Aspirin and Deadly Reye’s Syndrome: Warnings Can Be Missed

Jessica Van Dyke was an exceptionally bright 13-year-old. Her parents cannot believe she would have taken aspirin for chicken pox if she had thought it anything but safe.

“Our philosophy has always been, when there’s any doubt, you don’t do it,” said Roger D. Heller, her stepfather. “That’s what we always taught Jessica.”

Jessica liked to write poetry and played field hockey at Wiley Middle School in University Heights, a suburb of Cleveland. She came down with chicken pox the week she was to perform in a school production of “Bye Bye Birdie,” the 1960 play that launched her grandfather, Dick Van Dyke, as a stage and screen star.

On the last Monday in March, Jessica, fighting a slight fever, took four tablets of acetylsalicylic acid, the substance known for nearly 100 years as aspirin.

Three days later she began vomiting. An infection--medical science has yet to isolate the cause--had entered her brain and liver. She entered Rainbow Babies’ and Children’s Hospital, where she died April 6.

“God knows,” her stepfather said, “we never knew about Reye’s syndrome.”

Recently Identified Illness

The illness that killed Jessica Van Dyke is rare. Reye’s syndrome progresses from vomiting to disorientation to loss of consciousness, sometimes with convulsions. It is almost always serious and often fatal. First identified in 1963, the federal Centers for Disease Control did not keep continuous records on it until 1977.

As of Aug. 22, 1986, known American cases of Reye’s totaled 2,729. Of these patients, 1,135 had died and about a third of the others had suffered serious brain damage. The oldest fatality was 59, but only a few were older than 20.

Research has found that more than 90% of those young victims first came down with chicken pox or the flu, then took aspirin or a similar medication.

Jessica’s parents had heard something about Reye’s syndrome afflicting small children with the flu, but nothing about chicken pox. “We had no conception that Reye’s was a disease that could affect a 13-year-old,” Heller said.

It was “horrible irony,” he said that just four days after Jessica died, the Public Health Service published a major study showing a fortyfold increased Reye’s risk associated with aspirin.

That study was not the first, however. Medical authorities have advised since 1982 that children and teen-agers should not be given aspirin for chicken pox or influenza, and all aspirin labels have carried mandatory warnings since May 30, 1986.

Warning on Bottles

“I know,” Heller said. “We looked, and they’re there. It’s a little difficult to read, of course, and we have old aspirin bottles that don’t have it on it.

“And who reads aspirin bottles?”

Aspirin makers say that the labels clearly warn that a doctor should be consulted before the medication is given to children with chicken pox or the flu. The warning mentions Reye’s syndrome, but does not say why.

Jessica’s parents did talk with her doctor. He did not tell them to give her aspirin, but he did not tell them not to. The Hellers also had consulted several medical guides, one of which they had bought only two months before. No book warned them against giving aspirin to a child with chicken pox. In fact, at least one guide recommended it.

Seven years have passed since the first evidence linking Reye’s syndrome and aspirin was published in the journal Pediatrics. It has been five years since the Food and Drug Administration first called for warning labels.

Five major government studies since 1980 have shown the same link, and each subsequent study has sent a stronger, clearer message, yet the mandatory warnings are less than a year old. The current edition of Dr. Spock’s Baby and Child Care Book recommends aspirin for flu symptoms, and gives dosages.

Industry Pressure Blamed

Some government researchers, public health authorities and consumer activists say that the aspirin industry has made every attempt to delay or prevent the widespread publication of information that threatened aspirin sales. They also charge that the deregulation-minded Reagan Administration helped to further that goal, at least in the beginning.

Dr. Sidney M. Wolfe, director of the Public Citizens Health Research Group, a Washington-based consumer lobby founded by Ralph Nader, is highly critical of aspirin companies:

“They have put pressure wherever they could, and they have been responsible for the years’ delay in getting these warning labels,” he said. “None of these companies has been anything but horrendous about this.”

Dr. Edward Mortimer Jr., professor of epidemiology, biostatistics and pediatrics at Case Western Reserve University in Cleveland, also questions the Administration’s role in the matter.

Mortimer, a consultant to the FDA, says that the Reagan Administration has been too willing to accommodate industry, and that federal policies designed to remove cumbersome regulations have also limited the government agencies’ ability to act effectively on matters of public health.

“For years after the FDA urged the warnings be put on the packages, we didn’t have warnings,” Mortimer said. “I’m not going to say that the Reagan Administration is responsible for this tragedy, but it is certainly a strong possibility.”

‘In Enough Trouble’

Others in the debate agreed, but would not speak publicly for fear of reprisal. One independent researcher, who helped to evaluate the most recent government study of Reye’s, said, “I’m already in enough trouble with the aspirin industry.”

Representatives of the aspirin manufacturers say that they are only interested in the truth, and that they have been responsible in warning the public when it appeared prudent.

“In the end, it’s the public who benefits from being cautious until the facts are known,” said Dr. Joseph M. White, president of the Aspirin Foundation, the lobby for most U.S. aspirin manufacturers and distributors.

“Is it right to alarm the public about something that might not be true?” he asked.

Mortimer countered: “Is it right to not warn the public about something that might be true?”

