The Deadly Dinner Party: and Other Medical Detective Stories

by Dr. Jonathan A. Edlow M. D.

  These much larger ticks are the vectors of all sorts of infectious agents. They carry the bacteria that cause Rocky Mountain spotted fever and tularemia and ehrlichiosis. They carry some viruses as well. But there is one disease that Dermacentor ticks cause that is not an infection at all: tick paralysis. This results not from a bacteria or virus passed along by ticks but from a neurotoxin that the ticks themselves produce in their salivary glands. However, tick paralysis is an extraordinarily rare disease, and it is virtually nonexistent in New Jersey. The vast majority of doctors go through their entire professional careers without ever seeing a single case of tick paralysis. Even at CHOP, with the collective experience of the emergency physicians and the neurologists, none had ever seen a case. Finding this tick changed everything though, and Annie’s doctors were cautiously optimistic.

  “At that point,” says Posner, “we figured that tick paralysis was the correct diagnosis, and if we were right, we had already treated it [by removing the tick]. But because none of us had ever seen a case, we still admitted her to the ICU because we didn’t know what to expect.”

  Tick paralysis is a disease of both humans and animals that occurs worldwide. In North America, it is most commonly seen in the western United States and Canada, but even in these areas it is quite rare. In one series of cases from the state of Washington, only thirty-three instances were identified over a fifty-year period. Tick paralysis mimics GuillainBarré syndrome; it presents as an ascending bilateral flaccid paralysis, although it usually progresses over hours to days, faster than the typical case of Guillain-Barré. The neurotoxin is produced when the female ticks of certain species feed. A tick that remains attached to a human or animal, feeding on its blood, secretes the toxin into the host’s bloodstream. Over the course of several days, the toxin is absorbed, and paralysis rapidly ensues. Also like Guillain-Barré, sensory function is spared, but as the paralysis tightens its grip on the victim, the respiratory muscles fail, and without intervention, many patients die.

  Once diagnosed, the treatment is simplicity itself—remove the tick. Within hours, patients begin to show meaningful signs of improvement. This is because, unlike with Lyme disease or other tick-borne infections, it’s not an infection at all that is causing the symptoms. Once the tick is removed, it stops secreting the toxin into the victim, and the toxin is cleared from the body and the nerves begin to work normally again. But if the tick is not found, some patients, as much as 12 percent, will die from the condition. Patients whose diagnoses remain obscure may stop breathing and require a ventilator to survive.

  In others, the offending tick probably feeds to repletion and then falls off, and the patient improves, possibly without ever being correctly diagnosed. As with any extremely rare disease, many patients with tick paralysis are not properly diagnosed, at least not initially, because the condition mimics more common problems.

  The earliest reference to tick paralysis in humans dates back to 1824, in Australia. In that year, William Howell referred in his diary to a certain tick, “which buries itself in the flesh and would in the end destroy either man or beast if not removed in time.” The first two reports of tick paralysis in North America appeared independently in 1912. One resulted from inquiries to physicians in British Columbia to learn whether Rocky Mountain spotted fever was present in their province. The responses from the physicians suggested nine cases of tick paralysis. That same year, an Oregon physician summarized reports of twelve cases that had occurred in Oregon and Idaho, three of which were fatal.

  A year later, a young pathologist named Seymour Hadwen was sent by the Department of Agriculture of British Columbia to investigate an outbreak of paralysis in sheep. One farmer had reported that, each spring for the previous three years, his sheep had been dying from paralysis. The local veterinarians had looked into the matter but were stumped. When Hadwen started his investigation, he found a fully engorged tick on the back of one recently paralyzed lamb. Two months later, he observed that, in another lamb, which was paralyzed in the hindquarters only, removal of an engorged tick was associated with rapid improvement in the animal’s condition. Wise enough to discuss the situation with local farmers, Hadwen learned that other animals— horses, birds, rabbits, and dogs—also became paralyzed in the same way.

