Anais Brasileiros de Dermatologia 2022;97(3):321---325

Anais Brasileiros de
Dermatologia
www.anaisdedermatologia.org.br

CASE REPORT

Hand, foot, and mouth disease in adults caused by

Coxsackievirus B1-B6夽
∗
Anama Di Prinzio , Dolores Pilar Bastard , Ana Clara Torre ,
Luis Daniel Mazzuoccolo

Department of Dermatology, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina

Received 18 July 2020; accepted 15 March 2021

Available online 7 March 2022

Abstract Hand, foot, and mouth disease is a viral rickettsial disease caused by Coxsackievirus
KEYWORDS A16 and Enterovirus 71 in most cases. It is commonly seen in children under ten years old,
Adults; who present oral enanthema and a macular, maculopapular, or vesicular rash on their hands
Enterovirus; and feet. However, an increase in cases caused by other viral serotypes was observed in adults
Hand, foot and mouth in recent years with various clinical presentations and a troublesome diagnosis. Three cases
disease of hand, foot, and mouth disease are reported to show the clinical variability and diagnostic
complexity that this disease may present in adult patients.
© 2022 Sociedade Brasileira de Dermatologia. Published by Elsevier España, S.L.U. This is an
open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Introduction isolated. According to literature, CA A6 is the most frequent

serotype in adults.1---6
Hand, Foot, and Mouth Disease (HFMD) is a rickettsial disease HFMD has a high infection rate. Person-to-person trans-
often caused by viruses of the Picornaviridae family, Human mission occurs through direct contact with nasal secretion,
Enterovirus genus, within which Coxsackievirus (CA) A16 and saliva, feces, or contaminated objects. The disease usually
Enterovirus (EV) 71 are the ones most frequently isolated. appears in the form of epidemic outbreaks in spring, sum-
In 97% of cases, HFMD affects children under 10-years old. mer, or early autumn. The incubation period is three to six
Serologic types A 5-7, A 10, B 1-3, and B5-B6 are sometimes days. After coming into contact, the virus is implanted in
the oral or ileum mucosae spreading from there to the blood;
this is known as primary viremia. After 24 hours in the blood,
the virus starts spreading to lymphatic tissue and different
organs. Respiratory elimination of the virus may persist for
夽 Study conducted at the Department of Dermatology, Hospital
three weeks and digestive elimination for eight weeks.2---5
Italiano de Buenos Aires, Buenos Aires, Argentina.
∗ Corresponding author. In most cases, mainly in children, HFMD appears as enan-
thema, papules, and/or blisters on the hands and feet,
E-mail: [email protected]
(A.C. Torre). which may resolve in one to two weeks.2

https://doi.org/10.1016/j.abd.2021.03.012
0365-0596/© 2022 Sociedade Brasileira de Dermatologia. Published by Elsevier España, S.L.U. This is an open access article under the CC
BY license (http://creativecommons.org/licenses/by/4.0/).
 A. Di Prinzio, D.P. Bastard, A.C. Torre et al.

Figure 1 Oral enanthema. Figure 2 Erythematous purpuric macules and papules, and
isolated blisters, located on the feet.

Case Report

Three cases of HFMD are reported in adult patients. Its eti-

ology, clinical manifestations, the differential diagnosis, the
diagnostic approach, the treatment provided, and the clin-
ical progress are described (Table 1) (Figs. 1, 2, 3, 4 and 5).

Discussion

HFMD is an uncommon viral disease in adults as a result of

cross-immunity with other enteroviruses and immunological
memory. However, an increase in cases with atypical clinical
presentation and a troublesome diagnosis has been observed
in this age group in recent years.5
Unlike international publications, the cases reported in
the present publication were caused by Coxsackievirus B1-
B6.
The clinical manifestations of HFMD in adults are differ-
ent from the typical manifestations seen during childhood
since they may appear as blisters and purpuric skin rashes
being more frequently serious and extensive.2---6
In the oral cavity, HFMD may appear as lesions rang-
ing from enanthema with blisters to ulcers that may affect
any area of the oral mucosa. Therefore, it must be dif-
ferentiated from other diseases that affect the oral cavity,
Figure 3 Multiple erythematous papules, with confluent
such as acute herpetic gingivostomatitis (AHGS), recurrent
areas, located on the hands.
aphthous stomatitis (RAS), herpes simplex, and herpang-
ina. In AHGS and RAS, the lesions tend to be bleeding
ulcers that affect the gums, tongue, hard palate, and, in none of these diseases concurrently affect the hands and
some cases, the pharynx. Herpangina appears as a painful feet as HFMD does.1---5,7
papulo-vesicular enanthema, which can progress to small The usual papulo-vesicular rash in HFMD involves the
grayish-yellow ulcers with erythematosus borders. In most hands (backs of fingers, interdigital area, palms) and feet
cases, it compromises the soft palate, tonsils, and posterior (tops of toes, lateral edges of feet, soles, and heels). The
pharynx and is usually preceded by a high fever. However, rash is usually asymptomatic, and it appears after the oral

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Table 1 Cases: Clinical record, clinical findings, laboratory, histopathology, diagnosis, treatment, and virus isolation.

