THE  ART  OF  MEDICINE

FURTHER EXCURSIONS in the GREY ZONE

The physician should not treat the disease, but the patient who is suffering from it. — Maimonides

In the last chapter, I reviewed a series of cases dealing with the complex challenges that physicians face in dealing with syndromes that cannot be clearly identified, despite the obvious physical and mental suffering they inflict on patients. In this chapter, I will look at a few cases in which we can make a firm diagnosis of physical illness, but offer no effective or lasting solution. Here, the art of medicine is likely to be measured by other factors — by the level of care, attention, empathy and advocacy a doctor brings to the bedside. Sadly, in such situations, it is often necessary to deliver bad news to these patients. But that, too, is an art that needs to be developed.

A few years ago, a colleague at a nearby hospital referred a very difficult case to me. Marnie was a 40-year-old woman that had been diagnosed with Erdheim-Chester disease. First identified by two pathologists in the 1930s —Austrian Jakob Erdheim and American William Chester — the syndrome is characterized by excessive production of histiocytes, a type of white blood cell that the body normally deploys to fight infection. When histiocytes over-produce, however, they invade the body's connective tissue and begin to play havoc with key. organs, including the heart, bone, kidneys and liver.

The disease is extremely rare: at any time, there are only a handful of cases in all of Canada, and relatively few are described in the annals of medical literature. In fact, when I first read Mamie's file, I had never heard of it. There is no known cause, nor, alas, a cure. Pending a research breakthrough, the best an attending physician can do is to use various drugs to ameliorate the symptoms. These typically include bone pain in the legs and arms, weight loss, difficulty walking, rapid eye movements and bulging eyes, fever, night sweats, muscle and joint aches, weakness and fatigue, excessive thirst and urination.

Mamie's condition generally fit the stereotype. In addition, several years earlier, she had had a pacemaker attached to her heart, the result of what she said had been some 200 fainting spells — actually, they were cardiac syncopal attacks. Although she had been for regular checkups, it seems that doctors had only tested the reliability of the pacemaker itself, not the functioning of her heart. If they had, they would have heard, as I immediately did, what we call a pericardial rub, a murmur that signals inflammation in tissue surrounding the heart. I had no doubt there was a connection between the malfunctioning heart and the bone pain and other problems she was experiencing. Erdheim-Chester was interfering with the conduction system of her heart.

A very intelligent young woman, Marnie became pro-active in using the internet to research her disease and reach out to other sufferers. We tried a number of drugs to ease the symptoms, including prednisone and Enbrel, but nothing seemed to work. In fact, Enbrel caused new and quite acute chest pain, a not uncommon side effect.

Then we learned about a French study that had used Kineret, a drug deployed to treat rheumatoid arthritis, on patients with Erdheim-Chester disease. Two patients had reported positive results. Unfortunately, Mamie's insurance company was initially reluctant to underwrite the costs of Kineret.

The situation speaks to what I think are two other important, but often ignored, aspects of the art of medicine — advocacy and empathy. Obviously, it would be impossible for physicians to spend long hours dealing with insurance companies or other agencies that can and do impact a patient's well-being. On the other hand, you should always want to do the very best you can for the patient, no matter how challenging the circumstances. In that context, knowing how and when to advocate for patients ought to be no less important a part of medical training than knowledge and team-playing.

The same goes for empathy. One can't help being moved by the sight of men and women in the prime of life debilitated by the effects of devastating illnesses. You can't ever afford to let your emotions cloud your judgment, but you will be a better practitioner if you genuinely care and if the patient actually senses that you care. I don't readily cry in the face of the human tragedies that I encounter every day. But I certainly feel their pain, anxiety and confusion deeply inside. And Fd like to think that my patients are aware of my empathy.

