Fever and Increased Gastrointestinal Uptake on Positron Emission Tomography after Anti-Tumour Necrosis Factor Therapy: A Case Report of Whipple's Disease.

Introduction: Whipple's disease is a rare condition that can present with atypical and non-specific features requiring a high index of suspicion for diagnosis. Case Presentation: We present a case of a man in his 40s with peripheral arthritis and bilateral sacro-ileitis for 4-5 years that was treated with an anti-tumour necrosis factor therapy, which led to worsening of his symptoms, elevation of the inflammatory markers, and the development of fever, night sweats, anorexia, and a significant weight loss. The patient had no abdominal pain, diarrhoea, or other gastrointestinal symptoms. An FDG-PET scan showed increased uptake in the stomach and caecum. Endoscopic examination showed inflammatory changes in the stomach and normal mucosa of the duodenum, jejunum, terminal ileum, caecum, and colon. Histopathology was inconclusive, but the diagnosis was confirmed with Tropheryma whipplei PCR testing. He had no neurological symptoms, but cerebrospinal fluid Tropheryma whipplei PCR was positive. He was treated with intravenous ceftriaxone 2 g daily for 4 weeks, followed by trimethoprim/sulfamethoxazole 160/800 mg twice daily for 1 year with close monitoring and follow-up. Conclusion: This case presents an atypical and challenging presentation of Whipple's disease and the importance of proactive testing for neurological involvement.

Ultrasound imaging of the dorsalis pedis artery as an early indicator of the precursory changes for rheumatoid vasculitis: A case series.

Introduction: Clinical verification of rheumatoid vasculitis (RV) persists as a mid-to-late diagnosis with medical imaging or biopsy. Early and subclinical presentations of RV, in particular, can remain underdiagnosed in the absence of adequate diagnostic testing. In this study, the research demonstrated the precursory changes for RV in patients with rheumatoid arthritis (RA) using non-invasive ultrasound imaging of a peripheral vessel. Method: Six participants were recruited: three participants with (RA) and three age- and gender-matched healthy controls. All participants completed a Foot Health Survey Questionnaire (FHSQ), and participants with RA completed a Rheumatoid Arthritis Disease Activity Index-5 (RADAI-5). Bilateral B-mode and Doppler ultrasound of the dorsalis pedis artery (DPA) was performed. The degree of inflammation, lumen and artery diameters, lumen diameter-to-artery diameter ratio and peak systolic velocity in the proximal DPA were compared between the two groups. Results: The mean RADAI-5 score (5.4 ± 0.8 out of 10) indicated moderate disease activity amongst participants with RA. Inflammation was observed in the DPA wall in all participants with RA, compared to no inflammation observed in the control group (Friedmans two-way analysis: χ2 = 15.733, P = 0.003). Differences between groups for inflammation, lumen diameter and lumen diameter-to-artery diameter ratio were found (P < 0.034), without differences for artery diameter and peak systolic velocity (P > 0.605). DPA wall inflammation did not correlate with FHSQ scores (r = -0.770, P = 0.073). Conclusion: Despite moderate RA disease activity, this is the first study to demonstrate the use of ultrasound to observe inflammation in small vessel disease. Our findings suggest ultrasound imaging may be a viable screening tool to demonstrate arterial wall inflammation, indicating the precursory changes of RV.

Reliability of Ultrasound Imaging in Examining Integrity and Inflammation in the Dorsalis Pedis Artery.

OBJECTIVE: Assessment of small vessel inflammatory diseases such as rheumatoid vasculitis is challenging. Small arteries such as the dorsalis pedis artery (DPA) are difficult to assess for changes in the arterial wall with medical imaging. Ultrasound imaging is a viable tool for examining the integrity and inflammatory changes in the arterial wall; however, no empirical data on its reliability have been described. METHODS: We measured the intra- and inter-rater reliability of ultrasound measurements across five parameters evaluating arterial integrity of the proximal DPA in participants with and without small vessel disease. We recruited 10 participants with rheumatoid arthritis and 10 healthy controls. Two sonographers using ultrasound independently measured DPA lumen diameter, artery diameter, lumen-to-arterial diameter ratio, arterial Doppler velocity and inflammatory changes in the proximal wall of the DPA. The intraclass correlation coefficient (ICC) was used to evaluate 95% confidence intervals within and between raters. Bland-Altman analyses were used to assess limits of agreement and were compared with minimal clinically important differences (MCID). RESULTS: Four of five selected parameters were found to have excellent intra- and inter-rater reliability within and between raters (ICC = 0.903-0.996). Acceptable reliability was found for measurement of arterial blood flow velocity within raters (ICC = 0.815-0.909), but not between raters (ICC = 0.634). Standard mean errors in all parameters were within minimal clinically important differences. CONCLUSION: Ultrasound imaging has been found to be a reliable method of assessment of arterial integrity and inflammation of the proximal DPA in people with small vessel disease. Evaluation of arterial blood flow velocity requires cautious interpretation.

