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

Abstract

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.

Atypical hand, foot, and mouth disease in an adult patient: a case report and literature review

“…Histopatho-logical findings were not entirely specific, but could be consistent with an older HFMD lesion as well as erythema multiforme in our patient. However, according to some authors, large numbers of neutrophils in parakeratosis in the viable epidermis or neutrophils forming intraepidermal collections, as well as more numerous extravasated erythrocytes in the epidermis and necrosis more emphasized in the upper part of the epidermis, are features more common in HFMD (24), which was also present in our case to some extent. The main histopathological difference between classic and CVA6-related HFMD is extensive necrosis of the epidermis, present in CVA6-related HFMD (21), as also observed in our patient.…”

Coxsackievirus A6-induced Hand-Foot-and-Mouth Disease Mimicking Stevens-Johnson Syndrome in an Immunocompetent Adult

“…It is not possible to completely confirm the Coxsackievirus infection by pathologic findings, it is considered appropriate to diagnose HFMD if such pathological findings are confirmed in the context of the patient's clinical features and Coxsackievirus neutralization test result as in the case of this patient. Plus, as described above, histopathologic features were more suitable for HFMD than SJS [17].…”

“…On the one hand, intraepidermal necrosis in HFMD is commonly localized in the upper third of the epidermis. On the other hand, EM is typically characterized by lymphocyte predominant interface dermatitis with necrosis in the lower third of the epidermis [17].…”

Hand-Foot-Mouth Disease in an Adult

“…In recent years, the description of cases in adults has increased [ 3 , 7 ], going from typical presentation (similar to children) to atypical presentation (which makes diagnosis difficult). The usual presentation is characterized by a typical vesicular eruption on the hands, feet, and oral mucosa, and fever [ 7 ].…”

“…Hand-foot-mouth disease (HFMD) is a common, highly contagious infectious disease usually occurring during childhood (usually under 10 years old) [1,2]. It is most frequently caused by coxsackievirus-A16 and enterovirus-A71 with reports of coxsackievirus B1-B6 increasing in adults [2][3][4][5][6]. More recently, worldwide outbreaks of atypical presentation in adulthood associated with the coxsackie-A6 virus have been reported [4][5][6].…”