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5. Hand, foot and mouth disease (HFMD)

Outline
● An eruption is caused by coxsackievirus A16 or
enterovirus 71. Breast-fed infants are most frequently
affected.
● Blistering is present in the distal portions of the extremi-
Clinical images are available in hardcopy only.
ties and oral mucosa. It disappears in 4 to 7 days. Oral
enanthema occurs on the buccal mucosa and tongue.
Erythema or aphtha-like eruptions may also occur.
● The only treatment that is usually necessary is oral

hydration.

Clinical features
a b c d e f g h Hand,i foot and
j mouthk disease
l (HFMD)
m occurs
n suddenly
o pafter 2q r
to 5 days of latency. In about half of cases, slight fever is present
for 1 or 2 days. Dispersed small blisters with red halos appear on
the hands, soles, knee joints and buttocks (Fig. 23.9). The blisters
are oval, and their long axis is often parallel to the dermatoglyph-
ic line. Some degree of tenderness, but not itching, may accom-
Clinical images are available in hardcopy only. pany these. The blisters disappear in 4 to 7 days without
rupturing. Painful erythema, blisters, or aphtha-like erosions that
number from a few to several dozen occur on the buccal mucosa
and tongue. They resolve in several days. When caused by
enterovirus 71, HFMD may be accompanied by aseptic meningitis.
a b c d e f g h i j k l m n o p q r
Pathogenesis, Epidemiology
The main causative viruses are coxsackievirus A16 and
enterovirus 71. These proliferate in the intestinal tract and are
found in stool and in pharyngeal secretions. The viruses are
Clinical images are available in hardcopy only. spread by droplet and oral infection. The infectiousness is so high
that widespread outbreaks sometimes occur in hospitals. HFMD
occurs most commonly in 1- to 2-year-old breast-fed infants and
in summer epidemics.
b c d e f g h i j k l m n o p q r
Fig. 23.9 Hand, foot and mouth disease. Treatment
a: Vesicles accompanied by red halo and slight No treatment is necessary. Symptomatic therapy is performed
tenderness. b: Eruptions on the knees. c: Vesicles
accompanied by sharp pain and aphtha in oral
only in cases with severe symptoms.
23 mucosa .

B. Viral infections whose main symptom is verruca

1. Verruca vulgaris

Outline
● It is caused by human papillomavirus (HPV) infection.
● It occurs most frequently on the fingers, toes, soles and
 B. Viral infections whose main symptom is verruca 433

dorsal surfaces of hands. It is largely asymptomatic.

● Liquid nitrogen cryotherapy, topical glutaraldehyde appli-
cation, carbon dioxide gas laser therapy, and electro-
surgery are useful. Some cases heal spontaneously.

Pathogenesis
Clinical images are available in hardcopy only.
Verruca vulgaris is caused by human papillomavirus (HPV), a
virus in the Papovaviridae family. The most frequent HPV infec-
tion is HPV-2, followed by HPV-4, HPV-7, HPV-26, and HPV-
27 (Table 23.1). The virus invades the skin from minor external
injury and infects the epidermal cells. It replicates simultaneously
with differentiation of epidermal cells, leading to maturation of
viral particles in the granular cell layer. The viral particles are
released concurrently with exfoliation of verruca, causing spread-
ing to other areas.

Clinical features Clinical images are available in hardcopy only.

Verruca vulgaris occurs most commonly on the hands and feet
of infants, after a latency of 3 to 6 months. It begins with small
papules. They enlarge, elevating in verrucous shape and becom-
ing several millimeters to several centimeters in diameter (Fig.
23.10). Usually multiple but sometimes solitary eruptions of ver-
ruca vulgaris aggregate, coalesce, and may form plaques. It is
largely asymptomatic and has specific clinical features. There are
some types of verruca vulgaris that are given characteristic clini-
cal diagnostic names according to the clinical features, type of Clinical images are available in hardcopy only.
virus and the affected site.
① Plantar wart
Verruca vulgaris occurs on the soles. A keratotic lesion forms
without distinct elevation. It resembles tylosis and clavus, but can
be differentiated from those by scraping. If surface scraping of
the keratotic lesion causes petechiae, the diagnosis is plantar wart. Fig. 23.10 Verruca vulgaris.
② Myrmecia
A small, dome-shaped nodule forms on the soles. It is caused
by HPV-1 infection (Fig. 23.11) and may resemble molluscum
contagiosum. It is also called deep palmoplantar wart. It has a
red, cratered appearance. Tenderness is often present. It is a type
of plantar wart.
Table 23.1 HPV types and clinical symptoms.
Type Symptoms 23
Clinical images are available in hardcopy only.
1 Myrmecia
2,4,7,26-29 Verruca vulgaris
3,10 Flat warts (verruca plana juvenilis)
5,8,9,12,14,15,17,19-26,36,47,50 Epidermodysplasia verruciformis
57,60 Epidermal cyst in the soles
6,11 Condyloma acuminatum
Fig. 23.11 Myrmecia.
16,18,31, 33-35, 39-41, 51-60 Cervical dysplasia, endocervical cancer
A dome-shaped nodule accompanied by tender-
13, 32 Oral focal epithelial hyperplasia ness occurred. Scraping the nodule revealed that
the lesion had invaded the deep intradermal por-
30, 40 Pharyngeal carcinoma
tion.
 434 23 Viral Infections

