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BackgroundMethodsResultsConclusion\nPlain Language SummaryIn this review article, we aimed to discuss the pathogenesis of sensorineural hearing loss (SNHL) in patients with different forms of chronic rhinosinusitis (CRS), with special reference to the connection of the immune response of the nasal and middle ear mucosa and inner ear structures.Articles for this review were identified using PubMed and Google© Scholar databases.Different phenotypes of CRS may be associated with impaired function of the inner and outer cells of the organ of Corti. This is primarily due to the secondary CRS, which occurs within systemic diseases, such as granulomatosis with polyangiitis (GPA) and eosinophilic granulomatosis with polyangiitis (EGPA). Also, the tetrad, which includes CRS with nasal polyps, non-allergic asthma, hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs), and so-called eosinophilic otitis media can lead to SNHL.Previous studies suggest that disrupted harmony between the immune response in the nasal and middle ear mucosa and inner ear structures may contribute to developing SNHL in CRS patients. This especially applies to CRS as part of NSAID-exacerbated respiratory disease and systemic necrotizing vasculitis, including GPA and EGPA. However, the exact mechanisms of development of SNHL in different forms of CRS have not been sufficiently investigated and new studies are necessary soon. Apart from the pathophysiological basis of SNHL, different therapeutic approaches in the clinical phenotypes of CRS have also been discussed.What is known about this topic?It is known that acute rhinosinusitis, both viral and bacterial, can be associated with hearing and balance disorders.Viral microorganisms can reach the structures of the inner ear through the bloodstream and directly damage the cells of the organ Corti or cause an immune response that leads to the deposition of small immune complexes in the labyrinthine artery, thus hindering the vascularization of the receptor structures of the inner ear.Toxic substances of viral and bacterial origin, as well as mediators of inflammation, can diffuse through the oval and, especially round window of the middle ear to the inner ear structures (perilymph, endolymph, membranous labyrinth) and damage the receptor cells of the sense of hearing and balance.Available evidence suggests a high prevalence of otologic symptoms in patients suffering from chronic rhinosinusitis (CRS), affecting up to 87% of patients.The association of CRS and sensorineural hearing loss (SNHL) is one of the least researched areas in otorhinolaryngology.What does this study add?Different phenotypes of CRS may be associated with impaired function of the inner and outer cells of the organ of Corti.Disrupted harmony between the immune response in the nasal and middle ear mucosa and inner ear structures may contribute to developing SNHL in CRS patients.This applies to CRS as part of aspirin-exacerbated respiratory disease (AERD) and systemic necrotizing vasculitis, including granulomatosis with polyangiitis (GPA) and eosinophilic granulomatosis with polyangiitis (EGPA).However, the exact mechanisms of development of SNHL in different forms of CRS have not been sufficiently investigated and new studies are necessary soon. [ABSTRACT FROM AUTHOR]

Objective ANCA-negative granulomatosis with polyangiitis (GPA) remains a diagnosis of exclusion. Clinical differences between patients with ANCA-negative vs ANCA-positive GPA have not been analysed in sizable case-control studies, and the effects of ANCA-seroconversion from negative to positive are not well documented. Methods A single-centre, sex and age matched case-control study evaluated ANCA-negative vs ANCA-positive GPA from 1 January 1996 to 31 December 2015. Patients who experienced seroconversion were the subject of a case-crossover study. Clinical data and outcomes were retrieved from electronic medical records. Results ANCA-negative GPA was identified in 110 patients; 65% were female; median age was 55 (IQR 39–65) years at time of diagnosis. Disease severity was milder in ANCA-negative GPA (BVAS/WG = 2 vs 6, P  < 0.001). Mucous membranous/eye manifestations were more frequent in ANCA-negative GPA. General symptoms, pulmonary and renal involvement were more frequent in ANCA-positive GPA. Patients with ANCA-positive GPA relapsed more over 60 months (21.8% vs. 9.1%, P =  0.009) compared with ANCA-negative GPA and had shorter time to event (P =  0.043). Patients with general manifestations, BMI > 30kg/m2 and necrotizing granulomatous inflammation were more likely to relapse. The 16 patients who seroconverted into ANCA-positive during follow-up had higher mean BVAS/WG at time of diagnosis (P <  0.001) and increased incidence of relapses (P =  0.004) after seroconversion. Necrotizing granulomatous inflammation on biopsy in ANCA-negative GPA patients was identified as a risk factor for subsequent seroconversion to ANCA-positivity. Conclusion Patients with ANCA-negative GPA have milder disease and a lower frequency of relapse than those with ANCA-positive GPA. ANCA appearance portended higher disease severity and an increased frequency of relapses. [ABSTRACT FROM AUTHOR]

