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CHAPTER

35

RASH AND FEVER

History

234

Physical examination

234

Important rashes in the newborn

235

Erythema toxicum
235
Staphylococcal skin infection
235
Localized herpes simplex virus (HSV) infection
Varicella zoster virus infection
236
Petechiae 236

Rashes in infancy and childhood

Vesicular rashes
236
Maculopapular rashes
237
Petechial and purpuric rashes
238
Papular rashes
239
Generalized erythroderma
240
Urticaria
241

Clinical problem

235

A rash is a visible lesion of the skin due to disease.

The condition can be a primary skin disorder or a
symptom of a systemic process. Rashes caused by
infection can be limited to skin involvement or be part
of a broader condition.
When considering the differential diagnosis of a
rash, it is important to be able to describe its features.
Ask the childs parents about the appearance, because
rashes often change with time.

236

History

243

Onset of the rash: sudden or gradual.

Type of lesion: see Table 35.1.
Distribution: whether central, peripheral or
generalized.
Progression: direction of spread, speed of
progression.
General well-being of the child, including prodromal illness or fever.
Infectious contacts.
Drug history: including over-the-counter preparations, topical treatments and drugs that have been
ceased.
Symptoms of the rash: itch, pain, burning.
Travel history.
Contact with pets and other animals.

Physical examination
Be sure to examine:

234

The entire skin surface:

To determine the true extent of the rash.
Type of lesions.
Distribution.
Evolving lesions.
The mucous membranes for involvement or
ulceration.
The conjunctivae for injection or episcleritis.

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Table 35.1

Description

Common causes

Vesicles

Small, fluid-filled blisters

Petechiae
Pustules

Small, non-blanching spots

Small blisters containing purulent fluid

Urticaria
Macules

Raised, itchy lesions

Flat spots, not palpable. Can form
large sheets
Elevated, palpable, small rounded
lesions
Elevated, flat-topped lesions

Varicella zoster, herpes simplex, enteroviruses

(particularly Coxsackie A)
Vasculitis, meningococcaemia, thrombocytopenia
Bacterial infection, e.g. Staphylococcus aureus.
NB: not necessarily infective
Drug eruptions, erythema marginatum, idiopathic
Drug eruptions, viral exanthems

Plaques

Terminology of cutaneous lesions

Type of lesion

Papules

235

The scalp and hair for areas of inflammation,

scaling or hair loss. Use of ultraviolet light (a
Woods light) can show fluorescence in some types
of fungal infection.
For lymphadenopathy.
For hepatosplenomegaly.
The joints for any associated arthritis.

Important rashes of infancy and childhood that are

commonly seen in general paediatric practice will
be discussed in the following section under descriptive headings, with a separate section for neonatal
conditions.

Important rashes in the newborn

Molluscum contagiosum, warts, enteroviruses

Psoriasis, pityriasis rosea

widespread skin loss (Fig. 35.1). This condition is life

threatening.

Localized herpes simplex virus (HSV)

infection
Neonatal HSV infection may be localized, at least
initially, to the skin, eyes and/or mouth, so-called
skineyemouth (SEM) disease. Vesicles are most
often found on the scalp or around areas of minor
trauma, e.g. scalp electrode sites. They can present as
shallow ulcers only. Rapid diagnosis can be obtained,
often within an hour or two, using specific immunofluorescent staining of cells swabbed from the base of
a lesion. Polymerase chain reaction (PCR) for viral
DNA is not usually helpful in this situation because of

Erythema toxicum
This appears as red macules with overlying small
yellow or white pustules. The condition is idiopathic
and non-infective. It can be mistaken for infection: a
Gram stain of the lesion shows multiple eosinophils.
The rash often appears during the first few days of life
and may persist up to a fortnight.

Staphylococcal skin infection

This can look similar to erythema toxicum: the skin
may be indurated and pustules may be interspersed
with vesicles and sometimes bullae. When bullous, it
is referred to as bullous impetigo. In its most severe
form, of staphylococcal scalded skin syndrome, there
is extensive erythema in a clinically septic child, with

Fig 35.1 Staphylococcal scalded skin syndrome in a

neonate. Skin desquamation with underlying
erythema. (Courtesy of Dr Maureen Rogers.)

