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1.
Martine Gayraud Loïc Guillevin Philippe Le Toumelin Pascal Cohen Franois Lhote Philippe Casassus Bernard Jarrousse 《Arthritis \u0026amp; Rheumatology》2001,44(3):666-675
Objective
To determine the long‐term outcome of patients with polyarteritis nodosa (PAN), microscopic polyangiitis (MPA), and Churg‐Strauss syndrome (CSS), to compare the long‐term outcome with the overall French population, to evaluate the impact on outcome of the type of vasculitis, prognostic factors, and treatments administered at diagnosis, and to analyze treatment side effects and sequelae.Methods
Data from PAN, MPA, and CSS patients (n = 278) who were enrolled between 1980 and 1993 were collected in 1996 and 1997 and analyzed. Two prognostic scoring systems, the Five‐Factors Score (FFS) and the Birmingham Vasculitis Activity Score (BVAS), were used to evaluate all patients at the time of diagnosis.Results
The mean (±SD) followup of the entire population was 88.3 ± 51.9 months (range 3 days to 192 months). Of the 85 deaths recorded, at least 41 were due to progressive vasculitis or its consequences. Death rates reflected disease severity, as assessed by the FFS (P = 0.004) and the BVAS (P < 0.0002), and the 2 scores were correlated (r = 0.69). Relapses, rarer in hepatitis B virus (HBV)–related PAN (7.9%) than in MPA (34.5%) (P = 0.004), occurred in 56 patients (20.1%) and did not reflect disease severity. Survival curves were similar for the subpopulation of 215 patients with CSS, MPA, and non–HBV‐related PAN who were given first‐line corticosteroids (CS) with or without cyclophosphamide (CYC). However, CS with CYC therapy significantly prolonged survival for patients with FFS scores ≥2 (P = 0.041). Relapse rates were similar regardless of the treatment regimen; only patients treated with CS alone had uncontrolled disease. CYC was associated with a greater frequency of side effects (P < 0.00001).Conclusion
Rates of mortality due to PAN (related or unrelated to HBV), MPA, and CSS reflected disease severity and were higher than the mortality rate in the general population (P < 0.0004). Rates of relapse, more common in MPA than HBV‐related PAN patients, did not reflect disease severity. Survival rates were better among the more severely ill patients who had received first‐line CYC. Based on these findings, we recommend that the intensity of the initial treatment be consistent with the severity of the disease. The use of the FFS and BVAS scores improved the ability to evaluate the therapeutic response.2.
Suzanne E. Lane Richard A. Watts Graham Bentham Nicholas J. Innes David G. I. Scott 《Arthritis \u0026amp; Rheumatology》2003,48(3):814-823
Objective
To investigate the association between primary systemic vasculitis (PSV) and environmental risk factors.Methods
Seventy‐five PSV cases and 273 controls (220 nonvasculitis, 19 secondary vasculitis, and 34 asthma controls) were interviewed using a structured questionnaire. Factors investigated were social class, occupational and residential history, smoking, pets, allergies, vaccinations, medications, hepatitis, tuberculosis, and farm exposure in the year before symptom onset (index year). The Standard Occupational Classification 2000 and job‐exposure matrices were used to assess occupational silica, solvent, and metal exposure. Stepwise multiple logistic regression was used to calculate the odds ratio (OR) and 95% confidence interval (95% CI) adjusted for potential confounders. Total PSV, subgroups (47 Wegener's granulomatosis [WG], 12 microscopic polyangiitis, 16 Churg‐Strauss syndrome [CSS]), and antineutrophil cytoplasmic antibody (ANCA)–positive cases were compared with control groups.Results
Farming in the index year was significantly associated with PSV (OR 2.3 [95% CI 1.2–4.6]), with WG (2.7 [1.2–5.8]), with MPA (6.3 [1.9–21.6]), and with perinuclear ANCA (pANCA) (4.3 [1.5–12.7]). Farming during working lifetime was associated with PSV (2.2 [1.2–3.8]) and with WG (2.7 [1.3–5.7]). Significant associations were found for high occupational silica exposure in the index year (with PSV 3.0 [1.0–8.4], with CSS 5.6 [1.3–23.5], and with ANCA 4.9 [1.3–18.6]), high occupational solvent exposure in the index year (with PSV 3.4 [0.9–12.5], with WG 4.8 [1.2–19.8], and with classic ANCA [cANCA] 3.9 [1.6–9.5]), high occupational solvent exposure during working lifetime (with PSV 2.7 [1.1–6.6], with WG 3.4 [1.3–8.9], and with cANCA 3.3 [1.0–10.8]), drug allergy (with PSV 3.6 [1.8–7.0], with WG 4.0 [1.8–8.7], and with cANCA 4.7 [1.9–11.7]), and allergy overall (with PSV 2.2 [1.2–3.9], with WG 2.7 [1.4–5.7]). No other significant associations were found.Conclusion
A significant association between farming and PSV has been identified for the first time. Results also support previously reported associations with silica, solvents, and allergy.3.
