In a Vital Signs column in this magazine 17 years ago, infectious-disease physician Abigail Zuger described the conundrum of a young woman with recurrent meningitis. Hospitalized four times in a matter of months, the patient exhibited high fevers, delirium, and a stiff neck—all signs of life-threatening
bacterial, septic meningitis. CAT scans were normal. Spinal taps revealed high white cell counts in the cerebrospinal fluid—usually a harbinger of severe infection—but bacterial and viral cultures grew nothing. The patient was becoming ill and then abruptly getting better. The fourth time, to general eye-rolling, a medical student was tasked with asking the woman for the umpteenth time whether she had taken anything, anything, prior to getting sick. He hit pay dirt: Advil.
Zuger’s patient hadn’t considered over-the-counter, everyday Advil a medication. It is also sold as Rufen or Motrin, and the chemical moniker is ibuprofen. Ubiquitous as this drug is, until reading Zuger’s article I hadn’t known that in rare cases it can cause meningitis.
Case reports are the lifeblood of diagnosis. The dry, reductionist, what-percent-have-cough and what-percent-have-fever lists in medical texts will put you to sleep. But good stories stick. Doctors trade odd diagnoses like baseball cards; we glean them from journals, TV, and friends, stockpiling them against the next tough diagnosis. Zuger’s story—even 16 years later—primed me to jump on one small clue.
“Advil!” I cried to Stacy. “Did he take any tonight before he came in?”
“Yes, when he went to bed. Three hours ago.”
“How about four days ago?”
“I didn’t ask.”
“Well,” I smiled, “let’s.”
John was up again, still too bright-eyed and staring, but more there.
“What are the results?” he demanded. “I require transportation home.” His wife stood
“Do you remember taking any medications last time?” I asked him.
“He had a headache that night.” The wife tapped her lips. “Maybe some Advil?”
I showed my cards.
“Look,” I began, “I can’t prove this, but I think all your symptoms are due to the Advil. The best evidence is whether you took some before each episode.”
The wife’s face lit up. “Yes. He definitely took some the first time. Could that really be it?”
“It’s poorly understood,” I said. “It’s probably a hypersensitivity immune reaction. The ibuprofen may bind to specific tissues, like the meninges that line the brain, and set off an antibody attack. Most reported cases are in patients with immune disorders like lupus. But some have been in healthy people. It can happen with other anti-inflammatory drugs, like Aleve. The hallmark, besides the confusion and meningeal irritation, is that you get better quickly off the Advil.”
I turned to Stacy and smiled, “Nice work, Sherlock.”
She blushed. “Thanks.”
(No, thank Dr. Zuger, I thought.)
To John I said, “I’m not going to scan or tap you.” I crossed my arms. “I think you’re OK.”
“You sure?” he asked.
I had an improving patient, a solid story, a negative recent workup, and a very intelligent and attentive spouse. I felt it was safe to release him.
“Go home,” I ventured. “Get some sleep and I’ll call you later this morning. Have your neurologists recheck everything this afternoon. What’s nonnegotiable is this: You come back lickety-split if anything feels worse.”
Still dubious, John asked, “Can I take off the mask?”
“Yes, dear, please,” his wife sighed.
Eight hours later we spoke.
“I’m better,” John ventured, still hesitant. “The legs are a bit tingly, but I can walk and the headache’s gone.”
“You have my cell number,” I said. “Please call me for anything.”
A week later, his wife phoned to tell me a neurologist had decided John had a form of temporal lobe seizure. These can cause bizarre behavior but none of the muscle clenching or loss of consciousness seen in “regular” grand mal seizures.
“He started John on Keppra,” she recounted, referring to a potent anticonvulsant. “But it’s making him very drowsy.”
John’s course after discharge was as I had predicted, give or take a few vague symptoms. And diagnosis of a seizure relies heavily on patient history. There is no test that proves it. While the neurologist was trying his best to make a diagnosis based on vague, nonspecific symptoms, I was sure I had it right. I decided to be blunt.
“Look,” I told the wife, “every specialty has its default diagnosis. Seizures can do just about anything, but they don’t cause white cells in spinal taps. I truly think John is OK. It boils down to so little data, so many competing hypotheses.”
She fell silent, then finally said, “I’m taking him off the Keppra.” A month later, he was doing fine.
No more than 100 cases of ibuprofen-induced meningitis have been reported in the
literature. But you have to
wonder, given that ibuprofen
is practically in the drinking water, how many more mistaken cases of “viral meningitis” are out there.