This study aims to investigate the clinical manifestations, imaging features, and treatment considerations in the rare occurrence of pneumatosis cystoides intestinalis (PCI) within the context of granulomatosis with polyangiitis (GPA). We present the case of a 71-year-old Chinese woman diagnosed with GPA, who, despite exhibiting fatigue, knee pain, and nasosinusitis, remained asymptomatic for PCI. Regular follow-up revealed laboratory and imaging evidence indicative of clinical relapse. The patient received GPA treatment but was not specifically managed for PCI. Serial abdominal CT scans were performed to monitor the progression of PCI. Radiological diagnosis confirmed the presence of gas within the colon wall, indicating pneumatosis cystoides intestinalis. Notably, the patient remained asymptomatic for abdominal complaints. Despite ongoing GPA treatment, a follow-up CT scan 2 months later revealed persistent gas within the colon wall, suggesting a persistent state of PCI. Patient consent was obtained for the publication of this case report, and ethical approval was not obtained as this study constitutes a retrospective review. This case underscores the importance of recognizing pneumatosis cystoides intestinalis as a potential complication in GPA patients, even in the absence of typical abdominal symptoms. Further research is warranted to elucidate the underlying mechanisms and optimal management strategies for this rare association. Key points • Rare association: This case report sheds light on the uncommon occurrence of pneumatosis cystoides intestinalis (PCI) within the context of granulomatosis with polyangiitis (GPA), adding to the understanding of the spectrum of manifestations of GPA. • Clinical manifestations: Despite being diagnosed with GPA and experiencing symptoms such as fatigue, knee pain, and nasosinusitis, the patient remained asymptomatic for PCI, emphasizing the importance of vigilant clinical monitoring in GPA patients. • Imaging features: Radiological imaging, including serial abdominal CT scans, played a crucial role in diagnosing and monitoring the progression of PCI in the absence of typical abdominal complaints, highlighting the utility of imaging modalities in detecting silent manifestations of gastrointestinal complications in GPA. • Treatment considerations: The case highlights the challenge of managing PCI in GPA patients, especially when asymptomatic, and raises questions about the optimal management strategies for such rare associations, underscoring the need for further research in this area. [ABSTRACT FROM AUTHOR]

Granulomatosis of polyangiitis (GPA) is a multisystem necrotizing vasculitis, which affects small- and medium-sized blood vessels and characterized by frequent involvement of the upper and lower respiratory tract and kidneys. Altough anti-neutrophil cytoplasmic antibodies (ANCA) are higly associated with GPA and play an important role in the pathogenesis of this disease, ANCA positivity is not essential for clinical diagnosis. We describe a patient with ANCA-negative granulamatosis of polyangiitis involving cerebellum, having complaints due to sinusitis. [ABSTRACT FROM AUTHOR]

The document provides a comprehensive overview of the diagnosis, monitoring, and treatment of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) with renal involvement, focusing on granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). It outlines the definitions, clinical presentation, histopathological classification, monitoring strategies, induction and maintenance treatments, as well as special considerations for relapsing, refractory, and frail patients with renal AAV. The document was prepared by the Catalan Group for the Study of Glomerular Diseases (GLOMCAT), which comprises nephrologists with extensive experience in the diagnosis and treatment of AAV patients. Several virtual and face-to-face meetings were held for coordination, section assignments, and content discussion. An exhaustive and systematic search of the literature was carried out, which included, among others, the following databases: PubMed, EMBASE, Cochrane Library, Google Scholar, and ClinicalTrials.gov, as well as the abstract books of national and international congresses. Overall, the document provides a comprehensive guide for clinicians managing patients with renal AAV, offering evidence-based recommendations for diagnosis, monitoring, and treatment across various clinical scenarios. [ABSTRACT FROM AUTHOR]

AbstractBackgroundCase reportConclusionsEosinophilic granulomatosis with polyangiitis (EGPA) is a multisystemic, immune-mediated disease that occurs in patients with asthma and eosinophilia. It is characterized by inflammation of small- and medium-caliber blood vessels.This report presents an unusual clinical case of EGPA with positive anti-neutrophil cytoplasmic antibodies who manifested bilateral pleural effusion. The diagnosis was confirmed through laboratory assessments and bronchial biopsies. The patient was treated with methylprednisolone showing improvement in symptoms.Our case appear interesting considering the limited evidence of pleural effusion in patients with EGPA documented in the literature. [ABSTRACT FROM AUTHOR]

ANCA-associated vasculitides (AAV) comprise granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis. All forms may involve different organ systems, yet kidney and lung involvement are common and fatal in many cases. Here, we aimed to determine the predictive value of pulmonary disease manifestation and individual CT findings in AAV patients. Available CT scans and clinical information on mortality, renal outcomes, occurrence of relapses and damage scores were analysed retrospectively from a tertiary rheumatology center in Germany. We included a total of 94 AAV patients (49 with GPA, 41 with MPA). Forty-four patients had lung involvement with available CT scans, 70.5% of which with GPA and 72.7% with renal involvement. Nodule formation and cavities were more frequent among GPA patients, whereas ground-glass opacities (GGO), ILD and pleural effusion were observed predominantly in MPA patients. Over a median follow-up of 37 months, GPA patients had a slightly higher overall mortality, whereas end-stage kidney failure rates were significantly increased in MPA patients. Relapse frequencies were comparable between both entities. The presence of GGO and pleural effusion were associated with higher relapse rates, whereas nodules were negatively correlated with relapses. Notably, RTX-treated patients had less infections as compared to individuals under different therapies. Our data demonstrate the outstanding importance of characteristic CT patterns in AAV diagnosis assessment. Especially certain CT patterns including GGO and pleura effusion may help to identify patients who are at higher risk for relapsing disease. [ABSTRACT FROM AUTHOR]