W. H. Schmitt R. Linder E. Reinhold‐Keller W. L. Gross 《Arthritis \u0026amp; Rheumatology》2001,44(8):1887-1896
Objective
To examine the operating characteristics of the American College of Rheumatology (ACR) classification criteria for Churg‐Strauss syndrome (CSS) and Wegener's granulomatosis (WG), and to develop and validate improved criteria for distinguishing CSS from WG.Methods
The ACR classification criteria for WG and CSS were applied to 40 consecutive CSS patients age‐ and sex‐matched with 40 patients with WG. Forty‐three clinical, laboratory, and biopsy parameters were assessed. Artificial neural networks (ANNs) were trained and tested with all 43 parameters (set A) and with 15 solely clinical parameters documented at the initial manifestation of the disease (set B). The ANNs were trained with data from the first 27 CSS and 27 WG patients and validated with data from the next 13 consecutive CSS and 13 WG patients. To compare the ANNs with established methods, traditional format and classification tree criteria were generated using the same data sets.Results
Fourteen of 40 CSS patients fulfilled the ACR criteria for WG, while 4 WG patients met the ACR criteria for CSS. The ANN, in contrast, reliably distinguished all CSS cases from WG cases (parameter set A, accuracy 100%). For parameter set B, the ANN achieved an accuracy of 100% in the training phase and 96% for validation. The newly formulated traditional format and classification tree criteria reached an accuracy of 81% and 88%, respectively.Conclusion
The ACR criteria for WG do not reliably differentiate between CSS and WG (specificity 65%). An ANN, however, could be trained to correctly allocate all but 1 patient on the basis of clinical data. Indeed, the ANN applied in this study proved superior to established methods of classification. We suggest that an ANN may be effectively applied in the classification of systemic vasculitides.4.
Mikkel Faurschou Lene Mellemkjaer Inge Juul Sorensen Bjarne Svalgaard Thomsen Lene Dreyer Bo Baslund 《Arthritis \u0026amp; Rheumatology》2009,60(4):1187-1192
Objective
Experimental studies indicate that patients with Wegener's granulomatosis (WG) experience accelerated atherosclerosis. The purpose of this study was to investigate whether the occurrence of overt ischemic heart disease (IHD) is increased in WG.Methods
A total of 293 WG patients were included in the study. Information on all hospitalizations for IHD in Denmark from 1977 to 2006 was obtained from the Danish National Hospital Register. The WG patients were compared with the Danish background population with respect to rates of hospitalization for clinical manifestations of IHD after the date of vasculitis diagnosis by calculating standardized ratios of observed to expected (O:E) events.Results
Sixty‐three first IHD events were registered in the WG group during the 2,482 patient‐years of followup, corresponding to a significantly increased O:E ratio for IHD of 1.9 (95% confidence interval [95% CI] 1.4–2.4). A significantly increased risk was found for acute myocardial infarction (MI) (O:E ratio 2.5 [95% CI 1.6–3.7]), but not for angina pectoris (O:E ratio 1.3 [95% CI 0.7–2.1]). In analyses stratified according to the time between the diagnosis of vasculitis and the cardiovascular event, increased O:E ratios were found for IHD and acute MI occurring <5.0 years after WG diagnosis (2.1 [95% CI 1.4–3.0] for IHD and 3.6 [95% CI 2.0–5.9] for acute MI) and for IHD occurring ≥10.0 years after WG diagnosis (2.2 [95% CI 1.3–3.4]). Significantly increased O:E ratios for IHD and acute MI were found in patients who were ≥50.0 years of age at the time of diagnosis of WG, in male patients, and in patients who received high cumulative doses of cyclophosphamide.Conclusion
Compared with the background population, WG patients seem to experience an increased number of both early and late cardiovascular events due to IHD.5.
