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Atypical exanthems in children
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Atypical exanthems in children
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Nov 2016. | This topic last updated: Aug 01, 2016.

INTRODUCTION — An "atypical exanthem" is an acute skin eruption that differs in appearance from classically described viral rashes such as measles, rubella, or erythema infectiosum. They are usually preceded or associated with nonspecific systemic symptoms, including low-grade fever, malaise, or upper respiratory or gastrointestinal tract infection.

Atypical exanthems are a common cause of pediatric urgent care visits. The most frequent cause is a viral infection, followed by drug reactions, and bacterial infections [1,2].

This section will review three uncommon diseases that present with an atypical rash: unilateral laterothoracic exanthem; coxsackievirus A6 hand, foot, and mouth syndrome; and papular-purpuric gloves and socks syndrome. Gianotti-Crosti syndrome, a papular eruption of childhood with acral distribution associated with viral infections is discussed separately [3]. (See "Gianotti-Crosti syndrome (papular acrodermatitis)".)

UNILATERAL LATEROTHORACIC EXANTHEM — Unilateral laterothoracic exanthem (ULE), also known as asymmetric periflexural exanthem of childhood, is a distinctive skin eruption that usually begins on one side of the trunk and then generalizes [4]. It typically affects children between one and five years of age, but has been also reported in adults [5-8].

ULE occurs year round, with a peak during spring. The cause is unknown. Indirect evidence, such as patients' age, occurrence of small epidemics, seasonal distribution, association with upper respiratory tract infections, and spontaneous resolution, suggests a viral etiology. However, microbiologic studies on throat, stool, blood, and skin samples from affected children have not identified a specific etiologic agent [9-11].

Clinical manifestations — The skin eruption typically begins on one side of the trunk and extends toward the axilla; less often, it starts in the inguinal crease or on an extremity (picture 1). The eruption is usually preceded by an episode of low-grade fever, upper respiratory tract infection, or gastroenteritis [10]. The eruption spreads centrifugally and may become bilateral, although unilateral predominance is maintained.

Early lesions may have a morbilliform appearance, sometimes with a surrounding pale halo. Over time, lesions tend to become more scaly or eczematous and occasionally develop a central dusky or gray color. Most patients experience pruritus, but it is usually mild. The eruption typically remits in two to five weeks with fine desquamation [5].

Diagnosis and differential diagnosis — The diagnosis of ULE is clinical. Laboratory tests are not indicated. A skin biopsy is not necessary for the diagnosis. If performed, it shows a mild-to-moderate mononuclear interface dermatitis, with some necrotic keratinocytes, and a dermal lymphocytic infiltrate more pronounced around the sweat glands [10].

The differential diagnosis of ULE includes tinea corporis, allergic contact dermatitis, atopic dermatitis, psoriasis, and other viral exanthems such as pityriasis rosea. (See "Dermatophyte (tinea) infections", section on 'Tinea corporis' and "Pityriasis rosea" and "Contact dermatitis in children" and "Guttate psoriasis" and "Pathogenesis, clinical manifestations, and diagnosis of atopic dermatitis (eczema)".)

Treatment — Treatment is symptomatic and includes bland emollients and antihistamines to control pruritus. Topical steroids are not helpful.

ERUPTIVE PSEUDOANGIOMATOSIS — Eruptive pseudoangiomatosis is a rare, asymptomatic exanthematous eruption characterized by the rapid appearance of small, angioma-like erythematous papules [12-14]. It affects predominantly young children, but has been reported also in adults [15-17]. The cause of eruptive pseudoangiomatosis is unknown. There are isolated reports of eruptive pseudoangiomatosis associated with viral infections (eg, echovirus 25 or 32, cytomegalovirus, Epstein-Barr virus, coxsackie B virus), or insect bites [18-22].

Clinical manifestations — Patients typically present with the acute eruption of numerous bright-red erythematous and telangiectatic papules 1.5 to 5 mm in diameter that blanch with pressure, disseminated mainly on the face and trunk (picture 2). Systemic symptoms, including fever, diarrhea, or upper respiratory symptom are often present in children. Lesions persist for 2 to 15 days and then resolve spontaneously without sequelae.

Diagnosis — The diagnosis of eruptive pseudoangiomatosis is based upon the clinical presentation. If performed, a skin biopsy examination reveals a perivascular lymphocytic infiltrate in the papillary dermis and dilated blood vessels with swollen, hobnail-shaped endothelial cells [12,23].

Treatment — No treatment is necessary. Lesions usually resolve spontaneously in one to two weeks.

