Erythema Toxicum Neonatorum

Background

Erythema toxicum neonatorum (ETN) is a benign self-limited eruption occurring primarily in healthy newborns in the early neonatal period. Erythema toxicum neonatorum is characterized by macular erythema, papules, vesicles, and pustules, and it resolves without permanent sequelae.^[1] See the image below.

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

Also see the article, Pediatric Erythema Toxicum.

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Pathophysiology

Increased levels of immunological and inflammatory mediators (eg, interleukins 1 and 8, eotaxin, the adhesion molecule E-selectin, the water-channel proteins aquaphorin 1 and aquaphorin 3, the chemotactic factor psoriasin, high-mobility group box chromosomal protein 1, nitric oxide and its isoforms, the antimicrobial peptide LL-37) suggest that erythema toxicum neonatorum may be an immune system reaction.^{[2, 3, 4]} The location of erythema toxicum neonatorum to primarily hair-bearing areas suggests that the hair follicle may be involved. Additionally, the number of mast cells is increased around hair follicles in involved skin.^[5]

The eosinophilic infiltrate of erythema toxicum neonatorum suggests an allergic- or hypersensitivity-related etiology, but no allergens have been identified. Newborn skin appears to respond to any injury with an eosinophilic infiltrate. Because erythema toxicum neonatorum is rarely seen in premature infants, it is believed that immunologically mature newborn skin is required to produce this reaction pattern.^[6]

Contactants and mechanical irritation have been considered and rejected as etiologies.

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Etiology

The cause of erythema toxicum neonatorum is unknown. Multiple theories have been proposed to explain this common disorder.

Neonates have an increased number of hair follicles compared with adults, and the occurrence of erythema toxicum neonatorum in non–hair-bearing areas such as palms and soles is rare. Inflammatory cells tend to concentrate around hair follicles, and coccilike microbes have been demonstrated in the follicular epithelium and inside the inflammatory cells. This suggests that erythema toxicum neonatorum may be a response to microbes that have penetrated the hair follicle. This process may possibly be integral in developing the new immune system.^[7]

The high frequency of eosinophilia suggests an allergic basis, leading some authors to suggest that erythema toxicum neonatorum may be an immediate hypersensitivity reaction to a substance passed from the mother transplacentally; however, convincing support is lacking for this theory.^[8]

No responsible exotoxin, allergen, component of sebum, or infectious agent has been linked credibly to erythema toxicum neonatorum.

Medications administered to newborns and the mode of feeding have no effect on incidence.

Other proposed theories include a transient adjustment reaction of the skin to mechanical or thermal stimulation or an acute graft-versus-host reaction induced by the maternal-fetal transfer of lymphocytes before or during delivery.^[9] Analysis of skin samples of 2 male patients with erythema toxicum neonatorum did not support a graft-versus-host reaction because no maternal cells were found in the samples using fluorescence in situ hybridization identification of cells with 2 XX chromosomes.^[10]

Risk factors include higher birth weight, greater gestational age, and vaginal delivery. A positive correlation has been recognized between the length of labor and both the incidence of erythema toxicum neonatorum and the duration of the cutaneous manifestations.^{[11, 12]}

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Epidemiology

Frequency

United States

A review of incidence in the United States across a range of ethnic groups revealed an incidence of 7%.^[13] Studies involving US populations have reported an incidence of up to 30%.^[14]

International

International studies have found a similar range in the incidence of erythema toxicum neonatorum, occurring in approximately one third to one half of full-term infants. A Brazilian study reported a prevalence rate of 21.3%.^[15]

Race

No racial or ethnic predisposition is known.

Sex

The prevalence is higher in males (55%) than in females (30%),^{[11, 15]} except among females born of first pregnancies, who have a higher rate than males of first pregnancies.

Age

Erythema toxicum neonatorum presents within the first 4 days of life in full-term infants, with the peak onset occurring within the first 48 hours following birth. Rare cases have been reported at birth.^{[16, 17]}

Incidence rises with increasing gestational age and birth weight.^[6]

Delayed onset rarely may occur in full-term and preterm infants up to age 14 days.^{[18, 19]}

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Prognosis

Prognosis of erythema toxicum neonatorum is excellent. Erythema toxicum neonatorum is a transient eruption with spontaneous resolution and no associated long-term morbidity. Erythema toxicum neonatorum may recur in approximately 11% of patients up to age 6 weeks. Recurrences tend to be mild and resolve without sequelae. Although one study found that infants with erythema toxicum neonatorum had an increased risk of atopy,^[20] subsequent studies have failed to support this finding.