M. Kiene E. Csernok A. Müller C. Metzler A. Trabandt W. L. Gross 《Arthritis \u0026amp; Rheumatology》2001,44(2):469-473
Objective
To investigate cytokine production patterns of T cell lines (TCL) from patients with Churg‐Strauss syndrome (CSS).Methods
Short‐term polyclonal TCL were generated from peripheral blood of patients with CSS or Wegener's granulomatosis (WG) and healthy controls (HC). TCL were established in the presence of interleukin‐2 (IL‐2) and phytohemagglutinin and were phenotypically characterized by flow cytometry. Th1/Th2 cytokine production by stimulated TCL (72 hours) was analyzed by enzyme‐linked immunosorbent assay.Results
TCL that represented the progeny of in vivo–activated T cells from CSS patients displayed a heterogeneous immunophenotype, with a predominance of CD4+ T cells when compared with WG TCL, which were predominantly CD8+. All CSS TCL shared the ability to produce large amounts of interferon‐γ (IFNγ), IL‐4, and IL‐13 compared with HC (P = 0.014 for all 3). Production of IL‐4 and IL‐13 was higher in CSS TCL than in WG TCL (P = 0.014 for both). IL‐5 production was up‐regulated in WG TCL compared with CSS TCL (P = 0.014). Compared with HC, WG TCL showed increased production of IFNγ (P = 0.021), IL‐5 (P = 0.043), and IL‐13 (P = 0.021).Conclusion
Our results indicate that, while there is evidence for both a type 1 and a type 2 response in CSS, type 2 cytokine production pattern appears to predominate in this disease when compared with WG and HC.6.
Christian Agard Luc Mouthon Alfred Mahr Loïc Guillevin 《Arthritis care & research》2003,49(5):709-715
Objective
To describe initial clinical symptoms attributable to microscopic polyangiitis (MPA) or polyarteritis nodosa (PAN).Methods
We retrospectively reviewed the medical files of 72 patients (mean followup 6.7 years) with biopsy‐proven MPA (n = 36) or PAN (n = 36).Results
Initial manifestations were similar in both entities except for peripheral neuropathy (P = 0.02) and gastrointestinal tract involvement (P = 0.006), which were significantly more frequent in PAN, and general signs alone in MPA (8%; P = 0.02). The mean time to diagnosis was 9.8 ± 19.4 months; 35% of the patients died and 26% relapsed; significantly more MPA than PAN patients relapsed (P = 0.03). Time to diagnosis ≥90 days was associated with a trend toward more patients relapsing (P = 0.12), but not with an increased risk of mortality.Conclusion
Initial symptoms of MPA and PAN are usually nonspecific and last for several months before the diagnosis is made. A longer time to diagnosis is associated with a tendency to a higher relapse rate.7.
8.
Alfred D. Mahr Jeffrey C. Edberg John H. Stone Gary S. Hoffman E. William St.Clair Ulrich Specks Paul F. Dellaripa Philip Seo Robert F. Spiera Farshid N. Rouhani Mark L. Brantly Peter A. Merkel 《Arthritis \u0026amp; Rheumatology》2010,62(12):3760-3767
Objective
Deficiency of α1‐antitrypsin (α1AT) may be a determinant of susceptibility to Wegener's granulomatosis (WG). Several previous, mainly small, case–control studies have shown that 5–27% of patients with WG carried the α1AT deficiency Z allele. It is not clear whether the S allele, the other major α1AT deficiency variant, is associated with WG. This study investigated the relationship of the α1AT deficiency Z and S alleles with the risk of developing WG in a large cohort.Methods
We studied the distribution of the α1AT deficiency alleles Z and S in 433 unrelated Caucasian patients with WG and 421 ethnically matched controls. Genotyping was performed using an allele discrimination assay. Results were compared between cases and controls using exact statistical methods.Results
Among the patients with WG, the allele carriage frequencies of Z and S were 7.4% and 11.5%, respectively. The frequencies of the 6 possible genotypes differed in a statistically significant manner between cases and controls (P = 0.01). The general genetic 2‐parameter codominant model provided the best fit to the data. Compared with the normal MM genotype, the odds ratio (OR) for MZ or MS genotypes was 1.47 (95% confidence interval [95% CI] 0.98–2.22), and the OR for ZZ, SS, or SZ genotypes was 14.58 (95% CI 2.33–∞). ORs of similar direction and magnitude were observed within the restricted cohorts that excluded cases and controls carrying ≥1 Z or ≥1 S allele.Conclusion
Both Z and S alleles display associations with risk of WG in a codominant genetic pattern. These findings strengthen the evidence of a causal link between α1AT deficiency and susceptibility to WG.9.