Some also noted that the industry’s actions have not supported its stated concern.

“As little as two years ago,” Wolfe said, “you would see baby aspirin on the shelves (labeled) ‘For general relief of symptoms of flu’--basically telling parents to do something that could kill their children.”

The debate over Reye’s syndrome is one of threatened lawsuits, legal maneuvers and failed voluntary programs.

The American Academy of Pediatrics said that one aspirin company threatened to sue the group when it tried to alert its members to a suspected link between Reye’s and aspirin in 1982.

In the same year, the Aspirin Foundation acknowledges, it lobbied the Office of Management and Budget to delay the mandatory warning labels. The proposed warnings were tabled, although the FDA said that decision was based on its own analysis, not on pressure from the aspirin lobby.

Sources inside the FDA also say that the Aspirin Foundation prevented government warning pamphlets from being distributed through supermarkets around the country. Changes made in a later pamphlet obscured the aspirin-Reye’s link and removed a specific warning against giving aspirin to children with chicken pox or the flu.

FDA Message Targeted

In 1983, the Committee for the Care of Children, a group founded with aspirin industry money, sent an attorney’s letter to broadcasters advising them against using an FDA public-service spot on Reye’s and demanding equal time for rebuttal if they did. The group produced a counter-campaign on the issue that was criticized as being, at the very least, dangerously misleading.

The industry did agree to warning labels in 1985--although it was made clear that compliance, if not voluntarily, would be compelled. Some of those early warnings were so vaguely worded that new ones were mandated within a year.

As late as last fall, the Aspirin Foundation said, it lobbied for extension of a government study that the researchers and several experts said had already gathered conclusive evidence of the Reye’s-aspirin connection. Several aspirin makers have sponsored panels of experts who criticized research linking aspirin to Reye’s.

“If you ever wanted a case of an industry shooting itself in the foot, that’s the aspirin industry,” one FDA official said. “If they had put the labels on the bottle in 1982 like we wanted them to, they wouldn’t have created all this controversy and the bottom wouldn’t have fallen out of their market like it did.”

Aspirin Sales Plummet

Indeed, sales have dropped steadily in recent years as aspirin has been replaced by alternative pain relievers such as acetaminophen and ibuprofen. St. Joseph’s Aspirin for Children discontinued production in January, not because of the Reye’s controversy but because of declining sales, its manufacturer said.

Besides causing confusion and bad publicity, the aspirin industry has antagonized some of its strongest potential allies, the physicians.

“You know, they make good products,” Mortimer said. “Every physician in the country would have been standing up defending them if they hadn’t acted like they did.”

The aspirin industry is not looking for apologists. Its representatives say that the evidence linking aspirin to Reye’s is still not convincing.

“It may not specifically be aspirin,” the AFA’s White said. “It might have been something else.

“Someday, somebody might find out the cause of Reye’s syndrome,” he said. “Now, that’s going to be an interesting day.”

White acknowledged that his opinion is in the scientific minority. Indeed, it is contrary to that of the Academy of Pediatrics, the American Medical Assn., the FDA, the National Academy of Sciences’ Institute of Medicine and several other organizations.

“We realize we’re the underdogs in this,” he said.

A professor of epidemiology and medicine at Yale is somewhat in agreement with White. Dr. Alvin Feinstein said he is not convinced of an association between Reye’s and aspirin.

Feinstein said he is most concerned that publicity about the matter could bias research and falsely strengthen the association between the medicine and the syndrome. He and his colleagues have designed a three-year study, to be sponsored by several aspirin companies, that will take these concerns into account.

Doubt About Alarm

Until those results are in, Feinstein said, he is not sure that warning labels should appear on aspirin bottles. “That’s depends on how excitable you are,” he said.

The Yale study’s principal investigator, Dr. Brian Forsyth, disagrees with Feinstein on a fundamental point:

“I, like any pediatrician, would not recommend that a child or teen-ager take aspirin for chicken pox or the flu,” he said.

Other scientists just as critical of the government’s research as Feinstein say that public-health decisions do not need to be based on perfect studies.

In December, Dr. Sanford Cohen, provost at Wayne State University in Detroit, headed a panel of scientists convened by Schering-Plough. The panel’s pending report is harshly critical of earlier government efforts to study the aspirin-Reye’s connection, and predicts that the latest study is unlikely “to yield the unqualified and clear-cut answers that all would like.”

Cohen said that his concerns as a scientist and his concerns as a doctor are different:

Research Held Inconclusive

“A warning is certainly appropriate,” he said, “but a warning to the public and the profession is one thing. To come to a scientific conclusion is quite another.”

Consumer advocate Wolfe said he is heartened by such comments, but he wants more. He said the evidence is clear enough to demand stronger warnings, in larger print and harder to miss.

The Nader group is thinking of petitioning the FDA to alter the current labels, at least to have them mention that Reye’s syndrome can cause brain damage or death. That is the kind of label that teen-agers, even those less perceptive than Jessica Van Dyke, might heed, he said.

White disagrees:

“Every death is a tragedy, but we feel we have done what can be done. I don’t believe (Jessica) or any other child would have behaved any differently if we had written the label any differently.”