A Conversation with Dr. Ephraim Engleman on Six Decades of Advances

Dr. Ephraim P. Engleman, Director of the Rosalind Russell Medical Research Center for Arthritis at UCSF, has strongly influenced the modern practice of rheumatology and investigation of its diseases. Having launched his still-active career during the neonatal days of the field in the early 1940s, he offers a rare perspective.

Perhaps his single greatest contribution came from leading the National Commission on Arthritis in the mid-1970s, a Congressionally mandated task force charged with suggesting remedies for the inadequate status of arthritis research, teaching and patient care in the United States. In the late 1970s, Dr. Engleman became Founding Director of the Rosalind Russell Medical Research Center for Arthritis at UCSF, which was created by the U.S. Congress.

He continues to serve as director of the Center, which, over the years, has attracted major contributions from private individuals, enabling it to help underwrite numerous research initiatives at UCSF and provide supplemental support to the faculty and to more than 125 physicians who have received their training at UCSF to become rheumatologists and/or arthritis researchers. Dr. Engleman was recently profiled in the Frontiers of Medicine (page 5).

Q: "Dr. Engleman, you have described this new era in arthritis research as a "golden age" in terms of the promise it holds for major treatment and prevention breakthroughs. Can you give us a sense of how far we have come from when you first began treating patients?"
Dr. Engleman: Take rheumatoid arthritis as a striking example. When I was in training at Massachusetts General Hospital in 1940 and '41, the waiting room was filled with RA patients in wheelchairs. We had little to offer them other than prolonged bed rest—anywhere from 10 to 12 days to as much as four to six months. We had more than fifty hospital beds set aside at all times just for rheumatic disease patients, predominantly for those with RA. Other than that, there was only physical therapy—to try to minimize deformity and preserve as much motion as possible—and huge doses of aspirin for pain. We rarely used stronger medications, such as codeine or other narcotics. Gold salts were also very popular but their use was frowned upon at Mass General.

Q: "What kind of improvement did you see?"
Dr. Engleman: Some, but nothing like what we see today. We also had patients who experienced spontaneous remissions—as we do today—but they were primarily those whose disease had a recent onset. That's why I always frown upon studies that are done in patients who've had the disease only a short time.

Q: "What was the first big advance?"
Dr. Engleman: The first was in 1949 with the introduction of cortisone. That became the cornerstone of treatment. I remember when it was first formally introduced to the medical profession at a meeting of what was then the American Rheumatism Association, now the American College of Rheumatology. Phil Hench of Mayo Clinic, who did the early work, showed films of a patient before and after—only 24 hours after—a cortisone injection. It was so impressive. But, of course, problems came with large doses over time, including a weakening of the immune system. While we're more critical of cortisone now, I frankly can't imagine the practice of medicine today without it—and I don't mean just in rheumatology, but across the board in every specialty. And, of course, it is still a very important drug in the treatment of rheumatoid arthritis, lupus and other forms of arthritis.

Q: "What about the role of orthopedics?"
Dr. Engleman: Without question, the second big advance in the treatment of RA came with the introduction of joint replacement surgery. Orthopedics is not given sufficient credit for what it has done for the quality of life of people with arthritis. Then next, on the drug front, came new non-steroidal anti-inflammatories, the NSAIDS. But in large doses they produced gastrointestinal side effects in many people, which subsequently led to the introduction in 1998 of the Cox-2 inhibitors. Of course, as with all new drugs, we must be on the alert for undesirable effects, of which some serious ones have been recently observed with the Cox-2 inhibitors. And we won't know the full implications of these drugs until we see a definitive study focused on arthritis patients with coronary heart disease or at high risk of developing it."

Q: As we look to the next generation of arthritis drugs—the biologically-based rather than chemically-based treatments—what can we expect?
Dr. Engleman: They have remarkable potential and we're already seeing some extraordinary results with several rheumatic diseases—including serious rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. Lives are literally being transformed. And, of course, the whole exploration of genetic susceptibility is very exciting. The hope is that we will be able to determine, in advance, not only the person's risk of getting a specific type of rheumatic disease but also its expected severity. If the risk were very high, that would make it possible to begin drug intervention immediately—before symptoms occur—in order to minimize such problems as joint damage and progressive disability. I might add that the donors to our Center should be very proud that UCSF scientists are international leaders in these efforts. They're helping set the pace. We can't see the cure yet, but I think it's safe to say that, yes, we can now look forward to it.

(Published February 2005 in Arthritis Progress Report, the newsletter of the Rosalind Russell Medical Research Center for Arthritis. To be added to our mailing list, please send us a note with your name and address to rrac@medicine.ucsf.edu. Your information will not be shared with any other organizations.)



"We can't see the cure yet, but I think it's safe to say, we can now look forward to it."

--Dr. Engleman

  
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