Safety in the use of ultrasound in rheumatology during the COVID-19 Pandemic. Spanish Society of Rheumatology positioning paper. / Seguridad en el uso de la ecografía en reumatología durante la pandemia COVID-19. Documento de posicionamiento de la Sociedad Española de Reumatología.

Ultrasound is a widely implemented imaging modality in rheumatology practice that implies a great interaction between patient and professional. The COVID-19 pandemic requires a change in our clinical practice, through the adoption of new strategies that allow comprehensive care for our patients, guaranteeing the safety of both patients and healthcare professionals. OBJETIVE: Our objective was to develop practical recommendations, agreed among a panel of experts, on the use and safety of rheumatological ultrasound during the COVID-19 pandemic. METHODS: We performed a narrative review of the available literature. Based on the literature review, we produced preliminary recommendations that were subsequently agreed among a panel of experts using the Delphi methodology with a 1-5 Likert scale. Agreement for each recommendation was considered if 75% of the panel members scored the item ≥4 on the Likert scale. RESULTS: 5 overarching principles and 28 recommendations were issued and agreed among the panel. Group consensus was achieved in 100% of items. CONCLUSIONS: The document provides useful information about preventive measures in the practice of ultrasound in rheumatology in times of a COVID-19 pandemic based on the experience and literature available to date.

Vitamin D and bisphosphonate therapy in systemic lupus erythematosus patients who receive glucocorticoids: are we offering the best care?

OBJECTIVE: This study aimed to evaluate management practices for glucocorticoid (GC)-induced osteoporosis (GIOP) in systemic lupus erythematosus (SLE) patients using 2017 American College of Rheumatology guidelines as a gold standard. METHODS: We conducted a retrospective cohort study using a clinical database from the years 2011 to 2016. SLE cases with >90 days continuous prednisone use at doses of ≥7.51 mg daily were identified. Osteoporosis risk factors were assessed via chart review. The Fracture Risk Assessment (FRAX) score was estimated for patients > 40 years of age. Vitamin D, bisphosphonate prescriptions, and osteoporotic (OP) fractures were ascertained through chart review. A classification tree was used to identify the key patient-related predictors of bisphosphonate prescription. RESULTS: A total of 203 SLE patients met the inclusion criteria. The recommended dose of vitamin D supplement was prescribed to 58.9% of patients < 40 years of age and 61.5% of patients ≥ 40 years of age. Among patients aged ≥ 40 years, 25% were prescribed bisphosphonates compared to 36% who met indications for bisphosphonates per the ACR guidelines. Another 10% were prescribed a bisphosphonate, despite not having indication per the ACR guidelines, which was considered as overtreatment. Among patients aged ≥ 40 years, older age and a higher FRAX score for major OP fracture and hip fracture predicted bisphosphonate prescription. In a classification tree analysis, patients with FRAX scores (for major OP fracture) of ≥ 23.5% predicted bisphosphonate prescription in this SLE population. Among patients who had OP fractures in the follow-up period, nine (6.50%) were inpatients receiving appropriate GIOP care versus 12 (13.6%) who were inpatients not receiving ACR-appropriate care (p = 0.098). CONCLUSIONS: In clinical practice, fewer SLE patients with or at risk for GIOP are prescribed vitamin D and bisphosphonates than recommended by the 2017 ACR guidelines. Also, in this study, another 10% were prescribed a bisphosphonate, despite not having an indication per the ACR guidelines. Patients were most likely to receive a bisphosphonate prescription if they had a major OP FRAX score of > 23.5%.

Integrated gastroenterology and rheumatology ambulatory: an innovative approach for enteropathic spondyloarthritis early diagnosis.

Patients with inflammatory bowel disease (IBD) may develop rheumatic diseases, particularly enterophatic spondyloarthritis (ESpA). Similarly, an IBD may develop in patients with SpA. Management of these patients in a dedicated ambulatory could be advantageous. We pioneered an integrated "GastroReumatology" ambulatory where a gastroenterologist and a rheumatologist with a long-lasting expertise in IBD and spondyloarthritis, respectively, simultaneously visit those patients referred for a suspected ESpA. A total of 101 different patients with suspected or known IBD and/or a rheumatic disease were visited. A new diagnosis of ESpA was eventually achieved in 13 (12.9%) patients, and further 12 patients with an already known ESpA were referred for an appropriate management. No cases of IBD in those patients with an established rheumatic disease were observed. Early diagnosis of ESpA is possible in a "GastroReumatology" ambulatory.

