Publications by authors named "Chetan Mukhtyar"

48 Publications

Comment on: Evaluation of adjunctive mycophenolate for large vessel giant cell arteritis.

Rheumatol Adv Pract 2021 26;5(1):rkab011. Epub 2021 Feb 26.

Department of Rheumatology, Norfolk & Norwich University Hospital, NHS Foundation Trust, Norwich, UK.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/rap/rkab011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998050PMC
February 2021

Patient perceptions of co-morbidities in inflammatory arthritis.

Rheumatol Adv Pract 2021 11;5(1):rkaa076. Epub 2021 Jan 11.

Rheumatology Department, Norfolk and Norwich University Hospital, Norwich, UK.

Objective: Longer life expectancy has resulted in people living with an increasing number of co-morbidities. The average individual with inflammatory arthritis has two co-morbidities, which contribute to higher mortality, poorer functional outcomes and increased health-care utilization and cost. A number of studies have investigated the prevalence of co-morbidities, whereas this study was designed to look at patient perspectives.

Methods: The study comprised two parts: a patient questionnaire and an interview. Individuals with physician-verified inflammatory arthritis along with one or more Charlson co-morbidities were invited to participate. In-depth data were obtained by interviews with 12 willing participants.

Results: One hundred and forty-six individuals were recruited; 50 (35%) had one co-morbidity, 69 (48%) had two and 25 (17%) had more than four co-morbidities. Seventy-seven individuals (53%) reported that co-morbidities affected their health as much as their arthritis, and 82 (56%) reported dependence on others for activities of daily living. Lack of education was highlighted by 106 (73%) participants. Qualitative data provided further support for the challenges, with participants highlighting the lack of time to discuss complex or multiple problems, with no-one coordinating their care. This, in turn, led to polypharmacy and insufficient discussion around drug and disease interactions, complications and self-help measures.

Conclusion: This study highlights the challenges for individuals with inflammatory arthritis who suffer with multiple co-morbidities. The challenges result from limited resources or support within the current health-care environments. Individuals highlighted the poor quality of life, which is multifactorial, and the need for better educational strategies and coordination of care to improve outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/rap/rkaa076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884022PMC
January 2021

Ultrasonography in the diagnosis and follow-up of Giant Cell Arteritis.

Rheumatology (Oxford) 2021 Feb 18. Epub 2021 Feb 18.

Rheumatology, Norfolk and Norwich University Hospital, Colney Lane, NR4 7UY.

Colour-doppler ultrasonography is the first measure to allow objective bedside assessment of Giant Cell Arteritis (GCA). This paper discusses the evidence using the OMERACT filter. Consensus definitions for ultrasonography changes were agreed by Delphi process, with the 'halo' and 'compression' sign being characteristic. The 'halo' is sensitive to change, disappearing within 2-4 weeks of starting glucocorticoids. Ultrasonography has moderate convergent validity with temporal artery biopsy in a pooled analysis of 12 studies including 965 participants (k = 0.44, 95% CI 0.38-0.50). The interobserver and intraobserver reliabilities are good (k = 0.6, k = 0.76-0.78) in live exercises, and excellent when assessing acquired images and videos (k = 0.83-0.87, k = 0.88). Discriminant validity has been tested against stroke and diabetes mellitus (k=-0.16 for diabetes). Machine familiarity and adequate examination time improves feasibility. Ultrasonography in follow-up is not yet adequately defined. Some patients have persistent changes in the larger arteries but these do not necessarily imply treatment failure or predict relapses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/rheumatology/keab179DOI Listing
February 2021

Erdheim-Chester Disease: Two cases from an ophthalmic perspective.

Am J Ophthalmol Case Rep 2020 Dec 2;20:100984. Epub 2020 Nov 2.

Department of Ophthalmology, James Paget University Hospitals NHS Trust, Great Yarmouth, Norfolk, United Kingdom.

Purpose: We report two patients who presented initially to ophthalmology clinics with symptoms and signs of orbital inflammation that led to a diagnosis of Erdheim-Chester Disease (ECD).

Observations: ECD is a rare form of non-Langerhans cell histiocytosis (LCH) which is characterised by multi-system organ involvement and poor prognosis with standard therapies. Both patients were positive for the V600E mutation on genetic testing and were treated with the inhibitors Vemurafenib and Dabrafenib respectively. These cases highlight the variable clinical presentation and course of ECD, the classical radiological and histopathological findings, and the high degree of clinical suspicion necessary to reach this diagnosis.