Idiopathic orbital inflammation (IOI) is a diagnosis of exclusion, but the exclusion of other inflammatory diseases of the orbit is broad and relies on clinician experience, response to corticosteroid, or biopsy. This study aimed to investigate the presence of granulomatosis with polyangiitis (GPA) in patients initially diagnosed as IOI and describe its clinicopathological features, ANCA status, treatment, and outcome. We performed a retrospective case series study of children diagnosed with limited GPA (L-GPA) in patients with IOI. A systematic review of the literature was performed in children with GPA and orbital mass. Eleven of 13 (85%) patients with IOI had L-GPA. Two additional patients with orbital mass and L-GPA were included in this analysis. The median age was 10 years, and 75% were female. Twelve cases were ANCA positive and 77% were MPO-pANCA positive. Most patients had a poor response to treatment and had a high relapse rate. Based on literature review, 28 cases were found. Most (78.6%) were female with a median age of 9 years. Three patients were misdiagnosed as IOI. Patients with L-GPA more frequently had MPO-pANCA positivity (35%) than children with systemic GPA (18%) and were less often PR3-cANCA positive than patients with systemic GPA (18% vs. 46%). L-GPA accounts for a high prevalence of children diagnosed as IOI. The high prevalence of MPO-pANCA observed in our study may be related to L-GPA rather than with the orbital mass. Long-term follow-up, orbital biopsy, and serial ANCA testing are necessary to exclude GPA in patients with IOI. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate whether the serum extracellular newly identified receptor for advanced glycation end products binding protein (EN-RAGE) and the soluble form of RAGE (sRAGE) measured at diagnosis are associated with all-cause mortality in patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). Materials and Methods: Serum EN-RAGE and sRAGE were measured in 75 immunosuppressive drug-naïve MPA and GPA patients using an immunoassay, with their clinical and laboratory data reviewed. The optimal cut-off point of EN-RAGE and sRAGE was calculated by finding the threshold with the maximum sum of sensitivity and specificity. In addition, the least absolute shrink-age and selection operator regression was adopted to select variables included in the multivariable Cox proportional hazards (PH) regression model. Results: The median age of the patients was 67.0 years, and 34% were male. Neither serum EN-RAGE nor sRAGE at diagnosis was correlated with the Birmingham Vasculitis Activity Score. Furthermore, no correlation was observed between serum EN-RAGE and sRAGE. Deceased patients had significantly lower serum EN-RAGE and higher serum sRAGE at diagnosis compared to surviving patients. Patients with serum EN-RAGE at diagnosis ≤84.37 ng/mL and serum sRAGE at diagnosis ≥1.82 ng/mL showed significantly lower survival probabilities compared to those without. In multivariable Cox PH regression model, only serum sRAGE at diagnosis ≥1.82 ng/mL, rather than serum EN-RAGE at diagnosis ≤84.37 ng/mL, was independently associated with all-cause mortality (hazard ratio 7.094). Conclusion: This study is the first to demonstrate that serum sRAGE at diagnosis may independently predict all-cause mortality during follow-up in patients with MPA and GPA. [ABSTRACT FROM AUTHOR]

Objective. This study aimed to compare the 2022 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) classification criteria with the European Medicines Agency (EMA) algorithm for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Methods. All consecutive, newly diagnosed patients with AAV according to the 2012 Chapel Hill Consensus Conference who visited Keio University Hospital between March 2012 and May 2022 were retrospectively reviewed. Patients were reclassified according to the EMA algorithm and the 2022 ACR/EULAR criteria, and their clinical characteristics were statistically analyzed. Results. A total of 114 patients with AAV were included in the analyses. Using the EMA algorithm as a reference, reclassification of the patients revealed sensitivity and specificity of the 2022 ACR/EULAR criteria of 100% and 96% for eosinophilic granulomatosis with polyangiitis, 40% and 97% for granulomatosis with polyangiitis (GPA), and 90% and 49% for microscopic polyangiitis (MPA), respectively. Approximately half of patients classified as EMA-GPA or EMA-unclassifiable were reclassified as 2022-MPA; these patients were older, were more disposed to be positive for myeloperoxidase (MPO)-ANCA, and had interstitial lung disease (ILD) more frequently than patients with 2022-GPA or non--2022-MPA. Further, some patients positive for MPO-ANCA with biopsy-proven granulomatous inflammation were also reclassified from EMA-GPA to 2022-MPA. Over the mean observation period of 4.0 years, 16 patients died. Overall survival for each classification group differed significantly from the 2022 ACR/EULAR criteria (P = 0.02), but not with the EMA algorithm (P = 0.21). Conclusion. Among the patients classified as EMA-GPA or EMA-unclassifiable, older patients with MPO-ANCA and ILD tended to be reclassified as 2022-MPA. The 2022 ACR/EULAR criteria were more useful in prognostic prediction than the EMA algorithm. [ABSTRACT FROM AUTHOR]

