Herpes Simplex is usually an asymptomatic infection but sometimes presents as a localized or systemic disease in susceptible children who are exposed to the virus from an outside source. Recurrent herpes simplex is a localized vesicular eruption caused by activation of virus that lies latent in the lips or other tissues of persons with circulating antibody.
The virus of herpes simplex CHerpesvirus hominis) is the prototype of the Herpesvirus group, which range in size from 120 to 180 m/I and multiply primarily in cell nuclei. The infectious unit or virion is a three-layered structure consisting of a core of double-stranded DNA. a protein coat (capsid) made up of 162 capsomeric subunits arranged in icosahedral symmetry, and an outer lipid-containing envelope. There is one major antigenic type, but a minor antigenic variant, designated type 2. is associated with genital infections.
Man is the only natural host, but similar viruses are found in many vertebrates, and the human virus can be propagated readily in chick embryos, mice, rabbits, and tissue cultures derived from almost all vertebrate species. Other members of the Herpesvirus group include the viruses of varicella-zoster (H. varicellae), monkey B disease H. simiae), pseudorabies (H. suis), and cytomegalic inclusion disease. Herpeslike viruses are suspected to be causative agents of Burkitt’s lymphoma, infectious mononucleosis and carcinoma of the cervix.
Incidence and Prevalence.
Primary infection with herpes simplex virus usually occurs before the age of five years, but maternal antibodies often afford protection during the first six months of life. A higher infection rate at an earlier age is noted among children in lower socioeconomic groups. Serologic surveys have revealed the presence of herpes antibody in 90 per cent of adults. The virus is intermittently present in the mouths of healthy carriers. Epidemics are rare, but small outbreaks occur in nurseries and orphanages, and multiple cases of cutaneous herpes simplex have been noted among hospital personnel.
In primary herpes simplex the virus multiplies at the portal of entry in the oropharyngeal mucosa or, far less commonly, in the vagina, cornea, skin, or esophagus. Viremia sometimes occurs in nonimmune persons. After resolution of the primary infection and formation of antibody, intracellular virus apparently persists in the tissues throughout the life of each infected person. A great variety of stimuli can reactivate the latent virus and induce an attack of recurrent herpes simplex. Antibody prevents dissemination of virus to other tissues, but does not inhibit virus multiplication or evolution of local lesions. Tissue culture studies reveal that herpes simplex virus can spread from infected cells to contiguous uninfected cells by fusion and dissolution of adjacent cytoplasmic membranes.
The lesions of primary and secondary herpes simplex are indistinguishable microscopically, and can be differentiated from chickenpox and herpes zoster only by immunofluorescence. Vesicles or ulcerated areas contain degenerated epithelial cells with “ballooned” cytoplasm, multinucleated giant cells, and intranuclear eosinophilic inclusion bodies.
Primary herpes simplex is an inapparent infection in at least 90 per dfent of persons exposed to the virus for the first time. However, mild or severe illness, which runs its course in one to three weeks, may result from initial contact with the virus. Fever and malaise are often prominent manifestations. Lesions can develop at single or multiple mucosal and cutaneous sites, depending on the portal of entry of the virus and local tissue resistance. In herpetic gingivostomatitis, white plaques and vesicles appear in the oral cavity and sometimes extend to the posterior pharynx. These soon ulcerate and leave a denuded mucosal surface, which accounts for the bleeding gums, severe pain, fetid breath, secondary bacterial infection, and cervical adenopathy.
Herpetic keratoconjunctivitis usually involves one eye and the preauricular lymph node on the affected side. This disease is characterized by edema and inflammation of the cornea and extension of infection to the bulbar and palpebral conjunctivae. Herpetic vulvovaginitis occurs in susceptible infants and children who develop ulcerating and necrotizing lesions of the external genitalia similar to those of gingivostomatitis.
