Ординатура / Офтальмология / Английские материалы / Handbook of Pediatric Eye and Systemic Disease_Wright, Spiegel, Thompson_2006

Children with recurrent ocular herpes infections are less likely to develop skin and conjunctival involvement. Ocular findings in recurrent ocular HSV include stromal keratitis, endotheliitis or disciform keratitis, iridocyclitis, elevated intraocular pressure, and rarely retinitis.8 Complications of recurrent HSV keratitis such as stromal scar formation and induced astigmatism may lead to amblyopia in some children.10,95 The retinitis seen in HSV-1 and HSV-2 infections is a full-thickness necrotizing retinitis that may present as the acute retinal necrosis syndrome.

CLINICAL ASSESSMENT

In most cases, the diagnosis of HSV infection is based upon the clinical characteristics. However, laboratory testing may be useful in some patients with atypical manifestations. Cell culture is the most sensitive and specific method and can lead to a rapid diagnosis, typically within 3 days. Also, specimens can be examined directly using immunofluorescence, ELISA, and immunoperoxidase assays. Morphological tests such as the Tzanck smear can be used to identify syncytial giant cells and intranuclear inclusions, although similar findings may be present in the ocular lesions of varicella-zoster. Finally, serological tests may be useful in primary HSV infection although recurrent disease does not typically result in an increase in antibody titers.

SYSTEMIC ASSOCIATIONS AND NATURAL HISTORY

Congenital or neonatal herpes infections can be caused by either HSV-1 or HSV-2, although most cases are due to HSV-2 exposure. These infections are acquired either in utero or as the infant passes through an infected birth canal. Approximately 15% to 20% of infants with neonatal infection have ocular involvement.

Primary infections with HSV-1 are usually asymptomatic but may occasionally cause a gingivostomatitis or pharyngitis. After an incubation period of 2 to 12 days, fever and sore throat develop along with vesicles affecting the oral mucosa. Cervical adenopathy is relatively common in these patients. Symptoms and signs resolve spontaneously over the next 1 to 3 weeks in most children. Recurrent herpes labialis is a milder disease and presents with a mild tingling sensation that is followed by the development of painful vesicles. The vesicles crust during the ensuing 3 to 4 days and completely heal within 10 days.

HSV-2 infections are also typically asymptomatic. Primary infection develops after an incubation period of up to 1 week. Initial symptoms and signs include fever, malaise, inguinal lymphadenopathy, and vesicle formation. In most patients, the vesicles are confined to the genital areas; however, extragenital sites may occur. Eventually the vesicles ulcerate and heal completely, after several weeks in most cases. Recurrent HSV-2 infections, like HSV-1 infections, are typically milder than the initial episode. Recurrent disease often presents with itching or tenderness and is quickly followed by the development of vesicles. Complete healing of the lesions occurs in most patients during the next 7 to 10 days.

INHERITANCE

Not inherited.

TREATMENT

Therapy for congenital herpes infections mostly falls within the realm of the pediatric infectious disease specialist, but consultation with the ophthalmologist is essential. For systemic or posterior ocular disease, the mainstay of therapy is intravenous acyclovir. Conjunctival or corneal involvement should be managed with the use of topical trifluridine 1%.

Herpes simplex epithelial keratitis is treated with topical antiviral therapy, trifluridine solution every 2 h or vidarabine ointment every 3 h. HSV keratitis may also be treated by local debridement of the dendritic lesions, although this may not be well tolerated by younger children. Topical corticosteroids are also beneficial for children with stromal keratitis or uveitis.129

Oral acyclovir can be utilized in the treatment of herpes simplex keratitis or keratouveitis. Schwartz and Holland recently reported that oral acyclovir was useful for treating infectious HSV epithelial keratitis in children.107 Dosages of oral acyclovir used in this study were 20 mg/kg per dose four times daily in children up to 40 kg and 800 mg four times daily in children more than 40 kg. Additionally, the Herpetic Eye Disease Study Group has shown that oral acyclovir is effective in the prevention of recurrent herpetic eye disease and concluded that long-term suppressive oral acyclovir therapy reduces the rate of recurrent HSV epithelial keratitis and stromal keratitis.52

PROGNOSIS

The prognosis is good for HSV ocular disease confined to the eyelids or conjunctiva. Unfortunately, children with stromal keratitis have a guarded prognosis owing to the recurrent nature of the disease. HSV epithelial keratitis can resolve completely without sequelae in some patients whereas in others it can lead to stromal scarring or the development of stromal keratitis. Increased use of oral acyclovir in selected patients may prove useful in preventing some of these sight-threatening complications of HSV keratitis. The prognosis for patients with HSV iridocyclitis is often dependent on the associated keratitis. For children who develop acute retinal necrosis associated with HSV, the prognosis is similar to adults and dependent on the extent of retina involved and ocular complications such as optic neuropathy or rhegmatogenous retinal detachment.

