Acrodermatitis Enteropathica

History and Physical

The presentation is usually at the time of weaning in infants who are breastfed and earlier when they are formula-fed. In some cases, an infant who is breastfed may present with the manifestations of acrodermatitis enteropathica even before weaning. This could be due to the decreased secretion of zinc into breast milk due to a mutation in the mothers. The characteristic skin findings include sharply-demarcated, dry, scaly erythematous plaques that are usually periorificial on the face or the anogenital area. The upper lip usually is spared. The plaques can be psoriasiform, eczematous, vesiculobullous, pustular, or erosive with the characteristic crusted border in the periphery. Nail changes, including paronychia, may be present, and the hair becomes brittle, dry, and lusterless. In profound deficiency, diffuse alopecia may be seen. Angular cheilitis delayed wound healing and pigmentary abnormalities also have been reported.

The systemic features include diarrhea, irritability, lethargy, anorexia, growth retardation, anemia, amenorrhea, neuropsychiatric problems, perinatal morbidity, hypogonadism, hyposmia, and hypogeusia, and eye abnormalities including conjunctivitis, blepharitis, corneal opacities, and photophobia. Immunological abnormalities also are seen. Superinfection with Staphylococcus aureus and Candida albicans is reported. The classical triad of acrodermatitis enteropathica includes alopecia, diarrhea, and a periorificial and acral cutaneous rash. If untreated, the disease could be fatal. The differential diagnoses of AE include protein-energy malnutrition, psoriasis, seborrheic dermatitis, and glucagonoma syndrome. Acrodermatitis dysmetabolic is the term used for metabolic disorders that result in a clinical presentation resembling AE. The causes most often reported include acquired deficiencies of zinc, amino acids, or biotin.

Lab Test

The following investigations may be helpful if zinc deficiency and acrodermatitis enteropathica are suspected.

• Serum/plasma zinc levels — normal non-fasting levels are 9.0–17.0 µmol/L
• Serum alkaline phosphatase — this may support the diagnosis if low
• Serum albumin — note that zinc is a negative acute-phase reactant so low levels of zinc may be seen if albumin is low or in the presence of inflammatory disease. Special collection precautions may be required. Be aware of false positives and false negatives
• Urine, hair, and maternal milk zinc levels — if available
• A full blood count — anemia and leukopenia are typical.

A biopsy from an early skin lesion is not specific as the histology may be similar to eczema or psoriasis. Spongiosis with epidermal pallor may be seen initially. Confluent parakeratosis, keratinocyte necrolysis, a thin Malpighian layer, and an absence of granular layer may be seen later.

The measurement of plasma zinc levels helps to confirm the diagnosis. A level of less than 70 microgram/L in fasting or less than 65 microgram/dL in non-fasting individuals is considered diagnostic. However, adequate care must be exercised while testing for zinc levels to obtain accurate values. The use of contaminated tubes, catheters, needles, or rubber stoppers may lead to erroneously high levels of zinc. The zinc levels may vary with the time of day, stress, or inflammation. The sample should be drawn in the morning using specially acid-washed glass bulbs or tubes. Low albumin levels may lead to a low zinc level; therefore, serum albumin also should be measured. Measurement of alkaline phosphatase, a zinc-dependent enzyme, also may be useful in some cases. In cases where the diagnosis is doubtful, histopathological examination of the affected skin may be helpful but is not diagnostic. The characteristic changes include psoriasiform hyperplasia with necrolysis, a term used for describing cytoplasmic pallor, confluent parakeratosis, spongiosis, and focal dyskeratosis.