Perceptions of Doppler ultrasound for rheumatoid arthritis disease activity assessment and education.

AIM: The aim of this qualitative study was to report the findings of the Defining rheumatoid arthritis progression using Doppler Ultrasound in Clinical practice (DEDUCE) Medical Practice Activity, which was developed to facilitate the utilization of Doppler ultrasound (DUS) by Australian rheumatologists in the treatment of patients with rheumatoid arthritis (RA). METHOD: Twenty-one rheumatologists recruited a total of 80 patients with RA in Disease Activity Score of 28 joints (DAS28) remission for DUS assessment and completed a pre- and post-activity questionnaire assessing their experience with DUS, as well as a 6-month follow-up questionnaire. Rheumatologists discussed DUS results with patients using visual aids. Patients completed a pre- and post-DUS assessment questionnaire. Data were summarized using descriptive statistics. RESULTS: Following completion of the activity, 95% of rheumatologists (20/21) believed DUS was a useful assessment tool for patients with RA. The majority found the DUS results useful and more than half thought the DUS assessment fit well into their consultation. A majority of rheumatologists indicated they would use DUS imaging in patients with low disease activity and remission, and for disease activity assessment to inform in therapeutic decision-making. All patients who responded found the visual aids useful and most felt that discussing DUS results improved understanding of their disease and would help with medication adherence. CONCLUSION: Incorporation of DUS imaging into routine clinical practice is feasible, encourages rheumatologists to utilize and expand their clinical application of DUS imaging in patients with RA, and may improve patient understanding of their disease and adherence to medication.

Reduced efficacy of transcatheter and surgical revascularization in Takayasu arteritis.

A 55-year-old woman with newly diagnosed Takayasu arteritis was followed for 7 years, during which time she underwent bare metal stenting, drug eluting stenting and coronary bypass grafting for critical coronary and renal artery stenoses. Interventions were initially successful but restenosis occurred within 24 months for all modalities. In contrast, native vessel disease was largely stable after the introduction of immunosuppressive therapy. We advocate a conservative revascularization approach in Takayasu arteritis in the absence of critical end organ ischemia and early optimization of medical therapy.

AC-CUTE: An Open-Label Study to Evaluate Progression of Structural Joint Damage and Inflammation in Subjects with Moderate to Severe Rheumatoid Arthritis.

AIM: Examine the efficacy of once-weekly subcutaneous tocilizumab (SC-TCZ) on joint damage at 24 weeks based on radiography of the hands and feet and magnetic resonance imaging (MRI) of the hand in subjects with moderate to severe rheumatoid arthritis (RA). METHODS: In this Australian open-label, multicentre, prospective, single-arm study, subjects received 162 mg SC-TCZ weekly. Primary endpoint was change in radiographic Genant-modified Total Sharp Score (TSS) between baseline and Week 24. Secondary endpoints included change from baseline to Week 24 in RA MRI scoring (RAMRIS) of erosions, synovitis, and osteitis and Cartilage Loss Score (CARLOS) in the dominant hand and disease activity score 28 (DAS28). RESULTS: 52 subjects were enrolled (80% female, mean (SD) age 57 (12) years). Radiography showed mild but not significant progression of joint damage (mean (SD) change in TSS 0.46 (1.29)). Synovitis reduced significantly on MRI; however, osteitis, erosion, and cartilage loss did not change significantly. DAS28 improved significantly by Week 24; 78% of subjects achieved DAS28 remission. SC-TCZ was generally well tolerated. CONCLUSION: Synovitis and DAS28 decreased significantly; however, no significant change in osteitis or joint damage was observed at Week 24. TRIAL REGISTRATION: This trial is registered with Clinicaltrials.gov registration number NCT01951170 (ML28703).

Shear-wave elastographic ultrasound of metacarpophalangeal synovium in rheumatoid arthritis - A pilot study.

