Nanomedicine: an emerging era of theranostics and therapeutics for rheumatoid arthritis
AbstractRA is a multifactorial autoimmune inflammatory disease characterized by synovitis, bone destruction and joint dysfunction that leads to shortening of lifespan and increased mortality rates. Currently available treatments of RA, by controlling various symptoms, only delay disease progression and have their own side effects. Consequently, there is the need for a novel therapeutic strategy that offers a more sustainable and biocompatible solution. Nanomedicine is a modern branch of nanobiotechnology that provides targeted therapy to inflamed rheumatic joints and thus prevents unwanted off-target side effects. This rev...
Source: Rheumatology - August 3, 2019 Category: Rheumatology Source Type: research

Comment on: Short-term follow-up results of children with familial Mediterranean fever after cessation of colchicine: is it possible to quit?
Dear Editor, We read with great interest the recent article by Tanataret al. [1] ‘Short-term follow-up results of children with familial Mediterranean fever after cessation of colchicine: is it possible to quit’. The article underlines an important issue encountered in daily practice while handling FMF patients. It is not easy to decide to cease colchicine in FMF patients, c onsidering the possible unanticipated, insidious and hard-to-treat complications such as amyloidosis. We think some aspects need to be clarified and discussed. (Source: Rheumatology)
Source: Rheumatology - July 19, 2019 Category: Rheumatology Source Type: research

Comment on: Short-term follow-up results of children with familial Mediterranean fever after cessation of colchicine: is it possible to quit?: reply
Sir, We read the letter from Satis et al. [1] regarding our article ‘Short-term follow-up results of children with familial Mediterranean fever after cessation of colchicine: is it possible to quit?’ [2]. It was very nice to know that the article was noticed, due to the very important issue it concerns, i.e. quitting colchicine treatment. As the authors state, this issue is of great importance in clinical practice and it is hard to decide when to cease colchicine in FMF patients. (Source: Rheumatology)
Source: Rheumatology - July 19, 2019 Category: Rheumatology Source Type: research

Systemic lupus erythematosus – a disease of two halves?
This editorial refers to ‘Expanded circulating peripheral helper T cells in systemic lupus erythematosus: association with disease activity and B cell differentiation', Makiyamaet al., on pages 1861 –9. (Source: Rheumatology)
Source: Rheumatology - July 11, 2019 Category: Rheumatology Source Type: research

Comment on: Temporal relationships between systemic lupus erythematosus and comorbidities: reply
In this study, we used a looser definition proposed by Feinstein, specifically: ‘Any distinct additional entity that has existed or may occur during the clinical course of a patient who has the index disease under study’ [3]. The relationships between index disease and comorbidity are very complex [4] but can be broadly classified into three models: direct causation, associated risk factors and phenotypic variation [5]. Certainly, knowing the mechanism of the relationships may be useful. However, we intended not to delineate the relationship between the index disease (SLE) and comorbidities, as (i) the mechanis...
Source: Rheumatology - July 10, 2019 Category: Rheumatology Source Type: research

Comment on: Temporal relationships between systemic lupus erythematosus and comorbidities
Sir, We read with interest the paper entitled ‘Temporal relationships between systemic lupus erythematosus and comorbidities’ by Kuoet al. describing the increased risks of comorbidities in patients with SLE compared with age- and sex-matched subjects [1]. With the increase in life expectancy of SLE patients, the evaluation of comorbidities is an emerging issue. Even if overall health is what matters most, all physicians who take care of SLE patients should be aware of the fine line separating comorbidities from the effect of the disease itself. (Source: Rheumatology)
Source: Rheumatology - July 10, 2019 Category: Rheumatology Source Type: research

Biomarkers in systemic sclerosis-associated interstitial lung disease: review of the literature
AbstractSSc is a rare disease of unknown origin associated with multiple organ involvement. One of the major complications that drives the mortality of SSc patients is interstitial lung disease. The course of SSc-interstitial lung disease progression has a wide spectrum. Since the treatment is based on aggressive immunosuppression it should not be given to stable or non-progressing disease. The correct identification of disease with high risk of progression remains a challenge for early therapeutic intervention, and biomarkers remain urgently needed. In fact, eight categories of biomarkers have been identified and classifi...
Source: Rheumatology - July 10, 2019 Category: Rheumatology Source Type: research

