Abstract
Erythema toxicum neonatorum is a common rash of unknown etiology affecting healthy newborn infants. In this study, we postulated that the rash reflects a response to microbial colonization of the skin at birth, and that the hair follicle constitutes an “easily opened door” for microbes into the skin of the newborn. We collected microbial cultures from the skin of 69 healthy, 1-d-old infants with and without erythema toxicum to identify the colonizing flora and correlate culture results with clinical findings. We also analyzed biopsies from lesions of erythema toxicum with scanning and transmission electron microscopy in the search for microbes. Finally, each infant's body temperature was measured as a sign of acute phase response. We found that 84% of 1-d-old healthy infants, with and without erythema toxicum were colonized with coagulase-negative staphylococci. In all lesions of erythema toxicum, TEM identified cocci-like bacteria localized in the hair follicle epithelium and into recruited immune cells surrounding the hair follicle; morphology and dimension supported their identification as belonging to the genus Staphylococcus. SEM revealed 10 times more hair structures per skin surface unit in newborns compared with adults. Infants with erythema toxicum also had higher body temperature. In erythema toxicum, commensal microbes gain entry into the skin tissue, most probably through the hair canal. This triggers the local immune system and a systemic acute phase response, including an increase in body temperature. We speculate that early microbial exposure to the newborn may be important for the maturation of the immune system.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
Abbreviations
- CoNS:
-
coagulase-negative Staphylococcus
- SEM:
-
scanning electron microscopy
- TEM:
-
transmission electron microscopy
References
Harris JR, Schick B 1956 Erythema neonatorum. AMA J Dis Child 92: 27–33
Lehndorf H, Bartolomeus M 1951 Arch P. ediatr 68: 322–33.
Leiner C 1912 Uber eigenartige Erythemtypen und Dermatitiden des fruehen Säuglingsalters. F Deuticke, Leipzig-Wien, pp 4–15
Mayerhofer E 1927 Allergische Neugeborenen-exantheme. Arch Kinderheilk 111: 51
Freeman RG, Spiller R, Knox JM 1960 Histopathology of erythema toxicum neonatorum. Arch Dermatol 82: 586–589
Marchini G, Ulfgren AK, Loré K, Ståbi B, Berggren V, Lonne-Rahm S 2001 Erythema toxicum neonatorum: an immunohistological analysis. Pediatr Dermatol 18: 177–187
Marchini G, Lindow S, Brismar H, Ståbi B, Berggren V, Ulfgren AK, Lonne-Rahm S, Agerberth B, Gudmundsson GH 2002 The newborn infant is protected by an innate antimicrobial barrier: peptide antibiotics are present in the skin and vernix caseosa. Br J Dermatol 147: 1127–1134
Marchini G, Ståbi B, Kankes K, Lonne-Rahm S, Østergaard M, Nielsen S 2003 AQP1 and AQP3, psoriasin, and synthases 1-3 are inflammatory mediators in erythema toxicum neonatorum. Pediatr Dermatol 20: 377–384
Förster C, Mäkela S, Wärri A, Kietz S, Becker D, Hultenby K, Warner M, Gustafsson JÅ 2000 Involvement of estrogen receptor β in terminal differentiation of mammary gland epithelium. Proc Natl Acad Sci U S A 99: 15578–15583
Fang H, Edlund C, Hultenby K, Hedberg M 2002 Effects of cefoxitin on the growth and morphology of Bacteroides thetaiotaomicron strains with different cefoxitin susceptibility. Anaerobe 8: 55–61
Christoph T, Muller-Röver S, Audring H, Tobin DJ, Hermes B, Cotsarelis G, Ruckert R, Paus R 2000 The human hair follicle immune system: cellular composition and immune privilege. Br J Dermatol 142: 862–873
Paus R, Cotsarelis G 1999 Mechanisms of disease: the biology of hair follicles. New Engl J Med 12: 491–497
McNutt NS, Jones AL 1970 Observations on the ultrastructure of cytodifferentiation in the human fetal adrenal cortex. Lab Invest 22: 513–527
Irmak MK, Oztas E, Vural H 2004 Dependence of fetal hairs and sebaceous glands on fetal adrenal cortex and possible control from adrenal medulla. Med Hypotheses 62: 486–492
Baumann H, Gauldie J 1994 The acute phase response. Immunol Today 15: 74–80
Marchini G, Berggren V, Djilali-Merzoug R, Hansson LO 2000 The birth process initiates an acute phase reaction in the fetus-newborn infant. Acta Paediatr 89: 1082–1086
Kluger MJ, Kozak W, Conn CA, Leon LR, Soszynski D 1996 The adaptive value of fever. Infect Dis Clin North Am 10: 1–20
Acknowledgements
The authors thank Associate Professor Viveka Lindgren for critical advice.
Author information
Authors and Affiliations
Corresponding author
Additional information
Financial support was obtained from the Foundations Frimurarbarnhuset, Sällskapet Barnavård, and Kronprincessan Lovisas Fond.
Rights and permissions
About this article
Cite this article
Marchini, G., Nelson, A., Edner, J. et al. Erythema Toxicum Neonatorum Is an Innate Immune Response to Commensal Microbes Penetrated into the Skin of the Newborn Infant. Pediatr Res 58, 613–616 (2005). https://doi.org/10.1203/01.pdr.0000176836.27156.32
Received:
Accepted:
Issue date:
DOI: https://doi.org/10.1203/01.pdr.0000176836.27156.32
This article is cited by
-
Disrupted pathways associated with neonatal sepsis: Combination of protein-protein interactions and pathway data
BioChip Journal (2017)
-
Neonatal monocytes exhibit a unique histone modification landscape
Clinical Epigenetics (2016)
-
Kolonisation oder Infektion bei Früh- und Neugeborenen
Monatsschrift Kinderheilkunde (2014)
-
The role of the skin barrier in modulating the effects of common skin microbial species on the inflammation, differentiation and proliferation status of epidermal keratinocytes
BMC Research Notes (2013)
-
Attachment and Biofilm Forming Capabilities of Staphylococcus epidermidis Strains Isolated from Preterm Infants
Current Microbiology (2013)


