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

INCIDENCE

Cat scratch disease has been estimated to affect 22,000 patients annually in the United States.60 Children and young adults appear to be at increased risk for the disease, especially during the fall and early winter months.39 Ocular manifestations develop in up to 10% of patients with cat scratch disease.

ETIOLOGY

Bartonella henselae is the etiological agent in cat scratch disease. Cats are the primary mammalian reservoir for B. henselae, and most infections are transmitted through the scratch or bite of a cat, especially cats less than 1 year of age.64 Rates of cat infection are higher in kittens, free-ranging cats, and fleainfested cats.28,64 Additionally, B. henselae seropositivity of cats is higher in warmer regions and areas with higher amounts of annual rainfall.

CLINICAL FEATURES

Ocular complications are not uncommon in cat scratch disease. Parinaud’s oculoglandular syndrome is the most common ocular manifestation and typically develops within 1 to 2 weeks following exposure. The syndrome is characterized by unilateral granulomatous conjunctivitis with tender preauricular and submandibular adenopathy.18 Granulomatous nodules may occur on the palpebral or bulbar conjunctiva.28

Neuroretinitis characterized by optic disc edema with a partial or complete macular star occurs in up to 2% of patients with cat scratch disease (Fig. 9-1).18,89 Most cases are unilateral although several cases have been reported with bilateral involvement.127 Although most patients will develop a macular star, some manifest optic disc swelling alone or with subretinal and intraretinal exudates.29,126

Additional posterior segment manifestations of cat scratch disease have been described. Isolated foci of retinitis or choroiditis involving the outer retina or choroid or the superficial retina are not uncommon.117 These areas of retinitis or choroiditis have also been described in patients with neuroretinitis.46,128 Other posterior segment manifestations of cat scratch disease include serous retinal detachment, intermediate uveitis, retinal vascular occlusions, optic nerve granuloma, vitreous hemorrhage, and macular edema.63,90,117

FIGURE 9-1. Eye of 16-year-old girl with cat scratch disease and neuroretinitis. Disc edema and macular star are present. There is a small area of retinitis temporal to the fovea.

CLINICAL ASSESSMENT

The diagnosis of cat scratch disease is established by the presence of specific clinical manifestations combined with serological testing for B. henselae. Currently available serologic tests include enzyme immunoassay, Western immunoblot, and indirect fluorescent antibody test. The enzyme immunoassay is the most sensitive and specific of the available tests.69

SYSTEMIC ASSOCIATIONS AND NATURAL HISTORY

Most patients with B. henselae infection develop a systemic flulike illness. Typically, a papule or pustule develops at the site of inoculation approximately 3 to 10 days following a scratch or bite. One to 3 weeks later, patients develop constitutional symptoms including headache, nausea, vomiting, sore throat, anorexia, and tender regional lymphadenopathy.119 In most patients, the systemic symptoms are relatively mild and resolve over several months.

INHERITANCE

No inheritance pattern.

TREATMENT

There are no clear treatment guidelines for the ocular complications of B. henselae infection. Some authors have advocated the use of antibiotics while others have recommended conservative, symptomatic treatment only.55,68,98 The most effective antibiotics for B. henselae infection are rifampin, ciprofloxacin, intramuscular gentamicin, and trimethoprim-sulfamethoxazole.71 When considering treatment of children with B. henselae infection, consultation with a pediatric infectious disease specialist should be obtained.

PROGNOSIS

In most cases, cat scratch disease is a relatively benign and selflimited infection. In general, patients with neuroretinitis have a good long-term prognosis although some may eventually develop a mild optic neuropathy.98 Chorioretinal inflammatory foci typically resolve with no significant sequelae. Peripheral vascular occlusions also resolve without sequelae while vascular occlusions involving the macula may lead to visual impairment.117

Lyme Disease

Lyme borreliosis is a multisystem disease caused by the spirochete Borrelia burgdorferi which is transmitted by ticks of the Ixodes genus. Infection results in a progressive disease characterized by three stages: early, disseminated, and persistent. Ocular manifestations are not uncommon and can occur during any stage of Lyme disease.

INCIDENCE

In the United States, most cases of Lyme disease occur in the middle Atlantic states, southern New England, and the upper Midwest. Additional cases have been reported along the northern Pacific coast. Within these endemic areas, the annual incidence of Lyme disease ranges from 20 to 105 cases per 100,000 people.110 Children from 5 to 10 years of age have the highest incidence of Lyme disease.