Background: Traditional medical research infrastructures relying on the Centers of Excellence (CoE) model (an infrastructure or shared facility providing high standards of research excellence and resources to advance scientific knowledge) are often limited by geographic reach regarding patient accessibility, presenting challenges for study recruitment and accrual. Thus, the development of novel, patient-centered (PC) strategies (e.g., the use of online technologies) to support recruitment and streamline study procedures are necessary. This research focused on an implementation evaluation of a design innovation with implementation outcomes as communicated by study staff and patients for CoE and PC approaches for a randomized controlled trial (RCT) for patients with vasculitis. Methods: In-depth qualitative interviews were conducted with 32 individuals (17 study team members, 15 patients). Transcripts were coded using the Consolidated Framework for Implementation Research (CFIR). Results: The following CFIR elements emerged: characteristics of the intervention, inner setting, characteristics of individuals, and process. From the staff perspective, the communication of the PC approach was a major challenge, but should have been used as an opportunity to identify one "point person" in charge of all communicative elements among the study team. Study staff from both arms were highly supportive of the PC approach and saw its promise, particularly regarding online consent procedures. Patients reported high self-efficacy in reference to the PC approach and utilization of online technologies. Local physicians were integral for making patients feel comfortable about participation in research studies. Conclusions: The complexity of replicating the interpersonal nature of the CoE model in the virtual setting is substantial, meaning the PC approach should be viewed as a hybrid strategy that integrates online and face-to-face practices. Trial registrations: 1) Name: The Assessment of Prednisone In Remission Trial – Centers of Excellence Approach (TAPIR). Trial registration number: ClinicalTrials.gov NCT01940094. Date of registration: September 10, 2013. 2) Name: The Assessment of Prednisone In Remission Trial – Patient Centric Approach (TAPIR). Trial registration number: Clinical Trials.gov NCT01933724. Date of registration: September 2, 2013. [ABSTRACT FROM AUTHOR]

This case represents the first diagnosis of pachymeningitis due to granulomatosis with polyangiitis (GPA) in an elderly Iranian man who initially presented with persistent daily headaches. PCR tests of cerebrospinal fluid for tuberculosis, brucellosis, and fungal infections all yielded negative results. Given the pachymeningitis pattern observed on brain MRI and the absence of infectious and lymphoma diseases, along with positive anti‐PR3 and proteinuria (793 mg in a 24‐h urine sample), a diagnosis of GPA was established. The patient was treated with five doses of pulse methylprednisolone and one dose of pulse cyclophosphamide (1 g). Additionally, prednisolone 60 mg daily, monthly pulse cyclophosphamide, a daily calcium‐D tablet, and alendronate 70 mg weekly were prescribed. Subsequently, the patient's headaches, hearing loss, and vision loss were completely resolved. GPA should be considered in older individuals with persistent daily headaches, especially when pachymeningitis is evident. The use of contrast‐enhanced brain MRI is an essential diagnostic tool in such cases. [ABSTRACT FROM AUTHOR]

PurposeMethodsResultsConclusionsThe aim of this retrospective case review is to present a novel surgical technique used in the treatment of recalcitrant lower eyelid retraction.This study was performed as a retrospective case review of 4 patients who have failed standard conservative surgical interventions for lower eyelid retraction repair. 3 patients developed lower eyelid retraction following surgical intervention for orbital trauma and 1 patient developed lower eyelid retraction in the setting of granulomatosis with polyangiitis. The surgical technique was identical in each patient and performed by an oculofacial plastic surgeon, sometimes together with an oral and maxillofacial surgeon. Follow-up results for all patients were assessed at 1 week, 1 month, and 3 months.All four patients demonstrated initial improvement in lower eyelid position, fullness, and height. A common finding was mild lateral postoperative entropion, which was easily overcome with an upper eyelid tarsoconjunctival flap. There were no surgical complications sustained in any of the cases.This retrospective case review provides a novel surgical option for the correction of recalcitrant lower eyelid retraction. The excellent vascularity provided by this flap, location, and easy access support its use. A prospective study comparing alternative solutions would be useful in comparing the buccal fat pad vascularized pedicle to alternative methods used to correct refractory and cicatricial lower eyelid retraction. [ABSTRACT FROM AUTHOR]

Objectives: Ceruloplasmin is an inhibitor of myeloperoxidase (MPO) activity that plays an important role in the pathophysiology of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). This study aimed to evaluate the prognostic impact of serum level of ceruloplasmin at diagnosis in patients with anti-MPO antibody-positive AAV. Methods: This retrospective monocentric study in Caen University Hospital involved all consecutive adult anti-MPO antibody-positive patients with microscopic polyangiitis or granulomatosis with polyangiitis, diagnosed between January 2010 and January 2022 with available serum sample at inclusion. Patients outcomes were analyzed from two subgroups constituted according to the median serum level of ceruloplasmin. The same analyses were then performed in anti-proteinase 3 (PR3) antibody-positive patients. Results: Within the 92 patients analyzed, 50 patients had anti-MPO antibodies with a median ceruloplasmin level of 0.44 [quartiles 1–3, 0.40–0.49] g/L and a median Birmingham Vasculitis Activity Score of 19 [14–22]. After a median follow-up period of 40 [22–86] months, 13 (26%) patients had died: 10 (40%) in the low ceruloplasmin group and 3 (12%) in the high ceruloplasmin group (p = 0.03), with a significantly worse survival rate in the low ceruloplasmin group (p = 0.021). No significant differences in relapse rate or renal failure was observed between the two groups. The same analyses performed in the group of AAV patients with anti-PR3 antibody did not show any differences. Conclusion: In anti-MPO AAV patients, serum level of ceruloplasmin at diagnosis seems to be associated with a significant impact on survival. [ABSTRACT FROM AUTHOR]