Implementing a simple pharmacovigilance program to improve reporting of adverse events associated with biologic therapy in rheumatology: Preliminary results from the Calabria Biologics Pharmacovigilance Program (CBPP).

INTRODUCTION: Post-marketing surveillance activities (namely pharmacovigilance) are crucial to favor the early detection of unexpected adverse events (AEs) and/or serious adverse reactions (SAEs). Indeed, spontaneous reporting of AEs has been demonstrated to underestimate the number of events in different clinical settings. Aim of the present study is to report the preliminary data of a Regional (Calabria, Italy) Pharmacovigilance Program (CBPP) aimed at improving AEs' reporting associated with biologics use in rheumatology. MATERIALS AND METHODS: We developed a simple, cost-effective pharmacovigilance program based on regular training sessions for physicians (stimulated reporting), periodical phone calls by a clinical pharmacologist aimed at identifying new events and stimulating self-awareness and encouraging reporting to the physician during the subsequent follow-up visit for minor AEs. To test this approach, all consecutive patients undergoing treatment with one biologic agent at eight rheumatology centers during a two-years period were invited to participate. Collected AEs were compared to the number of AEs spontaneously reported for the same molecules in the same centers before starting the protocol. RESULTS: During the study period, 399 patients (245 females; mean age: 58 ± 11 years) were started on treatment with biologics for active RA (n = 211, 52.9%), PsA (n = 119, 29.8%) or AS (n = 69, 17.3%) at eight rheumatology centers. A total of 125 AEs (31.3%) and 9 SAEs (2.3%) were reported during the two-years study period. In the control cohort (comprising 368 consecutive patients started on treatment with bDMARDs during a two-years period before CBPP study) only 42 (11.4%) AEs and no SAEs were reported (p < 0.0001). The most common AEs were injection site reactions and skin disorders. CONCLUSIONS: In conclusion, our study provides further evidence of a critical role of active pharmacovigilance in detection, reporting and analysis of AEs in rheumatology.

How should we manage low-dose methotrexate-induced pancytopenia in patients with rheumatoid arthritis?

Low-dose methotrexate (ld-MTX) that is administered during rheumatoid arthritis (RA) treatment has hematological adverse effects such as pancytopenia, although rare. Although well-established and widely used for hematological adverse effects caused by high-dose MTX, leucovorin (folinic acid) treatment does not have an agreed-upon administration for ld-MTX-induced pancytopenia. Here, we aimed to figure out whether there was any difference in response time between the regimens with and without folinic acid prescribed to our patients who developed pancytopenia while on MTX therapy, and to identify risk factors for its development. Our cases were collectively assessed together with other rare cases available in the literature that were reported in a similar manner with an explicitly indicated response time, in days. Thereupon, we looked for any difference in response time between the regimens with and without folinic acid. In total, ten of our patients experienced pancytopenia while on ld-MTX treatment. Mean day on which hematological response was achieved was as follows: 7 days in one patient on folic acid monotherapy, 6 days in three patients on granulocyte-colony stimulating factor (G-CSF) monotherapy, 4.5 days in two patients on leucovorin monotherapy, and 4 days in the remaining three patients who were treated with G-CSF + folinic acid/leucovorin. When we collectively evaluated our patients and the patients with an explicitly stated response duration in the literature (15 patients) and compared regimens including folinic acid to those without folinic acid, duration until response/recovery from pancytopenia was significantly shorter in folinic acid group than that in the group without folinic acid (5.47 ± 2.9 days vs 10 ± 3.77 days, p = 0.002). Treatment modalities including folinic acid (leucovorin) either with or without G-CSF result in a shorter recovery/response time compared to other agents. Leucovorin should definitely be considered and applied in rescue therapy for ld-MTX-associated side effects.