Risa Miyashita Naoyuki Tsuchiya Toshio Yabe Shigeto Kobayashi Hiroshi Hashimoto Shoichi Ozaki Katsushi Tokunaga 《Arthritis \u0026amp; Rheumatology》2006,54(3):992-997
Objective
Genetic background and infection have been implicated in the etiology of microscopic polyangiitis (MPA). Killer cell immunoglobulin‐like receptors (KIRs) are a diverse family of activating and inhibitory receptors expressed on natural killer (NK) cells and T cells, the genes of which show extreme polymorphism. Some KIRs bind to HLA class I subgroups, and genetic interactions between KIR genes and their ligand HLA have been shown to be associated with several autoimmune and viral diseases. In this study, we examined possible associations of the presence or absence of KIR loci with a genetic predisposition to MPA.Methods
The presence or absence of 14 KIR loci was determined in 57 myeloperoxidase antineutrophil cytoplasmic antibody–positive Japanese subjects (43 patients with MPA and 239 healthy controls).Results
The carrier frequency of activating KIR2DS3 was significantly decreased among patients with MPA compared with healthy controls (4.7% versus 16.7%; P = 0.038, odds ratio [OR] 0.24, 95% confidence interval [95% CI] 0.06–0.94). When KIRs were analyzed in combination with their HLA ligands, the proportion of individuals carrying inhibitory KIR3DL1 and HLA–Bw4 but not activating receptor KIR3DS1, a combination presumed to be the most inhibitory of all KIR3DS1/3DL1/HLA–B combinations, was significantly increased in the MPA group compared with the control group (46.5% versus 27.0%; P = 0.014, OR 2.35, 95% CI 1.18–4.70). Furthermore, when subjects were classified according to KIR3DL1/3DS1/HLA–B and KIR2DL1/ HLA–C combinations, an increasing trend toward susceptibility was observed as combinations became more inhibitory.Conclusion
The decreased activation potential of NK and/or T cells associated with KIR/HLA genotypes may predispose to MPA, possibly through insufficient resistance against infections.10.
John H. Stone Misty L. Uhlfelder David B. Hellmann Sonya Crook Nita‐Marie Bedocs Gary S. Hoffman 《Arthritis \u0026amp; Rheumatology》2001,44(5):1149-1154
Objective
To evaluate the safety of etanercept (Enbrel) in patients receiving conventional treatment for Wegener's granulomatosis (WG).Methods
We performed a 6‐month open‐label trial of etanercept (25 mg subcutaneously twice weekly) which was added to standard therapies for WG (glucocorticoids, methotrexate, cyclophosphamide, azathioprine, cyclosporine) and prescribed according to disease severity. Evaluations of clinical response were determined by the Birmingham Vasculitis Activity Score for WG (BVAS/WG) in 20 patients with persistently active disease or with new flares of previously established WG. Fourteen of the 20 patients (70%) had etanercept added as the only new therapeutic variable.Results
Injection site reactions (ISRs) were the most common adverse event related to etanercept (8 episodes in 5 patients [25%]; <1% of all injections). All ISRs were mild. Two patients had a combined total of 5 hospitalizations (1 patient had 4), but no hospitalizations were attributable solely to etanercept‐related adverse events. One patient with severe subglottic stenosis developed pneumococcal tracheobronchitis and subsequently had a localized Herpes zoster infection. Nineteen patients (95%) were still taking etanercept at 6 months, the single exception being a patient who developed progression of orbital (retro‐bulbar) disease at 4 months. There were no deaths. The mean BVAS/WG at entry was 3.6 (range 1–8), which decreased at 6 months to 0.6 (P < 0.001, 95% confidence interval [95% CI] −4.0 to −2.1). Among the 14 patients in whom etanercept was the only new treatment variable, the mean daily prednisone dose decreased from 12.9 mg at entry to 6.4 mg at 6 months. This comparison did not achieve statistical significance (difference −6.5; P = 0.19, 95% CI −16.6 to +3.6). Sixteen of the patients (80%) achieved BVAS/WG scores of 0 at some point. However, intermittently active disease was observed in 15 patients (75%).Conclusion
In this open‐label trial, etanercept used in combination with standard treatments was well‐tolerated in patients with WG. Adverse events were few. BVAS/WG scores improved at 6 months, but intermittently active WG (occasionally severe) was common. A randomized, double‐masked trial to assess the efficacy of etanercept in WG has begun.11.
