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Objective To provide evidence-based recommendations and expert guidance for the management of antineutrophil cytoplasmic antibody-associated vasculitis (AAV), including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). Methods Clinical questions regarding the treatment and management of AAV were developed in the population, intervention, comparator, and outcome (PICO) format (47 for GPA/MPA, 34 for EGPA). Systematic literature reviews were conducted for each PICO question. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess the quality of evidence and formulate recommendations. Each recommendation required ≥70% consensus among the Voting Panel. Results We present 26 recommendations and 5 ungraded position statements for GPA/MPA, and 15 recommendations and 5 ungraded position statements for EGPA. This guideline provides recommendations for remission induction and maintenance therapy as well as adjunctive treatment strategies in GPA, MPA, and EGPA. These recommendations include the use of rituximab for remission induction and maintenance in severe GPA and MPA and the use of mepolizumab in nonsevere EGPA. All recommendations are conditional due in part to the lack of multiple randomized controlled trials and/or low-quality evidence supporting the recommendations. Conclusion This guideline presents the first recommendations endorsed by the American College of Rheumatology and the Vasculitis Foundation for the management of AAV and provides guidance to health care professionals on how to treat these diseases.

Objective To provide evidence-based recommendations and expert guidance for the management of giant cell arteritis (GCA) and Takayasu arteritis (TAK) as exemplars of large vessel vasculitis. Methods Clinical questions regarding diagnostic testing, treatment, and management were developed in the population, intervention, comparator, and outcome (PICO) format for GCA and TAK (27 for GCA, 27 for TAK). Systematic literature reviews were conducted for each PICO question. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of the evidence. Recommendations were developed by the Voting Panel, comprising adult and pediatric rheumatologists and patients. Each recommendation required ≥70% consensus among the Voting Panel. Results We present 22 recommendations and 2 ungraded position statements for GCA, and 20 recommendations and 1 ungraded position statement for TAK. These recommendations and statements address clinical questions relating to the use of diagnostic testing, including imaging, treatments, and surgical interventions in GCA and TAK. Recommendations for GCA include support for the use of glucocorticoid-sparing immunosuppressive agents and the use of imaging to identify large vessel involvement. Recommendations for TAK include the use of nonglucocorticoid immunosuppressive agents with glucocorticoids as initial therapy. There were only 2 strong recommendations; the remaining recommendations were conditional due to the low quality of evidence available for most PICO questions. Conclusion These recommendations provide guidance regarding the evaluation and management of patients with GCA and TAK, including diagnostic strategies, use of pharmacologic agents, and surgical interventions.

This systematic review compares treatment options for patients with giant cell arteritis (GCA) and evaluates the test accuracy of studies used in diagnosing and monitoring GCA. These studies were used to inform evidence‐based recommendations for the American College of Rheumatology (ACR)/Vasculitis Foundation (VF) vasculitis management guidelines. A systematic review and search of articles in English in Ovid Medline, PubMed, Embase, and the Cochrane Library was conducted. Articles were screened for suitability, and studies presenting the highest level of evidence were given preference. Three hundred ninety‐nine full‐text articles addressing GCA questions were reviewed to inform 27 Population, Intervention, Comparison, and Outcome questions. No benefit was found with intravenous glucocorticoids (GCs) compared with high‐dose oral GCs in patients with cranial ischemic symptoms (27.4% vs 12.3%; odds ratio [OR] 2.39 [95% confidence interval (CI) 0.75‐7.62], [very low certainty of evidence]). Weekly tocilizumab with a 26‐week GC taper was superior to a 52‐week GC taper in patients achieving remission (risk ratio 4.00 [95% CI 1.97‐8.12], [low certainty of evidence]). Non‐GC immunosuppressive therapies with GCs compared with GCs alone showed no statistically significant in relapse at 1 year (OR 0.87 [95% CI 0.73‐1.04], [moderate certainty of evidence]) or serious adverse events (OR 0.81 [95% CI 0.54‐1.20]; [moderate certainty of evidence]). Temporal artery biopsy has a sensitivity of 61% (95% CI 38%‐79%) and a specificity of 98% (95% CI 95%‐99%) in patients with a clinical diagnosis of suspected GCA. This comprehensive systematic review synthesizes and evaluates the benefits and harms of different treatment options and the accuracy of commonly used tests for the diagnosis and monitoring of GCA.

