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BACKGROUND More effective and safer treatments are needed for antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis. METHODS We conducted a randomized trial with a 2-by-2 factorial design to evaluate the use of plasma exchange and two regimens of oral glucocorticoids in patients with severe ANCA-associated vasculitis (defined by an estimated glomerular filtration rate of

The aim of this study is to adapt and feasibility test the narrative component of Narrative Enhancement and Cognitive Therapy (NECT) for late-onset psychosis. This study followed the development and feasibility phases of the Medical Research Council framework. The original NECT intervention was adapted based on consultations with service users, experts, and clinicians. The evaluation of the feasibility test of the adapted intervention was guided by Orsmond and Cohn (Occup Particip Health 35(3):169–177, 2015)’s model for feasibility studies. The final adaptations consist of language, readability, and delivery. The adapted intervention was tested for feasibility and acceptability with one group of five patients recruited from a National Health Service (NHS) Trust in UK Results were mixed in participant outcomes and a likelihood of acceptability of the intervention. This indicates the need for a larger scale feasibility test to explore the identified benefits and challenges of implementing NECT in NHS or community settings for late-onset psychosis.

Background IgG4-related disease (IgG4-RD) is a chronic systemic inflammatory disorder presenting with mass lesions in various organs and showing plasma cell infiltration, storiform fibrosis and obliterative phlebitis on histology. IgG4-RD has previously been identified as a rare cause of sudden cardiac death (SCD) in case reports, but in settings where pathology has been unexpectedly found on post-mortem examination. To our knowledge, there are no published case reports of SCD in patients during treatment for IgG4-RD. Methods A 43-year old chef with a 15 pack-year smoking history presented with portal vein thrombosis, widespread lymphadenopathy, proptosis and inflammatory lung changes. He was found to have IgG4-RD on submandibular lymph node biopsy with storiform fibrosis and abundance of IgG4-positive plasma cells. Test showed a high IgG and low complement levels and a persistent eosinophilia. He was anticoagulated with warfarin for the HPV thrombosis. Treatment with steroids (initially prednisolone 40mg/day) was initially successful and he continued at work and kept fit in the gym. There was also a good biochemical and radiological response to steroids, with normalisation of eosinophil count, IgG level, complements and CRP along with regression of imaging changes. After a period of 12 months steroid weaning (prednisolone 5mg) and having been well at OPD review, he was unexpectedly found dead at home. Post-mortem examination identified IgG4-RD coronary pan-arteritis as the cause of death. The finding of this unanticipated severe complication raises new questions about surveillance and prevention. Results Coronary involvement in IgG4-RD is thought to be rare but may reflect difficulty obtaining coronary artery tissue and clinically silent disease remaining undiagnosed. A systematic review of IgG4-RD outcomes (7 studies comprising 294 patients, follow-up mean of 29 months) identified 26 deaths (8.8%). One was from an aneurysm and four from other cardiovascular disease, while most deaths were from disease progression or cancer. Case reports describe IgG4-RD coronary artery disease pathologies, including inflammatory pseudotumour, periarterial thickening, coronary artery aneurysm and coronary artery stenosis. Conclusion This case raises important questions about identifying and monitoring for asymptomatic cardiovascular involvement in IgG4-RD. Steroid treatment may be less effective for coronary involvement, and in theory, could precipitate rupture or dilatation of the arteries. Recent IgG4-RD management guidelines have not addressed surveillance for cardiovascular disease. ECG and echocardiography are reasonable initial surveillance options, but we suggest clinicians have a low threshold for CT coronary angiography and/or cardiac MR. Invasive coronary angiography and CT-PET can then be used to provide additional information if required. We noted a normal CRP despite active coronary inflammation in our patient and therefore look forward to improved biomarkers for disease activity in IgG4-RD. Disclosures R. Haigh None. L. Smyth None. A. Ludman None.

© 2019 The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. Anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) encompasses three disease phenotypes: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). Considerable improvements in therapy mean induction of remission occurs in most patients with AAV [1-4]. However, disease relapse continues to pose a burden to patients. Morbidity accrues with relapses through disease-related damage and adverse effects of therapies to manage these relapses, negatively impacting on quality of life [5]. Rituximab (RTX), a monoclonal antibody targeting CD20, leads to peripheral B cell depletion. This has been successfully trialled, and is licensed, for the induction and maintenance of remission in AAV [2, 3]. RTX is increasingly being used for the maintenance of remission in patients with AAV, to reduce the risk of relapse and its consequences [6]. Other commonly used agents that have been trialled for the maintenance of remission in AAV include azathioprine, methotrexate and mycophenolate [7-9]. The decision to select RTX for the maintenance of remission is multifactorial, including but not limited to, patient-related factors and preferences, previous treatment and response, consideration of the overall risk of relapse, and access to therapy. These guidelines have been developed by a group of physicians practising in the UK.

SummaryRecently, the term ‘locked rehabilitation’ has spread from commissioning to now also clinical parlance. This is without any clear service description or category of patient which this service manages. Differences between this new term and an established definition of low secure services are examined and reasons for the introduction of this terminology are discussed. This is contextualised within service development, payment by results and measures of quality. It is argued that there is a need for ongoing measurements of types of patients admitted to, and treatments offered by, this ‘new’ ward, as well as those within psychiatric intensive and low secure care services.

