Residency · Residency · Dermatology

Viral Exanthems and Herpesvirus Infections

Overview

Viral infections of the skin produce a diverse range of presentations, from localized vesicular eruptions (herpes simplex, varicella-zoster) to diffuse exanthems. The herpesviridae family is particularly important in dermatology, causing recurrent, latent infections with significant morbidity. Eczema herpeticum represents a true dermatologic emergency requiring urgent recognition and treatment.

Herpes Simplex Virus (HSV)

Virology and Pathogenesis

HSV-1 and HSV-2 are double-stranded DNA viruses belonging to the alpha-herpesvirinae subfamily. Primary infection occurs through mucosal surfaces or skin breaks, after which the virus undergoes retrograde axonal transport to sensory ganglia (trigeminal for HSV-1 and sacral dorsal root ganglia for HSV-2), where it establishes lifelong latency in neuronal cell bodies. Reactivation is triggered by UV exposure, fever, stress, immunosuppression, trauma, or menses. Viral shedding can occur asymptomatically.

Clinical Presentations

Primary Herpes Gingivostomatitis (HSV-1)

This is the most common primary HSV-1 manifestation in children, presenting with fever, malaise, cervical lymphadenopathy, and painful vesicles and erosions on the gingiva, tongue, palate, lips, and perioral skin. It is self-limited, resolving in 10 to 14 days. The differential includes herpangina (coxsackievirus, affecting the posterior pharynx), hand-foot-mouth disease, and aphthous stomatitis.

Herpes Labialis ("Cold Sores")

Recurrent HSV-1 on the vermilion border of the lips typically begins with a prodrome of tingling and burning before vesicle eruption. Grouped vesicles on an erythematous base crust and heal in 7 to 10 days. Triggers include sun exposure, illness, and stress. Treatment includes topical acyclovir or penciclovir at the prodrome and oral valacyclovir for frequent recurrences.

Genital Herpes

HSV-2 causes the majority of genital herpes, though HSV-1 accounts for an increasing proportion, especially in young adults. The primary episode presents with multiple painful vesicles and ulcers on the genitalia, bilateral inguinal lymphadenopathy, dysuria, and systemic symptoms. Recurrences involve fewer lesions and a shorter duration, and HSV-2 recurs more frequently than HSV-1 genital infection. Suppressive therapy with valacyclovir 500 mg to 1 g daily or acyclovir 400 mg twice daily reduces outbreaks by approximately 70 to 80 percent and viral shedding by approximately 50 percent.

Herpetic Whitlow

Herpetic whitlow is an HSV infection of the distal finger presenting as a painful, swollen fingertip with deep-seated vesicles. It occurs in healthcare workers (historically in the pre-glove era) and children through autoinoculation from oral HSV. It should not be incised and drained, as it mimics paronychia or felon.

Herpes Gladiatorum

Herpes gladiatorum involves HSV-1 transmission through skin-to-skin contact in wrestlers, producing a vesicular eruption on the head, neck, and trunk at areas of contact.

Eczema Herpeticum (Kaposi Varicelliform Eruption)

Eczema herpeticum is a dermatologic emergency consisting of HSV superinfection of a pre-existing dermatosis, most commonly atopic dermatitis. It presents as widespread monomorphic, punched-out erosions and vesicles with hemorrhagic crusts, accompanied by fever, malaise, and lymphadenopathy. It can progress to disseminated HSV with encephalitis, hepatitis, and DIC. Diagnosis relies on Tzanck smear (showing multinucleated giant cells), viral PCR (the gold standard), and DFA. Treatment requires immediate systemic acyclovir (IV for severe cases, oral for mild-to-moderate). Topical calcineurin inhibitors are contraindicated until full resolution.

Diagnosis

The Tzanck smear involves scraping the base of a fresh vesicle and staining with Wright or Giemsa stain to identify multinucleated giant cells with "ballooning degeneration" and steel-gray nuclear molding. It cannot distinguish HSV from VZV and has a sensitivity of approximately 60 to 70 percent. Viral PCR is the gold standard, with high sensitivity and specificity, and can distinguish HSV-1 from HSV-2. DFA (direct fluorescent antibody) is rapid and type-specific. Viral culture takes 2 to 7 days and is declining in use due to PCR availability. Serology (type-specific IgG) is useful for determining prior infection but not for diagnosing acute episodes.