Usefulness of polymerase chain reaction for diagnosing Whipple's disease in rheumatology.

OBJECTIVES: To determine when Tropheryma whipplei polymerase chain reaction (PCR) is appropriate in patients evaluated for rheumatological symptoms. METHODS: In a retrospective observational study done in rheumatology units of five hospitals, we assessed the clinical and radiological signs that prompted T. whipplei PCR testing between 2010 and 2014, the proportion of patients diagnosed with Whipple's disease, the number of tests performed and the number of diagnoses according to the number of tests, the patterns of Whipple's disease, and the treatments used. Diagnostic ascertainment was based on 1- Presence of at least one suggestive clinical finding; 2- at least one positive PCR test, and 3- a response to antibiotic therapy described by the physician as dramatic, including normalization of C Reactive Protein. RESULTS: At least one PCR test was performed in each of 267 patients. Rheumatic signs were peripheral arthralgia (n = 239, 89%), peripheral arthritis (n = 173, 65%), and inflammatory back pain (n = 85, 32%). Whipple's disease was diagnosed in 13 patients (4.9%). The more frequently positive tests were saliva and stool. In the centres with no diagnoses of Whipple's disease, arthritis was less common and constitutional symptoms more common. The group with Whipple's disease had a higher proportion of males, older age, and greater frequency of arthritis. The annual incidence ranged across centres from 0 to 3.6/100000 inhabitants. CONCLUSION: Males aged 40-75 years with unexplained intermittent seronegative peripheral polyarthritis, including those without constitutional symptoms, should have T. whipplei PCR tests on saliva, stool and, if possible, joint fluid.

2017 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis.

OBJECTIVE: To develop recommendations for prevention and treatment of glucocorticoid-induced osteoporosis (GIOP). METHODS: We conducted a systematic review to synthesize the evidence for the benefits and harms of GIOP prevention and treatment options. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of evidence. We used a group consensus process to determine the final recommendations and grade their strength. The guideline addresses initial assessment and reassessment in patients beginning or continuing long-term (≥3 months) glucocorticoid (GC) treatment, as well as the relative benefits and harms of lifestyle modification and of calcium, vitamin D, bisphosphonate, raloxifene, teriparatide, and denosumab treatment in the general adult population receiving long-term GC treatment, as well as in special populations of long-term GC users. RESULTS: Because of limited evidence regarding the benefits and harms of interventions in GC users, most recommendations in this guideline are conditional (uncertain balance between benefits and harms). Recommendations include treating only with calcium and vitamin D in adults at low fracture risk, treating with calcium and vitamin D plus an additional osteoporosis medication (oral bisphosphonate preferred) in adults at moderate-to-high fracture risk, continuing calcium plus vitamin D but switching from an oral bisphosphonate to another antifracture medication in adults in whom oral bisphosphonate treatment is not appropriate, and continuing oral bisphosphonate treatment or switching to another antifracture medication in adults who complete a planned oral bisphosphonate regimen but continue to receive GC treatment. Recommendations for special populations, including children, people with organ transplants, women of childbearing potential, and people receiving very high-dose GC treatment, are also made. CONCLUSION: This guideline provides direction for clinicians and patients making treatment decisions. Clinicians and patients should use a shared decision-making process that accounts for patients' values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies.

Ten years of METEOR (an international rheumatoid arthritis registry): development, research opportunities and future perspectives.

