1 Rat Bite Fever Resembling Rheumatoid Arthritis in a 46 Year Old Female



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Rat Bite Fever Resembling Rheumatoid Arthritis in a 46 Year Old Female
Ripa Akter (Memorial University, St. John’s); Paul Boland (Memorial University, St. John’s); Peter Daley (Memorial University, St. John’s); Proton Rahman (Memorial University, St. John’s); Nayef Al Ghanim (Memorial University, St. John’s)
A 46 year old female was admitted with a 1 week history of fever and symmetrical inflammatory polyarthritis associated with morning stiffness of 30 minutes duration. Past medical history was significant for seizure disorder, irritable bowel syndrome, chronic back pain and iron deficiency anemia. Family history was unremarkable for any rheumatological disease. On examination, she was febrile (38 degree celsius) with synovitis of her wrists, ankles, bilateral 5th metatarsophalangeal joints and left 3rd metacarpophalangeal joint. ESR and CRP were found to be elevated (76 MM/HR and 149 mg/L). Initial blood culture and serological tests including hepatitis B and C, parvovirus B19, HIV, Lyme disease and Neisseria gonorrhea were negative. Rheumatological work up including rheumatoid factor, anti-nuclear antibody, anti-cyclic citrullinated peptide antibody, anti-neutrophil cytoplasmic antibodies, anti-dsDNA antibody and compliment levels were all within normal limits. The patient was treated with a presumed diagnosis of rheumatoid arthritis with oral prednisone with mild improvement in synovitis. She was discharged home on triple therapy (methotrexate, sulphasalazine and hydroxychloroquine). The patient then returned to the hospital next day with worsening synovitis, fever 39 degree celcius and significant worsening of lower back pain. Sulphasalazine and methotrexate were discontinued due to mild elevation of liver enzymes. She continued to be febrile intermittently with ongoing elevated ESR of 124 MM/HR and CRP of 170 mg/L. Synovial fluid culture of the left ankle was negative. She then received intravenous methylprednisone for 2 days for ongoing severe pain with no improvement. Repeat blood culture grew Streptobacillus moniliformis. MRI revealed L5-S1 diskiitis .On further questioning, patient admitted to having a pet rat and a pet cat, both of which had died of an unknown illness in the week prior to the initial presentation to hospital. She also reported receiving a rat scratch to her chest.
A diagnosis of Rat Bite fever (RBF) was made. The patient then was treated with intravenous ceftazidime with discontinuation of steroids and hydroxycholoquine. Synovitis improved significantly.
Conclusion: Rat bite fever is very uncommon and very difficult to diagnose. A history of zoonotic exposure is the key to diagnosis. Prognosis is good when treated appropriately but potentially lethal if left untreated. It is important for rheumatologists to be aware of RBF as a cause of symmetrical inflammatory polyarthritis and mimic of rheumatoid arthritis. This case highlights the potential hazard of misdiagnosis and treatment with immunosuppressive agents.
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RheumExam Atlas: A Web-Based Photographic Atlas to Support Physical Exam Teaching
Sonia Seto (University of Toronto, Toronto); Lori Albert (University of Toronto, Toronto)
Objectives: The diagnosis of rheumatic diseases often rests heavily on the physical examination.   Therapeutic advances in the last decade have made it more challenging to find individuals with early disease manifestations or persistent physical findings to participate in clinical instruction of trainees. Many pictures are available on an internet search, but in the absence of support by an experienced clinician, these pictures may be misinterpreted by learners and lead to chronic misconceptions.   In 2008 a bedside teaching atlas was developed to support learner recognition of physical findings in rheumatology during clinical teaching. (Albert LJ, Mills K and Roper N. Creation of a Bedside Teaching Atlas. Poster presented at: CRA-ASM 2009). This included pictures of real patients’ physical findings (eg.PIP joint effusions, sclerodactyly, etc.) and explanatory text for self-study or use by non-rheumatologist teachers. The atlas has been a very successful teaching tool locally.   Limitations of the atlas, however, include its lack of availability, its size and bulk (making it difficult to compare and contrast pictures such as PIP effusions vs Bouchard's nodes) and the inability to add new pictures.  Development of an electronic atlas was undertaken to overcome these limitations.