Objective The aim of this systemic review is to compare different treatments for patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) to inform evidence-based recommendations for the American College of Rheumatology (ACR)/Vasculitis Foundation (VF) Vasculitis Management Guidelines. Methods A systemic review was conducted by searching articles in English using OVID Medline, PubMed, Embase, and the Cochrane Library. Articles were screened for suitability in addressing PICO questions, with studies presenting the highest level of evidence given preference. Results A total of 729 full-text articles addressing GPA and MPA PICO questions were reviewed. For remission induction, rituximab was shown to be noninferior to cyclophosphamide (CYC) (odds ratio [OR]: 1.55, moderate certainty of evidence). The addition of plasma exchange to induction therapy in severe disease did not improve the composite end point of death or end stage renal disease (hazard ratio [HR]: 0.86 [95% confidence interval CI: 0.65, 1.13], moderate certainty of evidence). In nonsevere disease, methotrexate was noninferior to CYC for induction of remission (remission at 6 months of 90% vs. 94%). For maintenance of remission, methotrexate and azathioprine showed no difference in the risk of relapse over a mean follow-up of 29 months (HR: 0.92, [95% CI: 0.52, 1.65]low certainty of evidence). As maintenance therapy, rituximab was superior to a tapering azathioprine strategy in major relapse-free survival at 28 months (HR: 6.61, [95% CI: 1.56, 27.96], moderate certainty of evidence). In two randomized trials, longer-term azathioprine maintenance therapy (>24 months) is associated with fewer relapses without an increase in adverse events. Conclusion This comprehensive systematic review synthesizes and evaluates the benefits and toxicities of different treatment options for GPA and MPA.

OBJECTIVE Eosinophilic granulomatosis with polyangiitis (EGPA) is part of a group of vasculitides commonly referred to as antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), in addition to granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and renal-limited vasculitis. Patients with EGPA characteristically have asthma and marked peripheral eosinophilia with only approximately 30% to 35% of patients being myeloperoxidase (MPO)-ANCA positive, distinguishing it from other forms of AAV (1,2). The aim of this systematic review is to support the development of the American College of Rheumatology/Vasculitis Foundation guideline for the management of EGPA. METHODS A systematic review was conducted of the literature for seven forms of primary systemic vasculitis (GPA, MPA, EGPA, polyarteritis nodosa, Kawasaki disease, giant cell arteritis, and Takayasu arteritis). The search was done for articles in English using Ovid Medline, PubMed, Embase, and the Cochrane Library. Articles were screened for suitability in addressing population/patients, intervention, comparator, and outcomes (PICO) questions, with studies presenting the highest level of evidence given preference. Two independent reviewers conducted a title/abstract screen and full-text review for each eligible study. RESULTS The initial search, conducted in August 2019, included 13 800 articles, of which 2596 full-text articles were reviewed. There were 190 articles (addressing 34 PICO questions) reporting on the diagnosis and management of EGPA. CONCLUSION This comprehensive systematic review synthesizes and evaluates the accuracy of commonly used tests for EGPA as well as benefits and toxicities of different treatment options.

Objective: We sought to characterize microbiomes of thoracic aortas from patients with non-infectious aortitis due to giant cell arteritis (GCA) and clinically isolated aortitis (CIA) and to compare them to non-inflammatory aorta aneurysm controls. We also compared microbiomes from concurrently processed and separately reported temporal arteries (TA) and aortas. Methods: From 220 prospectively enrolled patients undergoing surgery for thoracic aorta aneurysm, 49 were selected. Inflammatory and non-inflammatory cases were selected based on ability to match for age (+/-10 years), gender, and race. Biopsies were collected under aseptic conditions and snap-frozen. Taxonomic classification of bacterial sequences was performed to the genus level and relative abundances were calculated. Microbiome differential abundances were analyzed by principal coordinates analysis. Results : Forty-nine patients with thoracic aortic aneurysms (12 CIA, 14 GCA, 23 non-inflammatory aneurysms) were enrolled. Alpha ( P = 0.018) and beta ( P = 0.024) diversity differed between specimens from aortitis cases and controls. There were no significant differences between CIA and GCA ( P > 0.7). The largest differential abundances between non-infectious aortitis and non-inflammatory control samples included Enterobacteriaceae , Phascolarctobacterium , Acinetobactor , Klebsiella , and Prevotella. Functional metagenomic predictions with PICRUSt revealed enrichment of oxidative phosphorylation and porphyrin metabolism pathways and downregulation of transcription factor pathways in aortitis compared to controls. Microbiomes of aortic samples differed significantly from temporal artery samples from a companion study, in both control and GCA groups ( P = 0.0002). Conclusion: Thoracic aorta aneurysms, far from being sterile, contain unique microbiomes that differ from those found in temporal arteries. The aorta microbiomes are most similar between aneurysms that were associated with inflammation, GCA, and CIA, but differed from those associated with non-inflammatory etiologies. These findings are promising in that they indicate that microbes may play a role in the pathogenesis of aortitis-associated aneurysms or non-inflammatory aneurysms by promoting or protecting against inflammation. However, we cannot rule out that these changes are related to alterations in tissue substrate that favor secondary changes in microbial communities.

