Hospital Medicine

Viral Skin Infections

I. Problem/Condition.

Viral skin infections can produce localized or disseminated lesions. The diagnosis, which is based on typical patterns of presentation, occasionally requires laboratory testing.

Patients can present with oropharyngeal complaints, or systemic symptoms (e.g., malaise, fever), followed by a maculopapular or vesicular rash. Vesicular rashes contain replicating viral organisms and are infectious.

Outbreaks of superficial viral infections have been reported among athletes (college wrestlers, rugby players) and in daycares or schools.

II. Diagnostic Approach

A. What is the differential diagnosis for this problem?

Common viral skin infections include the following:

Herpes simplex virus (HSV)

The seroprevalence of HSV-1 and HSV-2 infection is ~75 percent in the US though many infections are subclinical. Twenty percent of sexually active subjects are seropositive for HSV-2. The virus is principally transmitted through direct exposure of mucus membranes and is incurable, persisting in latent form for the lifetime of the host. Most commonly, HSV-1 presents as stomatitis, and HSV-2 presents as genital herpes (although the reverse presentation can also occur). HSV-1 infection occurs during childhood and may reactivate later in life in the trigeminal nerve distribution. Reactivation is triggered by fever or stress and presents with paresthesias followed by vesicular eruption and scabbing. In healthy adults you can expect clinical resolution within 2 weeks, though viral shedding persists for several weeks.

Varicella zoster

Infections present as varicella (chicken pox) in childhood or can reactivate and present as zoster (shingles) in adulthood.

Varicella presents with fever, malaise, and rapidly progressive maculopapular lesions followed by vesicles in different stages of evolution (vesicles, ruptured vesicles, crusts). The infectivity period is usually one week, spanning from 2 days prior to appearance of the lesions until crusting of the lesions. Complications include secondary bacterial infection, viral pneumonia, encephalitis, sepsis, and fetal damage if the patient is pregnant. Disseminated varicella infection can present in immunocompromised patients.

Herpes zoster infection (shingles) presents as a painful vesicular rash in older subjects (>50 years). Unlike the diffuse scattered rash of Varicella, the Herpes Zoster rash is localized to a single dermatome of the sensory roots of the thoracic and lumbar areas. It is a result of reactivation of the latent varicella virus often due to stress or immunosuppression (diabetes, malignancy, HIV/ AIDS). The presence of severe or multidermatomal zoster in a young adult requires further investigation. The rash is preceded by paresthesias, burning sensation, pain, and hyperalgesia of the skin. The ophthalmic branch of the fifth cranial nerve is often affected. Involvement of the seventh cranial nerve (facial palsy, vesicles in external auditory meatus, dizziness) constitutes Ramsay-Hunt syndrome. Involvement of any of the cranial nerves increases the risk of encephalitis. Skin lesions are absent in less than 5 percent of subjects with zoster infection (zoster sine herpete). Persistent pain (post-herpetic neuralgia) is the most dreaded complication.

Measles and rubella

These viruses may present with systemic symptoms of malaise and fever followed by a maculopapular rash.

Fever, sore throat, the three “Cs” (cough, coryza, conjunctivitis), and oral Koplik's spots are characteristic of measles and precede the rash. The maculopapular rash has discrete erythematous patches that coalesce. It starts centrally (head and trunk) about 2 weeks after exposure, spreads to the extremities, and lasts for 3-7 days. Koplik’s spots are bluish-white raised lesions on an erythematous base on the buccal mucosa. Complications include bacterial pneumonia, otitis media, and post-infectious encephalitis. A rare complication is subacute sclerosing panencephailitis. Measles is highly infectious and is transmitted via the respiratory route. Persons are considered contagious 4 days before to 4 days after the rash. Outbreaks have been reported among adolescents and institutionalized subjects even if vaccinated.

Rubella symptoms are milder than in measles and include low-grade fever, rash, and lymphadenopathy (usually head and neck). The rash is similar to that of measles (discrete maculopapular patches that coalesce, begin on head, spread to trunk and extremities), however, it lasts for only a few days, earning it the name “3-day measles”. The virus may compromise the joints, kidneys, and placenta. Rubella acquired during pregnancy can have many serious sequelae including stillbirth and Congenital Rubella Syndrome (triad of cataracts, heart defects, and deafness).

Molluscum contagiosum

Molluscum contagiosum is the primary poxvirus affecting humans and is often transmitted sexually or via contact sports. It is spread by skin-to-skin contact or via autoinoculation. The typical lesions are a papular rash or pearly waxy umbilicated nodules in the skin or mucosa which result from epidermal hyperplasia. Typically there are less than twenty nodules in an immunocompetent adult. Lesions can occur anywhere on the body with the exception of palms and soles, though most are commonly found on the neck, trunk, genital area, and thighs. Systemic symptoms are absent. A single lesion often persists for 1-2 months, but the mean duration of infection is 8 months. Lesions last longer in immunocompromised patients and can indicate advancing immunosuppression. Scarring is not common after resolution. Affected individuals do not need to be removed from daycare, school, or contact sports though lesions should be covered.