ETIOLOGY

Lyme disease is a zoonosis caused by the spirochete Borrelia burgdorferi. The disease is transmitted by infected ticks of the Ixodes genus. In the Middle Atlantic states and the upper Midwest, the deer tick Ixodes scapularis is the vector for Lyme borreliosis, whereas the western black-legged tick Ixodes pacificus is the vector for the disease along the northern Pacific

coast.110,120

CLINICAL FEATURES

The ophthalmic manifestations of Lyme disease vary with the stage of the disease. Ocular manifestations during the early stage of Lyme disease include follicular conjunctivitis and episcleritis. Most of the ocular manifestations occur during disseminated disease and include cranial nerve palsies, optic nerve disorders, and uveitis. The most common cranial neuropathy is seventh cranial nerve palsy, which is bilateral in as many as one-third of cases.25 Other cranial neuropathies include abducens nerve palsy, third, fourth, and fifth cranial nerve palsy, and multiple cranial nerve palsies. Optic nerve disorders include optic neuritis, papillitis, and papilledema.67,116

The spectrum of intraocular inflammation seen in Lyme disease includes intermediate uveitis, anterior uveitis, neuroretinitis, panuveitis, retinal vasculitis, and choroiditis.62,130 Intermediate uveitis is one of the most common forms of uveitis and may be severe, with vitreous snowballs, vitreous cells, and marked vitreous haze.16 Anterior uveitis may be nongranulomatous or granulomatous with mutton-fat keratic precipitates and iris nodules.

Stromal and subepithelial keratitis can occur during the persistent stage of the disease. Typically, bilateral focal infiltrates are located within the subepithelial layer and the stroma. Diffuse stromal keratitis may also occur in some patients.6,37,65 The keratitis may be associated with keratic precipitates and corneal edema.

CLINICAL ASSESSMENT

Isolation of B. burgdorferi from a patient with specific clinical findings is considered diagnostic of Lyme borreliosis; however, positive cultures have been obtained only during the early stage of the disease.11,110,120 Serological tests are insensitive during the

TREATMENT

For children older than 8 years of age with early localized or disseminated disease, doxycycline for 14 to 21 days is recommended. For children less than 8 years of age, amoxicillin should be used.120 Cefuroxime axetil may be used as a third choice in children allergic to either of these drugs. Children with neurological manifestations should be treated with intravenous ceftriaxone for 2 to 4 weeks. Lyme arthritis may be treated with doxycycline or intravenous ceftriaxone.

Currently, no specific guidelines have been established for the treatment of intraocular inflammation associated with Lyme borreliosis. Therapeutic options include oral doxycycline or intravenous ceftriaxone. Children with intraocular inflammation should undergo a neurological evaluation including cerebrospinal fluid examination. Intravenous ceftriaxone should be used in children with associated central nervous system manifestations. Isolated intraocular inflammation may be treated with doxycycline; however, the disease may recur after the antibiotic is discontinued.130 In children with persistent or recurrent intraocular inflammation following doxycycline therapy, intravenous ceftriaxone may be useful.122

In addition to systemic antibiotic therapy, topical corticosteroids and cycloplegics are useful in the management of anterior uveitis. Topical corticosteroids are also useful for subepithelial and stromal keratitis. To avoid recurrence of keratitis, topical corticosteroids should be gradually tapered before discontinuation.

PROGNOSIS

The conjunctivitis and episcleritis seen during early disease are typically mild and self-limited.120 Cranial nerve palsies also resolve in most patients with no long-term sequelae although they may recur in some cases. The keratitis responds to topical corticosteroid therapy, although recurrent cases have been described following abrupt cessation of therapy. Intraocular inflammation typically responds to systemic antibiotic therapy; however, some patients may develop chronic or relapsing uveitis despite appropriate antibiotic therapy.122 Optic nerve involvement may result in optic atrophy in some patients.

Syphilis

Congenital syphilis continues to be an important cause of infant morbidity, especially in areas where prenatal care is inadequate. Children born to infected mothers acquire the disease through transplacental transmission or during passage through the birth canal. Approximately 50% of children born to infected mothers will develop congenital syphilis.33 Acquired syphilis is also a significant public health problem for children and adolescents. The majority of cases of acquired syphilis in children and adolescents are sexually transmitted; however, children may also acquire syphilis during early childhood as a consequence of child abuse, breast-feeding, kissing, or handling.104

INCIDENCE

In 2000, 529 cases of congenital syphilis were reported to the Centers for Disease Control, resulting in a rate of 13.4 per 100,000 liveborn infants in the United States.24 Minority populations and those in the southeastern United States have some of the highest rates of syphilis in the United States. The incidence of ocular manifestations in children infected with syphilis is uncertain.

ETIOLOGY

Syphilis is a systemic disease caused by the spirochete Treponoma pallidum. Sexual contact is the usual mode of transmission, although infection can occur by direct contact with infectious lesions.

