitis enteropathica from acquired zinc deficiency.[1]

Histologic Findings

Light microscopy

Histological evaluation of a skin biopsy specimen is characteristic, but the same findings can be seen in other nutritional disorders. The histological findings vary with the age of the lesion. Early lesions show confluent parakeratosis associated with a reduced granular layer. Often, exocytosis of neutrophils into the epidermis is noted, which may be acanthotic and exhibit slight spongiosis. The intracellular edema eventuates into pallor of the upper third of the epidermis.[27] Subsequently, subcorneal and intraepidermal clefts may develop as a result of massive ballooning and reticular degeneration, with necrosis of the keratinocytes.[28] In late lesions, psoriasiform hyperplasia of the epidermis and less epidermal pallor are noted.[29]

Electron microscopy

Extracellular edema is associated with degenerate keratinocytes with multiple cytoplasmic vacuoles and slender, fingerlike protrusions. Few desmosomes are present, and the basal lamina is well preserved. Additionally, accumulation of cytoplasmic lipid droplets and intracellular edema in the spinous layer of the epidermis are seen.[30]

 

Treatment

Medical Care

Treatment of acrodermatitis enteropathica requires lifelong zinc supplementation. Typically, 1-3 mg/kg of zinc gluconate or sulfate is administered orally each day.[9, 13] Clinical improvement occurs prior to any significant change in the plasma zinc levels, usually within days to weeks of initiating treatment. Monitor serum zinc levels and alkaline phosphatase values every 3-6 months.[9]

Acrodermatitis enteropathica exacerbation during pregnancy or the stress of disease may require an increase in therapy.[1, 31]

Warm compresses to remove the scale crust, followed by application of white petrolatum to eroded skin lesions, may enhance reepithelialization when used concurrently with zinc replacement.

Diet

Although no special diet is required for acrodermatitis enteropathica patients, as long as zinc supplementation is continued, certain foods contain increased levels of zinc, including oysters, crab, beef, pork, and fowl. Zinc content is directly related to protein content.[19, 32]

Activity

No activity restrictions are necessary for acrodermatitis enteropathica patients.

Long-Term Monitoring

Outpatient follow-up care is critical for acrodermatitis enteropathica patients to ensure proper growth and development.

 

Medication

Medication Summary

Treatment of acrodermatitis enteropathica requires lifelong zinc supplementation. Typically, 1-3 mg/kg of zinc gluconate or sulfate is administered orally each day.

Mineral supplements

Class Summary

These agents are used to reduce morbidity and to prevent complications in acrodermatitis enteropathica.

Zinc (Galzin, ZnCl2)

One 10-mg tablet contains 1.4 mg of elemental zinc.

 

Questions & Answers

Overview

What is acrodermatitis enteropathica?

What is the pathophysiology of acrodermatitis enteropathica?

What causes acrodermatitis enteropathica?

What is the prevalence of acrodermatitis enteropathica in the US?

What is the global prevalence of acrodermatitis enteropathica?

What are the racial predilections of acrodermatitis enteropathica?

What is the sexual predilection of acrodermatitis enteropathica?

At what age does acrodermatitis enteropathica typically present?

What is the prognosis of acrodermatitis enteropathica?

What is included in the patient education about acrodermatitis enteropathica?

Presentation

Which clinical history findings are characteristic of acrodermatitis enteropathica?

Which physical findings are characteristic of acrodermatitis enteropathica?

What are the possible complications of acrodermatitis enteropathica?

DDX

Which conditions are included in the differential diagnoses of acrodermatitis enteropathica?

What are the differential diagnoses for Acrodermatitis Enteropathica?

Workup

What is the role of lab tests in the workup of acrodermatitis enteropathica?

Which histologic findings are characteristic of acrodermatitis enteropathica?

Treatment

How is acrodermatitis enteropathica treated?

Which dietary modifications are used in the treatment of acrodermatitis enteropathica?

Which activity modifications are used in the treatment of acrodermatitis enteropathica?

What is included in the long-term monitoring of acrodermatitis enteropathica?

Medications

Which medications are used in the treatment of acrodermatitis enteropathica?

Which medications in the drug class Mineral supplements are used in the treatment of Acrodermatitis Enteropathica?