When rheumatology and infectious disease come together
22-08-2019 – George E Fragoulis,Nikolaos V Sipsas
Therapeutic approaches to osteosarcopenia: insights for the clinician
07-08-2019 – Mizhgan Fatima,Sharon L. Brennan-Olsen,Gustavo Duque
Journal Article, Review
Osteopenia/osteoporosis and sarcopenia are both age-related conditions. Given the well-defined bone and muscle interaction, when osteopenia and sarcopenia occur simultaneously, this geriatric syndrome is defined as ‘osteosarcopenia’. Evidence exists about therapeutic interventions common to both bone and muscle, which could thereby be effective in treating osteosarcopenia. In addition, there are roles for common nonpharmacological strategies such as nutritional intervention and physical exercise prescription in the management of this condition. In this review we summarize the evidence on current and upcoming therapeutic approaches to osteosarcopenia.
Update on the management of hypophosphatasia
01-08-2019 – V. Choida,J. S. Bubbear
Journal Article, Review
Hypophosphatasia is a rare inherited disease caused by a loss of function mutations in the gene that codes for the tissue-nonspecific alkaline phosphatase enzyme. It is autosomally inherited and at least 388 different genetic defects have been identified. The clinical presentation is variable from a severe perinatal form, that is fatal if untreated, to adult-onset disease. This review covers the pathophysiology, diagnosis and current management option including the recently licensed enzyme replacement therapy asfotase alfa.
The role of microbiome in rheumatoid arthritis treatment
30-07-2019 – Rahul Bodkhe,Baskar Balakrishnan,Veena Taneja
Journal Article, Review
Rheumatoid arthritis (RA) is an autoimmune disorder with multifactorial etiology; both genetic and environmental factors are known to be involved in pathogenesis. Treatment with disease-modifying antirheumatic drugs (DMARDs) plays an essential role in controlling disease progression and symptoms. DMARDs have immunomodulatory properties and suppress immune response by interfering in various pro-inflammatory pathways. Recent evidence has shown that the gut microbiota directly and indirectly modulates the host immune system. RA has been associated with dysbiosis of the gut microbiota. Patients with RA treated with DMARDs show partial restoration of eubiotic gut microbiome. Hence, it is essential to understand the impact of DMARDs on the microbial composition and its consequent influences on the host immune system to identify novel therapies for RA. In this review, we discuss the importance of antirheumatic-drug-induced host microbiota modulations and possible probiotics that can generate eubiosis.
Update on novel pharmacological therapies for osteoarthritis
23-07-2019 – Asim Ghouri,Philip G. Conaghan
Journal Article, Review
Osteoarthritis (OA) is a chronic painful arthritis with increasing global prevalence. Current management involves non-pharmacological interventions and commonly used pharmacological treatments that generally have limited analgesic efficacy and multiple side effects. New treatments are therefore required to relieve patient symptoms and disease impact. A number of existing pharmacological therapies have been recently trialled in OA. These include extended-release triamcinolone and conventional disease-modifying anti-rheumatic drugs (DMARDs) used in the management of rheumatoid arthritis; generally, DMARDs have not shown a benefit in treating OA. Novel analgesic therapies are in development, including those targeting peripheral pain pathways. Disease-modifying osteoarthritis drugs (DMOADs) target key tissues in the OA pathophysiology process and aim to prevent structural progression; a number of putative DMOADs are in phase II development. There is preliminary evidence of structural improvement with some of these therapies but without concomitant symptom improvement, raising new considerations for future DMOAD trials.
Thrombocytosis as a prognostic factor in polymyalgia rheumatica: characteristics determined from cluster analysis
19-07-2019 – Keigo Hayashi,Keiji Ohashi,Haruki Watanabe,Ken-Ei Sada,Kenta Shidahara,Yosuke Asano,Sumie Hiramatsu Asano,Yuriko Yamamura,Yoshia Miyawaki,Michiko Morishita,Yoshinori Matsumoto,Tomoko Kawabata,Jun Wada
This study aimed to identify the clinical subgroups of polymyalgia rheumatica (PMR) using cluster analysis and compare the outcomes among the identified subgroups. We enrolled patients with PMR who were diagnosed at Okayama University Hospital, Japan between 2006 and 2017, met the 2012 European League Against Rheumatism/American College of Rheumatology provisional classification criteria for PMR, and were treated with glucocorticoids. Hierarchical cluster analysis using variables selected by principal component analysis was performed to identify the clusters. Subsequently, the outcomes among the identified clusters were compared in the study. The primary outcome was treatment response at 1 month after commencement of treatment. The secondary outcome was refractory clinical course, which was defined as the requirement of additional treatments or relapse during a 2-year observational period. A total of 61 consecutive patients with PMR were enrolled in the study. Their mean age was 71 years, and 67% were female. Hierarchical cluster analysis revealed three distinct subgroups: cluster 1 ( Thrombocytosis could predict the clinical course in patients with PMR.
