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Current standard therapy for Wegener's granulomatosis and microscopic polyangiitis combines corticosteroids and cyclophosphamide to induce remission, followed by a less toxic immunosuppressant. This prospective, open-label, multicenter trial indicated that the safety and efficacy of azathioprine and methotrexate are similar for maintenance therapy after initial remission in these two conditions. This trial indicated that the safety and efficacy of azathioprine and methotrexate are similar for maintenance therapy after initial remission in Wegener's granulomatosis and microscopic polyangiitis. Combined corticosteroid and cyclophosphamide therapy remains the standard care for antineutrophil cytoplasmic antibody (ANCA)–associated vasculitides, despite the potential risk of adverse events, particularly with the long-term use of cyclophosphamide. 1 , 2 Moreover, even after induction with daily oral or pulse intravenous cyclophosphamide therapy, relapse rates remain as high as 15% at 12 months 3 and reach 38% at 30 months. 4 A decisive step in the approach to the treatment of Wegener's granulomatosis and microscopic polyangiitis was the development of a staged induction–maintenance strategy to reduce cumulative exposure to cyclophosphamide. This strategy uses cyclophosphamide to induce remission, followed by a less toxic immunosuppressant. . . .

In 2000, Tropheryma whipplei was finally identified as the cause of Whipple's disease, a chronic condition with protean manifestations that was first described in 1907. This review discusses the epidemiology, pathogenesis, diagnosis, and treatment of this rare and elusive chronic disease. This review discusses the epidemiology, pathogenesis, diagnosis, and treatment of this rare and elusive chronic disease. The discovery of Whipple's disease and its causative bacterium, Tropheryma whipplei, is a prime example of how modern technologies have contributed to medical knowledge. Although Whipple's disease was first described in 1907, 1 the first successful culture of T. whipplei was performed nearly a century later, in 2000. This accomplishment led to a new level of understanding of the disease. During the 20th century, knowledge of this chronic disease slowly accumulated (Table 1). 2 – 6 At the dawn of the 21st century, two major events — molecular amplification of the 16S ribosomal RNA (rRNA) of T. whipplei by polymerase-chain-reaction (PCR) assay and . . .

Objectives To evaluate the effect of adding a 10-week treatment of adalimumab to a standardised treatment with corticosteroids on the ability to taper more rapidly corticosteroid doses in patients with newly diagnosed giant cell arteritis (GCA). Methods Patients included in this double-blind, multicentre controlled trial were randomly assigned to receive a 10-week subcutaneous treatment of adalimumab 40 mg every other week or placebo in addition to a standard prednisone regimen (starting dose 0.7 mg/kg per day). The primary endpoint was the percentage of patients in remission on less than 0.1 mg/kg of prednisone at week 26. Analysis was performed by intention to treat (ITT). Results Among the 70 patients enrolled (adalimumab, n=34; placebo, n=36), 10 patients did not receive the scheduled treatment, seven in the adalimumab and three in the placebo group. By ITT, the number of patients achieving the primary endpoint was 20 (58.9%) and 18 (50.0%) in the adalimumab and placebo arm, respectively (p=0.46). The decrease in prednisone dose and the proportion of patients who were relapse free did not differ between the two groups. Serious adverse events occurred in five (14.7%) patients on adalimumab and 17 (47.2%) on placebo, including serious infections in three patients on adalimumab and five on placebo. Two patients died in the placebo arm (septic shock and cancer) and one in the adalimumab group (pneumonia). Conclusions In patients with newly diagnosed GCA, adding a 10-week treatment of adalimumab to prednisone did not increase the number of patients in remission on less than 0.1 mg/kg of corticosteroids at 6 months. Clinical trial registration number NCT00305539.

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 compare long-term efficacy of remission-maintenance regimens in patients with newly diagnosed or relapsing antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitides.MethodsThe 28-month Maintenance of Remission using Rituximab in Systemic ANCA-associated Vasculitis trial compared rituximab with azathioprine to maintain remission in patients with newly diagnosed or relapsing granulomatosis with polyangiitis, microscopic polyangiitis or renal-limited ANCA-associated vasculitis. Thereafter, prospective patient follow-up lasted until month 60. The primary endpoint was the major-relapse rate at month 60. Relapse and serious adverse event-free survival were also assessed.ResultsAmong the 115 enrolled patients, only one was lost to follow-up at month 60. For the azathioprine and rituximab groups, respectively, at month 60, the major relapse-free survival rates were 49.4% (95% CI 38.0% to 64.3%) and 71.9% (95% CI 61.2% to 84.6%) (p=0.003); minor and major relapse-free survival rates were 37.2% (95% CI 26.5% to 52.2%) and 57.9% (95% CI 46.4% to 72.2%) (p=0.012); overall survival rates were 93.0% (95% CI 86.7% to 99.9%) and 100% (p=0.045) and cumulative glucocorticoid use was comparable. Quality-adjusted time without symptoms and toxicity analysis showed that rituximab-treated patients had 12.6 months more without relapse or toxicity than those given azathioprine (p<0.001). Antiproteinase-3-ANCA positivity and azathioprine arm were independently associated with higher risk of relapse. HRs of positive ANCA to predict relapse increased over time.ConclusionThe rate of sustained remission for ANCA-associated vasculitis patients, following rituximab-based or azathioprine-based maintenance regimens, remained superior over 60 months with rituximab, with better overall survival.Trial registration numberNCT00748644.