COXSACKIEVIRUS A6 HAND, FOOT, AND MOUTH DISEASE — Hand, foot, and mouth disease (HFMD) is a common enteroviral illness typically affecting children younger than five years during the late summer and fall months. HFMD is usually caused by coxsackievirus A16 and typically presents with fever, deep-seated, small oval vesicles on the palms and soles, and painful vesicles and erosions on the buccal mucosa and tongue (picture 3A-D). (See "Clinical manifestations and diagnosis of enterovirus and parechovirus infections", section on 'Hand, foot, and mouth syndrome' and "Hand, foot, and mouth disease and herpangina: An overview", section on 'Hand, foot, and mouth disease'.)

Outbreaks of HFMD caused by coxsackievirus A6 and characterized by an atypical presentation have been reported in Asia and in Europe since 2008 and in the United States since 2011 [24-27]. Coxsackievirus A6 HFMD has been reported also in young adults [28]. In 2015, an outbreak of 53 cases of HFMD caused by coxsackievirus A6 was reported among basic military trainees in Texas [29].

HFMD is transmitted person-to-person via oral or respiratory route following contact with vesicle fluid, respiratory secretions, and feces, and initial viral replication takes place in the pharynx and intestine. Subsequent amplification within lymphoid tissue produces a viremia with distant multiorgan spread, including the skin. Hand washing and routine disinfection of surfaces help preventing spreading.

Clinical manifestations — Patients with coxsackievirus A6 HFMD present with fever and systemic symptoms as in typical HFMD, but usually have a more severe cutaneous involvement. Vesiculobullous lesions may involve the dorsum of hands and feet, calves, forearms, trunk, and neck (picture 4A-B) [25,30,31]. The involvement of the perioral area may be a clinical marker of A6 HFMD [31].

In children with atopic dermatitis, lesions tend to concentrate in areas previously or currently affected by the dermatitis, similar to eczema herpeticum ("eczema coxsackium") (picture 5) [30]. In young adults, the disease may present with erythematous papulovesicular lesions on the face, oral mucosa, extensor surfaces of the upper and lower extremities, and palms and soles; confluent, hemorrhagic and crusted lesions can also be seen on the extremities (picture 6) [29].

The course of the acute illness and the benign outcome are similar in classic and atypical HFMD. Systemic symptoms usually subside in a few days; the skin lesions resolve without scarring in days to weeks.

Onychomadesis (separation of the proximal nail plate from the nail matrix and nail bed) due to arrest of nail matrix growth is frequent and most often occurs three to eight weeks after the disease onset. It is usually asymptomatic, and the nails regrow normally within several months. (See "Overview of nail disorders", section on 'Transverse grooves (Beau lines and onychomadesis)'.)

Diagnosis and differential diagnosis — The diagnosis of coxsackie A6 HFMD is based upon the clinical presentation and detection of the virus in the blister fluid by polymerase chain reaction (PCR). Although PCR can detect enteroviruses with a sensitivity of approximately 90 percent, it does not allow the serotype identification. Coxsackievirus A6 nucleotide sequencing can be performed on PCR positive specimens to confirm the diagnosis [30]. (See "Clinical manifestations and diagnosis of enterovirus and parechovirus infections".)

A skin biopsy is usually not necessary. If performed, it reveals a spongiotic dermatitis with focal areas of interface dermatitis and subepidermal separation, edema of the papillary dermis, and a mixed dermal inflammatory infiltrate [30].

The differential diagnosis of atypical HFMD includes varicella zoster virus infection (picture 7A-C), eczema herpeticum (picture 8A-B), and bullous impetigo (picture 9A-B). Maintaining coxsackievirus A6 HFMD in the differential diagnosis of patients thought to have eczema herpeticum may prevent inappropriate antiviral treatment and concern for herpes simplex virus-associated morbidity. (See "Diagnosis of varicella-zoster virus infection" and "Clinical manifestations and diagnosis of herpes simplex virus type 1 infection", section on 'Eczema herpeticum' and "Impetigo", section on 'Bullous impetigo'.)

Treatment and prognosis — Treatment of coxsackievirus A6 HFMD is supportive. Affected children are expected to recover fully without permanent scarring. In children with darker skin types, there is frequently extensive postinflammatory pigmentation that can last months to years but ultimately resolves.

PAPULAR-PURPURIC GLOVES AND SOCKS SYNDROME — Papular-purpuric gloves and socks syndrome (PPGSS) is a distinctive manifestation of parvovirus B19 infection, usually seen in adolescents and adults [32,33]. A juvenile variant that occurs in children has also been described [34].

As the name implies, there is a striking acral distribution of the rash, in contrast to the "slapped cheek" appearance of erythema infectiosum, the better recognized manifestation of parvovirus B19 infection in young children. (See "Clinical manifestations and diagnosis of parvovirus B19 infection", section on 'Erythema infectiosum'.)