Human papillomavirus (HPV)

The type of HPV determines which epithelium it affects. Plantar, common, flat, and butcher warts are often found on the hands and feet, with transmission by direct contact or fomites. Genital warts (condyloma acuminatum) are sexually transmitted and are usually caused by HPV- 6 or HPV-11. HPV-16 and HPV-18 have been associated with cervical cancer and is part of routine screening with pap smears. Among immunocompromised patients, HPV has been associated with squamous cell carcinoma.

Parvovirus B19

Parvovirus B19 infection is discussed elsewhere.

Herpesvirus 6

Infection is usually mild, self-limited, and occurs in children. Roseola infantum presents with high fever followed by a pinkish macular rash (exanthema subitum). The rash begins on the trunk, spreads to the neck and extremities, and lasts for a few days.

Coxsackievirus (A, B)

Coxsackievirus (A, B) causes hand, foot, and mouth disease in children. It is characterized by oral vesicles, tender cutaneous lesions, and fever. Infected individuals are most contagious during the first week of symptoms when there are open mouth and skin lesions. After the rash resolves, the virus can be shed through the stool for weeks following infection. Herpangina is also caused by the coxsackievirus and has a similar presentation with fever and painful oral lesions.

B. Describe a diagnostic approach/method to the patient with this problem

The diagnosis is based on typical patterns of presentation and occasionally requires laboratory testing.

1. Historical information important in the diagnosis of this problem.

Stressors, immunosuppression (diabetes, HIV risk factors), exposures (sexual transmission), pattern of distribution and evolution, and sick contacts are all important historical information in the diagnosis.

2. Physical examination maneuvers that are likely to be useful in diagnosing the cause of this problem.

Herpes simplex virus (HSV)

HSV-1: stomatitis, buccal mucosa redness, cervical adenopathy, vesicles on denuded skin in the lips (herpes labialis)

HSV-2: vesicles in clusters in the genital area or perineal/ gluteal area

Varicella

Vesicles occurring in different stages of evolution at the same time, including intact vesicles, ruptured vesicles, and crusts. Vesicles are often on an irregular area of erythema leading to “dew-drop on rose petal” appearance.

Herpes zoster

Varicella vesicular rash in dermatomal distribution, most often thoracic, cranial nerve V, and cranial nerve VII. If there is ophthalmic distribution, examine the cornea or get an Ophthalmology consult.

Measles

Discrete erythematous patches that spread from head to trunk to extremities. Oral Koplik’s spots (bluish-white raised lesions on an erythematous base) on the buccal mucosa.

Rubella

Head and neck lymphadenopathy. Discrete erythematous patches that spread from head to trunk to extremities.

Human papillomavirus (HPV)

Warts (extremities, anogenital), hyperkeratotic, papule or plaque with small black dots (thrombosed capillaries).

Coxsackievirus

Oral vesicles, tender cutaneous nodules.

3. Laboratory, radiographic and other tests that are likely to be useful in diagnosing the cause of this problem.

Herpes simplex virus (HSV)

HSV can be diagnosed by viral culture, serology, polymerase chain reaction (PCR), Tzanck smear, or direct fluorescent antibody (DFA). Viral culture remains the standard diagnostic method. Tzanck smear is the most rapid and inexpensive, though cannot differentiate between the herpes viruses including VZV. Vesicles contain the highest titer of virus in the first 24-48 hours, so when culturing ask the patient which lesions are the newest.

Herpes zoster

Viral culture, DFA. Serologic tests are available but are not preferred due to the need for rapid diagnosis.

Human papillomavirus (HPV)

Testing of cervical cytology or biopsy is the only FDA-approved test. There are no available tests for other sites.

Measles

IgM antibody, ribnonucleic acid (RNA) by polymerase chain reaction (PCR). Obtain both a serum sample and a throat swab.

Rubella

Adult - IgM antibody

Congenital – serology or virus isolation

Herpesvirus 6

Lab evaluation is not necessary, however, can be used for atypical presentations. Serology and PCR are available but high prevalence and lagging virus levels in blood make interpreting lab results difficult.

Coxsackievirus

Viral culture, PCR, serology

C. Criteria for diagnosing each diagnosis in the method above.

Herpes simplex virus (HSV): Clinical diagnosis, Positive culture or Tzanck smear

Herpes zoster: Clinical diagnosis

Measles / Rubella: Clinical diagnosis. Positive IgM or PCR

Human papillomavirus (HPV): Clinical diagnosis of wart, positive HPV cervical cytology

Molluscum contagiosum: Clinical diagnosis.