Helpful, albeit hazardous! Esophageal stem-cell injection in systemic sclerosis
17-07-2019 – Franziska Durchschein,Florentine Moazedi-Fuerst,Sonja Kielhauser,Angelika Lackner,Maria Wiedner,Horst Koch,Ivo Justich,Andreas Eherer
Over 90% of patients with systemic sclerosis suffer from gastroesophageal reflux. Esophageal motility disturbances are associated with a reduced life quality and may force interstitial lung disease progression. We wanted to determine whether we can improve gastroesophageal reflux in these patients by esophageal stem-cell injection. We performed a pilot study including eights patients with systemic sclerosis and symptomatic gastroesophageal reflux. Sampling of adipose tissue was performed by an experienced plastic surgeon under local anesthesia. The collected fat was injected into the submucosa of the distal esophagus, each time 1 ml in all four quadrants starting 2, 4 and 6 cm proximal to the Z line (ending up to a total volume of 12 ml). Before the intervention, 3, 6 and finally 12 months after the procedure, patients answered the Gastroesophageal Reflux Disease Health-Related Quality of Life Questionnaire (GERD HRQL) and a high-resolution manometry was performed to quantify changes in motility function. All patients showed an improvement in the GERD HRQL score after the stem-cell injection and a lower dosage of proton-pump inhibitors. The manometric findings showed no change throughout the time. A serious adverse event occurred, as one patient developed multiple cerebellar embolic infarcts. Because of the favorable effect in all patients, a safe route for esophageal fat injection needs to be developed.
Does periodontitis represent a risk factor for rheumatoid arthritis? A systematic review and meta-analysis
10-07-2019 – Railson de Oliveira Ferreira,Raíra de Brito Silva,Marcela Baraúna Magno,Anna Paula Costa Ponte Sousa Carvalho Almeida,Nathália Carolina Fernandes Fagundes,Lucianne Cople Maia,Rafael Rodrigues Lima
Journal Article, Review
Periodontitis is an inflammatory disease of dental supporting tissues (gingiva, periodontal ligament, and bone) and it has been suggested as a possible etiology for rheumatoid arthritis (RA). In this systematic review, we aim to verify if periodontitis represents a risk factor for RA. Electronic databases were consulted until March 2018 considering eligibility criteria focusing on: (P, participants) adults; (E, exposure) with periodontitis; (C, comparison) without periodontitis; and (O, outcome) development of RA. Quality assessment of studies and risk-of-bias evaluation were also performed. To undertake a quantitative analysis, the number of persons with RA and a total number of participants for the case group (with periodontitis) and control group (without periodontitis) were used to calculate the odds ratio (OR) with a 95% confidence interval (CI). A total of 3888 articles were identified, and nine studies were considered eligible. Seven of 9 articles suggested an association among diseases by the common pro-inflammatory profiles. The pooled analysis of 3 articles showed a higher RA prevalence for persons with periodontitis (
Functional risk for fracture by safe functional motion testing: a short version of the safe functional motion test
24-06-2019 – Christopher P. Recknor,Daniel Van Dussen,Norma MacIntyre,Julie Recknor
‘Unsafe’ movement strategies used to perform everyday activities were quantified using scores for tasks included in the Short Form Safe Functional Motion test series (SSFM). Baseline scores were independently associated with incident fractures after adjusting for factors known to effect fracture risk. The purpose of the present study is to determine whether the SSFM, a series of tests of habitual motion, is associated with incident fragility fracture at any skeletal sites.