Methods: A student enrolled in the MSc program in Biomedical Communications at University of Toronto (SS) was engaged through the Office of Integrated Medical Education summer Educational Information Technology program to build a tablet-responsive app to replace the hardcopy atlas. A web-based application was used that is compatible with Android or iOS, and can be used on a standard desktop computer if tablet or Wifi are unavailable.  Functionality relevant to a clinical teaching session was built into the design: user-friendly index; capacity to move easily through the picture bank and toggle easily between pictures; concealable text for self-study; functionality for videos (eg. Bulge sign for knee effusions); capacity to add new pictures; an imbedded evaluation/rating template.     
Results: RheumExam Atlas (rheumatlas.utorontoeit.com) is now widely available at no cost.  It will be of value for clinical teachers and trainees. It can be used by all health professions and all specialities, in urban or remote communities, with or without a rheumatologist  teacher. 
Conclusion: A web-based atlas is readily accessible and provides a resource to support learning and recognition of a broad range of key physical findings in the rheumatic diseases. It is hoped that rheumatologists across Canada will submit photographs and other relevant content for uploading to RheumExam Atlas to enhance and further build this teaching resource. 
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Use of Antibiotics and Subsequent Risk of Systemic Lupus Erythematous: A Matched Case-Control Study
Neda Amiri (University of British Columbia, Vancouver); Mehyar Etminan (University of British Columbia, Vancouver); Rachel Lipson (EMMES Canada, Burnaby); Darby Thompson (EMMES Canada, Burnaby); Sharan Rai (Arthritis Research Canada, Richmond); Antonio Avina-Zubieta (Arthritis Research Centre of Canada, Richmond)
Objectives: Objective: To examine the association of exposure to cyclines, macrolides, and penicillins antibiotics with the development of subsequent Systemic Lupus Erythematosus (SLE).  
Methods: Methods:  We conducted a nested case-control study using an administrative health database in British Columbia, Canada, from 1997-2010. Cases were defined using a validated algorithm that includes a combination of ICD-9 and ICD-10 codes and SLE drug therapy. Incident cases were age-, sex-, and entry time-matched to 10 controls using density-based sampling. We evaluated cumulative exposure to any cyclines, macrolides, and penicillins prior to SLE diagnosis allowing for removal of cases with any exposure in the year prior to the index date. Adjusted odds ratios were computed using conditional logistic regression.    
Results: Results: We identified 3,639 new SLE cases corresponding to 361,032 matched controls. All three classes of antibiotics had a statistically significant association with the development of SLE in the unadjusted models (Table 1). However, after adjusting for the Charlson comorbidity index, hormone use, healthcare resource use and socioeconomic status only females exposed to cyclines showed a statistically significant association [OR = 1.6 (95% CI, 1.3–1.9)].  
Conclusion: Conclusion: Females exposed to cyclin antibiotics had a 60% increased risk of developing SLE.
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What is the Location of Dactylitis in Ankylosing Spondylitis and Psoriatic Arthritis Patients and How Do They Respond to Anti-TNF Treatment?
Regan Arendse (University of Saskatchewan, Saskatoon); Proton Rahman (Memorial University, St. John’s); Denis Choquette (Institut de rhumatologie de montréal, Montréal); Antonio Avina-Zubieta (Arthritis Research Centre of Canada, Richmond); Michel Zummer (Université de Montréal, Département de médecine, Montreal); Milton Baker (University of Victoria, Victoria); Jaqueline Stewart (Penticton); Isabelle Fortin (CH Rimouski, Rimouski); Michelle Teo (n/a, Penticton); Emmanouil Rampakakis (JSS Medical Research, Montreal); Eliofotisti Psaradellis (JSS Medical Research, St-Laurent); Brendan Osborne (Janssen Inc, Toronto); Cathy Tkaczyk (Janssen Inc, Toronto); Karina Maslova (Janssen Inc, Toronto); Francois Nantel (Janssen Inc, Toronto); Allen Lehman (Janssen Inc, Toronto)
Objectives: Dactylitis is one of the most commonly reported features in spondyloarthritis. It has been hypothesized that dactylitis is a functional enthesitis at the proximal interphalangeal joints, resulting in synovitis, tenosynovitis, bone and soft tissue oedema to the digit, and may simultaneously involve multiple digits.  Our objective was to identify the location of dactylitis in ankylosing spondylitis (AS) and psoriatic arthritis (PsA) patients and to determine their response to anti-TNF treatment. 
