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Environmental factors amplified by climate change contribute significantly to the global burden of disease, disproportionately impacting vulnerable populations, such as individuals with rare diseases. Researchers require innovative, dynamic data linkage methods to enable the development of risk prediction models, particularly for diseases like vasculitis with unknown aetiology but potential environmental triggers. In response, we present the Semantic Environmental and Rare Disease Data Integration Framework (SERDIF). SERDIF was evaluated with researchers studying climate-related health hazards of vasculitis disease activity across European countries (NP1 = 10, NP2 = 17, NP3 = 23). Usability metrics consistently improved, indicating SERDIF's effectiveness in linking complex environmental and health datasets. Furthermore, SERDIF-enabled epidemiologists to study environmental factors in a pregnancy cohort in Lombardy, showcasing its versatility beyond rare diseases. This framework offers for the first time a user-friendly, FAIR-compliant design for environment-health data linkage with export capabilities enabling data analysis to mitigate health risks posed by climate change. [ABSTRACT FROM AUTHOR]

Background: Sequential B cell-targeted immunotherapy with BAFF antagonism (belimumab) and B cell depletion (rituximab) may enhance B cell targeting in ANCA-associated vasculitis (AAV) through several mechanisms. Methods: Study design: COMBIVAS is a randomised, double-blind, placebo-controlled trial designed to assess the mechanistic effects of sequential therapy of belimumab and rituximab in patients with active PR3 AAV. The recruitment target is 30 patients who meet the criteria for inclusion in the per-protocol analysis. Thirty-six participants have been randomised to one of the two treatment groups in a 1:1 ratio: either rituximab plus belimumab or rituximab plus placebo (both groups with the same tapering corticosteroid regimen), and recruitment is now closed (final patient enrolled April 2021). For each patient, the trial will last for 2 years comprising a 12-month treatment period followed by a 12-month follow-up period. Participants: Participants have been recruited from five of seven UK trial sites. Eligibility criteria were age ≥ 18 years and a diagnosis of AAV with active disease (newly diagnosed or relapsing disease), along with a concurrent positive test for PR3 ANCA by ELISA. Interventions: Rituximab 1000 mg was administered by intravenous infusions on day 8 and day 22. Weekly subcutaneous injections of 200 mg belimumab or placebo were initiated a week before rituximab on day 1 and then weekly through to week 51. All participants received a relatively low prednisolone (20 mg/day) starting dose from day 1 followed by a protocol-specified corticosteroid taper aiming for complete cessation by 3 months. Outcomes: The primary endpoint of this study is time to PR3 ANCA negativity. Key secondary outcomes include change from baseline in naïve, transitional, memory, plasmablast B cell subsets (by flow cytometry) in the blood at months 3, 12, 18 and 24; time to clinical remission; time to relapse; and incidence of serious adverse events. Exploratory biomarker assessments include assessment of B cell receptor clonality, B cell and T cell functional assays, whole blood transcriptomic analysis and urinary lymphocyte and proteomic analysis. Inguinal lymph node and nasal mucosal biopsies have been performed on a subgroup of patients at baseline and month 3. Discussion: This experimental medicine study provides a unique opportunity to gain detailed insights into the immunological mechanisms of belimumab-rituximab sequential therapy across multiple body compartments in the setting of AAV. Trial registration: ClinicalTrials.gov NCT03967925. Registered on May 30, 2019. [ABSTRACT FROM AUTHOR]

Objectives: To assess self-reported symptoms of neuropathy, disability, pain, health-related quality of life (HR-QOL) and autonomic dysfunction in patients with vasculitis., Methods: Patients with vasculitis (with or without neuropathy) were invited by Vasculitis UK to complete an anonymous online survey., Results: Three hundred and twelve patients (71% female) responded. Median age was 61-70 years. Median duration of vasculitis was 4 years (<2 months to >15 years). Vasculitic types included granulomatosis with polyangiitis (34%), unspecified ANCA-associated vasculitis (13%), microscopic polyangiitis (11%), eosinophilic granulomatosis with polyangiitis (11%), giant cell arteritis (10%), non-systemic vasculitic neuropathy (2%) and other (19%). Many patients reported foot/hand symptoms suggestive of neuropathy, including numbness (64%), pain (54%) or weakness (40%). Two hundred and forty-two patients (78%) met our definition of probable vasculitic neuropathy: diagnosis of neuropathy by vasculitis team OR numbness OR weakness in feet/hands. Only 52% had been formally diagnosed with neuropathy. Compared with 70 patients without neuropathy, neuropathy patients had greater disability measured by the inflammatory Rasch-built Overall Disability Scale (centile mean 63.1 [s.d. 17.3] vs 75.2 [16.7]; P < 0.0001), Inflammatory Neuropathy Cause and Treatment scale (median 2 [interquartile range 1-4] vs 0.5 [0-2]; P < 0.0001) and modified Rankin scale (median 2 [interquartile range 1-3] vs 2 [1-2)]; P = 0.0002); greater pain on an 11-point rating scale (mean 4.6 [s.d. 2.6] vs 3.5 [2.8]; P = 0.0009); and poorer HR-QOL on the EQ5D-3L (summary index mean 0.58 [s.d. 0.29] vs 0.69 [0.28]; P < 0.0001). Two-thirds reported autonomic symptoms (not associated with neuropathy)., Conclusion: Neuropathy is common and associated with significant disability, pain and impaired HR-QOL in patients with systemic vasculitis., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Biospectroscopy offers the ability to simultaneously identify key biochemical changes in tissue associated with a given pathological state to facilitate biomarker extraction and automated detection of key lesions. Herein, we evaluated the application of machine learning in conjunction with Raman spectroscopy as an innovative low-cost technique for the automated computational detection of disease activity in anti-neutrophil cytoplasmic autoantibody (ANCA)-associated glomerulonephritis (AAGN). Consecutive patients with active AAGN and those in disease remission were recruited from a single UK centre. In those with active disease, renal biopsy samples were collected together with a paired urine sample. Urine samples were collected immediately prior to biopsy. Amongst those in remission at the time of recruitment, archived renal tissue samples representative of biopsies taken during an active disease period were obtained. In total, twenty-eight tissue samples were included in the analysis. Following supervised classification according to recorded histological data, spectral data from unstained tissue samples were able to discriminate disease activity with a high degree of accuracy on blind predictive modelling: F-score 95% for >25% interstitial fibrosis and tubular atrophy (sensitivity 100%, specificity 90%, area under ROC 0.98), 100% for necrotising glomerular lesions (sensitivity 100%, specificity 100%, area under ROC 1) and 100% for interstitial infiltrate (sensitivity 100%, specificity 100%, area under ROC 0.97). Corresponding spectrochemical changes in paired urine samples were limited. Future larger study is required, inclusive of assigned variables according to novel non-invasive biomarkers as well as the application of forward feature extraction algorithms to predict clinical outcomes based on spectral features. [ABSTRACT FROM AUTHOR]

The use of rituximab (MabThera®), an anti-CD20 monoclonal antibody, is the most significant development in the management of anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) since the introduction of cytotoxic therapy in 1950. Truxima® is the first anti-CD20 biosimilar approved for the same indications, and has been available in the UK since 2017. Significant cost savings have been reported when switching to biosimilars, which could lead to greater patient access to such treatment. Therefore, it is important to know whether patients' clinical and laboratory parameters respond equally well to biosimilars as to reference medicines, tested in clinical trials. We retrospectively reviewed the clinical outcomes and laboratory parameters in 257 consecutive patients treated with anti-CD20 depletion therapy using MabThera or Truxima, for induction and maintenance of remission, in two tertiary renal centres between 2010 and 2019. We demonstrated no difference between patients treated with MabThera or Truxima in rates of remission, relapse, and hospitalization with infection when used for either induction or maintenance of remission of AAV. In one hospital subgroup analysis, we showed comparable levels of hypogammaglobulinaemia, B-cell depletion, and frequency of infusion reactions, with no significant differences. The efficacy and safety of the rituximab biosimilar Truxima are not inferior to the originator MabThera in patients with AAV. Truxima represents a cheaper and safe therapeutic alternative that could increase patient access to rituximab. [ABSTRACT FROM AUTHOR]