Conclusions And Importance: The combination of xanthelasma and bilateral, diffuse intraconal orbital masses must suggest to the clinician the possibility of ECD; and consideration to arrange further investigation with a full body CT or FDG PET/CT scan should be given, even in the absence of wider systemic symptoms or signs. With the advent of targeted therapies such as inhibitors, it is of even more importance that a diagnosis of ECD is established in a timely manner in order to give these patients the best chance of reduced morbidity and increased survival.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajoc.2020.100984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649437PMC
December 2020

Comment on: The nose is an organ too: reply.

Rheumatology (Oxford) 2020 11;59(11):e114

Norwich Medical School, University of East Anglia, Norwich.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/rheumatology/keaa334DOI Listing
November 2020

The relationship between glycated haemoglobin levels and the risk of giant cell arteritis - a case-control study.

Rheumatol Adv Pract 2020 28;4(2):rkaa018. Epub 2020 May 28.

Norwich Medical School, University of East Anglia.

Objectives: The EULAR core dataset for observational studies in GCA does not include glycated haemoglobin (HbA). A multivariable score to stratify the pre-test probability of GCA also does not include HbA. There have been contradictory reports about diabetes mellitus being a risk factor for GCA. We report the first study analysing the relationship of pre-diagnosis HbA with the risk of GCA.

Methods: This was a single-centre retrospective case-control study conducted in Norfolk, UK. All GCA cases were diagnosed with imaging or biopsy. Each case was assigned two age- and sex-matched controls. The primary outcome measure was the glycaemic status (HbA categorized into euglycaemia, pre-diabetes or diabetes mellitus) at diagnosis between cases and controls. The HbA was compared between two groups using the Mann-Whitney test. The glycaemic categorization was compared using the χ test.

Results: One hundred and twelve cases and 224 controls were included. The median (interquartile range) of HbA of cases and controls was 40 (37, 43) and 41 (39, 47) mmol/mol ( < 0.001), respectively. Ten of 112 cases and 52 of 224 controls had diabetes mellitus. The χ test demonstrated a significant interaction between glycaemic state and GCA ( = 0.006). Individuals with diabetes mellitus had an odds ratio (95% CI) of 0.32 (0.13, 0.74) ( = 0.008) of having GCA compared with euglycaemic individuals.

Conclusion: HbA in the diabetic range reduces the probability of GCA. HbA should be considered in any multivariable score to calculate the risk of GCA, and in future development of diagnostic and classification criteria. There is a need for an epidemiological study looking at the possibility of a protective nature of diabetes mellitus against GCA or whether it is only a mimic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/rap/rkaa018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7380559PMC
May 2020

Hydroxychloroquine and coronavirus disease 2019.

Authors:
Chetan Mukhtyar

J R Coll Physicians Edinb 2020 06;50(2):102-104

Department of Rheumatology, Norfolk and Norwich University Hospital, Colney Lane, Norwich NR4 7UY, UK Email:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4997/JRCPE.2020.202DOI Listing
June 2020

Testicular vasculitis: a diagnostic conundrum.

Oxf Med Case Reports 2020 Apr 23;2020(4):omaa028. Epub 2020 May 23.

Norfolk & Waveney Cellular Pathology Service, The Cotman Centre, Norfolk and Norwich University Hospital, Norwich, UK.

Vasculitis is rare in the context of testicular lesions but, when found, can be classified as a single organ vasculitis or part of a multi-organ inflammatory process. In the context of a patient with a pre-existing autoimmune disorder, this finding might cause diagnostic confusion and preferentially bias a physician towards attributing the condition to the known diagnosis or its treatment. This diagnostic bias can interfere with patient care and lead to over caution, resulting in a worse outcome for the patient involved. We describe such a patient with rheumatoid arthritis on biologic therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/omcr/omaa028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7243723PMC
April 2020

The nose is an organ too.

Rheumatology (Oxford) 2020 06;59(6):1196-1197

Norwich Medical School, University of East Anglia, Norwich.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/rheumatology/keaa073DOI Listing
June 2020

Feasibility and Face Validity of Outcome Measures for Use in Future Studies of Polymyalgia Rheumatica: An OMERACT Study.

