Background
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]
Erythema toxicum neonatorum. Five-day-old newborn with erythematous papules with surrounding indistinct blotchy erythema visible on abdomen. Image from Jining I Wang, MD.
Pathophysiology
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]
Etiology
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]
Epidemiology
United States and international statistics
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]
Age-, sex-, and race-related demographics
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.
Prognosis
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.
Patient Education
It is important to reassure parents that ETN is not inherited or infectious, has no complications, and has an excellent prognosis with spontaneous resolution.
-
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.