Systemic autoimmune diseases are an important cause of pericardial involvement and contribute to up to ∼22% cases of pericarditis with a known aetiology. The underlying mechanism for pericardial involvement varies with each systemic disease and leads to a poor understanding of its management. Multimodality imaging establishes the diagnosis and determines the type and extent of pericardial involvement. In this review, we elaborate upon various pericardial syndromes associated with different systemic autoimmune and autoinflammatory diseases and the multitude of imaging modalities that can be used to further characterize autoimmune pericardial involvement. Lastly, these forms of pericarditis have a greater likelihood of recurrence, and clinicians need to understand their unique treatment approaches to improve patient outcomes.

Objective To provide evidence-based recommendations and expert guidance for the management of systemic polyarteritis nodosa (PAN). Methods Twenty-one clinical questions regarding diagnostic testing, treatment, and management were developed in the population, intervention, comparator, and outcome (PICO) format for systemic, non-hepatitis B-related PAN. Systematic literature reviews were conducted for each PICO question. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess the quality of evidence and formulate recommendations. Each recommendation required ≥70% consensus among the Voting Panel. Results We present 16 recommendations and 1 ungraded position statement for PAN. Most recommendations were graded as conditional due to the paucity of evidence. These recommendations support early treatment of severe PAN with cyclophosphamide and glucocorticoids, limiting toxicity through minimizing long-term exposure to both treatments, and the use of imaging and tissue biopsy for disease diagnosis. These recommendations endorse minimizing risk to the patient by using established therapy at disease onset and identify new areas where adjunctive therapy may be warranted. Conclusion These recommendations provide guidance regarding diagnostic strategies, use of pharmacologic agents, and imaging for patients with PAN.

PubMedID: 28864648 Objective. To arrive at consensus for candidate outcomes for disease activity assessment in largevessel vasculitis (LVV) in clinical trials. Methods.A Delphi survey including 99 items was circulated among international experts for 3 rounds. Results. Fifty-seven items were accepted for both giant cell arteritis and Takayasu arteritis. Sixty-seven percent of experts voted to have a common approach for both diseases with additional disease-specific items such as weight loss, scalp tenderness/necrosis, morning stiffness, dizziness, visual symptoms, and imaging. Conclusion. This study highlights similarities and differences in experts' perspectives for assessing clinical activity in LVV and may guide a consensus-driven core set of validated outcomes. Copyright © 2017. All rights reserved. National Institute of Arthritis and Musculoskeletal and Skin Diseases: U01 AR51874 04, U54 AR057319 National Center for Research Resources: U54 RR019497 Sponsored by the Vasculitis Clinical Research Consortium, which has received support from the US National Institute of Arthritis and Musculoskeletal and Skin Diseases (U54 AR057319 and U01 AR51874 04), the National Center for Research Resources (U54 RR019497), and the Office of Rare Diseases Research. Additional support for the work of the OMERACT Vasculitis Working Group was received through a Patient-Centered Outcomes Research Institute Pilot Project Grant. S.Z. Aydin, MD, Associate Professor, Division of Rheumatology, The Ottawa Hospital Research Institute, University of Ottawa; H. Direskeneli, MD, Professor of Rheumatology, Division of Rheumatology, Marmara University Faculty of Medicine; P.A. Merkel, MD, MPH, Professor of Medicine and Epidemiology, Division of Rheumatology, and Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania. Address correspondence to Dr. P.A. Merkel, Section of Rheumatology, University of Pennsylvania, White Building, 5th Floor Penn, 3400 Spruce St., Philadelphia, Pennsylvania 19104, USA. E-mail: pmerkel@upenn.edu Accepted for publication June 3, 2017.

