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Objectives Previous studies have shown that adipokines may serve as potential biomarkers reflecting disease activity in various autoimmune diseases. Here, we investigated the relationship between four adipokines and clinical/laboratory findings in patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). Methods Sera from 63 patients with MPA and GPA who were registered in a prospective cohort were used to detect serum levels of adiponectin, chemerin, resistin, and vaspin using commercial enzyme-linked immunosorbent assay kits. Associations between adipokines and clinical and laboratory data was assessed using Pearson’s correlation analysis. Results The median age was 65.0 years, 24 patients were male, and 42 patients were diagnosed with MPA. The median levels of adiponectin, chemerin, resistin, and vaspin in patient sera were 13.9 ng/mL, 9.2 ng/mL, 23.7 ng/mL, and 0.1 ng/mL, respectively. A significant correlation between chemerin level and five-factor score (FFS) was found (r = 0.320, p = 0.011), and resistin was correlated with both Birmingham vasculitis activity score and FFS (r = 0.256, p = 0.043 and r = 0.320, p = 0.011). Regarding laboratory data, adiponectin level was associated with creatinine, and chemerin level was associated with creatinine, albumin, and erythrocyte sedimentation rate (ESR). On the other hand, resistin was found to be associated with white blood cell count, creatinine, ESR, and C-reactive protein. Age did not have a significant impact on the levels of adipokines. Conclusions The expression of adipokines in the sera of patients with MPA and GPA differs depending on clinical and laboratory features, and serum resistin may be suggested as a potential biomarker reflecting disease activity.

Background and Aim: The prevalence and clinical significance of extrahepatic autoimmune diseases (EHAIDs) have not been evaluated in a large cohort of primary biliary cholangitis (PBC). Methods: The medical records of 1554 patients with PBC from 20 international centers were retrospectively reviewed. Development of decompensated cirrhosis (ascites, variceal bleeding, and/or hepatic encephalopathy) and hepatocellular carcinoma were considered clinical endpoints. Results: A total of 35 different EHAIDs were diagnosed in 440 (28.3%) patients with PBC. Patients with EHAIDs were more often female (92.5% vs 86.1%, P&nbsp

International audience; A 62-year-old man, who was a heavy drinker, presented with deep asthenia, isolated fever, inflammatory syndrome (CRP 120 mg/l) and cytopenias (Hb 6.5 g/dl, platelet count 100 G/l). A whole-body CT scan found dysmorphic hepatomegaly and splenomegaly. Endoscopy revealed bleeding gastrointestinal angiodysplasia and non-bleeding oesophageal varices. After coagulation for angiodysplasia and blood transfusions, the Hb level remained around 8.5 g/dl. To investigate blood malignancy, a bone marrow biopsy revealed small-vessel vasculitis (Fig. 1A, 2), fibrinoid necrosis affecting the small vessel walls (Fig. 1A, 3), multinucleated giant cells (Fig. 1A, 1) constituting microgranulomas (Fig. 1A, 4) and...

Eosinophilic Granulomatosis with Polyangiitis (EGPA, Churg-Strauss syndrome) is a rare anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) characterised by respiratory manifestations and systemic organ involvement [1]. Particularly, cardiac manifestations occur in 40–60% of patients, representing the leading cause of mortality [2]. Recent reports suggest that venous thromboembolic events might also represent a consistent burden of disease [3, 4], as already known for the other AAVs [5–7], possibly due to eosinophil-mediated vascular inflammation [5]. Nevertheless, the occurrence of arterial and venous thrombotic events (AVTE) has never been systematically explored in EGPA. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of interest: Alessandra Bettiol Conflict of interest: Renato Alberto Sinico Conflict of interest: Franco Schiavon Conflict of interest: Sara Monti Conflict of interest: Enrica Paola Bozzolo Conflict of interest: Franco Franceschini Conflict of interest: Marcello Govoni Conflict of interest: Claudio Lunardi Conflict of interest: Giuseppe Guida Conflict of interest: Giuseppe Lopalco Conflict of interest: Giuseppe Paolazzi Conflict of interest: Angelo Vacca Conflict of interest: Gina Gregorini Conflict of interest: Pietro Leccese Conflict of interest: Matteo Piga Conflict of interest: Fabrizio Conti Conflict of interest: Paolo Fraticelli Conflict of interest: Luca Quartuccio Conflict of interest: Federico Alberici Conflict of interest: Carlo Salvarani Conflict of interest: Silvano Bettio Conflict of interest: Simone Negrini Conflict of interest: Carlo Selmi Conflict of interest: Savino Sciascia Conflict of interest: Gabriella Moroni Conflict of interest: Loredana Colla Conflict of interest: Carlo Manno Conflict of interest: Maria Letizia Urban Conflict of interest: Alfredo Vannacci Conflict of interest: Maria Rosa Pozzi Conflict of interest: Paolo Fabbrini Conflict of interest: Stefano Polti Conflict of interest: Mara Felicetti Conflict of interest: Maria Rita Marchi Conflict of interest: Roberto Padoan Conflict of interest: Paolo Delvino Conflict of interest: Roberto Caporali Conflict of interest: Carlomaurizio Montecucco Conflict of interest: Lorenzo Dagna Conflict of interest: Adriana Cariddi Conflict of interest: Paola Toniati Conflict of interest: Dr. Tamanini reports other from Glaxo Smith Kline, outside the submitted work. Conflict of interest: Federica Furini Conflict of interest: Alessandra Bortoluzzi Conflict of interest: Elisa Tinazzi Conflict of interest: Lorenzo Delfino Conflict of interest: Iuliana Badiu Conflict of interest: Giovanni Rolla Conflict of interest: Vincenzo Venerito Conflict of interest: Florenzo Iannone Conflict of interest: Alvise Berti Conflict of interest: Roberto Bortolotti Conflict of interest: Vito Racanelli Conflict of interest: Guido Jeannin Conflict of interest: Angela Padula Conflict of interest: Alberto Cauli Conflict of interest: Roberta Priori Conflict of interest: Armando Gabrielli Conflict of interest: Milena Bond Conflict of interest: Martina Tedesco Conflict of interest: Giulia Pazzola Conflict of interest: Paola Tomietto Conflict of interest: Marco Pellecchio Conflict of interest: Chiara Marvisi Conflict of interest: Federica Maritati Conflict of interest: Alessandra Palmisano Conflict of interest: Christian Dejaco Conflict of interest: Johann Willeit Conflict of interest: Stefan Kiechl Conflict of interest: Iacopo Olivotto Conflict of interest: Peter Willeit Conflict of interest: Domenico Prisco Conflict of interest: Augusto Vaglio Conflict of interest: Giacomo Emmi

