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Erythema Toxicum Neonatorum

  • Author: Neil F Gibbs, MD; Chief Editor: William D James, MD  more...
 
Updated: Apr 12, 2016
 

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.

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

Also see the Pediatrics article, 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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Epidemiology

Frequency

United States

A review of incidence in the United States across a range of ethnic groups revealed an incidence of 7%.[7] Studies involving US populations have reported an incidence of up to 30%.[8]

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.

Race

No racial or ethnic predisposition is known.

Sex

The prevalence is higher in males (55%) than in females (30%),[9] except among females born of first pregnancies, who have a higher rate than males of first pregnancies.

Age

See the list below:

  • 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.[10, 11]
  • 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.[12, 13]
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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,[14] 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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Contributor Information and Disclosures
Author

Neil F Gibbs, MD Voluntary Associate Professor, Departments of Pediatrics and Medicine (Dermatology), University of California, San Diego School of Medicine; Residency Program Director, Pediatric Dermatologist, Department of Dermatology, Naval Medical Center, San Diego; Clinical Professor of Dermatology and Clinical Professor of Pediatrics (Secondary), Uniformed Services University of the Health Sciences, Bethesda, Maryland

Neil F Gibbs, MD is a member of the following medical societies: American Academy of Dermatology, Association of Military Dermatologists, Society for Pediatric Dermatology

Disclosure: Nothing to disclose.

Coauthor(s)

Meghan E Seago, MD Staff Dermatologist, US Naval Hospital Guam

Meghan E Seago, MD is a member of the following medical societies: American Academy of Dermatology, Massachusetts Medical Society, Undersea and Hyperbaric Medical Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Michael J Wells, MD, FAAD Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine

Michael J Wells, MD, FAAD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, Texas Medical Association

Disclosure: Nothing to disclose.

Van Perry, MD Assistant Professor, Department of Medicine, Division of Dermatology, University of Texas School of Medicine at San Antonio

Van Perry, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Chief Editor

William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American Academy of Dermatology, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Eleanor E Sahn, MD Director, Division of Pediatric Dermatology, Associate Professor, Departments of Dermatology and Pediatrics, Medical University of South Carolina

Eleanor E Sahn, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, Southern Medical Association

Disclosure: Nothing to disclose.

Acknowledgements

Trisha C Beute, MD Staff Physician, Department of Dermatology, Naval Medical Center, Portsmouth

Trisha C Beute, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology

Disclosure: Nothing to disclose.

Robert Huff, MD Dermatology, Inc

Robert Huff, MD is a member of the following medical societies: American Academy of Dermatology and Phi Beta Kappa

Disclosure: Nothing to disclose.

Eleanor E Sahn, MD Director, Division of Pediatric Dermatology, Associate Professor, Departments of Dermatology and Pediatrics, Medical University of South Carolina

Eleanor E Sahn, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, and Southern Medical Association

Disclosure: Nothing to disclose.

References
  1. Schwartz RA, Janniger CK. Erythema toxicum neonatorum. Cutis. 1996 Aug. 58(2):153-5. [Medline].

  2. Marchini G, Hultenby K, Nelson A, et al. Increased expression of HMGB-1 in the skin lesions of erythema toxicum. Pediatr Dermatol. 2007 Sep-Oct. 24(5):474-82. [Medline].

  3. Marchini G, Lindow S, Brismar H, et al. The newborn infant is protected by an innate antimicrobial barrier: peptide antibiotics are present in the skin and vernix caseosa. Br J Dermatol. 2002 Dec. 147(6):1127-34. [Medline].

  4. Marchini G, Stabi B, Kankes K, Lonne-Rahm S, Ostergaard M, Nielsen S. AQP1 and AQP3, psoriasin, and nitric oxide synthases 1-3 are inflammatory mediators in erythema toxicum neonatorum. Pediatr Dermatol. 2003 Sep-Oct. 20(5):377-84. [Medline].

  5. Nelson A, Ulfgren AK, Edner J, Stabi B, Brismar H, Hultenby K. Urticaria Neonatorum: accumulation of tryptase-expressing mast cells in the skin lesions of newborns with Erythema Toxicum. Pediatr Allergy Immunol. 2007 Dec. 18(8):652-8. [Medline].

