Other Viral Diseases

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Other Viral Diseases

Viral infections frequently have cutaneous manifestations, especially in children. This chapter covers classic childhood exanthems, poxvirus infections, and several other viral infections with characteristic skin findings. Nonspecific viral exanthems, typically presenting with blanchable erythematous macules and papules in a widespread distribution, are also common in children infected with enteroviruses (see below) and a variety of respiratory viruses, generally resolving spontaneously within a week. Fig. 68.1 outlines clinical features to consider when evaluating a patient with a morbilliform (‘maculopapular’) exanthem, and Chapter 3 addresses considerations in patients with fever and a rash. HIV, human papillomavirus, and herpesvirus (including infectious mononucleosis and roseola infantum) infections are discussed in Chapters 65–67.

Fig. 68.1 Approach to the patient with a presumed morbilliform or macular/papular viral exanthem. *Gram-positive rod; may result in severe pharyngitis and scarlatiniform exanthem in adolescents and young adults. ^†Intracellular inclusions in endothelial cells are another finding. **Usually febrile seizures.

Enterovirus Infections

• Non-polio enteroviruses (e.g. coxsackieviruses, echoviruses) are single-stranded RNA picornaviruses with a worldwide distribution; they cause a variety of exanthems, enanthems, and systemic manifestations.

• Spread via fecal–oral (e.g. swimming pools, ingestion of oysters) and respiratory routes, with an incubation period of 3–6 days; most common in the summer and fall in temperate climates, favoring young children.

• Hand, foot, and, mouth disease (HFMD; in the United States, coxsackievirus A16 > others) features oval vesicles on the hands and feet (palms/soles > dorsally) and buttocks plus an erosive stomatitis (e.g. tongue, buccal mucosa, palate, tonsils), often associated with fever and malaise (Fig. 68.2A–D); onychomadesis occasionally occurs 1–2 months later.

Fig. 68.2 Hand, foot, and mouth disease (HFMD). A Oval vesicle and erythematous macules on the plantar surface. B Multiple erythematous macules on the palm, some with a dusky appearance reminiscent of erythema multiforme. C Small oval erosions on the buccal mucosa resembling aphthae. D Discrete erythematous papules and crusted erosions in an area of previous diaper dermatitis. The differential diagnosis in this patient with coxsackievirus A6 infection might include eczema herpeticum. E Extensive vesicles and crusts in the perioral area in a patient with HFMD due to coxsackievirus A6. Herpes simplex virus infection or impetigo may be considered in the differential diagnosis for lesions in this location. Note koebnerization to the site of a healing laceration on the chin. A, B, D, E, Courtesy, Julie V. Schaffer, MD; C, Courtesy, Kalman Watsky, MD.

• Recently, coxsackievirus A6 infection has been associated with a more widespread vesiculobullous exanthem favoring the perioral area, extremities > trunk, and areas of previous dermatitis (‘eczema coxsackium’) or injury as well as the classic sites of HFMD (Fig. 68.2B, D, E; see Fig. 3.5B, C).

• Herpangina presents with fever and oropharyngeal erosions, but usually no exanthem.

• The diverse spectrum of enteroviral exanthems also includes morbilliform, scarlatiniform, Gianotti–Crosti syndrome-like, petechial, and pustular eruptions (see Fig. 3.5A); eruptive pseudoangiomatosis is an uncommon manifestation.

• Organ systems that can be affected by enteroviral infections include the respiratory (upper > lower) and gastrointestinal tracts, liver, CNS (meningitis > encephalitis; especially with enterovirus 71), eyes (hemorrhagic conjunctivitis), joints, muscles, and heart.

• Spontaneous resolution typically occurs within 1–2 weeks.

Measles (Rubeola)

• Incidence has decreased dramatically since introduction of a live vaccine for this single-stranded RNA paramyxovirus in 1963; however, measles outbreaks still occur in both low- and high-income countries, often because of unfounded fears of vaccination.

• Highly contagious and spread by respiratory droplets, with an incubation period of 10–14 days.

• Prodrome of fever, cough, coryza, and conjunctivitis (the 3 C’s), followed in 2–4 days by the appearance of pathognomonic Koplik spots (gray-white papules on the buccal mucosa).

• An exanthem develops 3–5 days after the onset of symptoms, with erythematous macules and papules spreading cephalocaudally from the forehead, hairline, and behind the ears to the trunk and extremities (Fig. 68.3); after 5 days, the eruption fades in the order it appeared.

Fig. 68.3 Measles. Pink macules and minimally elevated papules. Courtesy, Louis Fragola, MD.

• Complications include otitis media, pneumonia, and encephalitis; subacute sclerosing panencephalitis occasionally develops 5–10 years later.

• Atypical measles in the setting of partial immunity features high fevers, cough, and a variable exanthem that may be vesicular, petechial, or associated with acral edema.

• Rx: vitamin A administration for children with acute disease; prevention via vaccination.