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time constraints. Urgent early treatment of localized

neonatal HSV infection with intravenous acyclovir is
essential because, without treatment, 70% of affected
babies will progress to disseminated HSV infection
with encephalitis, hepatitis, DIC and an extremely
poor prognosis.

Varicella zoster virus infection

Neonatal varicella is usually seen in the context of
maternal chickenpox (or more rarely zoster) or of
contact with an infected sibling. Rapid diagnosis can
be obtained by specific immunofluorescence of vesicle
fluid. Neonatal varicella resulting from perinatal
transmission can be life threatening and, if severe,
requires intravenous acyclovir.

has remained latent in nerve cells following earlier

chickenpox. The rash is characteristic, with the eruption of crops of vesicles in a dermatomal distribution,
although there are often one or two spots outside the
dermatome. Confusion with herpes simplex stomatitis may occur when facial nerve dermatomes are
involved. Pain is surprisingly rare in children, although
older children may sometimes have painful lesions.
Although zoster is common in immunocompromised
children, it is not uncommon in normal children, and
is virtually never the first presentation of underlying
malignancy or immune compromise. Zoster in young
children often results from having chickenpox in the
neonatal period, or from intrauterine exposure due to
maternal VZV in pregnancy.

Herpes simplex virus (HSV)

Petechiae
The most common cause of neonatal petechiae is
thrombocytopenia, either from platelet destruction by
maternal antibodies, or from congenital infection such
as CMV. Congenital rubella is extremely rare in most
developed countries, because of immunization.

Rashes in infancy and childhood

Vesicular rashes
Varicella (chickenpox)

While HSV infection is often asymptomatic, the most

common presentation during childhood is with gingivostomatitis. The child is febrile and develops ulcers
of the gums, buccal mucosa and pharynx, and often
on the cheek where saliva dribbles. There may be
marked facial swelling and redness. Involvement of
a finger can occur (herpetic whitlow), and may
mimic paronychia. HSV infection of eczematous skin
(eczema herpeticum) can spread rapidly (Fig. 35.2)
and, if the vesicular nature of the lesions is overlooked,
may be misdiagnosed as worsening eczema or bacterial superinfection. A clinical diagnosis of eczema
herpeticum can be confirmed rapidly with specific

Chickenpox is caused by primary infection with varicella zoster virus (VZV). Classically, there is a short
prodrome of about a day of sore throat and fever, after
which varicella commences as crops of itchy, circumscribed, vesicular lesions on the scalp and trunk. These
become pustular before becoming crusted and then
resolve without scarring, if not superinfected. A range
of lesions at different stages is usually seen at any one
time. Mucous membranes may be involved. There is
often only a mild prodromal illness of fever and mild
lethargy. When varicella occurs in the context of significantly damaged skin, such as eczema, the risk of
serious illness is much higher, and careful monitoring
and treatment are indicated.

Herpes zoster (shingles)

Zoster is caused by the same virus as chickenpox
VZV but occurs due to reactivation of VZV, which

Fig 35.2 Eczema herpeticum. Widespread

inflammation, but discrete vesicular lesions are
distinguishable.

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immunofluorescence, and affected children usually

require intravenous acyclovir.

Enteroviruses
Non-polio enteroviruses are a common cause of
vesicular rashes, especially in summer and autumn.
Hand, foot and mouth disease is caused by different
enteroviruses, most commonly Coxsackievirus type
A16. It often occurs in epidemics in daycare centres or
schools. It is associated with a papulovesicular eruption on the palms, soles, mucous membranes and
sometimes the buttocks. There may be mild associated
respiratory or gastrointestinal symptoms, but the clinical course is benign.
Enterovirus 71 can cause hand, foot and mouth
disease, but differs from the other enteroviruses in that
infections may be accompanied by significant neurological manifestations, such as aseptic meningitis,
brainstem encephalitis with neurogenic pulmonary
oedema, and acute flaccid paralysis.