  Hadwen was aware of what little information existed at this time in the medical literature and began to investigate further. He experimented with three lambs, allowing ticks to feed on them, and found that as the female ticks engorged, usually after six to eight days of feeding, he could reproduce the paralysis. He also observed that when he removed the ticks, the animals recovered. From these and other experiments, he made three deductions. First, the symptoms were clearly related to the feeding of adult female Dermacentor ticks and would begin to occur at about day six. Second, he theorized that the illness starts when the tick injects a toxin coincident in time with when the tick has completely engorged. He thought an infectious agent was unlikely. Last, he observed that the progression of symptoms from isolated hindquarter weakness to total paralysis, including respiratory failure, was rapid and predictable. He added, “It would appear advisable . . . to remove the ticks from the affected animals.”

  Hadwen’s observations remain accurate nearly a century later. In humans, there is a tendency for tick paralysis to occur in children, probably because, pound for pound, the dose of the toxin in children is higher than in adults. Among children, girls are affected more often than boys; the likely explanation is that many young girls have long hair, which makes it harder to see the ticks, allowing them to feed undetected long enough to secrete their toxin. The ticks that produce tick paralysis can feed for a week or more, and it usually takes one that has been feeding for about five days to cause symptoms.

  Because tick paralysis is so rare, it’s frequently misdiagnosed, often as Guillain-Barré syndrome. In one series of six patients from Mississippi, all were initially diagnosed with Guillain-Barré; in one five-year-old girl, the correct diagnosis was made only after she was already receiving treatment for that problem. While the mother was bathing the child in the ICU, she found an engorged tick and removed it. The child rapidly improved. The same thing happened when a nurse in Colorado found an engorged tick on the scalp of a six-year-old while she bathed her. This youngster was on a ventilator in the ICU for presumed Guillain-Barré syndrome.

  There is a long list of other instances in which the diagnosis was made almost by accident. One was a six-year-old girl from Georgia, on whom a pediatric doctor in training found a tick while he was preparing to insert a central intravenous catheter for plasmapheresis. In that case, three pediatricians, a pediatric neurologist, and an intensive care specialist had all missed the tick. In another, while a technician was applying electrodes for an electroencephalogram (EEG) onto the scalp of a threeyear-old, the child’s mother found a tick. In a case from North Carolina, an MRI scan showed a tick embedded in the scalp. So it is completely understandable that the diagnosis could be missed initially.

  “She was down in the emergency department for a while,” Dr. Posner recalls about Annie, “and before she went upstairs to the ICU, I remember her saying, ‘I don’t see double anymore, Mom!’ By the next morning, her symptoms had improved 99 percent, and twelve hours after that, she was entirely normal.” Annie recovered fully, and the next day she was discharged from the hospital feeling perfectly well. This was a happy ending for Annie, but as it turned out, it was not the end of the story.

  On July 22, two months to the day after Annie’s presentation, Dr. Reza Daugherty got a phone call. “We do the medical command for transports of patients that are being referred to CHOP from outside hospitals. I was in the office that day, and carrying the medical command pager, when I got a call from an outside hospital. The doctor on the line said, ‘We’ve got this little girl with ataxia and weakness . . . ’ the story began.” The doctor from the referring facility relayed a familiar tale. He had a seven-year-old who began complaining of pain in both legs
and then, over the next twenty-four hours, became so weak that she could not walk. As a result of her weakness and clumsiness, she could not feed herself because she could not bring a fork to her mouth.

  “At the outside hospital,” recalls Daugherty, “they did some routine blood work and a brain CT scan; all the results were normal. They diagnosed Guillain-Barré syndrome. I asked that they not do any further tests or the lumbar puncture, but to just transfer the patient to us. I remember saying to the transport nurse, ‘this sounds like that last case but there’s no way she’s got tick paralysis.’ It was early afternoon when she physically got to the emergency department. I was in the office, but I ran down to see her as soon as she arrived. I remember that the mom was remarkably calm. The resident was already examining the girl. She was moderately weak in the lower extremities and slightly so in her arms. Her right eyelid was a bit droopy, and she was very clumsy when moving her arms and legs.