To determine outcomes in relation to duration of maintenance therapy in patients with granulomatosis with polyangiitis (Wegener’s) (GPA), we conducted a retrospective chart review of patients with GPA seen at a single vasculitis center from 1992 to 2010. All patients achieved remission defined by a Birmingham Vasculitis Activity Score for Wegener Granulomatosis (BVAS/WG) of 0 with either cyclophosphamide or methotrexate. After achieving remission all patients were started on maintenance therapy with either methotrexate or azathioprine. The study comprised 157 patients with a median follow-up of 3.1 years. Using a univariate model, the continuation of maintenance medications for >18 months showed a 29% reduction in hazard ratio (HR) for relapse (HR, 0.71; 95% confidence interval [CI], 0.42–1.19; p = 0.19). Treatment for >36 months showed a 66% reduction in hazard ratio for relapse (HR, 0.34; 95% CI, 0.15–0.76; p = 0.008). When length of treatment was considered as a continuous factor, longer courses had an inverse relationship with the risk of relapse (HR, 0.70; 95% CI, 0.58–0.84; p < 0.001), which remained significant after adjusting for prednisone dose (HR, 0.59; 95% CI, 0.42–0.83; p = 0.003). Fifty-two percent of relapses occurred while the patients were off maintenance therapy. Among all patients who relapsed on therapy, 52% of those receiving methotrexate were on

To review the association of thrombosis and vasculitis and discuss some of the proposed causal mechanisms.It is becoming increasingly evident that various systemic inflammatory diseases such as vasculitis are associated with an increased risk of both venous and arterial thrombosis. Increasing evidence supports the use of immunosuppression in the management of venous thrombosis in Behçet's disease. An increased incidence of thromboembolic disease in antineutrophil cytoplasmic antibody-associated vasculitis has been recognized, especially during periods of active disease. In addition, a higher risk of ischemic heart disease in these patients has also been observed. As in giant cell arteritis, recent evidence supports the role of aspirin in the prevention of ischemic events in Takayasu's disease.Thromboembolic disease is an important complication of several forms of systemic vasculitis, and it may result in significant morbidity and mortality. Many questions such as the role for screening of asymptomatic patients, prevention of thrombosis, and duration of anticoagulation in patients with vasculitis remain unanswered. Future studies exploring the mechanisms of thrombosis and its link to inflammation may provide insights in predicting patients at a higher risk for thrombosis and improve outcomes.

Granulomatosis with polyangiitis is a common form of small-vessel vasculitis, remarkable for its tendency toward multisystem manifestations. Standard induction treatment calls for the use of low-dose daily cyclophosphamide (CYC) and glucocorticoids. Treatment goals for newly diagnosed patients include increased survival, induction of remission, reduction of relapse frequency, and minimization of treatment toxicity. Induction and maintenance treatments with CYC, glucocorticoids, and other immunosuppressive therapies improve the disease course, but relapse- and treatment-related toxicity and infections demand consistent, patient-specific monitoring.

Cardiovascular disease is a common and under-recognized problem in patients with systemic rheumatic conditions. Patients may present with disease associated heart involvement at the time of diagnosis or later in the course of the illness. The manifestations vary by disease, and all structures in the heart can be affected and may result in significant morbidity and mortality. Manifestations of cardiac disease in these patients range from subclinical to severe and may require aggressive immunosuppressive therapy. Early recognition is important for prompt institution of appropriate therapy. Treatment of disease associated cardiac involvement is based on severity of disease with more severe manifestations often requiring a combination of corticosteroid and cytotoxic agent. Premature atherosclerosis has been increasingly recognized in patients with systemic lupus erythematosus and rheumatoid arthritis and may result in premature coronary death when compared to the general population. Aggressive control of systemic inflammation in these diseases may result in a reduction in the risk of ischemic heart disease. Although aggressive treatment of the primary rheumatic disease has been associated with an improvement in mortality rates, specific guidelines for prevention of ischemic heart disease in this group of patients have not been formulated and recommendations at this time include aggressive control and monitoring of traditional risk factors.