Rubella (German Measles)

• Incidence has markedly declined since introduction of a live vaccine for this single-stranded RNA togavirus in 1969.

• Spread via respiratory droplets, with an incubation period of 16–18 days.

• Mild prodrome of fever, headache, and upper respiratory symptoms, followed in 1–5 days by an eruption of erythematous macules and papules that spreads downward from the face and lasts ~3 days; Forchheimer’s spots (red or petechial macules on the soft palate) and tender lymphadenopathy (especially occipital and posterior auricular) are characteristic findings.

• Although usually self-limited, complications include arthralgias/arthritis (especially in adolescent girls and women), thrombocytopenia, and encephalitis.

• Congenital rubella syndrome, most common with maternal infection in the first 16 weeks of pregnancy; can result in cataracts, deafness, congenital heart defects, and microcephaly; a ‘blueberry muffin baby’ presentation occasionally occurs (see Fig. 67.15).

Parvovirus B19 Infection (Erythema Infectiosum, Fifth Disease, ‘Slapped Cheek Disease’)

• Single-stranded DNA virus with tropism for erythroid progenitor cells; found worldwide.

• Transmitted via respiratory secretions and blood products as well as vertically from mother to fetus, with an incubation period of 4–14 days; peak incidence in the winter and spring, favoring children 4–10 years of age.

• A mild prodrome (e.g. low-grade fever, myalgias, headache) is followed in 7–10 days by bright red, macular erythema on the cheeks; a few days later, a lacy, reticulated pattern of erythematous macules and papules may appear on the extremities > trunk, lasting 1–3 weeks and fluctuating in intensity (with flares upon sun exposure and overheating) (Fig. 68.4).

Fig. 68.4 Erythema infectiosum. Bright macular erythema on the cheeks, with characteristic sparing of periorificial areas (A). Lacy, reticulated erythematous eruption on the thigh (B) and arms (C) during the second stage of the exanthem. A, Courtesy, Louis Fragola, MD; B, Courtesy, Julie V. Schaffer, MD; C, Courtesy, Kalman Watsky, MD.

• Papular–purpuric gloves and socks syndrome (parvovirus B19 > other viruses) features painful acral edema, erythema, and petechiae/purpura (especially on the palms and soles; Fig. 68.5).

Fig. 68.5 Papular–purpuric gloves and socks syndrome. Erythematous patches with petechiae on the plantar surface. Courtesy, Anthony Mancini, MD.

• More widespread petechial eruptions and an enanthem (petechiae, erosions) can also occur.

• Complications include arthritis/arthralgias favoring small joints of the hands (especially in young adults) and aplastic anemia > pancytopenia in susceptible individuals (e.g. with red blood cell disorders or immunosuppression).

• Fetal parvovirus B19 infection may lead to self-limited anemia, hydrops fetalis (extensive edema), or miscarriage/stillbirth (2–6%, especially if in first half of pregnancy).

• Rx: NSAIDs for arthropathy, RBC transfusions for severe aplastic crises, serial fetal ultrasonography for infections during the first two trimesters of pregnancy.

Unilateral Laterothoracic Exanthem (Asymmetric Periflexural Exanthem of Childhood)

• A consistent causative infectious agent has not been identified.

• Most often occurs in the spring and favors preschool-aged children.

• Morbilliform or eczematous eruption that begins unilaterally (axilla > trunk or thigh) and then spreads to contralateral sites (Fig. 68.6).

Fig. 68.6 Unilateral laterothoracic exanthem. Erythematous macules and papules involving the left axilla and upper flank (A) and a slightly more extensive distribution on the left lateral trunk (B).

• Often pruritic and may be preceded by upper respiratory or gastrointestinal symptoms.

• DDx: allergic contact dermatitis, eczematous reaction to molluscum contagiosium, pityriasis rosea, scabies; eruptions with a more widespread distribution may overlap with Gianotti–Crosti syndrome.

• Resolves spontaneously, usually within 3–8 weeks.

• Rx: topical CS are often of limited benefit.

Gianotti–Crosti Syndrome (Papular Acrodermatitis of Childhood)

• Associated with a variety of infectious triggers, most often Epstein–Barr virus, hepatitis B virus (outside the United States), and vaccines.

• Most common in the spring and early summer, favoring young children.

• Often preceded by a low-grade fever and/or upper respiratory symptoms.

• Rapid onset of monomorphic, skin-colored to pink-red, edematous papules > papulovesicles in a symmetric distribution on the extensor surfaces of the extremities, buttocks, and face (Fig. 68.7); pruritus, purpuric lesions, and extension to the trunk occasionally occur.

Fig. 68.7 Gianotti–Crosti syndrome. A Monomorphic erythematous papules on the thigh. B A more exuberant eruption of multiple edematous, erythematous papules on the thighs and knees. B, Courtesy, Anthony Mancini, MD.

