CHAPTER35 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 236 235 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 child’s 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 241 236 History I I I Clinical problem 243 I I I I I I I 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: I I I 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. 234 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.g. e. at least initially. This condition is life threatening. there is extensive erythema in a clinically septic child. meningococcaemia. palpable. Use of ultraviolet light (a Wood’s light) can show fluorescence in some types of fungal infection. it is referred to as bullous impetigo.1 Terminology of cutaneous lesions Description Small. with Fig 35. Can form large sheets Elevated. For lymphadenopathy. Skin desquamation with underlying erythema. NB: not necessarily infective Drug eruptions. scalp electrode sites. enteroviruses Psoriasis. Localized herpes simplex virus (HSV) infection Neonatal HSV infection may be localized. of staphylococcal scalded skin syndrome. with a separate section for neonatal conditions. not palpable. Staphylococcus aureus. so-called skin–eye–mouth (SEM) disease.1 Staphylococcal scalded skin syndrome in a neonate. For hepatosplenomegaly. It can be mistaken for infection: a Gram stain of the lesion shows multiple eosinophils. herpes simplex. The joints for any associated arthritis. (Courtesy of Dr Maureen Rogers. 35.Important rashes in the newborn 235 Table 35. often within an hour or two. 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. to the skin. They can present as shallow ulcers only. non-blanching spots Small blisters containing purulent fluid Raised. widespread skin loss (Fig. idiopathic Drug eruptions. scaling or hair loss. warts. e. The rash often appears during the first few days of life and may persist up to a fortnight. In its most severe form. viral exanthems Molluscum contagiosum. using specific immunofluorescent staining of cells swabbed from the base of a lesion. enteroviruses (particularly Coxsackie A) Vasculitis. thrombocytopenia Bacterial infection. Important rashes in the newborn Erythema toxicum This appears as red macules with overlying small yellow or white pustules. pityriasis rosea Type of lesion Vesicles Petechiae Pustules Urticaria Macules Papules Plaques I I I I The scalp and hair for areas of inflammation.g. fluid-filled blisters Small. erythema marginatum. Vesicles are most often found on the scalp or around areas of minor trauma. itchy lesions Flat spots. Rapid diagnosis can be obtained. small rounded lesions Elevated.1). eyes and/or mouth.) . The condition is idiopathic and non-infective. flat-topped lesions Common causes Varicella zoster. with the eruption of crops of vesicles in a dermatomal distribution. Involvement of a finger can occur (herpetic whitlow). but discrete vesicular lesions are distinguishable. the most common presentation during childhood is with gingivostomatitis. and is virtually never the first presentation of underlying malignancy or immune compromise. While HSV infection is often asymptomatic. without treatment. it is not uncommon in normal children. although there are often one or two spots outside the dermatome. DIC and an extremely poor prognosis. because of immunization. may be misdiagnosed as worsening eczema or bacterial superinfection. has remained latent in nerve cells following earlier chickenpox. HSV infection of eczematous skin (eczema herpeticum) can spread rapidly (Fig. hepatitis. after which varicella commences as crops of itchy. . There may be marked facial swelling and redness.2 Eczema herpeticum. Although zoster is common in immunocompromised children. buccal mucosa and pharynx. A range of lesions at different stages is usually seen at any one time. or from intrauterine exposure due to maternal VZV in pregnancy. These become pustular before becoming crusted and then resolve without scarring. A clinical diagnosis of eczema herpeticum can be confirmed rapidly with specific Rashes in infancy and childhood Vesicular rashes Varicella (chickenpox) Chickenpox is caused by primary infection with varicella zoster virus (VZV). Widespread inflammation. such as eczema. either from platelet destruction by maternal antibodies. When varicella occurs in the context of significantly damaged skin. the risk of serious illness is much higher. vesicular lesions on the scalp and trunk. circumscribed. Mucous membranes may be involved. The child is febrile and develops ulcers of the gums. There is often only a mild prodromal illness of fever and mild lethargy. and may mimic paronychia. Zoster in young children often results from having chickenpox in the neonatal period. Herpes simplex virus (HSV) Petechiae The most common cause of neonatal petechiae is thrombocytopenia. Confusion with herpes simplex stomatitis may occur when facial nerve dermatomes are involved. requires intravenous acyclovir. 