The Rheumatologist’s editor, David Pisetsky, MD, PhD, invited me to contribute regular commentaries about articles appearing in the literature. I accepted this opportunity with alacrity, delight, and enthusiasm.
The responsibility of identifying important articles in the literature and presenting these to colleagues is daunting and humbling. My own view of journal articles has changed over the years. As a fellow, I watched my mentor, Peter Schur, MD, (who is now the rheumatology editor for UpToDate), set out for the Countway Library, that magnificent facility at Harvard Medical School, for an afternoon each week. I was impressed by his methodological review of the clinical and scientific literature of rheumatology and immunology and how he listed every citation. I was grateful when allowed to copy his reference lists at the end of my fellowship, naively hoping that I might then possess the knowledge he accumulated. I too began to scan and collect the literature as he did, not then entirely appreciating the difference between knowledge and understanding, between information and wisdom. In some ways, the more I learned, the less I knew. Fundamental appreciations of rheumatic diseases remained (and still are) elusive.
Much published literature goes uncited (41% for biological sciences, 46% for medicine) and presumably unread. This suggests that a substantial proportion of scientific papers make negligible contributions to knowledge. Medical students also apparently read a small portion of assigned material. Second-year students, for example, were given approximately 11,161 pages of material, which could be mastered by reading an estimated 175 hours during their 168-hour week!
Rheumatology includes a good deal of material that is not particularly important—or that becomes less important over time. In 1988, James Fries, MD, surveyed rheumatologists to identify the greatest breakthroughs of the preceding 20 years. Although not cited in terms of specific references, 69 meaningful advances were presented in nine categories in about 2.5 pages of printed text, which is meager considering that our current major textbooks are thousands of pages.
My own view of the literature is considerably more critical than it was earlier in my career. I now read less extensively and more selectively, and no longer peruse some specialty journals. My criterion for an “important” contribution is an article that affects my understanding or practice of rheumatology, that influences my thinking or clinical behavior. I will share these with you here. I will comment on, not necessary “review,” literature selections, focusing on articles of potential interest to clinicians, affecting rheumatologic practice or thinking about rheumatology; perhaps more articles from sources other than major journals (that some readers might not have seen); and articles allowing me latitude to think more broadly about rheumatology, medicine, and, indeed, life.
I served on the editorial board of The Yearbook of Rheumatology, Arthritis, and Musculoskeletal Disease throughout its lifetime, three years as an associate editor to John Sergent, MD, and 10 years as editor. (Dr. Pisetsky served as an associate editor.) We took pride in creating something special and thought ours was the best of the Yearbook series. We valued critical thinking, eclectic selections, and eloquent and provocative expositions. The perspectives were refreshing and erudite. Presentations were personalized, relevant, practical, entertaining, and challenging. It is that style I will try to introduce for this department in The Rheumatologist.
I welcome your comments, responses, suggestions for inclusions, or disagreements. Together we will have fun thinking and learning about rheumatology.
THERE’S NOTHING NEW UNDER THE SUN. NOT!
Whenever possible, I will make thematic selections and from literature that perhaps not all clinical rheumatologists would routinely read or be aware of. The story line for today is new diseases and syndromes of clinical and intellectual interest to rheumatologists.
When I spoke with John Stone at his poster about immunoglobin 4 (Ig 4)–related systemic disease at last fall’s ACR meeting in Philadelphia, I was embarrassed at not being familiar with this, until I realized it is a relatively new concept (Arthritis Care Res. 2010;62:316-322). Until recently, most reports were single cases, focused on pathology or immunopathology, or were reported in obscure journals. We will probably encounter this as “noninfectious” aortitis or chronic periaortitis. These patients should have elevated serum IgG4 levels and may have systemic disease such as Sjögren’s syndrome or involvement of biliary tract, liver, lung, kidney, lymph nodes, pancreas, or retroperitoneum. Aortitis responds well to glucocorticoids. This is something I will now look for.
I probably won’t look for patients with deficiency of the interleukin (IL)-1 receptor antagonist (DIRA) (N Engl J Med. 2009;360:2426-2437). These patients have neonatal sterile multifocal osteomyelitis, periostitis, pustolosis, osteopenia, lytic bone lesions, respiratory insufficiency, and thrombosis. The absence of the IL-1-receptor antagonist, caused by autosomal recessive mutations, permits unopposed action of IL-1, allowing elaboration and overproduction of proinflammatory chemokines and cytokines, leading to these devastating clinical manifestations. Patients responded to treatment with ankinra. Why, though, would this immunodeficiency be associated with these particular clinical symptoms?