OBJECTIVES: Ten years ago, the METEOR tool was developed to simulate treatment-to-target and create an international research database. The development of the METEOR tool and database, research opportunities and future perspectives are described. METHODS: The METEOR tool is a free, online, internationally available tool in which daily practice visits of all rheumatoid arthritis patients visiting a rheumatologist can be registered. In the tool, disease characteristics, patient- and physician-reported outcomes and prescribed treatment could be entered. These can be subsequently displayed in powerful graphics, facilitating treatment decisions and patient-physician interactions. An upload facility is also available, by which data from local electronic health record systems or registries can be integrated into the METEOR database. This is currently being actively used in, among other countries, the Netherlands, Portugal and India. RESULTS: Since an increasing number of hospitals use electronic health record systems, the upload facility is being actively used by an increasing number of sites, enabling them to benefit from the benchmark and research opportunities of METEOR. Enabling a connection between local registries and METEOR is a well established but time-consuming process for which an IT-specialist of METEOR and the local registry are necessary. However, once this process has been finished, data can be uploaded regularly and relatively easily according to a pre-specified format. The METEOR database currently contains data from >39,000 patients and >200,000 visits, from 32 different countries and is ever increasing. Continuous efforts are being undertaken to increase the quality of data in the database. CONCLUSIONS: Since METEOR was founded 10 years ago, many rheumatologists worldwide have used the METEOR tool to follow-up their patients and improve the quality of care they provide to their patients. Combined with uploaded data, this has led to an extensive growth of the database. It now offers a unique opportunity to study daily practice care and to perform research regarding cross-country differences in a large, worldwide setting, which could provide important knowledge about disease and its treatment in different geographic and clinical settings.

A nurse-led rheumatology clinic versus rheumatologist-led clinic in monitoring of patients with chronic inflammatory arthritis undergoing biological therapy: a cost comparison study in a randomised controlled trial.

BACKGROUND: Recommendations for rheumatology nursing management of chronic inflammatory arthritis (CIA) from European League Against Rheumatism (EULAR) states that nurses should take part in the monitoring patients' disease and therapy in order to achieve cost savings. The aim of the study was to compare the costs of rheumatology care between a nurse-led rheumatology clinic (NLC), based on person-centred care (PCC), versus a rheumatologist-led clinic (RLC), in monitoring of patients with CIA undergoing biological therapy. METHODS: Patients with CIA undergoing biological therapy (n = 107) and a Disease Activity Score of 28 ≤ 3.2 were randomised to follow-up by either NLC or RLC. All patients met the rheumatologist at inclusion and after 12 months. In the intervention one of two annual monitoring visits in an RLC was replaced by a visit to an NLC. The primary outcome was total annual cost of rheumatology care. RESULTS: A total of 97 patients completed the RCT at the 12 month follow-up. Replacing one of the two annual rheumatologist monitoring visits by a nurse-led monitoring visit, resulted in no additional contacts to the rheumatology clinic, but rather a decrease in the use of resources and a reduction of costs. The total annual rheumatology care costs including fixed monitoring, variable monitoring, rehabilitation, specialist consultations, radiography, and pharmacological therapy, generated € 14107.7 per patient in the NLC compared with € 16274.9 in the RCL (p = 0.004), giving a € 2167.2 (13 %) lower annual cost for the NLC. CONCLUSIONS: Patients with CIA and low disease activity or in remission undergoing biological therapy can be monitored with a reduced resource use and at a lower annual cost by an NLC, based on PCC with no difference in clinical outcomes. This could free resources for more intensive monitoring of patients early in the disease or patients with high disease activity. TRIAL REGISTRATION: The trial is registered as a clinical trial at the ClinicalTrials.gov (NCT01071447). Registration date: October 8, 2009.

Ultrasound in crystal-related arthritis.

In the last decade, an increasing number of rheumatologists have been using ultrasound (US) for assessing patients with gout and calcium pyrophosphate deposition (CPPD) disease. The high reflectivity of the crystalline aggregates and the ability of US to detect even minimal crystal deposits explain the high sensitivity of this imaging technique. Furthermore, the peculiar distribution within the target tissues results in the generation of typical US patterns and explains the excellent specificity of some US findings. The large spectrum of US findings and their wide combination generate different scenarios in different patients and also in the same subject. Such a high variety impaired the standardisation of the definitions of each US finding. This review presents the main US findings indicative of crystal deposits, discusses the available evidence supporting the use of US in patients with gout and CPPD disease, and provides a research agenda to guide further investigations. The combined US examination of the target tissues and the clinically involved sites represents the key issue to obtain the best compromise between accuracy and feasibility, in the daily US assessment of patients with crystal-related arthropathies. Moreover, the US guided aspiration of synovial fluid may enhance the possibility to reach a crystal-proven diagnosis, making US a complementary tool, not in contrast, with microscopy, which rests the current gold standard. Finally, even if at moment other US findings are not included among the typical ones for crystal-related arthropathies, it is possible that in the future, thanks to continuous technological advances, we will be able to identify other specific patterns of pathology.