PPGSS usually occurs in the spring and summer and has occasionally been linked with etiologic agents other than B19 [35,36]. Transmission occurs through respiratory secretions and saliva. Infected patients are most contagious during the phase of active viral replication, which usually precedes the appearance of skin lesions. (See "Microbiology, epidemiology, and pathogenesis of parvovirus B19 infection".)

Clinical manifestations — PPGSS is often preceded by prodromal symptoms including low-grade fever, myalgias, arthralgias, and fatigue. The rash is rapidly progressive, with edema and redness of hands and feet followed by the appearance of petechial and/or purpuric lesions on the palms and soles (picture 10A); the dorsal surfaces may also be involved (picture 10B). There is often a sharp cutoff at the wrists or ankles, although elbows and knees may also be involved. Neurologic symptoms are sometimes associated; lymphadenopathy is common.

Routine laboratory tests are usually normal. Some patients may have lymphopenia, neutropenia, or thrombocytopenia.

Complications of parvovirus B19 infection include transient aplastic crisis (especially in pregnancy or HIV infection), hepatitis, arthritis, and cardiomyopathy. Parvovirus-B19 infection is also associated with miscarriages and hydrops fetalis. (See "Clinical manifestations and diagnosis of parvovirus B19 infection" and "Parvovirus B19 infection during pregnancy".)

Diagnosis and differential diagnosis — The diagnosis of PPGSS is usually clinical. In immunocompetent patients, the detection of specific IgM antibodies in serum samples by enzyme immunoassays can confirm the diagnosis. Detectable levels of B19-specific IgM can be found within 7 to 10 days of virus exposure and remain measurable for several months.

Nucleic acid amplification testing is considered the most sensitive test to detect the virus in serum or tissues and is now available in many clinical laboratories. It is especially useful for the diagnosis of parvovirus B19 infection in immunocompromised patients. (See "Microbiology, epidemiology, and pathogenesis of parvovirus B19 infection".)

A skin biopsy is not helpful for the diagnosis of PPGSS. Histopathologic findings are nonspecific and include a mild lymphohistiocytic perivascular inflammatory infiltrate, degeneration of basal layer, and red blood cell extravasation.

The differential diagnosis of PPGSS includes meningococcemia (picture 11), Rocky Mountain spotted fever (picture 12), Henoch-Schönlein purpura (picture 13), perniosis, and other petechial viral exanthems (eg, echovirus, parechovirus). (See "Clinical manifestations of meningococcal infection" and "Clinical manifestations and diagnosis of Rocky Mountain spotted fever" and "Henoch-Schönlein purpura (immunoglobulin A vasculitis): Clinical manifestations and diagnosis".)

Treatment and prognosis — Treatment is symptomatic. Spontaneous resolution occurs in several weeks without sequelae.

SUMMARY AND RECOMMENDATIONS

Atypical viral exanthems are skin eruptions that differ in appearance from classically described viral rashes (eg, measles, rubella) and a common cause of pediatric urgent care visits. They are usually preceded or associated with nonspecific systemic symptoms, including low-grade fever, malaise, or upper respiratory or gastrointestinal tract infection. (See 'Introduction' above.)

Unilateral laterothoracic exanthem is a skin eruption of unknown etiology that typically begins on one side of the trunk and then generalizes (picture 1). The diagnosis is clinical. Spontaneous resolution occurs in several weeks without scarring. (See 'Unilateral laterothoracic exanthem' above.)

Outbreaks of atypical hand, foot, and mouth disease (HFMD) caused by coxsackievirus A6 in children and young adults have been reported in Asia and in Europe since 2008 and in the United States since 2011. In contrast with classic HFMD caused by coxsackievirus A16, skin involvement is more extensive and severe (picture 4A). The diagnosis may be confirmed by Coxsackievirus A6 nucleotide sequencing in blister fluid. Treatment is supportive; spontaneous resolution occurs in days to weeks. (See 'Coxsackievirus A6 hand, foot, and mouth disease' above and "Clinical manifestations and diagnosis of enterovirus and parechovirus infections", section on 'Hand, foot, and mouth syndrome' and "Hand, foot, and mouth disease and herpangina: An overview", section on 'Hand, foot, and mouth disease'.)

Papular-purpuric gloves and socks syndrome (PPGSS) is a distinctive manifestation of parvovirus B19 infection, usually seen in adolescents and adults. It presents with edema and redness of hands and feet, followed by the appearance of petechial and/or purpuric lesions on the palms and soles (picture 10A-B). The diagnosis may be confirmed by the detection of specific IgM antibodies in serum samples. Spontaneous resolution occurs in several weeks. (See 'Papular-purpuric gloves and socks syndrome' above.)

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