Valrie Martinez Pascal Cohen Christian Pagnoux Stphane Vinzio Alfred Mahr Luc Mouthon Laurent Sailler Claire Delaunay Alain Sadoun Loïc Guillevin 《Arthritis \u0026amp; Rheumatology》2008,58(1):308-317
Objective
To evaluate at 9 months and 24 months the safety and efficacy of intravenous immunoglobulins (IVIGs) administered for 6 months to treat relapses of Wegener's granulomatosis (WG) or microscopic polyangiitis (MPA) occurring either under treatment or during the year following discontinuation of corticosteroids and/or immunosuppressants.Methods
Patients received IVIGs (0.5 gm/kg/day for 4 days) as additional therapy administered monthly for 6 months and were assessed every 3–6 months. Corticosteroids could be maintained or reintroduced at the time of relapse; immunosuppressants could be continued but could not be reintroduced. At months 9 (end point) and 24 (followup), the following information was collected: complete or partial remission, relapse as assessed with the Birmingham Vasculitis Activity Score (BVAS) 2005, and tolerance and safety of IVIG therapy.Results
Twenty‐two Caucasian patients (7 men and 15 women) were studied: 19 had WG, and 3 had MPA. Their median age was 53 years (range 19–75 years), and their median duration of systemic vasculitis was 27 months (range 7–109 months). Their median BVAS 2005 score was 11 (range 3–25). At study entry, 21 patients were ANCA positive, and 21 patients were taking steroids and/or immunosuppressants. All patients experiencing relapse were treated with the same drug(s) plus IVIGs. All patients initially responded to IVIG therapy. By month 9, 13 patients had complete remission, 1 had partial remission, 7 had relapse, and 1 had treatment failure. In 8 of the 14 patients who had remission, the response persisted at month 24. Seven patients experienced minor side effects.Conclusion
IVIGs induced complete remissions of relapsed ANCA‐associated vasculitides in 13 of 22 patients at month 9. Because of the good safety and tolerance profiles of IVIGs, these agents can be included in a therapeutic strategy with other drugs used to treat relapses of WG or MPA.12.
Christian Pagnoux Raphale Seror Corneliu Henegar Alfred Mahr Pascal Cohen Vronique Le Guern Boris Bienvenu Luc Mouthon Loïc Guillevin 《Arthritis \u0026amp; Rheumatology》2010,62(2):616-626
Objective
Previous studies of polyarteritis nodosa (PAN) included patients with microscopic polyangiitis, because these entities were not distinguished prior to the Chapel Hill Consensus Conference (CHCC). This study was undertaken to describe the main characteristics of and long‐term outcomes in patients with well‐characterized PAN diagnoses.Methods
We conducted a systematic retrospective study of 348 patients who were diagnosed as having PAN between March 1963 and October 2005, were registered in the French Vasculitis Study Group database, and satisfied the American College of Rheumatology and CHCC criteria. Patient characteristics and outcomes were analyzed and compared according to hepatitis B virus (HBV) status.Results
At diagnosis, the mean ± SD age was 51.2 ± 17.3 years. The most frequent findings were general symptoms (93.1%), neurologic manifestations (79%), skin involvement (49.7%), abdominal pain (35.6%), and hypertension (34.8%); 66.2% had renal artery microaneurysms; 70.1% had histologically proven PAN. Patients with HBV‐related PAN (n = 123) had more frequent peripheral neuropathy, abdominal pain, cardiomyopathy, orchitis, and hypertension compared with patients with non–HBV‐related PAN (n = 225). During a mean ± SD followup of 68.3 ± 63.5 months, 76 patients (21.8%) relapsed (63 with non–HBV‐related PAN [28%] versus 13 with HBV‐related PAN [10.6%]; P < 0.001); 86 patients (24.7%) died (44 with non–HBV‐related PAN [19.6%] versus 42 with HBV‐related PAN [34.1%]; P = 0.003). Five‐year relapse‐free survival rates were 59.4% (95% confidence interval [95% CI] 52.6–67.0) versus 67.0% (95% CI 58.5–76.8) for non–HBV‐related PAN and HBV‐related PAN, respectively. Multivariate analysis retained age >65 years, hypertension, and gastrointestinal manifestations requiring surgery or at least consultation with a surgeon as independent predictors of death, whereas patients with cutaneous manifestations or non–HBV‐related PAN had a higher risk of relapse.Conclusion
Our findings indicate that the rate of mortality from PAN remains high, especially for the elderly, and relapses do occur, particularly in patients with non–HBV‐related PAN with cutaneous manifestations.13.