Treatment

Acyclovir is given at 200 to 400 mg five times daily (oral) or 5 to 10 mg/kg IV every 8 hours for severe or disseminated disease. Valacyclovir, a prodrug of acyclovir with better bioavailability, is dosed at 500 mg to 1 g two to three times daily. Famciclovir, a prodrug of penciclovir, is dosed at 250 to 500 mg two to three times daily. Resistance is rare and occurs in immunocompromised patients through thymidine kinase mutations, treated with IV foscarnet or cidofovir.

Varicella-Zoster Virus (VZV)

Primary Varicella (Chickenpox)

Varicella is highly contagious through airborne and contact transmission, with an incubation period of 14 to 21 days. A prodrome of fever and malaise precedes crops of vesicles described as "dew drops on rose petals" on an erythematous base, with centripetal distribution (trunk more than extremities) and involvement of the face and scalp. Lesions in all stages simultaneously (vesicles, pustules, crusts) produce the characteristic "crops" appearance. The eruption is pruritic. Complications include secondary bacterial infection, pneumonia, encephalitis, cerebellar ataxia, and hepatitis. Treatment is symptomatic in healthy children, with oral acyclovir or valacyclovir for adolescents, adults, and immunocompromised patients, and IV acyclovir for severe or disseminated disease. Prevention relies on the varicella vaccine (live attenuated), given as two doses.

Herpes Zoster (Shingles)

Herpes zoster represents reactivation of latent VZV from dorsal root or cranial nerve ganglia, presenting in a dermatomal distribution that is unilateral and band-like and does not cross the midline. Prodromal pain or burning precedes the eruption by 1 to 5 days. Grouped vesicles on an erythematous base appear within one or adjacent dermatomes, with thoracic dermatomes (T3 to L2) being most common. It is most common in the elderly and immunosuppressed due to declining VZV-specific T-cell immunity.

Special Forms

Herpes zoster ophthalmicus (HZO) involves the V1 (ophthalmic) branch of the trigeminal nerve. The Hutchinson sign (vesicles on the nasal tip indicating nasociliary branch involvement) predicts ocular involvement and warrants urgent ophthalmology referral. Ramsay Hunt syndrome results from VZV reactivation in the geniculate ganglion (CN VII), producing facial nerve palsy with vesicles in the ear canal and auricle plus vertigo and hearing loss. Disseminated zoster, defined as more than 20 vesicles outside the primary and adjacent dermatomes or involvement of more than 2 dermatomes, occurs in immunocompromised patients and is treated as varicella with airborne precautions and IV acyclovir. Zoster sine herpete presents as dermatomal pain without rash and is diagnosed by VZV PCR.

Postherpetic Neuralgia (PHN)

PHN is persistent pain lasting more than 90 days after rash onset. Risk increases with age, affecting more than 30 percent of patients over 60 years. Risk factors include severe acute pain, severe rash, ophthalmic involvement, and older age. Treatment includes gabapentin, pregabalin, TCAs (nortriptyline, amitriptyline), topical lidocaine 5% patch, and topical capsaicin 8% patch. Prevention relies on the Shingrix vaccine (recombinant, adjuvanted), given as two doses for adults 50 and older; it is also approved for immunocompromised adults 18 and older.

Treatment of Herpes Zoster

Oral antivirals should be started within 72 hours of rash onset, though benefit exists even if started later with active vesiculation. Valacyclovir 1 g three times daily for 7 days is preferred, with famciclovir 500 mg three times daily for 7 days and acyclovir 800 mg five times daily for 7 days as alternatives. IV acyclovir is used for disseminated zoster, immunocompromised patients, or HZO with severe ocular involvement. Analgesics address acute pain. The use of corticosteroids is controversial, as they may reduce acute pain but do not prevent PHN.

Common Viral Exanthems of Childhood

Measles (Rubeola)

Measles is caused by a paramyxovirus and is highly contagious through airborne transmission. A prodrome of fever, cough, coryza, and conjunctivitis (the "3 Cs") precedes the rash. Koplik spots, blue-white papules on the buccal mucosa, are pathognomonic and appear before the rash. The morbilliform rash begins on the face and spreads cephalocaudally as confluent erythematous macules and papules, with desquamation during resolution. Complications include pneumonia, encephalitis, and subacute sclerosing panencephalitis (SSPE).

