Acute hepatitis E in an immunocompromised patient with seropositive rheumatoid arthritis on rituximab and long-term methotrexate.

We report the case of a 61-year old female with a 20-year history of seropositive rheumatoid arthritis (RA) who developed acute hepatitis. Her arthritis had been treated with methotrexate (MTX) since 2003 and, following an increase in disease activity, Rituximab (RTX) was commenced in January 2017. In May 2020, routine blood tests showed a new elevation in her liver profile, although synthetic function was preserved. A standard liver screen found no cause for her acutely abnormal lab values. Upon additional serological testing, the patient was confirmed to have acute hepatitis E virus (HEV). Her primary complaint at the time was fatigue. Within a month, her liver blood tests spontaneously improved and her symptoms resolved with conservative management.

Benefits of exercise in patients with rheumatoid arthritis: a randomized controlled trial of a patient-specific exercise programme.

BACKGROUND: Patients with rheumatoid arthritis (RA) tend to be more overweight, take less physical exercise, exhibit decreased cardiorespiratory fitness and demonstrate reduced muscle strength compared with age- and sex-matched controls. Impaired cognitive function in RA is an important associated factor, although it has been less well-recognized. The aim of this study was to investigate the effects of a specifically designed exercise programme on body composition, aerobic capacity, muscle strength and cognition in RA. METHODS: Sixty-six patients with RA were randomized to a specifically designed, personalized exercise programme or standard care. Assessments included body composition, fitness, grip strength and cognitive testing, in addition to disease related measures. RESULTS: Significant improvements in C-reactive protein (p = 0.025), fatigue scores (p = 0.047) and truncal fat (p = 0.004) were observed in the exercise group compared with controls. Median waist circumference was significantly reduced (94.0 to 91.4 cm, p < 0.0001). Improvements were also seen in aerobic capacity (23.2 to 27.6 ml/kg/min, p = 0.002) and in median right (12.0 to 13.0 kg, p = 0.025) and left grip strength (8.0 to 10 kg, p = 0.005). Cognitive function improved in the exercise group, with median Montreal Cognitive Assessment score 25.5 at 0 months compared to 28.0 at 3 months (p = 0.001). CONCLUSION: This study demonstrates that exercise has a significant and positive impact on cognitive function in RA. Furthermore, physical activity is safe and effective in chronic inflammatory joint disease and is recommended as a vital component in the holistic management of these patients.Key Points• A dedicated physical exercise programme is feasible and safe in patients with rheumatoid arthritis (RA).• Physical exercise helps reduce fatigue scores and improves cardiovascular fitness in stable RA patients.• Physical exercise has a positive impact on cognition in patients with RA.• A structured exercise programme should be an integral part of chronic disease management protocols for patients with RA.

High prevalence of abnormalities on chest radiography in rheumatoid arthritis.

INTRODUCTION: Chest radiography (CXR) is commonly performed in rheumatoid arthritis (RA), particularly for the diagnosis of pulmonary disease. However, other structures are visible on CXR, abnormalities of which may contribute to morbidity and early mortality. This study was undertaken to evaluate the extent of CXR abnormalities in RA patients. METHODS: Consecutive out-patients meeting the 2010 ACR/EULAR classification criteria for RA were included. The most recent CXR was assessed by two independent reviewers. Abnormalities identified were recorded and compared to the formal CXR report. Predictors of abnormalities on CXR were assessed using chi-squared tests. SPSS 18.0 was used for statistical analysis. RESULTS: One hundred and ninety-eight patients were included. Mean age was 62 years (range 18-90). One hundred and nine (55.1%) were current or ex-smokers. One hundred and fifty-six (79%) patients were seropositive and 123 (62.1%) had joint erosions. A recent CXR was available in 163 (82%) cases. Abnormalities were identified in 129 (79.1%). Ninety-seven (60%) had bony abnormalities. Seventy-one (43.6%) had pulmonary abnormalities; old tuberculosis in 34 (20.9%), hyperinflation in 24 (14.7%), interstitial changes in 20 (13.3%), nodules in 4 (2.4%), consolidation in 2 (1.2%), and pneumothorax in 1 (0.6%). Cardiomegaly was identified in 37 (22.7%) and aortic calcification in 24 (14.7%). Age (p = 0.001), male gender (p = 0.01), and seropositivity (p = 0.04) were significantly associated with lung abnormalities. Cardiomegaly was associated with hypertension (p = 0.012) and ischaemic heart disease (p = 0.018). CONCLUSION: Abnormalities were identified in 79% of chest radiographs in RA patients. Sixty-six percent of these were not reported. Clinicians need to be aware of the need to check for abnormalities.Key Points• RA patients have a high prevalence of CXR abnormalities.• Many of these are of clinical significance.• Age, being male, and seropositivity were associated with lung abnormalities.