Comment on: European consensus-based recommendations for diagnosis and treatment of immunoglobulin A vasculitis —the SHARE initiative
Sir, I read with great interest the article by Ozenet al. [1]. However, I disagree with the recommendation and make a note concerning the efficacy and use of ciclosporin A in the treatment of IgA vasculitis, formerly called Henoch –Schönlein nephritis. (Source: Rheumatology)
Source: Rheumatology - June 26, 2019 Category: Rheumatology Source Type: research

Treatment failure in inflammatory arthritis: time to think about syndemics?
This article discusses the concept of syndemics, which although well-described in some conditions, represents a novel concept in the context of rheumatic and musculoskeletal diseases. Written in the form of a viewpoint, the article focuses on a novel theoretical framework for studying inflammatory arthritis, based on a syndemic approach that takes into account the social context, biocultural disease interaction, and socio-economic characteristics of the setting. Syndemics involving inflammatory arthritis may be most likely in a social context involving limited access to health care, lack of physical activity and obesogenic...
Source: Rheumatology - June 24, 2019 Category: Rheumatology Source Type: research

Fc-gamma receptors and S100A8/A9 cause bone erosion during rheumatoid arthritis. Do they act as partners in crime?
AbstractBone erosion is one of the central hallmarks of RA and is caused by excessive differentiation and activation of osteoclasts. Presence of autoantibodies in seropositive arthritis is associated with radiographic disease progression. ICs, formed by autoantibodies and their antigens, activate Fc γ-receptor signalling in immune cells, and as such stimulate inflammation-mediated bone erosion. Interestingly, ICs can also directly activate osteoclasts by binding to FcγRs on their surface. Next to autoantibodies, high levels of alarmins, among which is S100A8/A9, are typical for RA and they ca n further activate...
Source: Rheumatology - June 10, 2019 Category: Rheumatology Source Type: research

Comment on: Assessments of the unmet need in the management of patients with rheumatoid arthritis: analyses from the NOR-DMARD registry: reply
Sir, We thank Drs Kaltsonoudis and Pelechas and Profs Voulgari and Drosos for their interest in our article [1]. In our study, we concluded that there exists a substantial unmet treatment and management need for patients with RA. The support for this conclusion was our analyses on data from the Norwegian DMARD (NOR-DMARD) registry. In their comment, Kaltsonoudiset al. [2] challenge our conclusion with a reference to their own research. In the study by Kaltsonoudiset al., patients were registered in the early stages of RA (disease duration
Source: Rheumatology - June 6, 2019 Category: Rheumatology Source Type: research

Comment on: Assessments of the unmet need in the management of patients with rheumatoid arthritis: analyses from the NOR-DMARD registry
In this study, the authors reported a high proportion of MTX-na ïve patients who received MTX monotherapy as having an inadequate response and a large proportion of patients who discontinued MTX therapy, primarily due to a lack of efficacy. In addition, they reported that a significant number of RA patients receiving biologic DMARDs (bDMARDs) as monotherapy or in combination with MTX discontinued therapy over 24 months of treatment. All the above showed that a large proportion of patients treated with MTX as monotherapy or with bDMARDs had a huge gap in RA management and the unmet needs for treatment is very high. The...
Source: Rheumatology - June 6, 2019 Category: Rheumatology Source Type: research

Comment on: European consensus-based recommendations for diagnosis and treatment of immunoglobulin A vasculitis – the SHARE initiative
Sir, We read with great interest the European consensus-based recommendations for diagnosis and treatment of immunoglobulin A vasculitis (IgAV) in children, published recently online inRheumatology [1]. These recommendations, accepted with a perfect 100% agreement, aim to provide optimal care for children with IgAV across different European countries, and represent a truly commendable step forward in paediatric rheumatology. Similar recommendations are unlikely to be developed any time soon for adults with IgAV. IgAV in adults has been long neglected due to its perceived rarity and assumed benignity. We strongly believe th...
Source: Rheumatology - June 6, 2019 Category: Rheumatology Source Type: research