Impetigo
Impetigo is the most common skin infection encountered in infants and school-aged children. It is caused
by Streptococcus pyogenes or Staphylococcus aureus. The
early lesion is an erythematous papule, which
progresses to transient vesicles and then becomes a
shallow ulcer with surrounding honey-coloured
crusted exudate. The lesions are often found in an area
of traumatized skin, and are commonly around the
nose, mouth and extremities. It is spread among individuals through close physical contact.

Maculopapular rashes
Many virus infections, especially enteroviruses,
produce maculopapular exanthems. These are often
non-specific and generalized in distribution (Fig.
35.3). They can be difficult to differentiate from allergic drug reactions. Features that favour a viral aetiology are:

Occurrence along scratch marks.

Some lesions in straight lines.
Exaggeration in areas of sunburn.
Occurrence under hospital arm bands or on prior
skin disease.
Presence of lymphadenopathy.

Fig 35.3 Viral exanthem. Widespread macules,

some in a characteristically linear pattern.

Measles
Measles is rare in countries with high levels of immunization. While the diagnosis should be considered in
a child with a blotchy, geographical, erythematous
exanthem, other causes are usually more likely in an
immunized child. Characteristic features of measles
are:

35 days of prodromal features of fever, malaise,

conjunctivitis, coryza and cough.
High fever, which persists after the rash appears.
Downward spread of the rash from the preauricular area and the face to involve the body.
Tendency of the rash to become confluent on the
trunk and remain discrete lower down.
Tendency of the rash to become brown and then
desquamate after 23 days.

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Rubella
Rubella virus infection results in an erythematous, discrete exanthem that is often faint but may be morbilliform (measles-like) and spreads down from the face.
Occipital and/or post-auricular lymphadenopathy is
typically (but not exclusively) associated, and arthritis
and conjunctivitis can occur. There are relatively few
systemic symptoms in children. It is important to trace
and investigate pregnant contacts of a case.

Kawasaki disease
This is an important differential diagnosis of a child
with rash and fever. Clinical features include persistent
high fever with characteristic marked irritability,
rash, cervical lymphadenopathy (sometimes unilateral
resembling abscess), non-exudative conjunctivitis,
stomatitis, and swelling or redness of hands and feet.
The rash is not specific and can take many forms. It
may resemble erythema multiforme, scarlet fever,
measles, urticaria or a drug reaction. It is usually nonpruritic, and may be transient or evanescent (comes
and goes).

Erythema infectiosum (slapped cheek disease,

fifth disease)
Parvovirus B19 infection produces a rash that develops
in two stages. The initial appearance is of slapped
cheeks: an intense erythema of the malar areas resembling sunburn in a child who may be well, or have mild
systemic symptoms of malaise and fever. The patient
then develops a reticulated macular erythema over the
limbs (Fig. 35.4). This is often asymptomatic or may be

associated with arthralgias. This form of the rash may

wax and wane for weeks after the initial illness. Children
are no longer infectious once the rash has appeared.

Roseola infantum
Roseola is a condition that affects infants and young
children. Children initially have 35 days of high fever
and mild systemic symptoms, before the rash then
appears with simultaneous defervescence. The rash
consists of small rose-pink macules or papules, which
may be morbilliform and are most prominent on the
trunk and face. The most common aetiological agent
is human herpesvirus 6 (HHV-6). Children with
measles are febrile and miserable when the rash is
present; in contrast, the child with roseola becomes
afebrile and well as the rash appears.

Meningococcal infection
A transient macular rash, mimicking an enteroviral
rash, can occur early in infection with Neisseria meningitidis in up to 20% of cases. It typically disappears in
less than a day, and purpura may then appear.

Petechial and purpuric rashes (Table 35.2)

Meningococcal infection
In a febrile child without an infectious focus, a localized petechial or purpuric rash can be the first sign of
N. meningitidis septicaemia (Fig. 35.5). The lesions
may be very subtle early in the course. Purpuric lesions

Table 35.2 Differential diagnosis of child with

purpura or petechiae

Fig. 35.4 Fifth disease. Lacy, reticular rash.

(Courtesy of Dr Maureen Rogers.)