• DDx: inflammatory response to molluscum contagiosum, id reaction (e.g. due to allergic contact dermatitis to nickel), papular urticaria, another viral exanthem (e.g. coxsackievirus A6), drug eruption, scabies.

• Resolves spontaneously, usually within 3–8 weeks (longer than a classic viral exanthem); laboratory evaluation for specific viral agents can be performed if indicated by clinical findings and geographic region.

• Rx: topical CS are often of limited benefit.

Molluscum Contagiosum (MC)

• Common cutaneous infection caused by a poxvirus.

• Spread by skin-to-skin contact > fomites (e.g. towels), favoring young children but also occurring via sexual contact in adults; larger and more numerous lesions may be seen in immunocompromised hosts, especially those with HIV infection.

• Firm, skin-colored to pink papules or papulonodules with a waxy surface and central umbilication; predilection for the skin folds (e.g. axillae, neck, groin), lateral trunk, thighs, buttocks, genitals, and face (Fig. 68.8).

Fig. 68.8 Molluscum contagiosum. Multiple pearly, umbilicated papules in the genital area (A) and on the face (B); note the inflamed lesion on the right cheek. Inflammatory reactions are a sign of the host immune response to the virus. C Inflamed lesions surrounded by ‘molluscum dermatitis.’ D Furuncle-like presentation of an inflamed molluscum. A culture revealed only normal skin flora. E Monomorphic eruption of pruritic pink papules with crusting on the elbow. These reactive lesions were also present on knees of this child with molluscum contagiosum on the trunk. A, C, Courtesy, Anthony Mancini, MD; B, D, E, Courtesy, Julie V. Schaffer, MD.

• Inflammatory reactions frequently occur, including eczematous dermatitis (diffuse or nummular) in the skin surrounding MC lesions, furuncle-like inflammation of individual MC lesions, and a Gianotti–Crosti syndrome-like eruption of pruritic erythematous papules favoring the elbows and knees (see Fig. 68.8B–E).

• DDx (in addition to above): multiple lesions – verrucae, condyloma acuminata, papular eczema; solitary to few lesions – juvenile xanthogranuloma or Spitz nevus in a child, BCC in an adult; in immunocompromised hosts – cryptococcosis, histoplasmosis, other dimorphic fungal infections.

• Microscopic evaluation following curettage of lesional contents or biopsy shows large, round intracytoplasmic inclusion bodies (see Chapter 2); dermoscopy can identify a characteristic yellow-white, lobular central structure surrounded by a ‘crown’ of blood vessels.

• Resolves spontaneously over months to several years in immunocompetent children, with larger numbers of lesions often developing in those with atopic dermatitis.

• Rx: options are listed in Table 68.1.

Other Poxvirus Infections

• The most historically significant poxvirus infection was smallpox, which has been responsible for millions of human deaths; the world was declared free of smallpox in 1980, although two reference collections remain (in the United States and Russia) and it is feared that smallpox could be exploited for bioterrorism.

• The clinical manifestations of smallpox and varicella are compared in Table 68.2, and selected poxvirus infections and complications of smallpox vaccination are presented in Figs. 68.9, 68.10 and Table 68.3.

Table 68.2

Comparison of varicella/disseminated zoster to smallpox.

	Varicella/Disseminated Zoster	Smallpox
Prodrome	None or mild fever and malaise	Fever ≥101°F/38.3°C for 1–4 days prior to rash onset, plus malaise, headache, backache and/or abdominal pain
Distribution of lesions	Initially on face/scalp; trunk > distal extremities May have an enanthem	Concentrated on face and limbs; can progress to involve entire body surface Oropharyngeal lesions often precede cutaneous eruption
Stage of lesions	Different stages occur simultaneously in any one area of the skin (nonsynchronous)	Adjacent lesions are all at same stage of development (synchronous)
Types of lesions	Superficial papules, vesicles, and pustules	Papulovesicles → firm, deep-seated pustules with a tendency to confluence
Course	Lesions appear in crops over a 3-day period	Lesions spread over 1–2 weeks Crusting develops over 1 week
Scarring	Rare in uncomplicated cases	Common and marked

Fig. 68.9 Smallpox vaccine. A Crusted papule at the site of vaccination, 14 days following administration. B Eczema vaccinatum in a patient with atopic dermatitis. Spread from the vaccination site (arrow) to areas of eczema. C Erythema multiforme-like reaction associated with marked erythema and edema at the vaccination site. B, C, Courtesy, Louis Fragola, MD.

Fig. 68.10 Orf. Vesiculopustule and ulceration on the finger. Courtesy, Anthony Mancini, MD.

Table 68.3

Selected poxvirus infections.

Real-time PCR is currently the diagnostic method of choice. Other poxviruses that occasionally lead to skin lesions (single or few) in humans include deer-associated parapoxvirus (eastern United States; reported in deer hunters) and tanapox (equatorial Africa; endemic in nonhuman primates, likely arthropod vector).