From coagulation to inflammation: novel avenues for treating rheumatoid arthritis with activated protein C
This editorial refers to ‘Activated protein C targets immune cells and rheumatoid synovial fibroblasts to prevent inflammatory arthritis in mice', Xueet al., on pages 1850 –60. (Source: Rheumatology)
Source: Rheumatology - May 23, 2019 Category: Rheumatology Source Type: research

Sirt1 ameliorates monosodium urate crystal –induced inflammation by altering macrophage polarization via the PI3K/Akt/STAT6 pathway
ConclusionOur studies revealed that Sirt1 ameliorates MSU-induced inflammation by altering macrophage polarization via the PI3K/Akt/STAT6 pathway. (Source: Rheumatology)
Source: Rheumatology - May 18, 2019 Category: Rheumatology Source Type: research

Chronic myelomonocytic leukaemia associated with large- and medium-sized arteries vasculitis of the small bowel
Rheumatology key messageMyelodysplastic syndromes associated vasculitis can be lethal and require early treatment of the haematological neoplasm. (Source: Rheumatology)
Source: Rheumatology - May 16, 2019 Category: Rheumatology Source Type: research

Proximal patellar enthesitis treatment with ustekinumab in a patient with psoriatic arthritis: significant response documented by ultrasound and magnetic resonance imaging
Rheumatology key messageSuccessful treatment of enthesitis with ustekinumab was documented by clinical US and MRI findings. (Source: Rheumatology)
Source: Rheumatology - May 11, 2019 Category: Rheumatology Source Type: research

Efficacy of sarilumab in adult-onset Still ’s disease as a corticosteroid-sparing agent
Rheumatology key messageSarilumab is effective as a corticoid-sparing agent in corticodependent adult onset Still ’s disease. (Source: Rheumatology)
Source: Rheumatology - May 5, 2019 Category: Rheumatology Source Type: research

Checkpoint inhibitor-induced eosinophilic fasciitis following high eosinophilia associated with complete response
Rheumatology key messageEosinophilic fasciitis is a rare immune-related adverse event associated with complete responses in melanoma patients. (Source: Rheumatology)
Source: Rheumatology - May 5, 2019 Category: Rheumatology Source Type: research

Two populations of circulating PD-1hiCD4 T cells with distinct B cell helping capacity are elevated in early rheumatoid arthritis
ConclusionTwo populations of PD-1hiCD4 T cells with distinct phenotype and B cell helping capacity are increased in the peripheral blood of seropositive eRA patients. Whereas cTph cells are present only in patients with an active disease, cTfh cells seem to be constitutively elevated. (Source: Rheumatology)
Source: Rheumatology - May 5, 2019 Category: Rheumatology Source Type: research

Comment on: Comparative effectiveness of abatacept, rituximab, tocilizumab and TNFi biologics in RA: results from the nationwide Swedish register
In this study it is shown that non-TNFi had a similar or even better response rate on both TNFi-na ïve and -resistant patients. (Source: Rheumatology)
Source: Rheumatology - May 5, 2019 Category: Rheumatology Source Type: research

Comment on: Comparative effectiveness of abatacept, rituximab, tocilizumab and TNFi biologics in RA: results from the nationwide Swedish register: reply
Sir, We are grateful for the interest in our work [1] shown by Dr Sat ışet al. and agree that it would have been interesting to also compare the effectiveness seen for tofacitinib and other Janus kinase inhibitors to the therapies we included. As they guess in their letter, however, the reason why we did not include data on tofacitinib was that it entered the Swedish market in 2017,after the period included for analysis in our study. We look forward to returning to this topic in the future, when more data have been accumulated. (Source: Rheumatology)
Source: Rheumatology - May 5, 2019 Category: Rheumatology Source Type: research

