What is acrodermatitis enteropathica?
Acrodermatitis enteropathica is a rare genetic disorder of zinc metabolism characterised by the triad of dermatitis, diarrhoea, and alopecia . It is an autosomal recessive condition caused by a mutation in the SLC39A4 gene, which codes for a zinc transporter protein [1,2].
What is an acrodermatitis enteropathica-like condition?
An acrodermatitis enteropathica-like condition presents with similar features to acrodermatitis enteropathica, but is caused by acquired zinc deficiency or a disorder of amino acid or fatty acid metabolism .
Acrodermatitis enteropathica-like conditions include:
- Acrodermatitis metabolica when secondary to a metabolic disorder
- Acrodermatitis acidemica when secondary to an organic acidaemia .
Who gets an acrodermatitis enteropathica-like condition?
An acrodermatitis enteropathica-like condition can be categorised as secondary to acquired zinc deficiency or to a metabolic disorder unrelated to zinc deficiency .
Acquired zinc deficiency
Causes of acquired zinc deficiency include [1-4]:
- Inadequate zinc intake (due to low breast milk levels, anorexia nervosa, total parenteral nutrition, or inadequate diet)
- Intestinal malabsorption (coeliac disease, Crohn disease, ulcerative colitis, cystic fibrosis, pancreatic dysfunction, high copper/iron/phytate intake, short bowel syndrome, medications)
- Increased urinary zinc excretion (nephrotic syndrome, liver cirrhosis, infection, diabetes mellitus, excessive alcohol ingestion, diuretics)
- Increased digestive fluid loss (intestinal fistula, diarrhoea)
- Increased requirements (pregnancy, lactating mothers, preterm infants)
- Low albumin and high metabolic demands (thermal burn, excessive sweating, liver cirrhosis, haemolysis).
An acrodermatitis enteropathica-like condition related to a metabolic disorder can be secondary to:
- A congenital condition present in the newborn period
- An acquired deficiency of protein or biotin deficiency, which can present at various stages of life [1,3].
Acrodermatitis enteropathica-like conditions secondary to metabolic disorders are caused by abnormalities disrupting the metabolism of amino acids or fatty acids . This can be direct, through disruption of the urea cycle, or by affecting co-factors, notably biotin [1–3].
Metabolic disorders responsible for acrodermatitis enteropathica-like conditions include [1–3]:
- Organic acidaemias, including:
- Propionic acidaemia
- Methylmalonic acidaemia
- Glutaric aciduria type 1
- Multiple carboxylase deficiency
- Maple syrup urine disease
- Ornithine transcarbamylase deﬁciency
- Carbamoyl phosphate synthetase deﬁciency
- Kwashiorkor [see Protein-energy malnutrition]
- Acquired biotin deficiency due to a restrictive diet (rare).
Necrolytic migratory erythema can present with a rash similar to acrodermatitis enteropathica in adults and is associated with glucagonoma .
What causes an acrodermatitis enteropathica-like condition?
When an acrodermatitis enteropathica-like condition is related to acquired zinc deficiency, the lack of zinc leads to abnormal keratinisation, cell proliferation, and defective immune response .
In metabolic disorders, amino acid or fatty acid deficiency leads to reduced keratinocyte growth and differentiation .
What are the clinical features of an acrodermatitis enteropathica-like condition?
Like its namesake, an acrodermatitis enteropathica-like condition typically presents with the triad of dermatitis, diarrhoea, and alopecia .
The cutaneous features of an acrodermatitis enteropathica-like condition include [1–3]:
- Acral and periorificial distribution
- Well-demarcated, symmetrical, erythematous, eczematous, or psoriasiform plaques and vesiculobullous lesions
- Angular cheilitis
- Poor wound healing.
Other features of an acrodermatitis enteropathica-like condition depend on the underlying cause, but often include [1,3,5]:
- Failure to thrive
- Neurological defects, such as developmental delay, seizures, and hypotonia
- Ophthalmic abnormalities, such as cataracts and retinitis pigmentosa
- Metabolic abnormalities, such as acidosis, ketosis, and hyperammonaemia.
What are the complications of an acrodermatitis enteropathica-like condition?
An acrodermatitis enteropathica-like condition can be complicated by secondary bacterial infection or candidiasis .
Decompensation of a congenital metabolic disorder during periods of illness or stress may result in acidosis, which is potentially fatal . Long-term neurodevelopmental problems are not uncommon in congenital metabolic disorders [1,5,6].
How is an acrodermatitis enteropathica-like condition diagnosed?
Acquired zinc deficiency is associated with low serum zinc levels and alkaline phosphatase . Zinc levels and alkaline phosphatase tend to be normal in acrodermatitis enteropathica-like conditions related to metabolic disorders .
A full blood count may reveal cytopenias in both acquired zinc deficiency and metabolic disorders [2,5].
The initial blood tests for an organic acidaemia may include :
- The partial pressure of carbon dioxide
Levels of specific amino acids or enzyme activity and the presence of organic acids in the urine may support a specific diagnosis [1,5].
Newborn screening detects many of the congenital metabolic causes of acrodermatitis enteropathica-like conditions and is available in many parts of the world including New Zealand, Australia, the United Kingdom, the United States, and Canada .
A skin biopsy of an acrodermatitis enteropathica-like condition has non-specific histopathology; epidermal pallor and confluent parakeratosis may be observed .
What is the differential diagnosis for an acrodermatitis enteropathica-like condition?
The differential diagnosis of an acrodermatitis enteropathica-like condition includes:
- Acrodermatitis enteropathica — genetic analysis of the SLC39A4 gene distinguishes this 
- Atopic dermatitis — this uncommonly affects the napkin area and lacks systemic symptoms
- Psoriasis — psoriasis causes erythematous scaly plaques and does not cause vesiculobullous and eczematous lesions [1,3]
- Napkin dermatitis — this is confined to the napkin area and has no systemic features.
What is the treatment for an acrodermatitis enteropathica-like condition?
An acrodermatitis enteropathica-like condition secondary to acquired zinc deficiency will resolve after oral zinc supplementation, usually at an initial dose of 0.5–1 mg/kg/day of elemental zinc . Whether there is an ongoing need for zinc replacement will depend on the cause [2,8].
An acrodermatitis enteropathica-like condition secondary to a metabolic disorder generally responds to dietary manipulation and medication in the form of specific organic supplements to correct metabolic deficiencies . Expert assistance should be sought from a nutritionist.
What is the outcome for an acrodermatitis enteropathica-like condition?
The outcome for an acrodermatitis enteropathica-like condition depends on the underlying condition.
Acquired zinc deficiency
An acrodermatitis enteropathica-like condition secondary to acquired zinc deficiency has a favourable prognosis if identified early [8,9]. The dermatological, gastrointestinal, and psychological manifestations tend to resolve within days to weeks following zinc replacement .
An acrodermatitis enteropathica-like condition secondary to a metabolic disorder can have a high mortality rate in the newborn period if undiagnosed. This is mitigated to some extent by detection in the newborn period with the help of screening programmes . A significant number of children diagnosed early with congenital metabolic disorders will still have ongoing problems with metabolic crises and neurocognitive development [5,6].