Bacterial infections

Other causes

Neisseria meningitidis
infection
Staphylococcus aureus
sepsis
Streptococcus pneumoniae
sepsis
Listeria monocytogenes
sepsis
Group A streptococcal
pharyngitis

Viral illnesses, e.g.

enteroviruses,
EBV, CMV
Rickettsial infections
HenochSchnlein
purpura
Thrombocytopenia
(ITP, malignancy)

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rash. This is usually accompanied by a history of easy

bruising, malaise or fatigue, bone pain, and often
pallor caused by the associated anaemia. Fever may
also be present due to infection.

Papular rashes
Molluscum contagiosum

Fig 35.5 Purpura. Discrete purple lesions > 2 mm in

diameter, which will not blanch on pressure.

do not blanch with pressure. A simple test is to press

a glass slide or a drinking glass on the lesions and
observe through the glass whether the lesions stay
purple or go white (blanch).

Molluscum is a poxvirus infection, which causes multiple, 25 mm diameter, flesh-coloured papules with
a central dimple (umbilication). Initially firm, the
lesions become softer and waxier with time. Some
lesions have a mildly erythematous base and lesions
may become superinfected. The lesions can occur on
all parts of the body, but are least common on the
palms or soles. Auto-inoculation and spread to others
via close contact can occur. In the vast majority of
cases, the condition will resolve over some months
without specific treatment. Immunodeficiency, e.g.
HIV, predisposes to severe molluscum.

HenochSchnlein purpura (HSP)

HSP is an immunologically mediated vasculitis,
thought to be a reaction to an infectious agent,
although no single organism has been implicated. It
is usually preceded by an upper respiratory tract
infection. It is the most common cause of nonthrombocytopenic purpura in children. The rash
characteristically involves the buttocks and extensor
surfaces, starting off as pink, blanching maculopapules, which progress to palpable non-blanching
purpura that evolves from red to purple and then
brown, before fading over 23 days. The lesions occur
in crops and may recur at intervals over days to
months after the initial episode. Fever is uncommon.

Acral papular viral exanthem

While classically attributed to the exanthem associated
with hepatitis B (GianottiCrosti syndrome), acral
papular exanthems can occur with a number of virus
infections, especially enteroviruses. There are many
terms used for this exanthem, including papular acrodermatitis of childhood and papulovesicular acrolocated syndrome (PALS). The appearance is of papular
and occasionally vesicular lesions, restricted to the
acral part of the limbs and occasionally the face (Fig.
35.6). There is often associated pruritus. The predominant age group affected is 2- to 4-year-olds. The reaction has a prolonged course and may take up to 10
weeks to resolve.

Idiopathic thrombocytopenic purpura (ITP)

ITP is an immunologically mediated disease, in which
platelet destruction by auto-antibodies leads to
petechiae, and occasionally a purpuric rash with frank
bleeding. Many different viral infections can sometimes be triggers for the occurrence of ITP (which is
not really idiopathic in those cases). Children are not
usually febrile at the time of onset of the rash of ITP.

Leukaemia
Children with marrow infiltration by malignant cells,
particularly leukaemia, may present with a petechial

Erythema multiforme (EM)

EM is characterized by an abrupt eruption of erythematous macules or plaques, usually most prominent
on the extensor surfaces of the upper limbs (Fig. 35.7).
The diagnostic lesion is doughnut shaped, with an erythematous outer ring, and a pale inner ring around a
dusky or necrotic centre (target lesions). The lesions
are mostly asymptomatic, but may be mildly uncomfortable or pruritic. The lesions remain fixed in position, and are often characteristically symmetrical
bilaterally. They fade after a week to 10 days. Oral
lesions may occur (but other mucosal surfaces are not

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Fig 35.6 Acral papular viral exanthem. Raised

papules on the hands of a child. (Courtesy of Dr
Maureen Rogers.)

Fig 35.8 StevensJohnson syndrome. Haemorrhagic

lesions, some bullous, plus severe mucosal
involvement.
Fig 35.7 Erythema multiforme. Oval, erythematous
target lesions with dusky centres. (Courtesy of Dr
Maureen Rogers.)

Generalized erythroderma
Staphylococcal scalded skin syndrome

involved), and 25% of cases involve the oral mucosa

alone. The most common infective cause is HSV.

