Faculty Bibliography

The use of musculoskeletal ultrasound (MSKUS) has increased in a variety of rheumatic conditions, particularly rheumatoid arthritis (RA). MSKUS complements the physical examination by allowing for superior visualization of synovitis and erosive changes compared to conventional radiography and provides detail comparable or supplementary to magnetic resonance imaging (MRI). This modality is also less expensive than MRI and CT scans, without claustrophobia or other contraindications, while uniquely providing dynamic, rather than static imaging. A growing body of literature for MSKUS in RA is contributing significantly to the understanding of diagnostic and prognostic utility, longitudinal assessment, and disease remission. Furthermore, scoring systems focusing on the patient level rather than individual joints have been developed, allowing for simplification of exams while still retaining accuracy and utility. The combination of these advances has led to increased use of MSKUS in RA in the realm of research as well as at the bedside and in the clinic

Complement receptor 2-negative (CR2/CD21(-)) B cells have been found enriched in patients with autoimmune diseases and in common variable immunodeficiency (CVID) patients who are prone to autoimmunity. However, the physiology of CD21(-/lo) B cells remains poorly characterized. We found that some rheumatoid arthritis (RA) patients also display an increased frequency of CD21(-/lo) B cells in their blood. A majority of CD21(-/lo) B cells from RA and CVID patients expressed germline autoreactive antibodies, which recognized nuclear and cytoplasmic structures. In addition, these B cells were unable to induce calcium flux, become activated, or proliferate in response to B-cell receptor and/or CD40 triggering, suggesting that these autoreactive B cells may be anergic. Moreover, gene array analyses of CD21(-/lo) B cells revealed molecules specifically expressed in these B cells and that are likely to induce their unresponsive stage. Thus, CD21(-/lo) B cells contain mostly autoreactive unresponsive clones, which express a specific set of molecules that may represent new biomarkers to identify anergic B cells in humans.

Osteoarthritis (OA) is often a progressive and disabling disease, which occurs in the setting of a variety of risk factors--such as advancing age, obesity and trauma--that collude to incite a cascade of pathophysiological events within joint tissues. An important emerging theme in OA is a broadening of focus from a disease of cartilage to one of the 'whole joint.' The synovium, bone and cartilage are each involved in pathological processes that lead to progressive joint degeneration. Additional themes that have emerged over the past decade are novel mechanisms of cartilage degradation and repair, the relationship between biomechanics and biochemical pathways, the importance of inflammation and the role of genetics. In this article, we review the molecular, clinical and imaging evidence that synovitis is not an 'incidental finding of OA', but plays a significant role in disease pathogenesis, and could therefore represent a target for future treatments

BACKGROUND: A lack of biomarkers that identify patients at risk for severe osteoarthritis (OA) complicates development of disease-modifying OA drugs. OBJECTIVE: To determine whether inflammatory genetic markers could stratify patients with knee OA into high and low risk for destructive disease. METHODS: Genotype associations with knee OA severity were assessed in two Caucasian populations. Fifteen single nucleotide polymorphisms (SNPs) in six inflammatory genes were evaluated for association with radiographic severity and with synovial fluid mediators in a subset of the patients. RESULTS: Interleukin 1 receptor antagonist (IL1RN) SNPs (rs419598, rs315952 and rs9005) predicted Kellgren-Lawrence scores independently in each population. One IL1RN haplotype was associated with lower odds of radiographic severity (OR=0.15; 95% CI 0.065 to 0.349; p<0.0001), greater joint space width and lower synovial fluid cytokine levels. Carriage of the IL1RN haplotype influenced the age relationship with severity. CONCLUSION: IL1RN polymorphisms reproducibly contribute to disease severity in knee OA and may be useful biomarkers for patient selection in disease-modifying OA drug trials

Cerebrovascular disease appears to have implications on rheumatic diseases, including gout. Accumulating evidence suggests that hemiparesis exerts a protective effect against gout via the down-regulation of mechanical and neural modulators of inflammation in neurologically impaired extremities. We present 2 divergent cases of unilateral gout following cerebrovascular events. One patient with a hemorrhagic stroke developed polyarticular gout only on the ipsilateral side to his hemiparesis, while another patient with basilar artery thrombosis and locked-in syndrome suffered a polyarticular gout flare only on the side that had regained limited function. As suggested by these cases, the effect of hemiparesis on gout is complex. Further insight into the interplay between gouty flares and hemiparesis may lead to novel therapeutic strategies for gout

The use of musculoskeletal ultrasound (MSKUS) in rheumatology practice and research has increased steadily over the last decade. An ever-growing body of literature shows parity and even superiority of MSKUS when compared to physical examination, plain radiography, and more expensive and static imaging modalities such as MRI. While many use the modality for procedure guidance, investigators continue to demonstrate its ability to impact diagnoses in a variety of rheumatic diseases. Initial efforts focused on establishing MSKUS as a helpful tool for rheumatoid arthritis (RA), especially in the detection of synovitis and joint erosions, but numerous studies are validating the use of MSKUS as a helpful diagnostic tool for the spondyloarthropathies, crystal diseases, osteoarthritis, and other rheumatic diseases. Advances in ultrasound technology are translating into more sensitive and accurate studies. Within the research community, current efforts aim at maximizing the direct clinical impact of MSKUS by developing global or patient level assessments and simplified joint scoring systems, with improvements in intra- and inter-reader reproducibility

Fewer United States rheumatologists perform or utilize musculoskeletal ultrasound (MSUS) than those in Europe, though this disparity is narrowing. To document perceptions and use of MSUS in the U.S. rheumatology community, we sent an anonymous electronic survey to American College of Rheumatology (ACR) physicians and tailored versions to fellows and program directors. A separately-conducted survey was sent to a smaller group of rheumatologists already utilizing MSUS. Acknowledging survey bias, we found that 20% of rheumatologists and fellows who responded are utilizing MSUS, and those using it primarily do so for diagnosis and injection guidance. Many rheumatologists across the country think that ultrasound should become a standard tool in rheumatology training, practice, and research. Despite an inherent survey bias likely overstating interest in MSUS, this study is valuable as the first to document this trend among U.S. rheumatologists