Granulomatosis with polyangiitis (GPA) is an autoimmune disease affecting mainly small blood vessels. B-cells are important in the GPA pathogenesis as precursors of autoantibody-producing cells but likely also contribute (auto)antibody-independently. This has been underlined by the effectiveness of B-cell-depletion (with Rituximab) in inducing and maintaining disease remission. Mycophenolate-mofetil (MMF) and azathioprine (AZA) are immunosuppressive therapies frequently used in GPA-patients. Interestingly, MMF-treated GPA-patients are more prone to relapses than AZA-treated patients, while little is known about the influence of these drugs on B-cells. We investigated whether MMF or AZA treatment (or their active compounds) alters the circulating B-cell subset distribution and has differential effects on in vitro B-cell proliferation and cytokine production in GPA-patients that might underlie the different relapse rate. Circulating B-cell subset frequencies were determined in samples from AZA-treated (n = 13), MMF-treated (n = 12), untreated GPA-patients (n = 19) and matched HCs (n = 41). To determine the ex vivo effects of the active compounds of MMF and AZA, MPA and 6-MP respectively, on B-cell proliferation and cytokine production, PBMCs of untreated GPA-patients (n = 29) and matched HCs (n = 30) were cultured for 3-days in the presence of CpG-oligodeoxynucleotides (CpG) with MPA or 6-MP. After restimulation (with phorbol myristate acetate, calcium-ionophore), cytokine-positive B-cell frequencies were measured. Finally, to assess the effect of MMF or AZA treatment on in vitro B-cell proliferation and cytokine production, PBMCs of MMF-treated (n = 18), and AZA-treated patients (n = 28) and HCs (n = 41) were cultured with CpG. The memory B-cell frequency was increased in AZA- compared to MMF-treated patients, while no other subset was different. The active compounds of MMF and AZA showed in vitro that MPA decreased B-cell proliferation in GPA-patients and HCs. B-cell proliferation in MMF- and AZA-treated patients was not different. Finally, the IL-6+ B-cell frequency was decreased by MPA compared to 6-MP. No differences in IL-10+, IL-6+ or TNFα+ B-cell proportions or proliferation were found in MMF- and AZA-treated patients. Our results indicate that MMF could be superior to AZA in inhibiting B-cell cytokine production in GPA-patients. Future studies should assess the effects of these immunosuppressive drugs on other immune cells to elucidate mechanisms underlying the potential differences in relapse rates.

Patient: Female, 67 Final Diagnosis: GPA and GCA Symptoms: Blurry vision • headache • nosebleed • sinus congestion Medication: — Clinical Procedure: — Specialty: Rheumatology Objective: Rare co-existance of disease or pathology Background: Systemic vasculitis can present with a multitude of symptoms involving multiple organ systems. Clinicians should avoid anchoring bias and be cognizant that different types of vasculitides can be present in the same patient and that the diagnosis of one should not preclude the subsequent diagnosis of another. Case Report: A 67-year-old woman was referred for evaluation of episodes of epistaxis and recurrent severe sinusitis. Her physical examination showed nasal congestion and purpuric rash on the lower extremities. CT of the sinuses showed severe mucosal thickening. ANCA serologies were positive with a c-ANCA titer of 1: 5120 and anti-proteinase-3 (anti-PR3) antibodies of 1061 units. Serum creatinine was elevated at 1.32 mg/dL (GFR of 40.62 ml/min). Urine analysis showed proteinuria and hematuria. The patient declined treatment initially, but while awaiting kidney biopsy she developed episodes of headache and blurry vision. She underwent right temporal artery biopsy 4 days later, which confirmed the diagnosis of GCA. The biopsy showed characteristic histopathology findings and she was started on 60 mg of prednisone daily. The kidney biopsy showed pauci-immune crescentic glomerulonephritis (PICGN) consistent with ANCA-associated vasculitis. We identified all the cases of co-presentation of GCA and GPA in the literature and summarized their clinical features in this report. Conclusions: Astute clinicians should be cognizant of overlapping and atypical presentations of vasculitides to avoid delayed diagnosis and errors in management.

Introduction This is an empirical study to better understand commonly used medical school admission measures and disenrollment decisions during undergraduate medical education as well as graduate medical education (GME) probation or termination decisions. Materials and Methods Based on the data of USUHS medical students matriculating between 1998 and 2011 (N = 2,460), we compared medical school graduates and those disenrolled from medical school on MCAT scores, undergraduate BCPM (Biology, Chemistry, Physics, Math) GPA, and undergraduate overall GPA. We also reported more specific reasons for disenrollment decisions. Next, we compared the students who were referred to the student promotion committee (SPC) with other students on these measures. Moving onto GME, we compared trainees who were put on probation or terminated from training with those who were not on MCAT and undergraduate GPA measures. In addition, we examined the association between being referred to the SPC and GME probation or termination. Results There were 2,347 graduates and 113 disenrolled students from medical school (4.8%). For the disenrolled students, 43 (38.7%) students were disenrolled for exclusively (or primarily) non-academic reasons, and 68 (61.3%) were disenrolled for exclusively (or primarily) academic reasons. The t-tests showed statistically significant differences on the MCAT score of the first attempt (t(2,449) = 7.22, P < 0.01, Cohen's d = 0.70), average MCAT score (t(2,449) = 4.22, P < 0.01, Cohen's d = 0.41), and highest MCAT score (t(2,449) = 3.51, P < 0.01, Cohen's d = 0.34). Logistic regression model selection also revealed that the best predictor for disenrollment was the first MCAT score (exp(b) = 0.83, 95% CI = (0.78, 0.88)). No significant differences on these measures were found from the group comparisons on SPC and GME probation or termination. There was no significant association between SPC appearance and GME probation or termination. Conclusions Academic difficulties, especially in the basic sciences, appear to be the most common factor for disenrollment from medical school. These students also had lower MCAT scores, particularly on the first attempt. The MCAT performance indicators and undergraduate GPA were consistently lower, but not statistically significant, for those who appeared before SPC or were put on probation or terminated from training during GME.