Resumen La enfermedad cardiovascular es un problema frecuente e insuficientemente reconocido en pacientes con trastornos reumaticos sistemicos. Los pacientes pueden presentar una enfermedad asociada a afeccion cardiaca en el momento del diagnostico o en una fase posterior del curso de la enfermedad. Las manifestaciones varian segun la enfermedad de que se trate, y todas las estructuras del corazon pueden verse afectadas y pueden causar morbilidad y mortalidad importantes. Las manifestaciones de la enfermedad cardiaca en estos pacientes van de subclinicas a graves y pueden requerir un tratamiento inmunosupresor agresivo. La deteccion temprana es importante para instaurar con rapidez un tratamiento apropiado. El tratamiento de la afeccion cardiaca asociada a la enfermedad se basa en la gravedad; las manifestaciones mas graves requieren a menudo un tratamiento combinado con corticoides y farmacos citotoxicos. Se ha identificado de manera creciente aterosclerosis prematura en los pacientes con lupus eritematoso sistemico y artritis reumatoide, lo que puede conducir a una muerte coronaria prematura respecto a la poblacion general. Un control agresivo de la inflamacion sistemica en estas enfermedades puede conducir a reducir el riesgo de cardiopatia isquemica. Aunque el tratamiento agresivo de la enfermedad reumatica primaria se ha asociado a una reduccion de las tasas de mortalidad, no se han formulado directrices especificas para la prevencion de la cardiopatia isquemica en este grupo de pacientes y las recomendaciones actuales incluyen el control agresivo y el seguimiento de los factores de riesgo tradicionales.

To discuss the European League Against Rheumatism recommendations in the management of primary systemic vasculitis.Important developments in the classification and treatment of systemic vasculitis have led the European League Against Rheumatism to publish recommendations in the diagnosis, treatment and monitoring of the small, medium and large-vessel vasculitides. These recommendations resulted from a combination of evidence from systematic analysis of selected studies and the experience of experts in vasculitis when data were not available.The purpose of formulating clinical recommendations is to improve quality of care and guide the clinician inexperienced with vasculitis. Nevertheless, patients with vasculitis should be managed by a vasculitis expert whenever possible. As our understanding of this rare and complex group of diseases advances, novel therapeutic options are being developed.

Wegener granulomatosis (WG) is a systemic disease that is often associated with an immune-mediated form of glomerulonephritis (GN). Renal disease most often manifests as microscopic hematuria with or without red blood cell or mixed cellular casts, proteinuria, and an elevated serum creatinine concentration. We conducted the current study to determine whether persistent hematuria, in the setting of apparent clinical remission, may reflect glomerular injury and not active renal disease. We performed a retrospective analysis of data from 82 patients with new-onset WG, of whom 25 had GN at presentation. Twenty of 25 patients with GN achieved sustained remissions (>6 consecutive months' duration). During initial periods of active disease the median peak serum creatinine was 1.9 mg/dL (range, 0.6-13.6 mg/dL). The median time to remission was 4 months (range, 2-13 mo). After effective therapy, median creatinine was 1.1 mg/dL (range, 0.4-1.8 mg/dL). Ten of 20 patients had prolonged hematuria over a period of >6 months. Within this subset, 5 subsequently normalized urine over a median period of 11 months and 5 did not achieve normal urine sediment over a median follow-up of 38 months. Thus, 10 of 25 patients with WG and GN had sustained hematuria in spite of apparent prolonged clinical remission. Patients with WG and GN may achieve enduring remissions that allow withdrawal of medications in spite of continued microscopic hematuria with or without red blood cell casts that may persist for months or even years. Continued use of aggressive immunosuppressive therapies in such patients would be ill-advised and could lead to irreversible and even life-threatening side effects from cyclophosphamide or high-dose corticosteroids.

Purpose of review To review the current uses of antitumor necrosis factor alpha (TNFalpha) therapies for non-rheumatoid arthritis inflammatory joint diseases. Emphasis is given to important questions regarding long-term use of anti-TNFalpha therapies. Recent findings TNFalpha blockade is one of the anticytokine therapies with major impact in the treatment of rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and juvenile idiopathic arthritis among the inflammatory joint diseases. As a result of the impressive response to TNFalpha inhibitors, new agents continue to be developed and a few are currently being tested in phase III trials. The evaluation of a potential relationship between inflammation and structural damage in ankylosing spondylitis has been an important focus of recent studies and will likely result in a better understanding and use of anti-TNFalpha therapy. Other aspects of treatment such as long-term safety and selection of patients who will likely have a major response have been evaluated in recent studies and will continue to be important topics in future research. Summary As TNFalpha inhibitors have been a major advance in the treatment of a number of inflammatory joint diseases and have been widely available in clinical practice, future research will need to continuously assess longitudinal efficacy and safety.