I may, however, consider the syndrome of autoimmune polyendocrinopathy type I with chronic mucocutaneous candidiasis (J Exp Med. 2010;207:291-297). These patients have autoantibodies against IL-17A, IL-17F, and/or IL-22. (These cytokines are important in host defense against candida in mice, which formed the basis of the rationale for this study.)
These two reports of associating selective perturbations of the immune system with specific clinical syndromes should not be surprising to rheumatologists. These observations are simply elegant and a contemporary extension of principles familiar to us. They remind us of the intricacy and complexity of immune homeostasis and that there are doubtless many more such examples to be identified. Indeed, a very nice paper appeared in the Journal of Immunology (2010;184:4605-4609) showing that IL-23R–deficient lpr/lpr lupus-prone mice were protected from lupus nephritis. IL-23 is important for proinflammatory Th17 cells implicated in the pathogenesis of lupus.
Nature here is trying to teach us something. These examples should suggest both clinical and therapeutic insights. What gene mutations will be associated with what symptoms? To what might heterozygotes be predisposed? Can we develop therapeutic interventions affecting IL-17 and IL-22 without attenuating host defenses? We should look for such contributions in future literature.
ON PROFESSIONALISM
“In a place where there is no man (of integrity), strive to be one” is a loose translation of Talmud Avot 2:6. I always interpreted this as an exhortation to character, decency, morality, high ethical standards, and menschlichkeit— “professionalism” in medical terms. After problems with money and regulatory requirements, issues of physician behavior are probably most challenging to those of us in leadership positions in medicine. This article reminds us that physicians suffer the same foibles as mere mortals. Some behave poorly and others cross the pale into criminality.
I’m now in my 35th year as a division chief or department chair. I see much to savor, appreciate, and celebrate every day and every year—spectacular individual and collective professional accomplishments at the bench and the bedside. They can be extraordinary, particularly when viewed through the perspective of four decades. But I also see things that profoundly disappoint, indeed disturb, me. One of these is the sometimes disheartening lack of professionalism in our profession. I’m anguished in my roles as mentor, supervisor, teacher, professor, program director, and institutional and organizational leader when I witness how badly we sometimes do this. I’ve editorialized about my profound concerns with our failures of ethics in relationships with industry and, yes, even in our ACR.
This selection highlights another concern about which I’ve privately worried greatly: how badly we sometimes behave toward one another and toward subordinates. There is a depressingly robust literature about professional misbehavior by colleagues, residents, students, and others; it is pernicious and pervasive. We have documented this at our institution and it troubles me profoundly. We have had shouting, yelling, accusations, harassment, probably destruction of data, and real threats of and acts of violence. During my many years of active participation in the ACR, we had some similar experiences. The daunting question is what to do to remedy this. I believe that, just as we must accept responsibility for the dilemma, we must develop a solution. I can no longer tolerate colleagues acting disrespectfully to one another, regardless of the times, circumstances, or provocations. We must do better, and I sincerely believe that we can.
I love the story I know as “the Rabbi’s gift” (JAMA. 2001;286:648-650). It tells of a once grand monastery that fell upon hard times. In desperation, the abbot consulted with his friend, a rabbi from a nearby town. After reflecting on the dilemma, the rabbi told his colleague that he had no answers or suggestions. He added, though, that one among the monks was the messiah. The abbot returned with this peculiar message. The monks tried to understand. Could one among them be the messiah? They began, slowly but surely, to treat one another, and themselves, with more respect, for perhaps one of them was the messiah. Gradually, the monastery transformed, flourished, and again became a beacon for others.
Perhaps this is where we need to begin, cherishing everyone’s unique individuality, remembering that we are all deserving of respect. This is a fundamental message we attempt to communicate in our novel humanities and medical humanism curriculum. It generalizes.
Dr. Panush is chair of the department of medicine at Saint Barnabas Medical Center and professor of medicine at the University of Medicine and Dentistry–New Jersey Medical School in Livingston. He is moving soon to be professor of medicine, division of rheumatology, department of medicine, Keck School of Medicine, University of Southern California in Los Angeles.