New onset of granulomatosis with polyangiitis (GPA) occurring in patients previously diagnosed with rheumatoid arthritis (RA) is very uncommon. In older individuals, this condition is associated with high mortality, especially in those with renal involvement. We describe the first case of GPA in a patient older than 65 years diagnosed with RA without exposure to biologic disease-modifying anti-rheumatic drugs, presenting with pulmonary nodules due to a limited form of anti-neutrophil cytoplasmic antibody-negative GPA.

IntroductionGranulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are forms of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). AAV most commonly affects the upper and lower respiratory tract as well as the kidneys. The first symptoms are often nonspecific, requiring careful differential diagnosis with infections and malignancies.Materials and methodsWe analyzed the clinical and radiological data of 38 patients (20 females and 18 males) diagnosed with ANCA-associated vasculitis. Lung involvement was observed in 29 cases. Lung ultrasound (LUS) was performed on 21 patients from the study group and compared to chest CT. For 7 patients the examination was conducted repeatedly.ResultsIn total, 35 LUS and CT examinations were performed, revealing the following lesions: nodules, infiltrates with and without features of disintegration, caves (n = 17), diffuse alveolar hemorrhage (n = 3), and features of interstitial lung disease (ILD) with pulmonary fibrosis (PF) (n = 11). In 2 cases LUS and CT were negative. In 4 cases LUS was negative, despite a positive CT result.ConclusionsBoth in CT and LUS, images of pulmonary lesions were consistent though highly variable. Therefore, further studies are required for a larger group of patients.

AimsCytomegalovirus (CMV) infection under immunosuppression sometimes causes death. This study aimed to elucidate risk factors for CMV infection in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV).MethodsPatients with AAV who underwent remission induction treatment at Okayama University Hospital between 2006 and 2016 were retrospectively analyzed. The primary outcome was the development of CMV infection within 3 months.ResultsOf the 111 patients, 13 (11.7%) patients developed CMV infection. Patients with CMV infection were older (p = 0.030) and had a higher body mass index (p = 0.029) in comparison to those without CMV infection. A higher proportion had a severe form (p = 0.001) and granulomatosis with polyangiitis (GPA) (p = 0.001), as well as a higher Birmingham Vasculitis Activity Score (p = 0.018) and C-reactive protein (p = 0.018) levels at baseline. Using logistic regression analysis, severe form and GPA were independent risk factors (odds ratio [OR] = 9.68, 95% confidence interval [CI] = 1.92-60.23, and OR = 7.46, 95% CI = 1.46-47.60, respectively). In addition, patients with CMV infection were more likely than those without infection to be glucocorticoid-related diabetes mellitus (p = 0.025).ConclusionOur study highlights disease severity and subgroups of AAV as risk factors for CMV infection.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV), including granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), are autoimmune conditions associated with small vessel inflammation. Earlier studies indicate that complement activation via the alternative pathway plays a major role in the pathogenesis. In this study we have investigated if ANCA-activation of neutrophils from AAV patients leads to activation of the alternative complement pathway. C5a-primed neutrophils (PMN) from 10 AAV patients and 10 healthy controls (HC) were stimulated with PMA or IgG purified from PR3-ANCA positive patients (ANCA IgG). The supernatants were analyzed for release of complement proteins and markers of different granules by ELISA, and release of microparticles (MP) by flow cytometry. The ability of the supernatants to activate the alternative complement pathway was determined by incubation with normal serum and C3bBbP and C5a were measured by ELISA. MP were analyzed by flow cytometry and removed by centrifugation. The supernatants from the AAV patients' neutrophils produced significantly more C3bBbP compared with HCs (p = 0.0001). C3bBbP levels correlated with the number of MP. After removal of MP from the supernatants, alternative pathway activation was significantly lower. This study shows that primed and ANCA-stimulated neutrophils from AAV patients have a greater ability to activate the alternative complement pathway compared to primed neutrophils from healthy controls. This finding emphasizes the role of complement in the pathogenesis of AAV - underlining the therapeutic potential of C5a and other complement blockade.

Wegener's granulomatosis, is a rare form of systemic vasculitis characterized by necrotic granulomas around the blood vessels. We report a case of a healthy 43-year-old man presented with multiple ulcerated lesions in head and all over the body, that has appeared spontaneously. It was characterized by a giant deep ulceration covered by thick purulent, in size from 3 to 4 cm, deep; sub febrile temperature, and minimal pain associated. Skin biopsies results pyoderma gangrenosum (PG)-like features: anti-neutrophil cytoplasmic antibody (cANCA) positive. Six months later, the patient developed dispea episodes. CT scan (CT) result with multiple focal opacities. He was diagnosed with wegener granulomatosis (WG) and was treated with corticosteroids and ciclophosphamide. Skin involvement in WG is not common and lesions in the skin vary from purpura, paniculitis to ulceration. In our case, skin elements are the first manifestations. Whether these elements are Wegener manifestation or we have coexistence of PG with WG, it remains a still uncertain question to answer. There is no histopathologic pathognomic elements for both. Skin involvement in WG with PG-like lesions have been rarely reported. In front of this type of widespread ulcerations, resistant to treatment we should be aware that one of the reasons may be a disease of autoimmune etiology such as WG.

PURPOSE OF THE REVIEW: Most of the primary vasculitis in children and adults has different clinical manifestations for the same disease, which suggests that they might not be part of the same clinical spectrum and requires a different approach in order to reduce the morbidity and mortality of these patients. In this work, we review the most recent literature and the most important studies that describe and compare adult and children primary vasculitides pathogenesis, clinical presentation, and treatment approach. Accordingly, we discuss recent research involving clinical trials, comparison studies, and pathogeny for these vasculitides. RECENT FINDINGS: Clinical manifestations in the different primary vasculitis change in predominance from adults to children. There is a female sex predominance for the ANCA vasculitides in children compared with adults, but the same treatment works in most cases for both groups. Identifying the diverse clinical spectrum in both adults and children primary vasculitides will reduce the need to extrapolate the diagnostic criteria from one group to another and individualize it, which will allow the clinician to establish a better approach.