Herein we report the case of a 20-year-old woman who presented with multiple skin ulcers on her legs, severe pansinusitis, and chronic lung disease. She was initially thought to have Wegener's granulomatosis (WG). However, serologic studies indicated an HLA class I deficiency, which was confirmed by flow cytometry. Complementation studies and reverse transcriptase-polymerase chain reaction followed by direct DNA sequencing revealed a mutation in the gene encoding subunit 1 of the peptide transporter associated with antigen processing (TAP1). This mutation, which has not been previously described in the literature, results in a stop codon in the catalytic domain of TAP1. Although TAP mutations are rare, clinicians may encounter them in the evaluation of patients with suspected WG. In patients with WG-like symptoms it is important to consider this alternative genetic diagnosis as early as possible, not only so that appropriate antibiotic therapy can be initiated to prevent bronchiectasis, but also to avoid inappropriate immunosuppressive therapy that worsens the disease.

Granulomatosis with polyangiitis (formerly, Wegener’s granulomatosis) is a systemic necrotizing and granulomatous vasculitis predominantly affecting small-sized vessels. It is also one of the three vasculitides associated with anti-neutrophil cytoplasm antibodies (ANCA). The incidence rate is 2–12 cases per year and the prevalence 23–160 cases per million population. The cause remains unknown, but the pathophysiological mechanisms are being progressively defined. Disease onset can occur at any age, most commonly about 40–50 years. The main clinical characteristics include manifestations in the upper respiratory tract (erosive rhinitis and sinusitis, saddle-nose deformity), lungs (nodules, alveolar hemorrhage) and/or kidney. Biopsy of an affected organ can support the diagnosis, as can detection in serum of ANCA with a cytoplasmic labelling pattern (cANCA) by immunofluorescence and proteinase 3 (PR3) specificity by ELISA. Current therapy, based on a staged induction–maintenance strategy, can achieve remission in most patients. However, the toxicity of conventional treatment and relapse rate remain high, which calls for diligent efforts to further optimize therapy. Rituximab is now an alternative to cyclophosphamide, which increases the therapeutic armamentarium for inducing remission, but the optimal subsequent maintenance strategy remains to be defined. Refractory and/or relapsing diseases, as well as several morbidities, such as subglottic stenoses, continue to be challenges.

Churg-Strauss syndrome (CSS) is a rare small-vessel vasculitis typically associated with adult-onset asthma, peripheral and tissue hypereosinophilia, migratory pulmonary infiltrates, upper respiratory tract symptoms, and clinical evidence of systemic vasculitis. Cardiac involvement is a well-recognized complication with an estimated prevalence of 60%. Heart disease is associated with poor prognosis, accounting for almost 50% mortality in CSS. We present a case of a 48-year-old woman with CSS complicated by congestive heart failure with left ventricular ejection fraction of 25%, who was initially treated with long course of high-dose steroids without any clinical or echocardiographic improvement. She was referred to our hospital 1 year later and was initiated with cyclophosphamide 2 mg/kg per day and prednisone 60 mg/d followed by slow taper. Subsequently, the patient had remarkable improvement. Patient was then transitioned to azathioprine for 1.5 years with sustained disease remission. It may be difficult to determine myocardial disease activity status versus tissue damage in CSS with prolonged duration of heart failure symptoms. This is the first case report demonstrating that CSS cardiac disease may remain active despite 1 year of corticosteroid therapy, and significant improvement or remission can still be achieved by administering more aggressive cytotoxic immunosuppressive therapy.

