In his treatise on ocular toxoplasmosis, Hogan states that retinochoroiditis is one of the most constant features of congenital toxoplasmosis.1 In the newborn, diagnosis of ocular toxoplasmosis is most easily made in those infants who have a concurrent systemic infection; the classic symptoms include encephalomyelitis, hepatosplenomegaly, skin changes, and failure to thrive. More commonly, however, infants born with congenital toxoplasmosis are asymptomatic.2 Unless specific serologic screening for toxoplasmosis is performed, ocular involvement in these infants goes undetected until the development of systemic symptoms (eg, failure to thrive, seizures, hydrocephalus) or ocular signs (eg, squint or grossly decreased vision) prompt further work-up. We describe a case of acute bilateral retinochoroiditis with vitreous spillover that was detected on routine physical examination of an otherwise healthy neonate. Acute ocular toxoplasmosis in a neonate, in the absence of apparent systemic toxoplasmosis, has not been reported previously.
The patient was a full-term infant weighing 2.220 kg at birth. Her Apgar score was 9 at both one and five minutes. The pregnancy had been uneventful except for a mild upper respiratory tract infection in the mother during the second trimester. The infant's general physical examination was normal except that red reflexes were diminished bilaterally. The patient was referred to an ophthalmologist at ten days of age. The corneas were clear, but there was 1 + cell and flare in the anterior chambers of both eyes. Extensive posterior synechiae with pupillary membranes and non-reactive 4 mm pupils were noted. Bilateral punched-out macular and peripheral lesions with 3+ overlying vitreous debris were seen. Ocular toxoplasmosis was diagnosed and treatment was initiated with pyrimethamine, sulfadiazine, prednisone, folinic acid, topical prednisolone, and scopolamine.
The work-up, done at initial presentation, included the Sabin-Feldman dye test for toxoplasmosis. The titer was 1:8000 in the mother and infant, and IgM ELISA for toxoplasmosis was negative. Titers determined for cytomegalovirus (CMV) and herpes simplex virus were 1:64 and 1:16, respectively. Urine and pharyngeal cultures for CMV and herpes virus were negative. A cerebral spinal fluid tap showed 13 monocytes and a protein level of 60 gm/dL. A skull x-ray showed no calcifications and the VDRL test was negative.
By 7 months a clear view of the posterior poles of both eyes revealed large punched-out scars with a few overlying vitreous strands.
Bilateral retinochoroiditis in newborns is a nonspecific finding because syphilis, herpes virus, CMV, and toxoplasmosis all may present in this manner. Because different treatments now exist for each of these entities, however, it is very important that correct diagnosis be made.
Clinical appearance may be helpful in differentiating these conditions because toxoplasmic retinochoroiditis is seen typically as large and rather discrete areas of posterior retinitis with spillover into the vitreous.2 Herpes virus infection may result in a similar retinochoroiditis, but is usually associated with keratoconjunctivitis.3 On the other hand, CMV characteristically produces a peripheral retinochoroiditis,4-6 while syphilitic retinochoroiditis is usually associated with other symptoms of syphilis.
Because the etiology of isolated bilateral retinochoroiditis in the neonate cannot be determined with certainty on the basis of clinical appearance, serologic testing and virus cultures are needed to make the specific diagnosis (Table). Cytomegalovirus can be cultured from the urine in over 90% of neonates with systemic infection. Similarly, herpes virus can be cultured from the urine, pharynx, or conjunctiva. Because herpes is transmitted to the fetus via the birth canal at or shortly before birth, additional evidence of herpes infection can be obtained by culture of maternal genitalia. The sensitivity of these culture methods for CMV and herpes is very high; negative cultures are strong evidence that these agents do not cause infection.
Although the toxoplasma organism cannot be cultured by conventional methods, the diagnosis of toxoplasmosis usually can be supported through serologic tests. The Sabin-Feldman dye test, which measures the level of antitoxoplasmosis IgG, is the most common serologic test. In the neonate, however, IgG is not produced in significant amounts, and neonatal serum levels of IgG represent the passive accumulation of transplacental IgG from maternal circulation.7 In spite of this, very high titers (ie, greater than 1:4000 of antitoxoplasmosis IgG in the neonate) have been shown by Remington and Desmonts to indicate congenital toxoplasmosis infection.8 The titers in the case we have described were 1:8000. Conversely, neonatal IgM is produced endogenously and detection of antitoxoplasmosis IgM in the neonate is highly specific for congenital infection. Unfortunately, the sensitivity is only about 30%, 9 so a negative IgM test does not rule out toxoplasmosis. In addition to cultures and toxoplasmic serologic tests, studies to be performed on the infant include VDRL, lumbar puncture, and skull x-ray. Examination of the cerebral spinal fluid of neonates infected with herpes, CMV, or toxoplasmosis typically reveals increased protein and pleocytosis; in toxoplasmosis, however, the cerebral spinal fluid protein elevation is often quite severe, with levels in the range of grams per deciliter.10 Skull films may reveal intracranial calcifications, but this is again a non-specific finding that may occur with herpes, CMV, or toxoplasmic infections. These changes typically are not present in the neonate, but develop later in life.
In his 1957 monograph on toxoplasmosis, Hogan et al reviewed previously proven as well as probable cases of congenital ocular toxoplasmosis.11 Of 28 cases examined before 6 months of age, none were described as having the isolated ocular involvement apparent in our patient. With the development of the Sabin-Feldman dye test, identification of subclinical infections became possible. Wilson et al followed 13 infants with serologically diagnosed congenital toxoplasmosis who were otherwise asymptomatic at birth.12 They reported that 85% of these infants subsequently developed retinochoroiditis, making this the most common sequela of the infection. In their report, however, the earliest documentation of ocular involvement was at 1 month; no ocular involvement was seen in the neonatal period, and the average age at diagnosis of retinochoroiditis was 3.7 years.
With increased awareness among pediatric primary care physicians of the importance of testing the red reflex, the diagnosis of isolated acute neonatal toxoplasmic retinochoroiditis may become more frequent. Any infant having bilateral retinitis and vitritis should be suspected of having toxoplasmosis, and a thorough work-up should be performed. In most cases, a presumptive diagnosis should be made and treatment for toxoplasmosis begun; waiting for the results of serologic testing may risk loss of vision.
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