In the end, we were able to persuade Mamie's insurers to pay for a three-month trial of Kineret. They agreed to defer a decision on future funding depending on the outcome. Initially, the results were positive, far beyond my expectations. Her pain decreased dramatically. Within two days, this once-bedridden woman felt well enough to shovel snow, although she probably should have to resisted the temptation. The pain in her chest and legs went from a nine or 10 on a scale of 10 to a far more manageable three or less. For about six months, she was truly her old self. Unfortunately, the effects were finite. Slowly, the drug began to lose efficacy and the pain returned. We then tried another drug, Actemra, which is administered once a month by infusion. At the time, one patient in the United States had experienced some relief with this medication. But the insurers want evidence of efficacy, preferably in trials involving thousands of patients. They agreed to fund it if, after three months, it seemed to be working. So our own Centre for Excellence in Education and Practice paid for the first three months. Unfortunately, it was unsuccessful. We then tried radiation, but that, too, proved unavailing. Sadly, the progress of Erdheim-Chester is inexorable and all that remains for attending physicians is to make the patient as comfortable and pain free as possible.

A patient's testimony—Mamie K. 

I was a professional photographer doing family portraiture and landscape, but I had to stop. The disease usually manifests itself as bone lesions, then spreads to the organs and eventually shuts them down. I happen to have the cardiac involvement. It hasn't been classified as a cancer, but it acts like a cancer in the way that it spreads. As far as we know, there is no genetic component. The cause could be environmental. It could be stress. I have had a stressful life. The pain can be quite intense at times. On a scale of 10, it is sometimes a 15. And I've given birth, so I know what pain is. There is no medication proven to be effective. There are pain management techniques, but I am allergic to the whole family of opiate drugs. Morphine, Vicodin, Percocet are all off limits for me. It became very difficult to continue working.

It started in my legs. I began an exercise program and noticed pain. I went to see my family doctor, who ordered x-rays and they did show a single-unit mass extending far up my leg. Then I went to see an orthopedic surgeon who said, "Don't worry about it. It's just a birthmark on the bone. It shouldn't hurt."

I said, "It does hurt."

He was very dismissive of me. I called a friend whose husband was a back surgeon and asked for advice. He pulled some strings and got me in to see an orthopedic oncologist at Mount Sinai. He looked at the bone scan and ordered a biopsy. They called within a few days to say it wasn't cancer, but then called me to come in discuss it further, which was quite unnerving. So it was at that point that they said they had done other tests indicating that I had Erdheim-Chester disease. It's a form of histiocitosis, which itself is rare. But Erdheim-Chester is even rarer. There have only been four or five hundred cases diagnosed worldwide. When I'm presented to residents and interns, Dr. Ho Ping Kong lets them deduce my symptoms, but no one ever guesses what I have. They've never heard of the disease.

The orthopedic oncologist suggested we could remove the bone lesions, but I decided against that, as I did not want to spend six months in a hospital bed. In the end, he sent me to see Dr. Ho Ping Kong. By coincidence, HPK had gone to high school in Jamaica with my ex-husband's father, so I knew he had a soft spot for the family.

When we met, he was very gentle, very caring and forthright in saying he did not know a lot about Erdheim- Chester disease, and that it would be learning process for all of us. He said he would do what he could to find treatment for me, but in the event that he could do nothing, he would be there for me throughout to make sure I was comfortable until the end. That was an experience I had not had before in the medical system, just in terms of humanity. HPK made it clear that I would not be allowed to fall between the cracks. And I've never felt with him that I was falling between the cracks. Sometimes there are very sad things to discuss, but I know I am in good hands. There may be things he has not shared with me yet, but I trust him with that. My daughter, who often comes with me to appointments, said to me, "It's a weird thing, but it's always fun coming here."

It often happens with so-called orphan diseases, for which there is no known drug treatment, that getting funding for off-label use of drugs is very difficult. Kineret costs more than $20,000 a year. It helped for six to seven months, but then stopped working.