Lymphocytic Choriomeningitis Virus

Lymphocytic choriomeningitis virus (LCMV) is a human zoonosis that can result in congenital or acquired disease. Congenital infection is an underdiagnosed cause of chorioretinitis in affected children.

INCIDENCE

Worldwide, 49 cases of congenital LCMV infection have been reported. Of these, 21 have occurred in the United States.5

ETIOLOGY

LCMV is a member of the arenavirus family of single-stranded RNA viruses. Rodents, including common household and laboratory mice as well as pet hamsters, are the major reservoirs.7 Infections from house mice have been associated with areas of substandard housing such as inner city dwellings as well as cleaning of rodent-infested farm buildings.76 Laboratory workers handling mice and hamsters are also at increased risk for infection.57

Human infection occurs by inhalation of aerosolized virus, direct contact with rodents, rodent bites, or contact with fomites contaminated by LCMV.53 Acquired LCMV infection can occur in all age groups and manifests as an asymptomatic infection or an acute febrile illness with meningeal signs.76 Intrauterine

infection occurs by transplacental transmission of the virus during maternal viremia.

CLINICAL FEATURES

The most common ocular manifestation in children born with congenital LCMV infection is chorioretinitis with peripheral or macular chorioretinal scarring. Additional ocular manifestations include optic atrophy, nystagmus, strabismus, cataract, and microphthalmos.5

CLINICAL ASSESSMENT

The differential diagnosis of congenital LCMV infection includes the infectious agents associated with the TORCH complex; specifically, toxoplasmosis, rubella, cytomegalovirus (CMV), herpes simplex virus, and syphilis. Clinical findings that may help distinguish between one of the TORCH infections and LCMV include hepatosplenomegaly, deafness, salt-and-pepper retinopathy, and skeletal abnormalities. Hepatosplenomegaly is common in children with neonatal CMV infection while deafness is common in children infected with rubella. Salt- and-pepper retinopathy is common in children with rubella and syphilis but is not seen in congenital LCMV infection.5 However, the congenital infection most difficult to distinguish clinically from LCMV is toxoplasmosis. The pattern of intracerebral calcifications may be useful to distinguish the two diseases. Diffuse intracerebral calcifications are associated with congenital toxoplasmosis whereas periventricular calcifications are associated with LCMV infection. The presence of LCMV antibodies detected by the immunofluorescent antibody test is useful to confirm the diagnosis of congenital LCMV infection.

SYSTEMIC ASSOCIATIONS AND NATURAL HISTORY

Intrauterine infection with LCMV may result in spontaneous abortion or cause congenital hydrocephalus and chorioretinitis in newborns. Systemic findings in children with congenital LCMV infection include hydrocephaly, microcephaly or macrocephaly, and intracranial calcifications. Long-term neurological sequelae are common including seizures, cerebral palsy, and mental retardation.5

INHERITANCE

No inheritance pattern.

TREATMENT

No specific therapy is indicated for intrauterine infection with LCMV; however, preventive measures to reduce the risk of transmission may be useful. Community and household rodent control, elimination of infected laboratory rodents, and avoidance of rodents during pregnancy can reduce the risk of infection.

PROGNOSIS

The visual prognosis for children with chorioretinal scars located in the macula is guarded because they often have decreased visual acuity and may develop nystagmus and strabismus. On the other hand, children with peripheral chorioretinal scarring have a much better visual prognosis.

Measles

Measles is a highly contagious infection that is typically seen in children. The acute infection is caused by the rubeola virus and is characterized by fever, cough, coryza, and conjunctivitis. Although the incidence of measles has markedly decreased in the United States, it continues to be a significant public health problem in developing countries.

INCIDENCE

Measles is no longer endemic in the United States; however, imported measles remains a potential source of transmission. In 1999, a total of 100 cases of confirmed measles was reported to the Centers for Disease Control and Prevention.21 Approximately one-third of these cases were imported cases from either international visitors or U.S. residents exposed while traveling abroad.

ETIOLOGY

Measles is a single-stranded RNA virus that primarily affects the respiratory epithelium of the nasopharynx. The virus is spread by contact with aerosolized droplets from respiratory secretions of infected persons.

sequelae. Children with acquired measles retinitis also have a good visual prognosis in most cases. On the other hand, the prognosis is guarded in developing countries. Up to 1% of children in developing countries will develop permanent ocular damage as a consequence of acquired measles.31,80,81

The prognosis for patients with SSPE is poor, with progression to death in 1 to 3 years in almost all patients. However, up to 5% of patients with SSPE may experience a spontaneous remission.

Rubella

Rubella is an acute viral infection of children and adults characterized by low-grade fever, rash, and lymphadenopathy. In many cases, rubella infection causes a mild self-limited illness. Unfortunately, infection during pregnancy can result in fetal infection with severe congenital defects.