Previous studies have evaluated the risk factors for relapse of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and the biomarkers of AAV for predicting relapse. However, little is known about the association between the presence of sinusitis and relapse and changes in the ANCA levels in AAV. This single-center, retrospective cohort study included 104 consecutive patients who were newly diagnosed with myeloperoxidase (MPO)-ANCA-positive microscopic polyangiitis (MPA) between 2006 and 2018 and were treated at the Aichi Medical University Hospital in Japan. The relationships between sinusitis and relapse of vasculitis and elevated MPO-ANCA levels were assessed using multivariate Cox proportional hazards models that were adjusted for clinically relevant factors. During the entire follow-up period (median, 24 months; interquartile range, 7–54 months), 93 (89.4%) patients achieved remission. After achieving remission, 38 (40.9%) patients experienced at least one relapse (13 [65.0%] in the sinusitis group; 25 [34.3%] in the non-sinusitis group). Sinusitis was identified as a significant predictor of relapse (adjusted hazard ratio: 2.41, 95% confidence interval [CI]: 1.19–4.88; P = 0.015). Furthermore, sinusitis was more likely to be associated with elevated MPO-ANCA levels (adjusted hazard ratio: 2.59, 95% CI: 1.14–5.92; P = 0.024). In conclusion, sinusitis was associated with a higher risk of relapse and elevated MPO-ANCA levels in MPA patients, suggesting that careful management may be required to reduce the risk of relapse in patients with sinusitis. Further studies are needed to elucidate the optimal treatment strategy for these patients.

Background Pyoderma gangrenosum (PG) is caused by immune system dysfunction, and particularly improper functioning of neutrophils. At least half of all PG patients also suffer from autoimmunological diseases, one of which is Wegener granulomatosis (WG). The purpose of this article was to compare cases of patients with WG and PG in terms of their clinical course, histopathology, and applied treatment. In both, histopathological features are not fully distinct. Data from microbiological and immunological evaluation and clinical presentation are required to establish the diagnosis. We also present the case of a patient with WG and deep facial skin lesions not responding to standard treatment. Methods Systematic review of the literature in PubMed using the search terms "Wegener granulomatosis AND Pyoderma gangrenosum" and case report. Results The finding of 22 reports in the literature (PubMed) suggests that it is a rare phenomenon. This study revealed a similar rate of comorbidity of WG and PG in both genders and an increased incidence of both diseases after the age of 50. Among skin lesions there was a dominance of ulceration, most often deep and painful, covering a large area with the presence of advanced necrosis and destruction of the surrounding tissue. The most common location proved to be the cervical-cephalic area. The most popular treatment included steroids with cyclophosphamide. Discussion The rarity of the coexistence of these two diseases results in a lack of effective therapy. In such cases sulfone derivatives are still effective and provide an alternative to standard immunosuppression methods. Hyperbaric therapy and plasmapheresis can also play an important complementary role.

Wegener granulomatosis has recently been renamed as granulomatosis with polyangiitis (GPA). In this review, we examine the clinical criteria and pathologic and pathophysiologic mechanisms of GPA, with an emphasis on findings encountered in the realm of head and neck imaging. Particular attention is paid to generating an appropriate differential diagnosis, because many of the imaging features of GPA overlap with those of other diseases, most notably lymphoma and sarcoidosis. Recent therapeutic advancements have underscored the importance of the radiologist in suggesting the diagnosis early, resulting in earlier treatment and decreased patient morbidity. This is particularly true for the head and neck manifestations of GPA; although they are less common, they often herald a refractory disease course that requires aggressive immunosuppressive therapy. Knowledge of common and uncommon imaging findings enables the radiologist to diagnose GPA early enough to start treatment promptly and reduce patient morbidity.Although there are no reliable pathognomonic imaging features for GPA, the present article attempts to identify patterns of disease that are suggestive of the disease. The diagnosis ultimately relies on a constellation of radiographic findings, laboratory values, and accurate clinical history.

Granulomatous diseases of the airway are challenging lesions to diagnose and effectively manage not only because they are uncommon but also because they can occur in different forms, each with unique clinical and radiological characteristics. Most such lesions can be effectively managed conservatively with repeated airway dilatation, use of intraluminal stents, and specific antimicrobial treatment. The only exception is those lesions presenting with localized airway obstruction wherein surgical resection may be indicated and beneficial.

Background Secondary pulmonary hemorrhage increases the risk of mortality in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV); plasma exchange therapy may improve outcomes in these patients. We conducted a retrospective cohort study to investigate the effect of plasma exchange therapy on short-term prognoses in patients with pulmonary hemorrhage secondary to AAV. Methods This study utilized the Diagnosis Procedure Combination database, which is a nationwide inpatient database in Japan. We checked the abstract data and medical actions and identified the patients with pulmonary hemorrhage secondary to AAV who required proactive treatment between 2009 and 2014. To compare the in-hospital mortality, we performed propensity score matching between the plasma exchange and non-plasma exchange groups at a ratio of 1:1. Results Of the 52,932 patients with AAV, 940 developed pulmonary hemorrhage as a complication. A total of 249 patients from 194 hospitals were eligible for the study. Propensity score matching at a ratio of 1:1 was performed, and 59 pairs were formed (plasma exchange group, n = 59; non-plasma exchange group, n = 59). A statistically significant difference was found in the all-cause in-hospital mortality between the plasma exchange and non-plasma exchange groups (35.6% vs. 54.2%; p = 0041; risk difference, -18.6; 95% confidence interval (CI), -35.4% to -0.67%). Conclusion Thus, plasma exchange therapy was associated with improved in-hospital mortality in patients with pulmonary hemorrhage secondary to AAV.

