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EXANTHEMS AND RELATED CONDITIONS

Most exanthems occur in childhood and are followed by immunity. Their morphologic lack of specificity is a problem. Many appear as diffuse maculopapular rashes that may be confused with reactions to antibiotics prescribed on the basis of prodromal features, sore throat, etc. It should also be noted that the morphologic pattern of an exanthem may correlate poorly with the actual cause. Thus a morbilliform rash may result from infection with any of a number of viruses (indeed, bacterial infections such as those due to streptococci may also mimic a morbilliform exanthem); conversely, some viruses, such as measles, can cause several different clinical patterns of exanthem. The main differential diagnoses of any exanthema therefore includes all other exanthems, see Table 25.1.

    Some viral exanthems also occur in adults. This may reflect organisms of lower infectivity or patterns of exposure (e.g. parents may be exposed to viruses via their school age children). Some rashes in adults have an exanthem behavior but an infective cause remains unproved; pityriasis rosea is discussed here on that basis.

Fifth disease (erythema infectiosum)

Etiology and pathogenesis

    Fifth disease is caused by parvovirus B19, a single-stranded DNA virus with a preference for erythroid progenitor cells. The vast majority of patients are children who recuperate without complication. However, rare cases of myocarditis or encephalitis have been reported. In adults, complications of infection by parvovirus B19 include spontaneous abortions in the first trimester for pregnant women, transient aplastic crisis in those with a hemolytic anemia, and arthritis in women.

    Of note, this virus may also cause a rash-free fever or asymptomatic infection in children. It has also been noted to cause idiopathic thrombocytopenic purpura, gloves and socks syndrome (see later), and Henoch–Schönlein purpura.

Clinical

The condition is characterized by bright-red cheeks and a reticulate rash. The facial eruption gives the appearance of slapped cheeks, and is followed by a lace-like erythema on the extremities and buttocks (Fig.25.1). A sore throat, cough, headache, nausea, and fever may accompany the rash.

Differential diagnosis

The diagnosis is clear once the reticulate erythema appears. Prior to that, when only the cheeks are red, a febrile illness with facial flushing may appear similar. It can be proved serologically subsequent to the clinical eruption.

Treatment

This is neither effective nor is it needed. However, contact with pregnant women should be avoided.

Asymmetric periflexural exanthem

Etiology and pathogenesis

Asymmetric periflexural exanthem, also known as unilateral laterothoracic exanthem, causes an exanthem in young children. It represents a reaction pattern to any of several viral infections. Parvovirus B19 has been documented in some cases but not in all. It is most common in the spring. It typically occurs in children aged 1–3 years, with girls affected more often than boys. Only rarely are siblings affected.

Clinical

A scarlatiniform or eczematous eruption unilaterally on the lateral trunk or axilla of a child is characteristic (Fig.25.2). It may also begin in the inguinal folds. The regional lymph nodes may be moderately enlarged. A mild fever may be present. It may spread, for example, to the other side of the thorax, creating a symmetric distribution, or to the elbows, thighs, and knees. The right side seems to be preferred.

Figure 25.1 Erythema infectiosum. In this infection by parvovirus B19, a child will develop prominent erythema of the cheeks, ‘slapped cheeks’ (a), followed by a lace-like erythema on the extremities (b) and buttocks. It is also known asfifth disease.

Differential diagnosis

The truncal rash often appears eczematous, prompting the clinician to consider an allergic or irritant contact dermatitis. The absence of a relevant topical exposure helps exclude this possibility.

Treatment

Clearing occurs spontaneously after 2–4 weeks. Antibiotics and topical steroids are not effective. Simple emolliation may be prescribed.

Measles

Etiology and pathogenesis

Measles is caused by an RNA paramyxovirus. The exanthem it causes is the classic maculopapular rash from which the term morbilliform arose. Currently in the USA, protection is given as measles–mumps–rubella (MMR) vaccine at 12 months of age. Cases in the USA are therefore attributable to unvaccinated children, children with primary vaccine failure, or young children (e.g. age 6–12 months). Those 0–6 months of age usually have maternal antibody protection. There is an approximate 5% failure rate of the vaccine, so sustained school outbreaks may occur in highly immunized areas.

Clinical

After an incubation period of 10–12 days and a prodrome of fever, malaise, coryza, conjunctivitis, and cough, the patient will develop a maculopapular rash, starting behind the ears and along the hairline, and progressing to involve the trunk and extremities by the third day (Figs 25.3 and 25.4). Punctate whitish spots like salt grains on a red base on the buccal mucosa (Koplik spots) are classic, developing in the prodromal period and disappearing by the height of the exanthem.

    A secondary bacterial infection is the most common complication of measles (e.g. pneumonia and otitis media). The three major central nervous system complications are:

Figure 25.2 Asymmetric periflexural exanthem.

Figure 25.3 The rash of measles in an adult who also had measles pneumonia.

Figure 25.4 Measles causes a classic maculopapular or morbilliform eruption.

    Measles often occurs in outbreaks or clusters, so often there is no need to do a confirmatory test. Otherwise, one can culture the virus from the nasopharynx. On day 2, IgM is positive in many, so one can get acute and convalescent titers.

