Herpes simplex (herpes infection)

Herpes infection (herpes simplex) is a widespread anthroponotic viral disease with a predominantly contact mechanism of transmission of the pathogen, characterized by damage to the outer skin, nervous system and a chronic relapsing course.

Herpes simplex virus (types 1 and 2) causes recurrent infection characterized by lesions of the skin, mouth, lips, eyes, and genitals. Severe infection may result in encephalitis, meningitis, neonatal herpes, and, in immunocompromised patients, disseminated herpes. Single or multiple clusters of small vesicles filled with clear fluid appear on the skin or mucous membranes on a slightly raised, inflamed base. Diagnosis of herpes simplex (herpes infection) is clinical; laboratory confirmation of the diagnosis includes culturing, PCR, direct immunofluorescence, or serologic methods. Treatment of herpes simplex (herpes infection) is symptomatic; in severe infection, acyclovir, valacyclovir, and famciclovir are useful, especially if the infection begins early enough, or in relapses or primary infections.

ICD-10 codes

• B00.0. Herpetic eczema.
• B00.1. Herpetic vesicular dermatitis.
• B00.2. Herpetic viral gingivostomatitis and pharyngostomatitis.
• B00.3. Herpes viral meningitis (G02.0).
• B00.4. Herpes viral encephalitis (G05.1).
• B00.5. Herpes viral eye disease.
• B00.7. Disseminated herpes virus disease.
• B00.8. Other forms of herpes virus infection.
• B00.9. Herpes viral infection, unspecified.

What causes herpes simplex (herpes infection)?

The disease simple herpes (herpes infection) is caused by the herpes simplex virus (HSV). There are two immunological types. HSV-1 usually causes herpes of the lips and keratitis. HSV-2 usually affects the genitals and skin. Infection occurs mainly through direct contact with the affected areas, mainly during close contact.

The herpes simplex virus persists in a latent state in the nerve ganglia; recurrences of herpes rashes are provoked by excessive exposure to sunlight, diseases with elevated temperature, physical or emotional stress, weakening of the immune system. Often the provoking factor remains unknown. Relapses are usually less severe and generally become less frequent over time.

What are the symptoms of herpes simplex (herpes infection)?

Symptoms of simple herpes (herpes infection) and the course of the disease depend on the localization of the process, the age of the patient, the immune status and the antigenic variant of the virus.

The most common lesions are those of the skin and mucous membranes. Eye lesions (herpetic keratitis), CNS infections, and neonatal herpes are rare, but have very severe clinical manifestations. HSV in the absence of skin manifestations rarely causes fulminant hepatitis. Herpes infection is especially severe in patients with HIV infection. Progressive and persistent esophagitis, colitis, perianal ulcers, pneumonia, encephalitis, and meningitis may occur. HSV may begin with erythema multiforme, possibly as a result of an immune response to the virus. Herpetic eczema is a complication of HSV infection in patients with eczema when herpes affects eczematous areas.

Lesions of the skin and mucous membranes. The rash may appear anywhere on the skin and mucous membranes, but most often around the mouth, on the lips, conjunctiva and cornea, and on the genitals. After a short prodromal period (typically less than 6 hours with a relapse of HSV-1), when tingling and itching are felt, small tense vesicles appear on an erythematous base. Single clusters of vesicles vary from 0.5 to 1.5 cm in diameter, sometimes groups of them merge. Skin lesions firmly fused with underlying tissues (for example, on the nose, ears, fingers) can be painful. After a few days, the vesicles begin to dry out, forming a thin yellowish crust. Healing occurs 8-12 days after the onset of the disease. Individual herpetic lesions usually heal completely, but as a result of recurrence of rashes in the same areas, atrophy and scarring are possible. Occasionally, secondary bacterial infection may occur. In patients with reduced cellular immunity due to HIV infection or other causes, skin lesions may persist for weeks or more. Localized infection may disseminate frequently and dramatically in immunocompromised patients.

Acute herpetic gingivostomatitis often results from primary HSV-1 infection and is typical in children. Occasionally, HSV-2 may cause the disease through oral-genital contact. Blisters inside the mouth and on the gums break open within hours or days, forming ulcers. Fever and pain are common. Difficulty eating and drinking may lead to dehydration. After resolution, the virus remains dormant in the semilunar ganglia.

Herpes labialis is usually a relapse of herpes simplex virus. It develops as ulcers on the vermilion border of the lips or, less commonly, as ulcers of the mucosa on the hard palate.
Herpetic whitlow is a swollen, painful, erythematous lesion of the distal phalanx resulting from penetration of the herpes simplex virus through the skin and is most common in health care workers.

Genital herpes is the most common ulcerative disease in developed countries transmitted through sexual contact. It is usually caused by HSV-2, although 10-30% have HSV-1. The primary lesion develops 4-7 days after contact. The blisters usually open to form ulcers that can merge. In men, the frenulum, head and body of the penis are affected, in women - the labia, clitoris, vagina, cervix, pyreneum. They can be localized around the anus and in the rectum during anal sex. Genital herpes can cause urinary disorders, dysuria, urinary retention, constipation. Severe sacral neuralgia may occur. After recovery, scars may form, relapse is observed in 80% of cases with HSV-2 and 50% with HSV-1. Primary genital lesions are usually more painful (compared to relapse), prolonged and widespread. They are usually bilateral, involving regional lymph nodes with development of systemic symptoms. Relapses may have pronounced prodromal symptoms and may involve the buttocks, groin and thigh.