Objective
To systematically review the effectiveness of cyclobenzaprine in the treatment of fibromyalgia.Methods
Articles describing randomized, placebo‐controlled trials of cyclobenzaprine in people with fibromyalgia were obtained from Medline, EMBase, Psyclit, the Cochrane Library, and Federal Research in Progress Database. Unpublished literature and bibliographies were also reviewed. Outcomes, including global improvement, treatment effects on pain, fatigue, sleep, and tender points over time, were abstracted.Results
Five randomized, placebo‐controlled trials were identified. The odds ratio for global improvement with therapy was 3.0 (95% confidence interval [95% CI] 1.6–5.6) with a pooled risk difference of 0.21 (95% CI 0.09–0.34), which calculates to 4.8 (95% CI 3.0–11) individuals needing treatment for 1 patient to experience symptom improvement. Pain improved early on, but there was no improvement in fatigue or tender points at any time.Conclusion
Cyclobenzaprine‐treated patients were 3 times as likely to report overall improvement and to report moderate reductions in individual symptoms, particularly sleep.14.
Augusto Vaglio Davide Martorana Umberto Maggiore Chiara Grasselli Adele Zanetti Alberto Pesci Giovanni Garini Paolo Manganelli Paolo Bottero Bruno Tumiati Renato A. Sinico Mario Savi Carlo Buzio Tauro M. Neri 《Arthritis \u0026amp; Rheumatology》2007,56(9):3159-3166
Objective
To explore the association between HLA alleles and Churg‐Strauss syndrome (CSS), and to investigate the potential influence of HLA alleles on the clinical spectrum of the disease.Methods
Low‐resolution genotyping of HLA–A, HLA–B, and HLA–DR loci and genotyping of TNFA −238A/G and TNFA −308A/G single‐nucleotide polymorphisms were performed in 48 consecutive CSS patients and 350 healthy controls.Results
The frequency of the HLA–DRB1*07 allele was higher in the CSS patients than in controls (27.1% versus 13.3%; χ2 = 12.64, P = 0.0003, corrected P [Pcorr] = 0.0042, odds ratio [OR] 2.42, 95% confidence interval [95% CI] 1.47–3.99). The HLA–DRB4 gene, present in subjects carrying either HLA–DRB1*04, HLA–DRB1*07, or HLA–DRB1*09 alleles, was also far more frequent in patients than in controls (38.5% versus 20.1%; χ2 = 16.46, P = 0.000058, Pcorr = 0.000232, OR 2.49, 95% CI 1.58–3.09). Conversely, the frequency of the HLA–DRB3 gene was lower in patients than in controls (35.4% versus 50.4%; χ2 = 7.62, P = 0.0057, Pcorr = 0.0228, OR 0.54, 95% CI 0.35–0.84). CSS has 2 major clinical subsets, antineutrophil cytoplasmic antibody (ANCA)–positive, with features of small‐vessel vasculitis, and ANCA‐negative, in which organ damage is mainly mediated by tissue eosinophilic infiltration; analysis of HLA–DRB4 in patients categorized by different numbers of vasculitic manifestations (purpura, alveolar hemorrhage, mononeuritis multiplex, rapidly progressive glomerulonephritis, and constitutional symptoms) showed that its frequency strongly correlated with the number of vasculitis symptoms (P for trend = 0.001).Conclusion
These findings indicate that HLA–DRB4 is a genetic risk factor for the development of CSS and increases the likelihood of development of vasculitic manifestations of the disease.15.
