Rethinking the approach to some autoimmune disorders
Dr. Stephen Paget
What if the standard treatment approach was the wrong one? In the case of several autoimmune disorders, it’s a theory that is gaining traction bolstered by recent research findings.
Stephen A. Paget, MD, FACP, FACR, MACR, physician-in-chief emeritus at the Hospital for Special Surgery in New York City, has spent his career researching and treating a range of inflammatory and autoimmune disorders. The rheumatologist, who is also a professor of Medicine and Rheumatic Disease at the Weill Medical College of Cornell University, said the potential exists for a paradigm shift in how clinicians view and treat some disorders including reactive arthritis, Whipple’s disease and persistent Lyme disease.
Paget said the accepted concept has been “that in a genetically predisposed person, with some type of environmental trigger … probably virus or bacteria … they develop disease.” Although the initiation was from a microorganism, he continued, the conventional wisdom has been that the self-perpetuation of symptoms is due to the body’s subsequent response. “What you were left with was an inflammatory problem that was no longer tied to the previous organism,” Paget explained.
A good example would be persistent Lyme disease. The infectious trigger is the Borrelia burdorferi, a bacterial species of the spirochete class, which is transmitted to humans through a tick bite. Skin rash in a bull’s-eye pattern (erythema migrans), fever, fatigue, chills and headaches are among early symptoms. Later symptoms could involve the joints, heart or central nervous system. For most, a prescribed course of oral or intravenous antibiotics takes care of the infection and symptoms. However, in some patients, synovial inflammation persists even after the bacteria have been nearly or totally eradicated. This has given rise to the belief that in predisposed patients, the initial Lyme disease triggers an ongoing autoimmune disorder.
In his 2012 paper, “The Microbiome, Autoimmunity and Arthritis: Cause and Effect: An Historical Perspective,” which was published in Transactions of the American Clinical and Climatological Association, Paget noted that for more than 100 years, there has been “tantalizing but often inconclusive evidence” about the role of microorganisms in autoimmune diseases. He wrote, “Current therapy focuses on the pathogenesis rather than the etiology of these disorders. In order to rein in the overactive immune system we believe to be causing the disease, we employ immunosuppressive drugs, an act that would be counterintuitive if infection were the root cause of the problem.”
A small but intriguing study out of the Division of Rheumatology at the University of South Florida College of Medicine published in the journal Arthritis Rheum in May 2010, found a six-month combination antibiotic regimen was effective in treating patients with the autoimmune condition Chlamydia-induced reactive arthritis. In the nine-month, prospective, double-blind, triple-placebo trial, researchers assessed a six-month course of combination antibiotics with a primary end point of the number of patients who improved by 20 percent or more in at least four of six variables without worsening in any variable.
At month six, the authors found significantly more patients in the active treatment group became negative for C trachomatis or C pneumonia. The primary end point was achieved in 63 percent of patients in the active arm of the trial, with 22 percent of those patients believing their disease had gone into complete remission. No patient in the placebo group achieved remission.
Pointing to this study, Paget noted that one of the failures of antibiotic regimens in the past in treating autoimmune disorders might be the duration of the therapy. “If you give long courses of antibodies, you may very well calm the problem down,” he said. However, he noted, physicians currently switch to steroids, T-cell inhibitors, and other immunosuppressive drugs to ameliorate the ongoing inflammatory issue after treating the triggering microorganism with antibiotics or antivirals for a relatively short course,
“It may very well be we have to improve the immune system response instead of suppress it, and that’s the interesting twist,” Paget continued. If the root cause of an autoimmune condition is infection, “You’d want the army active,” he said of augmenting the immune system.
While much more research must be done, Paget said mounting evidence of the important connection between microorganisms and a number of autoimmune disorders provides ‘food for thought’ when it comes to the best course of action for treating these conditions and could ultimately portend a paradigm shift in the delivery of care.
“In some of these, the organism is slow, smoldering … but still there in a low-grade way that is triggering the inflammatory response. We have to be appreciative of the fact that we want to do the best thing for our patients … but what we’re doing (now) may be the worst thing,” he concluded.