An Association between MicroRNA-21 Expression and Vitamin D Deficiency in Coronary Artery Disease.

BACKGROUND: Atherosclerosis-related cardiovascular disease and osteoporosis (OP) occur concurrently and may share a common pathogenesis. Aberrant expression of miR-21 and vitamin D deficiency have been independently linked to the pathogenesis of atherosclerosis and OP. OBJECTIVES: To examine the relationship between miR-21 expression and vitamin D in aorta and bone in atherosclerotic disease. METHODS: Aorta, internal mammary artery (IMA) and sternal bone samples were collected from patients undergoing coronary artery bypass graft (CABG) surgery. Bone density was measured by dual x-ray absorbtiometry (DXA). MiR-21 was quantified using a two-step reverse transcription-polymerase chain reaction. RESULTS: Ten patients were included for analysis; 5 were vitamin D deficient (<25nmol/L). MiR-21 was expressed at a greater level in aorta compared with the IMA (p = 0.003), and sternal bone (p = 0.002). Expression of miR-21 between the IMA and bone was similar (p = 0.7). A positive correlation between the magnitude of difference (fold-difference) of miR-21 expression between aorta and IMA and CRP (correlation coefficient 0.9, p = 0.009) was found. Vitamin D deficient patients had greater expression of miR-21 in aorta compared with non-deficient patients (p = 0.03). Increasing CRP and vitamin D deficiency were independent predictors of miR-21 expression in aorta. The lower the difference in miR-21 expression between aorta and bone, the lower the bone density. CONCLUSION: In atherosclerosis, miR-21 is increased in the aorta and associated with vitamin D deficiency. Vitamin D deficiency may influence aberrant miR-21 expression in vasculature and bone contributing to the concurrent development of atherosclerosis and osteoporosis.

The effect of exercise on sleep and fatigue in rheumatoid arthritis: a randomized controlled study.

OBJECTIVE: Sleep disturbance and chronic fatigue are common in rheumatoid arthritis (RA) and contribute to disability, symptomatology, and healthcare use. It has long been recognized in other populations that exercise can improve sleep and diminish fatigue. The effect of exercise on sleep quality and fatigue in RA has not been evaluated. METHODS: Ours is a randomized controlled study in RA to determine the effect of an exercise program on sleep quality and fatigue. These were measured using the Pittsburgh Sleep Quality Index and the Fatigue Severity Scale. Patients were randomized to either a 12-week, home-based exercise intervention or usual care. The exercise program consisted of specific exercises to target individual deficiencies identified using the Health Assessment Questionnaire (HAQ) with cardiovascular work as per the guidelines. The intervention group was evaluated on a 3-week basis. Full evaluation was carried out at baseline and at 12 weeks. RESULTS: Forty patients were randomized to the intervention with 38 controls. In the exercise intervention group, there was a statistically significant improvement in HAQ (p = 0.00), pain (p = 0.05), stiffness (p = 0.05), sleep quality (p = 0.04), and fatigue (p = 0.04). In our control group, there was a statistically significant improvement demonstrated in their overall perceptions of the benefits of exercise, but none of the other variables. CONCLUSION: Our study demonstrates that an exercise program resulted in significant improvement in sleep quality and fatigue. This is particularly interesting given the importance of fatigue as an outcome measure in RA and gives us yet another reason to prescribe exercise in this population.

The association of cytokines with disease activity and damage scores in systemic lupus erythematosus patients.

