VIRAL INFECTIONS
Acute childhood exanthems
Penelope A Bryant
Cathryn M Lester
Abstract
Exanthems are rashes that in childhood are most commonly caused by vi-
ruses. This article describes the common exanthems, including measles,
rubella, varicella, erythema infectiosum, papular-purpuric gloves and
socks syndrome, roseola infantum, hand, foot and mouth disease, Gia-
nottieCrosti syndrome, unilateral laterothoracic exanthem and pityriasis
rosea. It outlines their transmission, infectivity, prodrome, clinical presen-
tation, complications and treatment. Although it is often difficult to iden-
tify the specific virus, polymerase chain reaction analysis has improved
diagnostic accuracy, which is particularly important in immunocompro-
mised individuals and pregnant women. Alternative diagnoses include
bacterial and non-infectious causes.
Keywords erythema infectiosum; exanthem; measles; rash; roseola;
rubella; varicella; virus
Exanthems are rashes that are usually generalized and associated
with systemic symptoms including fever. The commonest cause
in childhood is viral infection although other causes include
bacterial infection and drug exposure. Diagnosis of the aetiology
of a viral exanthem is often difficult, and relies on relevant his-
tory of prodromal symptoms, evolution, associated symptoms,
exposure to infections, foreign travel, time of year and immuni-
zation history.1 Examination findings that guide diagnosis
include the nature of the rash, its distribution, and other mani-
festations including oral enanthems. Most viral exanthems can
be diagnosed serologically or by identifying viral RNA by poly-
merase chain reaction (PCR) in blood, respiratory specimens or
cerebrospinal fluid.
Viral exanthems are predominantly maculopapular rashes
that may be difficult to distinguish. They should be differentiated
from rashes associated with bacterial infection, such as menin-
gococcal septicaemia, scarlet fever, toxic shock syndrome and
staphylococcal scalded skin syndrome, tick-borne diseases such
as Lyme disease and rickettsial diseases, and Kawasaki’s disease.
In addition it is important to consider non-infectious causes, such
as HenocheScho €nlein purpura, juvenile idiopathic arthritis,
leukaemia and drug exposure.
Penelope A Bryant MA BM BCh MRCP MRCPCH FRACP PhD is a Consultant in
Paediatric Infectious Diseases and General Paediatrics at the Royal
Children’s Hospital, Melbourne, Australia. Conflict of interest: none
declared.
Cathryn M Lester B Bus (MKTG) MBA is a Practitioner in Child Health and
Childhood Immunisation Advocate at Abbotsford Child Health,
Abbotsford, Australia. Conflict of interest: none declared.
MEDICINE 42:1
What’s new?
C The number of confirmed measles cases in the UK is still
increasing
C There has been an increase in rubella outbreaks in unimmu-
nized individuals relating to returned travellers from Europe
C Vaccine coverage of measles, mumps and rubella (MMR) in the
UK, having dropped significantly, is now increasing again
C Shingles (varicella-zoster virus) vaccine has been added to the
routine immunization schedule in the UK for those over 70
years old.
Viral exanthems are often difficult to differentiate from each
other even after careful history-taking and examination. The
availability of PCR has greatly increased diagnostic accuracy,
important in contacts of pregnant women or immunocompro-
mised patients, but results are rarely available immediately.
Although most viral exanthems are benign and self-limiting, it is
important to treat potentially life-threatening diseases in the
differential diagnosis urgently.
Although severe complications occur occasionally, viral ex-
anthems are generally self-limiting illnesses (Table 1).
Measles
Measles (rubeola) is caused by a paramyxovirus and is spread by
respiratory contact. It remains a significant cause of childhood
mortality in developing countries, although global mortality from
measles has decreased since the introduction of comprehensive
immunization programmes from 873,000 deaths in 1999 to
345,000 in 2005.2 Controversy and media reporting in 1998,
following publication of a small study suggesting an association
between MMR (measles, mumps and rubella) vaccination and
childhood autism, led to a decrease in the uptake of the MMR
vaccine in the developed world reaching a nadir in 2003.3 This
led to outbreaks of measles in children and adults due to a loss of
individual and herd immunity. The original study has since been
discredited and withdrawn and numerous other studies have
shown no relationship between MMR and neurodevelopmental
or gastrointestinal conditions.4e6 MMR uptake is increasing once
again, and although currently only 86% of children in the UK
have had two doses by their fifth birthday, this reflects a steady
increase from 75% in 2008.7 However, the incidence of measles
is still increasing in the UK with 2016 laboratory-confirmed cases
in 2012, greater than double the figure of 990 in 2007.8 Over 60%
of these are in infants, preschool and primary school age chil-
dren. Unimmunized children are also at risk of acquiring measles
when travelling to, or being in contact with recent travellers
from, high-prevalence countries.
Measles has a prodromal period of fever, coryza, conjuncti-
vitis and cough for several days before the rash develops. The
morbilliform rash has maculopapular lesions of a few millimetres
that may be confluent (Figure 1). Koplik’s spots are pathogno-
monic white spots on the buccal mucosa. Complications include
otitis media, pneumonia, pneumonitis, myocarditis and pericar-
ditis. Encephalitis may occur, either acutely, or months to years
later as subacute sclerosing panencephalitis.
52 Ó 2014 Published by Elsevier Ltd.
 VIRAL INFECTIONS