Methods: BioTRAC is an ongoing, prospective registry of patients initiating treatment for rheumatoid arthritis (RA), AS, or PsA with infliximab (IFX) or golimumab (GLM). Eligible people for this analysis included AS and PsA patients treated with IFX who were enrolled since 2005 or with GLM since 2010 who had available information on dactylitis. The McNemar (paired Chi-square) test was used to compare the presence of dactylitis over time. 
Results: A total of 260 AS and 261 PsA patients were enrolled with a mean (SD) age at baseline of 46.1 (13.0) vs. 50.0 (12.0) years, disease duration of 6.4 (9.8) vs. 5.2 (6.8) years, and proportion of females 40.6% vs. 48.5%, respectively. Among patients with AS, dactylitis was reported in 6.2% and 2.2% of patients at baseline and 6 months, respectively; at 6 months of treatment 73.3% of AS patients with dactylitis at baseline had no dactylitis and 1.6% developed dactylitis (P=0.057).  For PsA higher proportions of dactylitis were observed with 30.7%, and 12.7%, respectively; at 6 months of treatment 69.0% of PsA patients with dactylitis at baseline had no dactylitis and 4.6% developed dactylitis (P<0.001). The highest prevalence of dactylitis observed was for feet in AS and PsA patients. Among AS patients, the baseline distribution of dactylitis amongst hand digits (HD) and foot digits (FD) included HD1(1.9%), HD2(3.1%), HD3(3.1%), HD4(1.5%), HD5(1.5%), FD1(2.7%), FD2(3.8%), FD3(2.3%), FD4(2.3%), FD5(1.5%).  Among PsA patients, baseline dactylitis included HD1(4.2%), HD2(9.2%), HD3(8.0%), HD4(8.0%), HD5(5.4%), FD1(8.0%), FD2(12.6%), FD3(11.1%), FD4(14.9%), FD5(10.0%). Presence of dactylitis in hands or feet (any digit) was associated with significantly higher HAQ in AS and PsA (AS: ΔHAQ=1.36 (P≤0.001); PsA: ΔHAQ=0.64 (P≤0.001)).  
Conclusion: A considerable proportion of PsA patients had dactylitis at anti-TNF initiation in this Canadian real-world cohort. Although a lower proportion of patients had dactylitis among AS patients, the presence of dactylitis was associated with higher functional disability in both AS and PsA patients. Treatment with IFX or GLM for 6 months was associated with significant reduction in the prevalence of dactylitis. 
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What is the Variability of HAQ over Time in Patients with Rheumatoid Arthritis Treated with Anti-TNF?
Regan Arendse (University of Saskatchewan, Saskatoon); Boulos Haraoui (Institut de Rhumatologie de Montréal, Montreal); Denis Choquette (Institut de rhumatologie de montréal, Montréal); John Kelsall (Mary Pack Arthritis Centre, Vancouver); Philip Baer (Private Practice, Scarborough); Dalton Sholter (University of Alberta, Edmonton); William Bensen (McMaster University, St. Joseph`s Healthcare Hamilton, Hamilton); Mary Bell (University of Toronto, Toronto); Michelle Teo (n/a, Penticton); Emmanouil Rampakakis (JSS Medical Research, Montreal); Eliofotisti Psaradellis (JSS Medical Research, St-Laurent); Brendan Osborne (Janssen Inc, Toronto); Cathy Tkaczyk (Janssen Inc, Toronto); Karina Maslova (Janssen Inc, Toronto); Francois Nantel (Janssen Inc, Toronto); Allen Lehman (Janssen Inc, Toronto)
Objectives: The Health Assessment Questionnaire (HAQ) remains the gold standard for measuring patient-reported functional status in rheumatoid arthritis (RA) and is included among the measures suggested by the American College of Rheumatology for making treatment decisions in routine care. We have previously shown that significant variability exists in the correlation of individual HAQ questions with patient-reported and clinical outcomes. The aim of this analysis was to assess, in routine care, the timelines of HAQ improvement as compared to clinical improvement and to examine possible differences in the improvement of individual questions.