We report a rare case of squamous cell carcinoma (SCC) of the nasal cavity arising in a patient with granulomatosis with polyangiitis (GPA). The patient was a 35-year-old man who had been diagnosed 15 years earlier with GPA and treated medically for sinonasal, pulmonary, and renal involvement. He presented to us with left-sided orbital and cheek pain and nasal obstruction. Endoscopy detected a friable, exophytic mass that involved the left lateral nasal wall and septum. Biopsy analysis identified the mass as an SCC. A definitive endoscopic resection was performed, followed by chemoradiation, but the patient exhibited progression of disease 2 months after the cessation of therapy. He then underwent an open craniofacial resection and a second round of chemoradiation. At 7 months of follow-up, he remained disease-free. Sinonasal symptoms in GPA are consistent with those in chronic rhinosinusitis, but the presence of unilateral symptoms may suggest a neoplastic process. Immunosuppressants are implicated in the pathophysiology of this malignancy, but equally plausible is the oncogenic role of chronic inflammation.

Recent data suggest the existence of a complement alternative pathway activation in the pathogenesis of antineutrophilic cytoplasmic antibody (ANCA)-associated vasculitis (AAV), a condition that remains poorly understood. This study aims to assess the clinical characteristics and outcomes of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) patients with regard to their plasma complement levels at diagnosis. A retrospective monocentric study carried out at Caen University Hospital led to the identification of proteinase-3- or myeloperoxidase-ANCA-positive GPA and MPA patients from January 2000 to June 2016 and from September 2011 to June 2016, respectively. All patients with available C3 and C4 levels at diagnosis were included. Patients were categorized in the hypocomplementemia group if their C3 and/or C4 levels at diagnosis were below the lower limit of the normal range. Among the 76 AAV patients (43 GPA, 33 MPA), 4 (5%) had hypocomplementemia, and the 72 remaining patients exhibited normal plasma complement levels. All 4 hypocomplementemia patients had renal involvement. Hypocomplementemia was followed in 1 patient whose post-treatment complement level normalized within 1 month. Among all clinical and ANCA specificity, including relapse-free survival (p = 0.093), only overall and renal survival rates were significantly lower in the hypocomplementemia group (p = 0.0011 and p

Background Narrow band imaging (NBI) endoscopy is a technique that allows for real-time visualization of mucosal and submucosal vascular patterns. Objective Because granulomatosis with polyangiitis (GPA) (Wegener granulomatosis) is an autoimmune disease defined by vascular inflammation, we examined patients with GPA and with NBI to evaluate whether disease-specific mucosal vascular patterns were present. To the best of our knowledge, the use of NBI endoscopy for assessment of an immune system disease such as GPA has never been previously attempted. Methods We conducted a prospective observational study by performing an endoscopic evaluation of upper airways with NBI on patients diagnosed with GPA; on patients with symptoms and signs suggestive for GPA, who were scheduled to undergo nasal biopsy to confirm diagnosis; on patients affected by chronic rhinosinusitis with nasal polyps; and on healthy controls. Results We enrolled 69 patients. NBI vascular patterns in patients with GPA were consistently and recognizably different from healthy mucosal patterns in 53% of our cases. In patients with GPA, biopsy and NBI results were for the most part comparable, except for three cases. Conclusion Nasal mucosa NBI endoscopy can be considered a promising rapid and noninvasive live imaging technique for nasal mucosa GPA that, based on further study, could become a supplementary diagnostic tool in the complex workup of GPA and vasculitis.

Patient: Male, 70 Final Diagnosis: Metastatic micropapillary urothelial carcinoma Symptoms: Dry cough • dyspnea • hematuria Medication: Cyclophosphamide Clinical Procedure: Pulmonary wedge resection Specialty: Pulmonology Objective: Unusual clinical course Background: Granulomatosis with polyangiitis (GPA) relapse can complicate the differential diagnosis of pulmonary lesions. Case Report: A 70-year-old male smoker with GPA and emphysema presented with dyspnea, dry cough, and a right upper lobe pulmonary ground-glass opacity that persisted despite antibiotics. A trans-bronchial biopsy did not reveal active vasculitis, malignancy, or infection. He was treated for presumed GPA relapse based on pulmonary manifestations, renal failure, and elevated PR3-ANCA. Later, hematuria led to the cystoscopic discovery of a bladder wall lesion, which was diagnosed as micropapillary urothelial carcinoma not involving the muscularis propria. The patient developed an increasing pulmonary infiltrate with a new solid component, satellite lesions, and regional lymphadenopathy. A right upper lobe wedge resection showed metastatic urothelial carcinoma. Conclusions: The simultaneous presentation of a pulmonary lesion and GPA relapse is a diagnostic challenge. The differential diagnosis should include the rare possibility of metastatic urothelial carcinoma, regardless of how the lesion appears radiographically.

To report a case of frosted branch angiitis in a patient with granulomatosis with polyangiitis.Clinical case report. Imaging was obtained with pseudo-color scanning laser ophthalmoscope photographs, fluorescein angiography, spectral domain optical coherence tomography, and B-scan ultrasound.A 24-year-old woman with a clinical history of granulomatosis with polyangiitis who presented with acute vision loss was found to have frosted branch angiitis with concurrent posterior scleritis and orbital inflammation. These findings improved rapidly after initiation of high-dose intravenous solumedrol.This is a unique case of frosted branch angiitis associated with granulomatosis with polyangiitis. The authors are not aware of a previous report of this association. Although rare, retinal vasculitis should be recognized as a potential complication of granulomatosis with polyangiitis and can respond rapidly to prompt initiation of therapy.

Objectives Patients with granulomatosis with polyangiitis (GPA) are prone to disease relapse. Currently, no good biomarkers are available to predict relapses in individual patients. This study aimed to determine whether patients at risk for relapse can be distinguished based on increased in vitro autoantibody production. Methods Eighty-four proteinase 3 (PR3) anti-neutrophil cytoplasmic antibody (ANCA) positive GPA outpatients were prospectively monitored for up to two years and 32 healthy controls were included. At periodic intervals peripheral blood mononuclear cells were isolated, cultured and in vitro production of total and PR3-ANCA-specific IgG was determined. Moreover, serum ANCA titers were measured by indirect immunofluorescence. Results Sixteen patients (21%) relapsed during the follow-up period. At time of inclusion no significant differences were present for ANCA production between relapsing and non-relapsing patients. Samples before relapse exhibited increased serum ANCA titers and in vitro PR3-ANCA IgG levels compared with inclusion samples from non-relapsing patients. When evaluating changes over time, increasing serum ANCA titers were observed prior to relapse compared to a 1-year follow-up from non-relapsing patients. No significant change in in vitro PR3-ANCA levels occurred prior to relapse, compared to non-relapse patients. Conclusions While differences were observed for the serum ANCA titer in relapsing and non-relapsing patients, monitoring in vitro PR3-ANCA IgG production does not improve relapse prediction in GPA patients.

