THE ART OF MEDICINE
CONFRONTING RARE DISEASES
Medicine is a science of uncertainty and an art of probability. — Sir William Osier
One of the most challenging aspects of a career in diagnostic internal medicine is the opportunity it inevitably presents to treat rare diseases. Typically, patients arrive in our offices after a primary health care physician and two or more specialists have done as much as they can and then, metaphorically, thrown up their hands and asked for diagnostic help.
Sometimes, the right answer turns out to have been hiding in plain sight. But just as often, the solution is diffcult because it involves a rare, seldom-seen disease. Both the diagnostic process and the subsequent treatment are important aspects of the art of medicine.
Some years ago, I was invited to become consulting physician in internal medicine to a professional sports team in Toronto. The players needed attention from various specialists, including of course orthopedic surgeons, but they very seldom felt the need to seek my services. They were essentially too healthy. Then someone suggested it might be more useful if I consulted on members of the team's executive management, so I agreed.
Thus did I get to meet John C, then 62 years old. Although initially reluctant, he did allow me to take a family history. Among other things, it indicated a genetic predisposition for colonic polyps, and I eventually persuaded him to have a colonoscopy. As it turned out, he had more than 100 polyps, which are generally considered precursors for colon cancer. Needless to say, he was very grateful. After the polyps were removed, we worked on a new regimen for diet, exercise and blood pressure control.
Some months later, I bumped into John in the hospital atrium and immediately noticed he was limping and dragging his leg.
"What's the matter?"
"I'm not sure," he said. "This happened last night. I just feel a little funny."
"Well, go upstairs. It's important to examine you."
It did not take long to discover that he had a hemiparesis, a partial paralysis, affecting an entire side of his body. It was the result, I suspected, of a small stroke. An MRI later confirmed that diagnosis. It had affected an important part of the brain but, fortunately, only a small portion.
I gave John another lecture at that point on the importance of diet, exercise and staying on his medications.
John travelled frequently to the United States with his pro team. On one of his next trips, he fell into conversation with a rival executive who denigrated the quality of medical care John was receiving in Canada. He advised him to come to the U.S. where, he assured him, surgeons could perform angioplasty — essentially, a balloon opening — for the blood vessel in his brain.
When John returned, he conferred with me and others about that idea. After sending him to see a Toronto neurologist, we recommended a conservative approach that, for the moment, excluded angioplasty. We had made the assumption that there was some atherosclerosis in the brain, but we considered surgery too dangerous at that point.
"The choice is yours," I explained to him, "but we think it's more prudent to be less aggressive."
He agreed. "If you say, 'Don't do it,' I won't do it."
John did well for the next few years. He made a full recovery from the stroke, regaining his strength and his ability to walk without a limp. But one day, he suffered a cardiac arrest while sitting at his desk. He might have died, except that a colleague happened to pass by his office within two minutes of the event and saw him slumped over. He immediately called 911 and began to administer cardiac massage. John was very lucky. The survival rate for heart attack victims that suffer unwitnessed cardiac arrests is very low.
Interestingly, a subsequent angiogram indicated there were no serious blockages in his coronary arteries. In other words, he did not have conventional coronary artery disease.
Again, John made a good recovery and returned to work. Two years later while attending a social function, he experienced acute abdominal pain and was rushed to an emergency ward. I saw him the next day and ordered a CT scan that revealed swelling of the bowel. An astute colleague, imaging specialist Anthony Hanbidge, suggested it might be amyloidosis, a rare, not well-understood disease. In my lifetime, I have seen it less than half a dozen times.
In fact, it is safe to say there is more that we don't yet know about the pathophysiology of amyloidosis than we do. What we know is that it creates amyloids, deposits of fibrous proteins, which interfere with the normal functioning of the body. We also know that it has been implicated in a wide variety of diseases, including Alzheimer's, diabetes, Parkinson's and heart arrhythmias — the very kind that might have precipitated John's cardiac arrest. Moreover, amyloidosis is related to multiple myeloma, a cancer of the white blood cells.
If Hanbidge's assessment was correct, we should have been able to find distinct markers for amyloid in the blood, including so-called immunoglobulin light chains — defective proteins involved in the body's immune system. There's another indicia for the disease — dark, purplish rings around the eyelids; John, it turned out, had these, too. We biopsied the eyelid tissue and confirmed the presence of amyloids. Finally, we did a bone marrow test and it, too, confirmed the diagnosis.