J Rheumatol 2020 09 1;47(9):1379-1384. Epub 2020 Feb 1.

From the Epidemiology Centre Versus Arthritis, Norwich Medical School, University of East Anglia, Norwich, UK; Department of Rheumatology, East Suffolk and North Essex Foundation Trust, Ipswich, UK; Department of Rheumatology, Austin Health; Department of Medicine, University of Melbourne, Melbourne, Australia; Primary Care Centre Versus Arthritis, Research Institute for Primary Care and Health Sciences, Keele University, Keele; PMRGCA Scotland, Scotland, UK; Department of Epidemiology and Biostatistics, and Amsterdam Rheumatology and Immunology Center, Amsterdam University Medical Centers, Vrije Universiteit, Amsterdam, the Netherlands; Leeds Institute of Health Sciences, University of Leeds, Leeds, UK; Department of Rheumatology, and Department of Medicine, Hospital for Special Surgery, New York, New York, USA; Department of Rheumatology and Immunology, Medical University Graz, Graz, Austria; Department of Rheumatology, Hospital of Bruneck, Bruneck, Italy; Department of Rheumatology, Norfolk and Norwich University Hospital, Norwich, UK; Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark; Department of Rheumatology, Faculty of Health and Applied Sciences, University of the West of England, Bristol, UK; SDG LLC, Cambridge, Massachusetts, USA; School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada; Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds; National Institute for Health Research (NIHR) Leeds Biomedical Research Centre, Leeds Teaching Hospitals National Health Service (NHS) Trust, Leeds, UK; Discipline of Medicine, The University of Adelaide; the Rheumatology Unit, The Queen Elizabeth and Royal Adelaide Hospitals, Adelaide, Australia.

Objective: To survey participants with polymyalgia rheumatica (PMR) to evaluate the face validity, acceptability, and domain match of proposed candidate outcome measures.

Methods: A structured, online, anonymous survey was disseminated by patient support groups through their networks and online forums. The candidate outcome measures comprised (1) visual analog scale (VAS) and numerical rating score (NRS) to assess pain; (2) VAS, NRS, and duration to assess stiffness; (3) the modified Health Assessment Questionnaire and Health Assessment Questionnaire Disability Index to assess physical function; and (4) C-reactive protein and erythrocyte sedimentation rate to assess inflammation. Free-text answers were analyzed using descriptive thematic analysis to determine respondents' views of the candidate instruments.

Results: Seventy-eight people with PMR from 6 countries (UK, France, USA, Canada, Australia, and New Zealand) participated in the survey. Most respondents agreed candidate instruments were acceptable or "good to go." Free-text analysis identified 5 themes that participants considered inadequately covered by the proposed instruments. These related to (1) the variability, context, and location of pain; (2) the variability of stiffness; (3) fatigue; (4) disability; and (5) the correlation of inflammatory marker levels and severity of symptoms, sometimes reflecting disease activity and other times not.

Conclusion: Participants reported additional aspects of their experience that are not covered by the proposed instruments, particularly for the experience of stiffness and effect of fatigue. New patient-reported outcome measures are required to increase the relevance of results from clinical trials to patients with PMR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3899/jrheum.190575DOI Listing
September 2020

The need to establish standards of care for Giant Cell Arteritis.

Rheumatology (Oxford) 2020 04;59(4):702-704

Department of Medicine, University College London, London.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/rheumatology/kez548DOI Listing
April 2020

Validating a diagnostic GCA ultrasonography service against temporal artery biopsy and long-term clinical outcomes.

Clin Rheumatol 2020 Apr 1;39(4):1325-1329. Epub 2019 Oct 1.

Department of Ophthalmology, Norfolk and Norwich University Hospital, Norwich, UK.