An osteoporosis clinic database was queried for adults with baseline SSFM scores and corresponding data for prevalent fractures, femoral neck bone mineral density (fn
BMD), osteoporosis medication use, and incident fractures at 1-year and 3-year follow ups [ An Sfm-3 score was a significant independent predictor of any fracture at 1 year [adjusted odds ratio (95% CI) = 1.118 (1.025, 1.219) for each 10-point decrease in Sfm-3; Scores on the SSFM predict fracture risk such that for each 10-point drop in score the odds of fracture are increased by up to 18% independent of risk associated with age, bone mineral density, use of bone-sparing medications, and history of a fracture.
Real-world data on secukinumab use for psoriatic arthritis and ankylosing spondylitis
19-06-2019 – Ashley Elliott,Gary Wright
Is there a role for cherries in the management of gout?
17-05-2019 – Marcum W. Collins,Kenneth G. Saag,Jasvinder A. Singh
Journal Article, Review
Despite the availability of effective urate-lowering therapy (ULT) and anti-inflammatory drugs for the treatment of gout, there is considerable interest in novel treatment approaches. Patients with gout often have a multitude of comorbidities, leading to concern over drug-drug interactions and medication adverse events. The cherry is a small nutrient-rich fruit that has garnered a great deal of attention in recent years as a nonpharmacologic option for the treatment of a multitude of disease manifestations. Perhaps a quarter of patients with gout try cherries or cherry products to treat their gout, which have antioxidant and anti-inflammatory (IL-6, TNF-α, IL-1β, IL-8, COX-I and -II) properties, hypouricemic effects, and the ability to downregulate NFk
B-mediated osteoclastogenesis. Based on these properties, cherries may reduce both the acute and chronic inflammation associated with recurrent gout flares and its chronic destructive arthropathy. In this review, we explore the potential benefits of cherries and cherry products as a nonpharmacologic option for the treatment of gout.
Corticosteroid injections for knee osteoarthritis are supported by the literature: in the affirmative
27-04-2019 – Nicolas S. Piuzzi,Michael A. Mont
Recent developments in advanced imaging in gout
16-04-2019 – Joseph Davies,Philipp Riede,Kirsten van Langevelde,James Teh
Journal Article, Review
The plain radiographic features of gout are well known; however, the sensitivity of plain radiographs alone for the detection of signs of gout is poor in acute disease. Radiographic abnormalities do not manifest until late in the disease process, after significant joint and soft tissue damage has already occurred. The advent of dual-energy computed tomography (DECT) has enabled the non-invasive diagnosis and quantification of gout by accurately confirming the presence and extent of urate crystals in joints and soft tissues, without the need for painful and often unreliable soft tissue biopsy or joint aspiration. Specific ultrasound findings have been identified and may also be used to aid diagnosis. Both ultrasound and magnetic resonance imaging (MRI) may be used for the measurement of disease extent, monitoring of disease activity or treatment response, although MRI findings are nonspecific. In this article we summarize the imaging findings and diagnostic utility of plain radiographs, ultrasound, DECT, MRI and nuclear medicine studies in the assessment as well as the implications and utility these tools have for measuring disease burden and therapeutic response.
New-onset cutaneous sarcoidosis under tocilizumab treatment for giant cell arteritis: a quasi-paradoxical adverse drug reaction. Case report and literature review
12-04-2019 – Rosaria Del Giorno,Alfonso Iodice,Cristina Mangas,Luca Gabutti
New-onset sarcoidosis has been previously described in three case reports in patients affected by rheumatoid arthritis treated with tocilizumab (TCZ). The existence of a cause-effect mechanism between the biological treatment and the onset of the illness is still being debated. A 74-year-old woman was diagnosed with giant cell arteritis (GCA). The first-line treatment with glucocorticoids; and the second-line with methotrexate and low-dose glucocorticoids were stopped due to multiple pathological vertebral fractures and insufficient biological and clinical response. The cytotoxic agent, cyclophosphamide, was then introduced and in turn stopped, because of gastrointestinal side effects. Thereafter a treatment with TCZ was begun. The patient experienced good clinical response; however, 8 months later she developed painful hyper-pigmented reddish cutaneous micronodular lesions localized to the abdomen and thorax. A cutaneous biopsy was performed, and histological analysis showed noncaseating epithelioid granulomas in the hypodermis. The diagnosis of cutaneous sarcoidosis was made. Topical corticosteroids were administered and, as requested by the patient, TCZ was discontinued with slow but complete resolution of the skin lesions. After TCZ discontinuation however, the GCA flared and the patient’s symptoms and biological abnormalities reappeared. Thus, after a 6-month suspension, TCZ was re-administered. At 2 months later the skin lesions compatible with cutaneous sarcoidosis reappeared. Topical corticosteroids were once again prescribed and as suggested by the patient the TCZ posology was reduced. The patient’s symptoms disappeared, and the cutaneous lesions resolved. The time elapsed from TCZ treatment start and the onset of cutaneous sarcoidosis, as well as its recurrence after TCZ suspension and rechallenge supported the diagnosis of a drug-induced reaction. To the best of our knowledge, this case report represents the first instance of cutaneous sarcoidosis most likely induced by TCZ in patients affected by GCA. In addition, our case emphasizes that although TCZ in monotherapy confirms to be an effective treatment for GCA, further immunological disorders could be unmasked, and the discussed side effect of the drug could be dose-dependent.