Subclassifying ANCA-associated vasculitis: a unifying view of disease spectrum
This editorial refers to ‘Clinical impact of subgrouping ANCA-associated vasculitis according to antibody specificity beyond the clinicopathological classification', Deshayeset al., on pages 1731 –9. (Source: Rheumatology)
Source: Rheumatology - May 3, 2019 Category: Rheumatology Source Type: research

Recommendations for acquisition and interpretation of MRI of the spine and sacroiliac joints in the diagnosis of axial spondyloarthritis in the UK
ConclusionA joint rheumatology and radiology consensus on the acquisition and interpretation of MRI in axSpA diagnosis was achieved, and a research agenda formulated. This consensus should help standardize practice around MRI and ensure a more informed, consistent approach to the diagnosis of axSpA. (Source: Rheumatology)
Source: Rheumatology - May 2, 2019 Category: Rheumatology Source Type: research

Short-term follow-up results of children with familial Mediterranean fever after cessation of colchicine: is it possible to quit?
ConclusionLife-long colchicine treatment may not be required in all FMF patients. There are no current guidelines to determine in which patients it is safe to stop colchicine. We found that younger age during cessation and shorter duration of colchicine treatment lead to a higher risk of needing to restart colchicine. (Source: Rheumatology)
Source: Rheumatology - April 28, 2019 Category: Rheumatology Source Type: research

Functional and structural magnetic resonance imaging correlates of fatigue in patients with rheumatoid arthritis
ConclusionFatigue in RA is associated with functional and structural MRI changes in the brain. The newly identified and reproduced neural imaging correlates provide a basis for future targeting and stratification of this key patient priority. (Source: Rheumatology)
Source: Rheumatology - April 28, 2019 Category: Rheumatology Source Type: research

Thrombotic microangiopathy associated with anti-neutrophil cytoplasmic antibody-associated vasculitis: a French nationwide retrospective case –control study and literature review
Rheumatology key messageThrombotic microangiopathy should be suspected in ANCA-associated vasculitis with severe organ failure, thrombocytopenia and high lactate dehydrogenase levels. (Source: Rheumatology)
Source: Rheumatology - April 28, 2019 Category: Rheumatology Source Type: research

Can serum interleukin-17 and interleukin-10 levels predict response to biologic treatments in patients with rheumatoid arthritis?
Rheumatology key messageIL-17 levels do not predict response/non-response to anti-TNF drugs. (Source: Rheumatology)
Source: Rheumatology - April 27, 2019 Category: Rheumatology Source Type: research

Bone-marrow derived mesenchymal stromal cells infusion in therapy refractory juvenile idiopathic arthritis patients
ConclusionMSC infusions in six refractory JIA patients were safe, although in sJIA stopping the ‘failing’ biologic treatment carries a risk of a MAS flare, as the drug might still suppress the systemic features.Trial registrationTrial register.nl,http://https://www.trialregister.nl, NTR4146. (Source: Rheumatology)
Source: Rheumatology - April 27, 2019 Category: Rheumatology Source Type: research

Th17 cells: do regulatory B-cells (Breg) take control in ANCA-vasculitis?
This editorial refers to ‘Circulating CD24hiCD38hi regulatory B cells correlate inversely with the ThEM17 cell frequency in granulomatosis with polyangiitis patients ’, by von Borstelet al., on pages 1361 –6. (Source: Rheumatology)
Source: Rheumatology - April 27, 2019 Category: Rheumatology Source Type: research

Translational validation of the Global Antiphospholipid Syndrome Score in patients with thrombotic APS
Rheumatology key messageHigher adjusted-Global Antiphospholipid Syndrome Scores are associated with higher levels of pro-thrombotic molecules in APS. (Source: Rheumatology)
Source: Rheumatology - April 26, 2019 Category: Rheumatology Source Type: research

Development of semiquantitative ultrasound scoring system to assess cartilage in rheumatoid arthritis
ConclusionOur study demonstrates that ultrasound is a reliable tool for evaluating cartilage changes in the MCP joints of patients with RA and supports further development of a new reliable semiquantitative ultrasound scoring system for evaluating cartilage involvement in RA. (Source: Rheumatology)
Source: Rheumatology - April 26, 2019 Category: Rheumatology Source Type: research