Currently, there is no mechanism for service validation of diagnostic ultrasonography (US) for giant cell arteritis (GCA). Temporal artery biopsy (TAB) and classification criteria are poor benchmarks. We validated our service against physician-verified diagnosis at 100 weeks (100wD). Twenty-five patients underwent US within 7 days, and TAB within 28 days, of commencing prednisolone. US, TAB and baseline diagnosis (bD) were all compared with 100wD using Cohen's kappa. Fourteen US and 8 TABs were positive. Twenty at baseline and 14 at 100 weeks had diagnosis of GCA. The kappa (95% CI) were 0.4 (0.1, 0.7) for US vs. TAB; 0.5 (0.2, 0.8) for US vs. bD and 0.2 (0.0, 0.4) for TAB vs. bD. Versus 100wD, the kappa (95% CI) were 0.8 (0.6, 1.0) for US; 0.4 (0.1, 0.7) for TAB and 0.6 (0.3, 0.9) for bD. Seven cases were US+/TAB-. Four had alternate confirmation: 18FDG-PET (n = 1), CT Aorta (n = 1) and US at relapse (n = 2). At 100 weeks, 4 cases (all US-/TAB-) with bD of GCA had alternative diagnoses including cancer (n = 2). This is the first study validating US service provision for GCA. Twenty-five US with a robust kappa on comparison with long-term diagnosis validates our service. A diagnosis of GCA should be made with extreme caution for US-/TAB- cases.Key Points• This is the first study offering a way to validate a new diagnostic US service by validation against TAB and long-term physician-verified diagnosis.• US has substantial to near-perfect agreement with long-term physician-verified diagnosis and is more reliable than TAB in our hands.• Alternative diagnoses should be sought in patients with dual negativity for US and TAB.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10067-019-04772-2DOI Listing
April 2020

Development of an evidence-based regimen of prednisolone to treat giant cell arteritis - the Norwich regimen.

Rheumatol Adv Pract 2019 1;3(1):rkz001. Epub 2019 Feb 1.

Department of Ophthalmology, Norfolk and Norwich University Hospital, Norwich, UK.

We have reviewed the literature to form a bespoke regimen for daily oral prednisolone (DP) in GCA. Initial DP in clinical trials is 40-60 mg daily, but relapse rates are 67-92%. Cumulative prednisolone (CP) of 3.2 and 3.9 g (at 6 months) resulted in a relapse rate of 83 and 67%, respectively; and 3 and 3.9 g (at 12 months) resulted in 92 and 82% relapse, respectively. CP was 6.2-7.1 g in the first year. Mean DP was 18.8 mg at 3 months and 6.6-7.4 mg at 12 months. The duration of treatment with prednisolone for GCA was 22-26 months. The CP to achieve discontinuation was 6.5-12.1 g. Using these data, the Norwich regimen starts DP at 1 mg/kg/day of lean body mass, discontinuing over 100 weeks. For the average UK woman, initial DP is 45 mg daily, reaching 21 mg daily by 12 weeks and 6 mg daily by 52 weeks. The CP for the average UK woman would be 6.5 g at 52 weeks and 7.4 g to discontinuation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/rap/rkz001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6649920PMC
February 2019

Iatrogenic antibody deficiency from B-cell targeted therapies in autoimmune rheumatic diseases.

Lupus Sci Med 2019 30;6(1):e000337. Epub 2019 Jul 30.

Pathology, Sidra Medical and Research Center, Doha, Qatar.

B-cell targeted therapies (BCTT) are now widely used in autoimmune rheumatic diseases, including SLE, antineutrophil cytoplasmic antibody-associated vasculitis and rheumatoid arthritis. Early studies suggested that rituximab did not influence serum immunoglobulins. However, subsequently, with increased patient numbers, longer follow-up duration and many patients having received multiple BCTT courses, multiple subsequent studies have identified hypogammaglobulinaemia as a potential side effect. Patients developing hypogammaglobulinaemia appear to fit into two principal categories: the majority who develop transient, often mild reduction in immunoglobulins without increased infection and a much smaller but clinically significant group with a more sustained antibody deficiency, who display increased risk of infection. Monitoring immunoglobulin levels represents an opportunity for the early detection of hypogammaglobulinaemia, and the prevention of avoidable morbidity. In the two major studies, approximately 4%-5% of BCTT-treated patients required immunoglobulin replacement due to recurrent infections in the context of hypogammaglobulinaemia. Despite this, monitoring of immunoglobulins is suboptimal, and there remains a lack of awareness of hypogammaglobulinaemia as an important side effect.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/lupus-2019-000337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6667775PMC
July 2019

Pattern recognition is a sequential process-accurate diagnosis and treatment 20 years after presentation.

