Explore the vast range of titles available.

ObjectiveTo evaluate whether the classification of patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) according to ANCA type (anti-proteinase 3 (PR3) or anti-myeloperoxidase (MPO) antibodies) predicts treatment response.MethodsTreatment responses were assessed among patients enrolled in the Rituximab in ANCA-associated Vasculitis trial according to both AAV diagnosis (granulomatosis with polyangiitis (GPA)/microscopic polyangiitis (MPA)) and ANCA type (PR3-AAV/MPO-AAV). Complete remission (CR) was defined as disease activity score of 0 and successful completion of the prednisone taper.ResultsPR3-AAV patients treated with rituximab (RTX) achieved CR at 6 months more frequently than did those randomised to cyclophosphamide (CYC)/azathioprine (AZA) (65% vs 48%; p=0.04). The OR for CR at 6 months among PR3-AAV patients treated with RTX as opposed to CYC/AZA was 2.11 (95% CI 1.04 to 4.30) in analyses adjusted for age, sex and new-onset versus relapsing disease at baseline. PR3-AAV patients with relapsing disease achieved CR more often following RTX treatment at 6 months (OR 3.57; 95% CI 1.43 to 8.93), 12 months (OR 4.32; 95% CI 1.53 to 12.15) and 18 months (OR 3.06; 95% CI 1.05 to 8.97). No association between treatment and CR was observed in the MPO-AAV patient subset or in groups divided according to AAV diagnosis.ConclusionsPatients with PR3-AAV respond better to RTX than to CYC/AZA. An ANCA type-based classification may guide immunosuppression in AAV.Trial registration numberNCT00104299; post-results.

The RITUXVAS trial reported similar remission induction rates and safety between rituximab and cyclophosphamide based regimens for antineutrophil cytoplasm antibody (ANCA)-associated vasculitis at 12 months; however, immunosuppression maintenance requirements and longer-term outcomes after rituximab in ANCA-associated renal vasculitis are unknown. Forty-four patients with newly diagnosed ANCA-associated vasculitis and renal involvement were randomised, 3:1, to glucocorticoids plus either rituximab (375 mg/m(2)/week×4) with two intravenous cyclophosphamide pulses (n=33, rituximab group), or intravenous cyclophosphamide for 3-6 months followed by azathioprine (n=11, control group). The primary end point at 24 months was a composite of death, end-stage renal disease and relapse, which occurred in 14/33 in the rituximab group (42%) and 4/11 in the control group (36%) (p=1.00). After remission induction treatment all patients in the rituximab group achieved complete B cell depletion and during subsequent follow-up, 23/33 (70%) had B cell return. Relapses occurred in seven in the rituximab group (21%) and two in the control group (18%) (p=1.00). All relapses in the rituximab group occurred after B cell return. At 24 months, rates of the composite outcome of death, end-stage renal disease and relapse did not differ between groups. In the rituximab group, B cell return was associated with relapse. ISRCTN28528813.

The treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is based on remission-induction and remission-maintenance. Methotrexate is a widely used immunosuppressant but only a few studies explored its role for maintenance in AAV. This trial investigated the efficacy and safety of methotrexate as maintenance therapy for AAV. In this single-centre, open-label, randomised trial we compared methotrexate and cyclophosphamide for maintenance in AAV. We enrolled patients with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA), the latter with poor-prognosis factors and/or peripheral neuropathy. Remission was induced with cyclophosphamide. At remission, the patients were randomised to receive methotrexate or to continue with cyclophosphamide for 12 months; after treatment, they were followed for another 12 months. The primary end-point was relapse; secondary end-points included renal outcomes and treatment-related toxicity. Of the 94 enrolled patients, 23 were excluded during remission-induction or did not achieve remission; the remaining 71 were randomised to cyclophosphamide (n = 33) or methotrexate (n = 38). Relapse frequencies at months 12 and 24 after randomisation were not different between the two groups (p = 1.00 and 1.00). Relapse-free survival was also comparable (log-rank test p = 0.99). No differences in relapses were detected between the two treatments when GPA+MPA and EGPA were analysed separately. There were no differences in eGFR at months 12 and 24; proteinuria declined significantly (from diagnosis to month 24) only in the cyclophosphamide group (p = 0.0007). No significant differences in adverse event frequencies were observed. MTX may be effective and safe for remission-maintenance in AAV. clinicaltrials.gov NCT00751517.

