So common was it that in 1911, a physician collected reports of 682 cases of atropine poisoning, 60 of whom died. Of the total, 379 were accidental cases caused by the use of belladonna eye drops, bandages, and salves, and another 303 were from the pure alkaloid. However, 37 were suicides, and 14 were deemed to be murders.
The symptoms of atropine poisoning result from an imbalance in the autonomic nervous system. Patients often have hallucinations; many can be seen muttering unintelligibly or picking at invisible objects in their clothes or bed sheets. They tend to be agitated and restless. Their gait is unstable. In short, they can appear intoxicated by alcohol. Their pulse is quick and their temperature is often elevated. The skin is dry and sometimes appears red. Doctors have a mnemonic for this classic cluster of symptoms—“hot as a hare, blind as a bat, dry as a bone, red as a beet, and mad as a hatter.”
The “blind as a bat” refers to the effects of atropine on the eye; it dilates the pupil, sometimes so much that there is no iris left to see. Atropine also reduces the ability of the iris to accommodate to changes in ambient light and distance. This results in blurry vision.
A synthetic atropine-like drug can be aerosolized and used for a chemical attack. In the early 1960s, the United States stockpiled this agent, but as it became clear that its effects would be very unpredictable, the government destroyed these reserves in the 1980s. It has been alleged (but not proved) that the Bosnian Serbs used this agent, which NATO refers to as BZ, in a chemical attack in July 1995 on civilians escaping from Srebrenica to Tuzla.
The other side of the coin is medical, therapeutic uses of atropine. Because of atropine’s effect on the heart, doctors have used it for years to speed up dangerously slow heart rhythms. When patients have some kinds of heart block and other forms of slow heartbeats, intravenous atropine will often instantly and dramatically remedy the problem. Ophthalmologists occasionally use atropine drops in the eyes to intentionally dilate the pupils.
Over the years, from time to time, reports have appeared in the medical literature about cases not unlike the chemistry student that Dr. Setnik had seen. They have been infrequent, but interesting in their details.
In a striking case from 1992, a fifty-four-year-old man complained of sudden onset of blurred vision in his right eye after lifting a heavy flowerpot. On examination, his right pupil was found to be extremely dilated, but he was otherwise normal. The patient took no medications that could have this effect and had no exposure to eye drops. After taking an exhaustive history, the physicians learned that the man had been cutting a plant called angel’s trumpet (Datura suaveolens), a member of the nightshade family and a plant known to secrete atropine. His symptoms resolved. To be 100 percent certain, one of the examining doctors obtained some of the same plant that the man had been working with. He applied a drop of the berry of the plant onto his own eye. Predictably, the doctor’s pupil dilated.
In the past decade, additional reports have been published. In one Swedish article, ophthalmologists reported six separate cases of gardeners and botanists who had somehow gotten the sap from angel’s trumpet into their eyes and developed dilated pupils and blurred vision. The plant is inordinately beautiful, so it is not surprising that it has become very popular in Sweden. Large delicate branches grow toward the sky and then plummet earthward. At the end of each shoot is a large white flower, about six inches long and shaped like a bell or trumpet that hangs several feet above the ground.
In a case remarkably similar to that of Shawn Matthews, doctors in San Diego reported on a twelve-year-old boy whose parents had brought him to the emergency room because of a “funny feeling” in the eye and a dilated left pupil. The remainder of his examination was normal, and he too denied having taken, touched, or been exposed to any medications or eye drops. On requestioning the boy about the details of his recent activities, the doctors found that he had been playing in his backyard that morning and had run into a plant—an angel’s trumpet. The parents remembered seeing the boy playing with some of the flowers near their pond.
