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1st Annual Clinical Rheumatology Symposium

Fortunate circumstances brought together Dr. Robert Jackson from PSN and Dr. Richard Brasington, Professor of Medicine from Washington University School of Medicine, Division of Rheumatology at a recent St Louis Rheumatology Association meeting.

The American College of Rheumatology has an annual scientific meeting where the clinical results from the year are presented. The improved patient outcomes from the research need to filter down to practicing rheumatologist in the field.

It turns out, Dr. Brasington has a weekend home near Tecumseh and Dr. Jackson is familiar with the local resort named Dawt Mill. A plan was made to have a CME symposium of clinical research outcomes in the spring.

Dr. Brasington and two of his former trainees, now faculty, Alfred Kim, M.D., Ph.D. and Jonathan Miner, M.D., Ph.D. plus Anne Winkler, M.D., Ph.D., PSN physician, also joined as presenters at the conference.

Dawt Mill provided a natural backdrop to Dr. Brasington’s combined love of rheumatology and fishing. Having the conference at a natural location brought home the reality of practice life outside of an academic center. After the conference, fishing stories were shared over a nice dinner and entertainment at Dawt Mill.

Dr. Miner’s presentation on the Chikgunya virus was cutting edge, straight from the newspapers, when he relayed that the lab is also working on the Zika virus.

The unanimous conclusion was to have the conference again next year.

Deactivating A Cell Protein May Halt Progress Of Rheumatoid Arthritis

Rheumatoid arthritis is an autoimmune disease that leads to inflammation and bone erosion in the joints. One of the hallmarks is swelling and pain caused by white blood cells flooding into the fluid around the joints. Now researchers have shown for the first time that the activation of a single protein on the surface of these cells could be the trigger for the disease.

The cell protein they investigated is toll-like receptor 5 (TLR5) that is found on myeloid – or marrow-derived – cells that migrate from the blood into affected joints.

“TLR5 does it all,” says one of the researchers, Shiva Shahrara, associate professor of rheumatology at the University of Illinois at Chicago College of Medicine.

She and her colleagues write about the study in the Journal of Immunology. They suggest the findings may lead to new drugs that target the cell protein and break the vicious cycle of inflammation and bone degradation in rheumatoid arthritis. Myeloid cells of rheumatoid arthritis patients have far more TLR5 receptors.

When they compared the myeloid cells from the joints of healthy people with those of rheumatoid arthritis sufferers, they found the myeloid cells from the arthritis patients had far more TLR5 on their surfaces.

One of the hallmarks of rheumatoid arthritis is swelling and pain caused by white blood cells flooding into the fluid around the joints. From previous work, they had already established that activation of the receptor leads to abnormal development of blood vessels in the joints of patients with rheumatoid arthritis.

In this latest work, they discovered the receptor also boosts the activity of TNF-alpha, an inflammatory molecule that summons even more myeloid cells into the joints, whereupon they change into osteoclasts, cells that cause bone erosion.

The researchers also carried out a series of experiments to show activating TLR5 triggers several disease processes. For example, they showed if myeloid cells with active TLR5 are placed next to joint fluid taken from rheumatoid arthritis patients, they migrate into the fluid, but switching TLR5 off reduces migration significantly.

In other experiments, the researchers showed that when the joint fluid of patients with rheumatoid arthritis contained myeloid cells with activated TLR5, this increased levels of TNF-alpha, and the myeloid cells of patients taking anti-TNF-alpha drugs have fewer TLR5 receptors. This suggests there is a positive feedback loop between TLR5 and TNF-alpha: when one increases, so does the other, as Prof. Shahrara explains:

“Not only do TLR5 and TNF-alpha regulate each other, but they work synergistically to attract more myeloid cells into the joint, where they are transformed into bone-eroding cells.”

In a final set of experiments, the team showed giving mice with rheumatoid arthritis an antibody to block TLR5 significantly reduced joint swelling and bone erosion compared to mice that did not receive the drug. The team suggests that blocking TLR5 with the antibody reduced myeloid cells migrating into the joints and turning into bone-eroding osteoclasts. Prof. Shahrara believes this means a drug that stops TLR5 activation could slow or even prevent the joint inflammation and bone erosion that occurs in later-stage rheumatoid arthritis. She suggests when the receptor is switched on, it triggers a “vicious feedback loop” that worsens the inflammation and bone erosion of rheumatoid arthritis.

“The receptor is a major driver of inflammation and bone degradation,” she explains. “Blocking this receptor could have significant therapeutic value in interrupting joint swelling and bone loss in patients with rheumatoid arthritis.”

Funds from the National Institutes of Health, the Department of Defense, the American College of Rheumatology and the Arthritis Foundation helped finance the study.

In June 2014, Medical News Today learned how researchers identified the T cells that drive rheumatoid arthritis. Using cutting-edge tetramer technology, the scientists studied how the disease starts, how current therapies may affect the immune response directed to the joint, and how to target these specific cells with drugs.