To analyze the clinical and immunological characteristics at enrollment in a large prospective cohort of patients with primary Sjögren's syndrome (pSS) and to investigate the association between serum BAFF, beta2-microglobulin and free light chains of immunoglobulins and systemic disease activity at enrollment. Three hundred and ninety five patients with pSS according to American-European Consensus Criteria were included from fifteen centers of Rheumatology and Internal Medicine in the \"Assessment of Systemic Signs and Evolution of Sjögren's Syndrome\" (ASSESS) 5-year prospective cohort. At enrollment, serum markers were assessed as well as activity of the disease measured with the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI). Patient median age was 58 (25(th)-75(th): 51-67) and median disease duration was 5 (2-9) years. Median ESSDAI at enrollment was 2 (0-7) with 30.9% of patients having features of systemic involvement. Patients with elevated BAFF, beta2-microglobulin and kappa, lambda FLCS had higher ESSDAI scores at enrollment (4 [2]-[11] vs 2 [0-7], P = 0.03; 4 [1]-[11] vs 2 [0-7], P< 0.0001); 4 [2]-[10] vs 2 [0-6.6], P< 0.0001 and 4 [2-8.2] vs 2 [0-7.0], P = 0.02, respectively). In multivariate analysis, increased beta2-microglobulin, kappa and lambda FLCs were associated with a higher ESSDAI score. Median BAFF and beta2-microglobulin were higher in the 16 patients with history of lymphoma (1173.3(873.1-3665.5) vs 898.9 (715.9-1187.2) pg/ml, P = 0.01 and 2.6 (2.2-2.9) vs 2.1 (1.8-2.6) mg/l, P = 0.04, respectively). In pSS, higher levels of beta2-microglobulin and free light chains of immunoglobulins are associated with increased systemic disease activity.

Background In patients with tracheobronchial involvement, the differential diagnosis between granulomatosis with polyangiitis (GPA) and relapsing polychondritis (RP) can be challenging. The aim of this study was to describe the characteristics of airway abnormalities on chest computed tomography (CT) in patients with GPA or RP and to determine whether specific imaging criteria could be used to differentiate them. Methods GPA and RP patients with tracheobronchial involvement referred to a national referral center from 2008 to 2020 were evaluated. Their chest CT images were reviewed by two radiologists who were blinded to the final diagnosis in order to analyze the characteristics of airway involvement. The association between imaging features and a diagnosis of GPA rather than RP was analyzed using a generalized linear regression model. Results Chest CTs from 26 GPA and 19 RP patients were analyzed. Involvement of the subglottic trachea (odds ratio for GPA=28.56 [95% CI: 3.17; 847.63]; P=0.001 ) and extensive airway involvement (odds ratio for GPA=0.02 [95% CI: 0.00; 0.43]; P=0.008 ) were the two independent CT features that differentiated GPA from RP in multivariate analysis. Tracheal thickening sparing the posterior membrane was significantly associated to RP (odds ratio for GPA=0.09 [95% CI: 0.02; 0.39]; P=0.003 ) but only in the univariate analysis and suffered from only moderate interobserver agreement (kappa=0.55). Tracheal calcifications were also associated with RP only in the univariate analysis (odds ratio for GPA=0.21 [95% CI: 0.05; 0.78]; P=0.045 ). Conclusion The presence of subglottic involvement and diffuse airway involvement are the two most relevant criteria in differentiating between GPA and RP on chest CT. Although generally considered to be a highly suggestive sign of RP, posterior tracheal membrane sparing is a nonspecific and an overly subjective sign. Highlights • The presence of subglottic involvement is in favor of GPA. • Extensive airway involvement is in favor of RP. • Posterior tracheal membrane sparing is a nonspecific and an overly subjective sign.