Introduction This study aims to elucidate the prognosis and the effectiveness of current treatments for Japanese patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). Methods Patients with newly diagnosed MPA and GPA were enrolled in a nationwide, prospective, inception cohort study from 22 tertiary Japanese institutions, and treatment patterns and responses were evaluated for 24 months. Primary outcome measures were rates of remission (Birmingham Vasculitis Activity Score, 0) and remission with low-dose glucocorticoids (GC) (prednisolone ≤ 10 mg) (GC remission). Results Of 156 enrolled patients, 78 MPA patients and 33 GPA patients were included. Concomitant cyclophosphamide (CY) was used in 24 MPA (31 %) and 20 GPA (60 %) patients during the initial 3 weeks of treatment. After 6 months, remission was achieved in 66 MPA (85 %) and 29 GPA (87 %) patients, while GC remission was obtained in only 31 MPA (40 %) and 13 GPA (39 %) patients. During the 24-month period, 14 MPA patients and 2 GPA patients died; end stage renal disease (ESRD) was noted in 13 MPA patients but no GPA patients. Patients with severe disease, according to the European Vasculitis Study Group (EUVAS) classification, showed poorer ESRD-free and overall survival rates than those with generalized disease (p < 0.0001). There were no differences in relapse-free survival rates between GPA and MPA, among EUVAS-defined disease severity categories, and between anti-neutrophil cytoplasmic antibody subspecialties. Conclusions The majority of Japanese patients with MPA and GPA received treatment with high-dose GC and limited CY use, and showed high remission and relapse-free survival rates but low GC remission rates in clinical practice. Trial registration University Hospital Medical Information Network Clinical Trials Registry UMIN000001648 . Registered 28 February 2009.

Microscopic colitis is an inflammatory bowel disease divided into two subtypes: collagenous colitis and lymphocytic colitis. With an increasing incidence of microscopic colitis exceeding those of ulcerative and Crohn’s disease among elderly people in some countries, microscopic colitis is a debilitating life experience. Therefore, physicians should be familiar with its clinical features and management strategies because the disease deserves the same attention as the classical inflammatory bowel diseases. Here, state-of-the-art knowledge of microscopic colitis is provided from a global perspective with reference to etiopathology and how to establish the diagnosis with the overall aim to create awareness and improve rational management in clinical practice. The immune system and a dysregulated immune response seem to play a key role combined with risk factors (e.g. cigarette smoking) in genetically predisposed individuals. The symptoms are characterized by recurrent or chronic nonbloody, watery diarrhea, urgency, weight loss, and a female preponderance. As biomarkers are absent, the diagnosis relies on colonoscopy with a histological assessment of biopsy specimens from all parts of the colon. Although the disease is not associated with a risk of colorectal cancer, a recent nationwide, population-based cohort study found an increased risk of lymphoma and lung cancer. Budesonide is the first-line therapy for management, whereas immunomodulatory drugs (including biologics) and drugs with antidiarrheal properties may be indicated in those failing, dependent, or intolerant to budesonide. In microscopic colitis induced by checkpoint inhibitors, a drug class used increasingly for a wide range of malignancies, a more aggressive therapeutic approach with biologics introduced early seems reasonable. However, particular attention needs to be drawn to the existence of incomplete forms of microscopic colitis with the risk of being overlooked in routine clinical settings.

Microscopic colitis (MC) is a relatively common cause of chronic watery diarrhea, especially in older persons. Associated symptoms, including abdominal pain and arthralgias, are common. The diagnosis is based upon characteristic histological findings in the presence of diarrhea. The two types of MC, collagenous and lymphocytic colitis, share similar clinical features, with the main difference being the presence or absence of a thickened subepithelial collagen band. There are several treatment options for patients with MC, although only budesonide has been well studied in multiple controlled clinical trials. This review will describe the clinical features, epidemiology, pathophysiology, diagnostic criteria, and treatment of patients with MC.

ObjectiveMicroscopic colitis (MC) encompasses the two histopathological distinct entities of collagenous colitis (CC) and lymphocytic colitis (LC). In this Danish population-based cohort study, we examined the risk of MC following stool culture with Campylobacter concisus, C. jejuni, non-typhoidal Salmonella or a culture-negative stool test.DesignWe identified patients with a first-time positive stool culture with C. concisus, C. jejuni, non-typhoidal Salmonella or negative stool test, from 2009 through 2013 in North Denmark Region, Denmark, and matched each with 10 population comparisons. All subjects were followed up until 1 March 2018 using Systematised Nomenclature of Medicine codes from The Danish Pathology Register for incident diagnoses of CC and LC. We computed risk and adjusted HRs with 95% CIs for MC among patients and comparisons.ResultsWe identified 962 patients with C. concisus, 1725 with C. jejuni, 446 with Salmonella and 11 825 patients with culture-negative stools. The MC risk and HR versus comparisons were high for patients with C. concisus (risk 6.2%, HR 32.4 (95% CI 18.9 to 55.6)), less for C. jejuni (risk 0.6%, HR 3.7 (95% CI 1.8 to 7.7)), low for Salmonella (risk 0.4%, HR 2.2 (95% CI 0.5 to 10.8)) and for patients with negative stool testing (risk 3.3%, HR 19.6 (95% CI 16.4 to 23.4)). After exclusion of the first year of follow-up, the HRs were 9.3 (95% CI 4.1 to 20.1), 2.2 (95% CI 0.9 to 5.4), 1.3 (95% CI 0.2 to 11.1) and 5.6 (95% CI 4.6 to 7.2), respectively.ConclusionA high risk of MC was observed following C. concisus in stools. Further studies are needed to elucidate any underlying biological mechanisms.