Methods: BioTRAC is an ongoing, prospective registry of patients initiating treatment for RA, AS, or PsA with infliximab (IFX) or golimumab (GLM). Eligible people for this analysis included RA patients treated with IFX who were enrolled since 2002 or with GLM since 2010. Time to achieving minimal important difference (MID; Δ≥0.22) in HAQ, HAQ≤1, minimal disease (MD) in individual HAQ questions (no or some difficulty), CDAI low disease activity (LDA), or CDAI remission was assessed with the Kaplan-Maier estimator of the survival function and cox regression.
Results: 1205 patients (75.3% female) were included with mean (SD) age of 56.0 (13.6) years and disease duration of 8.4 (8.9) years at baseline. Mean (SD) HAQ and CDAI were 1.55 (0.72) and 33.8 (17.4), respectively.  Statistically significant and clinically meaningful improvements in both HAQ and CDAI were observed over time. The cumulative probability of achieving HAQ MID, HAQ≤1, CDAI LDA, and CDAI remission by 12 months was 69.5%, 54.5%, 54.1%, and 18.1%, respectively. Time to achieving HAQ MID [Hazard Ratio (95% CI): 3.6 (3.2-4.2)], HAQ≤1 [2.9 (2.6-3.4)], and CDAI LDA [3.1 (2.7-3.6)] was significantly lower as compared to CDAI remission. With respect to individual HAQ questions, at baseline, the most predominant usual activities that patients were unable to do were taking a tub bath (27.9%), reaching and getting down a 5-pound object from the head (21.8%), and doing chores such as vacuuming or yard work (23.2%). In accordance, time to having no or some difficulty in these activities was significantly higher compared to the remaining HAQ items.      
Conclusion: The Results show that the timelines for achieving HAQ targets in routine care is comparable to that of achieving CDAI LDA. Significant differences were observed in terms of improvement in individual HAQ items with the inability to take a tub bath, getting heavy overhead objects down, and doing chores being the most persistent.
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Improving the Ordering of Hand and Wrist Ultrasound to Manage Inflammatory Arthritis
Angela Arisz (University of Toronto Faculty of Medicine, Toronto); Dana Jerome (Women's College Hospital, Toronto); Wei Wu (Women's College Hospital, Toronto); Natasha Gakhal (Women's College Hospital, Toronto)
Objectives: Musculoskeletal ultrasound (US) is a reliable and sensitive tool increasingly used to assess for subclinical synovitis in the diagnosis and management of rheumatologic disease. There is little literature exploring how often active joint inflammation is detected via US and which clinical characteristics are associated with US-detected synovitis. This study aims to inform effective US ordering practices in the management of inflammatory arthritis by determining the clinical and laboratory correlates of positive US Results.
Methods: A retrospective chart review was conducted for hand/wrist ultrasounds ordered in an academic outpatient rheumatology clinic between May 1 2014 and April 30 2015. Data extracted included indication for US, and evidence of joint effusion, synovial thickening, or Doppler flow by radiologist report. Clinical data obtained included age, gender, treatment, the presence and duration of a.m. stiffness, swelling, or pain on history, and joint tenderness or swelling on exam. Laboratory parameters (ESR, CRP, ANA, RF, and anti-CCP), and whether or not clinical management changed post-US were also collected. Ultrasounds were characterized as positive if they showed evidence of synovial thickening and/or active Doppler flow. Univariate statistical analysis was conducted using the Wilcoxon Mann-Whitney test and Fisher’s exact test, and multivariate analysis was conducted using a logistic regression model.
