Finding a way to help: Cutting edge research and modern medicine are not always enough

One day recently, my new consult in clinic, Mr. C, was a middle-aged man who had moved to the area just a few years ago from halfway around the world. He came from a large family and had three young children of his own. Upon arriving in the United States, he took a job as a cook at an airport restaurant and lived modestly. At the time of his move, he had been in good health. Eighteen months ago, though, he was consumed by the seemingly sudden onset of a constellation of symptoms, both systemic and abdominal. He was hospitalized locally, and an extensive workup revealed hepatomegaly, cirrhosis and volume overload. An echocardiogram showed a reduced ejection fraction, and biopsies of the liver and duodenum stained positively with Congo red. He was given a diagnosis of amyloidosis.

During the next year, Mr. C’s symptoms progressed. His right upper quadrant pain worsened. He reported stiffness and discomfort in his joints. He developed dyspnea with exertion and several pillow orthopnea. He continued to work but found himself fatigued by the end of his shift, during which he also developed considerable nausea. He was referred to see me so that I might determine whether he had AL amyloidosis and, if so, that I might recommend and implement a treatment plan.

I remember being fascinated as a medical student by uncommon diseases with multiple end organ manifestations. I still remember my first internal medicine rotation as a second-year student, memorizing long lists of trivia associated with lupus, endocarditis, sarcoidosis, amyloidosis and others. To me, at the time, intellectualizing mysterious maladies was at the heart of internal medicine.

William Wood

Of course, the reality of caring for a patient affected by one of these diseases is much different. Most of these diseases do not have easy fixes, and the consequences of disease progression are tragic.

On this day, though, my task was to get to the heart of the matter, by determining what kind of amyloidosis this was, and what I could do to help. That morning, I struggled to understand what had been a complicated presentation. I had to explain sophisticated and difficult concepts about the nature of the disease, and its diagnosis to this patient who speak English and who was assisted in translation by his longtime friend. Past the verbal communication barriers, I could read clearly on Mr. C’s face the emotions that needed no words to be conveyed: desperation, fear and cautious hope.

Amyloidosis

I am not the only one who has been fascinated with amyloidosis — tremendous progress has been made in understanding the variations of the disease by researchers at centers that have developed specialized expertise. Just a few months ago in Blood, a brief report was published about a new technique for classifying amyloidosis by laser microdissection and mass spectrometry-based proteomic analysis in clinical biopsy. In Mr. C’s case, I obtained an serum protein electrophoresis and a bone marrow biopsy, both of which were unrevealing.

The Blood approach seemed a promising possibility, so I e-mailed the senior author, Ahmet Dogan, MD, at the Mayo Clinic to see if he might be able to apply this technique to the 2007 liver and duodenal biopsies from which the original diagnosis had been made. Dr. Dogan’s reply was rapid and helpful, and I had the slides sent. Within two weeks, I was provided a report with an answer: The amyloid deposition was of the transthyretin/prealbumin type, suggestive of familial amyloidosis. Interestingly, Mr. C did have one cousin in his large extended family who seemed in retrospect to have suffered from a similar disease, and so the diagnostic possibility was not unreasonable.

Upon Dr. Dogan’s suggestion, I obtained peripheral blood from Mr. C and sent it to Mayo for DNA sequencing analysis. The result was again available within two weeks and revealed a DNA change in exon 3 (c.236C > A, ACA > AAA) responsible for a specific amino acid change (p.T59K, Thr59Lys), which was in fact a known pathogenic mutation and consistent with a diagnosis of TTR-associated familial amyloidosis.

I had an answer, thanks to the wonders of cutting-edge research, modern medicine and the availability of rapid electronic communication. And if this were a multiple choice test in medical school (the 2010 version, anyway), I knew the correct treatment: liver and, possibly, heart transplantation. As a hematologist, there were no specific therapies that I could personally offer.

Unfortunately, Mr. C was underinsured. He was seen and evaluated by multiple transplant teams, but it seemed to be the case that this would not be an option for him. His cardiac medications were adjusted — important, clearly, in the optimal medical management of a patient with heart failure — but palliative, mostly, and not able to reverse the disease. It appeared that there was nothing that anyone could do.

Supportive care

A few weeks ago, Mr. C came back to my clinic. I entered the room with a sense of confusion and of existential frustration — having made a complicated diagnosis, there was really not much that I could do or offer for treatment, and I had thought that Mr. C had understood that when we had last talked. Not knowing what else to say, I went back to words that have always served me well. Through the translation of Mr. C’s friend, I said: “What can I do for you today? I want to help, and please let me know how I can help.”

Mr. C and his friend paused. Then, we began to talk about his abdominal pain and his discomfort, about his fatigue, and about the effects that his symptoms were having on his ability to function from day to day. We talked about supportive care and about approaches that I could employ to improve quality of life and to ease suffering.

We talked too about Mr. C’s children. A few weeks ago, all three had begun to develop abdominal pain and vomiting. Worriedly, he asked: Could he have given them his disease? I probed gently: Did they know their father was sick and what was wrong? They did. Was this something that they could talk about, and did they have anyone else that they could discuss this with? They seem to. Did they have a doctor? Unfortunately, for insurance reasons, the three of them had gone without medical care since the family’s move to the United States. Mr. C wanted to know if they should be genetically tested. I talked about the variable penetrance of the disease and the pitfalls of testing, particularly if the result for any of them was positive. I also talked about the low likelihood that this was what was causing his children’s symptoms, and discussed the psychological impact that a parent’s illness could have on a child, and what could be done.

Mr. C will come back to see me in a few weeks. Despite our incredible technological advances, only been able to give him an answer without a solution, and certainly not a solution that I can personally provide. But we are doctors first and technicians second, and here, as always, there are still things that I can do to help.

William Wood, MD, is a third-year hematology/oncology fellow at the University of North Carolina Chapel Hill and is a member of the HemOnc Today Editorial Board.

For more information:

• Vrana JA. Blood. 2009;114:4957-4959.