Rubella
Incubation and infectivity periods for acute viral Caused by a togavirus, rubella (German measles) is spread by
exanthems respiratory droplets and is most prevalent in late winter and
Exanthem Incubation Duration of infectivity spring. In countries with comprehensive childhood immuniza-
(days) tion and effective catch-up campaigns in adolescence and in
women of child-bearing age, there has been a dramatic decrease
Measles 8e12 Two days before prodrome to in the incidence of rubella.11 However, many countries have no
5 days after rash appears anti-rubella immunization programmes and globally the inci-
Rubella 14e21 Seven days before rash to dence of congenital rubella syndrome is estimated to be over
5 days after rash appears; in 100,000/year. In Europe the majority of cases of rubella are
congenital infection viral shedding from eastern Europe, including recent small outbreaks in the
can persist for months UK involving unimmunized adolescents returning from
Varicella 10e21 Two days before rash to 5 days Europe.12
after rash appears Rubella is an asymptomatic infection in up to 50% of in-
Erythema 4e14 Before the onset of the rash dividuals. In symptomatic children there is a mild prodromal
infectiosum febrile period with lymphadenopathy and conjunctivitis, whereas
Papular-purpuric 10 During shedding of virus, which in adults the symptoms are usually more prominent, with
gloves and socks can persist until after the rash anorexia, nausea and fever. The prodrome precedes a facial
syndrome disappears after 7e14 days maculopapular rash that spreads to the trunk and limbs and
Roseola 9 During shedding of virus, which fades after about 3 days. The rash, lymphadenopathy and
infantum can persist for weeks conjunctivitis may initially be mistaken for adenoviral infection
Hand, foot and 4e7 During shedding of the virus, or Kawasaki’s disease. Rarely, there are also red papules on the
mouth disease which can persist in the stool hard palate (Forschheimer spots). Complications are unusual,
for several weeks although occasionally adults develop transient arthropathy, and
rarely peripheral neuritis or encephalitis. If a pregnant woman
Table 1 contracts rubella in the first trimester, transplacental infection
can cause congenital rubella syndrome in the developing fetus.
This leads to a high probability of fetal loss or premature birth,
Treatment of measles is primarily supportive, although in and a constellation of severe symptoms in the baby, including
immunocompromised individuals intravenous immunoglobulin cerebral, cardiac, ophthalmic and auditory defects. It is a pro-
(IVIG) and ribavirin have been used to try to decrease the gressive disease and all abnormalities may not be present at
duration of viraemia. Vitamin A supplementation is widely birth.
used to reduce mortality, although a Cochrane review showed Rubella vaccine is contraindicated in pregnancy. However,
that this was likely to be of most benefit in children under the inadvertent vaccination during the first trimester does not
age of 2 years.9 A further Cochrane review suggested that necessarily cause congenital disease and is not an indication for
concurrent antibiotic treatment may prevent pneumonia and termination.13
otitis media.10 The mainstay of secondary prevention com-
prises contact tracing with implementation of catch-up immu- Varicella (see also Herpesvirus on pages 34e38 of this issue)
nization and, in immunocompromised individuals, prophylaxis
with intramuscular human normal immunoglobulin. Varicella (chicken pox) is caused by a herpesvirus, varicella-zoster
virus (VZV). The highest incidence is in young children, although
non-immune adults are also at risk. It is highly infectious and the
chance of a susceptible second household member becoming
infected is 80e95%. Although the disease is spread primarily by
respiratory droplets, the vesicle fluid is also infectious.
The prodromal period consists of fever, cough, coryza and
sore throat, and is followed by an intensely pruritic rash. Initially
papular, the lesions develop into clusters of vesicles that spread
from the face and trunk to the limbs, occasionally becoming
haemorrhagic (Figure 2). New crops of vesicles develop every
few days until they crust over and lesions exist concurrently at
several different stages. Secondary bacterial infection, usually in
the form of otitis media or group A streptococcal cellulitis, occurs
in about 10%. Rarely, the more severe manifestation of group A
streptococcal necrotizing fasciitis occurs, which is characterized
by severe pain. This is a surgical emergency and must be
considered in an individual with varicella with these symptoms.
The rate of complications following varicella, such as pneumo-
Figure 1 Measles. nitis, encephalitis and cerebellar ataxia, is higher in adults than