So a mystery had finally been solved. John's ailments through the years — the stroke, the cardiac arrest and the bowel disorder— were in the end the result of a single rare disease, amyloidosis.
It is potentially lethal, but also potentially treatable. John was given chemotherapy and responded well.
The art of medicine often involves precisely this kind of difficult process, where the clinician struggles to identify the interrelationship of symptoms and to integrate knowledge that may affect different organs over a long period of time. But you have to follow the clues. A cardiac arrest that was not caused by arterial blockages should have alerted us to the possibility of amyloidosis earlier.
In a similar case, I was recently introduced to Gregory, a 64-year-old university professor. He'd been an athlete in his youth and had remained active, carefully watching his diet and his weight. After experiencing some shortness of breath, he'd been to another hospital and been diagnosed with hypertrophic cardiomyopathy, a genetic disease in which the muscles of the heart harden or thicken. If the muscles enlarge in the wrong places, they can interfere with the organ's delicate balance of rhythm and cause sudden death. Athletes often have enlarged hearts and are thus more susceptible to complications in the organ.
Despite the diagnosis, confirmed by listening to the heart and an MRI, Gregory was insistent that something else was going on. He had complained to his family doctor of feeling tiredness in his legs when he walked. He could only complete half his usual routine on a treadmill.
At that point, he was referred to me. More than most patients, he was assertive in pushing for tests that would get to the borttom of things.
"Well, there is a heart problem, because we can hear it" I told him. "And the weariness in your legs may be a natural consequence of what's happening in the heart. Your heart isn't pumping as well as it should."
"Absolutely not," he insisted. "The legs are a separate issue." I then suggested we take another, closer look at the heart. In fact, Toronto General Hospital runs a clinic especially for patients with hypertrophic cardiomyopathy. I wanted to send him there.
"Don't send me there," he pleaded. "I was warned that they would do invasive procedures and then start chopping up my heart."
Apart from the heart, his physical exam was normal, except for some mild parasthesia — tingling — in his feet.
"If I'm right," he said, "and it's not just the heart, what could it be?'
"It could be spinal stenosis," I said. "At your age, you're entitled to have some arthritis. That may affect bony parts of your spine, which impinge on the spinal cord and give you these feelings of tiredness when you walk. We call it spinal claudication."
A good theory, perhaps, but erroneous. A subsequent MRI showed no compression of the spine.
My next idea was to consult with a colleague, cardiologist Dr. John Janevski. After reviewing the case, he noted that Gregory's heart voltage readings were lower than they should have been — a potentially important clue. The best option, we agreed, was to send him to the hypertrophic cardiomyopathy clinic — the very place he was refusing to go.
We continued to do battle — Gregory maintaining that his heart was not the cause of his leg fatigue and me insisting that it was. Somehow, Dr. Janevski and I managed to persuade him to visit the clinic and see Dr. Harry Rakowski, among the world's reigning experts on the condition. It did not take long for Rakowski to report back, but the diagnosis surprised all of us — cardiac amyloidosis. A bone marrow test later confirmed the presence of amyloid, protein-rich deposits that gradually replace heart muscle and impair the organ's function. The patient promptly began chemotherapy but, sadly, it was by then too late. He succumbed soon afterward.
Many rare diseases, of course, are rare only in the context of the developed world. In my native Jamaica and in the tropical Third World generally, the rare can be quite common. Perhaps with my origins in mind, a colleague once sent me a patient that he suspected was suffering from a disease known as ciguatera. Well known in the Caribbean, it is caused by toxins that may reside within several varieties of reef fish. Eating the fish can give you the disease. It also gave me one of the most complex cases I have ever dealt with.
Nigel was a retired businessman of about 70. He had a history of coronary heart disease and had received a triple bypass some years previously. It did not relate directly to the reported diagnosis of ciguatera, but it was something to consider in terms of possible drug treatments.
After the initial episode of vomiting and diarrhea in the Bahamas, Nigel returned home and soon started to complain of chronic fatigue, with acute pain and tingling of the hands and feet.-The pain was severe enough to interrupt his sleep. Eventually, these symptoms subsided, but then returned, with swelling in his legs. His family doctor thought it might be poly-myalgia rheumatica, an autoimmune disorder, and prescribed prednisone. If it was PMR, then the drug would likely alleviate his symptoms. In fact, after the first day, he was much better. But on the second day, he relapsed and by the third day was so sick that he stopped the medication.