Objectives 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. Methods 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. Results 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. Conclusions MTX may be effective and safe for remission-maintenance in AAV. Trial registration clinicaltrials.gov NCT00751517.

Purpose: To evaluate the diagnostic performance of minimum apparent diffusion coefficient (ADCmin) and lesion-to-spinal cord signal intensity ratio (LSR) in the differentiation of benign and malignant pulmonary lesions. Materials and Methods: Forty-seven patients (36 men, 11 women; range, 17–81 years) with 62 pulmonary lesions underwent magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) performed using a 1.5T scanner during free-breathing using b 600 s/mm2. The ADCmin values and LSR were calculated. A receiver operating characteristic (ROC) curve analysis was performed to detect the threshold value of the ADCmin and LSR values for discrimination between benign and malignant pulmonary lesions. Results: There were 42 malignant (33 primary tumors, 9 metastases) and 20 benign lesions. The mean ADCmin ± standard deviations (×10-3 mm2/s) were 1.45 ± 0.33 for malignant tumors, and 2.4 ± 0.69 for benign lesions (P < 0.001). The mean LSR ± standard deviations for lung cancer was 1.24 ± 0.78, and for benign lesions was 0.55 ± 0.57 (P < 0.001). The area under the ROC curve for ADCmin (0.931; 95% confidence interval [CI]: 0.868–0.993) was greater than that for LSR (0.801; 95% CI: 0.675–0.926) (P = 0.029). For benign/malignant discrimination, the ROC curve showed threshold value of ADCmin to be 1.78 × 10-3 mm2/s and that of LSR to be 0.86. Using these cutoff values, accuracy of ADCmin and LSR were 89%, 74%, respectively (P = 0.383). Conclusion: Being a contrast-free and radiation-free technique, DWI allows discrimination of benign and malignant lung lesions. The ADCmin value performed marginally better than LSR values in distinction of benign and malignant lesions. Level of Evidence: 1. J. Magn. Reson. Imaging 2017;45:845–854. © 2016 International Society for Magnetic Resonance in Medicine

Granulomatosis with polyangiitis is an ANCA-associated systemic vasculitis with a low incidence in the pediatric population. Lung involvement is a common manifestation in children affected by granulomatosis with polyangiitis, both at disease’s onset and during flares. Its severity is variable, ranging from asymptomatic pulmonary lesions to dramatic life-threatening clinical presentations such as diffuse alveolar haemorrhage. Several radiologic findings have been described, but the most frequent abnormalities detected are nodular lesions and fixed infiltrates. Interstitial involvement, pleural disease and pulmonary embolism are less common. Histology may show necrotizing or granulomatous vasculitis of small arteries and veins of the lung, but since typical features may be patchy, the site for lung biopsy should be carefully chosen with the help of imaging techniques such as computed tomography. Bronchoalveolar lavage is helpful to confirm the diagnosis of alveolar haemorrhage. Pulmonary function tests are frequently altered, showing a reduction in the diffusion capacity for carbon monoxide, which can be associated with obstructive abnormalities related to airway stenosis. Nodular lung lesions tend to regress with immunosuppressive therapy, but lung disease may also require second line treatments such as plasmapheresis. In cases of massive diffuse alveolar haemorrhage, ventilator support is crucial in the management of the patient.

Human faces contain dozens of visual features, but viewers preferentially fixate just two of them: the eyes and the mouth. Face-viewing behavior is usually studied by manually drawing regions of interest (ROIs) on the eyes, mouth, and other facial features. ROI analyses are problematic as they require arbitrary experimenter decisions about the location and number of ROIs, and they discard data because all fixations within each ROI are treated identically and fixations outside of any ROI are ignored. We introduce a data-driven method that uses principal component analysis (PCA) to characterize human face-viewing behavior. All fixations are entered into a PCA, and the resulting eigenimages provide a quantitative measure of variability in face-viewing behavior. In fixation data from 41 participants viewing four face exemplars under three stimulus and task conditions, the first principal component (PC1) separated the eye and mouth regions of the face. PC1 scores varied widely across participants, revealing large individual differences in preference for eye or mouth fixation, and PC1 scores varied by condition, revealing the importance of behavioral task in determining fixation location. Linear mixed effects modeling of the PC1 scores demonstrated that task condition accounted for 41% of the variance, individual differences accounted for 28% of the variance, and stimulus exemplar for less than 1% of the variance. Fixation eigenimages provide a useful tool for investigating the relative importance of the different factors that drive human face-viewing behavior.

Wegener's granulomatosis (WG) is a systemic vasculitis affecting small and medium-sized vessels with granulomatous formation. Though it is known for respiratory tract and kidney involvement, neurologic manifestation has been also reported. Herein we report a patient who suffered pansinusitis with multiple lower cranial nerve palsies but reached remission by immunosuppressant after the diagnosis of WG. A 54-yr-old female visited with headache, hearing difficulty, and progressive bulbar symptoms. She experienced endoscopic sinus surgeries due to refractory sinusitis. Neurologic examination revealed multiple lower cranial nerve palsies. Vasculitic markers showed no abnormality. Nasal biopsy revealed granulomatous inflammation and vasculitis involving small vessels. Given cyclophosphamide and prednisolone, her symptoms were prominently improved. WG should be considered in the patient with multiple cranial nerve palsies, especially those with paranasal sinus disease. Because WG can be lethal if delayed in treatment, prompt immunosuppressant is warranted after the diagnostic tissue biopsy.

