Corneal scars commonly affect the vision requiring hard contact lens or cornea transplantation interventions. Postherpetic neuralgia occurs in Prognosis is greatly variable and dependent on long-term sequelae. Long-term vision loss, need for surgery, and long-term antiviral prophylaxis are all possible.
Create account Log in. Main Page. Getting Started. Recent changes. View form. View source. Jump to: navigation , search. Enroll in the Residents and Fellows contest. Enroll in the International Ophthalmologists contest. Residents and Fellows contest rules International Ophthalmologists contest rules. Original article contributed by :. John B. Cason MD. All contributors:. Brad H. Feldman, M. Cason MD , Shannon S. Joseph, M. Assigned editor:. Herpes Zoster Ophthalmicus.
Ophthalmology ;S3-S The incidence of shingles and its implications for vaccination policy. Vaccine ; Racial differences in the occurrence of herpes zoster. J Infect Dis ; Clinical features of human immunodeficiency virus-associated disseminated herpes zoster virus infection —a review of the literature.
Clin Exp Dermatol ; Herpes zoster ophthalmicus and delayed contralateral hemiparesis caused by cerebral angiitis: diagnosis and management approaches.
Ann Neurol ; Herpes zoster and human immunodeficiency virus infection. Herpes zoster and postherpetic neuralgia in older adults. Clin Geriatr Med ;23 3 American Academy of Ophthalmology. Accessed March 13, Create account Log in. Main Page. Getting Started. Recent changes. View form. View source. Jump to: navigation , search. Enroll in the Residents and Fellows contest. Enroll in the International Ophthalmologists contest. Residents and Fellows contest rules International Ophthalmologists contest rules.
Original article contributed by :. Lisa M Nijm. All contributors:. Brad H. Feldman, M. Assigned editor:. Victoria Chang, MD. Herpes simplex epithelial and stromal keratitis: an epidemiologic update. Surv Ophthalmol. Association between atopy and herpetic eye disease: results from the pacific ocular inflammation study. JAMA Ophthalmol. Risk factors for herpes simplex virus epithelial keratitis recurring during treatment of stromal keratitis or iridocyclitis.
Herpetic Eye Disease Study Group. Br J Ophthalmol. Pathogenesis of herpes simplex keratitis: The host cell response and ocular surface sequelae to infection and inflammation. Ocul Surf. Clin Exp Optom. Management of herpes simplex virus epithelial keratitis. Curr Opin Ophthalmol. Diagnosis of herpes simplex virus-1 keratitis: comparison of Giemsa stain, immunofluorescence assay and polymerase chain reaction. Curr Eye Res.
Epithelial changes in early primary herpes simplex virus keratitis. Photomicrographic observations in a case of human infection. Acta Ophthalmol Scand. In contrast to the alpha herpesviruses, beta herpesviruses have a restricted host range.
Their reproductive life cycle is long days , with infection progressing slowly in cell culture systems. A characteristic of these viruses is their ability to form enlarged cells, as exemplified by human cytomegalovirus infection. These viruses can establish latent infection in secretory glands, cells of the reticuloendothelial system, and the kidneys. Finally, the gamma herpesviruses have the most limited host range. They replicate in lymphoblastoid cells in vitro and can cause lytic infections in certain targeted cells.
Latent virus has been demonstrated in lymphoid tissue. Epstein-Barr virus is a member of this sub-family. In addition, human herpesvirus 6 and 7 are probably best classified as a gamma herpesvirus. However, the latter has host range properties of the beta sub-family. Further studies will need to clarify the most appropriate classification of this virus. Kaposi's sarcoma herpesvirus is most closely related genetically to Epstein-Barr virus.
Replication of all herpesviruses is a multi-step process. Following the onset of infection, DNA is uncoated and transported to the nucleus of the host cell. This is followed by transcription of immediate-early genes, which encode for the regulatory proteins. Expression of immediate-early gene products is followed by the expression of proteins encoded by early and then late genes.
Assembly of the viral core and capsid takes place within the nucleus. This is followed by envelopment at the nuclear membrane and transport out of the nucleus through the endoplasmic reticulum and the Golgi apparatus. Glycosylation of the viral membrane occurs in the Golgi apparatus. Mature virions are transported to the outer membrane of the host cell inside vesicles. Release of progeny virus is accompanied by cell death.
Replication for all herpesviruses is considered inefficient, with a high ratio of non-infectious to infectious viral particles. A unique characteristic of the herpesviruses is their ability to establish latent infection. Each virus within the family has the potential to establish latency in specific host cells, and the latent viral genome may be either extra-chromosomal or integrated into host cell DNA.
