Plaques and erosions around orifices and acral regions in an infant - Clinical Advisor

Plaques and erosions around orifices and acral regions in an infant

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A 7-month-old male who had been born prematurely presents with a 2-month history of diarrhea, failure to thrive, alopecia, and rash involving the perioral, perianal, and acral areas. He had been treated unsuccessfully for presumed atopic dermatitis with topical corticosteroids. He was exclusively breastfed until 2 months ago, when he was transitioned to formula. Examination reveals an irritable, thin infant with sharply demarcated red, inflamed, scaly plaques and erosions around his mouth, anus, eyes, hands, and feet. Diffuse hair loss is noted on the scalp, eyebrows, and eyelashes. Paronychia and nail dystrophy are noted on his upper and lower extremities.

Acrodermatitis enteropathica (AE) is a rare, autosomal recessive disease characterized by pink, scaly plaques and erosions around the orifices and acral regions and caused by poor zinc absorption.1-3 It is linked to mutations in the SLC39A4 gene (solute carrier family...

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Acrodermatitis enteropathica (AE) is a rare, autosomal recessive disease characterized by pink, scaly plaques and erosions around the orifices and acral regions and caused by poor zinc absorption.1-3 It is linked to mutations in the SLC39A4 gene (solute carrier family 39 [zinc transporter], member 4) on chromosome 8q24.3.2,4 Zinc forms the critical component of the catalytic site of hundreds of enzymes and is essential for healthy immune function, wound healing, central nervous system development, normal taste and smell, and gastrointestinal and reproductive function; it can be found in nuts, oats, soy flour, cheese, leafy vegetables, and shellfish.2-4

Clinical findings of AE are highly variable, reflect the severity of AE, and are equivalent to those observed in dietary zinc deficiency.2,3 However, in AE, symptoms manifest approximately 4 to 6 weeks after weaning from breast milk, or in weeks 4 to 10 of life in formula-fed infants, as existing zinc stores are depleted.1,3 This phenomenon is thought to occur as a result of low molecular weight-binding agents in human milk, which increase the bioavailability of zinc and delay the onset of symptoms.3 In contrast, cow milk contains more zinc-binding phytates, which prevent zinc absorption in the duodenum and jejunum.

Early signs include perioral, perianal, and acral dermatitis.4 Classically, these lesions are well demarcated, pink to red, erythematous, scaly, and variably eroded plaques.2 Pustules, blisters, and bullae may develop.2 In more advanced disease, alopecia, nail dystrophy, diarrhea, delayed wound healing, angular stomatitis, conjunctivitis, blepharitis, increased susceptibility to infection, and failure to thrive are observed.1,2 Infants manifesting signs of AE are irritable, withdrawn, and sensitive to light.1 If the zinc deficiency is not addressed, patients develop hypogonadism, delayed puberty, pica, impaired taste and smell, night blindness, and neuropsychiatric symptoms, including mood changes, tremors, and jitteriness.1

 

AE is diagnosed through clinical history and examination. Laboratory testing, response to zinc supplementation, and cutaneous histopathology can help confirm the diagnosis. Historically, AE was defined by a triad of symptoms including periacral and periorificial dermatitis, alopecia, and diarrhea; however, the complete triad only manifests in 25% of cases.5 The most common clinical symptoms are cutaneous lesions.5

Low serum alkaline phosphatase (ALP) and zinc levels are also diagnostic and improve with zinc therapy.1 Plasma zinc deficiency is defined by levels lower than 70 mcg/dL in morning fasting samples and lower than 65 mcg/dL in nonfasting samples.3 Blood samples should be obtained before breakfast and before taking multivitamins or supplements containing zinc.3 Up to 60% to 80% of serum zinc is bound to albumin; therefore, the zinc value must be corrected for abnormal albumin levels.3 ALP is a zinc-dependent metalloenzyme, and low serum ALP levels support a diagnosis of zinc deficiency, although levels may be normal in mild cases.1,3 If plasma zinc and serum ALP levels are normal and clinical suspicion remains high, a trial of zinc supplementation can be conducted to assess clinical response.3,5 Although transient neonatal zinc deficiency, also known as acquired zinc deficiency of lactogenic origin, responds rapidly to zinc supplementation as well, interruption of zinc therapy should not induce a relapse in symptoms in these patients unlike in patients with AE.5

