AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Background

Acrodermatitis enteropathica (AE) is an inborn error of zinc metabolism that is inherited as an autosomal recessive disorder. Symptoms in infancy typically include periorificial and acral dermatitis, diarrhea, behavioral changes, and neurologic disturbances. In older children, failure to thrive, anorexia, alopecia, nail dystrophy, and repeated infections are most common.

Zinc deficiency may be due to inadequate intake, malabsorption, excessive loss, or a combination of these factors. If treated early, most of the symptoms are reversible and usually cause no sequelae.

Pathophysiology

The pathophysiology of AE remains unclear and continues to be debated. Zinc is an essential trace element for life It is not only an important nutrient and cofactor of enzymes and transcription factors but also an intracellular mediator, similar to calcium.

Zinc homeostasis results from a coordinated regulation by different proteins involved in uptake excretion and intracellular storage of zinc. Intracellular molecular pathways were recently discovered to be involved in zinc homeostasis.

In 2001, Wang et al mapped the AE genetic locus to band 8q24.3. More recently, a group of proteins, the SLC39 proteins that are members of the broad ZIP family of metal ion transporters, were implicated in playing a role in zinc uptake across the plasma membrane of various cell types. These proteins transport metal ions from the cell exterior or lumen of intracellular organelles into the cytoplasm. Their principal function is to provide zinc to new synthesized proteins, a process important for several functions, such as gene expression, immunity, reproduction or protection against free-radical damage. The human genome encodes for 14 SLC39-related proteins. SLC39A4 is specifically implicated in the uptake of dietary zinc into intestinal enterocytes. Mutations in its gene have been identified in patients with AE.

In infants with AE, an absence of a binding ligand may contribute to zinc malabsorption during weaning. Such a ligand has been identified in normal pancreatic secretions as well as in human milk. Other causes, such as high phytate concentrations found in cereals and soy milk, inhibit zinc absorption. Geophagia, which Prasad (1995) described, decreases zinc absorption.

AE was recently reported as a presentation of food allergy. Serum total immunoglobulin E (IgE) and food-specific IgE levels to milk, soybean, wheat, and peanut have been measured to evaluate for food allergy. Undiagnosed food allergy can lead to profound zinc deficiency. Food allergy should be suspected in children with acquired AE.

Mortality/Morbidity

Untreated patients usually die in the first few years of life. They have severe growth retardation, dermatitis, alopecia, secondary bacterial and fungal infections, and neurologic and behavioral changes. All of these conditions are reversible with therapy. Therapy achieves a survival rate of 100%.

Race

No race predilection is reported.

Sex

No sex predilection is reported.

Age

Symptoms typically appear in the first few months of life, when an infant is weaned from breastfeeding. However, symptoms of AE can develop in full-term breastfed infants as a result of zinc deficiency in breast milk and decreased maternal plasma zinc levels.

AE-like symptoms have also been described in older children and adults who are receiving prolonged parenteral nutrition without zinc supplementation

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

History

Obtain information any siblings or relatives who have similar symptoms. Any history of diarrhea, anorexia, photophobia, behavioral changes, suggest AE as a possibility in the differential diagnosis.

Physical

In general, patients are miserable and depressed. Infants are inconsolable and may withdraw from contact.

• Dermatitis: Erythematous, vesiculobullous, or pustular lesions that lead to dry, scaly, or eczematoid lesions distributed around periorificial and acral areas of the body are characteristic of AE. The borders of affected areas are sharply demarcated and have an accentuation of craquelé-like scale at the periphery. Paronychia may be present.
• Alopecia: Partial or total hair loss may be evident. Wells and Winkelman (1961) described these symptoms in a series of 58 cases. They found that 91% of their patients had diarrhea, 98% had alopecia, 96% had nail dystrophy, and 100% had dermatitis.

Causes

Zinc deficiency causes all the aforementioned clinical symptoms, which are easily and rapidly reversible with zinc supplementation.

DIFFERENTIALS

Section 4 of 10  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Other Problems to be Considered

Other than acquired zinc deficiency, most differential diagnoses are excluded easily. A successful trial of zinc supplementation confirms the diagnosis.

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)
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

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Lab Studies

• 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 not diagnostic.
  • Zinc concentrations in 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 shows 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 of epidermal keratinocytes. This finding is not pathognomonic and may be observed in other states of nutritional deficiency.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Medical Care

• Zinc gluconate or sulfate is administered orally at a dosage of 1-3 mg/kg/d. Although the intravenous dosage has not clearly been estimated, amounts of 300-1000 mcg/kg/d may be sufficient for rapid reversal of symptoms.
• • Clinical response is observed within 5-10 days.
  • In AE, maintain zinc therapy throughout the patient's life span, though periods of remission are reported.
  • Exacerbation during pregnancy or the stress of disease may require an increase in therapy.
  • In acquired zinc deficiency, treatment can be stopped after the precipitating cause is resolved.
• Warm compresses and petrolatum applied 3 times a day to areas of weeping or crusted dermatitis may enhance reepithelialization when used concurrently with zinc replacement.

Consultations

Consultation with pediatricians, dermatologists, pediatric gastroenterologists, and/or nutritionists may be necessary.

Diet

The zinc content of some relatively zinc-rich foods is listed in Table 1 below.

Table 1. Zinc Content of Zinc-Rich Foods

Table 2. Recommended Dietary Allowances for Zinc

NA = not applicable.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Drug Category: Zinc supplements

Zinc is essential to normal growth and tissue repair and is important to protein and carbohydrate metabolism.

Drug Category: Skin protectants

These protectants may enhance reepithelialization when used concurrently with zinc replacement.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Further Outpatient Care

• In infants and children, outpatient follow-up care is critical to ensure proper growth and development.

In/Out Patient Meds

• Zinc gluconate or sulfate therapy is lifelong for patients with AE.

Complications

• High-dose zinc supplementation occasionally causes gastric upset.
• High-dose zinc supplementation may also adversely affect copper metabolism.

Prognosis

• Patients with AE uniformly respond to zinc therapy with a 100% survival rate.
• With zinc supplementation, various symptoms completely resolve or substantially improve.
• In a noncompliant patient, many of the described complications (including death) can occur.

Patient Education

• Provide information regarding zinc deficiency as the cause of AE.
• Emphasize the importance of lifelong compliance in taking zinc supplements.

MULTIMEDIA

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Media file 1:  Skin lesions in the diaper area.
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Media file 2:  Skin lesions in the diaper area (see Image 1) a few weeks after treatment with zinc.
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Media file 3:  Facial lesions.
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Media file 4:  Foot lesions.
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REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

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Article Last Updated: Jul 10, 2006