His GP then sent him to Dr. Jay Keystone, an infectious disease specialist. He thought Nigel's symptoms might have been the legacy of his encounter with ciguatera, but recommended I see him. I confessed to no special expertise, despite my Caribbean background, but found a resident eager to explore the ciguatera mystery. Little did we know how difficult and complex Nigel's case would become.
A series of blood tests quickly revealed inflammation of some kind — above normal levels of ESR and C-reactive protein. Those results supported the family doctor's diagnosis — poly-myalgia rheumatica (PMR). In the meantime, my colleague Dr. David Frost examined Nigel and discovered that his fingers were oversized and spade-like. It was Frost who first raised the possibility of acromegaly, a rare disease caused by excess production of the human growth hormone in the brain's pituitary gland. Spade like fingers is one sign of the disease.
Interestingly, it takes seven years on average to make an acromegaly diagnosis — precisely the length of time Nigel had complained of his symptoms — because its manifestations unveil themselves so slowly. And the disease typically affects middle-aged men. Rare though it is, acromegaly has affected many famous people including U.S. president Abraham Lincoln, motivational speaker Tony Robbins and former heavyweight champion boxer Primo Camera.
Frost's diagnosis remained, for the moment, speculative, though it was supported by other evidence as well, including carpal tunnel syndrome. If you shook Nigel's hand, he literally screamed in pain. The pain was so intense that he had become deeply depressed; we enlisted a psychiatrist to try and help. We prescribed an anti-depressant medication to help him sleep, but he continued to lament his condition and insist there was no point in living like this.
We ordered yet another CT scan, this time concentrating on his frontal lobe. It revealed enlarged sinuses, yet another feature of acromegaly. Sensing that we were closer to a firm diagnosis, we reexamined his hands. They showed changes of the terminal phalanx, the bones at the tips of our fingers, also compatible with the ailment.
Finally, we x-rayed his feet and compared the results against an x-ray taken three years earlier. It showed that his heel pad had grown from 21 to 26 millimetres. By then, we were beginning to feel confident we had found the right answer — a long way from the original diagnosis, ciguatera. Acromegaly is usually amenable to hormonal treatment and, if necessary, surgery to remove the pituitary tumour that causes it.
On his next visit, I told Nigel that I doubted whether ciguatera was the cause of his problems. The changes in sensation in his hands suggested peripheral neuropathy— some degree of nerve entrapment at the wrist, caused by carpal tunnel syndrome. We sent him to see Dr. Robert Chen, a specialist in nerve conduction, who confirmed median nerve neuropathy — in other words, carpal tunnel syndrome (CTS).
Despite that finding, Dr. Chen wasn't convinced that it was CTS alone; he thought it could be vasculitis, a rare (1 in 2,000) autoimmune condition in which the body essentially attacks its own blood vessels. The same thought had already occurred to me, and I had ordered a CT angiogram scan to test for what is known as medium vessel vasculitis. It proved negative.
Nigel, meanwhile, continued to suffer. He reported severe pain in his arms, knees and hands, which continued to swell. I knew that relatively minor surgery on the hands could relieve the pain, so that was scheduled and performed. But while the swelling was reduced, he insisted that he was not appreciably better. However, nerve conduction tests conducted four weeks showed marked improvement and validated the carpal tunnel diagnosis.
My own instinct, though it seemed impossible to prove, was that his family doctor's instinct had been correct —this was likely poly-myalgia rheumatica. PMR is another one of those Grey Zone diseases that can never be definitively proven or disproven. But his range of symptoms was most consistent with that condition. Then Nigel himself, who had a doctor in the family, came up with his own suggestion — a milder variant of PMR known as RS3PE. Its real name is remitting seronegative symmetrical synovitis with pitting edema, which makes its abbreviation to alphanumeric form entirely understandable.
Nigel's did indeed exhibit several symptoms characteristic of RS3PE, including carpal tunnel syndrome and swelling of his hands. But by any name, the treatment would be the same — prednisone, on a reducing dosage, over a year to 18 months, starting at 20 milligrams. Given his prior adverse reaction, Nigel was reluctant to start the therapy. But he eventually agreed, and within days, he sent me an email reporting that he was much improved and having fun. PMR tends to be an illness that burns itself out after a period of time. Hopefully, that will be Nigel's experience as well.