This article discusses two cases of severe hypercalcemia in lung transplant recipients, which were diagnosed as Pneumocystis jirovecii pneumonia (PJP). Both patients were successfully treated with trimethoprim-sulfamethoxazole (TMP-SMX) and showed improvement in symptoms and calcium levels. The article highlights the importance of considering PJP as a possible cause of hypercalcemia in immunocompromised patients and suggests further research on risk factors and prophylaxis strategies. [Extracted from the article]

The differential diagnosis between granulomatosis with polyangiitis (GPA) and infective endocarditis (IE) is crucial. Both diseases show clinical similarities and serologic c-ANCA overlap. We present the case of a 45-year-old patient with inflammatory and anemic syndrome, c-ANCA positivity and initial respiratory and renal symptoms that raised the suspicion of GPA. Subsequent evolution revealed severe valve involvement and the presence of Streptococcus gallolyticus in blood cultures, confirming the diagnosis of infective endocarditis. Antibiotic treatment and surgical intervention were crucial for the patient's recovery. This case demonstrates the importance of imaging and microbiological examinations for the correct differentiation of these diseases and the importance of a multidisciplinary approach. [ABSTRACT FROM AUTHOR]

Granulomatosis with polyangiitis (GPA), previously known as Wegener's granulomatosis, is a vasculitis that primarily affects the respiratory tract and kidneys(1). Known as a rare disease, predominantly affects Caucasian adults aged between 45 and 60 years(2). While the specific cause remains unclear, it is believed that environmental factors play a role in triggering the condition in individuals who are genetically predisposed(3). There is a wide range of clinical manifestations, comprising both general nonspecific symptoms(4) and organ-specific symptoms, with lung involvement in nearly 90% of patients(5). The diagnosis relies on clinical and imaging criteria, along with histopathological confirmation(2). Treatment consists of an induction phase, followed by a maintenance phase, utilizing glucocorticoids and immunosuppressants, which has greatly enhanced the prognosis for these patients(6). The objective of this paper is to illustrate the complexity of GPA through the presentation of a clinical case. The patient is a 59-year-old man with a professional background involving exposure to respiratory toxins who presented to the clinic with intermittent mucopurulent cough, episodes of hemoptysis, nonspecific chest pain, bilateral knee pain, weight loss, and excessive nocturnal sweating. The imaging findings indicated significant polymorphic lesions in the lungs, and the diagnosis of GPA was confirmed via transthoracic biopsy. Using a therapeutic strategy of immunosuppression and oral corticosteroid therapy, the patient's clinical condition showed a modest improvement. The particularity of this case lies in the need to revise the treatment strategy for a patient identified as a non-responder to cyclophosphamide, given the imaging, functional and biological decline observed under the initial immunosuppressive therapy. [ABSTRACT FROM AUTHOR]

Primary ciliary dyskinesia (PCD) is predominantly an autosomal recessive disorder that is characterized by recurrent respiratory infections stemming from impaired ciliary motility. Granulomatous polyangiitis is a necrotizing vasculitic disease marked by granulomatous inflammation in the vascular wall that often manifests in the lungs with cavitating nodules, masses and consolidations. A 24-year-old female patient presented to our clinic complaining of dyspnea, productive cough and pleuritic chest pain, and was diagnosed with Kartagener Syndrome based on her situs inversus, bronchiectasis and sinusitis. Subsequent genetic tests and further clinical evaluations, including thoracic CT, revealed findings of cavitating nodules, PR3-ANCA positivity and leukocytic vasculitis from a skin biopsy pathology, confirming the coexistence of PCD and granulomatous polyangiitis. [ABSTRACT FROM AUTHOR]