INCIDENCE

The incidence of rubella in the United States has continued to decline over the past 30 years. In 1999, only 271 cases of postnatal rubella infection were reported in the United States. The number of cases of congenital rubella syndrome has also dramatically decreased, with 26 cases reported in the United States from 1997 to 1999.20

ETIOLOGY

Rubella is a single-stranded RNA virus and a member of the Togavirus family. Before widespread vaccination with rubella vaccine, rubella was responsible for epidemics every 6 to 9 years.27 Humans are the only known host for rubella, and transmission occurs by droplets from respiratory secretions. Rubella infection is often categorized according to the period that the infection is acquired, postnatal or congenital.

CLINICAL FEATURES

The ocular manifestations of acquired rubella are limited and included conjunctivitis, keratitis, and rarely retinitis. Nonpurulent conjunctivitis occurs in up to two-thirds of patients. Epithelial keratitis is less common and in most cases is transient and self-limited. Retinitis occurs rarely and presents with

visual loss associated with dark atrophic lesions visible at the level of the retinal pigment epithelium and exudative retinal detachment.51

Ocular complications are a common occurrence in the congenital rubella syndrome, affecting approximately 45% of children. The characteristic “salt-and-pepper” retinopathy typically appears in the macula or periphery of both eyes in 24% to 62% of children with congenital infection.1,14,75 Often, the retinopathy results in loss of the foveal reflex that is due to atrophy and hyperplasia of the retinal pigment epithelium. Vision is rarely affected unless choroidal neovascularization develops; this can cause a sudden decrease in vision in one or both eyes and ultimately leads to disciform scar formation, typically later in life.

Other ocular manifestations of the congenital rubella syndrome include cataracts, microphthalmia, glaucoma, anterior uveitis, and corneal haze. Cataracts occur in up to 30% of children with congenital rubella and are bilateral in 75% of cases. These nuclear cataracts are often described as pearly, dense, and possibly surrounded by a clear zone or totally opaque. Complete liquefaction of the cortex may eventually occur if the cataract continues to develop.87 However, some lens opacities that are present at birth are found to be transient. Of all the ophthalmic manifestations of congenital rubella, cataracts account for the greatest ocular morbidity and visual loss.86 Mild microphthalmia with hypermetropia occurs commonly in children with cataracts.42,87 In children with congenital rubella, the lens can contain infectious virus up to 30 months of age and must be handled with caution during cataract extraction.

Glaucoma occurs in 9% of all children with congenital rubella and appears to develop by several mechanisms. A hypermature lens may cause a relative pupillary block or a phacolytic response.1,42 Another mechanism includes an immature anterior chamber angle with abnormal insertion of the longitudinal muscle of the ciliary body into the trabecular meshwork and incomplete maturation of trabecular meshwork.13

Corneal haze may also occur as a result of several mechanisms. In some children it may be transient and resolve spontaneously several days following birth. However, it can also be due to glaucoma or as a result of corneal decompensation in eyes with microphthalmos and lens contact with the cornea.

Iris and ciliary body abnormalities have also been described in congenital rubella. These manifestations include a mild nongranulomatous iridocyclitis with posterior synechiae, iris

atrophy, hypoplasia of the ciliary body, and hypoplasia of the iris dilator muscle.13 A decreased response in the affected iris is found with the use of mydriatics and cycloplegics because of the abnormal muscles.

CLINICAL ASSESSMENT

The diagnosis of congenital rubella requires isolation of the rubella virus, the presence of serum IgM antibodies, or the persistence of serum antibodies beyond the first year of age. Isolation of rubella virus is often difficult and requires culture of the nasopharynx, urine, or cerebrospinal fluid. Serum ELISA is the most commonly used serological test for congenital rubella. Additionally, rubella antigens can be detected in blood, cerebrospinal fluid, and tissue specimens by using specific monoclonal antibodies.

The diagnosis of postnatal rubella is often difficult because it is commonly a subclinical infection. Nonspecific findings include leukopenia and atypical lymphocytes. Acute infection is confirmed by a fourfold or greater increase in the titer of serum IgG antibodies obtained during the acute and convalescent phase of the infection.

SYSTEMIC ASSOCIATIONS AND NATURAL HISTORY

Postnatal rubella infections are typically seen in children 5 to 14 years of age and are typically mild. After a 2- to 3-week incubation period, postauricular and occipital adenopathy develops with a nondescript maculopapular rash and a low-grade fever. The rash develops on the face and extends over the trunk and extremities and typically resolves spontaneously in 1 to 4 days. The most common complication of postnatal rubella infection is a transient arthritis affecting the small and medium-sized joints.59 In rare cases, rubella infection can lead to severe complications including encephalitis, necrotizing vasculitis, and thrombocytopenic purpura.14,27

Unlike postnatal infections, congenital rubella infections are associated with significant morbidity. Early descriptions of the congenital rubella syndrome included hearing loss, heart malformations, and cataracts. Currently, the syndrome includes a comprehensive spectrum of findings, and the severity of manifestations is dependent on the gestational age of the fetus at the time of infection. Approximately 80% to 90% of children infected during the first 8 weeks of gestation have one or more