Jacob Karsh

Celiac disease arthropathy and autoimmunity study.

To evaluate presence of sero‐negative spondyloarthritis (SpA) in celiac disease (CD) patients, and whether compliance with a gluten free diet (GFD) improved arthritis manifestations in these patients.

A measure of limited joint motion and deformity correlates with HLA-DRB1 and DQB1 alleles in patients with rheumatoid arthritis

OBJECTIVE To assess factors associated with a poor outcome in rheumatoid arthritis (RA), a measure was developed of limited joint motion and deformity, a deformity index (DI), and correlated biochemical and genetic variables with the magnitude of the DI. METHODS Forty patients were evaluated in a cross sectional study. Clinical measures included the DI and Health Assessment Questionnaire, and disease variables included the erythrocyte sedimentation rate, C reactive protein, rheumatoid factor, and HLA-DRB1 and DQB1 alleles. RESULTS Significant correlations were noted between increasing DI and duration of RA and concentration of C reactive protein. Patients with a DQB1*301 allele or DR4 allele had a higher DI than those without, and a positive trend was noted between increasing DI and dose of DRB1 RA susceptibility alleles. The trend was lost when a non-linear regression technique was used to remove the effect attributable to C reactive protein, suggesting an interrelation between persistent inflammation and genetics in determining total joint damage. CONCLUSIONS The DI may be useful to study interactions between genetic and inflammatory processes in rheumatoid disease progression.

Preliminary results of severity of illness measures of rheumatoid arthritis using infrared imaging

For the first phase of a large project, we used an infrared imaging camera (thermograph) to obtain accurate measurements of body temperature in joints of twelve human normal subjects (control group) and for thirteen patients who had been diagnosed with rheumatoid arthritis (RA) by a rheumatologist. The ultimate goal is to create a low cost effective method to diagnose early synovitis. Temperature measurements of hands were analyzed with first order statistics. Results show significant temperature differences between control subjects and patients for every joint and hand portion measured. Future work will complete the analysis of knees, elbows, ankles, combine infrared (IR) imaging and intra-optical (IO) imaging, and incorporate feature extraction and classification approaches to stratify patients into severity of illness prior to, and after receiving treatment.

Rheumatologists lack confidence in their knowledge of cannabinoids pertaining to the management of rheumatic complaints

BackgroundArthritis pain is reported as one of the most common reasons for persons using medical herbal cannabis in North America. “Severe arthritis” is the condition justifying legal use of cannabis in over half of all authorizations in Canada, where cannabis remains a controlled substance. As champions for the care of persons with arthritis, rheumatologists must be knowledgeable of treatment modalities both traditional and non-traditional, used by their patients. As study of cannabinoid molecules in medicine is recent, we have examined the confidence in the knowledge of cannabinoids expressed by Canadian rheumatologists.MethodsThe confidence of rheumatologists in their knowledge of cannabinoid molecules and mechanisms relevant to rheumatology, and their ability to advise patients about cannabinoid treatments was recorded by an online questionnaire circulated via email to the entire Canadian Rheumatology Association membership.ResultsOver three quarters of the 128 respondents lacked confidence in their knowledge of cannabinoid molecules. While 45% of respondents believed there was no current role for cannabinoids in rheumatology patient care, only 25% supported any use of herbal cannabis. With 70% never having previously prescribed or recommended any cannabinoid treatment, uncertainty regarding good prescribing practices was prevalent. Concerns about risks of cannabis use were in line with the current literature.ConclusionsRheumatologists lacked confidence in their knowledge of cannabinoid molecules in general and in their competence to prescribe any cannabinoid for rheumatic complaints. In line with this uncertainty, there is reticence to prescribe cannabinoid preparations for rheumatology patients. Guidance is required to inform rheumatologists on the evidence regarding cannabinoids.