Systemic small vessel vasculitis is associated with antineutrophil cytoplasm antibodies (ANCAs). While there is mounting in vitro evidence to suggest that ANCAs are capable of enhancing leukocyte-endothelial interactions, no in vivo evidence for this has been provided. In this study a novel rat model of ANCA-associated experimental autoimmune vasculitis (EAV), induced by immunization with human myeloperoxidase (MPO), was used to analyze directly the potential effect of ANCAs on leukocyte-venular wall interactions in vivo as observed by intravital microscopy. These rats developed anti-MPO antibodies directed against rat leukocytes, showed pathologic evidence of small vessel vasculitis, and had enhanced leukocyte adhesion and transmigration in response to the chemokine Groα (CXCL1 [CXC ligand 1]). Passive transfer of immunoglobulin from rats with EAV to naive rats conferred enhanced adhesion and transmigration responses in the recipients. Furthermore, rats with EAV and recipients of ANCA-positive immunoglobulin developed extensive microvascular injury, as manifested by mesenteric hemorrhage, in response to CXCL1. This study provides the first direct in vivo evidence for the ability of ANCAs to enhance leukocyteendothelial interactions and cause microvascular hemorrhage, thereby providing a mechanism by which ANCAs could exert pathogenic effects in systemic vasculitis. (Blood. 2005;106:2050-2058)

Inherited abnormalities of complement are found in ∼60% of patients with atypical haemolytic uraemic syndrome (aHUS). Such abnormalities are not fully penetrant. In this study, we have estimated the penetrance of the disease in three families with a CFH mutation (c.3643CG; p. Arg1215Gly) in whom a common lineage is probable. 25 individuals have been affected with aHUS with three peaks of incidence-early childhood (n=6), early adulthood (n=11) and late adulthood (n=8). Eighteen individuals who have not developed aHUS carry the mutation.We estimated penetrance at the ages of 4, 27, 60 and 70 years as both a binary and a survival trait using MLINK and Mendel. We genotyped susceptibility factors in CFH, CD46 and CFHR1 in affected and unaffected carriers.We found that the estimates of penetrance at the age of 4 years ranged from0.01 to 0.10, at the age of 27 years from 0.16 to 0.29, at the age of 60 years from 0.39 to 0.51 and at the age of 70 years from 0.44 to 0.64. We found that the CFH haplotype on the allele not carrying the CFH mutation had a significant effect on disease penetrance. In this family, we did not find that the CD46 haplotypes had a significant effect on penetrance.

The therapeutic options for anti-neutrophil cytoplasm antibody (ANCA)-associated systemic vasculitis (AASV) remain limited and hampered by adverse effects. One potential novel therapeutic avenue involves inhibition of TNF-alpha, with encouraging uncontrolled data in humans with one agent (infliximab) but disappointing controlled data from another (etanercept). For investigating the potential role of TNF-alpha as a therapeutic target in AASV, the effect of an anti-rat TNF-alpha mAb (CNTO 1081) in a rat model of AASV was investigated. For testing the effect of TNF-alpha blockade in this model, starting on day 28 after immunization (a point when glomerulonephritis is established), animals were randomized to treatment with CNTO 1081 or control mouse IgG. Treatment with CNTO 1081 significantly reduced albuminuria (mean 1.1 +/- 0.3 mg/24 h CNTO 1081 versus 8.0 +/- 1.9 controls; P < 0.05) and crescent formation (0% CNTO 1081 versus 60% controls; P < 0.05). Lung hemorrhage was also reduced (CNTO 1081: median score 0, range 0 to 2; controls: 2, range 1 to 3; P < 0.05). When analyzed by intravital microscopy, there was a 43% inhibition of leukocyte transmigration in mesenteric venules in response to topical CXCL1 (a neutrophil chemoattractant) in the CNTO 1081 group compared with controls (P < 0.001). Anti-myeloperoxidase antibody titers were similar in both groups throughout the study. In conclusion, these findings indicate that TNF-alpha plays an important role in the pathogenesis of experimental autoimmune vasculitis and suggest that blockade of this cytokine with an mAb is effective in treating established vasculitis. The therapeutic action of anti-TNF-alpha reagents may be mediated, in part, by suppression of the enhanced leukocyte-endothelial interactions in this disorder.

Microscopic polyangiitis is a systemic vasculitis affecting smal-l and medium-sized vessels and is characteristically associated with a focal and segmental necrotizing glomerulonephritis. It may present as a pulmonary-renal syndrome with rapidly progressive glomerulonephritis and alveolar hemorrhage, but the pattern of disease will vary according to the organ systems involved. Granulomatous disease of the upper or lower respiratory tract is not a feature, and its presence suggests the diagnosis of Wegener's granulomatosis. The etiology of the condition is unclear, but most patients have antineutrophil cytoplasm antibodies (ANCA) with specificity for either myeloperoxidase (MPO) or proteinase 3 (PR3), and there is increasing evidence that these may be pathogenic. Current treatment includes an induction phase using cyclophosphamide and steroids to attain remission, followed by a maintenance phase in which the levels of immunosuppression are gradually reduced. Azathioprine may be substituted for cyclophosphamide at 3 months. Adjunctive plasma exchange or intravenous methylprednisolone is used in the management of either or both severe renal disease and alveolar hemorrhage, and new evidence suggests that plasma exchange is more effective in recovery of renal function. Overall, 1-year survival in systemic vasculitis is around 85%, and up to 50% of patients relapse, although relapse is less common in those with MPO-ANCA. Newer therapies are being explored in an attempt to increase the efficacy and reduce the toxicity of treatment.