INTRODUCTION: Shear-wave elastographic ultrasound (SW-EUS) assesses the stiffness of human tissues. It is used in liver, thyroid and breast imaging but has not been studied in synovium. Soft tissues have a slower shear-wave velocity (SWV) than stiff tissues. We hypothesised that rheumatoid arthritis (RA) patients would have softer synovium than controls and this could be quantified with a slower SWV. We also assessed whether SWV varied with disease activity. METHODS: Nine patients with RA were consecutively recruited and matched with five controls. Participants underwent clinical assessment, blood sampling, grey scale ultrasound (GSUS), power Doppler ultrasound and SW-EUS of MCP joints 2-5 on the dominant hand. RESULTS: Average age was 60. Mean RA disease activity (DAS28-ESR) was moderate at 3.65. Patients with RA had lower maximum synovial SWV than controls (6.38 m/s vs. 6.99 m/s P = 0.042). Negative Pearson's correlation coefficients (PCC) were observed between maximum SWV and disease activity markers including GSUS graded synovial thickness (PCC = -0.57, P = 0.03) and ESR (PCC = -0.46, P = 0.095). Intra- and interobserver reliability was good with intraclass correlation coefficients (ICC) of 0.66 and 0.58, respectively, for quantitative maximum SWV and ICC > 0.80 for colour scale rated SWV. CONCLUSION: This is the first pilot study of SW-EUS in synovium. Maximum synovial SWV was significantly lower in RA than controls. There was a negative correlation between maximum SWV and GSUS synovial thickening. Further study is warranted to confirm the role of SW-EUS in diagnosing and assessing disease activity in RA.

Autoantibodies directed to centromere protein F in a patient with BRCA1 gene mutation.

BACKGROUND: Autoantibodies directed to centromere protein F were first reported in 1993 and their association with malignancy has been well documented. CASE: We present the case of a 48-year-old Caucasian female with a BRCA1 gene mutation associated with bilateral breast cancer. Antinuclear autoantibody immunofluorescence performed for workup of possible inflammatory arthropathy showed a high titre cell cycle related nuclear speckled pattern, with subsequent confirmation by addressable laser bead immunoassay of the target antigen as an immunodominant epitope at the C-terminus of centromere protein F. CONCLUSION: Here we review the current literature on centromere protein F, its association with breast cancer and present the first case of this antibody being identified in a person with a BRCA1 gene mutation.

Medication adherence in patients with rheumatoid arthritis: the effect of patient education, health literacy, and musculoskeletal ultrasound.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease affecting <1% of the population. Incompletely controlled RA results in fatigue, joint and soft tissue pain, progressive joint damage, reduced quality of life, and increased cardiovascular mortality. Despite an increasing range of disease modifying agents which halt disease progression, poor patient adherence with medication is a significant barrier to management. OBJECTIVE: The goal of this review was to examine the effectiveness of measures to improve patient medication adherence. METHODS: Studies addressing treatment adherence in patients with RA were identified by trawling PsycINFO, Medline, Cochrane, Pubmed, and ProQuest for studies published between January 2000 and October 2014. Articles were independently reviewed to identify relevant studies. RESULTS: Current strategies were of limited efficacy in improving patient adherence with medications used to treat RA. CONCLUSION: Poor medication adherence is a complex issue. Low educational levels and limited health literacy are contributory factors. Psychological models may assist in explaining medication nonadherence. Increasing patient knowledge of their disease seems sensible. Existing educational interventions appear ineffective at improving medication adherence, probably due to an overemphasis on provision of biomedical information. A novel approach to patient education using musculoskeletal ultrasound is proposed.

Paraneoplastic polyarteritis nodosa with cerebral masses: case report and literature review.

Polyarteritis nodosa (PAN) as a paraneoplastic vasculitis is rarely described, especially in association with squamous cell carcinoma (SCC). Furthermore, only 5% of all PAN patients have central nervous system (CNS) involvement, almost exclusively in the form of cerebral infarction or intracerebral haemorrhage. We report the first case of PAN with multiple immunosuppressant-responsive, cerebral vasculitic lesions in association with metastatic SCC.

Palmar fasciitis and polyarthritis syndrome in pancreatic carcinoma.

Palmar fasciitis and polyarthritis syndrome is a rare paraneoplastic condition that may portend a diagnosis of malignancy. We describe the case of a 73-year-old man who presented with progressive palmar swelling, erythema, pain, and contractures of both hands, This presentation and associated weight loss eventually led to the diagnosis of metastatic pancreatic adenocarcinoma. This case highlights the often delayed, but important diagnosis of this unusual paraneoplastic phenomenon which can mimic arthropathy, Dupuytren contracture, and scleroderma. Our case is also the first documentation of the extensive inflammatory magnetic resonance imaging changes in palmar fasciitis and polyarthritis syndrome, which affects all tissue planes including the synovium and explains its confusing clinical manifestations.

Ultrasound applications for the practicing rheumatologist.

Musculoskeletal ultrasound is an increasingly used tool for the evaluation and management of rheumatologic diseases. Its utilisation by rheumatologists is varied around the world and is dependent upon training and local expertise. Its applications can be broadly categorised into three main areas; for the education of patients, to aid the rheumatologist in the diagnosis and monitoring of disease, and therapeutically for joint aspiration and injection. Ultrasound is a safe, portable, easily repeatable, dynamic images in multiple planes and cheap form of imaging. Ultrasound however, is operator dependent and has a number of artefacts that can result in misinterpretation. Musculoskeletal Ultrasound uses a number of modes to characterise joint pathology, including grey scale, colour and power Doppler, spectral Doppler, 3D imaging, elastography. Musculoskeletal ultrasound can detect and monitor multiple joint pathologies including synovitis, tenosynovitis, and tendon pathologies, entheseal processes, bone erosions and osteophytes, cartilage changes and bursal pathologies.