Differential diagnosis

This may include any exanthem (Table 25.1); the rash of rubella is probably the most important differential.

Treatment

The disease will run its course within approximately 2 weeks, and the patient should be treated symptomatically. The patient should be monitored for bacterial infection or other complications. Immunization for prevention is recommended. A study of vitamin A given as two doses of 200000IU separated by 24h significantly decreased morbidity and mortality.

    Serum IgG can be given to exposed individuals, for example a child under 1 year of age or immunocompromised individuals (e.g. those with HIV infection).

PRACTICE POINTS

Roseola

Etiology and pathogenesis

Roseola, also known as exanthem subitum, may be caused by human herpesvirus 6, human herpesvirus 7, and possibly other agents. Of note, human herpesvirus 6 commonly causes acute febrile illnesses in young children without a rash. It has also been reported to cause otitis, upper respiratory infection (URI), afebrile cervical lymphadenopathy, necrotizing lymphadenitis, a mononucleosis-like syndrome, and even Langerhans cell histiocytosis.

Clinical

The infant, aged 6–18 months, will develop a high fever but seem relatively well. Then, as the fever breaks, multiple, pale-pink, 1–5-mm macules and papules appear and last only hours to a few days (Figs 25.5 and 25.6). The trunk and the neck are involved first, followed by the extremities. The face is usually spared. The lesions rarely coalesce and may be missed if there is not a high index of suspicion. In one study, the age range was 3 weeks to 18 months, with 94% of cases occurring in the first year. Ninety-eight percent of patients had a fever, and the rash, which appeared within 24h of resolution of the fever, lasted an average of 4 days. Diarrhea, cervical lymphadenopathy, eyelid edema, and erythematous papules on the soft palate and uvula were also common. Seizures occurred in approximately 7% of the cases during the high fever. Isolated cases are more common than epidemics. The incubation period is variable but is usually between 5 and 15 days. Rare complications include encephalitis and thrombocytopenic purpura.

Differential diagnosis

This may include any exanthem (Table 25.1).

Treatment

Usually, no treatment is needed. Recurrences may occasionally occur, caused by infection from a second agent causing a similar morphology of exanthem.

Rubella

Etiology and pathogenesis

Rubella is caused by an RNA togavirus. Maternal infection during pregnancy can be devastating to the fetus (congenital rubella syndrome). Vaccination with a live attenuated rubella virus is performed in many countries (e.g. as MMR vaccine).

Clinical

The exanthem of rubella begins on the face and spreads downward over 1–3 days (Fig.25.7). It fades as it spreads, and may result in a delicate desquamation. A prodrome of cervical and suboccipital adenopathy is most common in adolescents and adults. An arthritis, most commonly of the fingers and wrists, affects girls and women more commonly. High fever and malaise may accompany the exanthem. Encephalitis and thrombocytopenic purpura are rare complications.

Figure 25.5 Roseola. The infant 6–18 months of age will develop a high fever but seem relatively well.

Figure 25.6 Roseola. As the fever breaks, multiple, pale-pink, 1–5-mm macules and papules appear and last only hours to a few days.

Differential diagnosis

This may include any exanthem (Table 25.1).

Treatment

The disease will run its course without treatment. The arthritis may be helped by non-steroidal antiinflammatory drugs.

Other generalized viral exanthems

A viral exanthem appears as a nondescript maculopapular eruption and may result from infection by several common viruses (Figs 25.8 and 25.9), including echovirus, coxsackievirus, and adenovirus. Constitutional symptoms (e.g. fever, nausea, vomiting, and diarrhea) or a family member who is also sick may suggest the diagnosis. If there is any suggestion of the presence of a sore throat, a bacterial throat culture should be done. Children are typically affected, but adults may be affected as well. Only supportive treatment is needed.

Gianotti–Crosti syndrome

Gianotti–Crosti syndrome (GCS) describes a papular eruption in young children and is a manifestation of one of several viral infections. The child, aged 6 months to 12 years, experiences the acute onset of red macules and papules on the face, extremities, and buttocks, with sparing of the trunk (Figs 25.10 and 25.11). It was first described in association with hepatitis B (ayw variant), but it has since been seen with varicella, coxsackievirus, and Epstein–Barr virus (EBV) infections. Several studies suggest that EBV is currently the most common cause. A hemorrhagic variant occurs in which the lesions fill with blood, being turned bright red. The distinction between GCS and papulovesicular acrolated syndrome is not possible, and these diseases should be considered the same. The isomorphic phenomenon, whereby lesions occur at areas of injury to the skin, is not uncommon.

    The differential diagnosis is that of an acral red rash in a child, and includes the gloves and socks syndrome, acute hemorrhagic edema of infancy, and eruptive pseudoangiomatosis (all discussed later).

Figure 25.7 Rubella. The rash may be very mild in rubella; when present, it is similar to measles, with maculopapular erythema starting on the face and spreading to the trunk. The spots are 1–2 mm in diameter and slightly raised. In rubella, there is also enlargement of the cervical and occipital lymph nodes.