BACKGROUND: We determined if PR3-ANCA is a biomarker that differentiates ulcerative colitis (UC) from Crohn's disease (CrD). METHODS: A total of 946 sera were tested, including 86 granulomatosis with polyangiitis (GPA) and 491 inflammatory bowel disease (IBD) patients (283 UC and 208 CrD), 264 pathological controls (various diseases) and 105 healthy individuals. All samples were tested for PR3-ANCA by ELISA (QUANTA Flash Lite(R), INOVA Diagnostics) and chemiluminescent immunoassays (CIA QUANTA Flash PR3). Conventional anti-neutrophil cytoplasmic antibody (ANCA) indirect immunofluorescence assays (IIF) was performed with NOVA Lite (INOVA Diagnostics). RESULTS: PR3-ANCA by CIA were detected in 31.1% UC vs. 1.9% CrD sera (p=2.2E-16), and by ELISA in 6% UC and 0% CrD (p=0.0003). In GPA patients, PR3-ANCA were detected in 75.6% by CIA and 61.6% by ELISA (p

Cyclophosphamide has greatly improved prognosis in antineutrophil cytoplasmic autoantibody-associated vasculitis (AAV) and proliferative lupus nephritis (LN). However, the side effects of long-term cyclophosphamide treatment are considerable prompting a search for alternatives to cyclophosphamide. For maintenance treatment in AAV, azathioprine is the preferred drug with methotrexate as an alternative in the case of intolerance to azathioprine. Data on mycophenolate mofetil (MMF) for the induction of remission in AAV are being awaited, but rituximab appears as effective as cyclophosphamide in newly diagnosed patients with AAV, and is probably even better for relapsing patients, while the possibility of maintenance treatment with intermittent low-dose infusions of rituximab is being explored. In LN, low-dose intravenous cyclophosphamide is as effective as high-dose cyclophosphamide for the induction of remission, with azathioprine being used for maintenance treatment. MMF can be used in the case of intolerance to cyclophosphamide and might be the first choice in black and Hispanic patients. In the case of intolerance to both cyclophosphamide and MMF, azathioprine with pulses of methylprednisolone can be used. Here, the role of rituximab has not been established. In conclusion, alternatives are available for cyclophosphamide both in AAV and proliferative LN.

Purpose Wegener’s granulomatosis has been renamed granulomatosis with polyangiitis (GPA). In this article, the authors refer to WG as “WG/GPA” to indicate the old and new names of this condition. WG/GPA is a systemic necrotizing granulomatous vasculitis that can affect, in particular, the lungs, sinuses, and kidneys. The authors report 2 cases with antineutrophil cytoplasmic antibodies (c-ANCA) positive WG/GPA whose initial presentations were in the form of both conductive and sensorineural hearing loss without systemic features. The authors contrast the reversal of hearing loss and prevention of disease progression with early recognition and treatment. Method The authors present 2 contrasting cases of WG/GPA. Changes in hearing were measured through use of a GSI 61 audiometer as well as guidelines from the British Society of Audiology. Serum ANCA were detected by indirect immunofluorescence and formalin fixed neutrophils. Proteinase 3 (PR3) and myeloperoxidase antibodies were measured through use of a fluoroenzyme immunoassay. Results Persistent deafness and systemic disease are more likely, and more aggressive therapy was required when the diagnosis of WG/GPA was delayed. Conclusion WG/GPA should be considered in acute or subacute deafness presenting over days to weeks and even in the absence of systemic symptoms. A negative or weak ANCA with absent antibodies to serine PR3 and myeloperoxidase should not exclude the possible diagnosis of WG/GPA, and a high index of suspicion should be maintained.

Purpose:To report a case series of two cases of granulomatosis with polyangiitis, previously known as Wegener granulomatosis, which developed macular necrosis, not previously associated with granulomatosis with polyangiitis, healed with fibrosis, despite aggressive immune-modulating therapy and good control of systemic disease.Methods:Case series of two cases with observation of treatment progress.Results:The results reported the progress of response to treatment in the two cases, which resulted in the final outcome of fibrosis in the macula region, despite being on aggressive immune-modulating therapy and good systemic control.Conclusion:Granulomatosis with polyangiitis can be associated with macular necrosis leading to fibrosis, unresponsive to immune-modulating therapy.

We describe a patient with Wegener granulomatosis whose complaint of wheezing was incorrectly attributed to asthma. Anesthesiologists must recognize that tracheal stenosis is extremely common in Wegener granulomatosis and can mimic other causes of wheezing.

Objectives Pentraxin 3 (PTX3), in common with myeloperoxidase and proteinase 3, is stored in human neutrophil granules and is expressed on apoptotic neutrophil surface. We therefore investigated the presence of anti-PTX3 autoantibodies (aAbs) in the sera of antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) patients. Methods Presence of anti-PTX3 autoantibodies was analysed by a specific enzyme-linked immunosorbent assay in sera from 150 patients with microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), and eosinophilic granulomatosis with polyangiitis (EGPA), and in sera of 227 healthy subjects (HS), 40 systemic sclerosis (SSc) patients, and 25 giant cell arteritis patients (GCA). Using indirect immunofluorescence on fixed human neutrophils, we also analyzed the staining pattern associated with the presence of anti-PTX3 aAbs. Results Anti-PTX3 aAbs were detected in 56 of 150 (37.3%) of the AAV patients (versus 12 of 227 (5.3%) of HS, p

Relapse in ANCA-associated vasculitis (AAV) has been studied previously, but there are few studies on renal relapse in particular. Identifying patients at high risk of renal relapse may aid in optimizing clinical management. We investigated which clinical and histological parameters are risk factors for renal relapse in ANCA-associated glomerulonephritis (AAGN). Patients (n = 174) were newly diagnosed and had mild-moderate or severe renal involvement. Data were derived from two trials of the European Vasculitis Society: MEPEX and CYCAZAREM. The Cox regression model was used to identify parameters increasing the instantaneous risk (= rate) of renal relapse (useful for instant clinical decisions). For identifying predictors of renal relapse during follow-up, we used Fine & Gray's regression model. Competing events were end-stage renal failure and death. The cumulative incidence of renal relapse at 5 years was 9.5% (95% CI: 4.8-14.3%). In the Cox model, sclerotic class AAGN increased the instantaneous risk of renal relapse. In Fine & Gray's model, the absence of interstitial infiltrates at diagnosis was predictive for renal relapse. In this study we used two different models to identify possible relationships between clinical and histopathological parameters at time of diagnosis of AAV with the risk of experiencing renal relapse. Sclerotic class AAGN increased the instantaneous risk of renal relapse. This association is most likely due to the high proportion of sclerosed glomeruli reducing the compensatory capacity. The absence of interstitial infiltrates increased the risk of renal relapse which is a warning sign that patients with a relatively benign onset of disease may also be prone to renal relapse. Renal relapses occurring in patients with sclerotic class AAGN and renal relapses occurring in patients without interstitial infiltrates were mutually exclusive, which may indicate that they are essentially different.