A PATIENT S PERSPECTIVE
About six years ago, I was stricken with ciguatera, a fish toxin in the Bahamas. It looks like food poisoning, but isn't. It comes on really fast and violently. People can die of dehydration very quickly. It's like lead poisoning and then starts to destroy your peripheral nerves, and thus starts to look like diabetes. I was very tired and kept going to my doctor and walked around with this for years. I had all kinds of tests. Dr. Keystone wasn't sure what to do and sent me to see Dr. Ho Ping Kong. I've changed his name, by the way. It's not Dr. Ho Ping to Find A Cure. It's Dr. Will Find A Cure.
Now, we're having a debate. He think it's PMR and I think it's RS3PE. One of the differences is bilateral systemic swelling in the hands. They took some readings of the nerve that showed poor conduction, so they did surgery to relieve the nerve. And the nerve problem is common in RS3PE, but abnormal in poly-myalgia rheumatica. Then there's dorsal pitting of hands and feet, which I had. I also had a meniscus problem in my knee, which I had surgically repaired, but the swelling and inflammation came back. And that, too, is characteristic of RS3PE. I'm 70 years old now, so this is what I do. My son, a pediatrician, told me about the disease and I researched it. What difference does the diagnosis make? With RS3PE, you are on the same drug, prednisone, but at a lower dose. So I'm pushing for my diagnosis so I can take a lower dose and hopefully have fewer side effects. I'm also on diabetes drugs. They claim I have diabetes, but I think it's all part of the same syndrome. Prednisone stops the pain. Other medications they tried did not, possibly because those other drugs stop nerve pain and my pain isn't nerve pain. What I like about HPK, among other things, is that you see him every week, and not for 15 minutes. He stays as long as it takes.
The practice of medicine is a humbling craft. Questions present themselves by the dozens; answers are often illusive. When I was a student, we were convinced that the study of human immunology would soon yield a treasure trove of solutions to a variety of disease puzzles. Immunology remains an exciting field of study, and we have made enormous strides. But our youthful optimism about causes and cures has not been redeemed.
Similarly, in genetics, we believed that if we could only determine the genetic basis of a pernicious disease such as cystic fibrosis (CE), we would be well launched on the road to a cure. In fact, researchers successfully identified the cf gene more than 20 years ago but, while we can now provide much better ancillary care to CE patients, we have produced no magic bullet to replace or repair the defective gene.
I was reminded of just how complicated medicine can be when I met Elizabeth G. She'd been sent to me with two potentially serious conditions. The first was Cushing's syndrome, first described by the brilliant American neurosurgeon Harvey Cushing in the 1930s. (Serving in the U.S. medical corps during the First World War, Cushing was called upon to treat Lieutenant Edward Osier, son of the legendary Sir William Osier, who had been wounded during the battle of Ypres. Alas, he could not be saved.)
Elizabeth had all of its classic symptoms — weight gain, a moon-like face and ulcerative sores in her mouth. The best evidentiary test for the syndrome is urinary free Cortisol, and Elizabeth registered a level that was almost off the charts. It turned out her mouthwash contained steroids, which her body had absorbed. The second condition was pemphigus vulgaris, which can be lethal, especially if the sores become infected. It's one of the few genuine emergencies in dermatology. But we were able to treat it successfully with medication.
Then, a new complication materialized — poly-myalgia rheumatica (PMR), another autoimmune disorder, PMR manifested for Elizabeth, as it often does, with morning achiness and stiffness in the neck, shoulders and trunk. There was also evidence of inflammation in key blood tests. But like many similar conditions, PMR is a disease that is almost impossible to prove or disprove. There is no specific test. However, if the standard treatment — prednisone — is effective, there's a good chance PMR is to blame.
With pemphigus vulgaris or PMR, the names, in a sense, are somewhat arbitrary since all are very likely offshoots of the same -fundamental disorder, faulty immune system mechanisms, and one manifestation can easily morph into something else.
In Elizabeth's case, a diminishing dosage of prednisone over about a year effectively eliminated the worst symptoms of pmr. But we continue to monitor her and regularly check her inflammation levels.
A patient's perspective —Elizabeth G.
One morning in 2008,1 woke up with ulcerative sores in my mouth. When they did not go away, I went to my dentist. He conducted an oral exam and ultimately concluded the problem was beyond his ability to solve. He sent me to a periodontist, who examined me and concluded the same thing—out of her league. Then I saw an oral surgeon. Same result. Then I was referred to an oral pathologist at a suburban Toronto hospital. By this time, I'd had three biopsies in search of cancer. All were negative. I'd also tried antibiotics, without effect. She referred me to yet another oral pathologist at Mount Sinai, who did an ultraviolet blood test. That came back positive for something called pemphigus vulgaris, a rare autoimmune disorder. It was very painful.