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 VIRAL INFECTIONS

combined varicella and MMR vaccine is used in Europe. A herpes

zoster vaccine (live attenuated VZV at higher concentrations
than VZV vaccine) has recently been added to the routine UK
immunisation schedule for adults over 70 years to prevent
shingles.16

Erythema infectiosum (see also Erythrovirus B19 on pages 39e41 of

this issue)
Erythema infectiosum (fifth disease, slapped cheek syndrome) is
caused by erythrovirus (formerly parvovirus) B19.17 It is spread
via respiratory droplets and predominantly affects preschool
children although adults can be affected.
Around half of infections with erythrovirus B19 are asymp-
tomatic. Erythema infectiosum has a mild prodromal period
with fever and malaise. The characteristic exanthem is a sym-
metrical erythematous rash over both cheeks, and the trunk and
limbs may also develop a lacy maculopapular rash (Figure 3).
Adults develop a flu-like illness and are more likely to develop
arthralgias than children. Complications of erythrovirus B19
infection relate to its tropism for pro-erythrocytes, causing
anaemia. This can lead to aplastic crises, particularly in those
with underlying haemolytic diseases. In immunocompromised
individuals infection may persist, leading to severe relapsing
remitting anaemia. Infection in non-immune pregnant women
can cause hydrops fetalis and fetal death. Intrauterine trans-
Figure 2 Haemorrhagic varicella. fusions can prevent some of the most severe outcomes if
hydrops is diagnosed early.
A second exanthem caused by erythrovirus B19 is papular-
in children. Rare complications include transverse myelitis,
purpuric gloves and socks syndrome, a self-limiting condition
nephritis and carditis. In children who are immunocompromised
affecting children and young adults first described in 1990.18
and who come into contact with varicella, it is possible to avert
Erythema, oedema and pruritus of the hands and feet in a
development of the disease by giving VZV-specific immuno-
glove and sock distribution are associated with mild fever. The
globulin (VZIG) within 72 hours of the contact. Owing to the high
erythema progresses to petechiae and purpura, and occasion-
viral dose via the placenta and the immaturity of the newborn
ally bullae on the palms and soles, which may be painful. In
immune system, babies of mothers who develop varicella be-
addition to erythrovirus B19, human herpesvirus 6 (HHV6),
tween 5 days before and 2 days after delivery should also be
HHV7, cytomegalovirus (CMV) and measles virus have been
given VZIG.
implicated in the aetiology. Treatment is symptomatic with
After primary infection, VZV exists latently in the sensory
antihistamines, and the rash usually resolves in 1e2 weeks
ganglia and can reactivate, particularly in the immunocompro-
without sequelae.
mised and elderly, as herpes zoster. This manifests as clusters of
vesicles in one or two contiguous dermatomes and can be
painful. In adults, treatment with aciclovir is recommended
within 72 hours of onset to prevent the complication of post-
herpetic neuralgia, a very uncommon sequela in children. In
immunocompromised individuals, intravenous aciclovir should
be started to prevent dissemination of varicella, which has a high
morbidity. A specific manifestation of herpes zoster, Ramsay
Hunt syndrome, affects the VIIth (and sometimes VIIIth) cranial
nerve. Individuals present with a facial palsy and vesicles may be
seen on the pinna and in the auditory canal.
Although aciclovir and corticosteroids are variously used for
treatment, there is no good evidence for their use as trials of
treatment for facial palsy have either excluded Ramsay Hunt
syndrome14 or have been too small to allow a conclusion to be
drawn.15
Vaccines against varicella have been available for a few years
although currently these are not part of the UK childhood im-
munization schedule. Vaccination of non-immune household
contacts of immunocompromised patients is often advocated. A Figure 3 Erythema infectiosum.