Severity classes in adults with hypermobile Ehlers-Danlos syndrome/hypermobility spectrum disorder
This editorial refers to ‘Severity classes in adults with hypermobile Ehlers-Danlos syndrome/hypermobility spectrum disorders: a pilot study of 105 Italian patients', Copettiet al., on pages 1722 –30. (Source: Rheumatology)
Source: Rheumatology - April 24, 2019 Category: Rheumatology Source Type: research

Placental transfer of tocilizumab in a patient with rheumatoid arthritis
Rheumatology key messageTocilizumab concentrations in cord blood and infant serum were 80 –90% of those in maternal serum. (Source: Rheumatology)
Source: Rheumatology - April 24, 2019 Category: Rheumatology Source Type: research

Lysyl-oxidase in systemic sclerosis-associated pulmonary arterial hypertension: a future still to be written
This editorial refers to ‘Lysyl oxidase—a possible role in systemic sclerosis–associated pulmonary hypertension: a multicentre study’, Vadaszet al., on pages 1547 –55. (Source: Rheumatology)
Source: Rheumatology - April 23, 2019 Category: Rheumatology Source Type: research

Autoantibodies to a novel Rpp38 (Th/To) derived B-cell epitope are specific for systemic sclerosis and associate with a distinct clinical phenotype
AbstractObjectiveDetection of antinuclear antibodies and specific autoantibodies is important in the diagnosis and classification of SSc. Several proteins of the Th/To complex, including Rpp25, Rpp38 and hPop1 are the target of autoantibodies in SSc patients. However, very little is known about the epitope distribution of this autoantigen. Consequently, we screened Rpp25, Rpp38 and hPop1 for B cell epitopes and evaluated their clinical relevance.MethodsSerum pools with (n = 2) and without (n = 1) anti-Th/To autoantibodies were generated and used for epitope discovery. Identified biomarker candidate sequences were then util...
Source: Rheumatology - April 22, 2019 Category: Rheumatology Source Type: research

Interhospital variation in mortality among patients with systemic lupus erythematosus and sepsis in the USA
ConclusionMortality among patients with SLE and sepsis varied widely between hospitals, and was lower at hospitals that treated more of these patients. (Source: Rheumatology)
Source: Rheumatology - April 22, 2019 Category: Rheumatology Source Type: research

Abatacept concentrations in maternal serum and breast milk during breastfeeding and an infant safety assessment: a case study
Rheumatology key messageAbatacept was secreted into breast milk at levels 1/200 –1/300 of those in serum. (Source: Rheumatology)
Source: Rheumatology - April 22, 2019 Category: Rheumatology Source Type: research

Orbital masses in ANCA-associated vasculitis: an unsolved challenge?
This editorial refers to ‘Orbital mass in ANCA-associated vasculitides: data on clinical, biological, radiological and histological presentation, therapeutic management, and outcome from 59 patients’, Durelet al., on pages 1565 –73. (Source: Rheumatology)
Source: Rheumatology - April 22, 2019 Category: Rheumatology Source Type: research

Long-term preservation of measles and rubella specific-IgG antibodies in children with enthesitis related arthritis on anti-TNF α treatment: a prospective controlled study
Rheumatology key messageEnthesitis related arthritis children on antiTNFa show accelerated measles and rubella antibody loss while retaining satisfactory seroprotection. (Source: Rheumatology)
Source: Rheumatology - April 22, 2019 Category: Rheumatology Source Type: research

Responders to intradiscal glucocorticoid among patients with chronic low back pain and active discopathy
Rheumatology key messageSick leave is associated with the response to intradiscal glucocorticoid in people with active discopathy. (Source: Rheumatology)
Source: Rheumatology - April 22, 2019 Category: Rheumatology Source Type: research

