Heading home from an office party in Stillwater, Okla., Angie Mendez became the main character in a frightening medical mystery. Suddenly, she felt so sick that she wasn’t sure she could drive the last few blocks to her house. Chills, nausea and stomach cramps hit with little warning, “like a lightning strike,” she said. She barely made it into the house before explosive vomiting and diarrhea started. Her temperature spiked to 102. Her back ached.
Ms. Mendez, the marketing director for a restaurant and clothing store, is the subject of an article published Wednesday in The New England Journal of Medicine by Dr. James N. George and other researchers. She was not named in the article, but was contacted through Dr. George, and agreed to be interviewed. Her illness occurred in 2009.
Still sick and in pain the morning after she first became ill, she went to an emergency room. There were hints that something might be seriously wrong. Her blood counts were abnormal: White cells were high, platelets a bit low. She couldn’t produce a urine sample. But she was 35 and healthy, and her main symptoms matched those caused by run-of-the-mill stomach bugs. Doctors gave her nausea medicine and intravenous fluid, and sent her home.
Two days later, she was back in the emergency room. Now, her body was clearly under siege. She had not urinated in days, not since the illness began. Something had shut down her kidneys.
She couldn’t eat or drink. Her blood pressure was high. Her back still hurt. Her white cell count was even higher than it had been two days before, her platelets even lower. She was becoming anemic. Her liver function was abnormal. Her red blood cells were damaged and fragmented.
She was rushed by ambulance to a larger hospital, Integris Baptist Medical Center in Oklahoma City. There, she was put on dialysis to cleanse her blood, since her kidneys weren’t working.
“I was on my deathbed,” she said. Doctors suspected that a rare blood disorder was causing clots in minute vessels all over her body, blocking blood flow and damaging vital organs like her kidneys and liver. So the medical team began the standard treatment for that disorder: a procedure to remove her blood plasma and replace it with plasma from donors.
She had been in the hospital for a few days when another expert was called in: Dr. George, a hematologist and professor at the University of Oklahoma Health Sciences Center, who has been practicing medicine since 1970. He agreed that clots were causing the trouble, but he had a different idea about what was causing them.
“I was sure this was an allergic reaction,” he said, explaining that the sudden onset was a tipoff, comparable to the almost instantaneous allergic reactions some people have to bee stings or peanuts. “She said it was like lightning. She could point to the exact place on the street where she felt suddenly ill.”
He asked her about foods and medicines known to trigger such reactions, but nothing stood out. He left to write up his notes, and then had another thought. He went back to her room.
“Do you ever drink gin and tonic?” he asked. No, Ms. Mendez said.
But then her boyfriend jumped into the conversation. What about a drink called a smoothie? It was on the bar menu at the restaurant where the party was held.
She had indeed tried one of those at the party, but she didn’t know the ingredients, Ms. Mendez said. Her boyfriend knew: vodka and tonic.
“I literally had just one sip,” Ms. Mendez said. “It tasted odd. My body just sort of reacted funny. I didn’t want any more. I threw it away. “
Had she ever had that drink before?, Dr. George asked.
Ms. Mendez suddenly said, “Oh my God!” Sixteen months before, she’d had a vodka and tonic at a wedding. She had quickly become violently ill, with chills, fever, vomiting, a severe headache and neck pain.
She wound up in an emergency room, where doctors initially suspected she might have meningitis. They even did a spinal tap. She did not have meningitis, and they never figured out what was wrong with her. No one ever connected it to the drink.
Dr. George thought he knew what was happening. Ms. Mendez was allergic to quinine, of all things — the ingredient that gives a bitter tang to tonic water, which people splash into drinks without a second thought.
Quinine, used for hundreds of years to treat malaria, is a well known cause of platelet and bleeding problems and other side effects, including allergic reactions, though they are rare.
Ms. Mendez spent two weeks in the hospital, and several months on dialysis. During that time she retained so much water that her weight, normally 125 to 130, ballooned to 170. Her kidney function recovered gradually, though not fully.
It was months before she could return to full-time work. She still suffers periodically from migraine headaches, which she’d never had before. The illness has also left her with trouble thinking of words she wants to say in conversation. Dr. George said others who had had immune reactions like hers also had lingering cognitive problems, most likely the result of damage to tiny blood vessels in the brain.
Ms. Mendez calls Dr. George her savior, and said his reputation as a diagnostician made him the Mick Jagger of the hospital.
Dr. George said that since 1995 he has seen 18 other cases of quinine allergy, a few from tonic but more often from quinine pills, which some people take to treat leg cramps that wake them up at night. Quinine is a popular remedy for treating leg cramps, though the pills can have serious side effects and the Food and Drug Administration discourages their use. Regulations have made it harder to get the pills, and Dr. George said he thinks that is why he hasn’t seen any new cases since Ms. Mendez got sick in 2009.
Recently, he and colleagues combed through the medical literature and found 112 definite cases of allergic reactions to quinine, and 30 other probable ones. In three cases, the reactions were fatal.
He said the problem occurs because some people have antibodies — proteins made by the immune system to help fight infection — that mistakenly react against the cells that line their blood vessels. Usually, those reactions are weak and do no harm.
But in some people, the quinine molecule can wedge itself into the antibodies, and maybe also the target tissue, altering them in a way that tremendously increases the tendency of the antibodies to harm the blood vessels. The damaged vessels set off a cascade of destructive bleeding and clotting.
Some of those reactions, Dr. George said, “just go crazy and hit organs right and left and kill the kidneys.”
In the case of Ms. Mendez, he said, blood tests confirmed the allergy to quinine.
There is no proven treatment, he said. It is not clear that plasma exchange helps. And there is no way to predict who might develop the allergy. But once people have one reaction, it is sure to happen again if they are exposed to quinine, so they have to avoid it for life. Even a minute amount can trigger a life-threatening reaction, as in Ms. Mendez’s case.
Of the 19 patients Dr. George has seen, 18 have been women, he said. Autoimmune diseases like lupus and rheumatoid arthritis are more common in women than in men — no one knows why — and the quinine reactions fit that pattern.
The condition is rare, something that few people have to worry about. There is no reason for tonic lovers to stop drinking it.
Ms. Mendez steers far clear of tonic now. Friends don’t drink it in her presence. She can smell it even from the other side of the table, and just the odor turns her stomach.
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