Oxf Med Case Reports 2019 Jul 5;2019(7):omz058. Epub 2019 Jul 5.

Rheumatology Department, Norfolk and Norwich University Hospital, Norfolk, UK.

A 25-year-old woman presented with ophthalmic and neurological manifestations. Her ocular manifestations included bilateral uveitis, multifocal retinal phlebitis, vitreitis and multiple retinal haemorrhages. Her neurological manifestations included migrainous headaches with visual aura, transient sensory symptoms and posterior circulation Transient Ischemic Attack (TIA). Magnetic resonance imaging of the brain demonstrated lesions that involved the deep white matter lesions initially and progressed to also involve the juxta cortical white and deep grey matter and brain stem, but without further neurological manifestations. She was sequentially treated with intravenous and oral glucocorticoid, cyclophosphamide and mycophenolate mofetil, but she continued to suffer with persistent episodes of retinal haemorrhages. Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL), Susac syndrome and Behcet's disease were considered in the differential diagnosis. Genetic workup and clinical picture were not suggestive of the former two. Further history of oro-genital ulceration in younger age emerged, which pointed strongly towards a diagnosis of Behcet's disease with neurological involvement. She was treated with infliximab and methotrexate with complete resolution of her symptoms and withdrawal of corticosteroids for the first time in over two decades.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/omcr/omz058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6611498PMC
July 2019

2018 Update of the EULAR recommendations for the management of large vessel vasculitis.

Ann Rheum Dis 2020 01 3;79(1):19-30. Epub 2019 Jul 3.

Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Science (NDORMs), University of Oxford, Oxford, UK.

Background: Since the publication of the European League Against Rheumatism (EULAR) recommendations for the management of large vessel vasculitis (LVV) in 2009, several relevant randomised clinical trials and cohort analyses have been published, which have the potential to change clinical care and therefore supporting the need to update the original recommendations.

Methods: Using EULAR standardised operating procedures for EULAR-endorsed recommendations, the EULAR task force undertook a systematic literature review and sought opinion from 20 experts from 13 countries. We modified existing recommendations and created new recommendations.

Results: Three overarching principles and 10 recommendations were formulated. We recommend that a suspected diagnosis of LVV should be confirmed by imaging or histology. High dose glucocorticoid therapy (40-60 mg/day prednisone-equivalent) should be initiated immediately for induction of remission in active giant cell arteritis (GCA) or Takayasu arteritis (TAK). We recommend adjunctive therapy in selected patients with GCA (refractory or relapsing disease, presence of an increased risk for glucocorticoid-related adverse events or complications) using tocilizumab. Methotrexate may be used as an alternative. Non-biological glucocorticoid-sparing agents should be given in combination with glucocorticoids in all patients with TAK and biological agents may be used in refractory or relapsing patients. We no longer recommend the routine use of antiplatelet or anticoagulant therapy for treatment of LVV unless it is indicated for other reasons.

Conclusions: We have updated the recommendations for the management of LVV to facilitate the translation of current scientific evidence and expert opinion into better management and improved outcome of patients in clinical practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/annrheumdis-2019-215672DOI Listing
January 2020

Immunoglobulin replacement for secondary immunodeficiency after B-cell targeted therapies in autoimmune rheumatic disease: Systematic literature review.

Autoimmun Rev 2019 May 4;18(5):535-541. Epub 2019 Mar 4.

Frimley Health NHS Foundation Trust, Portsmouth Rd, Frimley, UK. Electronic address:

Background: Consensus guidelines are not available for the use of immunoglobulin replacement therapy (IGRT) in patients developing iatrogenic secondary antibody deficiency following B-cell targeted therapy (BCTT) in autoimmune rheumatic disease.

Objectives: To evaluate the role of IGRT to manage hypogammaglobulinemia following BCTT in autoimmune rheumatic disease (AIRD).

Methods: Using an agreed search string we performed a systematic literature search on Medline with Pubmed as vendor. We limited the search to English language papers with abstracts published over the last 10 years. Abstracts were screened for original data regarding hypogammaglobulinemia following BCTT and the use of IGRT for hypogammaglobulinemia following BCTT. We also searched current recommendations from national/international organisations including British Society for Rheumatology, UK Department of Health, American College of Rheumatology, and American Academy of Asthma, Allergy and Immunology.

