recurrent herpes

**Pathophysiology** - Primary infection: HSV enters through mucosal surfaces or broken skin. It replicates in epithelial cells, then travels by retrograde axonal transport to sensory neuron cell bodies. - Latency: HSV-1 is classically latent in the trigeminal ganglion, and HSV-2 in the sacral (lumbosacral) ganglia. During latency the virus is transcriptionally quiet except for latency-associated transcripts (LATs), and no infectious virus is produced. - Reactivation: Triggers include stress, fever ("fever blisters"), UV exposure, menstruation, trauma, dental procedures, and immunosuppression (HIV, transplant, steroids). The virus travels by anterograde axonal transport back to the skin or mucosa. There it causes lesions or asymptomatic viral shedding. - Recurrent episodes are milder and shorter than primary disease because of pre-existing humoral and cell-mediated immunity. They often have a prodrome (tingling, burning, itching) and lesions localized to the same dermatome or site.

**Clinical forms** - Herpes labialis (HSV-1): recurrent vesicles at the vermilion border of the lip. - Genital herpes (HSV-2 more often, but HSV-1 is increasingly common): recurrent painful vesicles/ulcers. HSV-2 recurs more frequently than genital HSV-1. - Herpetic keratitis (HSV-1): dendritic ulcer on the cornea with fluorescein staining. Recurrences can cause scarring and blindness. - Herpetic whitlow: finger infection in healthcare workers. - Eczema herpeticum: disseminated skin infection in atopic dermatitis. - Recurrent HSV-associated erythema multiforme: target lesions that follow herpes outbreaks. - Mollaret meningitis: benign recurrent lymphocytic meningitis, usually from HSV-2. - Herpes zoster (shingles) is the recurrent (reactivated) form of VZV, not HSV. It involves dorsal root or cranial nerve ganglia, with a dermatomal rash.

**Diagnosis** - PCR of lesion fluid is the most sensitive and specific test. - Tzanck smear shows multinucleated giant cells with intranuclear Cowdry A inclusions. It is nonspecific because VZV looks the same. - Viral culture and direct fluorescent antibody testing are alternatives. - Serology (type-specific IgG) shows prior exposure but not lesion etiology.

**Treatment** - Nucleoside analogs: acyclovir, valacyclovir, famciclovir. They are activated by viral thymidine kinase and inhibit viral DNA polymerase, causing chain termination. - Episodic therapy shortens the duration of lesions. Suppressive therapy is for frequent recurrences (≥6 per year) and reduces transmission. - Acyclovir-resistant strains (thymidine kinase mutants), mostly in immunocompromised patients, are treated with foscarnet (a pyrophosphate analog that does not need TK activation). Cidofovir is an alternative. - Acyclovir toxicity: crystalline nephropathy, so hydrate the patient. - Topical trifluridine is used for keratitis.

**High-yield points** - Herpesviruses are enveloped, linear dsDNA viruses. - HSV-1 causes encephalitis (temporal lobe) and HSV-2 causes neonatal herpes. Treat suspected HSV encephalitis with IV acyclovir. - Transmission can occur during asymptomatic shedding. - Neonatal herpes risk is highest when a mother acquires primary genital HSV near delivery. Cesarean delivery is indicated with active lesions or prodromal symptoms at labor. - Latency is not eradicated by antivirals. There is no cure.