Detection of rheumatoid arthritis using infrared imaging

Rheumatoid arthritis (RA) is an inflammatory disease causing pain, swelling, stiffness, and loss of function in joints; it is difficult to diagnose in early stages. An early diagnosis and treatment can delay the onset of severe disability. Infrared (IR) imaging offers a potential approach to detect changes in degree of inflammation. In 18 normal subjects and 13 patients diagnosed with Rheumatoid Arthritis (RA), thermal images were collected from joints of hands, wrists, palms, and knees. Regions of interest (ROIs) were manually selected from all subjects and all parts imaged. For each subject, values were calculated from the temperature measurements: Mode/Max, Median/Max, Min/Max, Variance, Max-Min, (Mode-Mean), and Mean/Min. The data sets did not have a normal distribution, therefore non parametric tests (Kruskal-Wallis and Ranksum) were applied to assess if the data from the control group and the patient group were significantly different. Results indicate that: (i) thermal images can be detected on patients with the disease; (ii) the best joints to image are the metacarpophalangeal joints of the 2nd and 3rd fingers and the knees; the difference between the two groups was significant at the 0.05 level; (iii) the best calculations to differentiate between normal subjects and patients with RA are the Mode/Max, Variance, and Max-Min. We concluded that it is possible to reliably detect RA in patients using IR imaging. Future work will include a prospective study of normal subjects and patients that will compare IR results with Magnetic Resonance (MR) analysis.

Efficacy, Tolerability, and Safety of Cannabinoid Treatments in the Rheumatic Diseases: A Systematic Review of Randomized Controlled Trials.

To assess the efficacy, tolerability, and safety of cannabinoids (phyto‐ and syntheto‐) in the management of rheumatic diseases.

Celecoxib modifies glomerular basement membrane, mesangium and podocytes in OVE26 mice, but ibuprofen is more detrimental.

The role of COXs/PGs (cyclo-oxygenases/prostaglandins) in diabetic kidneys remains unclear. NSAIDs (non-steroidal anti-inflammatory drugs) that inhibit COXs/PGs are known for their renal toxicity, and COX-2 inhibitors worsen cardiovascular outcomes in susceptible individuals. Given the renal controversies concerning COX-2 inhibitors, we compared the effect of chronic NSAIDs (non-selective, ibuprofen; COX-2-selective, celecoxib) on diabetic kidneys in OVE26 mice from 8 weeks of age. Systolic BPs (blood pressures) were increased by NSAIDs in diabetic mice at 20 weeks, but were unchanged at 32 weeks. Although NSAIDs further increased diabetic kidney/body weight ratios, they did not affect albuminuria. Mesangial matrix was increased 2-fold by celecoxib but not ibuprofen. Electron microscopy revealed that NSAIDs reduced GBM (glomerular basement membrane) thickness and slit pore diameters. Although diabetics had increased glomerular diameters and reduced foot process densities, these were unaltered by NSAIDs. Celecoxib does not exacerbate the diabetic state, but PG inhibition may contribute to disease progression by modifying the GBM, mesangial area and podocyte structure in OVE26 mice. Despite these findings, celecoxib remains safer than a similar dose of ibuprofen. The present study substantiates the need to more closely consider selective COX-2 inhibitors such as celecoxib as alternatives to non-selective NSAIDs for therapeutic management in a setting of chronic kidney disease.

Treating Psoriasis and Psoriatic Arthritis: Position Paper on Applying the Treat-to-target Concept to Canadian Daily Practice

Objective. To develop preliminary treat-to-target (T2T) recommendations for psoriasis and psoriatic arthritis (PsA) for Canadian daily practice. Methods. A task force composed of expert Canadian dermatologists and rheumatologists performed a needs assessment among Canadian clinicians treating these diseases as well as an extensive literature search on the outcome measures used in clinical trials and practice. Results. Based on results from the needs assessment and literature search, the task force established 5 overarching principles and developed 8 preliminary T2T recommendations. Conclusion. The proposed recommendations should improve management of psoriasis and PsA in Canadian daily practice. However, these recommendations must be further validated in a real-world observational study to ensure that their use leads to better longterm outcomes.