Background The data from cohorts of childhood-onset granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) remain scarce and heterogeneous. We aimed to analyse the features at presentation, therapeutic approaches and the disease course of these rare diseases. Methods Electronic searches of Medline and the Cochrane Central Register of Controlled trials database were conducted. We also checked the reference lists of the studies included and other systematic reviews, to identify additional reports. We included all cohorts, cross-sectional studies or registries reporting features at presentation or outcomes in patients with a diagnosis of childhood-onset GPA or MPA (age <18 years). The pooled prevalence of clinical manifestations at presentation, ANCA and induction therapies for GPA and MPA was calculated. Results We reviewed 570 full texts and identified 14 studies on GPA and 8 on MPA. Childhood-onset GPA and MPA occurred predominantly in female subjects during adolescence. For GPA, ear-nose-throat (ENT) disease (pooled prevalence 82 % [95 % CI 78–87]), constitutional symptoms (73 % [95 % CI 55–88]), renal (65 % [95 % CI 49–79]), and lower respiratory tract (61 % [95 % CI 48–74]) manifestations were the most frequently reported at presentation. Renal disease was a hallmark of MPA (94 % [95 % CI 89–97]). ANCA were detected in >90 % of children with GPA or MPA. Combined corticosteroids and cyclophosphamide was the most frequently used first remission-inducing treatment for GPA (76 % [95 % CI 69–82]) and MPA (62 % [95 % CI 20–96]). Relapses occurred more frequently in GPA (67–100 %) than in MPA (25–50 %). The leading causes of death were the disease itself, and infections. Conclusions Childhood-onset MPA and GPA remain severe diseases with frequent relapses and a high cumulative morbidity. Survival and disease-free survival need to be improved.

ObjectiveTo develop and validate classification criteria for microscopic polyangiitis (MPA).MethodsPatients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in five phases: (1) identification of candidate items using consensus methodology, (2) prospective collection of candidate items present at the time of diagnosis, (3) data-driven reduction of the number of candidate items, (4) expert panel review of cases to define the reference diagnosis and (5) derivation of a points-based risk score for disease classification in a development set using least absolute shrinkage and selection operator logistic regression, with subsequent validation of performance characteristics in an independent set of cases and comparators.ResultsThe development set for MPA consisted of 149 cases of MPA and 408 comparators. The validation set consisted of an additional 142 cases of MPA and 414 comparators. From 91 candidate items, regression analysis identified 10 items for MPA, 6 of which were retained. The final criteria and their weights were as follows: perinuclear antineutrophil cytoplasmic antibody (ANCA) or anti-myeloperoxidase-ANCA positivity (+6), pauci-immune glomerulonephritis (+3), lung fibrosis or interstitial lung disease (+3), sino-nasal symptoms or signs (−3), cytoplasmic ANCA or anti-proteinase 3 ANCA positivity (−1) and eosinophil count ≥1×109/L (−4). After excluding mimics of vasculitis, a patient with a diagnosis of small- or medium-vessel vasculitis could be classified as having MPA with a cumulative score of ≥5 points. When these criteria were tested in the validation data set, the sensitivity was 91% (95% CI 85% to 95%) and the specificity was 94% (95% CI 92% to 96%).ConclusionThe 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for MPA are now validated for use in clinical research.

Background This study investigated poor prognostic factors for the relapse of interstitial lung disease (ILD) in patients with microscopic polyangiitis (MPA) after remission induction therapy. Methods We enrolled patients diagnosed with MPA complicated by ILD according to the Chapel Hill Consensus definition from 2001 to 2023 in multiple institutions in the REVEAL cohort. All patients who were treated with immunosuppressive therapy were followed up, and those who relapsed with ILD were extracted in this study. We explored the risk factors for predicting ILD relapse in patients with MPA-ILD by comparing the demographic, clinical, laboratory, and radiological findings and treatments between the relapsed and non-relapsed groups on admission. Results Of 243 patients with MPA, 134 (55.1%) with MPA-ILD were enrolled. Among them, 28 (20.9%) relapsed during a mean follow-up of 4.2 years. The initial serum Krebs von den Lungen-6 (KL-6) and surfactant protein-D (SP-D) levels and the prevalence of usual interstitial pneumonia (UIP) pattern were significantly higher in the relapsed group. The biomarkers were also risk factors for relapse in multivariate Cox regression analysis. The best cut-off values of KL-6, SP-D for predicting ILD relapse were 430 U/mL and 89.5 ng/mL, respectively. We created prediction models based on the best cut-off values for KL-6, SP-D, and the presence of the UIP pattern (KSU model). The 10-year relapse rate was significantly different among patients with MPA-ILD stratified by the number of risk factors based on the KSU model. A higher relapse rate was associated with higher all-cause mortality. Conclusions The initial serum high KL-6 and SP-D levels and the prevalence of the UIP pattern were associated with ILD relapse in patients with MPA-ILD. Our multicentre cohort study indicated that the KSU model, which consists of KL-6 ≥ 430 U/mL, SP-D ≥ 89.5 ng/mL, and the presence of the UIP pattern, is a useful predictor of ILD relapse in patients with MPA after immunosuppressive therapy.