Results: Over the study period 72 ultrasounds were ordered, of which 27 (37%) were positive and 45 (63%) were negative. 51 (71%) ultrasounds were ordered for diagnosis, and 21 (29%) for disease management. The median patient age was 56, and 57 (79%) patients were women. Treatment at the time of US was as follows: 23 (32%) patients were on NSAIDs, 17 (24%) were on DMARDs, 6 (8%) were on systemic steroids, and 19 (26%) had no treatment.  Predictors of positive US in the univariate analysis were disease control as the indication for US (p=0.035), positive ANA (p=0.002), and treatment with biologic/DMARD (p=0.048). Only positive ANA was predictive in a multivariate model (p=0.004). Positive ultrasounds were more likely to result in a change in clinical management (p=0.005).
Conclusion: This study did not demonstrate any clinical factors associated with positive hand/wrist US, and the majority of ultrasounds were negative, highlighting the importance of clinical assessment. This study is limited by small sample size. Further studies are needed to determine whether any clinical features can guide the ordering of ultrasounds, limiting US use to situations where it is more likely to change or inform disease management.
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Development, Sensibility and Validity of a Systemic Autoimmune Rheumatic Disease Case Ascertainment Tool
Susan Armstrong (University of Toronto, Toronto); Joan Wither (University of Toronto, Toronto); Alan Borowoy (Division of Rheumatology, Department of Medicine, Toronto Western Hospital, University of Toronto, Toronto); Carolina Landolt-Marticorena (Toronto Western Research Institute, University Health Network, Toronto); Aileen Davis (Health Care and Outcomes Research, Toronto Western Research Institute, University Health Network; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto); Sindhu Johnson (Division of Rheumatology, Department of Medicine, Toronto Western Hospital, Toronto)
Objectives: Case ascertainment in a population through self-report is a convenient way to collect information, but is often inaccurate. The purpose of this study was to develop, assess the sensibility and validate a tool to identify cases of systemic autoimmune rheumatic diseases (SARD) in the outpatient setting.
Methods: The SARD tool was administered to cases and controls consecutively sampled from specialty clinics. Determinants of sensibility: comprehensibility, feasibility, face validity, and acceptability were evaluated using a numeric rating scale from 1–7. Comprehensibility was evaluated using the Flesch Reading Ease and Flesch-Kincaid Grade Level. Medical records were used to validate the self-reported diagnoses using Cohen’s kappa statistic (κ).
Results: 141 participants (systemic lupus erythematosus (SLE), systemic sclerosis (SSc), rheumatoid arthritis, Sjögren’s disease (SjD), inflammatory myositis (PM/DM) and controls) completed the questionnaire. The Flesch Reading Ease score was 77.1, and the Flesch-Kincaid Grade level was 4.4. Respondents endorsed (mean rating ± standard deviation) comprehensibility (6.12±0.92), feasibility (5.94±0.81), face validity (5.35±1.10) and acceptability (3.10±2.03, where 1 = very unlikely). The SARD tool had a sensitivity of 0.91 (95% CI 0.88, 0.94) and a specificity of 0.99 (0.96, 1.00). For the whole cohort, the agreement between the SARD tool and medical record was κ= 0.82 (95% CI 0.77, 0.88). Subgroup analysis by SARD found kappa coefficients for SLE κ = 0.88 (95% CI 0.79, 0.97), SSc κ = 1.0 (95% CI 0.97, 1.0), PM/DM κ =0.72 (95% CI 0.49, 0.95), SjD κ = 0.85 (95% CI 0.71, 0.99) and rheumatoid arthritis κ = 0. 61 (95% CI 0.34, 0.87) with the confirmatory question. The screening questions had sensitivity ranging 0.96–1.0, and specificity ranging 0.88–1.