Effectiveness and safety of certolizumab pegol in rheumatoid arthritis patients in Canadian practice: 2-year results from the observational FαsT-CAN study
05-03-2019 – Louis Bessette,Boulos Haraoui,Andrew Chow,Isabelle Fortin,Sanjay Dixit,Majed Khraishi,Derek Haaland,Sami Elmoufti,Fabienne Staelens,Irina Bogatyreva,Jerry Syrotuik,Saeed Shaikh
The aim of this study was to assess the real-world effectiveness and safety of certolizumab pegol (CZP) in rheumatoid arthritis (RA) patients, and the impact on patients’ productivity, pain, and fatigue, in Canadian practice.
T-CAN, a 2-year prospective, observational study, evaluated CZP use in Canadian adults with moderate to severe, active RA. The primary objective was to assess the proportion of patients achieving 28-joint Disease Activity Scores (DAS28) <2.6 at Week 104. Secondary and additional endpoints assessed the improvements in Patients' Assessment of Arthritis Pain (Pt
AAP), fatigue, Health Assessment Questionnaire-Disability Index (HAQ-DI), and the proportion of patients achieving minimal clinically important differences (MCID) in HAQ-DI. Validated arthritis-specific Work Productivity Surveys (WPS-RA) assessed the RA-associated impact on productivity. Incidence of CZP-related treatment-emergent adverse events (TEAEs) was reported for patients receiving ⩾1 dose of CZP (safety set). The full analysis set (baseline DAS28 ⩾ 2.6, ⩾1 dose of CZP and ⩾1 valid post-baseline DAS28 measurement) included 451 of the 546 patients recruited into the study; a total of 229/451 (50.8%) patients completed Week 104. At Week 104, 90/451 (20.0%) patients achieved DAS28 < 2.6. Rapid improvements in disease activity, pain, and fatigue were observed. At Week 104, 66.2% of patients achieved HAQ-DI MCID. Patients employed at Week 104, reported reduced absenteeism, and improved productivity. CZP-related TEAEs were consistent with the known CZP safety profile. CZP was an effective RA treatment in Canadian practice, and no new CZP-related safety signals were identified. The improvements in household and workplace productivity are the first observations in a real-world Canadian setting.
Serum chitotriosidase and neopterin levels in patients with ankylosing spondylitis
02-03-2019 – Ferdi Yavuz,Bilge Kesikburun,Özlem Öztürk,Ümüt Güzelküçük
The aim of this study was to assess the serum chitotriosidase (Ch
T) and neopterin levels in patients with ankylosing spondylitis (AS) and to evaluate whether serum Ch
T and neopterin levels are related to disease activity. A total of 86 patients with AS were included in the study. Patients were divided into two groups based on Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores: The active AS patients group included 40 patients who had a BASDAI score ⩾4. The inactive AS patients group included 46 patients who had a BASDAI score <4. We compared the serum level of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Ch
T and neopterin between the two groups. Active AS patients had significantly higher ESR, CRP, serum Ch
T and neopterin levels compared with the inactive AS patients group ( The present study emphasized that serum Ch
T levels can be useful in the determination of the disease activity of AS patients.