Results: 222 abstracts were identified. Eight papers had original relevant data that met our search criteria. These studies were largely retrospective cohort studies with small patient numbers receiving IGRT. The literature highlights the induction of a sustained antibody deficiency, risk factors for hypogammaglobulinemia after BCTT including low baseline serum IgG levels, how to monitor patients for the development of hypogammaglobulinemia and the limited evidence available on intervention thresholds for commencing IGRT.

Conclusion: The benefit of BCTT needs to be balanced against the risk of inducing a sustained secondary antibody deficiency. Consensus guidelines would be useful to enable appropriate assessment prior to and following BCTT in preventing and diagnosing hypogammaglobulinemia. Definitions for symptomatic hypogammaglobulinemia, intervention thresholds and treatment targets for IGRT, and its cost-effectiveness are required.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.autrev.2019.03.010DOI Listing
May 2019

Recommendations for the management of secondary hypogammaglobulinaemia due to B cell targeted therapies in autoimmune rheumatic diseases.

Rheumatology (Oxford) 2019 05;58(5):889-896

Department of Pathology, Sidra Medicine, Doha, Qatar.

Objectives: The association of B cell targeted therapies with development of hypogammaglobulinaemia and infection is increasingly recognized. Our aim was to develop consensus recommendations for immunoglobulin replacement therapy for management of hypogammaglobulinaemia following B cell targeted therapies in autoimmune rheumatic diseases.

Methods: A modified Delphi exercise involved a 17-member Taskforce committee, consisting of immunologists, rheumatologists, nephrologists, haematologists, a gastroenterologist, an immunology specialist nurse and a patient representative. The first round identified the most pertinent topics to address in the recommendations. A search string was agreed upon for the identification of publications in PubMed focusing on these areas, for a systematic literature review. Original data was presented from this review to the Taskforce committee. Recommendations from the British Society for Rheumatology, the UK Department of Health, EULAR, the ACR, and the American Academy of Allergy, Asthma, and Immunology were also reviewed. The evidence was discussed in a face-to-face meeting to formulate recommendation statements. The levels of evidence and statements were graded according to Scottish Intercollegiate Guidelines Network methodology.

Results: Three overarching principles, eight recommendation statements and a research agenda were formulated. The Taskforce committee voted on these statements, achieving 82-100% agreement for each recommendation. The strength of the recommendations was restricted by the low quality of the available evidence, with no randomized controlled trial data. The recommendations cover risk factors, monitoring, referral for hypogammaglobulinaemia; indications, dosage and discontinuation of immunoglobulin replacement therapy.

Conclusion: These are the first recommendations specifically formulated for B cell targeted therapies related to hypogammaglobulinaemia in autoimmune rheumatic diseases. The recommendations are to aid health-care professionals with clinical decision making for patients with hypogammaglobulinaemia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/rheumatology/key394DOI Listing
May 2019

Conventional and biological immunosuppressants in vasculitis.

Best Pract Res Clin Rheumatol 2018 02 22;32(1):94-111. Epub 2018 Aug 22.

Norwich Medical School, University of East Anglia, Norwich Research Park, BCRE Floor 2, NR4 7UQ, UK. Electronic address:

The following chapter outlines the main findings from clinical trials, which provide information on the current best evidence-based management of the myriad of conditions that comprise vasculitis. Glucocorticoids (GCs) have been the mainstay of treatment of large-vessel vasculitis since Birkhead et al. used intramuscular cortisone daily and obtained good results in patients with giant cell arteritis. Recent trial data offer the hope that future treatment regimens may not need to be quite reliant on steroids. The use of GCs remains central to the management of many of the vasculitides, but recent advances owing to well run and coordinated clinical trials are changing the management approach. The strategy of aggressive induction of remission followed by a period of maintenance therapy has been established for patients with anti-neutrophil cytoplasm antibody-associated vasculitis. It remains unclear whether prediction can be made regarding which presentations or phenotypes should be treated with which drug regimen and when patients are likely to relapse. Currently, maintenance therapy is indicated for 2 years but whether there can be better tailored strategies remains to be proven. This chapter focuses on the main types of vasculitis, describing first the evidence for conventional immunosuppressants and then evidence for the use of biologics. Non-pharmacologic approaches are discussed in the next chapter.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.berh.2018.07.006DOI Listing
February 2018

Assessing Vasculitis in Giant Cell Arteritis by Ultrasound: Results of OMERACT Patient-based Reliability Exercises.