OBJECTIVE: The aim of this study was to explore the role of cytokines in the pathogenesis of SLE in a genetically homogeneous Caucasian SLE patient population. METHODS: Serum levels of the following cytokines were determined by ELISA in SLE patients (diagnosed as per ACR diagnostic criteria): IL-1ß, IL-10, IL-12p70 and TNF-α. Demographic data, disease activity as per the SLEDAI and damage scores (SLICC) at the 5-year follow-up were calculated. RESULTS: Enhanced production of TNF-α, IL-1 and IL-10 were observed in SLE patients compared with controls. A strong positive correlation was seen between levels of IL-12p70 and IL-10. In addition, IL-10, TNF-α and IL-1 demonstrated a significant relationship with disease activity. Interestingly, elevated levels of IL-10 were observed in SLE patients with CNS involvement while patients with elevated levels of TNF-α were more likely to have renal involvement and sustain damage over the follow-up period. Additionally, the ratio of all cytokines assayed to IL-12p70 levels were significantly higher in SLE patients when compared with controls, with an association seen between damage accrual and the IL-1ß/IL-12p70 ratio (r = 0.431, P = 0.003), IL-10/IL-12p70 ratio (r = 0.351, P = 0.018) and TNF-α/IL-12p70 ratio (r = 0.33, P = 0.028). When the respective ratios were analysed for organ-specific disease, significant differences were observed for the IL-1ß/IL-12p70 ratio (0.79 vs 0.47, P = 0.036), IL-10/IL-12p70 ratio (4.29 vs 1.87, P = 0.018) and TNF-α/IL-12p70 ratio (7.49 vs 5.21, P = 0.018) with respect to renal involvement. CONCLUSION: Increased levels of a number of immunomodulatory cytokines relative to IL-12p70 in this Caucasian SLE patient population are seen in patients with renal involvement and are associated with increased accrual of damage at the 5-year follow-up.

The impact of hepatitis screening on diagnosis and treatment in rheumatoid arthritis.

Identification of patients with exposure to viral hepatitis is an important part of the care of patients with inflammatory arthritis. This study was conducted to assess the extent of hepatitis B and C screening, and the prevalence of viral hepatitis in a cohort of patients with established rheumatoid arthritis (RA). The medical records of 100 consecutive RA patients were retrospectively analysed for screening of hepatitis B surface antigen, surface antibody and core antibody and hepatitis C antibody. A teaching session was then conducted with the rheumatology team, emphasising the rationale for viral hepatitis testing. We then prospectively analysed 100 more RA patients to see if hepatitis screening improved. In the initial 100 patients (21 % male, mean age 65 years), 85 % were taking methotrexate and 22 % biologic treatments. A complete hepatitis screen was present in 8 %, while 12 % had hepatitis B core antibody checked and 53 % had been tested for hepatitis C.The second cohort of patients was similar to the first in terms of demographics and treatment. A complete hepatitis screen was available in 63 %, while 65 % had hepatitis B core antibody checked and 81 % had been tested for hepatitis C.In total, we identified 4 new cases of positive hepatitis B core antibody, 11 cases of positive hepatitis B surface antibody and 1 case of positive hepatitis C antibody. Even in populations where hepatitis B or C is non-endemic, screening will reveal new cases. Educational initiatives are helpful in teaching staff to screen patients.

Estrogen receptor α regulates tripartite motif-containing protein 21 expression, contributing to dysregulated cytokine production in systemic lupus erythematosus.