70% of affected babies will progress to disseminated HSV infection with encephalitis. and careful monitoring and treatment are indicated. if not superinfected. if the vesicular nature of the lesions is overlooked. Rapid diagnosis can be obtained by specific immunofluorescence of vesicle fluid.236 Rash and fever time constraints. Herpes zoster (shingles) Zoster is caused by the same virus as chickenpox – VZV – but occurs due to reactivation of VZV. Congenital rubella is extremely rare in most developed countries. 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. Classically. which Fig 35. Pain is surprisingly rare in children. 35. Urgent early treatment of localized neonatal HSV infection with intravenous acyclovir is essential because.2) and. there is a short prodrome of about a day of sore throat and fever. The rash is characteristic. Neonatal varicella resulting from perinatal transmission can be life threatening and. or from congenital infection such as CMV. if severe. although older children may sometimes have painful lesions. and often on the cheek where saliva dribbles. coryza and cough.3). conjunctivitis. most commonly Coxsackievirus type A16. Downward spread of the rash from the preauricular area and the face to involve the body. which progresses to transient vesicles and then becomes a shallow ulcer with surrounding honey-coloured crusted exudate. which persists after the rash appears. While the diagnosis should be considered in a child with a blotchy. but differs from the other enteroviruses in that infections may be accompanied by significant neurological manifestations. Exaggeration in areas of sunburn.Rashes in infancy and childhood 237 immunofluorescence. Features that favour a viral aetiology are: I I I I I I I Occurrence along scratch marks. Widespread macules. mucous membranes and sometimes the buttocks. It is spread among individuals through close physical contact. Characteristic features of measles are: I Maculopapular rashes Many virus infections. and affected children usually require intravenous acyclovir. There may be mild associated respiratory or gastrointestinal symptoms. especially in summer and autumn. 35. Some lesions in straight lines. erythematous exanthem. Enteroviruses Non-polio enteroviruses are a common cause of vesicular rashes. Fig 35. some in a characteristically linear pattern. such as aseptic meningitis. Presence of lymphadenopathy. malaise. Occurrence under hospital arm bands or on prior skin disease. It is caused by Streptococcus pyogenes or Staphylococcus aureus. Tendency of the rash to become confluent on the trunk and remain discrete lower down. It often occurs in epidemics in daycare centres or schools. It is associated with a papulovesicular eruption on the palms. but the clinical course is benign. foot and mouth disease. especially enteroviruses. .3 Viral exanthem. I I 3–5 days of prodromal features of fever. and acute flaccid paralysis. They can be difficult to differentiate from allergic drug reactions. soles. foot and mouth disease is caused by different enteroviruses. mouth and extremities. Impetigo Impetigo is the most common skin infection encountered in infants and school-aged children. geographical. brainstem encephalitis with neurogenic pulmonary oedema. The early lesion is an erythematous papule. Enterovirus 71 can cause hand. These are often non-specific and generalized in distribution (Fig. and are commonly around the nose. produce maculopapular exanthems. High fever. The lesions are often found in an area of traumatized skin. Measles Measles is rare in countries with high levels of immunization. Tendency of the rash to become brown and then desquamate after 2–3 days. Hand. other causes are usually more likely in an immunized child. The most common aetiological agent is human herpesvirus 6 (HHV-6). 35. a localized petechial or purpuric rash can be the first sign of N. CMV Rickettsial infections Henoch–Schönlein purpura Thrombocytopenia (ITP. The lesions may be very subtle early in the course. Children with measles are febrile and miserable when the rash is present. malignancy) Fig. cervical lymphadenopathy (sometimes unilateral resembling abscess).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. (Courtesy of Dr Maureen Rogers.2) Meningococcal infection In a febrile child without an infectious focus. e. or have mild systemic symptoms of malaise and fever.5). reticular rash. scarlet fever. The initial appearance is of ‘slapped cheeks’: an intense erythema of the malar areas resembling sunburn in a child who may be well. and swelling or redness of hands and feet. and purpura may then appear. Purpuric lesions Table 35. The rash consists of small rose-pink macules or papules. This is often asymptomatic or may be Petechial and purpuric rashes (Table 35. in contrast. EBV. 35.4). Kawasaki disease This is an important differential diagnosis of a child with rash and fever. The rash is not specific and can take many forms. Children initially have 3–5 days of