Peri-Orificial Rash in an Infant

BMJ 2017;358:j3606 doi: 10.1136/bmj.j3606 (Published 2017 September 07) Page 1 of 4

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CASE REVIEW Peri-orificial rash in an infant

Hui Min Liew consultant, Jin Ho Chong consultant

Dermatology, KK Women’s and Children’s Hospital, Singapore

A 6 month old girl was brought to the paediatric dermatology outpatient clinic with a rash, irritability, and poor weight gain Answers for two months. She was born at 32 weeks’ gestation with intrauterine growth restriction as a result of placental 1. insufficiency. She was exclusively breastfed. There was no What are the differential diagnoses? family history of skin disorders. On examination, she had scaly Short answer erythematous plaques around her eyes, nose, mouth, ears, and Differential diagnoses include atopic dermatitis, psoriasis, neck (fig 1). impetigo, tinea infection, peri-orificial dermatitis, zinc deficiency, and, more rarely, Langerhans cell histiocytosis, other nutritional deficiencies, and metabolic disorders.

Discussion The differentiating features of the aforementioned conditions1 are described in Table 1⇓.

2. Which differential diagnosis is most likely? Short answer The likely diagnosis is acquired zinc deficiency as a result of Fig 1 Scaly erythematous plaques around the eyes, nostril, poor nutrition in the breastfeeding mother and the increased mouth, ears, and neck demand for zinc in the premature baby. In an infant, symptoms of zinc deficiency include faltering weight, irritability, and peri-orificial dermatitis. She had been recently prescribed mild topical corticosteroids to treat presumed atopic dermatitis, but there had been no improvement. Discussion Skin swab and scraping for bacterial and fungal microscopy The serum zinc level in the child’s mother was low at 665 μg/L 2 and culture were taken. The serum zinc level of the child and (normal range 724-1244 µg/L). Breastmilk zinc level was low her mother, and the full blood count and liver function tests for at 470 μg/L (normal range 1233 ±752 μg/L at 6 months). The the child were obtained. underlying cause for the zinc deficiency needs to be determined, as its management differs. Possible causes of zinc deficiency Questions include 3 1. What are the differential diagnoses? • Reduced zinc intake of the breastfeeding mother 2. Which differential diagnosis is most likely? • Increased maternal demand for zinc in a pregnant breastfeeding mother3 3. What is the most appropriate initial management for this 3 condition? • Zinc loss from chronic disease in mother or infant • Increased demand for zinc in premature infants3

Correspondence to H-M Liew [email protected]

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• Acrodermatitis enteropathica: abnormal absorption of zinc over-supplement child and mother because zinc toxicity can in the gastrointestinal tract of the infant as a result of induce copper and/or iron deficiency.7 If prolonged or long term SLC39A4 gene mutation4 supplementation is required, regular zinc levels should be 4 • Transient neonatal zinc deficiency: decreased zinc excretion checked every three to six months. via the maternal mammary epithelial cells into breastmilk due to maternal mutation of the SLC30A2 gene5 Patient outcome Low alkaline phosphatase might indicate zinc deficiency, As the infant’s serum zinc and breast milk zinc levels were low, although it can be normal in mild cases.4 transient neonatal zinc deficiency needed to be excluded using genetic testing, which was negative. A diagnosis was made of Acrodermatitis enteropathica and transient neonatal zinc acquired zinc deficiency caused by poor maternal nutrition in deficiency are genetic conditions, which were excluded in this the breastfeeding mother (in view of the borderline low serum case using genetic testing. Table 2 helps to differentiate these zinc level) and the history of prematurity. two conditions if genetic testing is not available.3-5 Both mother and child were supplemented with zinc sulphate 3. for 12 weeks while breastfeeding continued, and the baby was What is the most appropriate initial weaned to solids. The rash disappeared after a week and did not management for this condition? recur.

Short answer We have read and understood BMJ policy on declaration of interests Initial management involves zinc supplementation for the child. and declare no competing interests. Supplementation can be empirically administered in the absence Parental consent obtained. of zinc testing to assess for clinical improvement within two Provenance and peer review: not commissioned; externally peer days. reviewed.