IL-12/IL-23p40 identified as a downstream target of apremilast in ex vivo models of arthritis
23-02-2019 – Tue W. Kragstrup,Mary Adams,Søren Lomholt,Morten A. Nielsen,Line D. Heftdal,Peter Schafer,Bent Deleuran
Synovial fluid was obtained from patients with active rheumatoid arthritis (RA), Ps
A or peripheral spondyloarthritis (Sp
A; In SFMCs cultured for 48 h, apremilast decreased the production of interleukin (IL)-12/IL-23p40 (the shared subunit of IL-12 and IL-23), colony-stimulating factor 1, CD6, and CD40 and increased the production of C-X-C motif chemokine 5 dose-dependently. Apremilast had a very different response signature compared with the tumor necrosis factor alpha inhibitor adalimumab with a substantially greater inhibition of IL-12/IL-23p40. In SFMCs cultured for 21 days, apremilast increased the secretion of IL-10. In FLS cultures, apremilast decreased matrix metalloproteinase-3 production. Apremilast decreased osteoclastogenesis but did not affect mineralization by human osteoblasts. This study reveals the downstream effects of apremilast in
Health effects of direct triaging to physiotherapists in primary care for patients with musculoskeletal disorders: a pragmatic randomized controlled trial
16-02-2019 – Lena Bornhöft,Maria EH Larsson,Lena Nordeman,Robert Eggertsen,Jörgen Thorn
Physiotherapists and general practitioners (GPs) both act as primary assessors for patients with musculoskeletal disorders in primary care. Previous studies have shown that initial triaging to physiotherapists at primary healthcare centres has advantages regarding efficiency in the work environment and utilization of healthcare. In this study, we aimed primarily to determine whether triaging to physiotherapists affects the progression of health aspects over time differently than traditional management with initial GP assessment. The secondary aim was to determine whether triaging to physiotherapists affects patients’ attitudes of responsibility for musculoskeletal disorders. This was a pragmatic trial where both recruitment and treatment strategies were determined by clinical, not study-related parameters, and was initiated at three primary care centres in Sweden. Working-age patients of both sexes seeking primary care for musculoskeletal disorders and nurse assessed as suitable for triaging to physiotherapists were randomized to initial consultations with either physiotherapists or GPs. They received self-assessment questionnaires before the initial consultation and were followed up at 2, 12, 26 and 52 weeks with the same questionnaires. Outcome measures were current and mean (3 months) pain intensities, functional disability, risk for developing chronic musculoskeletal pain, health-related quality of life and attitudes of responsibility for musculoskeletal conditions. Trends over time were analysed with a regression model for repeated measurements. The physiotherapist-triaged group showed significant improvement for health-related quality of life at 26 weeks and showed consistent but nonsignificant tendencies to greater reductions of current pain, mean pain in the latest 3 months, functional disability and risk for developing chronic pain compared with traditional management. The triage model did not consistently affect patients’ attitudes of responsibility for musculoskeletal disorders. Triaging to physiotherapists for primary assessment in primary care leads to at least as positive health effects as primary assessment by GPs and can be recommended as an alternative management pathway for patients with musculoskeletal disorders. NCT148611.
Current advances in the treatment of giant cell arteritis: the role of biologics
13-02-2019 – Candice Low,Richard Conway
Journal Article, Review
Giant cell arteritis (GCA) is the most common form of systemic vasculitis. It is a potentially severe disease with 25% of patients suffering vision loss or stroke. Our treatment paradigm is based on glucocorticoids. Glucocorticoids are required in high doses for prolonged periods and subsequently are associated with a significant amount of treatment-related morbidity. Alternative treatment options are urgently needed to minimize these glucocorticoid adverse events. Many other agents, such as methotrexate and tumour necrosis factor alpha inhibitors have been used in GCA, with limited or no evidence of benefit. Our emerging understanding of the pathogenic processes involved in GCA has led to an increased interest in the use of biologic agents to treat the disease. Two randomized controlled trials have recently reported dramatic effects of the use of the interleukin-6 targeted biologic tocilizumab in GCA, with significant increases in remission rates and decreases in glucocorticoid burden. While encouraging, longer-term and additional outcomes are awaited to clarify the exact positioning of tocilizumab in the treatment approach. Emerging data for other biologic agents, particularly abatacept and ustekinumab, are also encouraging but less well advanced. We are at the dawn of a new era in GCA treatment, but uncertainties and opportunities abound.