SOURCE: Medical News Today

Prof. Shahrara says it is as though something in the joint fluid attracts the myeloid cells when their TLR5 receptors are switched on. She suggests perhaps a protein that binds to the receptor is present in the fluid of joints affected by rheumatoid arthritis. Switched on TLR5 may trigger ‘vicious feedback loop’ of inflammation and erosion.

Regional Rheumatologist Distribution Leaves Many Patients Under served

A Current Study Demonstrates That Regional Shortages Already Exist

Many areas of the United States have few or no practicing adult rheumatologists, and in some cases – particularly in smaller “micropolitan” areas – the closest practicing rheumatologist is 200 miles away, according to an analysis of U.S. Census data and information from the American College of Rheumatology membership database.  Patients with chronic rheumatic conditions in these areas likely have limited access to rheumatology care.

Patients with chronic rheumatic conditions in these areas likely have limited access to rheumatology care, reported Dr. John D. FitzGerald of the University of California, Los Angeles, and his colleagues. The authors are members of the American College of Rheumatology (ACR) Committee on Rheumatology Training and Workforce Issues.

What do the findings show?

These findings come in the wake of an American College of Rheumatology workforce study initiated in 2005, which showed that demand for rheumatologic care at that time was in balance with the supply of adult rheumatologists (with an estimated 1.67 rheumatologists per 100,000 persons), but which predicted that demand would outstrip supply over time, leading to a shortage of 2,500 adult rheumatologists by 2025. The ACR responded to that report by increasing funding for the training of new rheumatologists by targeting programs with unfilled Accreditation Council for Graduate Medical Education slots, the investigators said.

They noted, however, that the national estimates did not consider regional variation in the distribution of rheumatologists. “Clustering of rheumatologists in some regions can leave other areas of the country with too few adult rheumatologists in supply,” wrote Dr. FitzGerald and his associates, who mapped all adult practicing rheumatologists’ addresses as recorded in the 2010 ACR membership database, and assessed the number of rheumatologists in Core Based Statistical Areas (CBSAs), commonly referred to as micropolitan and metropolitan areas. CBSAs are “defined by regions with a high degree of social and economic integration (determined by commute to work) around a central urban core,” they said.

Shortage in Rheumatology

Traveling Clinics Could Ease the Burden

The findings of the current study demonstrate that regional shortages already exist. “If we simply use the 1.67 number of rheumatologists per 100,000 persons as a definition of insufficient rheumatology supply, then a majority (85%) of the CBSAs would be potentially underserved,” the investigators noted.

When a definition of no practicing rheumatologists within a 50-mile travel distance is used, 24% of CBSAs – representing 18.9 million persons – would still be affected by an insufficient supply of rheumatologists; with a 100-mile cut point, 5% of CBSAs –representing 2.5 million people – would be underserved.

“While this is no surprise to affected local patients, practitioners, or policy makers, this study identifies potential target communities … that might benefit most from addition of a local rheumatologist,” the investigators noted.

One possible intervention for addressing the shortage is simply providing up-to-date information about shortages, as this could lead to migration, expansion of existing practices, or attraction of new rheumatologists. Increasing the supply of trainees in areas with unmet needs and committing additional funds to training programs in underserved areas are also possible interventions, the authors said.

Approaches such as the use of traveling clinics and e-mail or video consultation, which have previously been used to address shortages in rural areas, could also be helpful, they said, adding that it has been suggested that midlevel providers could also effectively help fill workforce shortages.

According to the ACR database, there were 3,920 practicing adult rheumatologists in 2010; 90% practiced in metropolitan areas (areas with at least 50,000 population around a central urban core), 3% practiced in micropolitan areas (areas with 10,000 to less than 50,000 population, excluding rare exceptions centered around a less dense urban cluster), and 7% practiced in rural regions.

“Notably, a greater proportion of rheumatologists were practicing in metropolitan areas (over micropolitan areas) than would be expected based on population distribution alone. While only 31 metropolitan areas (9%) did not have a practicing member rheumatologist, the majority of micropolitan areas (84%) did not have a rheumatologist,” the investigators wrote.

As for areas with no rheumatologist, the distances to the nearest practicing rheumatologist varied widely. Only 1% of metropolitan areas, compared with 16% of micropolitan areas, had a distance of more than 75 miles to the nearest rheumatologist, and CBSAs with populations over 200,000 had a travel distance as great as 94 miles, while some smaller micropolitan regions had travel distances greater than 200 miles, for example.

Many smaller micropolitan areas with populations of at least 40,000 had no practicing rheumatologists, and several more populous areas with populations of 200,000 or more also had no practicing rheumatologist.

Conversely, areas with higher population densities; greater proportions of younger, female, white, and Asian populations; and the presence of an active adult fellowship training program had greater numbers of rheumatologists.