Objective To investigate the occurrence of venous thromboembolic events (VTE) in a large cohort of patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) across the European Union, Turkey, Russia, UK and North America. Methods Patients with a definite diagnosis of AAV who were followed for at least 3 months and had sufficient documentation were included. Data on VTE, including either deep vein thrombosis or pulmonary embolism, were collected retrospectively from tertiary vasculitis centres. Univariate and multivariate regression models were used to estimate odds ratios (ORs) and 95% CIs. Results Over a median follow-up of 63 (interquartile range: 29, 101) months, VTE occurred in 278 (9.7%) of 2869 AAV patients with a similar frequency across different countries (from 6.3% to 13.7%), and AAV subtype [granulomatosis with polyangiitis: 9.8% (95% CI: 8.3, 11.6%); microscopic polyangiitis: 9.6% (95% CI: 7.9, 11.4%); and eosinophilic granulomatosis with polyangiitis: 9.8% (95% CI: 7.0, 13.3%)]. Most VTE (65.6%) were reported in the first-year post-diagnosis. Multiple factor logistic regression analysis adjusted for sex and age showed that skin (OR 1.71, 95% CI: 1.01, 2.92), pulmonary (OR 1.78, 95% CI: 1.04, 3.14) and kidney [eGFR 15–60 ml/min/1.73 m2, OR 2.86 (95% CI: 1.27, 6.47); eGFR <15 ml/min/1.73 m2, OR 6.71 (95% CI: 2.94, 15.33)] involvement were independent variables associated with a higher occurrence of VTE. Conclusion Two-thirds of VTE occurred during the initial phase of active disease. We confirmed previous findings from smaller studies that a decrease in kidney function, skin involvement and pulmonary disease are independently associated with VTE. [ABSTRACT FROM AUTHOR]

The Burden of Wounds Study estimated the cost of wound care across the UK to be £5.3 billion, with £3 billion associated with hard-to-heal wounds. This article looks at potential cost savings of managing hard-to-heal leg ulcers in a specialist wound care service using a multidisciplinary team (MDT) approach. This unique approach includes: a consultant dermatologist; a podiatrist specialising in mobility and gait; a clinical psychologist; clinical nurse specialists; and allied health professionals from tissue viability and lymphoedema services. Bringing together specialists from supporting disciplines provides a one-stop service for the patient. We conducted a retrospective analysis (over 365 days) of wound healing in patients attending the service for management of leg ulcers with differing aetiologies, including venous and atypical leg ulceration. Many of the patients referred to the service had a long wound history, between two and nine years, with a duration up to 25 years in the most complex cases. Within this complex cohort of patients, higher levels of focused compression was required (Accelerate Strapping, Accelerate, UK) for retromalleolar ulceration and management of foot oedema needing toe bandaging or garments. Wound healing was achieved in 72% of patients across all wound aetiologies, demonstrating the impact that a specialist MDT team can have on positive healing outcomes, and which can result in cost savings to the health economy and an improved quality of life for the patient. [ABSTRACT FROM AUTHOR]

Objective ANCA-associated vasculitis (AAV) is a small vessel vasculitis that commonly presents in the elderly. However, there are few long-term outcome data for these patients. Here, we assessed long-term outcomes in a single-centre cohort of elderly patients with AAV. Additionally, we tested whether a pre-morbid frailty score could aid prognosis. Methods Using a prospectively-compiled dataset, we investigated patients over the age of 65 who presented with AAV between 2005 and 2017 to a regional vasculitis centre. We used a Cox model to determine the factors associated with mortality. We also compared outcomes in pre-specified subgroups stratified by baseline frailty score, ANCA serotype and induction immunosuppression (with cyclophosphamide, rituximab or mycophenolate mofetil used as the main glucocorticoid-sparing agent). Results 83 patients were included in the study and were followed for a median of 1203 days. Median age was 74 years (range 65–92). Two- and five-year survival in the overall cohort were 83% (95% CI 75, 92%) and 75% (95% CI 65, 86%), respectively. The median cumulative dose of oral prednisolone was 2030 mg during the first three months. Only one patient received intravenous glucocorticoids. Age, frailty score and CRP at presentation were independently associated with mortality; all deaths occurred in patients aged over 75 at presentation. Patients treated with a cyclophosphamide-based induction regimen tended to be younger than those treated with rituximab or mycophenolate mofetil. Survival was better in the cyclophosphamide-treated group. Conclusion In the contemporary era, the overall prognosis of AAV in elderly patients is good. Baseline frailty associates with disease outcomes including mortality. A low-dose glucocorticoid regimen (avoiding intravenous methylprednisolone) can be used to treat AAV effectively in elderly patients. [ABSTRACT FROM AUTHOR]

The article presents highlights from this issue of the publisher. Topics include information on Systemic lupus erythematosus and its response to Rituximab, durable treatment for Antineutrophilic cytoplasmic antibody associated vasculitis, and earlier recognition of immune checkpoint inhibitors induced inflammatory arthritis.

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. To evaluate the role of IGRT to manage hypogammaglobulinemia following BCTT in autoimmune rheumatic disease (AIRD). 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. 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. 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. • Immunoglobulin replacement therapy for secondary hypogammaglobulinemia is increasing in autoimmune rheumatic disease. • We review the currently available literature surrounding hypogammaglobulinemia after B-cell targeted therapy in AIRD. • Consensus guidelines are needed for appropriate assessment to prevent, diagnose and to treat hypogammaglobulinemia in AIRD. [ABSTRACT FROM AUTHOR]

Objectives. To evaluate the associations between granulomatosis with polyangiitis (GPA) and a wide range of comorbidities in patients with GPA compared with population-based non-vasculitis patients. Methods. Using the UK-based Clinical Practice Research Datalink we identified 570 incident patients with GPA in 1990-2014, and for each case, we selected up to 10 random non-vasculitis patients matched for age, sex, practice and years of history before the date of first GPA diagnosis. We compared the distribution of 13 pre-existing comorbidities and estimated the risk of each incident comorbidity after the cohort entry between GPA and non-vasculitis patients. Results. Patients with GPA were more likely to have a history of hypothyroidism at their initial diagnosis compared with non-vasculitis patients. Patients with GPA had increased risk of incident venous thrombo-embolism any time during follow-up compared with non-vasculitis patients, particularly during the first 3 years of follow-up: hazard ratio (HR) of 5.24 (95% CI: 2.83, 9.71). Risks were also increased for hyper- tension (HR= 2.45, 95% CI: 1.84, 3.26), type 2 diabetes (HR= 2.13, 95% CI: 1.36, 3.32), dyslipidaemia (HR= 1.98, 95% CI: 1.29, 3.04) and depression (HR= 1.77, 95% CI: 1.10, 2.86) among GPA patients during the first 3 years of follow-up, but not after 3 years post-diagnosis. Conclusion. Patients with GPA had a higher prevalence of hypothyroidism before the initial diagnosis, a strong risk of developing venous thromboembolism during follow-up and increased risks of hypertension, dyslipidaemia, type 2 diabetes and depression in the first few years after diagnosis, compared with non-vasculitis population. [ABSTRACT FROM AUTHOR]