Olaf Wiesner Kimberly A. Russell Augustine S. Lee Dieter E. Jenne Matteo Trimarchi Gina Gregorini Ulrich Specks 《Arthritis \u0026amp; Rheumatology》2004,50(9):2954-2965
Objective
Human neutrophil elastase (HNE) and proteinase 3 (PR3) are structurally and functionally related. PR3 is the prominent target antigen for antineutrophil cytoplasmic antibodies (ANCAs) in Wegener's granulomatosis (WG). Reported frequencies of HNE ANCAs in WG and other autoimmune diseases range from 0% to 20%. We previously detected HNE ANCAs in patients with cocaine‐induced midline destructive lesions (CIMDL). We tested the hypothesis that discrepancies in the reported frequencies of HNE ANCAs in patients with vasculitis may be related to differences in detection methods, and that HNE ANCA may be a marker for CIMDL.Methods
HNE ANCA reactivity in 25 patients with CIMDL was characterized and compared with that in a control cohort of 604 consecutive patients (64 with WG, 14 with microscopic polyangiitis [MPA], and 526 others) and 45 healthy volunteers. HNE ANCAs were measured by indirect immunofluorescence using a previously undescribed expression system for recombinant HNE and by direct and capture enzyme‐linked immunosorbent assays using purified native HNE as target antigen.Results
Among patients with CIMDL, HNE ANCAs were detectable by 1 assay in 84%, by 2 assays in 68%, and by all 3 assays in 36%. Fifty‐seven percent of HNE ANCA–positive CIMDL sera were also PR3 ANCA–positive by at least 1 assay. In contrast, only 8 (1.3%) of 604 control sera reacted with HNE in at least 1 assay, 3 (0.5%) reacted in 2 assays, and only 1 serum sample (0.16%) reacted in all 3 assays. Sera obtained from patients with WG or MPA were universally HNE ANCA–negative, as were sera obtained from healthy controls.Conclusion
Optimal sensitivity for HNE ANCA requires multimodality testing. HNE ANCAs are frequent in CIMDL but not in other autoimmune diseases, including classic ANCA‐associated vasculitis. HNE ANCAs may discriminate between CIMDL and WG, whereas a positive test result for PR3 ANCA may not.16.
Lene Dreyer Mikkel Faurschou Mette Mogensen Sren Jacobsen 《Arthritis \u0026amp; Rheumatology》2011,63(10):3032-3037
Objective
Patients with systemic lupus erythematosus (SLE) seem to experience an increased prevalence of oncogenic virus infections. The aim of the present study was to investigate whether SLE patients have an increased risk of virus‐associated malignancies, defined as malignancies potentially caused by virus infection.Methods
A hospital‐based cohort of 576 SLE patients was linked to the Danish Cancer Registry. The cohort was followed up for malignancies from the date of SLE diagnosis, and standardized incidence ratios (SIRs) were calculated for various forms of cancer.Results
The median duration of followup was 13.2 years. Compared to the general population, the patients experienced an increased overall risk of cancer (SIR 1.6 [95% confidence interval (95% CI)] 1.2–2.0). We observed an increased risk of virus‐associated cancers combined (SIR 2.9 [95% CI 2.0–4.1]). Among human papillomavirus (HPV)–associated malignant and premalignant conditions, high risk was found for anal cancer (SIR 26.9 [95% CI 8.7–83.4]), vaginal/vulvar cancer (SIR 9.1 [95% CI 2.3–36.5]), epithelial dysplasia/carcinoma in situ of the uterine cervix (SIR 1.8 [95% CI 1.2–2.7]), and nonmelanoma skin cancer (SIR 2.0 [95% CI 1.2–3.6]). Increased SIRs were also found for other potentially virus‐induced cancer types (liver cancer SIR 9.9 [95% CI 2.5–39.8], bladder cancer SIR 3.6 [95% CI 1.4–9.7], and non‐Hodgkin's lymphoma SIR 5.0 [95% CI 1.9–13.3]).Conclusion
The patients in this SLE cohort experienced an increased risk of HPV‐associated tumors and other potentially virus‐induced cancers during long‐term followup. Our findings call for clinical alertness to oncogenic virus infections in SLE patients.17.
Christina Gummesson Isam Atroshi Charlotte Ekdahl Ragnar Johnsson Ewald Ornstein 《Arthritis care & research》2003,49(5):697-702
Objective
To estimate the prevalence of self reported chronic upper extremity pain associated with physical impairment in a general population, and its co‐occurrence with chronic upper extremity numbness or tingling and chronic pain at other locations.Methods
A general health questionnaire was mailed to 3,000 persons (age 25–74 years) who were randomly selected from a general population register.Results
The response rate was 83%. The prevalence of chronic upper extremity pain associated with physical impairment was 20.8% (95% confidence interval [95% CI] 19.2–22.5), and that of co‐occurring numbness or tingling was 6.7% (95% CI 5.7–7.7). Among the responders with chronic upper extremity pain associated with physical impairment, 84% reported more than 1 painful area.Conclusion
Chronic upper extremity pain associated with physical impairment and co‐occurring chronic upper extremity numbness or tingling were common in the general population. The presence of more than 1 location for pain in the upper extremity as well as in other parts of the body was frequent.18.