The same effects have been reported as a result of contact with other, related plants. Several cases of dilated pupil from the moonflower (Datura inoxia) have occurred. Various medications have also caused similar effects. One of the earliest published reports concerned a twenty-eightyear-old woman who consulted her optometrist after three days of having difficulty reading due to difficulty focusing her eyes. Both her pupils were large and did not constrict when light was shined in. Detailed and repeated questioning did not reveal any medication use or handling of medications. She was referred to another doctor, who got the history that the patient had been using a medicated patch to treat her motion sickness. The active ingredient in the patch was scopolamine, which is an atropine-like alkaloid that causes dilated pupils. Somehow the patient must have handled the patch, got some of the substance on her fingers, and then touched her eyes.
In 2004, a twenty-year-old woman who was being treated for leukemia complained of headache and noticed a dilated pupil on her left side. Other than that, her neurological exam was normal, but because she was being treated with strong chemotherapy agents for her cancer, she underwent a CT scan of the brain, which was normal. After this testing, the patient recalled having taken a scopolamine patch off her scalp just before the headache started.
Other cases have occurred from eye drops and from the inhaled medications that asthmatics use for treating a flare-up. In all of these cases, the nature of the problem was not revealed until the doctor eventually unearthed information that had not been offered initially.
“In medicine, we feel about 80 percent of diagnoses can usually be made by the history alone,” says Setnik. “Despite all the high-technology tests we have available now, it is still the history that tells you what is wrong with somebody. If I did not have a ready explanation, I was seriously thinking about transferring him to the Boston Children’s Hospital for him to have an angiogram. And so I started over again.
“Now I wanted to know if there was any possible way Shawn had gotten something into his eye. Was anyone in the family using eye drops? Was there a visitor to the house using them? Were there any old medications in the house? Then Mrs. Matthews looked up and said, ‘Oh, my God! What are we putting in Fluffy’s eyes?’
“‘Who’s Fluffy?’ I asked. It turns out that Fluffy was the cat, and she had some type of eye problem that the veterinarian was treating with an ointment. Then Shawn volunteered, ‘Just before I got the headache, I was sitting at my desk and Fluffy jumped up and I petted her.’
“I literally said, ‘That’s it!’ But just to be sure, I asked Mrs. Matthews to go home and bring back Fluffy’s medication. Shawn and his father stayed in the ER. About thirty minutes later, she returned and handed me a standard fifteen-gram-size aluminum tube. The label, which had been neatly typed by the vet, read ‘1 percent atropine ointment.’
“I told the family that Shawn’s pupil would likely stay dilated for seven to ten days but that his eye would ultimately be completely normal.” This case shows how powerful the drug is: Shawn hadn’t put the medication in his eye. He only petted the cat, which must have gotten some of the ointment on her fur from cleaning herself. Shawn must have then rubbed his eye.
part three
The Internal Milieu
10 A Study in Scarlet
On Saturday, October 5, 1985, Dr. Bernard Guyer, a pediatrician and professor at the Harvard School of Public Health, sat having lunch at an inn in New Hampshire. He felt about as relaxed as could be. He was celebrating his forty-third birthday and enjoying the crisp air at a luxurious world-class resort nestled between the White Mountains and the Connecticut River. Just after noon, along with his wife and his mother, Guyer sat down for lunch. Joining them at the table were close friends: Dr. Mary Wilson and her husband, Dr. Harvey Fineberg, and Dr. Phil Stubblefield and his wife, Linda.
In addition to it being Guyer’s birthday, the group was there teaching and attending a medical conference
sponsored by the School of Public Health, and the morning session had just ended. Surrounded by friends and family, Guyer was ready to enjoy a great birthday meal.
Planners of medical conferences need to find a stellar teaching faculty, but one extremely important aspect is holding them in desirable locales at the right time of year to attract as many doctors as possible to attend. Family members are welcome to come along, and between teaching sessions, break times are generally built in so that the attendees and their families can enjoy the surroundings and facilities of the chosen spot.
So for its conference on maternal and child health issues, the School of Public Health decided on a luxury resort in Whitfield, New Hampshire. The organizers chose to hold the conference in the fall, and they planned it on a weekend. Fall in New England; what could be better? If the weather would cooperate, the setting would be perfect.
And Mother Nature did not disappoint.