We aimed to clarify the long-term safety and efficacy of rituximab (RTX) as a remission induction therapy following severe relapse in patients with antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV). We retrospectively collected the data of patients with severely relapsed AAV from a Japanese multicentre cohort. The primary exposure was RTX use; the primary outcome was complete remission (CR) proportions at week 24. Baseline characteristics were compared between the RTX and non-RTX groups. We performed multivariate logistic regression analysis and one-to-one propensity score matching analysis as a sensitivity analysis. Totally, 100 patients were enrolled: 52 in the RTX group and 48 in the non-RTX group. Baseline characteristics were comparable between the two groups, except for age, AAV subtype and ANCA serotype. The median age was 71 vs. 75 years, and the PR3-ANCA positivity rate was 44.2% vs. 18.8% in the RTX and non-RTX groups, respectively. No significant difference was observed in CR proportions at week 24 between the two groups (79.2% vs. 68.1%, p = 0.321), with an adjusted odds ratio of 1.27 (95% confidence interval [CI] 0.47–3.51). At week 48, CR proportions were significantly higher in the RTX group (91.7% vs. 64.9%, p = 0.005), with an adjusted odds ratio of 2.95 (95% CI 0.97–9.91). Serious infection rates were lower in the RTX group than in the non-RTX group, with no statistically significant difference. RTX was not superior to conventional immunosuppressive therapies at week 24 but showed significantly favourable results at week 48 for severely relapsed AAV. Key Points • RTX might be superior to traditional treatments as an induction therapy for severely relapsed AAV. • RTX has the potential to sustain long-term remission with fewer occurrences of infections in the treatment of severely relapsed AAV. [ABSTRACT FROM AUTHOR]

The article focuses on a 10-year-old female with a month-long history of intermittent fever, fatigue, joint pain, and rash, whose condition worsened despite outpatient evaluation, prompting a return to the pediatric emergency department. Topics include the patient's medical history including epilepsy and recent COVID-19 vaccination, laboratory findings such as anemia and a positive respiratory pathogen panel for Coronavirus OC43.

Purpose: To report a patient with bilateral scleritis who was initially treated for infectious scleritis, and subsequently diagnosed as granulomatosis with polyangiitis (GPA). Method: Retrospective chart review. Result: A 48-year-old female with a known history of diabetes presented with pain, redness, and blurring of vision in the right eye. She was diagnosed as scleritis with retinal detachment and underwent vitrectomy, with silicone oil tamponade and intravitreal injections of antibiotics, and antifungal agents. She presented with active scleritis with additional multiple pus points. Several scleral biopsies failed to yield any microorganism and finally, the painful blind eye was enucleated. The enucleated specimen grew gram-positive bacteria which were identified as Staphylococcus arlettae by polymerase chain reaction (PCR)-based sequencing of the 16S rRNA gene. Nine months after the onset of symptoms in the right eye, the patient developed necrotizing scleritis in the left eye. Laboratory investigation revealed a positive cytoplasmic- anti-neutrophil cytoplasmic autoantibody, which was previously negative during the right eye involvement. She was diagnosed with GPA by a rheumatologist and treated accordingly. Conclusion: Retinal detachment may be associated with scleritis, and ANCA testing may not detect GPA in its early stages. Once infection has been excluded, clinicians should not be afraid to use high-dose immunosuppression instead of surgery to treat retinal detachment associated with scleritis. [ABSTRACT FROM AUTHOR]

Children with anti-neutrophil cytoplasmic antibody-associated vasculitis benefit immensely from avacopan as it reduces the requirement for steroids. However, descriptions of adverse drug reactions in children are lacking, and the dosage and follow-up intervals are unclear. A 10-year-old boy with initial granulomatosis and polyangiitis presented with diffuse pulmonary hemorrhage. Rituximab and 30 mg avacopan were administered twice daily as induction therapy following methylprednisolone pulse therapy. However, sudden liver function test abnormalities were observed on day 31 of avacopan treatment, despite liver enzyme levels being within the normal range 5 days earlier. A drug-induced lymphocyte stimulation and various infectious disease tests yielded negative results. Discontinuation of rituximab and avacopan resulted in improved liver function; no change in the Birmingham Vasculitis Activity Score during liver function test abnormalities was observed. Avacopan-associated abnormalities in liver function tests suggest that drug-induced liver injury may occur rapidly in children, and appropriate dosing strategies should be reconsidered. [ABSTRACT FROM AUTHOR]

Background: Ocular involvement is relatively common in granulomatosis with polyangiitis (GPA); however, choroidal involvement is rare. We present a case of serous retinal detachment resulting from choroidal involvement in GPA. Case presentation: A 55-year-old male presented to our clinic with bilateral eye redness and pain. Ocular examination revealed bilateral conjunctival injection, and dilation of the episcleral and scleral vessels. Slit-lamp examination revealed anterior chamber cells. Optical coherence tomography (OCT) confirmed serous retinal detachment (SRD) in the left eye. The patient had recently been diagnosed with GPA following a lung biopsy and had received immunosuppressive therapy, including systemic steroids, cyclosporine, mycophenolate mofetil, and rituximab. Five weeks after treatment, the clinical symptoms of the patient, including SRD, improved with alleviation of systemic symptoms. However, tapering systemic steroids and immunosuppressants and discontinuing rituximab led to disease reactivation. OCT demonstrated a recurrence of subretinal fluid, which had previously resolved, and slit-lamp examination showed mild bilateral engorged scleral vessels. Conclusions: Choroidal involvement can present as SRD and may indicate disease activity in patients with GPA. [ABSTRACT FROM AUTHOR]

