Review Question - QID 214464

A child initially with cold-like symptoms with improvement, but then subsequent rash, vomiting, lethargy, and altered mental status, no evidence of meningismus, and recent medication intake most likely has Reye syndrome due to aspirin administration, an irreversible nonselective cyclooxygenase inhibitor.

Reye syndrome is a progressive neurologic disease that can present with neurologic and hepatic dysfunction. Although Reye syndrome can be post-viral, the majority of cases in children are due to aspirin. While the mechanism is unclear, it may be related to inhibition of fatty acid metabolism in the liver, especially in patients with undiagnosed inborn errors of metabolism. The initial stages of Reye syndrome include a rash on the hands and feet, vomiting, lethargy, confusion, headaches, and no fever. This eventually progresses to altered mental status, fatty liver, cerebral edema, and coma. Severe symptoms include seizures, organ failure, and death. Aspirin is an irreversible, nonselective inhibitor of the cyclooxygenase (COX) enzymes involved in the arachidonic acid pathways. By inhibiting COX-1 and COX-2, aspirin blocks the production of prostaglandins and thromboxanes. This reduces inflammation, pain, clotting, and fever. The exact mechanism for Reye syndrome associated with aspirin is unknown. Generally, aspirin is not recommended for use in children except for certain indications such as rheumatic fever and Kawasaki disease.

Incorrect Answers:
Answer 2: Lipoxygenase inhibitors include montelukast and zafirlukast, and are not associated with Reye syndrome. These medications are also involved in the arachidonic acid pathway, and prevent the synthesis of leukotrienes. Severe effects include angioedema, erythema multiforme, hepatotoxicity, and neuropsychiatric disturbances.

Answer 3: Reversible cyclooxygenase inhibitors include nonsteroidal anti-inflammatory drugs (NSAIDs), which are not associated with Reye syndrome. These reversibly inhibit COX-1 and/or COX-2. These help decreased the synthesis of prostaglandins and thromboxanes. Adverse effects include gastrointestinal bleeding, increased risk of myocardial infarction or stroke, and increased risk of chronic kidney disease.

Answer 4: Selective cyclooxygenase inhibitors refer to NSAIDs that selectively inhibit COX-2, which are not associated with Reye syndrome. Certain COX-2 inhibitors have been associated with increased risk of heart attacks and strokes. As a result, celecoxib is the only COX-2 inhibitor available in the United States.

Answer 5: Thromboxane synthase inhibitors include picotamide and are not associated with Reye syndrome. These drugs are antiplatelet drugs that prevent the formation of thromboxane A, which is also part of the arachidonic acid pathway.

Bullet Summary:
Reye syndrome in children presents with rash, altered mental status, and no fever, and is associated with aspirin, an irreversible, nonselective cyclooxygenase inhibitor.