Then I was referred to Toronto Western Hospital to see Dr. Sanjay Siddha, a dermatologist. In the meantime, however, I'd been put on an antibiotic mouthwash that contained a steroid. I had an adverse reaction, swelling up. I became moon-faced. Later, this was diagnosed as Cushing's syndrome, a complication of the Cortisol in the mouthwash. But I did not know it initially. It was at that point that Dr. Siddha sent me to Dr. Ho Ping Kong, because Cushing's isn't a condition he treats. HPK ordered a battery of new tests, MRI, CT scan, an endocrine test, looking for tumours of the adrenal gland. So I was driving in from Oakville every week to see either Siddha or HPK or Dr. Rowena Ridout, the endocrinologist.
I didn't mind because, despite the traffic, it was one-stop shopping. I'd see everyone at the same time. I'd be there the whole day. Fortunately, I had flexibility, because I worked in my husband's office. Prior to being diagnosed, I was in Oakville or Burlington or Mississauga. Weeks would go by, in between appointments, and I was getting no answers. Here, it's all under one roof. It saved me a lot of time.
I continued to work, but had to deal with self-esteem issues because I put on about 40 pounds with the swelling, most of it on my upper trunk. I also developed a hump [lump] on the back of my neck. We did not know what it was at first, but HPK kept saying, "It's a puzzle. We go through a process of elimination and rule out and rule out." Finally, we identified it as the steroid in the mouthwash. I was allergic and ballooned up. The pemphigus can flare at anytime. It isn't genetic.
I had a whole regime of different types of medicine, three or four for different periods of time. One of them had side effects for lymphoma, so they watched me closely and had blood work done every month. Management of the illness became my life. I became depressed — that's a big part of it. You get down on yourself, at least until the diagnosis. And even though I was reacting to the steroids, I needed to keep taking them, to reduce the inflammation. I've been on a reducing dosage over two years. It's taken that long to get it under control. But we experimented with different drugs to see what would work and give the least side effects.
Then, just when this seemed to be under control, I woke up one morning with very stiff shoulders. I could not lift my arms. I couldn't move my neck. I couldn't roll over in bed. I thought it was the air conditioning. I went to see my gp, and she thought it might be arthritis. Then I saw another specialist who ruled that out, and suggested I come back to Western to have it investigated. It turned out to be poly-myalgia rheumatica, PMR, another autoimmune disorder.
So I saw HPK, and we started all over again. I was here every week. I couldn't lift the blow-dryer to dry my hair. I needed an Advil to get out of bed, literally. So now this is another autoimmune disorder. I had to take prednisone again and started swelling up again. But I had to take it. I joined Weight Watchers eventually and, weaned off the prednisone, started to lose weight, about 30 pounds. The good news with PMR is that once it's over, you usually don't get it again, though I do get occasional symptoms. But that's my new normal — about 85 percent of what I was. That's how I feel. The mouth, however, is fine. I'm pain free and back to a normal diet. I function. I'm even about to try curling. It takes sometimes more than two hours to get here, but it's worth it. Things happen more quickly and I can see all the specialists, sometimes in team conferences. I trust HPK. He's been amazing with me. He's like a friend, very personable. He always asks about my family. We discuss our cottages. That's why I continue to come. I would not get this treatment anywhere else. I keep my fingers crossed that I won't get another autoimmune problem.
I BELIEVE STRONGLY IN CONSULTATION. I go out of my way to solicit the opinions of other physicians, junior or senior. However much you think you may know, however convinced you may be of your own diagnosis, there will always be someone who knows a little more or comes at the problem from a fresh and instructive perspective.
I was reminded of this lesson not long ago by Henry, a 55-year-old lawyer. He was referred to me after running a virtual marathon of the local medical system. He was plainly suffering from some sort of multi-system disease. One kidney had already been damaged irreparably, and the second had had to be surgically stented to save it.
In addition, he had iritis (painful inflammation of the eye), urticaria (hives), chronic pleuritis (inflammation of the lining of the lungs), pericardial disease (inflammation of the heart membrane) and polyarthritis (inflammation of several bodily joints). In pursuit of an answer to his many problems, he'd seen family doctors, eye specialists, dermatologists, nephrologists, rheuma-tologists and a cardiologist. When I saw him, he was completely fatigued and his joint inflammation was so severe that he could barely walk.