Management of Rheumatoid Arthritis 2012: A Canadian State of the Art

> Our thesis is that there is no specific therapy for rheumatoid arthritis. With early diagnosis, simple conservative measures plus salicylates can be so effective that there is little need to utilize more potent pharmacologic therapy with the attendant increase in danger. These words were one man’s opinion of the state of the art of the treatment of rheumatoid arthritis (RA) in 19661. Whether one agreed completely with that opinion or not in 19662, it needs to be acknowledged that the opinion was well argued and informed by a thorough, albeit not systematic, review of the literature of the time. The author found the published evidence on salicylates and personal experiences with bed rest convincing, decried the lack of well-done randomized clinical trials evaluating gold, noted that any longterm benefits of gold were not sustained, and concluded that the lack of sustained effect coupled with the well-known toxicities of gold could not justify its use. This opinion (level II/III evidence) led to a course of action (strength of recommendation C, D). > In the past 3 years, patients have been adequately managed with bed rest, salicylates, and physiotherapy at the Massachusetts Memorial Hospitals and Boston City Hospital. Indeed, gold salt therapy has not been used by any of a large group of Arthritis Clinic Staff Physicians in these clinics, and no patient has been started on this form of treatment. Revisiting the issue of care of RA in 1974, the editors opined that no developments had occurred to alter the conclusions of 19663. Since 1974, the … Address correspondence to Dr. Karsh; E-mail: jkarsh{at}ottawahospital.on.ca

Dr. Troppmann and Dr. Karsh reply

We do not dispute the principle that increasing the likelihood of a response to a treatment is desirable whether one uses expensive or inexpensive therapy. The Canadian Rheumatology Association/Spondyloarthritis Research Consortium of Canada (CRA/SPARCC) guidelines replace the expert’s opinion in the ASsessments in Ankylosing Spondylitis guidelines with an objective measure of inflammation, either an elevated acute-phase reactant or magnetic resonance imaging (MRI). This is quite reasonable. Our goal was to ascertain the proportion of patients with seronegative spondyloarthritis who might require an MRI according to the CRA/SPARCC guidelines. We did not include an opinion on the need for a tumor necrosis factor (TNF) inhibitor as an inclusion criterion because it is not part of the CRA/SPARCC guidelines. We clearly state that one of the limitations of our study2 is the small sample size. Thus the figure of 41% is not a gross exaggeration but simply a number, an estimate based on the sample size; the confidence interval is 26%–60%. We suspect that most rheumatologists in Canada and elsewhere include their opinion (and the patient’s opinion) on the need for an anti-TNF drug whether part of the guidelines or not. This form of self-restraint is probably one of the unspoken limits to the use of expensive medications. However, agencies paying for drugs generally do not deal well with gestalt. Currently in the province of Ontario there are no published provincial formulary guidelines for the use of an anti-TNF. When applying, we follow features common to several guidelines and provide a BASDAI ≥ 4 and as much other evidence in support of the diagnosis and increased disease activity such as radiographs, a Bath Ankylosing Spondylitis Functional Index, and blood tests (HLA-B27 and erythrocyte sedimentation rate/Creactive protein). We do not know which piece of information is critical to a positive response but suspect it is the BASDAI. In Ontario, at this date, the provincial formulary approves the use of etanercept and infliximab in AS but for unexplained reasons not adalimumab. We see the value of an MRI in providing objective evidence of inflammation. It could justify the use of an anti-TNF in a stoic patient with a BASDAI ≤ 4 who, in the doctor’s opinion, could benefit even if the patient might feel that they are in a patient-acceptable symptom state. However, the Ottawa region has the worst healthcare wait times in the province of Ontario, with a wait time of 12 months for an outpatient MRI being common1. Should our provincial formulary adopt the need for an MRI as eloquently described in the CRA/SPARCC guidelines, access to care in the Ottawa region would be delayed. We hope that the conclusion of our report2 is not that there are no advantages of an MRI, but rather that more means and resources are required for the timely diagnosis and treatment of the arthritic diseases.