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Editor,—Vitamin A deficiency remains a leading cause of blindness worldwide with xerophthalmia affecting 5–10 million children, resulting in 250 000–500 000 new cases of blindness each year. In the developed world, vitamin A deficiency is rare and usually occurs in the setting of malabsorptive states (such as cystic fibrosis and small bowel disease), liver disease, or malnutrition. Xerophthalmia is a medical emergency carrying a high risk of blindness, infection and death. Immediate administration of massive doses of vitamin A is required. Such rapid restoration of vitamin status is felt to be extremely safe at recommended doses. Appropriate dosing regimens in infants have been less clear than in older children and adults.1 Reports of side effects are limited, and therefore we report a case of acute sixth nerve palsy in an infant receiving intramuscular vitamin A for xerophthalmia secondary to cystic fibrosis.
A 5 month old male infant with a long history of feeding intolerance was admitted to our hospital for severe irritability and failure to thrive. In the course of his examination, a sweat test was performed confirming the diagnosis of cystic fibrosis. Appropriate nutritional therapy and pancreatic enzyme replacement was commenced.
The infant had also been treated by his paediatrician for “conjunctivitis” of his right eye for the preceding 2 months with topical antibiotics. On the ophthalmic examination, the infant's visual acuity was fix and follow bilaterally. Extraocular motility was full and the eyes were orthophoric. Anterior segment examination revealed conjunctival xerosis of both eyes, and an inferior corneal ulcer of the right eye measuring 2×4 mm. Fundus examination was normal in both eyes. A diagnosis of xerophthalmia was made.
Vitamin A therapy was promptly commenced, with 50 000 IU (water miscible retinyl palmitate) intramuscularly to be given immediately and then to be repeated on the following day. After the first 50 000 IU, prominent bulging of the fontanelle was observed, although the infant remained alert and happy, and was feeding well. The second dose of 50 000 IU was therefore postponed for 48 hours, to be administered in two divided doses over 2 consecutive days. These doses were well tolerated, with gradual improvement of the bulging fontanelle over a week. Five days after the initial vitamin A dose, a complete abduction deficit of the infant's left eye was noted, in keeping with an acute sixth nerve palsy of the left eye. The infant still remained alert and happy, and there were no other signs of raised intracranial pressure. The corneal ulcer of the right eye was fully healed at this time. The infant was followed for 2 months over which time the sixth nerve palsy fully resolved. There were no other neurological sequelae. The infant continued to receive oral vitamin A supplementation after discharge.
Prompt mega-dose administration of vitamin A is essential in the management of xerophthalmia. Oral administration is preferred because of its safety, cost, and effectiveness. The recommended regimen is 200 000 IU of vitamin A on the day of diagnosis, the next day, and 4 weeks later. In the rare instances in which children are unable to swallow or absorb oral vitamin A, intramuscular injection of water miscible retinyl palmitate 55 mg (100 000 IU) should be substituted—given immediately, the next day, and 4 weeks later. Children 6–11 months of age should receive half these doses and children less than 6 months of age one quarter of these doses.2 In our patient, because the child's age was approaching 6 months, we chose to administer 50 000 IU doses.
Acute vitamin A toxicity generally occurs in children when a single dose greater than 330 000 IU is ingested, although some infants can be adversely affected by single doses as low as 100 000 IU.3 4 Typical features include a bulging fontanelle in infants, raised cerebrospinal fluid (CSF) pressure, nausea and vomiting, vertigo, and blurred vision or diplopia. These side effects are generally transient and subside within 1–2 days. Chronic ingestion of large amounts of vitamin A can result in pseudotumour cerebri.
This case demonstrates acute toxicity occurring after a cumulative dose of 100 000 IU given over 4 days. The sixth nerve palsy occurred presumably from raised CSF pressure, a phenomenon that is not fully understood but may be due to altered CSF resorption or production.5 6 Acute toxicity from intramuscular vitamin A (particularly water miscible forms) may be more likely because of the higher serum levels that are achieved more rapidly compared with oral preparations.7 Nevertheless, this case attests to the relative safety of vitamin A administration in infants.