We quickly came to the obvious conclusion that this was a systemic illness, likely caused by an autoimmune disorder. One of my very bright fourth-year residents suggested it might be lupus — technically known as systemic lupus erythematosus. Although it is more common in women than in men, lupus affects the entire body in precisely the ways it had affected Henry. Predictably, his blood work showed evidence of suppressed hemoglobin and elevated levels of erythrocyte sedimentation and C-reactive protein, both indicia of inflammation. The lab tests also revealed high levels of immunoglobulin M, which would ultimately prove to be the key to the mystery.
I went into my consultative mode and called my Toronto Western Hospital colleague, Dr. Sanjay Siddha, a dermatologist. I explained Henry's myriad symptoms and said we had concluded that he likely had lupus. I wanted Dr. Siddha to perform a biopsy to help us confirm that diagnosis.
He soon did but, even before the results were ready, Dr. Siddha came to see me.
"I know what it is," he said. "It's Schnitzler syndrome."
I had never heard of the ailment.
Then he took out his smartphone and began reading. "Schnitzler syndrome, also known as IgM disease, a rare, autoimmune disorder characterized by chronic hives, bone and joint pain, joint inflammation, fatigue, swollen lymph glands and enlarged spleen and liver. Blood tests show a high concentration of specific gamma globulins of the IgM type. Fewer than 100 cases worldwide have been reported before 2008."
First described by the French dermatologist Liliane Schnitzler in the early 1970s, the disease seems to respond best to the drug anakinra (Kineret). We immediately started Henry on this medication. His response to the drug has been most encouraging. We are continuing to monitor his progress closely.
In practice, I probably see more of these rare and exotic illnesses than most physicians. Patients often come to me when other medical consultations have failed to provide an answer. They are difficult to diagnose, and sometimes challenging to treat. But the cases have allowed me to expose students and residents to a broader palette of disease that may help in the years ahead. And in exploring medical mysteries, they demonstrate the critical importance of integrating every aspect of the process — family and personal history, the physical examination — and of learning how to weigh the evidence and make connections that can yield solutions.
The value of experience is not in seeing much, but in seeing wisely. — Sir William Osier what does it mean to be a doctor? There are dozens of valid responses but, for me, fundamentally, to be a doctor is to be the beneficiary of a sacred trust. Your patient entrusts you with his or her most valuable possession — life itself.
It is not an easy matter to win that trust. It must be earned.
Nor is it always easy for the patient to confer it.
For many years, my wife and I have made a practice of spending most of our weekend evenings gliding across the floors of various Toronto dance halls. These are clubs of the old school, with old-school dances — waltzes, rhumbas, cha-chas, etc. It is one of our preferred forms of exercise. Among the regulars I have befriended is Ted H. who acts as the evening's disc jockey. In daily life, Ted is a building contractor. Relatively short in stature, he is strong and self-reliant and, I always surmised, physically fit. About 10 years ago, he had experienced periodic bouts of chest pain (angina), accompanied by dizziness and fatigue. But he never went to doctors, never took pills and never complained about feeling unwell, even to his wife and children.
Once, playing recreational hockey, he separated his shoulder, but continued playing. Finding it dislocated the next morning, he propped himself against a door and forced it back into place.
Then, a few years ago, the heart symptoms became so severe that Ted felt compelled, finally, to mention it to his wife. One Saturday night at the dance hall, she approached me to explain the situation. I was, she insisted, the only doctor he would agree to see.
I examined him the following Monday and immediately sent him for a stress test and a meeting with my cardiology colleague Dr. John Janevski. That led to an angiogram, which revealed two serious arterial blockages. Two weeks later, Ted underwent triple bypass surgery, as well as a procedure to repair an aortic aneurism. His life was saved because I had managed through the years to earn his trust. And I had won it not by practising medicine per se, or by behaving like a doctor, but by living a normal life.
Some years ago, I was privileged to teach a very bright young medical student named Michael Wong. Originally from Quebec City, he went on to enjoy a distinguished career in oncology, first in Buffalo and now in Los Angeles, where he is also a professor of medicine at the University of Southern California. While at Buffalo's Ro swell Park Cancer Institute, he wrote an article comparing how clinicians make decisions to writer Malcolm Gladwell's "blink" moment — "making a correct judgment without quite knowing how they reached it." The ability to perceive patterns and extract significant information "from a thin slice of reality ... plays an intangible yet crucial role in the practice of medicine and in training young physicians." Wong then described a case from his days as a medical resident.