J Rheumatol 2018 08 1;45(9):1289-1295. Epub 2018 Jul 1.

From the University Hospital Bonn III, Medical Clinic, Department of Oncology, Hematology and Rheumatology, Bonn; Immanuel Krankenhaus Berlin, Medical Center for Rheumatology Berlin-Buch, Berlin; Asklepios Medical Center, Bad Abbach, Germany; Hospital of Southwest Denmark, Esbjerg; Diagnostic Centre Region Hospital Silkeborg, Silkeborg; Odense University Hospital, Odense; Copenhagen Center for Arthritis Research (COPECARE), Glostrup, Denmark; Medical University Graz, Graz; Medical University Innsbruck, Innsbruck, Austria; Hospital of Bruneck, Bruneck; Università degli Studi di Torino, Turin; Epidemiology Unit - Italian Society for Rheumatology (SIR), Milan; Arcispedale Santa Maria Nuova, Reggio Emilia; University of Ferrara, Italy; MC Groep Hospitals, Lelystad; Leiden University Medical Center, the Netherlands; Hôpital Ambroise Paré, Boulogne-Billancourt, France; University Hospital La Paz, Madrid, Spain; Martina Hansens Hospital, Bærum, Oslo, Norway; University Medical Centre Ljubljana, Ljubljana, Slovenia; University of California at Los Angeles, Los Angeles, California; Mayo Clinic, Rochester, Minnesota, USA; Pomeranian Medical University, Szczecin, Poland; Norfolk and Norwich University Hospital, Norwich; Southend University Hospital, UK National Health Service (NHS) Foundation Trust and Anglia Ruskin University, Westcliff, UK; Rheumatology Research Unit, Instituto de Medicina Molecular, Faculty of Medicine, University of Lisbon; Rheumatology Department, Hospital de Santa Maria - CHLN, Lisbon, Portugal.

Objective: To test the reliability of Outcome Measures in Rheumatology Clinical Trials (OMERACT) consensus-based ultrasound definitions for normal and vasculitic temporal and axillary arteries in patients with giant cell arteritis (GCA) and in controls.

Methods: A preliminary 1-day meeting and a full 3-day meeting fulfilling OMERACT Ultrasound Group guidelines were held. Temporal and axillary arteries were examined at 2 timepoints by 12 sonographers on 4 patients with GCA and 2 controls. The aim was to test inter- and intrareader reliability for normal findings, halo sign, and compression sign. In both meetings, patients had established GCA. Pathology was more recent in the full meeting, which was preceded by 6 h of training. Scanning time was 15-20 min instead of 10-13 min.

Results: In the preliminary exercise, interreader reliabilities were fair to moderate for the overall diagnosis of GCA (Light κ 0.29-0.51), and poor to fair for identifying vasculitis in the respective anatomical segments (Light κ 0.02-0.46). Intrareader reliabilities were moderate (Cohen κ 0.32-0.64). In the main exercise, interreader reliability was good to excellent (Light κ 0.76-0.86) for the overall diagnosis of GCA, and moderate to good (Light κ 0.46-0.71) for identifying vasculitis in the respective anatomical segments. Intrareader reliability was excellent for diagnosis of GCA (Cohen κ 0.91) and good (Cohen κ 0.71-0.80) for the anatomical segments.

Conclusion: OMERACT-derived definitions of halo and compression signs of temporal and axillary arteries are reliable in recent-onset GCA if experienced sonographers (> 300 examinations) have 15-20 min for a standardized examination with prior training and apply > 15 MHz probes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3899/jrheum.171428DOI Listing
August 2018

Definitions and reliability assessment of elementary ultrasound lesions in giant cell arteritis: a study from the OMERACT Large Vessel Vasculitis Ultrasound Working Group.

RMD Open 2018 17;4(1):e000598. Epub 2018 May 17.

Medical Centre for Rheumatology, Immanuel Krankenhaus Berlin, Berlin, Germany.

Objectives: To define the elementary ultrasound (US) lesions in giant cell arteritis (GCA) and to evaluate the reliability of the assessment of US lesions according to these definitions in a web-based reliability exercise.