At this point, I'm a terminal case, so I'm in palliative care. The pain is tolerable. I rely heavily on a network of friends and hospice groups. I am told that survival is on average 32 months from time of diagnosis, so I'm already into bonus time. I've signed a DNR — do not resuscitate. I've been putting my affairs in order. My daughter will be power of attorney and Dr. Ho Ping Kong talks to her as well. It's not just me that he is taking care of. Before I separated, he looked after my husband as well. He wanted to be sure he was handling my illness.

The whole experience has been almost surreal. I was somewhat lucky to have it diagnosed early, though much of it came down to my gut instinct that something was wrong. And I've had an incredible team to look after me. I spend a lot of time resting, trying to save energy for things I want or need to do — cooking, buying groceries. Some days, all I can do is take a shower, which is very important to me. The pain is unpredictable. I don't drive anymore. I don't sleep well, so I use the iPad to read or email friends or play Scrabble and other games.

But it is what it is.

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NO one takes pleasure in the delivery of bad news. Inevitably, however, there are times — many times—when a physician must play that unenviable role. It is the hardest part of what we do.   

My first priority, of course, is to ensure that the facts are indeed correct. Every few years, I hear an account of a patient told that he or she is suffering from an incurable disease. They then bear all the terrible anxiety of that verdict, the tears and depression — only to later be advised that the information was wrong. Someone misread the MRI or CT scan or ultrasound images. Nothing destroys the essential bond of trust between doctor and patient as thoroughly or as fast as a misdiagnosis. So before everything else, I try to ensure that the diagnosis is accurate.

Even a grim diagnosis, however, is not a death sentence. There are interventions to consider, ameliorative treatments if not outright cures, therapies that may minimize symptoms and reduce pain. All of this data must be at your command before you meet the patient.

A cardinal principle applies: you must always speak the truth. However, I sometimes find it easier not to convey all of the truth all at once. Thus, after all the tests are complete, I might use a first session to suggest what the possibilities are, including the worst ones, but then say that I first need to confer with colleagues or review the medical literature, to see what options might be available.

It should be obvious that great sensitivity is required in the telling, though I know of cases where the presentation was heartless, if not cruel. I once treated an elderly woman in Montreal who, a decade earlier, had developed a lump on her breast. The presiding surgeon delivered the news in the worst possible way. "You have breast cancer," he bluntly declared. "And what do we do in these cases?" Then he stood and, reaching toward her with a claw-like hand, made a dramatic sweeping motion. "We cut it off!" When I met her 10 years later, she was still dealing with the trauma of that encounter.

Hopefully, I will have used earlier meetings with patients to prepare them psychologically for a dark outcome. For example, even before I know whether a spot on the lung or a lump on the breast is malignant, I will have told the patient that it could be serious. But I will also suggest that it could be benign. Often, I am asked by the adult children of a patient not to disclose that their aging parent has cancer. I usually agree, but always with the caveat that if I am asked directly by the patient, "Is it cancer?" I will be obliged to answer truthfully. I cannot tell a lie.

The children often fear that their parent may, hearing the prognosis, surrender the will to live. In fact, that almost never happens. The survival instinct is so deeply embedded in the human psyche that despite the pain and suffering, the anxiety and depression, we cling tenaciously to life.

As in so many other medical domains, we are often grappling here with uncertainty. We may not know how far the cancer has advanced or the rate of its metastasis (spread). In turn, we often cannot accurately determine life expectancy. I try to provide the most hopeful assessment that is faithful to the facts as I know them.

I recently had to deliver a diagnosis of acute myeloid leukemia to a patient. Ten years ago, that conversation would have constituted an inescapable death sentence. Today, with advances in stem-cell transplant therapy, the prospects have improved. I consulted the transplant hematologist, who placed the chance of a cure at 30 percent. The chemotherapist (hematologist) gave me better odds of recovery— 64 percent. I considered my patient, an otherwise healthy, symptom-free man of 70, and told him his chances of being cured were 40 percent. I want to give hope, where it is reasonable, but not more hope than is justified by the facts. The patient underwent induction chemotherapy, followed by stem cell transplant. He was doing well 120 days post-transplant.