  “By now, she was about twelve hours into her course. She had very long straight hair. When I examined her scalp, to my amazement, I found an engorged tick in almost the exact same location as in the first patient. I explained the situation to the parents, who were beginning to get anxious, and I removed the tick. By thinking of the diagnosis [and then finding the tick and removing it], we avoided all the imaging tests, the spinal tap, and the ICU admission. She began feeling better within two to three hours, and in eighteen hours, she felt normal and went home.

  With two cases of a rare and potentially fatal disease presenting to the same hospital in such a brief period of time, the physicians at CHOP notified the CDC in Atlanta. The CDC posted a notice on its Internet epidemic information exchange site on July 29, 2003. Following protocol, the epidemiologists also notified the New Jersey Department of Health and Senior Services. The state officials were fairly sure that the two cases represented just a very unusual coincidence. Nevertheless, they held a press conference to notify and warn the public. The commissioner of the department, Clifton Lacey, said: “Tick paralysis is very rare in this part of the country. This is extremely interesting to us. This may be the first two cases in New Jersey. Clearly we have not heard of cases in at least three decades.”

  He and his staff got the word out to parents about the importance of regular tick checks on their children. There were newspaper articles and television interviews. After receiving permission from the two families involved, the department conducted further interviews of those involved and evaluated their risk factors. These investigations did not find anything out of the ordinary for a dog-owning suburban family in southern New Jersey. In the end, the state officials were correct: it appeared to be a very unusual coincidence; no further cases were diagnosed.

  Dr. Daugherty recalls: “It was really amazing when I saw the second case; I was shocked that it could be true—to see two cases of such a rare disease in so short a period of time. I also felt terrific at how easy it was to ease the parents’ anxiety. I told them that I had seen a little girl with the same thing two months before and that she did very well. The ironic thing about the first case was that after about twenty doctors had seen the patient, and having lots of tests including an MRI and a spinal tap, that it was the mom who really made the diagnosis.”

  7 An Airtight Case

  “I got sick the first time in December,” recalls Philip Bradford (as I’ll call him). “At first I thought it was just the flu—the usual cough, fevers, chest pain, just feeling lousy, but it lasted a few weeks. When it didn’t clear up, I saw my doctor, who prescribed first erythromycin and then a tetracycline-type drug. Finally, he ordered a chest x-ray, which showed pneumonia. A month later, there was still no improvement, so he hospitalized me and I had a whole array of tests.”

  These included skin tests for tuberculosis, sputum cultures for more conventional bacteria, a biopsy of a suspicious lymph node from the area just above Bradford’s collarbone, and a bronchoscopy—a test in which a rigid scope is inserted through the throat and into the large bronchial tubes so that the physician can directly inspect the air passages in the lungs. This was in 1973, before CT scans of the chest, so he also had special lung x-rays called tomograms, where conventional x-ray machines narrowed their field of focus to examine thin slices of the lung in greater detail. The tomograms showed clusters of nodules in both lungs that were very concerning to the doctor. Despite this extensive evaluation, however, the physician was unable to make a definitive diagnosis, but he did reach a tentative one.

  Remembers Bradford: “The doctor’s conclusion, which he communicated to my wife in the hall outside of my room, was that I had lung cancer, and he advised a major operation to biopsy the lung. I will never forget that diagnosis.”

  The doctor thought the cancer had spread to the lungs from another, as yet undiscovered site. In order to make a definitive tissue diagnosis of this presumed metastatic cancer, he advised a thoracotomy—a major surgical procedure that is designed to open up the chest like a clamshell, so that suspicious tissues can be biopsied and examined under the microscope.

  But Bradford, thirty-three years old, was not frightened. “I simply didn’t believe that’s what I had,” he explains. “I was healthy and a nonsmoker. I wanted a second opinion. My wife telephoned some physician relatives who ultimately put us in touch with Dr. Earl Wilkins. Dr. Wilkins spent a lot of time with me. He asked me a lot of questions and examined me from head to toe. He didn’t know what I had, but he told me he didn’t think it was cancer.”