D. Over-utilized or “wasted” diagnostic tests associated with the evaluation of this problem.

Not applicable.

III. Management while the Diagnostic Process is Proceeding

A. Management of viral skin infections.

Herpes simplex virus (HSV)

As the virus is not curable, management is focused on the prevention of transmission, suppression of recurrence, attenuation of clinical course, and promotion of healing. Topical treatments (Docosanol 10% cream, Penciclovir 1% cream, Acyclovir 5% cream) are not as efficacious as systemic.

Primary: acyclovir 200 milligrams (mg) PO (PO) five times a day for 10 days; or famciclovir 500 mg PO twice a day (BID) or 250 mg three times a day (TID) for 7 days; or valacyclovir 1gram (g) PO BID for 10 days.

Recurrent: acyclovir 400 mg PO TID for 5 days; or famciclovir 1000 mg PO BID for 1 day; or valacyclovir 2 g PO BID for1 day.

Suppression: acyclovir 400 mg PO BID; or famciclovir 250 mg PO BID; or valacyclovir 1g or 500 mg PO daily

Varicella

Children: symptomatic treatment

Healthy Adults: can treat within 24 hours to limit rash and duration. Acyclovir 800 mg PO four times a day for 5 days, or valacyclovir 1g PO TID for 5 days, or famciclovir 500 mg PO TID for 5 days.

Prevention: Varivax ®, see guidelines for administration suggestions

Herpes zoster

Shingles (within 24-72hrs): acyclovir 800 mg PO five times a day for 7-10 days; or famciclovir 500 mg PO TID for 7 days; or valacyclovir 1g PO TID for 7 days.

Disseminated and ophthalmic: acyclovir 10 mg/kilogram every intravenously (IV) every 8 hours for 7 days.

Prevention: Zostavax®, see guidelines for administration suggestions.

Corticosteroids are not indicated.

Measles

Supportive care. Vitamin A supplementation has been associated with decreased morbidity and mortality, and is recommended by the World Health Organization (WHO) for those hospitalized with measles and all children with acute measles. Ribavirin has also has positive results though does not have efficacy data. Can give high-risk patients post-exposure prophylaxis Measles, Mumps, and Rubella (MM) vaccine within 72 hours or immunoglobulin within 6 days of measles exposure if no evidence of previous immunity.

Prevention: MMR vaccine, see guidelines for administration suggestions

Rubella

Supportive care. Immunoglobulin exists but has not proven effective and is not recommended.

Prevention: MMR vaccine, see guidelines for administration suggestions

Molluscum contagiosum

Generally self-limiting. If treatment is needed or desired, options are cryotherapy, curettage, laser/ photo/ beam therapies, topical treatments (canthacur, imiquimod, cidofovir), oral cimetidine, and IV cidofovir for refractory disease in immunocompromised adults.

Human papillomavirus (HPV)

Warts: cryosurgery, electrodissication, curettage, topical (trichloroacetic acid, salicylic acid, 5-flurouracil [FU], podophyillin, canthacur, imiquimod)

Prevention of genital HPV infection: quadrivalent HPV vaccine, see guidelines for administration suggestions

Coxsackievirus

Supportive care.

Herpesvirus 6 (HHV-6)

Benign self-limited. Therapy not necessary. HHV-6 has a susceptibility pattern similar to Cytomegalovirus. Treatments such as acyclovir, foscarnet, ganciclovir have some anecdotal reports but none have been studied.

B. Common pitfalls and side effects of management of this clinical problem

N/A

IV. What's the Evidence?

"Centers for Disease Control and Prevention". Measles (Rubeola). http://www.cdc.gov/measles/hcp/.

(Key features and worldwide view.)

Chen, X, Anstey, AV, Bugert, JJ. "Molluscum contagiosum virus infection". Lancet Infect Dis. vol. 13. 2013. pp. 877-88.

(Comprehensive review.)

Drutz, JE. "Rubella". Pediatr Rev. vol. 31. 2010. pp. 129-30.

(Comprehensive review.)

Fatahzadeh, M, Schwartz, RA. "Human herpes simplex virus infections: epidemiology, pathogenesis, symptomatology, diagnosis, and management". J Am Acad Dermatol. vol. 57. 2007. pp. 737-63.

(Comprehensive review.)

Han, Y, Zhang, J, Chen, N, He, L, Zhou, M, Zhu, C. "Corticosteroids for preventing postherpetic neuralgia". Cochrane Database of Systematic Reviews. 2013.

(Updated meta-analysis, steroids are not effective in preventing postherpetic neuralgia.)
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