Viral Skin Conditions

Grouped by viral mechanism

• Latency-capable DNA herpesviruses: HSV-1/HSV-2 (sensory ganglia), VZV (dorsal root/cranial ganglia), HHV-6 (roseola), and HHV-8 (Kaposi sarcoma, a spindle-cell vascular proliferation driven by viral GPCR and latency genes); disease reflects either primary infection or reactivation when cell-mediated immunity wanes
• Epitheliotropic DNA viruses causing proliferation: HPV drives keratinocyte proliferation via E6 (p53 degradation) and E7 (Rb inactivation) — low-risk types 6/11 cause condyloma acuminatum, high-risk 16/18 drive dysplasia; molluscum contagiosum virus (poxvirus) replicates entirely in cytoplasm producing Henderson–Paterson bodies
• Immune-mediated exanthems after viremia: measles, rubella, parvovirus B19, and enteroviruses (coxsackie A16/EV-71) produce rash largely through host antibody and T-cell responses to disseminated antigen, which is why rash timing lags systemic symptoms

Modifiable risk factors

• Immunosuppression: uncontrolled HIV (especially low CD4 for Kaposi sarcoma and giant/refractory molluscum), systemic corticosteroids, calcineurin inhibitors, TNF-alpha inhibitors, chemotherapy, and transplant regimens — all impair the T-cell surveillance that keeps herpesviruses and HPV latent
• Non-vaccination: measles, rubella, varicella, HPV, and recombinant zoster vaccine (Shingrix) are all ACIP-recommended; ACIP advises HPV vaccination routinely at age 11–12 with catch-up, and two-dose recombinant zoster vaccine for adults 50 and older and for immunocompromised adults 19 and older
• Barrier disruption and contact exposure: atopic dermatitis (predisposes to eczema herpeticum and widespread molluscum), shaving, wrestling/contact sports (herpes gladiatorum), shared towels and pool fomites, and unprotected sexual contact or multiple partners
• Tobacco use: promotes persistence of high-risk HPV and progression of cervical dysplasia

Non-modifiable risk factors

• Advancing age: the dominant risk factor for herpes zoster and postherpetic neuralgia via immunosenescence
• Age extremes and pregnancy: neonates (HSV, congenital varicella/rubella), infants 6–24 months (roseola), and pregnancy (severe varicella, fetal parvovirus B19)
• Inherited immune defects: DOCK8 deficiency and epidermodysplasia verruciformis (TMC6/TMC8) produce extensive recalcitrant warts and molluscum

• Viral entry and replication: Most viral skin infections occur through direct inoculation, respiratory droplets, or hematogenous spread following viremia; viruses replicate in keratinocytes and dermal fibroblasts, causing cytopathic effects and triggering inflammatory responses

• Vesicle formation in herpesvirus infections: Herpesviruses (HSV-1, HSV-2, VZV) cause acantholysis and intraepidermal vesicle formation through viral proteases that degrade cell-cell adhesion molecules (particularly desmoglein-1 and desmoglein-3); multinucleated giant cells with "molding" appear on microscopy

• Exanthem development: Many viruses trigger systemic viremia followed by disseminated skin manifestations through immune-mediated mechanisms (Type IV hypersensitivity and viral antigen-antibody complexes) rather than direct viral invasion of all affected skin; explains delayed onset relative to systemic symptoms

• Latency and reactivation: Herpesviruses establish lifelong latency in sensory nerve ganglia; reactivation occurs during immunosuppression, stress, or trauma via retrograde axonal transport, causing recurrent dermatomal or oral lesions

• Immune evasion strategies: Poxviruses and herpesviruses produce viral homologs of immune mediators (IL-10, TNF receptors) and block apoptosis; explains prolonged infections and chronic carrier states in some conditions

• Herpes simplex virus (HSV) infections: Primary infection presents with grouped painful vesicles on erythematous base ("dew drops on rose petals") often preceded by prodromal paresthesias; primary gingivostomatitis or genital herpes may include systemic symptoms (fever, lymphadenopathy), while recurrent episodes are shorter and preceded by characteristic burning/tingling; recurrent infections typically affect same anatomic site due to same nerve ganglion involvement

• Varicella-zoster virus (VZV): Varicella (chickenpox) presents with centripetal rash (more on trunk and face) in successive crops over 3-5 days, creating "crops of lesions in different stages of maturation" (macules → papules → vesicles → crusts simultaneously); associated with fever, malaise, and intense pruritus; herpes zoster (shingles) presents as unilateral dermatomal vesicular eruption preceded by burning pain, typically in older adults or immunocompromised patients