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  7. Kanada KN, Merin MR, Munden A, Friedlander SF. A prospective study of cutaneous findings in newborns in the United States: correlation with race, ethnicity, and gestational status using updated classification and nomenclature. J Pediatr. 2012 Aug. 161(2):240-5. [Medline].

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  10. Levy HL, Cothran F. Erythema toxicum neonatorum present at birth. Am J Dis Child. 1962 Apr. 103:617-9. [Medline].

  11. Marino LJ. Toxic erythema present at birth. Arch Dermatol. 1965 Oct. 92(4):402-3. [Medline].

  12. Akoglu G, Ersoy Evans S, Akca T, Sahin S. An unusual presentation of erythema toxicum neonatorum: delayed onset in a preterm infant. Pediatr Dermatol. 2006 May-Jun. 23(3):301-2. [Medline].

  13. Chang MW, Jiang SB, Orlow SJ. Atypical erythema toxicum neonatorum of delayed onset in a term infant. Pediatr Dermatol. 1999 Mar-Apr. 16(2):137-41. [Medline].

  14. Singh M, Arora NK, Sroa HS. Urticaria neonatorum--an earliest marker of atopy. Indian J Med Res. 1980 Feb. 71:273-7. [Medline].

  15. Monteagudo B, Labandeira J, Cabanillas M, Acevedo A, Toribio J. Prospective Study of Erythema Toxicum Neonatorum: Epidemiology and Predisposing Factors. Pediatr Dermatol. 2011 Nov 8. [Medline].

  16. Maffei FA, Michaels MG, Wald ER. An unusual presentation of erythema toxicum scrotal pustules present at birth. Arch Pediatr Adolesc Med. 1996 Jun. 150(6):649-50. [Medline].

  17. Marchini G, Nelson A, Edner J, Lonne-Rahm S, Stavreus-Evers A, Hultenby K. Erythema toxicum neonatorum is an innate immune response to commensal microbes penetrated into the skin of the newborn infant. Pediatr Res. 2005 Sep. 58(3):613-6. [Medline].

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  19. Bassukas ID. Is erythema toxicum neonatorum a mild self-limited acute cutaneous graft-versus-host-reaction from maternal-to-fetal lymphocyte transfer?. Med Hypotheses. 1992 Aug. 38(4):334-8. [Medline].

  20. Droitcourt C, Khosrotehran K, Halaby E, Aractingi S. Maternal cells are not responsible [corrected] for erythema toxicum neonatorum [corrected]. Pediatr Dermatol. 2008 May-Jun. 25(3):411-3. [Medline].

  21. Monteagudo B, Labandeira J, Cabanillas M, Acevedo A, Toribio J. Prospective study of erythema toxicum neonatorum: epidemiology and predisposing factors. Pediatr Dermatol. 2012 Mar-Apr. 29(2):166-8. [Medline].

  22. Ferrandiz C, Coroleu W, Ribera M, Lorenzo JC, Natal A. Sterile transient neonatal pustulosis is a precocious form of erythema toxicum neonatorum. Dermatology. 1992. 185(1):18-22. [Medline].

  23. Van Praag MC, Van Rooij RW, Folkers E, Spritzer R, Menke HE, Oranje AP. Diagnosis and treatment of pustular disorders in the neonate. Pediatr Dermatol. 1997 Mar-Apr. 14(2):131-43. [Medline].

  24. Freeman RG, Spiller R, Knox JM. Histopathology of erythema toxicum neonatorum. Arch Dermatol. 1960 Oct. 82:586-9. [Medline].

  25. Luders D. Histologic observations in erythema toxicum neonatorum. Pediatrics. 1960 Aug. 26:219-24. [Medline].

  26. Marchini G, Ulfgren AK, Lore K, Stabi B, Berggren V, Lonne-Rahm S. Erythema toxicum neonatorum: an immunohistochemical analysis. Pediatr Dermatol. 2001 May-Jun. 18(3):177-87. [Medline].

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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, MD.
Yellow pustules, some with evidence of rupture, in a full-term infant at 6 hours of life.
Erythematous blotchy patches localized to the trunk in a neonate.
A Wright-Giemsa stain performed on the contents of a ruptured pustule reveal numerous eosinophils.
 
 
 
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