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Patient Education

Reassure parents that erythema toxicum neonatorum is not inherited or infectious, has no complications, and has an excellent prognosis with spontaneous resolution.

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History

When evaluating for erythema toxicum neonatorum (ETN), focus the history on age at onset of the eruption, absence of systemic signs (eg, fever, irritability, lethargy, mucocutaneous involvement), or maternal history of herpes simplex/varicella viral infection, bacterial pyoderma, or candidiasis.^[21]

Infants with erythema toxicum neonatorum are otherwise healthy and lack systemic symptoms. The eruption is self-limited with most cases resolving within 5-14 days without residual sequelae. Recurrences are uncommon but have been reported up to the sixth week of life. They tend to be mild in severity.

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Physical Examination

Focus the physical examination on location, size, and distribution of macules, wheals, papules, and pustules on the skin. Note the absence of mucosal, palmar, or plantar involvement (ie, non – hair-bearing skin). Signs of systemic toxicity, including hypothermia or hyperthermia, lethargy, and irritability, are not associated with erythema toxicum neonatorum.

Erythema toxicum neonatorum most commonly presents with a blotchy, evanescent, macular erythema, often on the face or trunk.

The macules are irregular, blanchable, and vary in size.

In more severe cases, pale yellow or white wheals or papules on an erythematous base may follow. In approximately 10% of patients, 2-4 mm pustules develop.

Numbers and distribution of lesions vary from a few and widely scattered to numerous and extensive.

Sites of predilection include the most commonly include the trunk, buttocks, and proximal limbs, but lesions may occur anywhere, including the genitalia.^[22] Involvement of the mucous membranes and palms and soles rarely occurs.

See the images below.

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

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Yellow pustules, some with evidence of rupture, in a full-term infant at 6 hours of life.

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Erythematous blotchy patches localized to the trunk in a neonate.

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Complications

Complications of erythema toxicum neonatorum are not commonly reported. However, one reports describes a strong association between erythema toxicum neonatorum and eosinophilic esophagitis.^[23]

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Laboratory Studies

Erythema toxicum neonatorum (ETN) is diagnosed clinically based on history, physical examination, and peripheral smear of intralesional contents.

On a CBC count, eosinophilia are noted in approximately 15% of patients as up to 18% of the total WBC count. Eosinophilia may be more pronounced when the eruption shows a marked pustular component.

A Wright stain performed on intralesional contents will reveal primarily eosinophils. Inflammatory cells are present, with greater than 90% eosinophils and variable numbers of neutrophils.^{[12, 25]}

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Other Tests

If clinical symptoms warrant concern for systemic disease, Giemsa stain fails to show eosinophils, and/or clinical suspicion warrants an evaluation of other diagnoses, perform viral, bacterial, and fungal cultures to exclude herpes simplex virus, varicella, pathogenic bacterial, and yeast infections.

Perform potassium hydroxide preparation to exclude candidiasis.

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Procedures

A skin biopsy is diagnostic but rarely is required for diagnosis.

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Histologic Findings

Histologic examination of macules reveals mild dermal edema with a sparse predominantly perivascular inflammatory infiltrate composed primarily of eosinophils, with small numbers of neutrophils and monocytes. Papules have increased edema and inflammatory infiltrate with involvement of the superficial portion of the pilosebaceous unit. Eosinophilic invasion of the outer root sheath of the hair follicle is noted. Pustules are subcorneal or intraepidermal and are found associated with the pilosebaceous orifice. A variable infiltrate of eosinophils and monocytes may be seen with or without neutrophils in the surrounding dermis.^{[26, 27, 28]}

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Medical Care

Erythema toxicum neonatorum (ETN) diagnosis rests on recognizing the characteristic history and physical findings in an otherwise healthy newborn.

A complete history, physical examination, and Tzanck smear are required to differentiate between benign transient pustular eruptions of the newborn and life-threatening disease.

Erythema toxicum neonatorum is a benign self-limited disorder requiring no treatment. Reassure parents regarding the benign transitory nature of the condition.^[29]

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Long-Term Monitoring

Most erythema toxicum neonatorum (ETN) cases resolve within 3-4 days after onset without residua. Rare recurrences are seen in a small number of patients up to age 6 weeks. In these instances, follow-up examination may be needed.

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Medication Summary

No local or systemic treatment is required.

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