• Molluscum contagiosum: Flesh-colored, dome-shaped papules (2-5mm) with characteristic central umbilication and cheesy core; typically painless but may become inflamed; commonly affects children and can disseminate with scratching or in immunocompromised patients

• Warts (human papillomavirus): Common warts are hyperkeratotic, rough papules on hands; plantar warts are painful, deeper lesions often with black dots (thrombosed capillaries); genital warts are pink, friable, and multiply branching; juveniles typically have common warts while sexually active adults present with genital variants

• Hand-foot-and-mouth disease (Coxsackievirus A16, Enterovirus 71): Classic triad of oral ulcers, hand vesicles on palms/fingers, and foot vesicles on soles; prodromal fever precedes rash; associated with sore throat and difficulty swallowing; generally self-limited in immunocompetent children

• Measles (Rubeola): "3 C's" prodrome (cough, coryza, conjunctivitis) precedes rash by 3-4 days; Koplik spots (white spots on buccal mucosa opposite molars) are pathognomonic and appear 2-3 days before exanthem; maculopapular rash begins on hairline/face and spreads downward ("head to toe"), blanches with pressure

• Rubella: Milder than measles; rash is maculopapular, appears on face and spreads downward, typically non-confluent; minimal or absent prodrome (unlike measles); associated with lymphadenopathy (especially suboccipital and postauricular nodes); significant teratogenic risk in first trimester

• Erythema infectiosum (Fifth disease, Parvovirus B19): "Slapped cheek" appearance with circumoral pallor; subsequently develops reticular or lacy rash on extremities that may wax and wane over weeks; typically minimal systemic illness except in adults (arthralgia) and immunocompromised (chronic anemia)

• Roseola infantum (Sixth disease, HHV-6): Classic presentation in infants 6-24 months with high fever for 3-5 days followed by defervescence with rash appearance (fever ends when rash begins—"fever breaks, rash breaks out"); rash is fine maculopapular, nonpruritic, blanching, on trunk/neck

• Mumps (Paramyxovirus): Bilateral parotid swelling with fever, malaise, and myalgias; rash is uncommon but may present as nonspecific maculopapular exanthem; complications include meningitis, orchitis, and deafness

• Varicella pneumonia and other complications: Primarily in adults and immunocompromised; presents with cough, dyspnea, and chest pain during acute varicella

• Clinical diagnosis: Many viral exanthems are diagnosed clinically from characteristic presentation, seasonal context, and exposure history; essential to recognize "signature" presentations (e.g., Koplik spots in measles, slapped cheeks in parvovirus, dew drops on rose petals in HSV)

• Viral culture: Gold standard for HSV and VZV but has largely been replaced by PCR; requires vesicular fluid obtained by unroofing fresh lesion; sensitivity decreases rapidly as lesions crust over, so culture from new vesicles, not crusted lesions

• Polymerase chain reaction (PCR): Most sensitive and specific test for HSV, VZV, and enterviruses; can differentiate HSV-1 from HSV-2; becoming standard test in most centers; helpful for CNS infections (CSF PCR) and disseminated disease

• Tzanck smear and direct fluorescent antibody (DFA): Tzanck smear shows multinucleated giant cells with nuclear molding from vesicular fluid (non-specific for HSV vs. VZV); DFA allows rapid differentiation of HSV-1, HSV-2, and VZV; faster than culture but less sensitive than PCR

• Electron microscopy: Can demonstrate characteristic viral particles but rarely used clinically; mostly historical

• Serology: HSV serology unreliable for acute diagnosis (cross-reactivity between HSV-1 and HSV-2, delayed antibody response); useful for VZV immunity assessment (varicella vaccine verification)

• Histopathology: Shows acantholysis, intraepidermal vesicle formation, and multinucleated giant cells in herpesviruses; molluscum shows molluscum bodies (eosinophilic intracytoplasmic viral inclusions); not typically needed for diagnosis

• HPV testing: Pap smear and HPV DNA testing for cervical screening in genital wart patients; anogenital HPV testing becoming standard in sexually active populations

• Imaging: Chest X-ray for suspected varicella pneumonia; CT chest for severe cases; MRI brain if disseminated VZV with CNS involvement suspected

• Laboratory-confirmed diagnosis context: Most viral exanthems do NOT require laboratory confirmation and adding tests delays appropriate symptomatic treatment; reserve testing for immunocompromised patients, pregnant women, CNS involvement, or atypical presentations

