CHAPTER

35

RASH AND FEVER

History

234 234 235

Physical examination

Important rashes in the newborn

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

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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.

Rashes in infancy and childhood

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

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History
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Clinical problem

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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:
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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

Terminology of cutaneous lesions Description Small, uid-lled blisters Small, non-blanching spots Small blisters containing purulent uid Raised, itchy lesions Flat spots, not palpable. Can form large sheets Elevated, palpable, small rounded lesions Elevated, at-topped lesions Common causes 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 Molluscum contagiosum, warts, enteroviruses Psoriasis, pityriasis rosea

Type of lesion Vesicles Petechiae Pustules Urticaria Macules Papules Plaques

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

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 specic immunouorescent 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

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

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 rst 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 specic immunouorescence of vesicle uid. 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 rst 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. 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 nger 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 conrmed rapidly with specic

Rashes in infancy and childhood

Vesicular rashes Varicella (chickenpox)
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 signicantly 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 inammation, but discrete vesicular lesions are distinguishable.

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immunouorescence, 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 signicant neurological manifestations, such as aseptic meningitis, brainstem encephalitis with neurogenic pulmonary oedema, and acute accid 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.

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

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 conuent 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.

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.

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 specic 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).

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.

Erythema infectiosum (slapped cheek disease, fth 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

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 rst 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 Bacterial infections Neisseria meningitidis infection Staphylococcus aureus sepsis Streptococcus pneumoniae sepsis Listeria monocytogenes sepsis Group A streptococcal pharyngitis Other causes Viral illnesses, e.g. enteroviruses, EBV, CMV Rickettsial infections HenochSchnlein purpura Thrombocytopenia (ITP, malignancy)

Fig. 35.4 Fifth disease. Lacy, reticular rash. (Courtesy of Dr Maureen Rogers.)

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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

Molluscum is a poxvirus infection, which causes multiple, 25 mm diameter, esh-coloured papules with a central dimple (umbilication). Initially rm, 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 specic treatment. Immunodeciency, e.g. HIV, predisposes to severe molluscum.

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).

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.

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 xed 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

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

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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 signicant internal organ involvement and a prodrome of u-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 ssuring is common around the mouth, nose and eyes. Perioral erythema is prominent. Owing to skin loss, uid and electrolyte imbal-

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ances and secondary infection are common complications. The split in the skin layers is supercial, 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, ne, 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 inammation, with prominent papillae (a strawberry tongue) and circumoral pallor, with the rash sparing the skin around the mouth. There is often desquamation of ngers 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 dened reaction to bacterial toxin. By denition, 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 eeting 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 signicant, 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
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 nonspecically unwell. In the afternoon she complained of a few non-specic 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 signicant 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
1. What is the likely diagnosis?

Discussion
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. I 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. 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. I 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

2. What is the differential diagnosis of a child with fever and petechiae?

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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. I 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 uid 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. Gram staining of lms 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 uid from the spot onto a slide for staining. I 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 nal diagnosis of meningococcal infection was made.

4. Is there a rapid diagnostic procedure available?