Ultrasound in the evaluation of enthesitis: status and perspectives.

INTRODUCTION: An increasing number of studies have applied ultrasound to the evaluation of entheses in spondyloarthritis patients. However, no clear agreement exists on the definition of enthesitis, on the number and choice of entheses to examine and on ultrasound technique, which may all affect the results of the examination. The objectives of this study were to first determine the level of homogeneity in the ultrasound definitions for the principal lesions of enthesitis in the published literature and second, to evaluate the metric properties of ultrasound for detecting enthesitis according to the OMERACT filter. METHODS: Search was performed in PUBMED and EMBASE. Both grey-scale and Doppler definitions of enthesitis, including describing features of enthesitis, were collected and metrological qualities of studies were assessed. RESULTS: After selection, 48 articles were analyzed. The definition of ultrasound enthesitis and elementary features varied among authors. Grey-scale enthesitis was characterized by increasing thickness (94% of studies), hypoechogenicity (83%), enthesophytes (69%), erosions (67%), calcifications (52%), associated bursitis (46%) and cortical irregularities (29%). Only 46% of studies reported the use of Doppler. High discrepancies were observed on frequency, type of probe and Doppler mode used. Face and content validity were the most frequently evaluated criteria (43%) followed by reliability (29%) and responsiveness (19%). CONCLUSIONS: Ultrasound has evidence to support face, content validity and reliability for the evaluation of enthesitis, though there is a lack of well-reported methodology in most of the studies. Consensus on elementary lesions and standardization of exam is needed to determine the ultrasound definition of enthesitis in grey-scale and in Doppler for future applications.

Skin, muscle and joint disease from the 17th century: scurvy.

We report three cases of scurvy, with differing musculoskeletal presentations, from a tertiary teaching hospital in Sydney, Australia. Case 1 was a man with cerebral palsy who presented with knee swelling following a minor injury. In Case 2, a patient with thalassaemia major presented with purpuric rash, difficulty walking and distal thigh swelling and ecchymosis. Case 3 was a man with Down's syndrome who presented with acute ankle arthritis. Scurvy in Cases 1 and 3 were related to abnormal dietary preferences, whereas in Case 2, scurvy was thought to be related to thalassaemia. All three cases responded rapidly to vitamin C replacement. The subjects did not appear malnourished as they had adequate carbohydrate and protein intake.

Recurrent multi-organism keratoconjunctivitis manifesting as a first presentation of common variable immune deficiency (CVID).

Common variable immune deficiency (CVID) is characterized by hypogammaglobulinemia, impaired antibody production, and recurrent bacterial infections. Reports of ocular manifestations of CVID are rare. The authors discuss a patient with recurrent keratoconjunctivitis that presented as an initial manifestation of CVID. The diagnosis of CVID should be entertained where multiple recurrences of keratoconjunctivitis are unresponsive to antibiotic and steroid therapy and when other causes of immune deficiency have been excluded. Intravenous immunoglobulin (IVIG) was used successfully as treatment and is required lifelong as prophylaxis against further episodes of keratoconjunctivitis as well as the other infectious and inflammatory complications of this primary immunodeficiency syndrome.

Summary findings of a systematic review of the ultrasound assessment of synovitis.

This report presents the results of a recent systematic review performed by the OMERACT Ultrasound Group on the metric properties of ultrasound for the detection of synovitis in inflammatory arthritis. Reviews were conducted for the hand, wrist, elbow, shoulder, knee, ankle, and foot; most reports were related to the hand and knee, and the most common disease process was rheumatoid arthritis. The review highlights the current gaps in the literature, including a lack of reliability data with respect to intra-occasion and intra- and inter-reader reliability. Current work by our group is addressing these issues.

The OMERACT Ultrasound Group: status of current activities and research directions.

Ultrasound (US) is a relatively new imaging modality in rheumatology that offers great potential as a diagnostic and management tool. In 2004, an OMERACT Ultrasound Special Interest Group was formed to address the metric qualities of US as a potential outcome measure. A preliminary systematic review highlighted the deficiencies in the literature, particularly with regard to the reliability of interpreting and acquiring images; as a consequence, a number of exercises were proposed to address these issues. This report describes a series of iterative studies that have resulted in improved intra- and inter-reader reliability for detecting and scoring synovitis from both static and real-time images of the hand joints of patients with rheumatoid arthritis. The reliability of acquiring images was also enhanced using standardized positions. Future studies will assess the value of US in clinical trials.