Biopsy of AE lesions reveals findings consistent with nutritional deficiency.2 The first finding to appear is typically nonspecific cytoplasmic pallor.3 In advanced disease, a collection of findings referred to as necrolysis, including ballooning and reticular degeneration and necrosis of keratinocytes in stratum spinosum and granulosum, are observed.2,3 Chronic lesions typically exhibit psoriasiform hyperplasia with little to no cytoplasmic pallor.3

The simultaneous appearance of skin and gastrointestinal symptoms in the setting of the classic timing of symptom onset after weaning from breastfeeding should alert clinicians to consider zinc deficiency.4 The differential for AE includes acrodermatitis enteropathica-like eruption (AELE) of cystic fibrosis, AELE unrelated to zinc deficiency, biotin deficiency, kwashiorkor, and atopic dermatitis.3 Unlike AE, these conditions are not associated with decreased plasma zinc, and serum ALP levels are usually normal.3,4 In addition, patients with AELE associated with cystic fibrosis exhibit respiratory symptoms and will have positive sweat chloride test results; patients with AELE unrelated to zinc deficiency develop symptoms due to the low protein diet used for maintenance of underlying metabolic disorders; and patients with biotin deficiency have brittle hair, myalgias, and sensorineural hearing loss. Patients with kwashiorkor are edematous, have severely decreased muscle mass, and changes in hair color. Patients with atopic dermatitis have family members with other atopic conditions, have a pruritic rash, and do not have gastrointestinal or hair involvement.

Patients with AE are treated with oral zinc dosed at 2 to 3 mg/kg/d, which resolves all clinical manifestations within 1 to 2 weeks.1,2 However, supplementation must be continued through adulthood.1,4 Plasma zinc levels should be monitored every 3 to 6 months to ensure adequate supplementation.2 Copper levels should also be monitored because zinc administration can interfere with copper absorption.2 Clinicians should consider genetic testing in family members, as diagnosis has prognostic and treatment impact on other children in the family.4 Early diagnosis and treatment is critical because untreated AE can be fatal.4

The patient described in this case responded rapidly to oral supplemental zinc sulfate at 1 mg/kg/d. Clinical response was observed within 5 days, and the patient continues to be maintained on supplemental therapy.

Key points for acrodermatitis enteropathica.

Clinical presentation
  • •Characterized by erythematous, dry, scaly patches and plaques, which may evolve into crusted cesiculobullous, erosive, and psoriasiform lesions
  • •Lesions are classically perioral, perianal, and acral
  • •Loss of hair, nail dystrophy, mucosal findings, and delayed wound healing
  • •Infants are irritable and withdrawn and have growth impairment
Differential diagnosis AELE of cystic fibrosis, AELE unrelated to zinc deficiency, biotin deficiency, kwashiorkor, atopic dermatitis, cutaneous candidiasis, epidermolysis bullosa
Diagnosis
  • •Diagnoses clinically and can be confirmed through laboratory testing demonstrating low plasma zinc and serum ALP levels, response to zinc supplementation, and cutaneous histopathology
  • •Consider genetic testing for family members because this is a chronic condition requiring life-long zinc supplementation
Management
  • •Oral zinc (1-3 mg/kg/d) will cure all clinical manifestations within 1-2 weeks and needs to be continued through adulthood; plasma/serum zinc levels should be monitored every 3-6 months
  • •Copper levels should be evaulated

AELE, acrodermatitis enteropathica-like eruption; ALP, alkaline phosphate.

Melinda Liu, BA, is a medical student and Maura Holcomb, MD, is a dermatology resident at Baylor College of Medicine in Houston.

References

  1. Gupta M, Mahajan VK, Mehta KS, Chauhan PS. Zinc therapy in dermatology: a review. Dermatol Res Pract. 2014;2014:709152.
  2. Iyengar S, Chambers C, Sharon VR. Bullous acrodermatitis enteropathica: case report of a unique clinical presentation and review of the literature. Dermatol Online J. 2015;21(4). doj_26272.
  3. 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.e1-624.e1.
  4. Jung AG, Mathony UA, Behre B, et al. Acrodermatitis enteropathica: an uncommon differential diagnosis in childhood—first description of a new sequence variant. J Dtsch Dermatol Ges. 2011;9(12):999-1002.
  5. Küry S, Kharfi M, Schmitt S, Bézieau S. Clinical utility gene card for: acrodermatitis enteropathica [published online December 14, 2011]. Eur J Hum Genet. 2012;20(3). doi:10.1038/ejhg.2011.227.
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