At one point, we were trying to diagnose an elderly lady who'd been found unconscious in her rooming house. All the interns and residents in our department were stumped. Dr. Ho Ping Kong came in, did a brief physical exam and suggested an ultrasound test for abdominal carcinomatosis. We did the test and a subsequent biopsy found that his diagnosis was correct. When I asked, "How did you do that:1" he replied, "I've seen it before, and I learned how it looks." Although difficult to put into words, experienced physicians grasp the subtleties of the way certain illnesses present and can sense when something is amiss.
I have experienced many such "blink" moments during my career, some of them outlined earlier in this book. But, in fact, they are the exception, not the rule. Most diagnoses are made by the careful collection and analysis of all the relevant facts. Indeed, even the "blink" moments, as Michael Wong suggests, are simply a distillation of efforts previously expended and experience acquired.
The art of medicine is not — and cannot be — practised in a vacuum. Whatever success I may have enjoyed as a general internist in Jamaica, London, Edinburgh, Montreal and Toronto has been the result of working within a community of remarkable colleagues, willing to share their time, wisdom and expertise. The insights of surgeons, radiologists, pathologists and many other specialists have been indispensable. I make a point not only of meeting them, but of staying in contact, not only for the sake of collegiality, but because you never know when you might need to seek their advice and counsel. I have called upon them frequently. I owe an enormous debt to them all. It's been a privilege to work in a hospital setting where the quality of clinical work is so high. I could cite dozens of cases where their knowledge and observations were vital to making the correct diagnosis. One such case involved Nancy, a 50-year-old woman in apparently perfect health. Her only complaint was that every few months she would experience a bout of vomiting; she came to see me looking for the cause. My routine investigations were all negative, so I sent her to a gastroenterologist, who arranged a ct scan and performed a gastroscopy. Again, everything appeared normal. So we were left without an explanation.
I sent her home and advised her to call me if the vomiting resumed. Several weeks later, it did, on a Friday afternoon. By the time she arrived in my office later that day, the vomiting had stopped and she again seemed normal. But on the chance that it might resume, I suggested she be formally admitted to hospital. My thinking was that it might be advantageous to conduct further investigations while she was experiencing the problem. Sometime later, I received a call from the intern on her ward.
"We'd like to order the ultrasound you requested, Dr. Ho Ping Kong, but if I call radiology at this hour, they are likely to say no, whereas if you make the call..."
"Leave it to me," I said.
I then called my colleague, Dr. Anthony Hanbidge, in radiology, and explained the situation.
"Better to do another CT scan," he suggested. "It will show more than the ultrasound."
Soon after, he had the images and on them detected a small, cancerous-appearing lesion, the shape of an apple core, in the small bowel. This kind of lymphoma is one of the most difficult diagnoses to make. Why had the first CT scan missed it? Because it had been looking for pancreatic disease and the small bowel had not been adequately scanned.
We immediately sent Nancy to Dr. Todd Penner, one of our most gifted surgeons. He excised the lesion and she commenced a course of radiation and chemotherapy. She survived some years before the cancer returned and took her life.
So while I have argued that the CT scanner, the MRI and other mechanistic marvels should never serve as the crux of the doctor-patient relationship, cases such as Nancy's demonstrate that modern medicine would be greatly diminished — and outcomes adversely affected — without access to this important technology. It's an invaluable tool kit, for diagnosis, prognosis and follow-up care.
The challenge, of course, is to learn to become wise users of that technology — not to invoke it casually or indiscriminately or excessively. That caution applies for two compelling reasons: first, to avoid adding to the existing burden of rising health care costs; second because, as one of my colleagues observes elsewhere in this book, if we look hard and long enough at virtually any patient, we are almost certain to find something that, on an x-ray or ultrasound or magnetic resonance image, looks worthy of further investigation. In such instances, what you discover will be either innocuous and/or irrelevant to your principal line of inquiry and is apt to throw you off the trail.
The successful practitioner should therefore rely on technology largely to confirm diagnostic judgments already made — made, in most cases, by synthesizing the basic, bedside arts of seeing, listening and palpating, by taking a full history and by conducting a thorough physical examination. This combination, I submit, is most likely to yield the most desirable outcomes.
Let me give you a good example.
Through the years, I have treated many patients with complex medical histories. But few cases were as multi-faceted as that of Phirun, a 62-year-old Cambodian-Canadian I examined recently. He had been ill for many years but, through the tender ministrations of his good wife, who had been a midwife in Cambodia, and modern medical technology, he had managed to stay alive.