Herpes simplex virus 1 and 2 and varicella-zoster virus all establish latency in the dorsal root ganglia. Epstein-Barr virus can maintain latency within B lymphocytes and salivary glands. Cytomegalovirus, human herpesvirus 6 and 7, Kaposi's sarcoma herpesvirus and B virus have unknown sites of latency.
Latent virus may be reactivated and enter a replicative cycle at any point in time. The reactivation of latent virus is a well-recognized biologic phenomenon, but not one that is understood from a biochemical or genetic standpoint. It should be noted here that an anti-sense message to one of the immediate-early genes alpha-O may be involved in the maintenance of latent virus. Stimuli that have been observed to be associated with the reactivation of latent herpes simplex virus have included stress, menstruation, and exposure to ultraviolet light.
Precisely how these factors interact at the level of the ganglia remains to be defined. It should be noted that reactivation of herpesviruses may be clinically asymptomatic, or it may produce life-threatening disease. With the exception of cytomegalovirus retinitis, the definitive diagnosis of a herpesvirus infection requires either isolation of virus or detection of viral gene products. For virus isolation, swabs of clinical specimens or other body fluids can be inoculated into susceptible cell lines and observed for the development of characteristic cytopathic effects.
This technique is most useful for the diagnosis of infection due to herpes simplex virus 1 and 2 or varicella-zoster virus because of their relatively short replicative cycles. The identification of cytomegalovirus by cell culture requires a longer period of time due to its prolonged period of replication. Epstein-Barr virus does not induce cytopathic changes in cell culture systems and, therefore, can only be identified in culture by transformation of cord blood lymphocytes.
Similarly, human herpes virus 6 and 7 have unique growth characteristics which make identification in cell culture systems difficult. Newer and more rapid diagnostic techniques involve the detection of viral gene products.
This can be done by applying fluorescence antibody directed against immediate-early or late gene products to tissue cultures after 24 to 72 hours of incubation. A positive result is the appearance of intranuclear fluorescence. A method which utilizes monoclonal antibodies to an immediate-early gene has been most useful for the identification of CMV.
Alternatively, fluorescence antibodies may be applied directly to cell monolayers or scrapings of clinical lesions, with intranuclear fluorescence again indicating a positive result.
Recently developed diagnostic techniques that have clinical utility include in situ and dot-blot hybridization and, importantly, polymerase chain reaction DNA amplification. This latter technique has proved most successful in the diagnosis of herpes simplex virus infections of the central nervous system, particularly when applied to cerebrospinal fluid. Importantly, this tool has been utilized to study the natural history of genital herpes simplex virus infections as well as identify new herpesvirus infections i.
Kaposi's sarcoma herpesvirus. In addition to new tests for virus gene products and viral DNA, improved serologic assays are also becoming available, particularly the application of immunoblot technology to distinguishing herpes simplex virus 1 from 2 infections.
However, these tests are only useful for making a diagnosis in retrospect. Finally, the diagnosis of cytomegalovirus retinitis deserves special mention because it is made clinically by the presence of characteristic retinal changes. The diagnosis is further supported by the presence of cytomegalovirus viruria or viremia, but this is not an absolute requirement.
Of all the herpesviruses, herpes simplex virus type 1 and herpes simplex virus type 2 are the most closely related, with nearly 70 per cent genomic homology. These two viruses can be distinguished most reliably by DNA composition; however, differences in antigen expression and biologic properties also serve as methods for differentiation. A critical factor for transmission of herpes simplex viruses, regardless of virus type, is the requirement for intimate contact between a person who is shedding virus and a susceptible host.
After inoculation onto the skin or mucous membrane and an incubation period of four to six days, herpes simplex virus replicates in epithelial cells Figure As replication continues, cell lysis and local inflammation ensue, resulting in characteristic vesicles on an erythematous base.
Regional lymphatics and lymph nodes become involved: viremia and visceral dissemination may develop depending upon the immunologic competence of the host. In all hosts, the virus generally ascends the peripheral sensory nerves to reach the dorsal root ganglia. Replication of herpes simplex virus within neural tissue is followed by retrograde axonal spread of the virus back to other mucosal and skin surfaces via the peripheral sensory nerves.
Virus replicates further in epithelial cells, reproducing the lesions of the initial infection, until infection is contained through both systemic and mucosal immunity. Latency is established when herpes simplex virus reaches the dorsal root ganglia after anterograde transmission via sensory nerve pathways. In its latent form, intracellular herpes simplex virus DNA cannot be detected routinely unless specific molecular probes are utilized.