This article explores the challenges faced by women with systemic vasculitides, rare rheumatic diseases characterized by inflammation in blood vessel walls, during pregnancy. It emphasizes the importance of planning pregnancy when the disease is in remission and on stable pregnancy-compatible immunosuppressants. The article presents findings from a qualitative study that highlights the need for patient self-advocacy and improved communication between healthcare providers. It also discusses the outcomes of pregnancies in women with vasculitis, with most resulting in live births but some complications. The article acknowledges the need for further research to accurately estimate the risk of adverse pregnancy outcomes in women with vasculitis and suggests training more reproductive rheumatologists and creating multidisciplinary clinics to improve reproductive health management for these patients. [Extracted from the article]

Objective: Avacopan, an activated complement factor 5 receptor antagonist, has been approved as adjunct therapy for severe active antineutrophil cytoplasmic antibody–associated vasculitis (AAV). Current evidence supports the management of AAV presenting with diffuse alveolar hemorrhage (DAH) by administering glucocorticoids combined with either rituximab or cyclophosphamide in addition to supportive care. The role of avacopan in patients with DAH as a primary severe disease manifestation of AAV has not been well established. Furthermore, concerns remain regarding timely access to avacopan, the best glucocorticoid tapering regimen, and long‐term efficacy and safety of the drug. We sought to identify clinical features and outcomes of patients presenting with DAH secondary to AAV who received avacopan in addition to glucocorticoids and rituximab or cyclophosphamide. Methods: We performed a retrospective cohort study of all consecutive patients presenting with DAH as part of active severe granulomatosis with polyangiitis or microscopic polyangiitis. Demographic and clinical characteristics were collected at presentation and follow‐up. Results: Fifteen patients met inclusion criteria and were observed for a median time of 17 weeks (interquartile range [IQR] 6–37 weeks) after initiation of avacopan. Patients were predominantly female and White, had never smoked, and were a median age of 66 years (IQR 52–72 years) at diagnosis. The majority had newly diagnosed severe AAV with renal involvement. Three patients progressed to respiratory failure. The timing of avacopan introduction and patterns of glucocorticoid tapers varied widely in this cohort. Two serious adverse events related to infection were observed, including one opportunistic infection leading to the patient's death, although neither was directly attributed to avacopan administration. Conclusion: We describe the clinical course of patients who presented with the severe AAV disease manifestation of DAH and received avacopan as adjunct therapy. Most patients achieved remission during follow‐up, and adverse events, including infection, were observed. [ABSTRACT FROM AUTHOR]

Objective: Signal regulatory protein α (SIRPα) is found primarily on myeloid cells, including macrophages and neutrophils; binds to CD47; and regulates phagocytosis, antigen presentation, cellular fusion, cell proliferation, and migration. Therefore, SIRPα may be involved in the pathogenesis of autoimmune diseases, including systemic vasculitis. This study aimed to assess SIRPα expression in tissue samples from patients with vasculitis. Methods: Immunohistochemical staining for SIRPα was performed on temporal artery (TA), kidney, and lung biopsy samples from patients with giant cell arteritis (GCA), patients with microscopic polyangiitis (MPA), patients with granulomatosis with polyangiitis (GPA), and patients without vasculitis. A score of SIRPα+ expression was calculated, derived from the percentages of monocytes, macrophages, and dendritic cells and neutrophils with different staining intensities in affected tissues. Results: A total of 46 samples from patients with different vasculitides (GCA, MPA, and GPA) were included in the study. Tissue samples included TA samples from 15 patients with GCA; kidney samples from 11 and 9 patients with GPA and MPA, respectively; and lung samples from 11 patients with GPA. Most tissue samples from patients with active vasculitis (15 of 15 TA samples, 17 of 20 kidney samples, and 9 of 11 lung samples) showed SIRPα staining. SIRPα staining intensity was less in kidney samples compared to TA and lung samples. Conclusion: This study demonstrates high‐level expression of SIRPα in macrophages and monocytes in affected tissue in systemic vasculitis. These findings provide a foundation for further studies exploring the role of the SIRPα–CD47 pathway in the pathogenesis of systemic vasculitis and the potential for the blockade of SIRPα and/or the depletion of SIRPα+ cells as treatment of systemic vasculitis. [ABSTRACT FROM AUTHOR]

Objective: To compare the performance of the EMA (European Medicines Agency) algorithm for classification of necrotizing vasculitis and the new American College of Rheumatology (ACR)/European League of Rheumatology (EULAR) 2022 classification criteria in our single center long-term anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) cohort. Methods: Patients classified as granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) according to EMA algorithm were included into the study. ACR/EULAR 2022 classification criteria were implemented retrospectively. Antibody-based classification (ABC) was performed as a third model, which classify patients either GPA or MPA if anti-proteinase 3 (PR3) or myeloperoxidase (MPO) is positive, respectively. Kappa analysis was used to explore the agreement between criteria sets. Results: Data of 221 patients classified as GPA (85.6%) and MPA (14.5%) according to EMA algorithm were included. PR3-ANCA and MPO-ANCA was positive in 124 (56.1%) and 79 (35.7%) patients. ACR/EULAR 2022 classified 137 (62%) and 84 (38%) patients as GPA and MPA, respectively. Nine (4%) patients were classified as both GPA and MPA, nine (4%) patients were unclassifiable. The new criteria set was in weak agreement with EMA algorithm (kappa=0.28 for GPA and 0.24 for MPA). On the other hand, strong agreement with ABC was observed (kappa=0.88 for GPA and 0.89 for MPA). Conclusion: A significant number of patients who classified as GPA could be classified as MPA with the ACR/EULAR 2022 criteria and agreement with EMA algorithm was weak. The new criteria set was indecisive for some AAV patients. Strong agreement with ABC indicated the significant influence of serology in the ACR/EULAR 2022 criteria.

