Pediatric Erythema Toxicum

Erythema toxicum neonatorum (ETN) is a benign, self-limited, asymptomatic skin condition that only occurs during the neonatal period.[1, 2, 3, 4] The eruption is characterized by small, yellowish papules and pustules. The lesions are usually surrounded by an irregular erythematous macule or wheal. Individual lesions are transitory, often disappearing within hours and then appearing elsewhere on the body. They may occur anywhere on the body aside from the palms and soles. See the image below.

A 5-day-old newborn with erythematous papules with surrounding indistinct blotchy erythema visible on the abdomen. Image courtesy of Jining I. Wang, MD.

See 13 Common-to-Rare Infant Skin Conditions, a Critical Images slideshow, to help identify rashes, birthmarks, and other skin conditions encountered in infants.

The underlying mechanism of erythema toxicum neonatorum (ETN) is unknown, although various hypotheses have been described.[5]

The underlying pathophysiology is uncertain. The characteristic presence of eosinophils within the lesions has led some investigators to attribute this condition to an allergy. Work by Eitzman and Smith suggested that eosinophilia is part of the normal spectrum of the nonspecific inflammatory response in the neonate.[6] This hypothesis is supported by cases in which premature neonates have infrequent eruptions that resolve within a few weeks after birth when the neonatal immune response matures.

The etiology of erythema toxicum neonatorum (ETN) remains uncertain; however, more recent hypotheses explaining the appearance of this eruption include the following:

• Relative, increased, ground-substance viscosity in neonatal skin, with associated trauma leading to eosinophilic inflammation
• Self-limited, acute, cutaneous, graft versus host reaction caused by maternal lymphocytes in the relatively immunosuppressed fetal circulation, ^[7] although no maternal cells have been found within the lesions ^[8]
• An innate immunologic response to commensal microbes within hair follicle epithelium ^[9]
• An inflammatory response mediated by various inflammatory mediators, including aquaporins, psoriasin, and nitric oxide synthases

Frequency

United States

Erythema toxicum neonatorum (ETN) affects 30-70% of newborns.[10] Carr and associates studied 270 newborns and found an incidence of 48%.[11] Keitel and Yadav studied 207 consecutive newborns and found an incidence of 62%.[12]

International

Incidence is 25.3% in Spain, 33.7% in Taiwan, 20.6% in India, and 21.3% in Brazil.[4, 13, 14] In one geographically limited study in Brazil, the development of erythema toxicum neonatorum was correlated with birth during the spring through autumn months.[14]

Race

No significant differences based on race are apparent. A study by Saracli and associates documented a low incidence among black neonates; however, this may be caused by the relative difficulty of diagnosing neonates with darker skin.[15] Other sets of observations have noted no racial difference in incidence.

Sex

In previous studies, no significant difference in incidence is noted between the sexes. However, a study from China indicated a statistically significant predilection in boys.[16]

Age

This condition is limited to the neonatal period. In a study of 270 cases, the typical newborn with erythema toxicum neonatorum was of average birth weight and born at term.[11] Of the newborns affected, 88% weighed 2500 g or more. In addition, 98% were born at least 35 weeks' gestation, with 85% born at least 39 weeks' gestation.

The prognosis is excellent. The lesions typically resolve within 2 weeks, and no cutaneous or systemic sequelae are generally observed. This is a benign, asymptomatic, self-limited skin condition with no known sequelae.

Parents with older children often are not concerned by the appearance of erythema toxicum neonatorum, but first-time parents should be informed in the perinatal period that an evanescent rash is likely to appear within the first 2 weeks of life. They should be reassured regarding the benign, self-limited, asymptomatic nature of this and other eruptions.[17]

Review the clinical features with parents before they go home. If any concerns arise about an atypical rash, they should be comfortable contacting their primary care physician to discuss the issues. Before discharge, appropriately screen neonates who have risk factors for sepsis or neonatal herpes simplex virus infection.

Erythema toxicum neonatorum (ETN) typically presents in term neonates aged 3 days to 2 weeks. Although erythema toxicum neonatorum can occur in the first 48 hours, approximately 90% of cases occur after 48 hours. The eruption is characteristically evanescent, with lesions appearing and disappearing within minutes to hours.

Asymptomatic small, yellowish papules or pustules are present on the skin. These are usually seen on dependent areas, generally starting on the trunk. They then tend to spread centripetally. The lesions are surrounded by a distinctive blotchy erythematous halo on the trunk, extremities, and face. They do not occur on the palms and soles.

No complications or sequelae are noted with this eruption. Because of the presence of eosinophils within the lesions, investigators suspect an association with atopic disease; however, studies examining these potential links to atopy have not demonstrated any clear association.

Because of the distinctive appearance of the lesions, the nontoxic status of the neonate, and the evanescent nature of the eruption, the diagnosis is usually clear. If any doubt about the diagnosis exists, further studies may be needed to evaluate for an underlying bacterial, viral, or fungal disease.

A simple Gram stain or Wright stain should reveal evidence of a sterile pustule populated primarily by eosinophils. The presence of neutrophils suggests an infectious cause. Peripheral blood studies may also reveal a circulating eosinophilia.

Results from a direct slide (fluorescent antibody testing) of a smear or a Tzanck preparation should be negative for herpes simplex (or, rarely, varicella-zoster virus) because these are reasonably sensitive tests for these particular viruses.

A simple potassium hydroxide preparation can be performed to evaluate for fungal infection, such as congenital cutaneous candidiasis.

Blood cultures and appropriate workup for neonatal sepsis from group B Streptococcus, Listeria, Escherichia coli, and other pathogens should be considered in the appropriate context of illness in a neonate.

A skin biopsy may be necessary if the diagnosis is unclear.

Hyperkeratosis, follicular plugging, and accumulation of primarily eosinophils with some neutrophils in the follicular epithelium.

Erythema toxicum neonatorum (ETN) is a benign, asymptomatic, self-limited condition that requires no treatment. Education and reassurance should be given to the parents about the natural course of the condition. Guidelines for other similar dermatologic manifestations have been established.[18]

Erythema toxicum neonatorum (ETN) is often diagnosed easily by pediatricians and family physicians. If the features are atypical or the newborn appears ill or has risk factors for sepsis, consultation with a pediatric dermatologist may be advisable.

There is an association between developing eosinophilic esophagitis and erythema toxicum neonatorum (ETN) in the neonatal period.[19] It may be prudent to ask about neonatal rashes in children when eosinophilic esophagitis is suspected.

No pharmacologic treatment is indicated for erythema toxicum neonatorum (ETN).