MEDICINE 42:1 54 Ó 2014 Published by Elsevier Ltd.

 VIRAL INFECTIONS

Roseola infantum (see also Herpesvirus on pages 34e38 of this However, other infectious agents have been implicated, including
issue) EpsteineBarr virus (EBV) e the commonest cause e enterovi-
ruses, various respiratory viruses, erythrovirus B19 and CMV.
The first virus to be associated with roseola infantum (sixth
There are a few reports of GianottieCrosti syndrome following
disease, exanthem subitum) was HHV6, although it is also
various immunizations.23
caused by HHV7. These viruses are spread through contact with
It is generally a self-limiting condition usually lasting 10e14
saliva.
days and predominantly affecting preschool children. In adults, it
Roseola infantum affects infants and young children and is
is rare and exclusive to women. The exanthem is an erythema-
characterized by a high fever for about 3 days, which defervesces
tous papular or vesicular rash affecting the extensor surface of
abruptly with the appearance of a pink maculopapular rash. The
the extremities, face and buttocks, which may be pruritic. The
abrupt rise in temperature may be associated with febrile convul-
rash is often asymmetrical and lesions may coalesce to form
sions. Gastrointestinal and occasionally respiratory symptoms can
plaques. It is associated with fever and/or lymphadenopathy in
occur. Other clinical findings include mild oedema and occasion-
about one-third of individuals. Occasionally acute hepatitis de-
ally erythematous papules on the soft palate (Nagayama’s spots).
velops, particularly when the causative organism is hepatitis B,
Sterile pyuria may be a feature, which can result in some children
EBV or CMV, and very rarely this can become chronic. Treatment
receiving early antibiotics unnecessarily for urinary tract infec-
is symptomatic.
tion.19 Complications are rare, but include encephalitis, hepatitis
EBV is also the causative virus in infectious mononucleosis
and haemophagocytic syndrome. In the occasional adult who de-
(glandular fever). Classically the symptoms are fever, sore
velops the condition, roseola presents as a mononucleosis-like
throat, fatigue and enlarged lymph nodes with exanthem only
illness. Reactivation in children and adults who are immuno-
rarely described. However, if amoxicillin is prescribed for pre-
compromised with high viral loads is significantly associated with
sumed bacterial tonsillitis, a florid widespread maculopapular
mortality after bone marrow transplantation.20
rash can develop (Figure 4).
Treatment of roseola infantum is supportive, although gan-
ciclovir and cidofovir have been used to treat reactivation of
Unilateral laterothoracic exanthem
HHV6 in immunocompromised individuals.21
Also known as asymmetric periflexural exanthem of childhood,
Hand, foot and mouth disease (see also Enterovirus on pages unilateral laterothoracic exanthem was described in 18 patients
57e59 of this issue) in 1992.24 It usually occurs in winter and early spring and is most
common in children aged 1e5 years, although rarely it has been
Hand, foot and mouth disease is caused by enteroviruses, most
reported in adults. No single causative organism has been
commonly Coxsackievirus A subtypes and enterovirus 71. It is
highly contagious and is spread by the faecal-oral route, respi-
ratory droplets and contact with skin lesions. It predominates in
preschool age children and outbreaks in nurseries are common.
Incidence peaks in summer and autumn in temperate climates.
There is a prodrome of low-grade fever, anorexia and a sore
mouth lasting 1e2 days before the rash appears. Lesions initially
appear in the mouth as erythematous lesions on the buccal mucosa
and hard palate that become vesicular and ulcerate. Most in-
dividuals also develop vesicles with an erythematous base on the
palms, soles and between the digits that can be itchy. A macular
rash may also appear on the trunk, buttocks and genitalia. The rash
usually resolves in 3e6 days. Treatment is supportive, in particular
for painful stomatitis, which may lead to dehydration.
Coxsackieviruses and echoviruses also cause herpangina,
which has lesions similar to those in hand, foot and mouth disease
but which are limited to the posterior oral cavity, with none on the
hands or feet. Enteroviruses can cause several different types of
rash e maculopapular, vesicular, urticarial and petechial.
Enteroviruses can also cause meningitis, and rare complica-
tions of enteroviral infection include encephalitis, pneumonitis
and myocarditis. Spontaneous abortion has been reported during
infection in pregnancy, and infection in late pregnancy can lead
to severe disease in the newborn clinically resembling bacterial
sepsis.22