Juvenile dermatomyositis at a tertiary care hospital: is there any change in the last decade?

INTRODUCTION: Juvenile dermatomyositis (JDM) is a rare multisystem disorder of childhood primarily involving the skeletal muscles and skin. PATIENTS AND METHODS: The case records of patients with JDM seen at our centre in the last 10 years were reviewed and data on clinical presentation, management, outcome and complications were retrieved. RESULTS: Eighteen patients (nine boys) were diagnosed as JDM with median age at presentation of 12.5 years, duration of illness of 9.25 months and follow-up duration of 24 months. At presentation, rash was seen in all patients, 17 had muscle weakness, fever in 11 and arthritis in six. Gottron's lesions and heliotrope rash were seen in 14 and 11 patients, respectively. Calcinosis was seen in five patients and lipoatrophy in two patients. Four patients had dysphagia, one each had dilated cardiomyopathy and respiratory failure. Electromyograph was abnormal in 15 patients and antinuclear antibodies were positive in nine patients. Prednisolone and methotrexate were used in 17 patients. Other disease-modifying anti-rheumatic drugs used were hydroxychloroquine, azathioprine, cyclophosphamide and cyclosporine. Sixteen patients achieved remission. Five patients had pyogenic infections and one patient died of this. In addition two patients had tuberculosis. CONCLUSION: Compared to our experience in the previous decade we saw more girls, used methotrexate upfront but the median duration of illness and prevalence of calcinosis (30%) was the same, suggesting that we need to improve awareness about JDM among paediatricians for early referral.

Characterization of rheumatoid arthritis subtypes using symptom profiles, clinical chemistry and metabolomics measurements.

OBJECTIVE: The aim is to characterize subgroups or phenotypes of rheumatoid arthritis (RA) patients using a systems biology approach. The discovery of subtypes of rheumatoid arthritis patients is an essential research area for the improvement of response to therapy and the development of personalized medicine strategies. METHODS: In this study, 39 RA patients are phenotyped using clinical chemistry measurements, urine and plasma metabolomics analysis and symptom profiles. In addition, a Chinese medicine expert classified each RA patient as a Cold or Heat type according to Chinese medicine theory. Multivariate data analysis techniques are employed to detect and validate biochemical and symptom relationships with the classification. RESULTS: The questionnaire items 'Red joints', 'Swollen joints', 'Warm joints' suggest differences in the level of inflammation between the groups although c-reactive protein (CRP) and rheumatoid factor (RHF) levels were equal. Multivariate analysis of the urine metabolomics data revealed that the levels of 11 acylcarnitines were lower in the Cold RA than in the Heat RA patients, suggesting differences in muscle breakdown. Additionally, higher dehydroepiandrosterone sulfate (DHEAS) levels in Heat patients compared to Cold patients were found suggesting that the Cold RA group has a more suppressed hypothalamic-pituitary-adrenal (HPA) axis function. CONCLUSION: Significant and relevant biochemical differences are found between Cold and Heat RA patients. Differences in immune function, HPA axis involvement and muscle breakdown point towards opportunities to tailor disease management strategies to each of the subgroups RA patient.

The effect of neutralizing antibodies on the sustainable efficacy of biologic therapies: what's in it for African and Middle Eastern rheumatologists.