Abrasions of the skin or pre-existing dermatoses also predispose to primary herpetic infection. Traumatic (inoculation) herpes simplex is characterized by the appearance at the site of injury of large vesicles and pustules that sometimes assume a radicular distribution not unlike that of herpes zoster. Eczema herpeticum is a serious, sometimes fatal, form of primary herpes simplex that occurs as a generalized cutaneous eruption in children with chronic eczema. This disease is often mistakenly diagnosed as eczema vaccinatum; the confusion is compounded by application of the eponym “Kaposi’s varicelliform eruption” to both disorders.
On occasion, the virus of herpes simplex invades internal organs of persons who lack circulating antibody. A relatively rare consequence of primary infection is herpes meningoencephalitis, which presents as either a severe encephalitis or a benign aseptic meningitis. Even more uncommon is visceral herpes simplex, a fatal disease of newborn infants who contract the infection from mothers with recurrent herpetic vulvovaginitis. In this generalized form of infection, necrotizing lesions are found in liver, spleen, lungs, adrenals, kidneys, and brain.
Recurrent herpes simplex is thought to occur at the same site as the primary subclinical or symptomatic infection. If the virus is introduced initially onto the vaginal mucosa or abraded skin, herpetiform lesions similar to those of fever blisters may recur periodically in these areas. There are also rare cases of recurrent generalized cutaneous eruptions in children who recover from eczema herpeticum, and even rarer instances of relapsing herpes meningoencephalitis. A serious and more frequent form of recurrent infection follows primary herpetic keratoconjunotivitis. This progressive disease is characterized by punctate lesions at the corneal margins that either heal or coalesce to form dendritic ulcers and corneal opacities.
In the vast majority of cases, reactivation of latent virus takes the form of herpes labialis (fever blisters or cold sores). These lesions appear as superficial clear vesicles on an erythematous base, and are most frequently located at the mucocutaneous junction of the lips and face. In flagrant cases the vesicles extend from the lips to involve the skin of the chin, nose, cheeks, and ears. The fragile vesicles soon rupture, exude a sticky serous or serosanguineous fluid, and form a yellow crust. Unless secondarily infected with bacteria, the lesions heal without scarring in two to seven days. Individuals vary greatly in their susceptibility to recurrent herpes labialis.
Some fair-skinned people, for example, may be unable to tolerate even short exposure to sunlight or heat. Others may be regularly afflicted with fever blisters foil ,wing short febrile episodes, common respiratory infection, minor gastrointestinal disturbances, trauma, trigeminal neuralgia, or even physical exertion. Pregnancy, menstruation, or emotional strain may also precipitate attacks of herpes simplex in susceptible persons. However, if the stimulus is sufficiently intense, virtually every adult may be affected. Herpes simplex frequently follows severe pneumococcal pneumonia and bacterial meningitides.
Herpes Simplex Diagnosis.
Virus isolation and serologic studies are chiefly of value in confirming the diagnosis of primary herpes simplex. Laboratory data in recurrent herpes simplex are more difficult to interpret because neutralizing and complement-fixing antibody titers do not rise consistently. Virus can also be isolated from the mouth, feces, and even the cerebrospinal fluid of healthy persons. Such studies have led to invalid assumptions that herpes simplex virus causes aphthous stomatitis (“canker sores”), erythema multiforme, and a host of other diseases. The various forms of herpes simplex must sometimes be differentiated from chickenpox, herpes zoster, herpangina, thrush, Vincent’s angina, pyoderma, and eczema vaccinatum.
Herpes Simplex Treatment.
Antimicrobial drugs do not affect the course of herpes simplex uncomplicated by secondary bacterial infection. Topical application of nucleoside analogues that inhibit DNA synthesis, particularly 5-iodo-2′-deoxyuridine (IUdR), may ameliorate the acute manifestations of ocular herpes and prevent the sequelae associated with herpetic corneal infections. IUdR is much less effective in recurrent herpetic keratitis, presumably because of emergence of drug-resistant mutant viruses. Corticosteroids are said to be contraindicated in herpetic keratoconjunctivitis because they appear to induce perforation of corneal ulcers. Soothing dressings and topical anesthetics are occasionally required to alleviate severe inflammation, pain, and itching. The common practice of using smallpox vaccine to prevent recurrent herpes labialis has no rationale, and is not more effective than placebos or simple reassurance.