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Acrodermatitis enteropathica-like conditions

Author: Leah Jones, Medical Registrar, Christchurch, New Zealand. DermNet NZ Editor in Chief: Adjunct A/Prof Amanda Oakley, Dermatologist, Hamilton, New Zealand. Copy edited by Gus Mitchell. May 2020.


Acrodermatitis enteropathica-like conditions — codes and concepts
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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].

Acrodermatiits 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 (acquired protein deficiency)
  • 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].

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References

  1. Tabanlioğlu D, Ersoy-Evans S, Karaduman A. Acrodermatitis enteropathica-like eruption in metabolic disorders: acrodermatitis dysmetabolica is proposed as a better term. Pediatr Dermatol. 2009;26(2):150-4. doi:10.1111/j.1525-1470.2008.00803.x. PubMed
  2. Gehrig KA, Dinulos JG. Acrodermatitis due to nutritional deficiency. Curr Opin Pediatr. 2010;22(1):107-112. doi:10.1097/MOP.0b013e328335107f. PubMed
  3. Crone J, Huber WD, Eichler I, Granditsch G. Acrodermatitis enteropathica-like eruption as the presenting sign of cystic fibrosis--case report and review of the literature. Eur J Pediatr. 2002;161(9):475-8. doi:10.1007/s00431-002-0982-0. PubMed
  4. Corbo MD, Lam J. Zinc deficiency and its management in the pediatric population: a literature review and proposed etiologic classification. J Am Acad Dermatol. 2013;69(4):616-24.e1. doi:10.1016/j.jaad.2013.04.028. PubMed
  5. Bodamer O. Organic academias: an overview and specific defects. UpToDate, 2020. Available at: www.uptodate.com/contents/organic-academias-an-overview-and-specific-defects?search=acrodermatitis%20enteropathica&topicRef=2936&source=see_link [accessed 4 Apr 2020]
  6. Grünert SC, Müllerleile S, de Silva L, et al. Propionic acidemia: neonatal versus selective metabolic screening. J Inherit Metab Dis. 2012;35(1):41-9. doi:10.1007/s10545-011-9419-0. PubMed
  7. Lie E, Sung S, Yang SH. Adult autoimmune enteropathy presenting initially with acquired acrodermatitis enteropathica: a case report. BMC Dermatol. 2017;17(1):7. doi:10.1186/s12895-017-0059-4. PubMed
  8. Abrams SA. Zinc deficiency and supplementation in children. UpToDate 2020 [cited 2020 Apr 14]. Available at: www.uptodate.com/contents/zinc-deficiency-and-supplementation-in-children?search=acrodermatitis%20enteropathica&source=search_result&selectedTitle=1~20&usage_type=default&display_rank=1#H132777961 [accessed 14 Apr 2020]
  9. Krebs NF. Update on zinc deficiency and excess in clinical pediatric practice. Ann Nutr Metab. 2013;62 Suppl 1:19-29. doi:10.1159/000348261. PubMed

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