Clinical images are available in hardcopy only.
Fig. 23.12 Filiform wart.
③ Pigmented wart
This is caused by infection of HPV-4 or HPV-65, or of HPV-
60 in rare cases. It has the clinical features of verruca vulgaris
and blackish pigmentation; it is also called a black wart.
④ Punctate wart
This is caused by HPV-63 infection. Multiple, punctate, white
keratotic lesions of 2 mm to 5 mm in diameter occur on the hands
and soles.
⑤ Filiform wart
A long, small, thin protrusion of several millimeters in diame-
ter occurs on the face, head region or neck (Fig. 23.12).

Pathology
There is hyperkeratosis, incomplete keratinization and thicken-
ing of the papillary epidermis, accompanied by thickening of the
granular cell layer in the epidermis. Cells with vacuolar degener-
ation and large keratohyaline granules are found in the granular
cell layer. These cellular changes, called koilocytosis, are charac-
teristic of HPV infection (Fig. 23.13).

Fig. 23.13 Histopathology of verruca vul-
garis.
Clinical images are available in hardcopy only.
Treatment
The main treatment for verruca vulgaris is liquid nitrogen
cryotherapy. Local injection of bleomycin and cauterization by
electrical scalpel or carbon dioxide laser are conducted on sites
where cryotherapy is not fully effective, including hands and
soles. For multiple lesions, coix seed (Coix lacryma-jobi L.)
extract may be administered orally. Topical application of glu-
taraldehyde is useful. Topical vitamin D and oral retinoids have
been reported effective for severe cases.

2. Flat wart
Synonym: Verruca plana juvenilis

Clinical features
Multiple, slightly elevated, flat papules of 2 mm to 10 mm in
diameter occur on the face (forehead and cheeks). These may
coalesce or appear in linear pattern from autoinfection (Köbner
phenomenon) (Fig. 23.14). The papules are normal skin color or
light pink and nearly asymptomatic. They may disappear sponta-
23
Clinical images are available in hardcopy only. neously with scaling, which is followed by inflammatory symp-
toms such as itching and reddening. However, flat wart may
persist for several years.

Pathogenesis
Flat wart is a viral wart that is often caused by HPV-3 or HPV-10.
Fig. 23.14 Flat wart.
Treatment
Some cases heal spontaneously. Liquid nitrogen cryotherapy is
conducted. Coix seed (Coix lacryma-jobi L.) extract may be
administered orally.
 B. Viral infections whose main symptom is verruca 435

3. Condyloma acuminatum

Outline
● Genital verrucous papules are caused by HPV-6 or HPV-
11. This is an STD.
● Latency is 2 to 3 months.
● Cryotherapy and laser surgical removal are the main Clinical images are available in hardcopy only.

treatments.

Clinical features
The latency of condyloma acuminatum is 2 to 3 months. Mul-
tiple verrucous papules of papillary or cauliflower shape occur in
the genitalia or perianal region (Fig. 23.15). Keratinization is
rarely present. The papules are infiltrative at the surface and may
give off foul odor. Condyloma acuminatum may enlarge. Kera-
tinization and ulceration may closely resemble squamous cell
carcinoma (Buschke-Lowenstein tumor).

Pathogenesis Clinical images are available in hardcopy only.

Condyloma acuminatum is caused by HPV-6 or HPV-11.
Most cases occur in the sexually active years, transmitted through
sexual activity. The virus invades through minor external injury
of the genitalia, perianal region, or vaginal introitus, and infects
epidermal basal cells, inducing abnormal cellular proliferation.
Proliferation of the epidermis results in formation of papillary Fig. 23.15 Condyloma acuminatum.
tumors (warts). The verrucous papules resemble cauliflower.

Diagnosis, Differential diagnosis

Condyloma acuminatum can be diagnosed by the clinical fea-
tures; however, biopsy may be needed for differential diagnosis,
such as from Bowenoid papulosis, a tumor that is often caused by
HPV-16 and that histologically resembles Bowen’s disease.