Mucocutaneous infections are the most common clinical manifestations of herpes simplex virus 1 and 2. Gingivostomatitis, which is usually caused by herpes simplex virus 1, occurs most frequently in children less than five years of age. Gingivostomatitis is characterized by fever, sore throat, pharyngeal edema and erythema, followed by the development of vesicular or ulcerative lesions on the oral and pharyngeal mucosa.
Recurrent herpes simplex virus 1 infections of the oropharynx most frequently manifest as herpes simplex labialis cold sores , and usually appear on the vermillion border of the lip. Intraoral lesions as a manifestation of recurrent disease are uncommon in the normal host but do occur frequently in immunocompromised individuals. Genital herpes is most frequently caused by herpes simplex virus 2 but an ever increasing number of cases are attributed to herpes simplex virus 1.
Primary infection in women usually involves the vulva, vagina, and cervix Figure In men, initial infection is most often associated with lesions on the glans penis, prepuce or penile shaft.
In individuals of either sex, primary disease is associated with fever, malaise, anorexia, and bilateral inguinal adenopathy. Women frequently have dysuria and urinary retention due to urethral involvement. It is estimated that as many as 10 per cent of individuals will develop an aseptic meningitis with primary infection. Sacral radiculomyelitis may occur in both men and women, resulting in neuralgias, urinary retention, or obstipation.
The complete healing of primary infection may take several weeks. It has been recognized that the first episode of genital infection is less severe in individuals who have had previous herpes simplex virus infections at other sites, such as herpes simplex labialis. Recurrent genital infections in either men or women can be particularly distressing. The frequency of recurrence varies significantly from one individual to another. It has been estimated that one-third of individuals with genital herpes have virtually no recurrences, one-third have approximately three recurrences per year, and another one-third greater than three per year.
Recent seroepidemiologic studies have found that between 25 percent and 65 percent of individuals in the United States in had antibodies to herpes simplex virus 2, and that seroprevalence is dependent upon the number of sexual partners. If genital swabs from women with a history of recurrent genital herpes are subjected to polymerase chain reaction, virus DNA can be detected in the absence of culture proof of infection. This finding suggests the chronicity of genital herpes as opposed to a recurrent infection.
Herpes simplex keratitis is usually caused by herpes simplex virus 1 and is accompanied by conjunctivitis in many cases. It is considered the most common infectious cause of blindness in the United States. The characteristic lesions of herpes simplex keratoconjunctivitis are dendritic ulcers best detected by fluorescein staining. Deep stromal involvement has also been reported and may result in visual impairment.
Herpes simplex virus infections can manifest at any skin site. Common among health care workers are lesions on abraded skin of the fingers, known as herpetic whitlows Figure Similarly, wrestlers, because of physical contact may develop disseminated cutaneous lesions known as herpes gladiatorum. Neonatal herpes simplex virus infection is estimated to occur in approximately one in deliveries in the United States annually.
Approximately 70 percent of the cases are caused by herpes simplex virus 2 and usually result from contact of the fetus with infected maternal genital secretions at the time of delivery. Manifestations of neonatal herpes simplex virus infection can be divided into three categories: 1 skin, eye and mouth disease; 2 encephalitis; and 3 disseminated infection. As the name implies, skin, eye and mouth disease consists of cutaneous lesions and does not involve other organ systems Figure Involvement of the central nervous system may occur with encephalitis or disseminated infection, and generally results in a diffuse encephalitis.
The cerebrospinal fluid formula characteristically reveals an elevated protein and a mononuclear pleocytosis. Disseminated infection involves multiple organ systems and can produce disseminated intravascular coagulation, hemorrhagic pneumonitis, encephalitis, and cutaneous lesions. Diagnosis can be particularly difficult in the absence of skin lesions. The mortality rate for each disease classification varies from zero for skin, eye and mouth disease to 15 per cent for encephalitis and 60 percent for neonates with disseminated infection.
In addition to the high mortality associated with these infections, morbidity is significant in that children with encephalitis or disseminated disease develop normally in only approximately 40 per cent of cases, even with the administration of appropriate antiviral therapy. Herpes simplex encephalitis is characterized by hemorrhagic necrosis of the inferiomedial portion of the temporal lobe Figure Disease begins unilaterally, then spreads to the contralateral temporal lobe.
It is the most common cause of focal, sporadic encephalitis in the United States today, and occurs in approximately 1 in , individuals. Most cases are caused by herpes simplex virus 1.
The actual pathogenesis of herpes simplex encephalitis requires further clarification, although it has been speculated that primary or recurrent virus can reach the temporal lobe by ascending neural pathways, such as the trigeminal tracts or the olfactory nerves.