Discussion 1 Eichenfield LF, Frieden IJ, eds. Neonatal and infant dermatology. 3rd ed. Elsevier Saunders, 2016. The child should start zinc supplementation. Her mother can be 2 Choua G, El Haloui N, El Kari K, et al. Amount of zinc transferred in breast milk to breastfed prescribed zinc supplementation while establishing her own Moroccan babies with normal or low birth weight at 1, 3, and 6 months after birth. Int J Child Health Nutr 2014;358:48-54doi:10.6000/1929-4247.2014.03.01.6. diet with zinc rich food (such as red meat, poultry, baked beans, 3 Corbo MD, Lam J. Zinc deficiency and its management in the pediatric population: a and nuts). literature review and proposed etiologic classification. J Am Acad Dermatol 2013;358:616-24.e1. doi:10.1016/j.jaad.2013.04.028 pmid:23688650. The dose of zinc supplementation depends on the underlying 4 Maverakis E, Fung MA, Lynch PJ, et al. Acrodermatitis enteropathica and an overview cause and severity of zinc deficiency. In acquired and reversible of zinc metabolism. J Am Acad Dermatol 2007;358:116-24. doi:10.1016/j.jaad.2006.08. 015 pmid:17190629. cases, children should receive elemental zinc at 0.5 to 1 5 Lasry I, Seo YA, Ityel H, et al. A dominant negative heterozygous G87R mutation in the mg/kg/day4 and this can be given for three to four months6 or zinc transporter, ZnT-2 (SLC30A2), results in transient neonatal zinc deficiency. J Biol Chem 2012;358:29348-61. doi:10.1074/jbc.M112.368159 pmid:22733820. until the child is fully established on solid food. Lactating 6 Jen M, Yan AC. Syndromes associated with nutritional deficiency and excess. Clin mothers should have a balanced diet and the infant should be Dermatol 2010;358:669-85. doi:10.1016/j.clindermatol.2010.03.029 pmid:21034991. referred to a dietitian for advice on weaning to zinc rich solids. 7 Fosmire GJ. Zinc toxicity. Am J Clin Nutr 1990;358:225-7.pmid:2407097. Supplementation with zinc fortified formula milk can be Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/ considered if the amount of breast milk is insufficient. permissions Lifelong zinc supplementation at 1-3 mg/kg/day is required in acrodermatitis enteropathica.6 Exercise caution to not

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Tables

Table 1| Differential diagnoses of a peri-orificial rash

Differential diagnosis Clinical history Cutaneous findings Investigations Management Atopic dermatitis Family history of atopy Facial and flexural dermatitis None Responds to emollients and topical corticosteroid Psoriasis Possible family history of Erythematous scaly plaques over None Responds to emollients and topical psoriasis scalp, groin, or extensors. Nail corticosteroid changes Impetigo History of atopic dermatitis or Erythematous yellow crusted Skin swab for bacterial Antibiotics sibling/child in nursery plaques over peri-orificial, moist microscopy and culture intertriginous areas Tinea infection Similar rash in family members Annular rash Skin scraping for fungal Topical or oral antifungal. Might or contact with animals microscopy and culture respond partially to topical corticosteroids if inflamed, masking the tinea infection Peri-orificial dermatitis Topical/inhaled corticosteroid Acneiform rash over peri-orifices None Stop application of corticosteroid. use Topical calcineurin inhibitors, or oral erythromycin Zinc deficiency Poor weight gain, irritability, and Peri-orificial and diaper rash Liver function tests and serum Zinc supplementation. diarrhoea Alopecia. zinc level Zinc rich diet Langerhans cell Bone pain, multiple infections, Polymorphic rash with crusting Full blood count, liver function Observation if limited to the skin. If histiocytosis easy bruising or diabetes and petechiae on the scalp with tests, computed tomography bone is involved, corticosteroid, insipidus alopecia, retroauricular, and in the scan, skeletal survey, and skin chemotherapy, or radiotherapy inguinal creases biopsy +/−bone marrow aspiration Nutritional deficiencies History of restrictive diet and Peri-orificial dermatitis, diaper Metabolic analysis of cultured Avoid restrictive diet and replace and metabolic disorders chronic illness. Positive family rash, alopecia, and change in hair skin fibroblasts, biotinidase dietary deficiency of trace elements (biotin deficiency, history of consanguinity or such texture level, amino acids assay for methylmalonic acidemia, disorders inborn errors of metabolism. essential fatty acid Exclude cystic fibrosis deficiency)

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Table 2 Comparison of acrodermatitis enteropathica and transient neonatal zinc deficiency

Acrodermatitis enteropathica Transient neonatal zinc deficiency Time of onset Late: when child is weaned from breastmilk to formula Early: when child is exclusively breastfeeding milk Family history Autosomal recessive inheritance Autosomal dominant inheritance. History of affected breastfed infants Infant serum zinc level Extremely low (<50 µg/dL) Can be extremely low in severe unrecognised cases Maternal serum zinc level Normal Normal Breastmilk zinc level Normal Low Response to zinc supplementation Immediate response but flares after withdrawal Immediate response. Does not flare after withdrawal if the child is weaned or takes formula milk

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