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Histopathology of Hand–Foot–Mouth Disease in Adults and Criteria for Differentiation From Erythema Multiforme

Böer-Auer, Almut, MD*,†; Metze, Dieter, MD*

The American Journal of Dermatopathology: April 2019 - Volume 41 - Issue 4 - p 273–280
doi: 10.1097/DAD.0000000000001263
Original Study

Background: Hand–foot–mouth disease (HFMD) is a common contagious viral infection usually affecting infants and children. Recently, literature on HFMD in adults is increasing. It has been reported that adults often present with unusual exanthems with similarities to erythema multiforme (EM). No study has so far compared the histologic features of HFMD with those of EM.

Methods: Histopathologic features in 7 biopsies of 6 adult patients with HFMD are compared with biopsies from 9 patients with EM to identify the best criteria for differentiation.

Results: HFMD and EM both have a perivascular lymphocytic infiltrate together with epidermal necrosis, spongiosis, ballooning, and reticular alteration. However, large numbers of neutrophils in parakeratosis (P < 0.05), in the viable epidermis (P < 001), or neutrophils forming intraepidermal collections (P < 0.05) are significantly more common in HFMD. In HFMD, necrotic keratinocytes are emphasized in the upper third of the epidermis (P < 0.05), whereas the lower third is typically involved more in EM. Neutrophils are significantly more common and more numerous in the dermal infiltrate of HFMD compared with EM (P < 0.01) Extravasated erythrocytes in the epidermis are more common and more numerous in HFMD (P < 0.05).

Conclusions: Lesions of EM and HFMD can be differentiated based on the amount of neutrophils in the epidermis and in the dermal infiltrate, which are significantly more numerous in HFMD. In addition, necrosis is emphasized in the upper part of the epidermis in HFMD and in the lower part of it in EM.

*Department of Dermatology, University of Münster, Münster, Germany; and

Dermatologikum Hamburg, Hamburg, Germany.

Correspondence: Almut Böer-Auer, MD, Dermatologikum Hamburg, Stephansplatz 5, 20354 Hamburg, Germany (e-mail:

A. Böer-Auer and D. Metze have substantially contributed to the article.

The authors declare no conflicts of interest.

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