Phirun's health problems had begun some two decades earlier when he contracted hepatitis C. He recovered, but not, as we shall see, without causing permanent damage to his liver. About 10 years later, a cyst was spotted above his brain's pituitary gland - what we call a craniopharyngioma, a rare occurrence. Although it was not malignant, the neoplasm can, untreated, impair brain and pituitary function. He underwent surgery to remove as much of it as could be removed and was able to resume a normal life.
Then, when his liver began to show signs of failing further, doctors diagnosed hepatocellular carcinoma. This cancer, unfortunately, is usually an unavoidable death sentence because, by the time it is detected, the cancer has advanced too far to be cured. But after careful assessment, Phirun was deemed a viable candidate for a liver transplant.
In due course, the surgery was successfully performed by an accomplished transplant team at Toronto General Hospital. But his travails were not over. Only a year later, an x-ray turned up evidence of a mass on his lung. It turned out to be metastatic lung cancer, from the primary liver cancer. Again, the leading edge of modern medical technology was brought to bear to save Phirun — video-assisted thoracic surgery (vats) to remove the cancerous lung mass, performed by a team led by the University Health Network's Dr. Thomas Waddell. It was, Waddell later said, one of the first times he had been able to resect such a metastatic tumour using vats. And again, Phirun responded well.
Some months later, I received a call from Dr. Waddell. The patient, he explained, was suffering from an unidentified condition — pain, stiffness, fatigue, fever — that, in his judgment, was, unconnected to the lung surgery. Phirun had been ailing for at least six months. His liver doctor, Les Lilly, was happy with the transplant. Nurse practitioners tending to Phirun also believed something else was at work. Would I agree to see him?
I was initially reluctant, believing that the diagnostic answer was almost certainly connected to one of his previous conditions. Possibly, it was a reaction to the liver transplant graft. Perhaps it was related to the drugs he was taking to prevent rejection of the new organ. Maybe the liver cancer had spread to another site as hepatocellular cancers are prone to do. What would I be able to add?
"There's definitely something wrong," Waddell said, "but we don't think it's related either to the liver or the lungs."
So I finally agreed. The wear and tear on Phirun from his various ordeals was readily apparent. His eyes were sunken. He could barely walk. And, when I examined him, he was physically depleted, able to generate only a minimal level of muscle strength. The blood work showed evidence of inflammation or systemic ill-his sedimentation rate was 130 (about 10 times normal), although this might well have been caused by some underlying condition. His hemoglobin was low (100). After two visits and weighing all the evidence, I still felt the problem would be a legacy of his other illnesses.
On the other hand, two senior and highly respected colleagues had concluded it was something else. Perhaps they were right and I needed to look at Phirun from a different vantage point. In one sense, I already had: I had told Phirun and his wife at the first visit that if this was a new condition, it would likely be the autoimmune disorder poly-myalgia rheumatica (PRM).
My other concern was the craniopharyngioma. Was the remnant of that cyst somehow in play? His thyroid function was about 50 percent of normal, and his Cortisol level was also suppressed. But the radiologist I consulted to review the brain MRI concluded that the remaining portion of the cyst was unlikely to be the cause of Phirun's problems. To discuss the case further, we assembled an ad hoc think tank — the chief resident Dr. Lee Fidler and two fourth-year residents, Dr. Sean Leung and Dr. Patrick Darragh — and decided to treat with prednisone for an assumed case of PMR.
The response was almost instantaneous. Phirun could walk normally and his grip strength measurement went from 30 to 100. Phirun speaks no English, but when I saw him for the first time after this dramatic turnaround, he smiled broadly and flashed me a two thumbs-up signal.
I cite this difficult case to illustrate a potent symbiosis, the combination of high-tech in the form of sophisticated modern machines, and low-tech, the very human art of medicine. Both are often needed to reach the correct diagnosis.
If we do it right, the advance of technical forms of medicine can only serve to improve patient care and outcomes. But as specialization and sub-specialization continues apace, it is also clear to me that the role of the general internist — a specialist with broad, multi-disciplinary knowledge and skills — will gain in importance. There will be many challenges in the years ahead, but I remain optimistic. I hope that this modest volume can inspire doctors young and old, specialists and generalists, always to seek the good in others, to help those less fortunate, heal the sick and not let even insurmountable difficulties stand in the way of heroic deeds. There is no greater joy than being your brothers' and your sisters' keepers.
Herbert Ho Ping Kong