Loïc Guillevin Pascal Cohen Alfred Mahr Jean‐Pierre Arne Luc Mouthon Xavier Puchal Edouard Pertuiset Brigitte Gilson Mohamed Hamidou Patricia Lanoux Alain Bruet Marc Ruivard Philippe Vanhille Jean‐Franois Cordier 《Arthritis care & research》2003,49(1):93-100
Objective
Because the optimal cyclophosphamide (CY) treatment duration for severe polyarteritis nodosa (PAN) without virus infection and microscopic polyangiitis (MPA) has not been established, we conducted a trial to compare the effectiveness of 6 versus 12 CY pulses given in combination with corticosteroids (CS).Methods
Sixty‐five (18 PAN, 47 MPA) previously untreated patients were randomized to receive 12 (n = 34) or 6 (n = 31) CY pulses combined with CS. PAN and MPA were histologically proven or met ACR criteria. All patients presented ≥1 factor of severity according to the five factor score (FFS). CY pulses were administered every 2 weeks for 1 month, then every 4 weeks. The end point of the study was the number of events (relapses and/or deaths) occurring in each group, analyzed according to an intention‐to‐treat strategy. The outcome was evaluated by Cox proportional hazards analysis.Results
The baseline characteristics were similar for both groups. The mean (± SD) followup was 32 ± 21 months. Survival analysis showed a significantly lower relapse probability (P = 0.02; hazards ratio [HR] = 0.34) and higher event‐free survival (P = 0.02, HR = 0.44) for the 12 CY‐pulse group while the mortality rates were not significantly different (P = 0.47).Conclusion
These results suggest that 6 CY pulses are less effective than 12 CY pulses to treat severe PAN and MPA, particularly with respect to the risk of relapses.19.
Merete Pedersen Sren Jacobsen Peter Garred Hans O. Madsen Mette Klarlund Arne Svejgaard Bo V. Pedersen Jan Wohlfahrt Morten Frisch 《Arthritis \u0026amp; Rheumatology》2007,56(5):1446-1453
Objective
To study the role of shared epitope (SE) susceptibility genes, alone and in combination with tobacco smoking and other environmental risk factors, for risk of subtypes of rheumatoid arthritis (RA) defined by the presence or absence of serum antibodies against cyclic citrullinated peptides (CCPs).Methods
To address these issues, a nationwide case–control study was conducted in Denmark during 2002–2004, comprising incident cases of RA or patients with recently diagnosed RA (309 seropositive and 136 seronegative for IgG antibodies against CCP) and 533 sex‐ and age‐matched population controls. Associations were evaluated by logistic regression analyses, in which odds ratios (ORs) served as measures of relative risk.Results
Compared with individuals without SE susceptibility genes, SE homozygotes had an elevated risk of anti‐CCP–positive RA (OR 17.8, 95% confidence interval [95% CI] 10.8–29.4) but not anti‐CCP–negative RA (OR 1.07, 95% CI 0.53–2.18). Strong combined gene–environment effects were observed, with markedly increased risks of anti‐CCP–positive RA in SE homozygotes who were heavy smokers (OR 52.6, 95% CI 18.0–154), heavy coffee drinkers (OR 53.3, 95% CI 15.5–183), or oral contraceptive users (OR 44.6, 95% CI 15.2–131) compared with SE noncarriers who were not exposed to these environmental risk factors.Conclusion
Persons who are homozygous for SE susceptibility genes, notably those who are also exposed to environmental risk factors, have a markedly and selectively increased risk of anti‐CCP–positive RA. A distinction between anti‐CCP–positive RA and anti‐CCP–negative RA seems warranted, because these RA subtypes most likely represent etiologically distinct disease entities.20.
Sophia Lionaki Elizabeth R. Blyth Susan L. Hogan Yichun Hu Brent A. Senior Caroline E. Jennette Patrick H. Nachman J. Charles Jennette Ronald J. Falk 《Arthritis \u0026amp; Rheumatology》2012,64(10):3452-3462