But at some point, it may be necessary to state unequivocally that the patient has cancer and must consider surgery, chemotherapy or radiation. I then offer my assistance in finding the best possible specialist for what treatment is chosen. And I encourage them to focus on the positive — to do their best to make every day a good day.

If I am asked, "How much time do I have?" I say, "We cannot predict." People may survive for months or years beyond the textbook expectation. Sometimes, in defiance of the odds, the disease arrests itself, or there is a complete reversal.

Certain considerations are obvious. These decisive meetings should be held in private. You must be sure not to be interrupted by phone calls, emails or text messages, and you should avoid looking at your watch. You must allocate as much time as is needed to guide the patient through the discussion, explaining the options. He or she will decide when it is over. At some point, it may be necessary to raise the issue of the estate, which I usually couch in the form of simple questions. "Most people of our age have wills," I say. "Do you have one? Is it up-to-date?"

Generally, I try to meet with the patient alone, unless he or she insists on being accompanied by family members. But it is here again, in this closing chapter of our relationship, that the groundwork laid months or years earlier pays enormous dividends. If you have done a respectable job, you will be able to connect on any number of levels that transcend illness and provide comfort: a discussion of career, of children, of hobbies, of religion, of world affairs, etc. I always know who they are, beyond their status as a patient. Does a human relationship with a caring physician lessen the impact of hearing grave news? I believe it does. I'm neither a surgeon, nor a chemotherapist, but I can be there to help them navigate the system and assure them that I will not abandon them. They take comfort in that assurance.

The late Dr. Robert Buckman, an oncologist, writer and humanist, was perhaps the best physician I ever saw when it came to the delivery of bad news. Highly intelligent, he was also an extraordinary communicator and, in his native England and in Canada — to which he immigrated in 1985 — he worked both as

a doctor and as a radio and TV broadcaster. When he arrived here, he had to requalify as a general internist and spent six weeks with me preparing for his exam. He had a genuine knack for dealing with patients facing a grim prognosis. Each approach was different, but he made every patient feel that they were deeply cared for. He later wrote two books on how to render bad news and frequently delivered courses to medical students on the subject.

The explosion of information now available on the internet has changed the way patients approach and interact with the medical system. As often as not, they now arrive in my office armed with a dossier of symptoms and treatment options for the disease they have self-diagnosed. For the most part, it is better to deal with a well-informed consumer — they are likely to be more proactive about getting better — but there are occasions when their pre-examination research is actually a hindrance. Some are even unable to believe good news, when it is offered.

One 23-year-old young man had developed strange blotches on his skin. Somehow, he became convinced that he had developed leprosy. He had made the rounds of various doctors, all of whom tried to dispel him of his illusion, without success. When I saw him, he arrived with his father, from whom he had been estranged for about 15 years. Somewhere in that complex relationship, I was sure, lay the clue to his misguided self-diagnosis.

"You're my last hope, doctor," he complained when I saw him for the first time.

"Well, let's examine you and see what we can find," I said, neutrally.

We conducted all the necessary tests and soon reconfirmed categorically that he did not, in fact, have leprosy.

"Well, doctor, do I have it?" he asked anxiously at our third meeting.

"No," I said, "you do not have it."

"How do you know?"

"I've seen cases of leprosy," I said. "I've read a lot about it. You have some discolouration, but you have no actual skin changes, no nerve changes and you've had no exposure to other leprosy patients."

I thought I would be conveying joyous news. I was wrong. The young man became abusive, hurling profanities at his father. He had to be dragged out of the office.

I recall another case that demonstrates just how tricky it can be to navigate the shoals of the Grey Zone. The patient was Helena, a 78-year-old woman of Greek origin with a significant medical history. Some 12 years earlier, she had had a new mechanical mitral valve implanted, likely for rheumatic heart disease. The surgery had greatly enhanced her quality of life, but now she was complaining of weakness and fatigue. Helena's family doctor had sent her for blood work, which revealed a low hemoglobin count of 100. A second test showed that it was falling — to 90 — clear evidence of anemia. At that point, she was sent to me.