Objective. To evaluate the associations between GCA and vascular diseases and other comorbidities in patients with GCA compared with non-vasculitis patients. Methods. Using the UK-based Clinical Practice Research Datalink we identified 9778 newly diagnosed GCA patients in 1990-2014, and up to 10 non-vasculitis patients randomly matched to each case on age, sex, practice and years of history before cohort entry. We compared the distributions of 9 different preexisting vascular diseases and 11 other comorbidities, and risks of incident vascular diseases and other comorbidities after cohort entry between GCA and non-vasculitis patients. Results. Patients with GCA were more likely to have a history of vascular diseases and other comorbidities except myocardial infarction, type 2 diabetes, obesity and cancer, compared with non-vasculitis patients. Patients with GCA had increased risks for all types of incident vascular disease compared with non-vasculitis patients: adjusted hazard ratios were 1.57 (95% CI: 1.36, 1.82) for myocardial infarc-tion, 1.41 (95% CI: 1.29, 1.55) for stroke, 1.75 (95% CI: 1.49, 2.06) for peripheral vascular disease, 1.98 (95% CI: 1.50, 2.62) for aortic aneurysm and 2.03 (95% CI: 1.77, 2.33) for venous thromboembolism. Patients with GCA also had increased risks for other incident comorbidities (type 2 diabetes, depression, etc.), but not for cancer. Conclusion. Patients with GCA had more prior vascular diseases and other comorbidities before the diagnosis and they also had increased risks for incident vascular diseases and many other incident comorbidities after the diagnosis compared with non-vasculitis population. [ABSTRACT FROM AUTHOR]

Objective. To study the outcome of pregnancy in patients with systemic vasculitis (SV) compared with age-, BMI- and ethnicity-matched healthy pregnant controls. Methods. Fifty-one pregnancies in 29 SV patients were retrospectively studied. There were nine patients with granulomatosis with polyangiitis (GPA), three with eosinophilic GPA, seven with Takayasu's arteritis, two with ANCA-positive vasculitis with renal involvement, two with Behcet's disease, three with urticarial vasculitis, one with primary cerebral vasculitis, one with relapsing polychondritis and one with IgA vasculitis. BVAS and the vasculitis damage index were evaluated retrospectively. Sixty-two healthy women with 156 pregnancies matched in a 2:1 ratio for age, BMI and ethnicity formed the control group. Results. Median gestational age at delivery was lower in the SV group: 36 weeks and 2 days (34-42) vs controls 40 (37-42) weeks (P<0.03). Median birth weight in the SV group was 3.0 kg (2.0-5.2), whereas that of the controls was 3.5 (2.28-4.32) kg (P = 0.004). The median customized birth weight centile was 38.6 in the SV group and 37.2 in the control group. In the SV group, 9 patients had 13 miscarriages, 3 had pre-eclampsia, and 2 had an intrauterine death. In the control group, 20 patients had 27 miscarriages, 1 had pre-eclamptic toxaemia, and 1 had an antepartum haemorrhage. Eight patients with SV flared during pregnancy and 11 flared after delivery. Conclusion. Patients with SV had a lower median gestational age, but customized birth weights were similar to those of healthy women. Women with SV may flare during pregnancy and the post-partum period and may experience significant pregnancy morbidity. [ABSTRACT FROM AUTHOR]

Objective. Necrotizing and crescentic GN usually presents with rapidly declining renal function, often in association with multisystem autoimmune disease, with a poor outcome if left untreated. We aimed to describe the features of patients who have presented with these histopathological findings but minimal disturbance of renal function. Methods. We conducted a retrospective review (1995–2011) of all adult patients with native renal biopsy–proven necrotizing or crescentic GN and normal serum creatinine (<120 μmol/l) at our centre. Results. Thirty-eight patients were identified. The median creatinine at presentation was 84 μmol/l and the median proportion of glomeruli affected by necrosis or crescents was 32%. Clinicopathological diagnoses were ANCA-associated GN (74%), LN (18%), anti-GBM disease (5%) and HScP (3%). Only 18% of cases had pre-existing diagnoses of underlying multisystem autoimmune disease, although the majority (89%) had extra-renal manifestations accompanying the renal diagnosis. All patients received immunosuppression and most had good long-term renal outcomes (median duration of follow-up 50 months), although two progressed to end-stage renal disease within 3 years. We estimate that renal biopsy had an important influence on treatment decisions in 82% of cases. Conclusion. Necrotizing and crescentic GN may present in patients with no or only minor disturbance of renal function. This often occurs in patients with underlying systemic autoimmune disease; early referral for biopsy may affect management and improve long-term outcomes in these cases. [ABSTRACT FROM AUTHOR]

Abstracts of poster presentations during the 2014 annual conference of British Society of Paediatric and Adolescent Rheumatology are presented including "Standardized Mortality Rates are Increased in Patients with Severe JIA" by Rebecca Davies et al, "Certical-Spine Involvement in JIA: A Single-Centre Study" by Kamran Mahmood and "Clinical and Radiological Features of Down's Arthropathy" by Charlene Foley et al.

The article presents abstracts of studies on vasculitis which include the utility of fluoro-deoxy-glucose positron emission tomography in large vessel vasculitis, the management of giant cell arteritis and the clinical features of paediatric Takayasu's arteritis.

Objective. The aim of this study was to investigate the neurophysiological effects of fatigue among patients with granulomatosis with polyangiitis (GPA).Methods. A case–control functional MRI (fMRI) study was conducted. Stable GPA subjects were recruited according to fatigue status, with those reporting fatigue defined as cases and those not defined as controls. In addition, a control group of general population subjects with idiopathic fatigue were studied. During fMRI, all participants performed a fatigue-inducing cognitive task. Functional data were acquired with a 3 T MRI scanner during periods of task activity and rest. Analyses of the differences in blood oxygen level dependent (BOLD) signal were then performed using SPM8 software and comparisons were made between case and control groups.Results. GPA cases (n = 12) were demographically matched to GPA controls (n = 14) and were clinically similar apart from the higher reporting of fatigue, by design, and depressive symptoms (P = 0.0007). After adjusting for depressive symptoms, comparison of BOLD signals revealed significantly greater activation in the right thalamus, left paracentral lobule, left medial frontal gyrus and right medial globus pallidus among GPA cases. When compared with the similarly fatigued population control group (n = 13), GPA cases shared many overlapping areas of activation. However, in addition, the population control group revealed significantly greater activation elsewhere, principally the left precentral gyrus, right superior frontal gyrus and right cingulate gyrus.Conclusion. fMRI has identified specific differences in the neurophysiology of fatigued GPA subjects. Future application of this promising biomarker may inform the precise mechanisms of this clinically important symptom. [ABSTRACT FROM PUBLISHER]

Objectives. Systemic rheumatoid vasculitis (SRV) is a rare but potentially serious systemic disease manifestation of rheumatoid arthritis (RA) characterized by the development of necrotizing vasculitis. The incidence of SRV appears to be decreasing possibly reflecting progress in RA treatment. The aims of this study were to review the clinical manifestations of SRV in a stable well-defined population during 2001–10 and to compare with our previous cohort (1988–2000) and also a cohort from 1975 to 1981.Methods. Using Norfolk Vasculitis Register, a prospective register of patients with systemic vasculitis since 1988, all patients with a diagnosis of SRV from 1 January 2001 until 31 December 2010 were identified. SRV was defined according to the Scott and Bacon criteria (1984). Clinical features were obtained by retrospective case note review.Results. Eighteen patients with SRV were identified (10 male), median age at diagnosis was 72 years and average disease duration 15.6 years. The average annual incidence for 2001–10 was 3.9 per million. One-year mortality was 12% and 5-year mortality 60%. The clinical manifestations were similar apart from systemic and cutaneous features which were more common in the earlier cohorts.Conclusion. The incidence of SRV has declined significantly in the last 40 years; but the clinical manifestations remain similar. Systemic symptoms, and cutaneous manifestations such as infarcts and nodules, are slightly less common in the recent cohort. Despite modern immunosuppressive therapy the prognosis remains poor. [ABSTRACT FROM PUBLISHER]