As the group sat in the well-appointed dining room, the afternoon conference schedule was hours away. The hotel was a classic New England resort, a large five-story wood structure. The dining room featured huge glass windows that overlooked a vast lawn set up with deck chairs and a swimming pool. The sun was still high in the mid-day sky. Almost as if it had been placed there as a prop by central casting, a large white swan had settled in the pool. Beyond the lawn lay the full panorama of a forest full of evergreens, oaks, sugar maples, aspens, beeches, and birches. The day’s tempo was as slow as the metamorphosis of the surrounding trees, whose leaves were beginning to blush crimson, flash scarlet, blaze orange and yellow, against a backdrop of every shade of green imaginable.
The notion of targeting a conference in northern New England during the fall to take advantage of the foliage seems completely natural to us now, but it wasn’t always that way. Over a century and a half ago, during his time at Walden Pond, Henry David Thoreau was one of the first to describe the magical quality of fall in New England. In his 1862 essay “Autumnal Tints,” he wrote, “October is the month of painted leaves. Their rich glow now flashes round the world.” He described purple grasses, red maples, scarlet oaks, chrome yellow poplars, and lemon yellow elms. Thoreau was ahead of his time in his appreciation of the fall foliage season. The cottage industry of tourists flocking north to enjoy and photograph the brilliant rainbow of color was not part of the collective consciousness until the last quarter of the nineteenth century.
The first European settlers cleared large tracts of land for farming and grazing animals, so there was likely less color to be appreciated. But beyond that simple fact, the color did not seem to make an impression. Despite their recording extremely detailed notes about the nature around them, the early inhabitants rarely mentioned the changes of leaf color in autumn. Even Thoreau noted that “the autumnal change of our woods has not made a deep impression on our own literature yet. October has hardly tinged our poetry.” He continued: “A great many, who have spent their lives in cities, and have never chanced to come into the country at this season, have never seen this, the flower, or rather the ripe fruit, of the year. I remember riding with one such citizen, who, though a fortnight too late for the most brilliant tints, was taken by surprise, and would not believe that there had been any brighter. He had never heard of this phenomenon before.”
As fertile agricultural lands were developed in the West, the amount of undeveloped land in the Northeast increased; the expanse of forest grew. Some have suggested that New Englanders began appreciating the color of their forests each fall at around the same time as the Impressionist movement in painting became the rage in Europe. And of course the automobile opened this territory up to “leaf peepers,” visitors from southern New England and other more remote areas who travel to the region with the sole goal of observing the foliage. In modern times, fall in New England has become a full-fledged tourist industry.
Bernard felt lucky to be dining with family and friends in such a lovely place on his birthday. The group decided to have the inn’s planned luncheon menu, which included five courses—appetizer, soup, salad, entrée, and dessert. There were choices for each of the courses, seafood, pork, vegetables, beef, chicken, and more. They tried a variety of dishes, but for the entrée, Guyer and most of the others selected the fresh bluefish seasoned with paprika. The mood was lighthearted, the pace relaxed, until halfway through coffee and dessert, when the meal came to an abrupt halt as Guyer’s mother turned to her son and said, “You’re all red!”
Phil Stubblefield, a gynecologist, recalls joking, “You’re too young for hot flashes, Bernie. Maybe we ought to prescribe some estrogens.”
The group laughed, but then the room began to feel stuffy and oppressive to him, so Guyer decided to go outside. “I felt hot,” he recalls, “and a bit dizzy; I wanted fresh air. I left the dining room, and as I crossed the hotel lobby I passed by a mirror. Sure enough, my face was red as a beet! Then I went out onto the porch and tried to analyze what was happening.”
The symptoms had started abruptly; he felt flushed, hot, and dizzy. His skin, especially on his face, was intensely scarlet. He checked his pulse and it was racing.
Guyer’s initial self-diagnosis was an anxiety attack, but that theory suffered from one glaring and obvious problem: he wasn’t feeling the least bit anxious. Everyone at the table was a close friend or family member. He was away for a fun weekend in a beautiful location. Guyer had been thoroughly enjoying himself.
