Acrodermatitis enteropathica-like conditions

What is acrodermatitis enteropathica?

Acrodermatitis enteropathica is a rare genetic disorder of zinc metabolism characterised by the triad of dermatitis, diarrhoea, and alopecia [1]. It is an autosomal recessive condition caused by a mutation in the SLC39A4 gene, which codes for a zinc transporter protein [1,2].

Acrodermatitis enteropathica 

Acrodermatitis enteropathica 

Acrodermatitis enteropathica 

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 [1].

Acrodermatitis enteropathica-like conditions include:

• Acrodermatitis metabolica when secondary to a metabolic disorder
• Acrodermatitis acidemica when secondary to an organic acidaemia [1].

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 [1].

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).

Metabolic disorders

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 [1]. 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
• Phenylketonuria
• Ornithine transcarbamylase deficiency
• Citrullinaemia
• 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 [1].

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 [1].

In metabolic disorders, amino acid or fatty acid deficiency leads to reduced keratinocyte growth and differentiation [1].

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 [2].

Cutaneous features

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

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 [1].

Decompensation of a congenital metabolic disorder during periods of illness or stress may result in acidosis, which is potentially fatal [5]. 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 [2]. Zinc levels and alkaline phosphatase tend to be normal in acrodermatitis enteropathica-like conditions related to metabolic disorders [1].

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 [5]:

• pH
• The partial pressure of carbon dioxide
• Bicarbonate
• Lactate
• Electrolytes
• Urea
• Creatinine
• Glucose
• Pyruvate
• Ammonia.

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 [5].

A skin biopsy of an acrodermatitis enteropathica-like condition has non-specific histopathology; epidermal pallor and confluent parakeratosis may be observed [7].

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 [2]
• 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 [2]. 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 [5]. 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 [9].

Metabolic disorders

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 [5]. A significant number of children diagnosed early with congenital metabolic disorders will still have ongoing problems with metabolic crises and neurocognitive development [5,6].