Nejm 2004;350:1970 (type II)

Cause:Herpes simplex

Pathophys: Type I tends to be orolabial and have complications of encephalitis, while type II tends to be genital and neonatal with complications of meningeal involvement; but clinically full overlap. The 2 types are distinguishable bacteriologically by serotyping and genotyping (50% different)

Both types may be venereally spread, 2/3 of the time when active lesions are present, but even when no active lesion (Nejm 1986;314:1561) 1/3 of the time (Nejm 1995;333:770)

Type I: at age 14 yr, 25% of whites and 70% of blacks are seropositive (Nejm 1989;321:7). 2/3 new cases are symptomatic; 50% are oral and 50% genital (Nejm 1999;341:1432). Epidemics (herpes gladiatorum) among wrestlers (Nejm 1991;325:906)

Type II: about a 20% seropositive prevalence in US adults (Nejm 1997;337:1105); higher in women and blacks (Nejm 1989;321:7). 2/3 new cases are asx (Nejm 1999;341:1432) and shed virus as much (83%) as symptomatic pts (Nejm 2000;342:844)

Sx + Si:

Primary infections are sicker, have fever, tender adenopathy, gingivostomatitis (looks like aphthous stomatitis), pharyngitis, cervicitis, external genital lesions, paronychia (herpetic whitlow, primary and recurrent infection with lymphangitis)

Zoster-like syndrome in newborn (Nejm 1971;284:24)

Recurrent type manifests by classic cold sore or genital sores

Type I: recurs less frequently than type II (Nejm 1987;316:144)

Type II: primary infection lasts 10 d, recurs 1-2 ×/yr lasting 4 d (Nejm 1978;299:237)

Ocular keratitis by self-inoculation; colitis; aseptic meningitis esp with vulvovaginitis, or recurrently as MOLLARET'S MENINGITIS proven by PCR CSF studies (Ann IM 1994;121:334; Nejm 1991;325:1082); urinary hesitancy and sacral paresthesias esp with colitis (Nejm 1983;308:868) or vulvovaginitis; disseminated, systemic forms and encephalitis (Herpes; Disseminated, Systemic, or Encephalitis); neonatal HSV infection w 50% mortality if infection occurs <6 wk prior to delivery (Nejm 1997;337:509)

r/o erythema multiforme, hand-foot-mouth disease (base is not erythematous), tanapox (Nejm 2004;350:361) and African monkey pox herpes in monkeys (Ann IM 1990;112:833) and rodents (Wisconsin prairie dog pet epidemic—Nejm 2004;350:342)

Lab:

Bact: Culture, can read in 2-3 d; 77% sens in primary herpes (Nejm 1992;326:1533)

Path: Skin biopsy shows inclusions and giant cells; scraped Tzanck prep of skin lesion not specif

Serol: By Western blot or glycoprotein G immunodot (HerpeSelect) methods; use PCR for CSF

Rx:

Prevent:

• By keeping people with cold sores away from newborns and the immunosuppressed; good handwashing technique, condom use (Jama 2001;285:3100)
• In pregnancy (Nejm 2009;361:1376; Jama 2003;289:203), asx shedding is common and transmission rate low due to maternal Abs., avoid scalp FHT monitors; c-section only if primary HSV infection in 3rd trimester, clinical lesions when goes into labor because risk of infection in infant is <8% if recurrent disease, ~50% if primary (Nejm 1986;315:796; 1986;316:240), but <10% of mothers who cultured herpes at delivery have a h/o herpes lesion. Avoid fetal scalp monitoring.
• Vaccine, glycoprotein-D adjuvant type at 0, 1, and 6 mo, 75% effective in women seronegative for both type I and II (Nejm 2002;347:1652) but no help if seropositive for either, or in men

Prophylaxis w valcyclovir (Nejm 2004;350:11) 500 mg po qd, or perhaps acyclovir bid (C. Crumpacker—Nejm 2004;250:67) in couples discordant for HSV-2 (NNT-1 = 38)

of disease (CDC—Ann IM 2002;137:255; Med Let 2002;44:95):

• ORAL
• Acyclovir (Zovirax) (Med Let 1994;36:1) 200-400 mg po 5×/d × 7-10 d for primary; or × 5 d for recurrent episode, then 400 mg po bid prophylaxis reduces recurrences by >50% long term (Nejm 1993;118:268); for all neonatal (iv), whitlow, primary, or frequently recurrent herpes progenitalis, or oropharyngeal stomatitis; renal excretion, dialyzable; resistance appearing in immunocompetent and incompetent now (Nejm 1993;329:1777); $0.50/pill. In pregnancy, no apparent birth defects even if in 1st trimester (Jama 2010;304:859); use as prophylaxis for HSV infected mothers after 36 weeks gestation.
• Famcyclovir (Famvir) 125 mg po bid × 5 d at 1st sx of recurrence decr shedding and duration/severity of sx (Jama 1996;276:44); or 500 mg po tid × 7 d for primary or severe infection; 250 mg po bid long-term prophylaxis decr recurrence at 6 mo from 75% to 25% and safe (Jama 1998;280:887); 500 mg po bid preventively in AIDS pts w pos serology perhaps (Ann IM 1998;128:21)
• Valacyclovir (Valtrex) bid × 5-7 d (Arch IM 1996;156:1729); 2 gm po q 12 h × 2 for recurrent type I shortens crs × 1 d; 500 mg po qd for long-term suppression, cheapest regimen (Med Let 1999;41:90)
• TOPICAL (recurrent type I rx only)
• Ducosanol (Abreva) (Med Let 2000;42:108) OTC 10% cream 5×/d shortens duration × 1-2 d; works by blocking cell entry, not on viral synthesis like others so may help if used w 1st si of recurrence
• Penciclovir 1% cream q 2 h × 4 d; speeds healing and end of shedding × 1 d (Jama 1997;277:1374, Med Let 1997;39:57) vs no help at least in genital herpes (Med Let 1999;41:90)
• Acyclovir 5% ointment 6×/d shortens crs × 1/2 d
• HERBAL: Avoid Herp-Eeze (chaparral shrub), which is hepatorenal toxic (Arch IM 1997;157:913)