primary herpes

**Definition:** First HSV infection in a person with no prior HSV antibodies. Distinguish from (a) non-primary first episode (new infection with the other HSV type in someone already seropositive for one type; milder, because of partial cross-immunity) and (b) recurrent infection (reactivation of latent virus).

**Pathogen:** Herpes simplex virus 1 and 2 (Herpesviridae; enveloped, linear dsDNA, replicates in the nucleus). Typically HSV-1 is orofacial and HSV-2 is genital, but HSV-1 now causes a large share of primary genital herpes. Transmission is by direct contact with mucosal surfaces or secretions, and shedding can be asymptomatic.

**Pathophysiology:** - Virus enters through mucosal or abraded skin and replicates in epithelial cells. - It then travels by retrograde axonal transport to sensory ganglia: trigeminal ganglion for HSV-1 and sacral (S2–S5) dorsal root ganglia for HSV-2. - It establishes latency, with latency-associated transcripts (LATs) in neurons. - Reactivation is triggered by stress, fever, UV light, immunosuppression, or menses. - Lack of preexisting antibody makes primary disease more severe, with higher viral loads and a longer duration of shedding.

**Clinical features:** - *Primary orolabial:* Gingivostomatitis (most common in young children): fever, irritability, painful vesicles and ulcers of the gingiva, tongue, and buccal mucosa, and cervical lymphadenopathy. - *Primary genital:* Painful grouped vesicles that ulcerate, with dysuria, inguinal lymphadenopathy, fever, and myalgias. Lesions last about 2–3 weeks. Women may have cervicitis, and urinary retention or aseptic meningitis can occur (sacral radiculopathy). - *Other:* Herpetic whitlow, herpes gladiatorum, eczema herpeticum (Kaposi varicelliform eruption), keratoconjunctivitis (dendritic ulcer), and HSV encephalitis (temporal lobe; usually HSV-1). - Neonatal herpes risk is highest when the mother acquires primary HSV near delivery (about 30–50% transmission vs <1% with recurrent disease), because she lacks protective antibody and has high viral shedding.

**Diagnosis:** - PCR of lesion swab (preferred, most sensitive). - Viral culture. - Direct fluorescent antibody. - Tzanck smear shows multinucleated giant cells with Cowdry A intranuclear inclusions (nonspecific; it can't distinguish HSV from VZV). - Serology: type-specific IgG (gG-1 or gG-2) helps identify a prior infection. In primary infection, IgM and IgG may be negative early, and IgG appears over weeks.

**Treatment:** - Oral acyclovir, valacyclovir, or famciclovir for primary genital herpes, typically 7–10 days. - Acyclovir is a guanosine analog that is phosphorylated by viral thymidine kinase and inhibits viral DNA polymerase (chain termination). Toxicity includes crystal nephropathy. - Resistance is from thymidine kinase mutations. Treat with foscarnet (a pyrophosphate analog that doesn't need TK activation) or cidofovir. - Severe disease, encephalitis, and neonatal HSV need IV acyclovir. - Suppressive therapy reduces recurrences and transmission. - Pregnancy: a primary outbreak near term or active lesions at labor is an indication for cesarean delivery. Acyclovir or valacyclovir suppression from 36 weeks is recommended for those with a history of genital HSV.

**Board pearls:** - Primary infection is more severe than recurrence and includes systemic symptoms. - Latency sites: trigeminal ganglia (HSV-1) and sacral ganglia (HSV-2). - Recurrences are usually milder, shorter, and often preceded by a prodrome (tingling or burning). - The most common cause of sporadic fatal encephalitis is HSV-1. - Erythema multiforme can follow HSV infection. - Differential for genital ulcer: syphilis (painless chancre), chancroid (painful, with a ragged edge), LGV, and granuloma inguinale.