Rubella (German Measles)

Rubella, caused by a togavirus, is milder than measles. It presents as a pink maculopapular rash beginning on the face and spreading downward, lasting three days. Postauricular and posterior cervical lymphadenopathy is characteristic. The Forchheimer sign (petechiae on the soft palate) may be seen. The major concern is congenital rubella syndrome in pregnancy.

Erythema Infectiosum (Fifth Disease)

Caused by parvovirus B19, erythema infectiosum presents with "slapped cheek" facial erythema followed by a lacy, reticular rash on the trunk and extremities. It can cause aplastic crisis in sickle cell disease and other hemoglobinopathies, hydrops fetalis in pregnancy, and arthropathy in adults (symmetric, affecting small joints).

Roseola Infantum (Exanthem Subitum/Sixth Disease)

Caused by HHV-6 (and HHV-7), roseola infantum presents as high fever for 3 to 5 days in infants (6 to 12 months), with a rash of rose-pink macules and papules on the trunk, spreading to the face and extremities, appearing as the fever breaks. Febrile seizures are common during the febrile phase. The condition is self-limited.

Hand-Foot-and-Mouth Disease

Classic hand-foot-mouth disease is caused by coxsackievirus A16, with enterovirus A71 causing severe forms and coxsackievirus A6 causing atypical, widespread disease. It presents with vesicles on the palms, soles, oral mucosa, and buttocks. Onychomadesis (nail shedding) may occur weeks later. The condition is self-limited, with outbreaks common in daycare and school settings. Eczema coxsackium is a widespread vesicular eruption in atopic dermatitis patients, analogous to eczema herpeticum.

<image>Clinical photograph panel of herpesvirus infections: (A) herpes labialis showing grouped vesicles on erythematous base at the vermilion border, (B) eczema herpeticum with widespread monomorphic punched-out erosions on a background of atopic dermatitis, (C) herpes zoster showing unilateral dermatomal vesicular eruption on the trunk, (D) primary varicella with crops of vesicles in various stages on the trunk. Show on diverse skin tones.</image>

<image>Diagram of VZV pathogenesis showing primary varicella with viremia and disseminated vesicles, followed by retrograde transport to dorsal root ganglia and latency, then reactivation as dermatomal herpes zoster. Include the Hutchinson sign for HZO and the Ramsay Hunt syndrome with facial nerve involvement. Map treatment strategies at each stage (antivirals, vaccination).</image>

<image>Classic viral exanthems comparison chart showing side-by-side illustrations of: measles (cephalocaudal morbilliform rash with Koplik spots), rubella (pink maculopapular rash with postauricular lymphadenopathy), erythema infectiosum (slapped cheek appearance with lacy reticular body rash), roseola (truncal pink macules appearing after fever breaks), and hand-foot-mouth disease (oral vesicles with palmoplantar lesions). Include typical age of onset and causative virus for each.</image>

Key Clinical Pearls

Eczema herpeticum is a dermatologic emergency: suspect it when an atopic dermatitis patient develops monomorphic punched-out erosions with fever, and start IV acyclovir immediately pending confirmation. The Tzanck smear is a rapid bedside test that demonstrates multinucleated giant cells in HSV and VZV but cannot distinguish between them; viral PCR is the gold standard. The Hutchinson sign (vesicles on the nasal tip) in herpes zoster ophthalmicus indicates nasociliary nerve involvement and strongly predicts ocular complications, warranting urgent ophthalmology referral. The Shingrix vaccine is recommended for adults 50 and older and immunocompromised adults 18 and older; as a recombinant (not live) vaccine, it is safe in immunosuppressed patients. In varicella, lesions are present in all stages simultaneously (vesicles, pustules, crusts), and this "crops" appearance distinguishes it from smallpox, where all lesions are in the same stage. Coxsackievirus A6 causes an atypical, widespread form of hand-foot-mouth disease that can mimic eczema herpeticum; viral PCR can distinguish them.

References

• Gnann JW Jr, Whitley RJ. Clinical practice. Herpes zoster. N Engl J Med. 2002;347(5):340-346.
• Bolognia JL, Schaffer JV, Cerroni L. Dermatology. 4th ed. Elsevier; 2018. Chapters 80-82.
• Dworkin RH, Johnson RW, Breuer J, et al. Recommendations for the management of herpes zoster. Clin Infect Dis. 2007;44(Suppl 1):S1-S26.
• Anderson BJ. The epidemiology and clinical analysis of several outbreaks of herpes gladiatorum. Med Sci Sports Exerc. 2003;35(11):1809-1814.

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