  Dr. Earl W. Wilkins Jr., now retired but then a senior thoracic surgeon at the Massachusetts General Hospital in Boston, remembers the case clearly. “He brought a stack of records with him. I reviewed the medical records of the first hospitalization, then took my own history and carefully examined him,” he recalls. “[Cancer] was what he and I were worried about when we first met. The tomograms obtained at the outside hospital demonstrated multiple nodular densities, four on the right side and two on the left, that were highly suggestive of metastatic cancer.

  “[But] I was struck by two things: First, if this was metastatic cancer to the lung, I could detect no primary site. And second, I had the benefit of a longer time interval. Although the radiologist wasn’t sure, I thought that one of the nodules on the latest x-ray was slightly smaller than it had been on a previous film. If that was true, a cancer would be very unlikely. Neither I nor the patient was inclined to go ahead with the thoracotomy.”

  Another factor that was in the back of Wilkins’ mind was that if this was metastatic cancer that had already spread so extensively, there was little risk in waiting a short period of time. As it turned out, not doing the surgery was the right choice, because over the next few weeks, Bradford’s symptoms, along with the nodules on the chest x-ray, vanished as mysteriously as they had appeared.

  “I just gradually got better,” recalls Bradford, an executive with a large banking firm. He worked in downtown Boston and lived in a small town on Boston’s South Shore, in a marshy area, across from a farm. Despite the fact that there were no overt changes in his life, he remained well for almost a year. But then, in September 1974, he again started coughing and running a fever. And once again, his chest x-ray blossomed with ominous nodules; then, as with the previous episode, after a few weeks his symptoms mysteriously vanished.

  This time, Wilkins sent him to see Dr. Robert H. Rubin, an infectious disease specialist at Mass General, and now director of the hospital’s clinical investigation program. “At the time I was doing some general internal medicine as well as infectious diseases. After reviewing [all of the records from the first hospitalization], I was immediately impressed by three aspects of the case,” Rubin recalls. “First was that Bradford appeared healthy and athletic, not the picture of someone with a chronic disease. Second, between episodes, he continued to jog over five miles with no apparent problem. And third, his physical examination was normal.”

  Rubin reasoned that if the nodules that appeared on the x-rays were always in the same location, then
a chronic structural or anatomical lesion within the lung would be the likeliest cause. However, each x-ray showed that different parts of the lungs were involved during different episodes. The first time it was the right middle lobe and both lower lobes; the next time, it was the upper lobes. “There were clearly different segments of the lung involved each time. Therefore,” says Rubin, “it must have been something in the environment. And because none of the multiple tests had revealed the presence of a microbe that might have been the culprit, the question of hypersensitivity pneumonia immediately arose.”

  Pneumonia, or more properly, pneumonitis, simply means inflammation of the lung. The cause of that inflammation could be anything— bacteria, a virus, a chemical, or even radiation. In typical infectious pneumonia, the bacteria or virus directly causes damage to tissue. In an attempt to kill the invading pathogen, the body mounts a cellular and chemical war. The body’s immune system—antibodies and various types of specialized white blood cells called lymphocytes, plasma cells, and polymorphonuclear leukocytes—tries to contain the foreign material, and then kill it. Inflammation is the result of the clutter and debris left behind on the battlefield.

  Hypersensitivity pneumonia occurs when a lung becomes inflamed in response to breathing air that contains organic dusts laden with biologic stowaways. These stowaways are typically small amounts of mold, or fungi or bacteria or spores that are drawn in by the normal flow of air and are small enough to be deposited deep into the lungs. They land in the alveoli, the functional units of the lung. Blood flows past these tiny air-filled sacs to facilitate the exchange of gases—oxygen in, carbon dioxide out—which is the lung’s primary job. Although these biological stowaways are not necessarily as toxic or invasive as other viruses and bacteria that cause typical infectious pneumonia, the immune system still perceives them as foreign invaders and therefore seeks to contain them.