Introduction: To evaluate long-term outcome of patients with granulomatous polyangitis (GPA) followed up in a tertiary university hospital. Patients and Methods: We reviewed medical records of 22 patients with GPA diagnosis confirmed by tissue biopsies between 2004 and 2014. Results: The mean time from the onset of symptoms to diagnosis was 7.8 +/- 12.3 months [interquartile range (IR)= 4.0]. The most commonly involved organs were the upper respiratory tract (URT) (72.7%), lower respiratory tract (81.8%) and kidneys (72.7%). URT involvement indicated good prognosis (p= 0.046). Survival in the patients with and without URT involvement was 124.6 +/- 6.9 months and 59.7 +/- 22.9 months, respectively. End-stage renal failure (ESRF) requiring dilaysis and cardiac involvement were associated with mortality (p= 0.022 and p= 0.026, respectively). Of the 12 dialysis-dependent patients at diagnosis, 11 survived > 3 months and seven regained renal function permanently. Dialysis dependency was significantly lower in patients who received plasmapheresis (p= 0.047). Overall mortality rate was 18% (4/22). Mean survival was 55.9 +/- 42.8 months (IR= 84.0). Conclusion: Diagnosis of GPA may be delayed by the nonspecific nature of its symptoms. URT involvement was associated with good prognosis, whereas cardiac involvement and ESRF requiring dialysis were associated with poor outcome. Plasmapheresis may increase the rate of renal recovery in the patients with ESRF requiring dialysis.

Findings of several reports suggest that rituximab, a chimeric monoclonal anti-CD20 antibody causing B-lymphocyte depletion, might represent a treatment option for people with granulomatosis with polyangiitis (GPA) (former Wegener's granulomatosis). This study presents the results of rituximab treatment in two patients with treatment-refractory GPA. First patient received rituximab for a granulomatous posterior orbital mass lesion, and eye symptoms were resolved after three courses of treatment. The second patient had eye and paranasal sinus involvement and benefited from two courses of rituximab treatment, with significant clinical improvement. Rituximab may represent an effective novel treatment for remission induction in GPA.

Pyoderma gangrenosum is a rare neutrophilic disease of unknown origin that is associated with systemic diseases in 50% of cases. It is characterized by erythematous-violaceous nodular lesions that quickly progress to painful ulcers, with undermined edges, necrotic-hemorrhagic, varying in size and depth, located mainly in the lower limbs. Extracutaneous locations of pyoderma gangrenosum are rare, usually involving the lungs; the main differential diagnosis in these cases is Wegener granulomatosis. We report a case of pyoderma gangrenosum, which showed multiple cavitary lung nodules, with good response to high doses of steroids. Once excluded the possibility of Wegener granulomatosis, the authors concluded that it was the manifestation of systemic pyoderma gangrenosum with pulmonary involvement. Pioderma gangrenoso é doença neutrofílica rara de etiologia desconhecida, que se associa a doenças sistêmicas em 50% dos casos. Caracteriza-se clinicamente por lesão nodular eritematoviolácea ou pústula que progride rapidamente para úlcera dolorosa, de bordas irregulares, fundo necrohemorrágico e localização preferencial nos membros inferiores. Manifestações sistêmicas do Pioderma gangrenoso são raras, envolvem geralmente os pulmões e o principal diagnóstico diferencial nestes casos é a granulomatose de Wegener. Relatamos um caso de paciente portador de pioderma gangrenoso que apresentava múltiplos nódulos pulmonares cavitados, com boa resposta a altas doses de corticoterapia. Uma vez excluída a possibilidade de granulomatose de Wegener, os autores concluíram tratar-se da manifestação sistêmica do pioderma gangrenoso.

Wegener granulomatosis may rarely present with tumor masses that are in areas not typically involved by the disease. Although some cases have an associated positive anti-neutrophilic cytoplasmic antibodies, other cases do not, especially those of the limited form. To prevent misdiagnosis and ensure prompt treatment, it is extremely important to consider Wegener granulomatosis even in cases without the classic clinical findings. We report a case of a 19-year-old woman with no prior significant medical history who presented with persistent ventricular tachycardia and a papillary muscle mass in her left ventricle which upon excision and tissue evaluation demonstrated histologic changes of Wegener granulomatosis.

Wegener granulomatosis is an uncommon necrotizing vasculitis that classically manifests as a clinical triad consisting of upper and lower airway involvement and glomerulonephritis. Other less frequently involved organ systems include the central and peripheral nervous system and large joints. The diagnosis is based on a combination of clinical and laboratory findings. Because thoracic involvement often predominates, chest radiographic findings are often the first to suggest the diagnosis. However, chest computed tomography (CT) has superior sensitivity and specificity for evaluation of the airways, lung parenchyma, and mediastinum, particularly with the use of multiplanar reformatted and three-dimensional images. Common pulmonary radiologic findings include waxing and waning nodules, masses, ground-glass opacities, and consolidation. Airway involvement is usually characterized by circumferential tracheobronchial thickening, which can be smooth or nodular. Pleural effusions are the most common manifestation of pleural disease and can result from primary involvement or be secondary to renal failure. Mediastinal lymphadenopathy is a nonspecific finding and is usually reactive. Uncommon thoracic radiologic manifestations include involvement of the heart and great vessels. CT is the imaging modality of choice for diagnosis, surveillance, and follow-up in patients with Wegener granulomatosis.