Herpetic keratitis. HSV infection of the corneal epithelium causes pain, lacrimation, photophobia, corneal ulcers, which often have a branching pattern (dendritic keratitis).

Neonatal herpes. The infection develops in newborns, including those whose mothers were unaware of their previous herpes infection. Infection often occurs during childbirth, with type 2 virus. The disease usually develops in the 1st to 4th week of life, causing skin and mucous blisters or CNS involvement. The disease is a significant cause of morbidity and mortality.

Herpetic infection of the central nervous system. Herpetic encephalitis occurs sporadically and can be severe. Multiple seizures are typical. Aseptic meningitis may occur as a result of HSV-2 infection. They usually resolve on their own, but lumbosacral radiculitis may develop, which can lead to urinary retention and severe constipation.

How is herpes simplex (herpes infection) diagnosed?

Herpes simplex (herpes infection) is confirmed by typical symptoms. Laboratory confirmation is useful in severe infection, in immunocompromised patients, in pregnant women, or in atypical lesions. To confirm the diagnosis, a Tzanck test is performed - the base of the suspected herpes lesion is lightly scraped and the resulting skin or mucosal cells are placed on a thin slide. The cells are stained (Wright-Giemsa) and examined microscopically for the presence of cytological changes caused by the virus, including characteristic multinucleated giant cells. The diagnosis is definitive when it is confirmed by culture methods, an increasing titer of antibodies to the corresponding serotype (in primary infection), and biopsy. The material for cultivation is obtained from the contents of vesicles or from fresh ulcers. HSV can sometimes be identified by immunofluorescence of material obtained by scraping from the lesions. To diagnose herpes encephalitis, the PCR method in cerebrospinal fluid and MRI are used.

Herpes simplex can be confused with shingles (herpes zoster), but the latter rarely recurs and is characterized by greater pain and more extensive lesions that are located along the sensory nerves. Differential diagnostics of herpes simplex (herpes infection) also includes genital ulcers of other etiologies.

In patients with frequent relapses that are poorly responsive to antiviral drugs, immune deficiency, possibly HIV infection, should be suspected.

How is herpes simplex (herpes infection) treated?

Treatment for herpes simplex (herpes infection) is prescribed taking into account the clinical form of the disease.

Skin and mucosal lesions. Isolated lesions often remain untreated without sequelae. Acyclovir, valacyclovir, or famciclovir are used to treat herpes (especially primary). Acyclovir-resistant infection is rare and almost always occurs in immunocompromised individuals; foscarnet is effective. Secondary bacterial infection is treated with topical antibiotics (eg, mupiracin or neomycin-bacitracin) or, in severe lesions, systemic antibiotics (eg, penicillinase-resistant beta-lactams). Any form of herpetic skin and mucosal lesions is treated symptomatically. Systemic analgesics may be useful.

Gingivostomatitis typically requires topical anesthetics applied as swabs (eg, 0.5% dyclonine or 2-20% benzocaine ointment every 2 hours). If large areas are affected, 5% viscous lidocaine is applied around the mouth 5 minutes before meals (Note: Lidocaine should not be swallowed because it anesthetizes the oropharynx, larynx, and epiglottis. Children require observation because of the risk of aspiration). In severe cases, acyclovir, valacyclovir, and famciclovir are used.

Herpes labialis is treated with topical and systemic acyclovir. The duration of the rash can be reduced by applying 1% penciclovir cream every 2 hours after waking for 4 days, starting during the prodromal period and immediately after the first rash appears. Toxicity is minimal. There is cross-resistance with acyclovir. Cream with 10% docosanol is effective when applied 5 times a day.

Genital herpes is treated with antiviral drugs. For primary rashes, acyclovir is used at a dose of 200 mg orally 5 times a day for 10 days, valacyclovir at 1 g orally 2 times a day for 10 days, famciclovir at 250 mg orally 3 times a day for 7-10 days. These drugs are useful for severe infections. However, even early administration of drugs does not prevent relapses.

In recurrent herpes, the duration of the rash and its severity are critically reduced by using antiviral drugs. Acyclovir is used at a dose of 200 mg orally every 4 hours for 5 days, valacyclovir at 500 mg orally 2 times a day for 3 days, famciclovir at 125 mg orally 2 times a day for 5 days. Initially, when the first symptoms of a relapse appear, patients with frequent exacerbations (i.e. more than 6 per year) should receive acyclovir at a dose of 400 mg orally 2 times a day, valacyclovir at 500-1000 mg orally once a day, famciclovir at 250 mg orally 2 times a day. The dose should depend on the preservation of renal function. Side effects when taken orally are uncommon, but may include nausea, vomiting, diarrhea, headache, rash.

Herpetic keratitis. Treatment involves topical antiviral drugs such as idoxuridine or trifluridine under ophthalmologist supervision.
Neonatal herpes. Acyclovir 20 mg/kg intravenously every 8 hours for 14-21 days is used. CNS infection and disseminated forms are treated in the same doses for 21 days.

Herpes infection of the central nervous system. For the treatment of encephalitis, acyclovir 10 mg/kg is used intravenously every 8 hours for 14-21 days. Aseptic meningitis is treated with intravenous acyclovir. Side effects include phlebitis, rash, neurotoxicity (drowsiness, confusion, seizures, coma).