Erythema toxicumThis appears as red macules with overlying smallyellow or white pustules. The condition is idiopathicand non-infective. It can be mistaken for infection: aGram 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 infectionThis 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, withwidespread skin loss (Fig. 35.1). This condition is life threatening.

Localized herpes simplex virus (HSV)infectionNeonatal HSV infection may be localized, at leastinitially, to the skin, eyes and/or mouth, so-calledskin–eye–mouth (SEM) disease. Vesicles are mostoften found on the scalp or around areas of minortrauma, e.g. scalp electrode sites. They can present asshallow 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 oftime 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 infectionNeonatal varicella is usually seen in the context ofmaternal chickenpox (or more rarely zoster) or ofcontact with an infected sibling. Rapid diagnosis canbe obtained by specific immunofluorescence of vesicle fluid. Neonatal varicella resulting from perinatal transmission can be life threatening and, if severe, requires intravenous acyclovir.PetechiaeThe most common cause of neonatal petechiae isthrombocytopenia, either from platelet destruction bymaternal antibodies, or from congenital infection such as CMV. Congenital rubella is extremely rare in most developed countries, because of immunization.Rashes in infancy and childhoodVesicular rashesVaricella (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 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, whichhas 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 theneonatal period, or from intrauterine exposure due to maternal VZV in pregnancy.

Herpes simplex virus (HSV)While HSV infection is often asymptomatic, the mostcommon 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 immunofluorescence, and affected children usually require intravenous acyclovir.EnterovirusesNon-polio enteroviruses are a common cause ofvesicular rashes, especially in summer and autumn.Hand, foot and mouth disease is caused by differententeroviruses, most commonly Coxsackievirus typeA16. It often occurs in epidemics in daycare centres or schools. It is associated with a papulovesicular eruption on the palms, soles, mucous membranes andsometimes the buttocks. There may be mild associated respiratory or gastrointestinal symptoms, but the clinical course is benign.Enterovirus 71 can cause hand, foot and mouthdisease, 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.ImpetigoImpetigo 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 rashesMany virus infections, especially enteroviruses,produce maculopapular exanthems. These are oftennon-specific and generalized in distribution (Fig.35.3). They can be difficult to differentiate from allergicdrug reactions. Features that favour a viral aetiologyare:_ Occurrence along scratch marks._ Some lesions in straight lines._ Exaggeration in areas of sunburn._ Occurrence under hospital arm bands or on priorskin disease._ Presence of lymphadenopathy.

MeaslesMeasles 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 measlesare:_ 3–5 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 preauriculararea and the face to involve the body._ Tendency of the rash to become confluent on thetrunk and remain discrete lower down._ Tendency of the rash to become brown and thendesquamate after 2–3 days.

RubellaRubella 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 diseaseThis 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 infantumRoseola is a condition that affects infants and youngchildren. Children initially have 3–5 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 infectionA transient macular rash, mimicking an enteroviralrash, can occur early in infection with Neisseria meningitides 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 infectionIn 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 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).

Henoch–Schönlein 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 the brown, before fading over 2–3 days. The lesions occur in crops and may recur at intervals over days to months after the initial episode. Fever is uncommon.

Idiopathic thrombocytopenic purpura (ITP)ITP is an immunologically mediated disease, in which platelet destruction by auto-antibodies leads topetechiae, 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.

LeukaemiaChildren with marrow infiltration by malignant cells, particularly leukaemia, may present with a petechial 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 rashesMolluscum contagiosumMolluscum is a poxvirus infection, which causes multiple, 2–5 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.

Acral papular viral exanthemWhile classically attributed to the exanthem associated with hepatitis B (Gianotti–Crosti 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 popular 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.

Erythema multiforme (EM)EM is characterized by an abrupt eruption of erythematous macules or plaques, usually most prominenton the extensor surfaces of the upper limbs. 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 notinvolved), and 25% of cases involve the oral mucosa alone. The most common infective cause is HSV.

Stevens–Johnson syndromeAn 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. Mucosal ulceration of the mouth and genitalia may occur and is severely painful. There is often significantinternal 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.Generalized erythrodermaStaphylococcal scalded skin syndrome 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 aroundthe mouth, nose and eyes. Perioral erythema is prominent. Owing to skin loss, fluid and electrolyte imbal-involved), and 25% of cases involve the oral mucosa alone. The most common infective cause is HSV.

Drug reactionsCutaneous manifestations are the most common formof adverse drug reaction in children. While classicallydrug reactions are urticarial in nature, almost all morphologicalvariants are possible. Angioedema relatedto drug ingestion is more significant, as it implies anIgE-mediated pathway for the reaction and hence possiblerisk of anaphylaxis on re-exposure.