Objectives. To define the clinical, serological, histological and immunogenetic features of patients with scleroderma and ANCA-associated vasculitis (AAV).Methods. We examined a clinical database of 2200 patients with either limited or diffuse cutaneous systemic sclerosis (SSc). Patients with a confirmed diagnosis of vasculitis who were ANCA positive with either MPO or PR3 reactivity had their clinical features, serology, histology and HLA haplotypes examined in detail.Results. From this SSc cohort, 35 patients (1.6%) had evidence of vasculitis, and the SSc autoantibody profiles in this group were comparable to those previously published from the whole cohort. Of these 35 patients, 8 (0.4% of whole SSc cohort) had either anti-MPO or anti-PR3 antibodies and two further patients were ANCA positive without defined specificities. Of the eight ANCA-positive patients, seven had limited cutaneous SSc and anti-MPO antibodies and only one had anti-PR3 antibodies, associated with diffuse cutaneous SSc. Two ANCA-positive patients had anti-U3RNP antibodies, usually associated with overlap disease. None of the patients had granulomatous disease. The majority had glomerulonephritis, renal arteritis and pulmonary fibrosis. There were several shared HLA haplotypes from the DP and DQ loci in these overlap patients.Conclusion. SSc in overlap with ANCA-associated vasculitis is rare, and clinical features are more mixed than when either of these two conditions occurs separately. From our database, U3RNP antibodies may be more associated with overlap AAV than the other scleroderma-specific antibodies. [ABSTRACT FROM AUTHOR]

Objectives. To identify the determinants of fatigue among patients with ANCA-associated vasculitis (AAV).Methods. A multicentre cross-sectional study was conducted. Subjects fulfilling the European Medicines Agency criteria for granulomatosis with polyangiitis (Wegener’s), microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis (Churg–Strauss) were approached according to consecutive clinic attendance and invited to complete a questionnaire assessing fatigue and putative biopsychosocial determinants of this symptom. Concurrently, potential clinical determinants were recorded. Independent associations of fatigue were identified using forward stepwise logistic regression modelling and their overall impact expressed as population attributable risk (PAR).Results. The majority (74.8%) of participants (n = 410) reported high levels of fatigue that were found to be significantly associated with numerous biopsychosocial and clinical factors. Sleep disturbance [odds ratio (OR) 5.3, 95% CI 2.7, 10.5] and pain (OR 3.8, 95% CI 2.0, 7.3) were the strongest independent associations of fatigue and, on a population level, each was more than twice as important as any other putative determinant (PAR 18.1% and 16.5%, respectively). Female gender (OR 2.1, 95% 1.1, 4.0), elevated CRP (OR 3.7, 95% CI 1.7, 8.1) and the dysfunctional coping strategies of behavioural disengagement (OR 2.4, 95% CI 1.04, 5.6) and denial (OR 2.4, 95% CI 0.9, 6.7) were also independently associated with fatigue.Conclusion. The data suggest that AAV-related fatigue is multifactorial in origin. Sleep disturbance and pain were found to be most important, although inflammation, as measured by CRP, was also associated. This study has identified potentially modifiable determinants that will inform future interventions aimed at alleviating fatigue. [ABSTRACT FROM AUTHOR]

Objective: A common population sampling frame in countries with universal health care is health service registers. We have evaluated the use of such a register, in the United Kingdom, against a commercially available database claiming large population coverage, an alternative that offers ease of access and flexibility of use. Study Design and Setting: A case--control study of vasculitis, which recruited cases from secondary care clinics in Scotland, compared two alternative sampling frames for population controls, namely the registers of National Health Service (NHS) primary care practices and a commercially available database. The characteristics of controls recruited from both sources were compared in addition to separate case--control comparison using logistic regression. Results: A total of 166 of 189 cases participated (88% participation rate), while both the commercial database and NHS Central Register (NHSCR) controls achieved a participation rate of 24% among persons assumed to have received the invitation. On several measures, the NHSCR patients reported poorer health than the commercial database controls: low scores on the physical component score of the Short Form 36 (odds ratio [OR]: 2.3; 95% confidence interval [CI]: 1.3--4.1), chronic widespread pain (OR: 2.3; CI: 1.1--4.7), and high levels of fatigue (OR: 2.0; CI: 1.3--3.1). These had an important influence on the estimates of association with case status with one association (pain) showing a strong and significant association using commercial database controls, which was absent with NHSCR controls. Conclusion: There are important differences in self-reported measures of health and quality of life using controls from two alternative population sampling frames. It emphasizes the importance of methodological rigor and prior assessment in choosing sampling frames for case--control studies. [ABSTRACT FROM AUTHOR]

Background: Antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis and systemic vasculitis (AAGNV) is uncommon in childhood. Methods: This is a retrospective study of AAGNV cases diagnosed over a 13-year period in a tertiary pediatric nephrology department. Results: Thirteen cases of AAGNV were identified: seven Wegener granulomatosis (WG) and six microscopic polyangiitis (MPA). Acute renal failure/nephrotic range proteinuria (NRP) was found in 77 % of the patients (4 with WG, all with MPA). Eleven (85 %) patients showed necrotizing glomerulonephritis (NGN), with ≥50 % crescents identified in nine patients (69 %) (4 with WG, 5 with MPA). Treatment with methylprednisolone, cyclophosphamide and plasma exchange resulted in extra-renal remission and antibody reduction in all patients and renal function improvement/stabilization in 77 % of the patients. Three patients, all without oliguria at presentation and few sclerotic lesions, had normal renal function at follow-up. Chronic kidney disease (CKD) stages 2 and 3-4 were observed in four (WG) and three (MPA) patients, respectively. Three patients (23 %) developed end stage renal disease: two were MPA patients with severe presentation (markedly impaired glomerular filtration rate, oliguria, NRP, crescentic NGN, glomerular sclerosis) and one was a WG patient with extensive interstitial fibrosis/tubular atrophy. Conclusions: Severe renal involvement was more common in children with MPA than WG. Treatment with methylprednisolone, cyclophosphamide and plasma exchange induced extra-renal remission/serological response and renal function improvement/stabilization. Markedly decreased GFR, oliguria, NRP, and chronic glomerular lesions at presentation were predictors of poor outcome. [ABSTRACT FROM AUTHOR]

Objectives. Nailfold videocapillaroscopy is being increasingly used as a marker of SSc-related microvascular disease, including in response to treatment. However, it requires further validation. Our aim was to assess the inter-observer, intra-observer and test–retest variability of semi-automated measurement of capillary features as well as of a manual density measurement.Methods. All capillary apexes in images from 58 patients with SSc were marked up independently by two trained observers (inter-observer variability). The first observer then re-marked the images (intra-observer variability), and finally, the first observer marked up a second image of the same nailfold (test–retest). Mark-up of capillaries was carried out on cropped mosaic images (cropped independently by the observers to a fixed width, to allow the same length of nail bed to be studied for each patient) and on whole mosaic images (examining the whole nail bed).Results. Reproducibility of independently cropped mosaic images was poor and was due to the variation in the positioning of the cropped area. However, quantification of whole mosaic images was highly reproducible, e.g. for inter-capillary distance, the intra-class correlation coefficient for inter-observer, intra-observer and test–retest reliability was 0.95, 0.98 and 0.90 (compared with 0.88, 0.79 and 0.89 for cropped mosaic images), respectively. Intra-observer limits of agreement for whole mosaic images were better than inter-observer reproducibility.Conclusion. Quantitative assessment of SSc-related change in nailfold capillaries is unreliable if examination of the same set of capillaries cannot be guaranteed. Conversely a wide-field, high-magnification system that allows visualization of the whole nail bed offers a highly reproducible approach for quantitative assessment and therefore has potential as an outcome measure. [ABSTRACT FROM PUBLISHER]

Objectives. Granulomatosis with polyangiitis (Wegener's) (GPA) and microscopic polyangiitis (MPA) are uncommon and have unknown aetiology. The aim of the study was to investigate the epidemiology of GPA and MPA in a stable, well-defined population looking for differences in the pattern of occurrence, which might suggest a different aetiology.Methods. Since 1988, we have maintained a prospective register of all patients with systemic vasculitis attending the Norfolk and Norwich University Hospital. Patients presenting with new-onset GPA and MPA as defined by the European Medicines Agency algorithm and registered with general practitioners in the former Norwich Health Authority area between 1988 and 2010 were identified. The population in 2008 was estimated to be 459 000 (221 000 males).Results. One hundred and eleven GPA and 58 MPA incident cases were identified during 1988–2010. The overall annual incidence of GPA and MPA was 11.3/million and 5.9/million, respectively. There was evidence of a cyclical pattern of occurrence with a periodicity of 7.6 years for GPA with a peak incidence of 28.3/million in 2005 and the lowest in 2002 (2.2/million). Other lesser peaks occurred in 1990 and 1996. While the peak incidence of MPA was in 2008 (15.2/million), there was no convincing evidence of periodicity. The incidence of cANCA/PR3- or pANCA/MPO-positive vasculitis showed a similar pattern to GPA and MPA, respectively.Conclusion. This study lends support to the notion that the aetiology of GPA and MPA may be distinct conditions with different aetiologies. The cyclical incidence of GPA is possibly an indication for the influence of infection. [ABSTRACT FROM PUBLISHER]