Another possibility that crossed his mind was an allergic reaction, either to a food he had eaten, maybe an additive, or to something in the environment.
Allergic reactions are the body’s response to a foreign protein or other substance. Special types of white blood cells recognize the outside intruder (called an antigen) and begin to release chemicals that cause the allergic reaction; the best known of these chemicals is called histamine. Histamine and other mediators of allergic reactions can lead to skin rashes, especially hives, or constriction of the upper and lower airway passages, manifesting as shortness of breath. In severe reactions, the blood pressure can plummet to dangerous levels, and in the rare case, patients can die if the reaction goes unchecked.
A few minutes later, Phil Stubblefield strolled out onto the porch to check on his friend. “Phil and I talked for a while,” recalls Guyer. “Then I noticed the strangest thing. ‘Phil,’ I said, ‘you’re turning red too!’”
“That’s when I began to feel it,” Stubblefield recalls. “I was hot all over. I had a headache, and it was difficult to stand, I was so dizzy.”
Stubblefield and Guyer went to Stubblefield’s room, where, with their families clustered around, they lay on adjacent twin beds, scarletfaced and open-collared, comparing notes. Although they were both physicians, they followed the old adage, “A doctor who treats himself has a fool for a patient,” and consulted the hotel doctor. The hotel physician agreed with them that a hospital visit seemed unnecessary at the moment, as their symptoms were neither progressing nor seemed to be life threatening. At the same time, they all remained puzzled about the cause of these mysterious symptoms. An anxiety attack was now out of the question, and the likelihood that two men were both simultaneously suffering from an allergic reaction seemed remote. But if not that, what was causing this bizarre reaction?
They decided to call in Drs. Mary Wilson and Harvey Fineberg, one of the couples that had just eaten lunch with them. Wilson was the chief of infectious diseases at Mount Auburn Hospital in Cambridge, Massachusetts. As a specialist in infectious diseases, she was used to diagnosing unusual ailments and sorting through various clues to decipher which ones were germane and which could be discarded. In this case, however, she had suspected the diagnosis even before she left the lunch table. She was pretty sure that Guyer was suffering from scombroid poisoning, and she was equally certain that the bluefish was the culprit.
Scombroid poisoning is an acute illness caused by eating fish that has not been handled or refrigerated properly, which leads to contamination by bacteria an
d their toxic by-products. It is sometimes confused with an allergic reaction to eating fish because of the overlap of symptoms. The word itself derives both from the Greek skombros and the Latin scomber, both of which refer to a particular fish, the mackerel. In scientific terminology, the Scombridae are a family of fish that include such favorites as tuna, mackerel, albacore, bonito, and swordfish. These fish are large, pelagic (oceangoing), rapid swimming fish that have been an important source of human food for many centuries.
In spite of the name, it is not uncommon for nonscombroid fish (among them bluefish, herring, anchovies, mahi-mahi, and sardines) to also cause the exact same symptoms. Scombroid poisoning is common and occurs in both the tropics and temperate climates.
Fish and seafood are an incredibly important and usually safe food source. Like any product that originates in nature, however, there are potential risks. In 1987, for example, Americans purchased more than 3.5 billion pounds of commercially caught seafood—about fifteen pounds for every person per year. This figure does not count the two pounds per person that is recreationally caught. Not all of this food is safe, at least not by the time it reaches your dinner plate.
From 1980 to 1994, the New York State Department of Public Health documented 339 separate seafood-associated outbreaks of illness involving nearly 4,000 patients, 76 of whom were hospitalized, and 4 of whom died. During this period, seafood poisoning accounted for nearly 20 percent of all reported food-borne illnesses. Shellfish were the most frequently implicated type of seafood (two-thirds of all seafood-related outbreaks). In the cases where it was possible to pinpoint a specific cause, scombroid poisoning accounted for nearly half of them. Of the scombroid outbreaks, the most common source was tuna, followed by bluefish.
The Deadly Dinner Party: and Other Medical Detective Stories Page 16