Methods: Potential definitions of normal and abnormal US findings of temporal and extracranial large arteries were retrieved by a systematic literature review. As a subsequent step, a structured Delphi exercise was conducted involving an expert panel of the Outcome Measures in Rheumatology (OMERACT) US Large Vessel Vasculitis Group to agree definitions of normal US appearance and key elementary US lesions of vasculitis of temporal and extracranial large arteries. The reliability of these definitions on normal and abnormal blood vessels was tested on 150 still images and videos in a web-based reliability exercise.

Results: Twenty-four experts participated in both Delphi rounds. From originally 25 statements, nine definitions were obtained for normal appearance, vasculitis and arteriosclerosis of cranial and extracranial vessels. The 'halo' and 'compression' signs were the key US lesions in GCA. The reliability of the definitions for normal temporal and axillary arteries, the 'halo' sign and the 'compression' sign was excellent with inter-rater agreements of 91-99% and mean kappa values of 0.83-0.98 for both inter-rater and intra-rater reliabilities of all 25 experts.

Conclusions: The 'halo' and the 'compression' signs are regarded as the most important US abnormalities for GCA. The inter-rater and intra-rater agreement of the new OMERACT definitions for US lesions in GCA was excellent.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/rmdopen-2017-000598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5976098PMC
May 2018

Why subcutaneous methotrexate should be a prerequisite to biologic use in patients with rheumatoid arthritis.

Rheumatology (Oxford) 2019 04;58(4):559-560

Rheumatology Department, Norfolk and Norwich University Hospital, Norwich, UK.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/rheumatology/key097DOI Listing
April 2019

Are PR3 positive and MPO positive GPA the same disease?

Int J Rheum Dis 2019 Jan 3;22 Suppl 1:86-89. Epub 2018 Apr 3.

Department of Rheumatology, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, UK.

Granulomatosis with Polyangiitis is a necrotising systemic vasculitis predominantly affecting small and medium sized vessels. It is predominantly associated with antibodies directed against proteinase 3, but a small number of individuals with this disease have antibodies directed against myeloperoxidase. The premise of this paper is to explore the possibility that these two serotypes maybe two separate diseases. There is evidence that the same single nucleotide polymorphisms in the TLR 9 gene is associated with increased risk for PR3 ANCA positivity but protects against MPO ANCA positivity. There is some evidence that MPO ANCA positive GPA disease may be 'limited' in its expression and be associated with the more indolent phenotype. The genotype may affect the serotype, and the serotype might affect the phenotype. There has been limited success in identifying how the difference in phenotype might affect outcomes. We are at a very early stage in our understanding of how these serotypes might be treated differently. This paper attempts to critically appraise the evidence available so far.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1756-185X.13278DOI Listing
January 2019

Validation of the EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis by disease content experts.

RMD Open 2017 15;3(1):e000449. Epub 2017 Jun 15.

Department of Rheumatology, Norfolk and Norwich University Hospital, Norwich, UK.

The European League Against Rheumatism recommendations for the management of antineutrophil cytoplasmic antibody-associated vasculitis have been recently published. Unique to recommendation development, they were also voted on by members of a learned society. This paper explores the wider validity of the recommendations among people who self-identify as clinicians caring for patients with vasculitis. In addition to the task force, a learned society (European Vasculitis Society-EUVAS) was invited, through online survey, to rate independently the strength of evidence of each recommendation to obtain an indication of the agreement among the final target audience and ultimate end-users of the recommendations. The survey took place in June 2015. Of the 158 EUVAS members surveyed, there were 88 responses (55.7%). There was a large degree of agreement in the voting patterns between EUVAS survey participants and task force members. Notable exceptions were lower grades for the recommendation of the use of rituximab for remission induction in patients with eosinophilic granulomatosis with polyangiitis and for methotrexate and mycophenolate mofetil as remission maintenance agents in patients with granulomatosis with polyangiitis/microscopic polyangiitis by EUVAS members. These results are encouraging and suggest that the voting patterns of the task force are representative of the wider vasculitis community. We recommend future recommendations adopt this approach for data/expert-based treatment guidelines, especially for multisystem diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/rmdopen-2017-000449DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5604609PMC
June 2017