Henoch Schonlein Purpura (HSP) is the commonest systemic vasculitis of childhood typically presenting with a palpable purpuric rash and frequently involving the renal system. We are the first group to clinically assess, critically analyse and subsequently revise a nurse led monitoring pathway for this condition. A cohort of 102 children presenting with HSP to a secondary/tertiary level UK paediatric hospital over a five year period, were monitored using a nurse led care pathway. Using this cohort, the incidence (6.21 cases per 100,000 children per year) and natural disease course of HSP nephritis (46% initial renal inflammation; 9% subsequent renal referral; 1% renal biopsy and immunosuppression) was determined. Older patients were at higher risk of requiring a renal referral (renal referral 12.3 (8.4-13.5) years vs. normal outcome 6.0 (3.7-8.5) years; p<0.01). A normal urinalysis on day 7 had a 97% (confidence interval 90 to 99%) negative predictive value in predicting a normal renal outcome. Using this data and existing literature base, The Alder Hey Henoch Schonlein Purpura Pathway was developed, a revised pathway for the screening of poor renal outcome in HSP. This is based on a six-month monitoring period for all patients presenting with HSP, which importantly prioritises patients according to the urine findings on day 7 and thus intensively monitors those at higher risk of developing nephritis. The pathway could be easily adapted for use in different settings and resources. The introduction of a standardised pathway for the monitoring of HSP will facilitate the implementation of disease registries to further our understanding of the condition and permit future clinical trials. [ABSTRACT FROM AUTHOR]

Objectives. ANCA-associated vasculitis and interstitial lung disease (ILD) are uncommon conditions. The occurrence of both diseases in the same patient is increasingly recognized. Our aim was to ascertain the characteristics and outcomes of patients with ILD and ANCA-associated vasculitis.Methods. A retrospective observational cohort study was performed. Patients who presented to the Hammersmith Hospital, London, with ANCA-associated vasculitis [granulomatosis with polyangiitis (Wegener's), microscopic polyangiitis (MPA) or Churg–Strauss syndrome] who also had ILD were included. Following hospital discharge, all patients were followed up in a multi-disciplinary vasculitis clinic. We recorded patient demographics, diagnostic tests, treatment, complications and mortality.Results. ILD was observed in 2.7% (n = 14) of our patients with ANCA-associated vasculitis (n = 510); all had MPO-ANCA and a clinical diagnosis of MPA, giving a prevalence of 7.2% in patients with MPA (n = 194). There was no significant difference in survival between patients with MPA and ILD and those with MPA alone.Conclusion. It is important that physicians are aware of this clinical association and the presence of ILD should be considered in all patients with ANCA-associated vasculitis, especially those with MPO-ANCA. The possibility that patients with ILD may subsequently develop features of systemic vasculitis should also be remembered. [ABSTRACT FROM PUBLISHER]

Objectives. The epidemiological manifestations of ANCA-associated vasculitis (AAV) differ geographically. However, there have been no prospective studies comparing the incidence of AAV between Japan and Europe over the same time period using the same case definitions.Methods. The incidence of AAV was determined by a population-based method in Miyazaki prefecture, Japan, and Norfolk, UK, between 2005 and 2009. Patients with AAV were defined and classified according to the European Medicines Agency (EMEA) algorithm.Results. The number of incident cases of AAV in Japan and the UK were 86 and 50, respectively, and the average annual incidence over the 5-year period was 22.6/million (95% CI 19.1, 26.2) and 21.8/million (95% CI 12.6, 30.9) in Japan and the UK, respectively. The average age was higher in patients in Japan than in patients in the UK [mean (median), 69.7 (72) vs 60.5 (61) years]. Microscopic polyangiitis (MPA) was the predominant subtype in Japan (83%), while granulomatosis with polyangiitis (Wegener's) was more frequent in the UK (66%). As for the pattern of ANCA positivity, >80% of Japanese patients were pANCA/MPO positive, whereas two-thirds of UK patients were cANCA/PR3 positive. Renal involvement in MPA was very common in both countries, but was much less common in granulomatosis with polyangiitis in Japan compared with the UK.Conclusion. There was no major difference in AAV incidence between Japan and the UK, but this prospective study found MPA and MPO-ANCA to be more common in Japan and granulomatosis with polyangiitis and PR3-ANCA to be more common in the UK, in line with earlier reports. [ABSTRACT FROM PUBLISHER]

Objective. To characterize the long-term mortality in patients with WG compared with matched population-based controls.Methods. We used data from the General Practice Research Database, which contains the computerized records of 6.25 million patients and is representative of the population of the UK. We identified all subjects with a new diagnosis of WG in the period 1989–2004, and for each case, compared mortality with 10 controls matched for age, gender and practice.Results. We identified 255 patients with a new diagnosis of WG (mean age 58.1 years, range 9–90 years, 47% females) and 2546 controls (mean age 58.1 years, range 9–89 years, 47% females). Mean follow-up was 6.4 years. The mortality for patients with WG was significantly increased during the first year after diagnosis [HR 9.0 (95% CI 5.8, 13.9)], especially for those &leq;65 years of age [HR 19.9 (95% CI 8.8, 44.9)]. The excess mortality was less marked after the first year: 1–5 years [HR 1.68 (95% CI 1.08, 2.60)], 5–10 years [HR 2.41 (95% CI 1.43, 4.07)], but started to increase by 10–15 years [HR 4.4 (95% CI 2.0, 9.8)]. The Kaplan–Meier survival curve showed an increase in mortality after 8 years.Conclusions. Despite current therapy, patients with WG have a 9-fold increased risk of death in the first year of disease, attributed to infection, active vasculitis and renal failure. Between 1 and 8 years the risk is at its lowest, although higher than the control population. There is an increased mortality from 8 years onwards that remains unexplained. [ABSTRACT FROM PUBLISHER]

Objective. The objective of this study was to evaluate the effect of intravenous immunoglobulin (IVIg) therapy in diabetic lumbosacral radiculoplexus neuropathy (DLRPN) patients who did not respond to analgesic drug therapy and corticosteroids. Background. DLRPN is a rare painful condition that may occur in diabetes mellitus (DM). At the moment, there are limited therapeutic options for DLRPN. Methods. We recruited five patients affected by type 2 DM and DLRPN. They were selected from a cohort of 13 consecutive DLRPN patients. Inclusion criteria were severe pain (visual analog scale [VAS] > 4/10) and no response to pain symptomatic therapy and corticosteroids. Patients were treated with IVIg (0.4 g/kg/day for 5 days). Outcome measures were VAS, time of onset and duration of pain relief, the Medical Research Council (MRC) scale for lower limb muscle strength, and walking distance. Electrophysiology and needle electromyography (EMG) were retested after IVIg. Results. Four of the patients had positive pain response after IVIg. VAS reduction started 5–10 days after IVIg infusion. Two patients underwent additional IVIg infusions due to pain reappearance after 7–18 months, again with positive response. VAS, MRC scale, and walking distance significantly improved at 1 month (Wilcoxon nonparametric test, two-tailed, P < 0.05). Electrodiagnostic testing was unchanged, but needle EMG showed reduction of denervation signs after IVIg. Conclusions. IVIg may rapidly reduce pain and improve motor function in DLRPN despite previous negative response to corticosteroids. IVIg may be repeated in those patients who experience disease relapse. Future double-blind trials are needed to evaluate the role of IVIg in DLRPN. [ABSTRACT FROM AUTHOR]