Hemorrhagic necrosis of the temporal lobe due to HSV encephalitis. Clinical manifestations of herpes simplex encephalitis include headache, fever, altered consciousness, and abnormalities of speech and behavior. Focal seizures may also occur. The cerebrospinal fluid formula for these patients is variable, but usually consists of a pleocytosis with both polymorphonuclear leukocytes and monocytes present. The protein concentration is characteristically elevated and glucose is usually normal.
Historically, a definitive diagnosis could only be achieved by brain biopsy, since other pathogens may produce a clinically similar illness. However, the application of polymerase chain reaction for detection of virus DNA has replaced brain biopsy as the standard for diagnosis. The mortality and morbidity are high, even when appropriate antiviral therapy is administered. At present, the mortality rate is approximately 30 per cent one year after treatment.
In addition, approximately 70 per cent of survivors will have significant neurologic sequelae. Herpes simplex virus infections in the immunocompromised host are clinically more severe, may be progressive, and require more time for healing. Manifestations of herpes simplex virus infections in this patient population include pneumonitis, esophagitis, hepatitis, colitis, and disseminated cutaneous disease. Individuals suffering from human immunodeficiency virus infection may have extensive perineal or orofacial ulcerations.
Herpes simplex virus infections are also noted to be of increased severity in individuals who are burned. Transmission of herpes simplex virus is dependent upon intimate contact. Thus, herpes simplex virus 1 is usually transmitted by kissing or other contact with saliva, while herpes simplex virus 2 is usually a consequence of sexual contact.
Nosocomial spread of herpes simplex virus 2 has been documented, particularly in newborn intensive care units. Varicella-zoster virus is one of the most common viruses encountered by humans.
Varicella-zoster virus is usually transmitted by airborne routes droplet spread with initial replication in the oropharynx Figure In the susceptible or seronegative individual, replication of virus in the oropharynx leads to primary viremia, with subsequent development of a vesicular rash.
The replication of varicella-zoster virus in vitro is similar to that for herpes simplex virus, although the period of replication is somewhat prolonged. Varicella, or chickenpox, is the manifestation of primary varicella-zoster virus infection. This infection occurs most commonly in young children of preschool age and has a characteristic disseminated vesicular rash which appears after an incubation period of 14 to 17 days. The rash begins on the face and trunk and spreads to the extremities.
The lesions of chickenpox are initially vesicles which become pustular, crusted, and then scabbed prior to healing. The average duration of lesion formation is three to five days in the normal child; however, it is usually longer in adolescents and adults and certainly in the immunocompromised. At the time of primary infection, varicella-zoster virus may establish latency in dorsal root ganglia.
The recurrent form of varicella-zoster virus is herpes zoster or shingles. This form of infection, which is a reactivation of latent virus, typically manifests as a localized vesicular rash with a dermatomal distribution. The rash initially appears within the dermatome as erythema, which is soon followed by the development of vesicles Figure Some individuals will have coalescence of vesicles into bullous lesions.
New vesicles may form for five to seven days, then evolve through the sequence of healing described for the lesions of varicella. The average time to healing for individuals with shingles ranges from 10 to 21 days, depending upon the age and immune status of the individual. Characteristic of herpes zoster is the appearance of both acute neuritis and post-herpetic neuralgia.
Acute neuritis is present in most individuals with localized zoster, the exception being young children. Post-herpetic neuralgia will develop in as many as 50 per cent of adults, depending upon the age of the individual. The treatment of acute neuritis and post-herpetic neuralgia can be problematic for individual patients. Serious complications of chickenpox in the non-immunocompromised child are rare, but secondary bacterial infection can be problematic. Adults and immunocompromised children have a higher incidence of visceral disease.
It is estimated that as many as one out of three of immunocompromised children suffer visceral disease, with a mortality of 15 per cent in the absence of antiviral therapy.
Herpes zoster in the immunocompromised host may be associated with cutaneous dissemination and visceral complications. In the absence of antiviral therapy, as many as 25 per cent of individuals with lymphoproliferative malignancies will have cutaneous dissemination and 10 per cent will develop visceral complications with an overall mortality rate of approximately 8 per cent.
The spread of varicella-zoster virus depends upon airborne droplet transmission from a person who is shedding virus to a susceptible host. By adulthood, as many as 90 to 95 per cent of individuals have serologic evidence of infection with varicella-zoster virus. The epidemiology of herpes zoster is more complicated. It does not appear that herpes zoster can be transmitted from one individual to another.
However, spread of virus from the vesicles of herpes zoster may lead to the development of varicella in a susceptible host. Individuals over the age of 50 experience zoster at a frequency of approximately 1 per cent.
Cytomegalovirus infection can result in one of three distinct clinical syndromes.
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