GianottieCrosti syndrome
GianottieCrosti syndrome (papular acrodermatitis of childhood)
was originally described in association with hepatitis B infection. Figure 4 Epstein–Barr virus and amoxicillin.

MEDICINE 42:1 55 Ó 2014 Published by Elsevier Ltd.

 VIRAL INFECTIONS
identified although erythrovirus B19 and EBV have been asso-
ciated. It has been suggested that it is a skin eruption common to
several different viruses.
There is usually a prodrome of low-grade fever and mild
respiratory and gastrointestinal symptoms. The rash begins
unilaterally on the trunk, most frequently in the axilla and can be
accompanied by an enlarged axillary lymph node. It is a mor-
billiform or eczematous rash that may spread bilaterally but re-
tains a unilateral predominance. It is self-limiting and usually
resolves in about 4 weeks without complication.
Pityriasis rosea
Pityriasis rosea is an exanthem of unknown cause affecting older
children and young adults. A viral cause is suggested by seasonal
and geographic clustering although various drugs have also been
associated.
A sore throat can precede the exanthem, and constitutional
symptoms such as headache and low-grade fever can accompany
the rash. The rash is characterized by pink or red scaly oval le-
sions, often preceded by a single lesion, predominantly on the
trunk. It can be pruritic, and treatment with antihistamines
provides symptomatic relief. The rash usually resolves within
several weeks without treatment. Ultraviolet light has been used
anecdotally to shorten the course in pityriasis, but comparative
studies in a few patients have not shown good evidence for its
use.25 A Marrow Transplant 2008; 14: 831e9.
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FURTHER READING
aapredbook.aappublications.org e the Red Book online.
https://www.gov.uk/government/organisations/public-health-england/
series/immunisation-against-infectious-disease-the-green-book e the
Green Book online.
Pickering LK, ed. Red Book: 2009 Report of the committee on infectious
diseases. 28th edn. American Academy of Pediatrics, 2009 [The
definitive quick reference text of Paediatric Infectious Diseases].
Manual of childhood infections: the Blue Book. Royal College of Paedi-
atrics and Child Health, 2011 [Paediatric Infectious Diseases in a
practical and easy to read format].
The Green Book e immunisation against infectious disease. Department
of Health, 2006 [Immunization advice in the UK].
www.hpa.org.uk e the Health Protection Agency website for the current
status of various infectious diseases.
56 Ó 2014 Published by Elsevier Ltd.