high fever and mild systemic symptoms. It is usually nonpruritic. This form of the rash may wax and wane for weeks after the initial illness. measles. and arthritis and conjunctivitis can occur. Lacy. It is important to trace and investigate pregnant contacts of a case. Roseola infantum Roseola is a condition that affects infants and young children. Clinical features include persistent high fever with characteristic marked irritability. fifth disease) Parvovirus B19 infection produces a rash that develops in two stages. enteroviruses. and may be transient or evanescent (comes and goes).) . Erythema infectiosum (slapped cheek disease. associated with arthralgias.4 Fifth disease. stomatitis. urticaria or a drug reaction. It typically disappears in less than a day. non-exudative conjunctivitis. There are relatively few systemic symptoms in children. 35.238 Rash and fever Rubella Rubella virus infection results in an erythematous.g. can occur early in infection with Neisseria meningitidis in up to 20% of cases. which may be morbilliform and are most prominent on the trunk and face. mimicking an enteroviral rash. Children are no longer infectious once the rash has appeared. Occipital and/or post-auricular lymphadenopathy is typically (but not exclusively) associated. discrete exanthem that is often faint but may be morbilliform (measles-like) and spreads down from the face. rash. the child with roseola becomes afebrile and well as the rash appears. before the rash then appears with simultaneous defervescence. meningitidis septicaemia (Fig. It may resemble erythema multiforme. Meningococcal infection A transient macular rash. The patient then develops a reticulated macular erythema over the limbs (Fig. The lesions are mostly asymptomatic. starting off as pink. may present with a petechial . The diagnostic lesion is doughnut shaped. malaise or fatigue. The lesions occur in crops and may recur at intervals over days to months after the initial episode. and are often characteristically symmetrical bilaterally. the condition will resolve over some months without specific treatment. restricted to the acral part of the limbs and occasionally the face (Fig. It is usually preceded by an upper respiratory tract infection.7). although no single organism has been implicated. and often pallor caused by the associated anaemia. including papular acrodermatitis of childhood and papulovesicular acrolocated syndrome (PALS). Acral papular viral exanthem While classically attributed to the exanthem associated with hepatitis B (Gianotti–Crosti syndrome). It is the most common cause of nonthrombocytopenic purpura in children. The reaction has a prolonged course and may take up to 10 weeks to resolve. Erythema multiforme (EM) EM is characterized by an abrupt eruption of erythematous macules or plaques. particularly leukaemia. but may be mildly uncomfortable or pruritic. in which platelet destruction by auto-antibodies leads to petechiae. Fever may also be present due to infection. but are least common on the palms or soles. The predominant age group affected is 2. Initially firm. The lesions remain fixed in position. with an erythematous outer ring. Fever is uncommon.g. do not blanch with pressure. Papular rashes Molluscum contagiosum Molluscum is a poxvirus infection. which will not blanch on pressure. and occasionally a purpuric rash with frank bleeding. usually most prominent on the extensor surfaces of the upper limbs (Fig. They fade after a week to 10 days. Discrete purple lesions > 2 mm in diameter. In the vast majority of cases. Many different viral infections can sometimes be triggers for the occurrence of ITP (which is not really idiopathic in those cases). 2–5 mm diameter. which causes multiple.5 Purpura. The rash characteristically involves the buttocks and extensor surfaces.to 4-year-olds. The lesions can occur on all parts of the body. 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). 35. Immunodeficiency. Some lesions have a mildly erythematous base and lesions may become superinfected. Children are not usually febrile at the time of onset of the rash of ITP. especially enteroviruses.6). before fading over 2–3 days. which progress to palpable non-blanching purpura that evolves from red to purple and then brown. Auto-inoculation and spread to others via close contact can occur. HIV. blanching maculopapules. flesh-coloured papules with a central dimple (umbilication). e. This is usually accompanied by a history of easy bruising. Fig 35. and a pale inner ring around a dusky or necrotic centre (target lesions). Henoch–Schönlein purpura (HSP) HSP is an immunologically mediated vasculitis. Idiopathic thrombocytopenic purpura (ITP) ITP is an immunologically mediated disease. Oral lesions may occur (but other mucosal surfaces are not Leukaemia Children with marrow infiltration by malignant cells. bone pain. the lesions become softer and waxier with time. acral papular exanthems can occur with a number of virus infections. The appearance is of papular and occasionally vesicular lesions.Rashes in infancy and childhood 239 rash. There are many terms used for this exanthem. There is often associated pruritus. predisposes to severe molluscum. 