Figure 25.8 (a) Viral exanthem in a child. (b) Close-up view.

Figure 25.9 Viral exanthem sparing areas under pressure.

Figure 25.10 Gianotti–Crosti syndrome. The patient acutely develops hundreds of red macules and papules on the face, extremities, and buttocks, with sparing of the trunk.

    The rash resolves within 1–2 months without sequelae. No specific treatment is needed for the rash. Consideration should always be given to what virus has triggered this condition. Liver function tests (LFTs) may be performed in appropriate cases.

Eruptive pseudoangiomatosis

This acute and self-limiting eruption may be infectious in nature, as outbreaks in a small group living together have been described. Both adults and children may be affected. Viral studies have failed to reveal a cause.

    The characteristic eruption is acute, symmetric, multiple red papules, often with a surrounding white halo. The extremities, including the hands and feet, are typically affected, but truncal and facial lesions have been observed. Children may present with a prodrome of malaise, fever, headache, vomiting, diarrhea, and URI.

The condition in children often resolves over several days, whereas in adults it typically lasts a week or two, but occasionally up to a month.

Figure 25.11 Gianotti–Crosti syndrome. Clustered discrete papular lesions on the legs.

Figure 25.12 Acute hemorrhagic edema of infancy. Facial purpuric lesions are common.

Acute hemorrhagic edema of infancy

Acute hemorrhagic edema of infancy, also known as Finkelstein disease and Seidlmayer syndrome, is considered the infantile variant of Henoch–
Schönlein purpura. Indeed, a spectrum seems to exist, with edema and facial purpura more typical of younger patients, and gastrointestinal tract, renal, and joint symptoms increasing with age. Facial purpuric lesions are common in the infant (Fig.25.12), perhaps because standing and gravitational factors are not as much a factor in localization. The disease often follows a URI, intake of a drug, or vaccination. Biopsy is not necessarily indicated, but if performed will show leukocytoclastic vasculitis.

    There is rarely internal involvement, and the general lack of systemic symptoms contrasts with the appearance of the rash. Symmetric purpuric targetoid lesions on the face and extremities in an infant 5–24 months of age are characteristic of this condition. Occasionally, truncal or mucosal lesions may be seen. Neither systemic steroids nor antihistamines improve the cutaneous lesions, and the condition resolves spontaneously.

PRACTICE POINTS

Gloves and socks syndrome

Gloves and socks syndrome is an unusual exanthem that is usually caused by parvovirus B19. This rash seems to be a viral exanthem, associated most commonly with parvovirus B19 but also with other viruses, for example measles, human herpesvirus 6 (usually causes exanthem subitum), or coxsackievirus. One study in children showed the majority of cases to be caused by cytomegalovirus (CMV) or EBV.

    Confluent erythema of the palms and soles that stops at the wrists and ankle is characteristic of gloves and socks syndrome (Fig.25.13). Significant purpura often occurs. Lymphadenopathy, leukopenia, fever, and oral erythema or erosion may occur. The diagnosis of the rash can be made clinically, but to determine the causative virus, serologic studies must be done. Most patients have IgM antibodies to parvovirus B19. Symptomatic therapy is appropriate. The rash remits spontaneously.

Pityriasis rosea

Etiology and pathogenesis

This papulosquamous eruption is of unproven causation. There is some evidence suggesting that there may be a viral etiology, including:

Figure 25.13 (a,b) Gloves and socks syndrome. Note the bright erythema of the palms and the sharp demarcation at the wrist.

Herpesviruses, especially human herpesvirus 7, have been suggested as a cause in several studies but refuted by others; available evidence does not support a role for CMV, EBV, parvovirus B19 Legionella spp., Mycoplasma spp., or Chlamydia .

Clinical

The characteristic aspect of pityriasis rosea is the appearance of a solitary lesion 2–4 days before the main exanthem (Fig.25.14). This initial ‘herald patch' tends to be bigger than the subsequent lesions. The main rash is predominantly truncal, and consists of small, oval lesions aligned along a dermatomal pattern that might resemble a fir tree. Occasionally, it extends down the limbs, on to the scalp, or is quite purpuric; all these atypical presentations can give rise to diagnostic uncertainty.

Differential diagnosis

Other viral exanthems, drug eruptions, guttate psoriasis, and secondary syphilis are in the differential diagnosis.

Treatment

It usually causes few symptoms, but a topical corticosteroid speeds up the resolution. Erythromycin appears to be useful, although whether this is due to its antibacterial or its antiinflammatory action is unclear.

Figure 25.14 (a) Pityriasis rosea often shows a papulosquamous morphology. (b) A typical oval lesion. Note the typical peripheral collateral scaling. (c) ‘Herald patch’ on the arm, with subtle smaller spots on the trunk. (d) Herald patch. (e) Pityriasis rosea in the axilla. Note the darker color in this dark-skinned patient. (f) Pityriasis rosea in the groin. The condition prefers sun-protected areas. (g) Thefir tree pattern of oval lesions along dermatomal lines.

White/Cox: Diseases of the Skin, 2ed.(c) 2006, Elsevier Inc. All rights reserved.