CLINICAL FEATURES

Syphilis can affect most structures of the eye and adnexa in children. Clinical features seen in children with congenital infection include orbital periostitis, nasolacrimal duct stenosis, dacryoadenitis, papular skin rash of the eyelids, mucous patches of the conjunctiva, stromal keratitis, congenital cataract, acute iridocyclitis, glaucoma, chorioretinitis, chorioretinal scarring, and optic atrophy. In children with acquired syphilis, the ocular manifestations are similar to those seen in adults and vary by stage of the disease. In primary syphilis, chancres of the adnexa and conjunctiva may occur. Ocular manifestations of secondary syphilis include cranial nerve palsies associated with basilar meningitis, orbital periostitis, maculopapular rash of the eyelid

skin, papillary conjunctivitis, episcleritis, marginal keratitis, granulomatous or nongranulomatous anterior uveitis, iris roseolae, lens subluxation, vitritis, diffuse or localized choroiditis or chorioretinitis, disc edema, exudative retinal detachment, neuroretinitis, retinal vasculitis, chorioretinal scars, optic neuritis, and optic perineuritis.73

CLINICAL ASSESSMENT

All pregnant women should be screened for syphilis at the time of their initial prenatal visit and at delivery. Nontreponemal tests such as the Venereal Disease Research Laboratory (VDRL) or rapid plasma regain (RPR) should be used as screening tests. Infants suspected of infection with T. pallidum should undergo a thorough evaluation for evidence of congenital infection that should include the following: physical examination, quantitative nontreponemal serological test for syphilis performed on the infant’s serum, cerebrospinal fluid examination including VDRL, long bone X-rays, complete blood count with differential, platelet counts, and liver function tests. An ophthalmologic evaluation should be performed if there is evidence of infection. For those infants with no evidence of congenital syphilis following this evaluation, a specific antitreponemal IgM antibody test should be performed.121

Acquired syphilis in children is diagnosed using the methods for diagnosing syphilis in adults. Evaluation includes a direct fluorescent antibody test for T. pallidum in suspected lesions, as well as serological tests for syphilis. Children with a negative nontreponemal serological test for syphilis should have a treponemal test—fluorescent treponemal antibody absorption (FTA) or microhemagglutination treponema pallidum (MHA- TP)—performed.97

Neurosyphilis can occur during any stage of the disease. Ocular manifestations including syphilitic uveitis are often associated with neurosyphilis, and therefore children with these manifestations should have a cerebrospinal fluid examination.

SYSTEMIC ASSOCIATIONS AND NATURAL HISTORY

Congenital syphilis can be divided into early and late stages. Early congenital syphilis includes all the manifestations occurring from birth through the end of the second year of life. Clinical manifestations during early congenital syphilis include prematurity, low birth weight, respiratory symptoms,

hepatosplenomegaly, generalized lymphadenopathy, mucocutaneous lesions, and skeletal abnormalities.82 Snuffles is one of the earliest findings during early congenital syphilis. Copper-red macules and papules similar in appearance to acquired secondary syphilis may develop on the face, trunk, palms, soles, and genitalia. Other skin findings include condyloma lata and mucous patches. Skeletal abnormalities include osteochondritis, periostitis, and saddle-nose deformity. Ocular manifestations during this stage include chorioretinitis, uveitis, glaucoma, and optic atrophy. The chorioretinitis is typically bilateral and causes degeneration of the retinal pigment epithelium creating the “salt-and-pepper” appearance of the fundus.112

Late congenital syphilis occurs after the age of 2 years. This form of congenital syphilis may be difficult to differentiate from acquired syphilis. However, Hutchison’s triad is still considered pathognomonic for late congenital syphilis and consists of notched, wide-spaced central incisors, eighth nerve deafness, and interstitial keratitis. Additional manifestations of late congenital syphilis include periostitis of the frontal and parietal bones as well as the long bones, synovitis of the knee, saddle nose, mental retardation, seizures, and gumma. Ocular manifestations include interstitial keratitis, uveitis, and glaucoma. Interstitial keratitis develops between the ages of 5 and 20 years.

Acquired syphilis during childhood and adolescence is similar to syphilis acquired during adulthood. Children may present with primary chancres or signs of secondary or latent syphilis.97 Chancres seen in primary syphilis may occur on the genitalia similar to adults; however, children may develop lesions in other areas, depending on the site of inoculation.41 Painless regional lymphadenopathy is also common during this stage of the disease. Chancres resolve within 3 to 6 weeks of onset with or without treatment.

Signs of secondary syphilis typically develop 6 to 8 weeks following the development of the chancre. Cutaneous manifestations are the most characteristic features of secondary syphilis and include macular, papular, follicular, pustular, or nodular lesions. Classic lesions are copper-red macular lesions found on the face, trunk, and the extremities, including the palms and soles.91 This stage may include a prodrome of malaise, anorexia, fever, headache, sore throat, rhinorrhea, arthralgia, and lymphadenopathy. Other manifestations of secondary syphilis include patchy alopecia, asymptomatic central nervous system involvement or meningitis, uveitis, periostitis, polyarthritis,