OBJECTIVE: To examine the role of 17ß-estradiol in the regulation of the autoantigen tripartite motif-containing protein 21 (TRIM-21) in patients with systemic lupus erythematosus (SLE). METHODS: Monocytes isolated from healthy control subjects and patients with SLE were stimulated with 17ß-estradiol and/or the estrogen receptor α (ERα) antagonist methyl-piperidino-pyrazole dihydrochloride. TRIM-21, ERα, and CREMα expression was determined by real-time polymerase chain reaction (PCR) analysis. MatInspector software was used to identify putative binding sites within the TRIM-21 promoter. ERα binding to the TRIM-21 gene promoter region in monocytes was analyzed by chromatin immunoprecipitation (ChIP) assay. TRIM-21 and interferon regulatory factor 3 protein levels were analyzed by Western blotting. RESULTS: Real-time PCR analysis demonstrated a role of estrogen in the regulation of TRIM-21 expression in monocytes, which correlated positively with ERα gene expression in patients with SLE. Investigations into the human TRIM-21 promoter revealed the presence of an estrogen response element, with ChIP assays confirming ERα binding to this site. Studies into estrogen-induced TRIM-21 expression revealed a hyperresponsiveness of SLE patients to 17ß-estradiol, which led to the enhanced levels of TRIM-21 observed in these individuals. CONCLUSION: Our results demonstrate a role of estrogen in the regulation of TRIM-21 expression through an ERα-dependent mechanism, a pathway that we observed to be overactive in SLE patients. Treatment of monocytes with an ERα antagonist abrogated estrogen-induced TRIM-21 expression and, as a consequence, decreased the expression of interleukin-23. These findings identify TRIM-21 as a novel ERα-regulated gene and provide novel insights into the link between estrogen and the molecular pathogenesis of SLE.

Safety of joint and soft tissue injections in patients on warfarin anticoagulation.

Performance of joint and soft tissue injections in patients receiving anticoagulation is subject to different protocols, some of which suggest continuing treatment within the therapeutic range, while others recommend stopping the treatment prior to procedures. The aim of this study was to evaluate the safety of two approaches to the management of patients prescribed warfarin requiring joint or soft tissue injection. A systematic literature review on this subject was undertaken. Our departmental protocol was changed from one where anticoagulation treatment was temporarily stopped prior to joint/soft tissue injection to one where treatment was continued in the context of a therapeutic international normalised ratio (INR) level within 24 h of the procedure. In patients in whom warfarin was withheld, 32 procedures were performed in 18 patients (13 rheumatoid arthritis, 11 osteoarthritis, 5 spondyloarthritis and 1 each of adhesive capsulitis, rotator cuff tendinopathy and trochanteric bursitis). Of these, 30 were joint injections and 2 were soft tissue injections. In patients who continued warfarin, 32 procedures were performed in 21 patients (11 rheumatoid arthritis, 7 osteoarthritis, 6 crystal arthritis, 4 rotator cuff tendinopathy, 2 spondyloarthritis and 1 each of adhesive capsulitis and carpal tunnel syndrome). Of these, 27 were joint injections and 5 were soft tissue injections. There were no clinical hemarthroses or complications in either group. Joint and soft tissue injections appear to be safe in patients receiving warfarin anticoagulation with an INR <3. Continuation of anticoagulants reduces staff workload and patient inconvenience with no evidence of increased risk of complications.

Elevated B lymphocyte stimulator levels are associated with increased damage in an Irish systemic lupus erythematosus cohort.

OBJECTIVE: The overall aim of this study is to identify clinical and serological features that are associated with B lymphocyte stimulator (BLyS) elevation in a homogeneous Caucasian SLE population and thereby identify patients who are most likely to benefit from BLyS blockade. METHODS: Patients with SLE (as per ACR criteria) were recruited. Clinical history, disease activity measures and laboratory measures of disease were recorded. BLyS levels were determined by ELISA. RESULTS: BLyS elevation was defined as being higher than the 95th percentile of BLyS levels measured in controls. Patients were divided into two groups: those with elevated BLyS levels (group 1, n = 23) and those with normal BLyS levels (group 2, n = 22). Elevated BLyS levels were significantly associated with patients of younger age and shorter disease duration. In keeping with previous reports, patients with elevated BLyS levels had more active disease (SLEDAI 5.1 vs 0.86, P < 0.001); however, our analysis also demonstrates that BLyS elevation was significantly associated with increased organ damage at 5-year follow-up [Systemic Lupus International Collaborating Clinics/ACR Damage Index (SLICC/ACR DI) 0.53 vs 0.13, P = 0.012]. Furthermore, the presence of Sm autoantibody significantly predicted elevated BLyS levels in a Caucasian population. BLyS levels were significantly higher in those with musculoskeletal involvement, malar rash, renal disease and evidence of immunological activity. CONCLUSION: BLyS blockade may be most beneficial if introduced early in the course of disease in young Caucasian patients presenting with renal, musculoskeletal and skin disease in an effort to reduce long-term damage.

