Erythema toxicum neonatorum (ETN) is a benign self-limited eruption that occurs primarily in healthy newborns in the early neonatal period. It is characterized by macular erythema, papules, vesicles, and pustules (see the image below), and it resolves without permanent sequelae.[1]
 View Image | Erythema toxicum neonatorum. Five-day-old newborn with erythematous papules with surrounding indistinct blotchy erythema visible on abdomen. Image fro.... |
Increased levels of immunologic and inflammatory mediators (eg, interleukins [ILs] 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, and the antimicrobial peptide LL-37) suggest that ETN is an immune system reaction.[2, 3, 4, 5] The localization of ETN 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.[6]
Although the eosinophilic infiltrate of ETN suggests an allergic- or hypersensitivity-related etiology, no allergens have been identified. Newborn skin appears to respond to any injury with an eosinophilic infiltrate. The observation that ETN is rarely seen in premature infants suggests that immunologically mature newborn skin is required to produce this reaction pattern.[2]
The cause of ETN has not been established. Multiple theories have been proposed to explain this common disorder.
Neonates have an increased number of hair follicles as compared with adults, and the occurrence of ETN in non-hair-bearing areas (eg, 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 ETN represents a response to microbes that have penetrated the hair follicle.[2] This process may be integral in developing the new immune system.[7]
The high frequency of eosinophilia suggests an allergic basis, leading some authors to suggest that ETN may be an immediate hypersensitivity reaction to a substance passed from the mother transplacentally; however, this view has not received convincing support. No responsible exotoxin, allergen, component of sebum, or infectious agent has been definitively linked to ETN. Neither medications administered to newborns nor the mode of feeding has been shown to have an effect on incidence.
Other proposed theories have included a transient adjustment reaction of the skin to mechanical or thermal stimulation and an acute graft-versus-host reaction induced by the maternal-fetal transfer of lymphocytes before or during delivery. However, one analysis of skin samples from two male patients with ETN did not support a graft-versus-host reaction, because fluorescence in situ hybridization (FISH) examination of cells with two XX chromosomes did not find any maternal cells in the samples.[8]
Contactants and mechanical irritation have been considered and rejected as etiologies.
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 ETN and the duration of the cutaneous manifestations.[9, 10]
A review of cutaneous findings in US newborns across a range of ethnic groups found ETN to have an incidence of 7%.[11] Other studies involving US populations have reported incidence figures as high as 30%.[12]
International studies have found a similarly broad range in the incidence of ETN, from approximately one third to approximately one half of full-term infants. A Brazilian study reported a prevalence of 21.3%.[13] A cross-sectional observational study (N = 474) from India cited a prevalence of 8.43% for ETN.[14]
ETN 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.[15, 16] The incidence rises with increasing gestational age and birth weight. In rare cases, delayed onset may occur in full-term and preterm infants up to age 14 days.[17, 18]
The prevalence is higher in males (55%) than in females (30%),[9, 13] except among females born of first pregnancies, who have a higher rate than males of first pregnancies.
No racial or ethnic predisposition is known.
The prognosis for patients with ETN is excellent. ETN is a transient eruption with spontaneous resolution and no associated long-term morbidity. It may recur in approximately 11% of patients up to age 6 weeks; however, recurrences tend to be mild and to resolve without sequelae. Although one study found that infants with ETN had an increased risk of atopy,[19] this finding has not been supported by subsequent studies.
It is important to reassure parents that ETN is not inherited or infectious, has no complications, and has an excellent prognosis with spontaneous resolution.
In evaluating for erythema toxicum neonatorum (ETN), the history should focus on the following:
Infants with ETN are otherwise healthy and lack systemic symptoms. The eruption is self-limited; most cases resolve 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.
The physical examination should focus on the location, size, and distribution of macules, wheals, papules, and pustules on the skin. The absence of mucosal, palmar, or plantar involvement (ie, lesions on non-hair-bearing skin) is characteristic of ETN. Signs of systemic toxicity, including hypothermia or hyperthermia, lethargy, and irritability, are not associated with ETN.
ETN 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- to 4-mm pustules develop. (See the images below.)
View Image | Erythema toxicum neonatorum. Five-day-old newborn with erythematous papules with surrounding indistinct blotchy erythema visible on abdomen. Image fro.... |
View Image | Erythema toxicum neonatorum. Yellow pustules, some with evidence of rupture, in full-term infant at 6 hours of life. |
The number and distribution of lesions can range from a few and widely scattered to numerous and extensive. The most common sites include the trunk (see the image below), the buttocks, and the proximal limbs, but lesions may occur anywhere, including the genitalia.[21] As noted, involvement of the mucous membranes or the palms and soles is rare.
View Image | Erythema toxicum neonatorum. Erythematous blotchy patches localized to trunk in neonate. |
Complications of ETN are not commonly reported. However, one report described a strong association between ETN and eosinophilic esophagitis.[22]
Erythema toxicum neonatorum (ETN) is diagnosed clinically on the basis of history, physical examination, and peripheral smear of intralesional contents.
On a complete blood count (CBC), eosinophilia is noted in approximately 15% of patients as accounting for as much as 18% of the total white blood cell (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, including more than 90% eosinophils and variable numbers of neutrophils.[10, 24]
If clinical symptoms warrant concern for systemic disease, Giemsa stain fails to show eosinophils, or clinical suspicion warrants an evaluation of other diagnoses, viral, bacterial, and fungal cultures should be performed to exclude herpes simplex virus (HSV), varicella-zoster virus (VZV), pathogenic bacterial, and yeast infections.
A potassium hydroxide (KOH) preparation should be used to exclude candidiasis.
Histologic examination of ETN 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 in association with the pilosebaceous orifice. A variable infiltrate of eosinophils and monocytes may be seen with or without neutrophils in the surrounding dermis.[25]
The diagnosis of erythema toxicum neonatorum (ETN) rests on recognizing the characteristic history and physical findings in an otherwise healthy newborn. A complete history, a physical examination, and a Tzanck smear are required to differentiate between benign transient pustular eruptions of the newborn and life-threatening disease.
Because ETN is a benign self-limited disorder, no treatment is necessary. Parents should be reassured regarding the benign and transitory nature of the condition.
Most cases of ETN resolve within 3-4 days after onset without residua. Recurrences are rare but may be seen in a small number of patients up to age 6 weeks. In these instances, follow-up examination may be necessary.
Erythema toxicum neonatorum. Five-day-old newborn with erythematous papules with surrounding indistinct blotchy erythema visible on abdomen. Image from Jining I Wang, MD.
Erythema toxicum neonatorum. Five-day-old newborn with erythematous papules with surrounding indistinct blotchy erythema visible on abdomen. Image from Jining I Wang, MD.
Erythema toxicum neonatorum. Yellow pustules, some with evidence of rupture, in full-term infant at 6 hours of life.
Erythema toxicum neonatorum. Erythematous blotchy patches localized to trunk in neonate.
Erythema toxicum neonatorum. Five-day-old newborn with erythematous papules with surrounding indistinct blotchy erythema visible on abdomen. Image from Jining I Wang, MD.
Erythema toxicum neonatorum. Yellow pustules, some with evidence of rupture, in full-term infant at 6 hours of life.
Erythema toxicum neonatorum. Erythematous blotchy patches localized to trunk in neonate.
Erythema toxicum neonatorum. Wright-Giemsa stain performed on contents of ruptured pustule reveal numerous eosinophils.
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