Case 1: A ‘rash’-ional approach to recalcitrant diaper dermatitis

A five-month-old female infant who was born at 24 weeks gestational age presented with a five-week history of an erythematous eruption that began in the perineum. It progressed to involve the entire lower face, with areas of excoriations and erythematous crusted patches around the mouth and distal extremities.

The rash did not respond to oral nystatin or topical terbinafine. Due to the persistence of the rash and an intercurrent upper respiratory tract infection, the patient presented to the emergency department. Upon review of systems, the patient had mild diarrhea and no history of alopecia. She was exclusively breastfed. The patient’s past history included respiratory distress syndrome, bronchopulmonary dysplasia, retinopathy of prematurity and gastroesophageal reflux disease.

Physical examination revealed an irritable infant. She had an axillary temperature of 37.8ºC. The rest of her vital signs were normal. She had multiple confluent maculopapular lesions over her perioral and perineal area (Figures 1 and 2), with erosions, desquamation and crusting. Her fingers and toes were similarly affected, with sparing of the inframammary, labial and gluteal creases. The rest of the examination was normal.

Figure 1.

Face at presentation

Figure 2.

Buttocks at presentation

The infant was admitted to hospital and started on intravenous cloxacillin for impetigo. A diagnostic test was performed on admission, which revealed the diagnosis.

CASE 1 DIAGNOSIS: ACQUIRED ZINC DEFICIENCY (ACRODERMATITIS ENTEROPATHICA-LIKE ERUPTION) RELATED TO PREMATURITY

Zinc deficiency was suspected, and laboratory testing revealed a serum zinc level of 4 μmol/L (normal range 11 μmol/L to 18 μmol/L). The patient was started on 15 mg of oral zinc divided into three doses daily. The infant had significant improvement by 48 h. She was weaned off of zinc over the next two months, with no recurrence of the rash.

Diaper dermatitis is a frequent presenting problem in the newborn period. There are common and uncommon causes (Table 1). Irritant diaper dermatitis is the most common cause of diaper dermatitis and is due to irritation by the combination of urine, feces, friction and moisture. A candidal diaper eruption usually presents as beefy red plaques with peripheral scaling and satellite papules or pustules. This usually involves the folds and is often well demarcated. Seborrheic dermatitis presents as yellow, greasy, scaly patches on a red background on the scalp (cradle cap), in the axilla, neck folds, behind the ear and in the diaper area. Although these are all common causes of diaper dermatitis, if the rash does not fit one of these clinical scenarios or is persistent despite adequate treatment, other diagnostic possibilities need to be explored.

TABLE 1.

Diaper dermatitis

Common causes

Irritant diaper dermatitis

Candidal diaper dermatitis

Seborrheic dermatitis

Uncommon causes

Langerhans cell histiocytosis

Psoriasis

Congenital syphilis

Atopic dermatitis

Staphylococcal infection

Immunobullous diseases (epidermolysis bullosa, pemphigus vulgaris)

Nutritional deficiencies (niacin deficiency [pellagra], abnormalities in fatty acid metabolism and zinc deficiency)

Among the uncommon causes are nutritional deficiencies. Examples that may cause recalcitrant diaper dermatitis include fatty acid deficiencies, niacin deficiency and zinc deficiency, as in our patient. Zinc is an essential elemental nutrient required for normal growth and development Quantitatively, it is second in the human body, after iron, and deficiencies may be due to inherited or acquired causes. Zinc plays an important role in protein, carbohydrate and vitamin A metabolism; growth and development; cell proliferation; and healing and tissue repair. It is present in at least 100 metalloenzymes, such as carbonic anhydrase, alkaline phosphatase, RNA and DNA polymerase, and carboxypeptidases A and B. Not surprisingly, deficiencies in zinc can cause a number of clinical symptoms.

In 1973, Barnes and Moynahan established a link between congenital zinc deficiency and the symptoms caused, within the framework of acrodermatitis enteropathica.

This is a rare autosomal recessive disorder in which affected individuals suffer from a defective uptake of zinc in the duodenum and jejunum. Initial signs and symptoms usually occur during the first few months of life, often after weaning from breast to cow’s milk. The cutaneous eruption consists of vesiculobullous, eczematous, dry, scaly or psoriasiform skin lesions symmetrically distributed in the perioral, acral and perineal areas and on the cheeks, knees and elbows. Diarrhea and alopecia may also be present.

Acquired zinc deficiency can result in similar clinical symptoms. This occurs most commonly in premature infants. It can also be seen in infants being breastfed by mothers who have low or absent levels of zinc in their breast milk due to a defect in the transfer of zinc from maternal serum to breast milk. Other causes of acquired zinc deficiency include malabsorption, inborn errors of metabolism and long-term total parenteral nutrition. In premature infants, the greatest accumulation of zinc occurs in the third trimester, and total body zinc is inversely proportional to the degree of prematurity. Preterm infants are also prone to a negative zinc balance for up to 60 days secondary to poor zinc absorption, increased zinc secretion by the intestine and increased zinc demand because of rapid growth and development.

Zinc given through total parenteral nutrition (450 μg/kg/day to 500 μg/kg/day) is the only way to meet in utero accretion rates before 36 weeks postconceptional age, because of extensive resecretion of oral zinc into the gut. After that time, infants should be consuming formulas supplemented with 12 mg/L zinc for the rest of their infancy.

In transient symptomatic zinc deficiency, the effects of zinc replacement are prompt. It takes only three days to two weeks for the skin lesions to clear. Treatment is usually only required until weaning from the breast occurs. The differentiation between acrodermatitis enteropathica and acquired zinc deficiencies is important to define in reference to treatment duration. It is variable in the acquired forms, but always limited, and there is no recurrence when oral replacement is discontinued.

CLINICAL PEARLS

• Common causes of diaper dermatitis include irritant diaper dermatitis, candidal diaper dermatitis and seborrheic dermatitis.

• Suspect zinc deficiency in the at-risk population, and for patients with recalcitrant diaper dermatitis particularly when associated with similar perioral lesions.

• Premature infants have a negative zinc balance and need adequate zinc intake.