Increased body mass index in ankylosing spondylitis is associated with greater burden of symptoms and poor perceptions of the benefits of exercise.

OBJECTIVE: Increased body mass index (BMI) in patients with ankylosing spondylitis (AS) is associated with a greater burden of symptoms and poor perceptions of the benefits of exercise. In AS, the effect of obesity on disease characteristics and exercise perceptions is unknown. We evaluated the prevalence of obesity in AS, to assess the attitudes of patients toward exercise and to evaluate the effect of obesity on symptoms and disease activity. METHODS: Demographic data and disease characteristics were collected from 46 patients with AS. Disease activity, symptomatology, and functional disability were examined using standard AS questionnaires. BMI was calculated. Comorbidity was analyzed using the Charlson Comorbidity Index. Patients' attitudes toward exercise were assessed using the Exercise Benefits and Barriers Scale (EBBS). We compared the disease characteristics, perceptions regarding exercise, and functional limitations in those who were overweight to those who had a normal BMI. RESULTS: The mean BMI in the group was 27.4; 67.5% of subjects were overweight or obese. There was a statistically significant difference between those who were overweight and those with a normal BMI regarding their perceptions of exercise (EBBS 124.7 vs 136.6, respectively), functional limitation (Bath AS Functional Index 4.7 vs 2.5, Health Assessment Questionnaire 0.88 vs 0.26), and disease activity (Bath AS Disease Activity Index 4.8 vs 2.9). There was no difference between the groups in terms of their comorbid conditions or other demographic variables. CONCLUSION: The majority of patients in this AS cohort were overweight. They had a greater burden of symptoms, worse perceptions regarding the benefits of exercise, and enhanced awareness of their barriers to exercising. This is of particular concern in a disease where exercise plays a crucial role.

Attitudes towards exercise in patients with chronic disease: the influence of comorbid factors on motivation and ability to exercise.

BACKGROUND: Exercise is an integral part of a healthy lifestyle. It has a well defined role in maintaining health in chronic illness. This study was undertaken to determine attitudes towards exercise in patients admitted to hospital with medical illnesses. METHODS: A questionnaire on attitudes to and extent of exercise was devised and administered to patients admitted to an acute medical unit of a large university teaching hospital in 2008. Data were analysed using SPSS. RESULTS: 107 patients participated, mean age 57 years (range 20-92): 79% had at least one chronic disease, 60% were overweight, 42% did little or no exercise, while 81% did not achieve moderate physical activity. Factors associated with reduced activity included increasing age, alcohol excess, lower education level, and unemployment. Approximately 50% of the patients blamed health problems while the other half cited lack of time or motivation as reasons for not exercising. Only 3% were aware of national or international exercise recommendations. CONCLUSIONS: Much greater awareness of the importance of exercise and its impact on health and longevity is needed. Healthcare providers have an important role in exercise education in patients with acute and chronic disease.

Giant iliopsoas bursitis: a complication of chronic arthritis.

Iliopsoas bursitis is a poorly recognized cause of hip pain that requires early recognition to avoid potentially serious complications caused by compression of adjacent structures. It can occur in the setting of trauma in athletes or those who engage in heavy labor and is also associated with acute or chronic arthritis. We describe the cases of 2 patients, one of whom developed a femoral neuropathy, while the other had marked venous compression of the lower limb resulting from enlargement of the iliopsoas bursa. Magnetic resonance imaging offers the most accurate information on the extent of the problem. Recalcitrant cases may require bursectomy in addition to treatment of the underlying cause.

Treatment of relapsing polychondritis in the era of biological agents.

Relapsing polychondritis (RP) is a rare disorder, often requiring high doses of immunosuppressive therapy to control its potentially life-threatening consequences. The advent of biological agents has added to the armamentarium available to treat RP, but the lack of controlled trials, along with the small numbers of patients and disease heterogeneity means that new therapies are prescribed without the benefits of rigorous clinical research. Thus, information on individual cases is of value in expanding our knowledge of the use of biologic agents in rare conditions. We report on the use of rituximab in a patient who subsequently developed catastrophic aortic incompetence, and we review the literature in relation to the use of this drug in RP.