I ordered a number of tests, but was concerned most about one that found occult blood in the stool. We ruled out H. pylori, the common bacteria that causes gastric ulcers, and administered iron. But the hemoglobin level continued to fall, from 90 to 80, then 70 and then 60. Helena had to be anti-coagulated to prevent clotting on the mechanical valve (a standard treatment). She continued to have positive tests for occult blood in the stool. So despite a recent normal exam, we chose to repeat the colonoscopy. This time, the specialist found an ulcer in the cecum, a small pouch-like attachment located at the end of the ileum. The surgeon cauterized it, which stopped the bleeding, and for several months Helena was fine (and very grateful).

Then, a few years ago during the month of October, I learned from her daughter that Helena had been ill, suffering from a 103-degree temperature and chills and feeling disoriented. I saw her the next morning. She was indeed sick, barely able to walk, febrile, tachycardic (a fast pulse) and a little confused. My initial fears focussed on two possibilities. The first was endocarditis, an infection on her mechanical valve. My other thought was West Nile virus. Toronto had experienced a mini epidemic of this mosquito-borne illness some years earlier, which caused several deaths and left many others permanently debilitated. It often presents with features of encephalitis.

"Does your mother do any gardening?" I asked her daughter that morning.

"Why, yes," she said. "She likes to avoid the sun so normally goes out in the morning and evenings."

"And are there many mosquitoes."

"Oh, yes. Too many. She has even been using mosquito coils in the garden."

We subsequently admitted Helena on the assumption of endocarditis. West Nile, I knew, usually appears in August or September, but because incubation can last as long as three weeks, sometimes in October. So we also ran the West Nile blood test, which came back positive. In the meantime, we ran six separate cultures for endocarditis and they all came back negative. But part of the examination for endocarditis involves an echocardiogram, to check the functioning of the mechanical mitral valve. And on one of these images, we found a 1-2 centimetre mass. What was it — a vegetation on the valve, caused by endocarditis? Or was it a blood clot, caused by the mechanical valve? We didn't know and, short of invasive surgery, we could not answer the question.

Thus did we find ourselves in the Grey Zone, with an identifiable problem but an uncertain treatment approach. So what do you do? If it is endocarditis and you fail to treat it, the patient's life is at risk. She could die in six to eight weeks, or sooner if a staph infection was responsible. Or a piece of the clot, if there is one, could break off, travel to the brain and cause a stroke. Do we administer antibiotics on the assumption that endocarditis is in play? The answer depends on what is best for the patient — this patient, with all her medical history.

In the end, after several days of consultation, the cardiologists and I agreed to treat Helena — with intravenously administered antibiotics — for what we call culture-negative endocarditis, which involved a six-week hospital stay.

Today, Helena has been home for one year and, given her history, is in relative good health. But we still don't know for sure whether our assessment was correct. If you culture negatively for endocarditis — and she did six consecutive times — it's unlikely that you have the condition. But there is something called culture-negative endocarditis — that is, the organism is fastidious and hard to culture.

Even if you make the assumption, the next step is not easy. There's a risk of Clostridium difficile (C-difficile); or pseudomembranous colitis, a potentially lethal condition especially in the elderly; or kidney damage, potential complications of weeks of the antibiotics needed. Her regimen of Coumadin posed another potential complication. Still, for Helena, with the definite mass on the valve, this was the correct decision. My own feeling was that, in addition to the West Nile virus, which is not treatable, the mass was likely a clot on the valve. But because we could not be sure, and because of the dangers of doing nothing — death or disability by endocarditis, the infection itself, a heart condition or stroke — we were effectively forced to administer the six-week antibiotic treatment. It was in the patient's interests.

Grey Zone cases like Helena's — thorny and complex — are more common than you might expect. But they demonstrate again why the art of patient-centred medicine will never entirely go out of fashion.

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