Pathologic changes associated with Reye Syndrome are most marked in the liver. Diffuse, microvesicular fatty accumulation is seen within the cytoplasm. Mitochondrial swelling and pleiomorphism are observed on ultrastructural examination, as well as depletion of glycogen stores and swelling of smooth endoplasmic reticulum. Histochemical stains reveal a reduction in succinic acid dehydrogenase activity. Fatty changes may also be found in other organs, such as heart, skeletal muscle and kidney, although these are usually not as striking as the abnormalities found in liver.
Neuropathologic changes are nonspecific, and consist primarily of cerebral edema.
Occasionally, mitochondrial swelling and pleiomorphism may be encountered in brain tissue. The etiology of RS has not been established. Ingestion of salicylates during the prodromal viral illness has been implicated as a possible causative factor in the development of RS in the United States. However, this observation has not been replicated in other countries, and does not explain the development of the syndrome in children who were not exposed to salicylates. The incidence of RS has decreased dramatically over the past twelve years.