StevensJohnson syndrome
An important differential of EM, this eruption differs
in that two or more mucosal surfaces are involved,
lesions are more widespread, and there is progression
to bulla formation and haemorrhagic crusting (Fig.
35.8). Mucosal ulceration of the mouth and genitalia
may occur and is severely painful. There is often significant internal organ involvement and a prodrome
of flu-like upper respiratory tract illness. The most
common infectious agent implicated is Mycoplasma
pneumoniae; the other major causal agent is drugs.

This manifestation of S. aureus infection is mostly seen

in children under 5 years. Foci of infection include the
nasopharynx, urinary tract, umbilicus and skin abrasions. The skin reaction is mediated by staphylococcal
epidermolytic toxin A or B. It consists of a scarlatiniform, generalized erythroderma, accompanied in
severe forms by internal organ involvement and severe
systemic illness. The child may be irritable and unwell;
the erythroderma is markedly tender and may
progress to take on a wrinkled appearance, before
forming sterile bullae and erosions, with extensive epidermal loss. The conjunctivae may be erythematous
and purulent, and radial fissuring is common around
the mouth, nose and eyes. Perioral erythema is prominent. Owing to skin loss, fluid and electrolyte imbal-

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241

ances and secondary infection are common complications. The split in the skin layers is superficial, so that
with antibiotic treatment complete recovery occurs
with no scarring.

Scarlet fever
Scarlet fever is a systemic manifestation of Streptococcus pyogenes infection, resulting from exotoxin production. It affects mainly children aged 312 years and
is rare in infancy. Scarlatina is the name given to a
milder illness in which streptococcal infection causes
scarlatiniform rash alone, without the systemic features. True scarlet fever causes an erythematous, fine,
punctate rash which characteristically has a sandpaper
texture. It appears initially on the trunk and spreads
rapidly. Petechiae may be found on major skin folds.
Other distinctive features are glossal inflammation,
with prominent papillae (a strawberry tongue) and
circumoral pallor, with the rash sparing the skin
around the mouth. There is often desquamation of
fingers and toes on resolution.

Fig 35.9 Purple urticaria. Blotchy truncal rash,

purple in places. (Courtesy of Dr Maureen Rogers.)

Toxic shock syndrome (TSS)

Like scarlet fever, TSS is a severe, systemic, clinically
defined reaction to bacterial toxin. By definition, clinical features must include high fever, rash with desquamation, hypotension and involvement of at least three
organ systems. Organisms associated with this syndrome are S. aureus and S. pyogenes. While TSS is
usually recognized by the combination of all symptoms, the rash is typically a diffuse erythroderma, and
may be accompanied by conjunctival and other
mucous membrane hyperaemia. Its distribution and
intensity may alter from hour to hour during the
course of the illness.

Erythema marginatum
The rash associated with rheumatic fever (RF) is a
form of urticaria. It manifests in around 10% of
patients with RF, and is considered one of the major
diagnostic criteria for RF when present. The rash has
an erythematous macular component and a raised
edge (Fig. 35.10). It is non-pruritic and non-painful,
and the lesions coalesce to form a serpiginous pattern.

Urticaria
It is important to appreciate that, while classically
associated with hypersensitivity reactions, urticaria
in children under 5 years of age is most commonly
caused by a viral illness. In this situation, there is often
less associated pruritus than would be expected with
an allergic reaction. Severe lesions may be associated
with a purple discoloration due to bruising (purple
urticaria; see Fig. 35.9). Viral urticaria differs from
erythema multiforme because the position of the
lesions changes, and the erythema disappears from
individual lesions over a 24-hour period.

Fig 35.10 Erythema marginatum. Widespread

urticarial rash with thin, pink margin. (Courtesy of Dr
Maureen Rogers.)

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The rash may be fleeting and may reappear intermittently over weeks.

Drug reactions
Cutaneous manifestations are the most common form
of adverse drug reaction in children. While classically

drug reactions are urticarial in nature, almost all morphological variants are possible. Angioedema related
to drug ingestion is more significant, as it implies an
IgE-mediated pathway for the reaction and hence possible risk of anaphylaxis on re-exposure.