Treatment
Treatment for condyloma acuminatum is the same as for verru-
ca vulgaris. Liquid nitrogen cryotherapy and surgical removal
using electrical scalpel or carbon gas laser are conducted. Local Clinical images are available in hardcopy only.
injection of bleomycin is used in intractable cases.
23
4. Bowenoid papulosis
Multiple black papules of 2 to 20 mm in diameter occur on the
genitalia of young people (Fig. 23.16). Small papules may coa-
lesce and form plaques. HPV-16 is detected in the lesion.
Bowenoid papulosis is histopathologically indistinguishable from
Bowen’s disease. It rarely becomes malignant, and it may heal
spontaneously. The prognosis is good. Liquid nitrogen cryothera-
py and electrical cauterization are the main treatments. Bowenoid Fig. 23.16 Bowenoid papulosis.
The papules caused by Bowenoid papulosis are
papulosis is thought to be an atypical type of condyloma acumi- blackish in most cases or close to normal skin
natum. color in some cases.
 436 23 Viral Infections
Clinical images are available in hardcopy only.
Clinical images are available in hardcopy only.
Clinical images are available in hardcopy only.
Clinical images are available in hardcopy only.
23
Fig. 23.17 Epidermodysplasia verruciformis.
Large, flat, verrucous, reddish-brown keratotic
macules occur. The eruptions elevate and form
tumors in some cases.
5. Epidermodysplasia verruciformis
The main causes are HPV-5, HPV-8, HPV-17 and HPV-20
infection. Susceptibility to the virus is inherited, usually autoso-
mal recessively; however, some cases with autosomal dominant
and X-linked dominant patterns have been reported. Congenital
cellular immunocompromise against HPV is thought to be asso-
ciated with the occurrence. Relatively large, flat-wart-like, red-
dish-brown keratotic patches appear on the dorsal surfaces of the
hands and trunk of infants, often coalescing to form plaques or
reticular arrangements. Pityriasis-versicolor-like leukoderma and
erythema may occur (Fig. 23.17). Multiple cells containing
bright and enlarged cytoplasm are histopathologically observed
in the upper suprabasal cell layer. The eruptions gradually spread
on the whole body surface. Malignant skin tumor (e.g., squamous
cell carcinoma, basal cell carcinoma, Bowen’s disease) occurs in
about half of adolescent and older patients. There is no specific
treatment for epidermodysplasia verruciformis. Sunscreen is used
for prevention, because lesions on sun-exposed areas tend to
worsen. Oral retinoid administration is effective.
6. Molluscum contagiosum
Outline
●A wart forms as a result of infection by the molluscum
contagiosum virus.
● Infants are most frequently affected.
● Small, multiple, dome-shaped nodules of 2 mm to 10 mm
in diameter occur. Autoinfection is caused by wart con-
tents adhering to the epidermis.
● Tweezer excision of the wart is the most effective treat-
ment.
● Multiple molluscum contagiosum may appear on the face
of patients with AIDS.
Clinical features
The latency of molluscum contagiosum is between 14 and 50
days. Small, multiple, flat-surfaced, glossy, centrally concave,
dome-shaped nodules of 2 mm to 10 mm in diameter occur (Fig.
23.18). They contain an opaque white gruel-like substance. They
are asymptomatic except for mild itching. The trunk and extremi-
ties of infants are most frequently affected. When sexually trans-
mitted, the genitalia, lower abdomen, and medial thighs are
involved.
Pathogenesis, Epidemiology
Warts are produced by molluscum contagiosum, a virus in the
Poxviridae family. Cells at the center of the skin lesion are dis-
torted or destroyed, giving the appearance of large hyaline bodies
(molluscum bodies) that contain large amounts of cytoplasmic
 C. Viral infections whose main symptom is erythematous eruptions 437

Clinical images are available in Clinical images are available in

Clinical images are available in hardcopy only.
hardcopy only. hardcopy only.

Fig. 23.18 Molluscum contagiosum.

The small papules are glossy on the surface and umbilicated at the center.

virus material. Molluscum contagiosum is spread by contact

infection. The virus enters through a break in the skin or a hair
follicle, and proliferates in the suprabasal cell layer of the epider-
mis. When a wart is scratched, the contents adhere to the epider-
mis and cause autoinfection. Children with atopic dermatitis are
most commonly affected. In recent years, the numbers of infec-
tions in healthy children at swimming schools, in adults from STDs,
and in patients with immunodeficiency have been increasing.

Pathology
Molluscum contagiosum is characterized by lobulated, endo-
phytic hyperplasia that produces a circumscribed intracutaneous
pseudotumor. The keratinocytes contain very large intracytoplas- Fig. 23.19 Histopathology of molluscum
mic inclusions (molluscum bodies). contagiosum.

Diagnosis
Molluscum contagiosum is easily diagnosed by the clinical
features. In sudden occurrence of multiple molluscum contagio-
sum in adults, AIDS involvement is highly suspected.

Treatment
Tweezer excision of the lesions is most effective. Cryo-coagu-
lation therapy and application of 40% silver nitrate are also use-
ful. Molluscum contagiosum heals spontaneously in some cases.

C. Viral infections whose main symptom is erythematous eruptions 23

1. Measles

Outline
● Itis an infectious disease caused by the measles virus.
Young children are most frequently affected. It occurs in
epidemics with intervals of several years, often during
the spring.
● A fever and common-cold-like symptoms occur after an

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