Conclusion: This SARD case ascertainment tool has demonstrable sensibility and validity. The use of both screening and confirmatory questions confers added accuracy. 
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Safety and Effectiveness of Hyperbaric Oxygen Therapy for Systemic Sclerosis Ulcers
Susan Armstrong (University of Toronto, Toronto); Wayne Evans (Hyperbaric Medicine Unit, Department of Anaesthesia, Faculty of Medicine, University of Toronto, Toronto); Zareen Ahmad (Toronto Scleroderma Program, Division of Rheumatology, Toronto Western Hospital, Mount Sinai Hospital, Toronto); Sindhu Johnson (Division of Rheumatology, Department of Medicine, Toronto Western Hospital, Toronto)
Objectives: Vascular complications of systemic sclerosis (SSc, scleroderma) can result in ulcers in the distal extremities, which limit function and are often refractory to conventional treatments. Hyperbaric oxygen therapy (HBOT) has been used in the treatment of non-healing wounds, but its utility in patients with SSc is uncertain. The primary objective of this study was to evaluate the safety of HBOT for SSc ulcers. We secondarily evaluated the effectiveness of HBOT for SSc ulcers, and patient selection criteria for treatment of SSc ulcer patients with HBOT.
Methods: We conducted a retrospective cohort study of SSc patients who were evaluated for treatment with HBOT in the Toronto Scleroderma Program and the Toronto General Hospital Hyperbaric Unit between 2002 and 2015. HBOT treatments involved 30-50 sessions in a monoplace or multiplace chamber with compression to a maximum depth of 2.5 atm and breathing oxygen for a total of 90 minutes 5 days per week. Ulcers were defined as lesions with a visually discernable depth and loss of epithelial continuity. Reasons for declining access to HBOT, adverse events and effectiveness in ulcer healing were evaluated. An ulcer was categorized as healed if it achieved epithelial continuity or National Pressure Ulcer Advisory Panel (NPUAP) stage X (stable necrotic tissue core or eschar). Transcutaneous oxygen tension criteria for evaluating ‘healability’ in diabetic foot ulcers were applied as none have been validated for SSc.
Results: 2261 charts were reviewed to identify 24 HBOT treated ulcers in 8 SSc subjects. They had a mean ± SD age of 58.9 ± 15.4 years and disease duration of 13.8 ± 8.9 years. Seventy-five percent were female. Twelve SSc subjects did not receive HBOT due to reasons that included lack of achieving “healable” response to oxygen on transcutaneous oximetry and technical limitations in sensor placement options (n=4), presence of moderate - severe pulmonary arterial hypertension (n=2) and confinement anxiety (n=1). Of the HBOT treated subjects, adverse events included brief episodes of otic barotrauma (37.5%). Fifteen ulcers (62.5%) achieved epithelial continuity or NPUAP stage X after HBOT.
Conclusion: HBOT may be an effective option for SSc patients with non-healing ulcers. Therapy was generally well-tolerated, with no significant adverse events although transient self-limiting otic barotrauma was reported. Patient selection criteria specific to the SSc population may need to be developed.
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Concomitant Treatment Use During Treatment with Golimumab in Patients with Rheumatoid Arthritis.
Philip Baer (Private Practice, Scarborough); Mary Bell (University of Toronto, Toronto); Boulos Haraoui (Institut de rhumatologie de Montreal, Montréal); Louis Bessette (centre d'ostéoporose et de rhumatologie de Québec, Québec); John Kelsall (Mary Pack Arthritis Centre, Vancouver); Maqbool Sheriff (Nanaimo Regional Hospital, Nanaimo); Emmanouil Rampakakis (JSS Medical Research, Montreal); John Sampalis (JSS Medical Research Inc, Montreal); Allen Lehman (Janssen Inc, Toronto); Brendan Osborne (Janssen Inc, Toronto); Cathy Tkaczyk (Janssen Inc, Toronto); Francois Nantel (Janssen Inc, Toronto); Karina Maslova (Janssen Inc, Toronto)
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