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Clinical problem

243

Clinical problem
A 3-year-old girl was brought by ambulance to
the emergency department after a seizure at home.
On the day of presentation, she had been nonspecifically unwell. In the afternoon she complained
of a few non-specific aches and pains, and was
anorexic. Her mother thought she felt hot. She had
vomited once during the evening. She had no
rhinorrhoea, cough or rash. Just after midnight she
had a brief generalized tonicclonic seizure and
was brought to hospital.
Her only significant medical history was of a
febrile convulsion at 18 months of age, from which
she had recovered uneventfully. She had been born
at term, with no perinatal complications. Her
immunizations were up to date. She had no
siblings.
On examination in the emergency department

she was sleepy but easily rousable. Her temperature

was 39.4C, her heart rate was 130 beats per
minute and respiratory rate 24 breaths per minute.
Her throat was slightly red and there were a few
petechiae around her left eye. The remainder of
the examination was normal. Her blood sugar was
6.1 mmol/L. A diagnosis of febrile convulsion was
made and she was observed overnight. The
petechiae around her eye were considered to be
secondary to her vomiting. She vomited several
more times overnight.
On review the next morning she was sitting up
in bed watching television, but her father was
concerned that she did not seem well. On closer
examination she had further petechiae around her
face and a spreading purpuric rash was found over
her legs and chest.

Questions

Discussion

1. What is the likely diagnosis?

1. The most likely diagnosis in this child is

meningococcal septicaemia. The main clinical
features of meningococcal disease at
presentation are fever (88%), rash (68%),
vomiting (67%) and drowsiness (55%). Early
recognition of this condition is vital for
successful treatment. The classic spreading
purpuric rash discovered in this child is virtually
pathognomonic. Earlier diagnosis based on the
scattered petechiae around her eyes would have
required a higher degree of clinical suspicion.
Meningococcal disease may present with a
petechial rash alone, a maculopapular rash or no
rash. Atypical presentations may lead to delayed
diagnosis and a worse outcome.

2. What is the differential diagnosis of a child with

fever and petechiae?

2. There is a wide differential diagnosis to be

considered in the child presenting with fever
and petechiae. Only about 10% of children
presenting to hospital with fever and petechiae
in the USA and UK have meningococcal
infection.
Risk factors for serious bacterial infection in these
children include: appearing unwell or toxic,
signs of meningism, lack of pharyngitis,
numerous petechiae, the presence of purpura
and high (>15 109/L) or low (<5 109/L)
white cell counts. In the absence of these risk

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factors, much diagnostic information can be

obtained by a period of close observation,
looking for progression of or appearance of a
rash, the development or persistence of fever or
any deterioration in general condition. It is
important to periodically re-examine the skin
closely to detect any new changes early.
3. What should be the immediate diagnostic and
therapeutic steps?

3. Appropriate diagnostic procedures in this child

would include a full blood count, blood cultures,
throat swab for bacterial culture, culture of skin
lesions for meningococcus, a lumbar puncture if
there was any suspicion of meningitis and blood
PCR for meningococcus if available. This latter
test can be particularly valuable when antibiotics
have been given prior to blood cultures being
obtained.
In this child, a full blood count showed an
elevated white cell count of 15.1 109/L, with
13.3 109/L neutrophils. A Gram stain of the
serosanguineous fluid expressed from one of the
purpuric skin lesions showed Gram-negative
diplococci. Lumbar puncture was not performed.
She responded rapidly to intravenous penicillin
G. Blood and throat swab cultures were
negative, but blood PCR for N. meningitidis was
positive.

4. Is there a rapid diagnostic procedure available?

4. Gram staining of films obtained from petechial

lesions is an extremely useful diagnostic aid,
with a sensitivity of up to 80%. It can be
performed by pricking one of the purpuric spots
and squeezing some fluid from the spot onto a
slide for staining.
Intravenous or intramuscular antibiotic should be
given as soon as possible in suspected
meningococcal disease. Diagnostic procedures
(including lumbar punctures) should not delay
giving antibiotics by any longer than 1520
minutes. Children with meningococcal infection
require close monitoring, generally in an
intensive care setting, as they can deteriorate
rapidly due to toxaemia and cardiomyopathy.
A final diagnosis of meningococcal infection was
made.