Objective To determine the prevalence of antineutrophil cytoplasmic antibodies (ANCA) in patients with diseases that may mimic systemic vasculitides, such as severe multiorgan dysfunction (MOD) and parenchymal pulmonary disorders. Methods We conducted a prospective study of patients with MOD admitted to the medical intensive care unit and patients with various lung diseases seen at the outpatient pulmonary clinic of a tertiary care hospital. Patients with a documented diagnosis of Wegener's granulomatosis (WG) served as positive controls. ANCA were determined in serum samples from each patient by a combination of indirect immunofluorescence (IIF) and enzyme-linked immunosorbent assays (ELISAs) for antibodies to proteinase-3 and myeloperoxidase (anti-MPO). Results Ninety-nine patients with MOD, 29 outpatients with various lung disorders, and 18 patients with WG were included in the study. ANCA were detected by IIF alone in 16% (15/96) of patients with nonvasculitic MOD and 17% (5/29) of outpatients with various pulmonary disorders. The majority of the positive IIF specimens from each group displayed an atypical IIF pattern (73% and 80%, respectively). Only 1 specimen from patients with nonvasculitic disorders was positive for anti-MPO. ANCA by both IIF and ELISA were detected in 78% (12/14) of control patients with WG. Conclusion Detection of ANCA by the combination of IIF and antigen-specific assays for proteinase 3 and myeloperoxidase in diseases that mimic systemic vasculitides is highly specific for WG, microscopic polyangiitis, and Churg-Strauss syndrome.

Objective: It is controversial whether microorganisms play a role in the pathogenesis of large and medium vessel vasculitides (eg, giant cell arteritis [GCA], Takayasu arteritis [TAK] and focal idiopathic aortitis [FIA]). Recent studies have reported the presence of Varicella Zoster Virus (VZV) within formalin-fixed, paraffin-embedded temporal arteries and aortas of about three-quarters or more of patients with these conditions, and in a minority of controls. In a prospective study, we sought to confirm these findings using DNA extracted from vessels that were harvested under surgically aseptic conditions and snap frozen.Methods and Results: DNA samples extracted from 11 surgically sterile temporal arteries and 31 surgically sterile thoracic aortas were used in an attempt to identify the vessel-associated VZV genome. Two different validated PCR methods were used. Thirty-one thoracic aorta aneurysm specimens included biopsies from 8 patients with GCA, 2 from patients with TAK, 6 from patients with FIA, and 15 from patients without vasculitis, who had non-inflammatory aneurysms. Eleven temporal artery biopsies were collected from 5 patients with GCA and 6 controls. The presence of VZV was not identified in either the specimens from patients with large vessel vasculitis or from the controls.Conclusions: Using surgically sterile snap-frozen specimens, we were unable to confirm recent reports of the presence of VZV in either aortas or temporal arteries from patients with large vessel vasculitis or controls.Keywords: Aorta and temporal artery biopsies, Varicella Zoster Virus, Large Vessel Vasculitis

In 1995, the last World Health Organization (WHO)/International Society and Federation of Cardiology (ISFC) Task Force on the definition and classification of cardiomyopathies defined myocarditis (also named “inflammatory cardiomyopathy”) as an “inflammatory disease of the myocardium associated with cardiac dysfunction” [1]. In myocarditis, the inflammatory infiltrate of the myocardium is associated with necrosis and/or degeneration of adjacent myocytes, which is not typical of – nor consistent with – myocardial ischemic damage seen with coronary artery disease [1, 2]. The clinical presentation of myocarditis is dependent upon the magnitude of myocardial inflammation, thus it may be quite variable. Clinical signs and symptoms may range from subclinical disease (which may initially be unrecognized) to newonset acute heart failure or sudden death due to ventricular arrhythmias [3]. Moreover, the clinical course of myocarditis may be as variable as its clinical presentations: some individuals may develop acute myocarditis that resolves spontaneously within a few weeks, while others may develop symptoms of chronic heart failure due to dilated cardiomyopathy (DCM) [3]. Although many patients with hemodynamically stable heart failure may respond well to optimal medical therapy, a significant percentage of patients with DCM become medically refractory and progress to irreversible end-stage heart failure for which heart transplantation becomes the only hope of survival. Indeed, it is estimated that acute myocarditis resolves completely in approximately 50% of cases, with an additional 25% of patients having incom‐ plete recovery (i.e.; partial normalization of cardiac function), while the remainder 25% will inexorably progress to end-stage heart failure and death [1, 4-6].

Giant cell arteritis is the most common form of vasculitis affecting older people, and the diagnosis should be considered in older patients who present with the new onset of headache, visual dysfunction, polymyalgia rheumatica, or systemic inflammatory symptoms. Physicians should be familiar with its variety of clinical presentations and the abnormal laboratory findings associated with it.