The purpose of this study is to present the first report of a case of primary frosted branch angiitis from the UK and to review the characteristics of this rare disease. Primary frosted branch angiitis causes characteristic florid translucent retinal perivascular sheathing of both arterioles and venules in association with variable uveitis, retinal oedema and visual loss, normally with good recovery. A total of 57 cases have been reported in the world literature. Atypical, typically focal frosted branch angiitis may also occur secondary to other causes of intraocular inflammation, especially cytomegalovirus retinitis. Primary frosted branch angiitis has a characteristic presentation but a variable course, typically affecting children or young adults. The disease is likely to represent a common immune pathway in response to multiple infective agents. The optimal treatment is unclear. [ABSTRACT FROM AUTHOR]

Summary: Background: The frequency and ethnic variation of Henoch-Schonlein purpura, Kawasaki disease, and rarer vasculitides during childhood are not well characterised. Our aim was to ascertain the incidence and ethnic distribution of these conditions in children resident in a region of the UK with a diverse ethnic mix. Methods: 1.1 million children younger than age 17 years live in the West Midlands. Between Sept 1, 1996, and Aug 31, 1999, we surveyed this population with monthly questionnaires sent to 321 consultants, a single questionnaire sent to 2860 family doctors, and review of 406 case notes with diagnostic codes for vasculitis. We included in the analyses children who fulfilled established criteria for vasculitis with disease onset during the study, and calculated incidence rates from population rates derived from the census of 1991. Findings: We identified 586 new instances of vasculitis and connective tissue disease. The estimated annual incidence of Henoch-Schonlein purpura was 20.4 per 100 000, and was highest between the ages of 4 years and 6 years (70.3 per 100 000). The estimated annual incidence of Kawasaki disease was 5.5 per 100 000 in children younger than 5 years, and was highest in Indian subcontinent Asian children (14.6 per 100 000). Indian subcontinent Asian and black children had the highest incidence of systemic lupus erythematosus, juvenile dermatomyositis, and other primary systemic vasculitides. Interpretation: Childhood Henoch-Schonlein purpura is more frequent in the West Midlands than previously reported, and Kawasaki disease has a higher incidence than previously indicated in the UK, with the highest incidence in Indian subcontinental Asian children. Other vasculitis is rare in childhood. [ABSTRACT FROM AUTHOR]

SUMMARY: The kidney may be involved in several forms of systemic vasculitis, particularly those affecting small-calibre blood vessels. Hence, the majority of cases involve patients with Wegener's granulomatosis, Churg–Strauss syndrome or microscopic polyangiitis. Anti-neutrophil cytoplasmic antibodies (ANCA) are found in the majority of these patients and their detection has increased the sensitivity and specificity of diagnosis. However, the role of ANCA in the pathogenesis of these lesions remains uncertain. Moreover, the approach to treatment, both in terms of induction and maintenance of remission, remains problematic. This brief review discusses aspects of ANCA and current approaches to management. [ABSTRACT FROM AUTHOR]

In the Brown Norway rat, mercuric chloride (HgCl2) induces an autoimmune syndrome characterized by necrotizing vasculitis, predominantly affecting the caecum, and a polyclonal B-cell response. The time course of vasculitis is biphasic, with an αβ T-cell independent phase occurring within 24 h, and a T-cell and neutrophil dependent phase, maximal at two weeks. The pathogenesis of the early phase of vasculitis is unclear, and this study aims to examine the role of neutrophils. Rat neutrophils were depleted using cyclophosphamide. RP3, an antirat neutrophil monoclonal antibody, inhibited neutrophil leucocytosis but did not deplete neutrophils. Vasculitis was induced by subcutaneous HgCl2 injection. Serial measurements of peripheral blood leucocyte count were made. Rats were killed after 24 or 72 h. The macroscopic appearance of the caecum was scored by an experienced observer, and samples taken for histological examination. Caecums were excised and myeloperoxidase, a marker enzyme for neutrophil infiltration, assayed. Cyclophosphamide induced marked neutropaenia whereas RP3 inhibited the neutrophilia observed after HgCl2 injection. Vasculitis was present in both treated and control animals, with no significant differences in macroscopic or microscopic scores between the groups. Tissue myeloperoxidase activity was low in all animals and did not differ significantly between groups. The data do not support a role for neutrophils in the initial pathogenesis of vasculitis in this model. [ABSTRACT FROM AUTHOR]

The article offers information about the primary angiitis of the central nervous system in Great Britain. The primary angiitis of a nervous system is a rare disease to which the terms granulomatous angiitis and isolated cerebral vasculitis have also been applied. There are primary and secondary vasculitis and its clinical features includes vomiting, lethargy and headache. Angiitis is suspected when neurological signs and symptoms remain unexplained or consistent with arteritis.

Background Rituximab is an anti-CD20 chimeric monoclonal antibody that depletes pre-plasma B cells. It is used in paediatric rheumatology for conditions including juvenile systemic lupus erythematosus (jSLE), juvenile dermatomyositis (JDM), vasculitides and refractory juvenile idiopathic arthritis (JIA). We aim to describe the cohort of patients treated with rituximab in the Scottish Paediatric and Adolescent Rheumatology Network (SPARN) in a 5-year period, and assess the need for a network guideline. Methods A review of paper and electronic case records. Patients seen within the SPARN network who received Rituximab between 2014 and 2018 were included. Results Vasculitis Rituximab was given to 16 patients in 5 different SPARN centres between 2014 and 2018. Male: Female ratio was 1:4.3. Mean age at first dose of rituximab was 12.75 years. Mean disease duration pre rituximab was 1 year. 8 (50%) patients had jSLE, 7 multisystem and 1 isolated lupus nephritis. 3 had ANCA-positive vasculitis and 5 had other conditions. (1 had RF+ve JIA; 1 severe panuveitis; 1 had an unspecified autoinflammatory condition; 1 had COPA syndrome with severe interstitial lung disease and 1 had autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). Documentation of pre-rituximab checks was poor. Baseline bloods were done in all 16 patients. 11 patients had lymphocyte subsets and 13 immunoglobulins documented. Disease-specific antibodies were measured in all patients in whom applicable (11). 11 had a chest x-ray prior to rituximab. In 9 cases a pre-rituximab pregnancy test was indicated: none were documented. In only 3 patients was a pre-rituximab history of recent infections documented. In 8 patients a discussion regarding treatment risks and benefits was documented. Post-infusion lymphocyte subset monitoring was variable but documented in 15. 1 patient was never B cell deplete. 9 never fully reconstituted. RTX dose information was available for 14. All received doses of 750mg/m2 with 6 having the dose capped at 1g. Dose frequency information was available for all. The majority (9) received 2 doses. Of the rest, 1 patient received a single dose. 3 received 3 doses, 2 had 4 and 1 had 5. All patients in whom information was available, received pre-medication with paracetamol, chlorphenamine and methylprednisolone (n = 14). 4 patients had side effects noted (rash/itch in 1, anaphylaxis in 1, facial flushing in 1 and post-infusion infection in 1). Clinical response was clearly documented in 8 patients, 7 of whom showed clinical improvement (2 had systemic jSLE, 2 had ANCA +ve vasculitis, 1 had isolated lupus nephritis, 1 had COPA syndrome and 1 had RF+ JIA). Conclusion Rituximab is used for a range of conditions and in a number of centres within SPARN. This review highlights variation in and poor documentation of pre-rituximab discussions and investigations, prescribing, monitoring and response. A SPARN rituximab protocol is being developed to address this. Conflicts of Interest The authors declare no conflicts of interest. [ABSTRACT FROM AUTHOR]