Over the last decade, biologic therapeutic proteins have advanced the treatment of diseases such as rheumatoid arthritis (RA). Therapeutic antibodies such as infliximab, adalimumab, rituximab, tocilizumab, golimumab, certolizumab pegol, the receptor construct etanercept, and abatacept, an anticluster of differentiation (CD)80/anti-CD86 fusion protein, are used as treatment for RA and ankylosing spondylitis (AS). Infliximab, adalimumab, golimumab, certolizumab pegol, and etanercept are inhibitors of tumor necrosis factor (TNF), a key regulator of inflammation. Left untreated, progression of rheumatic diseases due to inflammation can lead to irreversible joint damage and serious disability. One limitation for the use of therapeutic antibodies is immunogenicity, the induction of antibodies by the adaptive immune system in response to foreign substances. The development of antidrug antibodies (ADAs) has a varying impact on the clinical efficacy of biologic agents for the treatment of RA and AS, depending on whether the ADAs are neutralizing or non-neutralizing. Studies have indicated that neutralizing ADAs are associated with a reduced efficacy, decreased drug survival, increased instances of dose escalation, and adverse events. Comparison studies of anti-TNF biologics have demonstrated that each drug has a different sustained efficacy profile depending on immunogenicity. The purpose of this review is to provide rheumatologists with information regarding the effect of neutralizing antibodies on the sustainable efficacy of anti-TNF biologic therapies. This information will be of value to practicing rheumatologists in Africa and the Middle East who should take into account the potential for changes in the efficacy and safety of biologic therapies and closely monitor patients under their care.

Osteoarthritis: a holistic approach.

Osteoarthritis represents a massive and rapidly increasing burden on our society and the NHS. Current treatments are limited in efficacy and have significant toxicities. A conference was organised in conjunction with the British Society of Rheumatology with the aim of updating frontline clinicians and researchers on the size and causes of this problem, with a focus on modern management.

Access to the next wave of biologic therapies (Abatacept and Tocilizumab) for the treatment of rheumatoid arthritis in England and Wales: addressing treatment outside the current NICE guidance.

Patients in England and Wales with rheumatoid arthritis (RA) receive treatment from the National Health Service (NHS) with therapies approved by the European Medicines Agency (EMA), under guidance from the National Institute for Health and Clinical Excellence (NICE). This document overviews the current NICE guidelines for the treatment of RA and identifies scenarios when such guidance may not represent the optimum management strategy for individual patients. Specifically, we consider the use of tocilizumab or abatacept as the most appropriate treatments for some patients. In such scenarios, it may be possible for the clinician to secure access to the required therapy through an application procedure known as an 'individual funding request', the process of which is described in detail here. At present, it is unclear the extent to which the proposed reform of the NHS will affect the role of NICE in providing guidance and setting standards of care. Until the full impact of the proposed changes are realized, individual funding requests will remain a valuable way of securing the optimal treatment for all patients suffering from RA.

Intervencionismo guiado por ecografía en reumatología / Ultrasound-guided intervention in rheumatology

Las aspiraciones e infiltraciones son procedimientos muy comunes en reumatología. La eficacia de ambos procedimientos depende de la posición correcta de la aguja dentro o alrededor del blanco elegido. Las intervenciones a ciegas con alta frecuencia son fallidas. La ultrasonografía (US) ha demostrado ser más eficaz y más segura como guía de procedimientos porque evita la lesión de estructuras nerviosas, tendinosas, óseas, etc., al facilitar observar la aguja hasta llegar al blanco. Dirigir una aguja por US hace que el procedimiento sea inocuo, de menor costo que la fluoroscopia o tomografía, con la posibilidad de acudir hasta la cama del paciente con los equipos portátiles. La terapia para infiltraciones no se reduce a los esteroides: actualmente se administra proloterapia, plasma rico en plaquetas, entre otros, para lesiones tendinosas con resultados alentadores. Otra de las ventajas del intervencionismo guiado por US es la realización de biopsias para el diagnóstico certero. En este artículo se hace una revisión de la técnica de infiltración de las diferentes regiones articulares y las ventajas que ofrece la US.

The aspirations and injections are common procedures in rheumatology. The efficacy of both procedures depends on the position of the needle within or around the chosen target. Blind interventions with high frequency are unsuccessful. Ultrasonography (U.S.) has proved more effective and safer procedures as a guide because in prevents injury to neural structures, tendon, bone, etc., to facilitate observing the needle to reach the target. U.S. direct needle makes the procedure is safe, lower cost than fluoroscopy or CT, with the possibility of going to the bedside with portable equipment. Therapy for infiltration is not limited to steroids, is currently given prolotherapy, platelet rich plasma for tendon injuries and others with encouraging results. Another advantage of U.S. interventionism is guided biopsies for diagnosis. In this article we review the technique of infiltration from the different regions and joint benefits of the U.S.