• HSV infections—first-line: **Acyclovir 400-800 mg orally 5

Herpes zoster and HSV — several are emergencies

• Postherpetic neuralgia: persistent burning/allodynia beyond rash healing from ganglionic damage and central sensitization; strongly age-dependent; managed with gabapentinoids, TCAs, or topical lidocaine
• Herpes zoster ophthalmicus (EMERGENCY): V1 involvement with Hutchinson sign (vesicles on nasal tip, nasociliary branch) signals risk of keratitis, uveitis, and vision loss — same-day ophthalmology plus systemic antiviral
• Ramsay Hunt syndrome: geniculate ganglion reactivation producing facial palsy with vesicles in the ear canal/auricle, often with hearing loss or vertigo
• Disseminated zoster (EMERGENCY): more than about twenty lesions outside the primary dermatome in an immunocompromised host, with pneumonitis, hepatitis, or encephalitis — requires IV acyclovir and airborne plus contact isolation
• Eczema herpeticum (EMERGENCY): HSV spreading across barrier-defective atopic skin as monomorphic punched-out erosions with fever; treat empirically with systemic acyclovir
• Neonatal HSV and HSV encephalitis (EMERGENCIES): vertical or reactivated infection causing SEM, CNS, or disseminated disease; temporal-lobe hemorrhagic encephalitis in adults — IV acyclovir before confirmation
• Bacterial superinfection of varicella (EMERGENCY if invasive): Staphylococcus aureus or group A streptococcus entering excoriated vesicles, progressing to necrotizing fasciitis or toxic shock; escalating pain out of proportion is the warning sign. Aspirin in varicella or influenza risks Reye syndrome

Other viral sequelae

• HPV malignancy: high-risk types cause cervical, anal, vulvar, penile, and oropharyngeal squamous carcinoma; types 6/11 acquired at delivery cause recurrent respiratory papillomatosis with hoarseness and stridor
• Measles: pneumonia (leading cause of death), otitis media, keratitis, acute disseminated encephalomyelitis, and subacute sclerosing panencephalitis years later
• Kaposi sarcoma: visceral GI bleeding and pulmonary involvement causing hypoxemia; lesions may flare as immune reconstitution inflammatory syndrome after ART initiation
• Molluscum: surrounding molluscum dermatitis, bacterial superinfection, and scarring — the beginning-of-the-end inflammatory flare precedes spontaneous clearance

Treatment-related

• Acyclovir crystal nephropathy and neurotoxicity: from rapid IV infusion or renal impairment — prevent with hydration and renal dosing
• Destructive/topical therapy: cryotherapy and cantharidin cause blistering, scarring, and dyspigmentation; imiquimod causes brisk local inflammation; podophyllin is contraindicated in pregnancy

• Vesicles on the tip of the nose = the eye is at risk: Hutchinson sign in V1 zoster predicts ocular involvement; the single best next step is urgent ophthalmology evaluation with systemic antiviral therapy, not topical steroids alone
• Antivirals work early: oral acyclovir, valacyclovir, or famciclovir for zoster is most beneficial when started within about 72 hours of rash onset, but immunocompromised or ophthalmic patients are treated regardless of timing
• Tzanck smear cannot separate HSV from VZV: multinucleated giant cells with nuclear molding appear in both — if the stem asks how to distinguish them, the answer is PCR (or DFA), the common distractor being "repeat Tzanck"
• Vaccine associations examiners love: ACIP recommends two-dose recombinant zoster vaccine (Shingrix) for adults 50 and older and immunocompromised adults 19 and older; the live zoster vaccine is no longer available in the US, and Shingrix is not live so it is not contraindicated in immunosuppression
• HPV type-to-disease mapping: 1/2/4 common and plantar warts, 6/11 condyloma and recurrent respiratory papillomatosis, 16/18 cervical and oropharyngeal cancer. Visible genital warts are diagnosed clinically — HPV DNA typing of a wart is the classic wrong answer; cervical screening follows USPSTF/ACS algorithms instead
• Violaceous plaques in a young man = HIV test: Kaposi sarcoma is HHV-8 driven; the best next step is HIV testing, and antiretroviral therapy is the backbone of treatment for epidemic KS, with chemotherapy reserved for visceral or extensive disease
• Molluscum is a poxvirus and self-limited: umbilicated papules with Henderson–Paterson bodies; observation is acceptable in healthy children, while extensive facial molluscum in an adult should prompt HIV testing
• Never give aspirin in varicella: Reye syndrome (encephalopathy plus microvesicular hepatic steatosis) is the tested association; likewise, ACE inhibitors and podophyllin are contraindicated in pregnancy when a pregnant patient with condyloma appears in the stem