Patient 1 Patient 2 Patient 3

Gender Male Male Male
Age (years) 33 39 21
Epidemiological --- Daughter with HFMD, 1 ---
Background week before
Skin Lesions Oral enanthema and painful Multiple purpuric macules Oral enanthema and oral
maculopapular rash and papules, itchy and ulcers, multiple
isolated blisters erythematous papules, and
itchy and painful blisters
Location of Skin Lesions Scalp, face, chest, hands, Scalp, face, auricular Oral mucosa, back of the
and feet (Fig. 1) pavilions, hands, thighs, tongue, and hard palate.
and feet (Fig. 2) Armpits, elbows, hands, and
feet (Fig. 3)
Systemic Symptoms Fever, odynophagia, and Fever, myalgia, and Odynophagia
general malaise bilateral orchitis
Presumptive Diagnosis Syphilis and HFMD Syphilis, HFMD, and Syphilis, HFMD, milker’s
blistering diseases nodules, blistering diseases,
and Kaposi’s
chickenpox-like rash
Laboratory No changes Leukocytosis (12000/mm3 ) Leukocytosis (13100/mm3 )
Serologies VDRL and HIV non-reactive HCV, HBV, VDRL, HIV, CMV, HCV, HBV, VDRL, HIV, CMV,
EBV, and Parvovirus EBV, HSV, HZV, Mycoplasma,
non-reactive and Parvovirus
non-reactive.
IgM for Coxsackie virus IgM for Coxsackie virus IgG for Coxsackie virus with
B1-B6 reactive B1-B6 reactive 4× titer increase 15 days
later
Skin Biopsy --- Compatible with viral Compatible with viral
infection, probable HFMD infection, probable HFMD
(Fig. 4)
Diagnosis Serological Serological and histological Serological and histological
Treatment NSAIDS NSAIDS and wet treatments NSAIDS and gargles with
of denuded blisters lidocaine
Clinical Progress Resolution in 10 days Resolution in 15 days Resolution in 20 days
Complications --- Onycholysis on hands and ---
feet (2 months later)

HFMD, Hand, Foot, and Mouth Disease; HCV, Hepatitis C virus; HBV, Hepatitis B virus; VDRL, Venereal Disease Research Laboratory; HIV,
Human Immunodeficiency Virus; CMV, Cytomegalovirus; EBV, Epstein-Barr Virus; HSV, Herpes Simplex Virus; HZV, Herpes Zoster Virus.

lesions. These manifestations must pose the differential involvement, the trunk may also be affected, and it usually
diagnosis with shingles, chickenpox, Gianotti-Crosti syn- does not present blisters.1---8
drome, Orf nodules, and syphilis. As seen in the present The diagnosis of HFMD is typically based on clinical
study’s patients, atypical skin manifestations spread beyond grounds. However, in adults and in cases of atypical mani-
the classic locations of HFMD, affecting the backs of the festations, complementary studies are generally required to
hands and tops of the feet, limbs, trunk, buttocks, peribu- allow for viral confirmation and to rule out other differential
cal region, and scalp. Shingles blisters are distinguished diagnoses.2---6
by their metameric distribution in clusters and for being IgM and IgG serologies must be requested on days 0
painful. In chickenpox, skin involvement is characterized by and 15 to assess seroconversion. Viral cultures have low
its cephalocaudal distribution, with itchy lesions in differ- sensitivity.5
ent stages of evolution. In the Gianotti-Crosti syndrome, the A skin biopsy is not necessary for an accurate diagno-
rash starts suddenly with monomorphic edematous papules, sis, but it is very useful to rule out differential diagnoses.
skin-colored or reddish-pink papulo-vesicles symmetrically In HFMD histology, intraepidermal blisters with neutrophil
distributed on the face, buttocks, and limb extensor sur- content, mononuclear cells, and eosinophilic proteinaceous
faces, and it usually does not appear on the trunk. Orf material are observed. Spongiosis, reticular degenera-
nodules are mainly located on the hands presenting as ery- tion of the granular layers and the upper part of the
thematosus maculopapular lesions, which progress to target stratum spinosum, keratinocyte mass necrosis, neutrophil
blisters and, eventually, to bluish nodules that may ulcerate. exocytosis, and basal-layer hydropic degeneration are also
In secondary syphilis lesions, though there is palmoplantar observed. These findings help perform a diagnosis by corre-

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 A. Di Prinzio, D.P. Bastard, A.C. Torre et al.

lating them with the clinical presentation and the remaining

laboratory tests. DNA amplification through RT-PCR is the
preferred method for an accurate diagnosis of an atypical
disease, but this is only performed at high-tech laboratories
and is not available at the present study’s institution.3,5
Treatment is symptomatic. A patient diagnosed with
HFMD is potentially contagious as long as they present skin
lesions. Therefore, they must be excluded from the group
and school activities until fever and skin, and mucosal
lesions have disappeared. Furthermore, as a preventive
measure, it is also recommended not to share objects or
utensils and to meticulously wash hands to stop the spread
of the disease.3
This entity must be recognized both in children and adults
to avoid unnecessary studies and treatments.3---5

Financial support

None declared.

Authors’ contributions

Anama Di Prinzio: Critical literature review; data col-

lection, analysis, and interpretation; effective participa-
Figure 4 Skin biopsy on the arm showing intraepidermal blis- tion in research orientation; intellectual participation in
ter and intense spongiosis (Hematoxylin & eosin, 40×). propaedeutic and/or therapeutic management of studied
cases; intellectual participation in propaedeutic and/or
therapeutic management of studied cases; study conception
and planning.
Dolores Pilar Bastard: Critical literature review; study
conception and planning.
Ana Clara Torre: Effective participation in research ori-
entation; intellectual participation in propaedeutic and/or
therapeutic management of studied cases; intellectual par-
ticipation in propaedeutic and/or therapeutic management
of studied cases; manuscript critical review; study concep-
tion and planning.
Luis Daniel Mazzuoccolo: Approval of the final version of
the manuscript; manuscript critical review.

Conflicts of interest

None declared.

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