Low molecular weight heparins (LMWHs) appear to be as safe and effective as unfractionated heparin (UFH) for venous thromboembolic disease (VTED) treatment or prophylaxis during pregnancy. Experience with other parenteral anticoagulant drugs is very limited, and no alternative oral anticoagulants are available to date. In addition to cost, challenges of long-term LMWH use during pregnancy that have not been addressed by controlled clinical trials include a) ideal dosing as pregnancy advances, b) the need for LMWH monitoring by anti-Xa activity levels, and c) ideal therapeutic management as the delivery date nears. Because therapeutic-intensity anticoagulation during pregnancy is challenging, many practitioners favor a more “aggressive” approach toward VTED prophylaxis in women perceived to be at very high risk of thrombosis during pregnancy. Best evidence to date suggests that most women with thrombophilias or with a previous “situational” VTED event probably do not require VTED prophylaxis antepartum, but postpartum anticoagulation prophylaxis is recommended for a few weeks. For those with a history of previous idiopathic VTED or VTED associated with “hormonal challenge” (such as with contraceptive use or previous pregnancy), prophylaxis beginning antepartum may be considered and discussed with the patient. Selected cases of “severe” thrombophilia are probably best managed by initiation of pharmacologic VTED prophylaxis antepartum. However, it must be emphasized that data from prospective controlled clinical trials are lacking.

Discussion of the 2007 British Society for Rheumatology guidelines for management of ANCA-associated vasculitis

We conducted a retrospective review to assess outcomes of therapy in patients with newly diagnosed Wegener granulomatosis (WG) using methotrexate (MTX) for mild to moderate disease and short-term treatment with cyclophosphamide (CYC) followed by MTX for severe disease. Patients with WG were included if their initial plan of therapy and subsequent care were directly supervised by the Cleveland Clinic Center for Vasculitis Care and Research. Severe disease (immediately life-threatening or involving critical organs) was initially treated with CYC and glucocorticoids. Mild to moderate disease was initially treated with MTX and glucocorticoids if serum creatinine was less than 2 mg/dL. Following initial improvement of severe disease, treatment was changed to MTX if serum creatinine was originally less than 2 mg/dL or had diminished to less than 2 mg/dL. Disease activity was determined at each visit and later converted to a Birmingham Vasculitis Activity Score, as modified for Wegener granulomatosis (BVAS/WG). Laboratory monitoring of disease and treatment toxicity was initially weekly and never less than monthly.Eighty-two (32%) of 253 patients with WG referred to the Center for Vasculitis Care and Research met eligibility criteria. Ineligible patients did not have new-onset disease or were not able to be followed principally in our center. Seventy percent of patients (57/82) initially had severe disease and received a short course of CYC for remission induction. In over half of these patients, illness was judged to be severe because of pulmonary hemorrhage; rapidly progressive glomerulonephritis, including need for dialysis; or neurologic abnormalities. All patients improved: remission was achieved in 50% (41/82) of patients within 6 months and in 72% (59/82) within 12 months. Sustained remission (BVAS/WG = 0 for at least 6 consecutive months) was ultimately achieved in 78% (64/82) of patients. Among the 75 (91%) patients who achieved remission of any duration, 45% relapsed within 1 year and 66% relapsed within 2 years following remission. Eighty-two percent of relapsed patients achieved subsequent remissions after additional treatment. About three-quarters of relapses were mild and promptly responded to treatment. Seventeen percent of patients developed serious infections. CYC-associated cystitis or bladder cancer did not occur in any patients. At least 1 form of permanent morbidity from WG alone was noted in 74.0% of patients. Three patients (3.7%) died over a median follow-up period of 4.5 years; no deaths were due to active disease. Although treatment was primarily directed toward achieving clinical improvement and not calculated to achieve marked lymphopenia, patients in whom treatment produced lymphocyte counts ofor=500/mm3, sustained over a median time of 4 (quartiles: 1, 8.5) months, were 3.8 times more likely to achieve a sustained remission (p = 0.015). Conversely, following remission, an absolute lymphocyte count of1000/mm was associated with a hazard ratio for relapse of 3.0, although the latter difference was not statistically significant. In patients with WG, a strategy that limits or avoids CYC therapy produced a frequency of remission comparable to that achieved with conventional CYC protocols, excellent survival, and avoidance of long-term CYC toxicity. However, relapses were common and incremental permanent morbidity occurred in most patients. While not a goal of therapy, when treatment produced marked lymphopenia, prolonged remissions were more likely.