Doctor, Heal Thyself

"Guys, I think I'm dying [as a third-year medical student in 2010 with the first symptoms of the disease that struck him]."
"I remember the doctor saying, 'We don't know what it was, but let's just hope it doesn't come back'."
"I felt like I was part of steering the ship [when his own research informed him how best to proceed]."
"My typical case is particularly severe. I’m conscious for such a short amount of time, and it’s so scary that the little bit of brain function that I have is me thinking to myself ‘I want to get help somehow.’ I want to think through things but, of course, I don’t have any higher brain function. It’s really really tough. But I’ve kind of tried to overcome that fear when I’m out of the hospital and in remission. I try to be in as advanced a state of understanding as much as I can."
"I didn't think that I would ever get to leave the hospital [as a patient whose condition was a mystery], and now here I am, fighting back [as a medical doctor]. It's the ultimate motivator."
Dr. David Fajgenbaum, Hospital of the  University of Pennsylvania

From his base at the University of Pennsylvania, David Fajgenbaum is trying to change the prospects for a dire disease—his own. Photo: April Saul

In the spring of 2013 David Fajgenbaum, a student at the University of Pennsylvania's medical school, earned his medical degree. Mission halfway accomplished; his aspiration to become a doctor and his determination to gain his medical degree had become reality. But there was another reality he also had to face. Among his friends at the university the tall, muscular gym addict, former football player at Georgetown University, was familiarly referred to as the "Beast".

His former roommate described him as fairly special: "This guy was a physical specimen". And then suddenly things happened. At age 25, he awoke one night in a deep sweat. He found his lymph nodes to be swollen; stabs of abdominal pain wrenched him, while peculiar red humps were spreading across his chest, and he felt very, very tired. Which was when he felt convinced that the Angel of Death had tracked him down prematurely and had arrived to collect its grim, premature due.

At the emergency department, an examining physician informed him his liver, kidneys and bone narrow were malfunctioning, and the doctor had no idea what had occurred and why. "What do you think is going on?" the doctor asked the patient. Well, what doctors felt was going on at first was that cancer was involved since a CT scan had revealed his body to be riddled with enlarged lymph nodes, signalling lymphoma. As his immune system continued to go awry he declined further.

Doctors ventured a large dose of steroids and his kidneys and liver seemed to respond, beginning to function normally. Seven weeks following his admission, David Fajgenbaum left the hospital, in September 2010. A month on, those symptoms suddenly re-appeared. Doctors in North Carolina, which was where he was convalescing at his family home, transferred a piece of his lymph node to the Mayo Clinic and there pathologists identified his problem.

The condition was a rare one; little wonder that the Raleigh doctors had no idea what he had presented with, but it was called Castleman disease. A disease that had been in the medical literature from the 1950s, but as a rare type of disease, little was known about it to classify it. What's more, his particular form of Castleman's -- multicentric Castleman disease -- happens to be singularly more rare and deadly. It is a disease that strikes roughly 1,200 to 1,500  people annually in the United States. People diagnosed with the condition are informed that 65 percent only live on for another five years.

The problem of rare diseases is one that eludes treatments and cures for these obscure conditions, since about 95 percent of all rare diseases are bereft of any approved drug treatments, leaving an estimated 30 million people in the United States alone -- about 10 percent of the population -- living with one of the nearly 7,000 rare diseases identified to date.

With his diagnosis of Castleman, and so little known about it, Dr. Fajgenbaum experienced extended periods of balanced health and then devastating relapses. On several occasions he was forced to undergo 21-day courses of chemotherapy. He was given emergency access to a developing drug for multicentric Castleman disease, not yet approved, but like other treatments previously attempted, the drug failed to work for him.

He responded by collecting weekly blood samples to serve as data of his immune system, and kept the results in a spreadsheet. When it became obvious that the disease symptoms had once again returned, he asked his doctors for a biopsy, to take a piece of a lymph node, to test it and to save it for future research purposes. Another round of chemotherapy allowed him to improve sufficiently for discharge and he began delving into what the tests could reveal.

Finally, he felt that if he could persuade his body to turn down the communication line known as the mTOR pathway, he might succeed in stopping his immune system from overreacting, and thus prevent yet another relapse. The next step was to identify drugs known to shut down the mTOR pathway. One that was promising was a drug used to prevent kidney transplant patients from rejecting the organ. He cut out cancer drugs and began taking sirolimus and the weekly blood tests indicated his immune system returning to normal.

"I feel 100 percent", he said when the three-year anniversary after beginning to use sirolimus had passed. Now 31 years of age, Dr. Fajgenbaum heads the Castleman Disease Collaborative Network he co-founded, from his office at the Hospital of the University of Pennsylvania. He also operates as an assistant professor of medicine at the Perelman School as well as the associate director of patient impact at the Penn Orphan Disease Center, which focuses on treating rare diseases.

Dr. David Fajgenbaum and his young patient, Katie Repasky.

Mileva Repasky