Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + Download Section PDF Listen ++ For further information, see CMDT Part 6-20: HERPES SIMPLEX (Cold or Fever Sore; Genital Herpes) + Key Features Download Section PDF Listen +++ +++ Essentials of Diagnosis ++ Recurrent small grouped painful vesicles, especially in the orolabial and genital areas, on an erythematous base May follow minor infections, trauma, stress, or sun exposure Regional tender lymphadenopathy may occur Direct fluorescent antibody tests are positive +++ General Considerations ++ The patient may have recurrent self-limited attacks, provoked by sun exposure, orofacial surgery, fever, or a viral infection Herpes simplex type 2 (HSV-2) causes lesions whose morphology and natural history are similar to those caused by herpes simplex type 1 (HSV-1) but are typically located on the genitalia; the infection is acquired by sexual contact Genital herpes may also be due to HSV-1 Risk factors for HSV transmission include Black race Female gender History of sexually transmitted infections An increased number of partners Contact with commercial sex workers Lower socioeconomic status Young age at onset of sexual activity Total duration of sexual activity Asymptomatic shedding of either virus is common and may be responsible for transmission Asymptomatic HSV-2–infected individuals shed the virus less frequently than those with symptomatic infection HSV-2 seropositivity increases the risk of HIV acquisition (it is threefold higher among persons who are HSV-seropositive than among those who are HSV-2 seronegative) Conversely, HSV-2 reactivates more frequently in advanced HIV infection +++ Demographics ++ Up to 85% of adults have serologic evidence of HSV-1 infections, most often acquired asymptomatically in childhood About 25% of the US population has serologic evidence of infection with HSV-2 In monogamous heterosexual couples where one partner has HSV-2 infection, seroconversion of the noninfected partner occurs in 10% over a 1-year period Up to 70% of such infections appeared to be transmitted during periods of asymptomatic shedding; uninfected female partners are at greater risk than males + Clinical Findings Download Section PDF Listen +++ +++ Symptoms and Signs ++ HSV-1 and HSV-2 disease Burning and stinging are principal symptoms Neuralgia may precede or accompany attacks Lesions consist of small, grouped vesicles on an erythematous base that can occur anywhere but that most often occur on the vermillion border of the lips, the penile shaft, the labia, the perianal skin, and the buttocks Any erosion in anogenital region can be due to herpes simplex Regional lymph nodes may be swollen and tender The lesions usually crust and heal in 1 week HSV-1 disease Largely involves the mouth and oral cavity Occasionally, primary infections may be manifested as severe gingivostomatitis Digital lesions (whitlows) are an occupational hazard in medicine and dentistry Contact sports (eg, wrestling) are associated with outbreaks of skin infections Primary infection is usually more severe than recurrences but may be asymptomatic Recurrences often Tend to be labial Involve fewer lesions Heal faster HSV-2 lesions Largely involve the genital tract, with the virus remaining latent in the presacral ganglia Lesions arising on the external genitalia are multiple, painful, small, grouped, and vesicular Occasionally, lesions arise in the perianal region or on the buttocks and upper thighs Dysuria, cervicitis, and urinary retention may occur in women +++ Differential Diagnosis ++ Impetigo Varicella zoster infection Chickenpox Herpes zoster (shingles) Scabies Trauma Other genital lesions Syphilis Chancroid Lymphogranuloma venereum Behçet syndrome Fixed drug eruption Other oral lesions Aphthous ulcers Herpangina (coxsackievirus) Erythema multiforme Pemphigus Primary HIV infection Candidiasis Reactive arthritis Systemic lupus erythematosus Behçet syndrome Bullous pemphigoid + Diagnosis Download Section PDF Listen +++ +++ Laboratory Tests ++ Viral cultures of vesicular fluid or direct fluorescent antibody staining of scraped lesions remain the standard of diagnosis Intranuclear inclusion bodies and multinucleated giant cells on a Tzanck preparation or Calcofluor stain are indicative of herpetic infection Polymerase chain reaction (PCR) is a more sensitive diagnostic assay A DNA microarray test for simultaneous detection of HSV-1, HSV-2, varicella zoster virus, cytomegalovirus, Epstein Barr virus, HHV-6, and adenovirus in immunocompromised patients is sensitive, specific, cost-effective, and time saving + Treatment Download Section PDF Listen +++ ++ Treatment is often not necessary in immunocompetent patients, but it can ameliorate and shorten the duration of symptoms if initiated early For first clinical episode Acyclovir is 400 mg orally five times daily (or 800 mg three times daily) Valacyclovir, 1000 mg orally twice daily Famciclovir, 250 mg orally three times daily Duration of treatment: 7–10 days, depending on the severity of the outbreak For mild recurrences Most cases do not require therapy If treatment is desired, recurrent genital herpes outbreaks may be treated with Valacyclovir, 500 mg orally twice daily for 3 days Acyclovir, 200 mg orally five times a day for 5 days Famciclovir, 125 mg orally twice daily for 5 days Valacyclovir, 2 g twice daily for 1 day, or famciclovir, 1 g once or twice in 1 day, are equally effective short-course alternatives and can abort impending recurrences of both orolabial and genital herpes The addition of a potent topical corticosteroid three times daily reduces the duration, size, and pain of orolabial herpes treated with an oral antiviral agent For frequent or severe recurrences Acyclovir, 400 mg orally twice daily Valacyclovir, 500 mg orally once daily Famciclovir, 125–250 mg orally twice daily Pritelivir, 100 mg orally once daily, may have superior reduction of viral shedding in HSV-2 compared to valacyclovir 500 mg daily oral dose Long-term suppression appears very safe, and after 5–7 years a substantial proportion of patients can discontinue treatment + Outcome Download Section PDF Listen +++ +++ Complications ++ Pyoderma Eczema herpeticum Herpetic whitlow Herpes gladiatorum (epidemic herpes transmitted by contact) Esophagitis Neonatal infection Keratitis Encephalitis Recurrent attacks lasting several days +++ Prognosis ++ Recurrent attacks last several days and patients generally recover without sequelae For frequent or severe recurrences, suppressive treatment reduces outbreaks by 85% and reduces viral shedding by more than 90%; this results in about a 50% reduced risk of transmission +++ Prevention ++ Sunscreens are very useful adjuncts in preventing sun-induced recurrences Any preventive antiviral medication should be started 24 hours prior to ultraviolet light exposure, dental surgery, or orolabial cosmetic surgery Although some studies have shown the use of latex condoms and patient education to be effective in reducing genital herpes transmission, others have not shown benefit No single or combination intervention absolutely prevents transmission +++ When to Refer ++ Refractory cases not responding to oral antiviral therapy + References Download Section PDF Listen +++ + +Chi CC et al. Interventions for prevention of herpes simplex labialis (cold sores on the lips). Cochrane Database Syst Rev. 2015 Aug 7;(8):CD010095. [PubMed: 26252373] + +Feltner C et al. Serologic screening for genital herpes: an updated evidence report and systematic review for the US Preventive Services Task Force. JAMA. 2016 Dec 20;316(23):2531–43. [PubMed: 27997660] + +Sauerbrei A. Optimal management of genital herpes: current perspectives. Infect Drug Resist. 2016 Jun 13;9:129–41. [PubMed: 27358569] + +Wald A et al. Effect of pritelivir compared with valacyclovir on genital HSV-2 shedding in patients with frequent recurrences: a randomized clinical trial. JAMA. 2016 Dec 20;316(23):2495–503. [PubMed: 27997653]