35. thought to be a reaction to an infectious agent. umbilicus and skin abrasions. (Courtesy of Dr Maureen Rogers.7 Erythema multiforme. nose and eyes. fluid and electrolyte imbal- . (Courtesy of Dr Maureen Rogers.6 Acral papular viral exanthem. the erythroderma is markedly tender and may progress to take on a wrinkled appearance.8). This manifestation of S. plus severe mucosal involvement. and radial fissuring is common around the mouth. Owing to skin loss. Perioral erythema is prominent. with extensive epidermal loss. Haemorrhagic lesions. and there is progression to bulla formation and haemorrhagic crusting (Fig. accompanied in severe forms by internal organ involvement and severe systemic illness. Foci of infection include the nasopharynx.) Generalized erythroderma Staphylococcal scalded skin syndrome involved). this eruption differs in that two or more mucosal surfaces are involved. The most common infective cause is HSV. Oval. The conjunctivae may be erythematous and purulent. The child may be irritable and unwell. urinary tract. Fig 35. The most common infectious agent implicated is Mycoplasma pneumoniae. Raised papules on the hands of a child. 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. some bullous.240 Rash and fever Fig 35. The skin reaction is mediated by staphylococcal epidermolytic toxin A or B. lesions are more widespread. generalized erythroderma.) Fig 35. the other major causal agent is drugs. Stevens–Johnson syndrome An important differential of EM. 35. and 25% of cases involve the oral mucosa alone. aureus infection is mostly seen in children under 5 years. erythematous ‘target’ lesions with dusky centres.8 Stevens–Johnson syndrome. It consists of a scarlatiniform. before forming sterile bullae and erosions. Erythema marginatum The rash associated with rheumatic fever (RF) is a form of urticaria. Fig 35. (Courtesy of Dr Maureen Rogers. resulting from exotoxin production. hypotension and involvement of at least three organ systems. TSS is a severe. while classically associated with hypersensitivity reactions. There is often desquamation of fingers and toes on resolution. systemic. It manifests in around 10% of patients with RF. It affects mainly children aged 3–12 years and is rare in infancy.Rashes in infancy and childhood 241 ances and secondary infection are common complications. the rash is typically a diffuse erythroderma. with the rash sparing the skin around the mouth. Petechiae may be found on major skin folds.9). Scarlatina is the name given to a milder illness in which streptococcal infection causes scarlatiniform rash alone. It is non-pruritic and non-painful. pink margin. there is often less associated pruritus than would be expected with an allergic reaction. By definition. While TSS is usually recognized by the combination of all symptoms. It appears initially on the trunk and spreads rapidly. without the systemic features. Organisms associated with this syndrome are S. 35. True scarlet fever causes an erythematous. and may be accompanied by conjunctival and other mucous membrane hyperaemia. fine. with prominent papillae (a ‘strawberry tongue’) and circumoral pallor. punctate rash which characteristically has a sandpaper texture. clinical features must include high fever. and is considered one of the major diagnostic criteria for RF when present.10 Erythema marginatum.9 Purple urticaria.) Toxic shock syndrome (TSS) Like scarlet fever. Other distinctive features are glossal inflammation. pyogenes. aureus and S. The rash has an erythematous macular component and a raised edge (Fig. purple in places.10). see Fig. Urticaria It is important to appreciate that.) . Scarlet fever Scarlet fever is a systemic manifestation of Streptococcus pyogenes infection. so that with antibiotic treatment complete recovery occurs with no scarring. and the erythema disappears from individual lesions over a 24-hour period. Its distribution and intensity may alter from hour to hour during the course of the illness. urticaria in children under 5 years of age is most commonly caused by a viral illness. Viral urticaria differs from erythema multiforme because the position of the lesions changes. rash with desquamation. clinically defined reaction to bacterial toxin. In this situation. Fig 35. and the lesions coalesce to form a serpiginous pattern. Severe lesions may be associated with a purple discoloration due to bruising (purple urticaria. The split in the skin layers is superficial. 