Background We describe the case of a 12 year-old boy with polyarteritis nodosa presenting with long thoracic nerve injury (LTNI) post flu vaccination. Polyarteritis nodosa is an inflammatory vasculitis treated with immunosuppressive medication. Children with immunosuppression require seasonal flu vaccination, and LTNI is a recognised complication, rare in children, with no incidence documented. Physiotherapy plays a role in the conservative management of LTNI, however, there is debate regarding the most effective regime. Methods Case description with literature review of aetiology, treatment strategies and recommendations for effective therapeutic approach. Results Our patient was diagnosed with polyarteritis nodosa following an admission with intra-abdominal bleed, coeliac axis thrombosis and mesenteric artery aneurysm seen on angiogram. He responded well to steroids and immunosuppressive medication. Due to the risk of infection from immune suppression, he received seasonal intra-muscular influenza vaccination to the right deltoid. There were no initial complications, however, two weeks later, burning shoulder pain and sleep disturbance were reported. There was paraesthesia in the right hand although grip strength was not impaired. Of note, the patient is left hand-dominant. Examination revealed elevation of the right shoulder girdle and winging of the medial border of the scapula. Range of movement at the shoulder was full and pain-free. Palpation of the gleno-humeral joint line and deltoid were unremarkable. The clinical findings suggested long thoracic nerve denervation. Physiotherapy assessment demonstrated weakness in the serratus anterior muscle and abnormal scapula movement patterns, including decreased protraction. Nerve conduction studies reported decreased activation of the long thoracic nerve. Scapula recruitment exercises were advised, as well as posture correction. After a year, scapula-humeral rhythm and strength of the scapula muscles improved. Conclusion Causes of scapula-winging in children include osteochondromas, exostoses and sports-related injuries. Scapula-winging associated with LTNI is a recognised complication of flu vaccine but very rarely reported in under 16-year olds. Treatment of LTNI is poorly evidenced in the literature. However, physiotherapy including bracing to enhance proprioception, mobility exercises in supine to correct scapula position and strengthening of scapula muscles is reported. There is a lack of evidence to inform the most effective approach. The literature outlines that general gleno-humeral muscle strengthening is beneficial in improving shoulder function in LTNI. However, there is limited research investigating the specific role of scapula muscle strengthening in LTNI in children. The literature suggests that poor scapula function can impair the biomechanics of the shoulder and exercises that address scapula muscle control can improve movement patterns. The time to recovery from LTNI is estimated between 1-2 years and maintaining muscle bulk is our challenge, as the nerve recovers. Clinicians need to be aware of LTNI complicating flu vaccine in immuno-compromised children. We highlight the importance of physiotherapy in improving scapula biomechanics. Conflicts of Interest The authors declare no conflicts of interest. [ABSTRACT FROM AUTHOR]

Background Kawasaki disease is the most common cause of acquired childhood heart disease in developed countries. If left untreated, 15 to 25% of children develop coronary artery aneurysms and more worryingly 2 to 3% will die from coronary vasculitis. Prompt recognition and management including referral to a cardiologist can ameliorate this. The clinical challenge however is the lack of any diagnostic tests and that many cases do not fit the typical diagnostic criteria. Here we present the results from an original audit assessing our practice against RCPCH guidelines. We show findings from audit cycles spanning six years from Leicester's children's hospital. We also take one step further to analyse this data looking for trends in presentation and lab findings. Methods Original audit data was collected from cases between 2008-2012 and 2015-2017 (audit standards are shown in figure 1). The data generated from these audits was re-analysed to assess for trends in presentation and laboratory findings. Open in new tab Download slide P32 Figure 1. Audit standards and results (IVIG = intravenous immunoglobulin). Open in new tab Download slide P32 Figure 1. Audit standards and results (IVIG = intravenous immunoglobulin). Results In six years we saw 41 cases: 23 were of atypical presentation and 18 were typical (figure 2); 27 patients were male and 14 were female. The age range was 1 month to 13 years. All patients received IVIG, aspirin and were referred to cardiology. No patients required biological therapies. Cardiological events: Data incomplete – patients disseminated across several tertiary units; acutely - 6 patients had a borderline/abnormal echocardiogram; long-term - 1 patient has persistent but resolving coronary artery aneurysms. Open in new tab Download slide P32 Figure 2. Presentations of Kawasaki disease defined by typical vs. atypical. Open in new tab Download slide P32 Figure 2. Presentations of Kawasaki disease defined by typical vs. atypical. Mortalities A 4-month old in 2008 died as a result of untreated atypical Kawasaki disease. This patient was diagnosed only at autopsy. Conclusion Over the 2 audit periods we noted a higher than expected caseload of atypical KD. At presentation: 88% had no desquamation, 30% had only mildly raised CRP, and 2% did not have fever for more than 5 days. Conflicts of Interest The authors declare no conflicts of interest. [ABSTRACT FROM AUTHOR]

Poster presentation Tuesday 8 October Background Antinuclear antibodies (ANA) are autoantibodies that recognise cellular antigens found predominantly in the cell nucleus. They are associated with numerous autoimmune diseases such as systemic lupus erythematosus, but may also be found in infectious diseases, malignancies and healthy individuals. ANA is requested as part of an initial work-up for autoimmune conditions. In healthy children (5-18%), positive ANA titres of 1/80 to 1/320 have been reported. A prospective study of healthy children with positive ANA found that children who developed autoimmune disease had clinical features at presentation that were suspicious for such an outcome. Therefore, the usefulness of a positive ANA result for diagnosing autoimmune conditions is limited without clinical correlation. The aim of our study was to assess whether high ANA titre and clinical features at presentation could predict final diagnosis. Methods Single centre retrospective study at Great Ormond Street Hospital for Children (GOSH). The immunology laboratory provided a list of positive ANA results (using indirect immunofluorescence technique) from January 2013 to July 2018. A retrospective chart review was performed to ascertain presence of clinical features at presentation under the five following titles: arthritis, skin involvement, eyes, CNS involvement and Raynaud's phenomenon. We then reviewed the last clinical contact to document confirmed diagnosis. Results We performed a retrospective chart review on 1,354 children (67% female; median age 7.5 years (0.1-17.5); median follow-up 4.8 years (0-18)) with positive ANA results (titres 1/160, 1/320, 1/640, 1/1280, 1/2560 and >1/2560). Table 1 reports ANA titres at first presentation in relation to final diagnosis. A titre of 1/640 or above was most commonly seen (>50%) in children with an autoimmune rheumatology condition. In fact, children with the highest titre (>1:2560) were significantly more likely to be diagnosed with one of these conditions. Finally, we looked at the number of presenting features and correlated with final diagnosis. Those diagnosed with a CTD were most likely to present with 2-5 clinical features (p < 0.0001). P24 Table 1: Percentage of patients grouped according to their diagnosis and ANA titres Final Diagnoses   ANA Titres   >1: 2560   1: 2560   1: 1280   1: 640   1: 320   1: 160     Connective Tissue Diseases  24%  9%  13%  16%  16%  22%  JIA and Uveitis  8%  11%  15%  22%  22%  22%  JIA  6%  8%  13%  24%  24%  25%  Autoimmune (other)  4%  5%  11%  19%  32%  29%  Unidentified autoimmune/ autoinflammatory  8%  12%  -  24%  12%  44%  Vasculitis  -  -  5%  26%  16%  53%  Sarcoidosis  -  20%  -  20%  -  60%  Autoinflammatory  7%  -  -  43%  -  50%  Malignancy  -  -  -  25%  -  75%  Other  3%  2%  3%  17%  28%  47%  Non-inflammatory MSK  3%  -  9%  18%  27%  43%  Final Diagnoses   ANA Titres   >1: 2560   1: 2560   1: 1280   1: 640   1: 320   1: 160     Connective Tissue Diseases  24%  9%  13%  16%  16%  22%  JIA and Uveitis  8%  11%  15%  22%  22%  22%  JIA  6%  8%  13%  24%  24%  25%  Autoimmune (other)  4%  5%  11%  19%  32%  29%  Unidentified autoimmune/ autoinflammatory  8%  12%  -  24%  12%  44%  Vasculitis  -  -  5%  26%  16%  53%  Sarcoidosis  -  20%  -  20%  -  60%  Autoinflammatory  7%  -  -  43%  -  50%  Malignancy  -  -  -  25%  -  75%  Other  3%  2%  3%  17%  28%  47%  Non-inflammatory MSK  3%  -  9%  18%  27%  43%  P24 Table 1: Percentage of patients grouped according to their diagnosis and ANA titres Final Diagnoses   ANA Titres   >1: 2560   1: 2560   1: 1280   1: 640   1: 320   1: 160     Connective Tissue Diseases  24%  9%  13%  16%  16%  22%  JIA and Uveitis  8%  11%  15%  22%  22%  22%  JIA  6%  8%  13%  24%  24%  25%  Autoimmune (other)  4%  5%  11%  19%  32%  29%  Unidentified autoimmune/ autoinflammatory  8%  12%  -  24%  12%  44%  Vasculitis  -  -  5%  26%  16%  53%  Sarcoidosis  -  20%  -  20%  -  60%  Autoinflammatory  7%  -  -  43%  -  50%  Malignancy  -  -  -  25%  -  75%  Other  3%  2%  3%  17%  28%  47%  Non-inflammatory MSK  3%  -  9%  18%  27%  43%  Final Diagnoses   ANA Titres   >1: 2560   1: 2560   1: 1280   1: 640   1: 320   1: 160     Connective Tissue Diseases  24%  9%  13%  16%  16%  22%  JIA and Uveitis  8%  11%  15%  22%  22%  22%  JIA  6%  8%  13%  24%  24%  25%  Autoimmune (other)  4%  5%  11%  19%  32%  29%  Unidentified autoimmune/ autoinflammatory  8%  12%  -  24%  12%  44%  Vasculitis  -  -  5%  26%  16%  53%  Sarcoidosis  -  20%  -  20%  -  60%  Autoinflammatory  7%  -  -  43%  -  50%  Malignancy  -  -  -  25%  -  75%  Other  3%  2%  3%  17%  28%  47%  Non-inflammatory MSK  3%  -  9%  18%  27%  43%  Conclusion This study suggests that, patients presenting with higher ANA titres and a combination of clinical features should be assessed systemically and followed-up as they may have increased risk of developing an autoimmune rheumatological conditions. Conflicts of Interest The authors declare no conflicts of interest. [ABSTRACT FROM AUTHOR]

