Pathophysiology: The underlying pathophysiology is unclear. Although the initial description of toxic erythema of the newborn is attributed to the 15th century physician Bartholomaeus Metlinger, this neonatal cutaneous eruption was recognized before the time of ancient Mesopotamia. Ancient Mesopotamian physicians believed this eruption to be "nature's method of cleansing the child of impure blood of the mother." In A Treatise on the Theory and Practice of Midwifery, the 18th century English physician William Smellie attributed the condition to "the costiveness of the child when the meconium hath not been sufficiently purged off."

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. 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 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

Frequency:

• In the US: The condition affects 30-70% of newborns. Carr and associates studied 270 newborns and found an incidence of 48%. Keitel and Yadav studied 207 consecutive newborns and found an incidence of 62%.

• Internationally: Incidence is 25.3% in Spain, 33.7% in Taiwan, and 20.6% in India.

Mortality/Morbidity:

• This is a benign, asymptomatic, self-limited skin condition with no known sequelae.

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. Other sets of observations have noted no racial difference in incidence.

Sex:

• No significant difference in incidence is noted between the sexes.

Age:

• This condition is limited to the neonatal period.

• In a study of 270 cases, the typical newborn with ETN was of average birth weight and born at term. 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.

History: ETN typically presents in term neonates aged 3 days to 2 weeks. Although ETN 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.

Physical: Asymptomatic small papules, vesicles, and, occasionally, pustules are present on the skin. These usually are 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 the face.

Lab Studies:
 

• Because of the distinctive appearance of the eruption, laboratory studies typically are not indicated. Microscopic examination of a skin lesion using a Wright stain reveals numerous eosinophils. Peripheral blood studies also may reveal a circulating eosinophilia.

• Given 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 are 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.

• 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.

Histologic Findings: Hyperkeratosis, follicular plugging, and accumulation of primarily eosinophils with some neutrophils in the follicular epithelium

Medical Care: ETN is a benign, asymptomatic, self-limited condition that requires no treatment.

Further Outpatient Care:

• This is a self-limited condition that typically resolves within 2 weeks after birth. If the condition persists or does not follow the usual course, prompt consultation with a specialist is advised.

Complications:

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

Prognosis:

• Prognosis is excellent. The lesions typically resolve within 2 weeks, and no cutaneous or systemic sequelae generally are observed.

Patient Education:

• Parents with older children often are not concerned by the appearance of ETN, 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 the eruption.

• 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.