35. (Courtesy of Dr Maureen Rogers. Blotchy truncal rash. Widespread urticarial rash with thin. . as it implies an IgE-mediated pathway for the reaction and hence possible risk of anaphylaxis on re-exposure. almost all morphological variants are possible. Drug reactions Cutaneous manifestations are the most common form of adverse drug reaction in children. Angioedema related to drug ingestion is more significant.242 Rash and fever The rash may be fleeting and may reappear intermittently over weeks. While classically drug reactions are urticarial in nature. Her blood sugar was 6. Just after midnight she had a brief generalized tonic–clonic seizure and was brought to hospital. her heart rate was 130 beats per minute and respiratory rate 24 breaths per minute. from which she had recovered uneventfully. The petechiae around her eye were considered to be secondary to her vomiting. A diagnosis of febrile convulsion was made and she was observed overnight. She had no rhinorrhoea. with no perinatal complications. but her father was concerned that she did not seem well. Her only significant medical history was of a febrile convulsion at 18 months of age. Her throat was slightly red and there were a few petechiae around her left eye. She had no siblings. signs of meningism. cough or rash. Atypical presentations may lead to delayed diagnosis and a worse outcome. She had vomited once during the evening. 2. vomiting (67%) and drowsiness (55%). The classic spreading purpuric rash discovered in this child is virtually pathognomonic. What is the likely diagnosis? Discussion 1. Only about 10% of children presenting to hospital with fever and petechiae in the USA and UK have meningococcal infection. a maculopapular rash or no rash. The most likely diagnosis in this child is meningococcal septicaemia. There is a wide differential diagnosis to be considered in the child presenting with fever and petechiae. Her temperature was 39. 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. On the day of presentation. lack of pharyngitis. Her immunizations were up to date. Her mother thought she felt hot. numerous petechiae. I Risk factors for serious bacterial infection in these children include: appearing unwell or toxic. In the afternoon she complained of a few non-specific aches and pains. The main clinical features of meningococcal disease at presentation are fever (88%). On review the next morning she was sitting up in bed watching television. and was anorexic. What is the differential diagnosis of a child with fever and petechiae? . She had been born at term. She vomited several more times overnight. The remainder of the examination was normal. Questions 1. Early recognition of this condition is vital for successful treatment. she had been nonspecifically unwell.4∞C. On closer examination she had further petechiae around her face and a spreading purpuric rash was found over her legs and chest. In the absence of these risk 2. the presence of purpura and high (>15 ¥ 109/L) or low (<5 ¥ 109/L) white cell counts. rash (68%).1 mmol/L. On examination in the emergency department she was sleepy but easily rousable.Clinical problem 243 Clinical problem A 3-year-old girl was brought by ambulance to the emergency department after a seizure at home. It is important to periodically re-examine the skin closely to detect any new changes early. I In this child. 4. meningitidis was positive. It can be performed by pricking one of the purpuric spots and squeezing some fluid from the spot onto a slide for staining. A final diagnosis of meningococcal infection was made. generally in an intensive care setting. as they can deteriorate rapidly due to toxaemia and cardiomyopathy. 3. with a sensitivity of up to 80%.244 Rash and fever factors. with 13. Appropriate diagnostic procedures in this child would include a full blood count.3 ¥ 109/L neutrophils. looking for progression of or appearance of a rash. throat swab for bacterial culture. Children with meningococcal infection require close monitoring. Diagnostic procedures (including lumbar punctures) should not delay giving antibiotics by any longer than 15–20 minutes. culture of skin lesions for meningococcus. Gram staining of films obtained from petechial lesions is an extremely useful diagnostic aid. I Intravenous or intramuscular antibiotic should be given as soon as possible in suspected meningococcal disease. a full blood count showed an elevated white cell count of 15. blood cultures. a lumbar puncture if there was any suspicion of meningitis and blood PCR for meningococcus if available. She responded rapidly to intravenous penicillin G. 4. Is there a rapid diagnostic procedure available? . but blood PCR for N. the development or persistence of fever or any deterioration in general condition. A Gram stain of the serosanguineous fluid expressed from one of the purpuric skin lesions showed Gram-negative diplococci. much diagnostic information can be obtained by a period of close observation.1 ¥ 109/L. This latter test can be particularly valuable when antibiotics have been given prior to blood cultures being obtained. Lumbar puncture was not performed. Blood and throat swab cultures were negative. What should be the immediate diagnostic and therapeutic steps? 3.