Background Anti-neutrophil cytoplasmic antibodies (ANCA) associated vasculitis (AAV) are rare small and medium vessel vasculitides that include granulomatosis polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). This retrospective review summarises the clinical features of a cohort of patients with childhood onset AAV at a single tertiary centre in the North West of England. Methods Identification of all patients with diagnosis of ANCA-associated vasculitis diagnosed from 2014 to 2019, using department database and PEDVAS data. Clinical information was collected retrospectively using electronic patient record and case notes. Results 10 patients with AAV were identified, with GPA being the most common diagnosis (7 patients). 2 patients had MPA and 1 had EGPA. All patients with GPA fulfilled consensus EULAR/PRES criteria. The EGPA patient fulfilled ACR classification criteria.1 MPA patient fulfilled Chapel Hill Consensus Conference criteria. MPA presented in a younger age group compared to EGPA. AAV was more common in females, 8:2 female to male ratio, Table 1. All patients had pulmonary and renal involvement, with the exception of one EGPA patient having pulmonary disease with no evidence of glomerulonephritis (GN). MPA patients had significant renal disease and presented early, within 1 month of clinical symptoms. GPA patients had an average duration of symptoms of 2.5 months before presentation. GPA patients were mainly cANCA PR3 positive and MPA patients were MPO positive. The EGPA patient was not ANCA positive but had histological diagnosis of granulomatous vasculitis. 3 patients with GPA underwent plasmapheresis, with evidence of proliferative GN and pulmonary disease at presentation. One of these patients sustained pulmonary haemorrhage. The 2 patients with MPA presented with significant renal failure; one patient died 19 months after diagnosis, the other had renal transplant. All patients received cyclophosphamide and required further immunosuppression with either DMARD or biologic. Most patients remain on MMF or rituximab as maintenance therapy which appears successful in maintaining remission so far. P31 Table 1: Demographics and clinical features of patients with AAV   GPA, n = 7  MPA, n = 2  EGPA, n = 1  Gender F:M  6:1  2:0  0:1  Mean age at onset  13.2 (8.7- 15)  5.9 (2.3- 9.6)  11.8  (years)  Mean duration of follow-up (months)  23.2 (5- 36)  28.5 (19- 38)  53  Mean duration of symptoms  2.5 (1-6)  1 (1)  11  pre-presentation (months)  ENT  4  1  1  Pulmonary  7  2  1  Renal  7  2  0  Asthma  0  0  1  Eosinophilia  0  0  1  ANCA PR3 +ve  6  0  0  ANCA MPO +ve  1  2  0  ESRF  0  2  0  Death  0  1  0  Plasmapheresis  3  2  0  Cyclophosphamide  7  2  1  Azathioprine  3  1  1  MMF  3  2  1  Rituximab  4  1  1    GPA, n = 7  MPA, n = 2  EGPA, n = 1  Gender F:M  6:1  2:0  0:1  Mean age at onset  13.2 (8.7- 15)  5.9 (2.3- 9.6)  11.8  (years)  Mean duration of follow-up (months)  23.2 (5- 36)  28.5 (19- 38)  53  Mean duration of symptoms  2.5 (1-6)  1 (1)  11  pre-presentation (months)  ENT  4  1  1  Pulmonary  7  2  1  Renal  7  2  0  Asthma  0  0  1  Eosinophilia  0  0  1  ANCA PR3 +ve  6  0  0  ANCA MPO +ve  1  2  0  ESRF  0  2  0  Death  0  1  0  Plasmapheresis  3  2  0  Cyclophosphamide  7  2  1  Azathioprine  3  1  1  MMF  3  2  1  Rituximab  4  1  1  P31 Table 1: Demographics and clinical features of patients with AAV   GPA, n = 7  MPA, n = 2  EGPA, n = 1  Gender F:M  6:1  2:0  0:1  Mean age at onset  13.2 (8.7- 15)  5.9 (2.3- 9.6)  11.8  (years)  Mean duration of follow-up (months)  23.2 (5- 36)  28.5 (19- 38)  53  Mean duration of symptoms  2.5 (1-6)  1 (1)  11  pre-presentation (months)  ENT  4  1  1  Pulmonary  7  2  1  Renal  7  2  0  Asthma  0  0  1  Eosinophilia  0  0  1  ANCA PR3 +ve  6  0  0  ANCA MPO +ve  1  2  0  ESRF  0  2  0  Death  0  1  0  Plasmapheresis  3  2  0  Cyclophosphamide  7  2  1  Azathioprine  3  1  1  MMF  3  2  1  Rituximab  4  1  1    GPA, n = 7  MPA, n = 2  EGPA, n = 1  Gender F:M  6:1  2:0  0:1  Mean age at onset  13.2 (8.7- 15)  5.9 (2.3- 9.6)  11.8  (years)  Mean duration of follow-up (months)  23.2 (5- 36)  28.5 (19- 38)  53  Mean duration of symptoms  2.5 (1-6)  1 (1)  11  pre-presentation (months)  ENT  4  1  1  Pulmonary  7  2  1  Renal  7  2  0  Asthma  0  0  1  Eosinophilia  0  0  1  ANCA PR3 +ve  6  0  0  ANCA MPO +ve  1  2  0  ESRF  0  2  0  Death  0  1  0  Plasmapheresis  3  2  0  Cyclophosphamide  7  2  1  Azathioprine  3  1  1  MMF  3  2  1  Rituximab  4  1  1  Conclusion Childhood onset AAV are severe diseases with significant morbidity and mortality. Rituximab was found to be effective in induction as well as maintenance therapy in our patients. In our cohort, children had multi-system involvement at presentation. Clinicians should investigate thoroughly for ENT, pulmonary and renal complications at diagnosis. Conflicts of Interest The authors declare no conflicts of interest. [ABSTRACT FROM AUTHOR]