The simultaneous analysis of mesenchymal stem cells and early osteocytes accumulation in osteoarthritic femoral head sclerotic bone
This study investigated the relationships between native osteocytes and native MSCs in osteoarthritic femoral heads.MethodsTo avoid culture manipulations, a bone treatment procedure was developed to simultaneously obtain pure osteocyte-enriched fragments and matched native CD45-CD271+ MSCs. Gene expression in osteocytes and MSCs was compared between healthy and OA bone and selected molecules were examined by immunohistochemistry in relation to OA tissue pathology. Cell sorting and standard trilineage differentiation assays were employed to test OA MSC functionality.ResultsNative osteocyte enrichment was confirmed histologi...
Source: Rheumatology - April 16, 2019 Category: Rheumatology Source Type: research

Improvement in cardiovascular biomarkers sustained at 4 years following an initial treat-to-target strategy in early rheumatoid arthritis
Rheumatology key messageInitial treat-to-target therapy in early rheumatoid arthritis has sustained cardiovascular risk benefits at 4 years. (Source: Rheumatology)
Source: Rheumatology - April 16, 2019 Category: Rheumatology Source Type: research

Using combinations of biomarkers to understand inflammation and bone formation in axial spondyloarthritis – is anything better than CRP?
This editorial refers to ‘Added value of biomarkers compared with clinical parameters for the prediction of radiographic spinal progression in axial spondyloarthritis’, Rademacheret al., on pages 1556 –64. (Source: Rheumatology)
Source: Rheumatology - April 16, 2019 Category: Rheumatology Source Type: research

Polypharmacy is associated with treatment response and serious adverse events: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis
AbstractObjectiveTo evaluate whether polypharmacy is associated with treatment response and serious adverse events (SAEs) in patients with RA using data from the British Society for Rheumatology Biologics Register (BSRBR-RA).MethodsThe BSRBR-RA is a prospective observational cohort study of biologic therapy starters and a DMARD comparator arm. A logistic regression model was used to calculate the odds of a EULAR ‘good response’ after 12 months of biologic therapy by medication count. Cox proportional hazards models were used to identify risk of SAEs. The utility of the models were compared with the Rheumatic Di...
Source: Rheumatology - April 14, 2019 Category: Rheumatology Source Type: research

A systematic review and meta-analysis of infection risk with small molecule JAK inhibitors in rheumatoid arthritis
ConclusionThe absolute SI rates were low. However across the JAK inhibitors, the incidence of HZ is higher than expected for the population (3.23 per 100 patient-years). While the risk was numerically greatest with baricitinib, indirect comparisons between the drugs did not demonstrate any significant difference in risk.Systematic review registration numberProspero 2017 CRD4201707879. (Source: Rheumatology)
Source: Rheumatology - April 14, 2019 Category: Rheumatology Source Type: research

Using biologics safely
This editorial refers to ‘The British Society for Rheumatology biologic DMARD safety guidelines in inflammatory arthritis—Executive summary’, Holroydet al., on pages 220 –6. (Source: Rheumatology)
Source: Rheumatology - April 14, 2019 Category: Rheumatology Source Type: research

Comorbidity burden in axial spondyloarthritis: a cluster analysis
ConclusionComorbidity is common among axSpA patients. The two most common comorbidities were hypertension and depression. Patients in the depression-anxiety and fibromyalgia-IBS clusters reported poorer health and increased axSpA severity. (Source: Rheumatology)
Source: Rheumatology - April 9, 2019 Category: Rheumatology Source Type: research

Clinical impact of artifactual hypoglycaemia and its diagnosis at the bedside
Rheumatology key messageKnowledge of artifactual hypoglycaemia is necessary to prevent unnecessary work-up, therapy and anxiety. (Source: Rheumatology)
Source: Rheumatology - April 9, 2019 Category: Rheumatology Source Type: research

Assessing joint inflammation —a way forward for SLE trials?
This editorial refers to ‘Responsiveness of clinical and ultrasound outcome measures in musculoskeletal systemic lupus erythematosus’, by Mahmoudet al., on pages1353–60. (Source: Rheumatology)
Source: Rheumatology - April 9, 2019 Category: Rheumatology Source Type: research