Abstract Background Chronic invasive rhinosinusitis with facial bone damage is a common cause of functional and social impairment in granulomatosis with polyangiitis (GPA) patients. To the best of our knowledge, there is no clinical or laboratory biomarker to predict bone damage. Methods This case-control study included 90 patients with GPA and 270 health controls (HCs). Patients were categorized according to the presence of tomographic facial bone erosions. Frequency of RANKL and osteoprotegerin single nucleotide polymorphisms (SNPs), analyzed by real-time polymerase chain reaction, were compared between patients and HCs, and between patients with and without bone damage. Clinical, therapeutic, and laboratory data were analyzed. Results Facial bone erosion was observed in 55.5% of patients. No difference was found in the frequency of SNPs between patients with GPA and HCs. GPA patients were compared according to the presence or absence of bone damage, and a difference was found in the frequencies of osteoprotegerin G1181C (rs2073618) and RANKL A290G (rs2277438). A multivariate analysis showed that the CC genotype of osteoprotegerin 1181 was independently associated with bone erosion (OR = 3.95, CI95%=1.20–13.00, P = 0.02), as were the presence of the G allele in RANKL A290G (OR = 6.13, CI95%=1.95–19.26, P = 0.002) and higher disease duration (OR = 1.08, CI95%=1,01-1.15, P = 0.04). Conclusion SNPs in osteoprotegerin G1181C and RANKL A290G may play a role in the development of destructive rhinosinusitis in patients with GPA. Genetic assessment may be useful for identifying high-risk individuals. This observational study might work as a basis for further research to better understand this association and clinical trials using RANKL/osteoprotegerin as therapeutic targets.

Abstract Background Traditional medical research infrastructures relying on the Centers of Excellence (CoE) model (an infrastructure or shared facility providing high standards of research excellence and resources to advance scientific knowledge) are often limited by geographic reach regarding patient accessibility, presenting challenges for study recruitment and accrual. Thus, the development of novel, patient-centered (PC) strategies (e.g., the use of online technologies) to support recruitment and streamline study procedures are necessary. This research focused on an implementation evaluation of a design innovation with implementation outcomes as communicated by study staff and patients for CoE and PC approaches for a randomized controlled trial (RCT) for patients with vasculitis. Methods In-depth qualitative interviews were conducted with 32 individuals (17 study team members, 15 patients). Transcripts were coded using the Consolidated Framework for Implementation Research (CFIR). Results The following CFIR elements emerged: characteristics of the intervention, inner setting, characteristics of individuals, and process. From the staff perspective, the communication of the PC approach was a major challenge, but should have been used as an opportunity to identify one “point person” in charge of all communicative elements among the study team. Study staff from both arms were highly supportive of the PC approach and saw its promise, particularly regarding online consent procedures. Patients reported high self-efficacy in reference to the PC approach and utilization of online technologies. Local physicians were integral for making patients feel comfortable about participation in research studies. Conclusions The complexity of replicating the interpersonal nature of the CoE model in the virtual setting is substantial, meaning the PC approach should be viewed as a hybrid strategy that integrates online and face-to-face practices. Trial registrations 1) Name: The Assessment of Prednisone In Remission Trial – Centers of Excellence Approach (TAPIR). Trial registration number: ClinicalTrials.gov NCT01940094 . Date of registration: September 10, 2013. 2) Name: The Assessment of Prednisone In Remission Trial – Patient Centric Approach (TAPIR). Trial registration number: Clinical Trials.gov NCT01933724 . Date of registration: September 2, 2013.

Background: Pauci-immune glomerulonephritis (PIGN) is typically secondary to antineutrophil cytoplasmic antibodies (ANCA) small-vessel vasculitis. However, some cases lack detectable circulating ANCA and are called ANCA-negative PIGN (seronegative PIGN). The reported incidence of this varies greatly. Its relationship to ANCA-associated vasculitis (AAV) is unclear. Summary: This review explores the pathophysiology of seronegative PIGN and summarizes findings from 12 studies focusing on this disease. The role of neutrophils appears to be central, with activation through cellular and humoral mechanisms. Most studies have noted less extrarenal involvement and more chronic changes in the kidney biopsy in seronegative PIGN compared to ANCA-positive cases. Studies have mostly reported using corticosteroids with cyclophosphamide for induction therapy and azathioprine for maintenance. The renal survival was noted to be lower compared to ANCA-positive PIGN. Key Messages: Whether ANCA-negative PIGN represents a distinct disease or is part of the AAV spectrum remains unclear. Prospective large-scale studies are needed to understand this disease for optimal diagnosis and management.

Antineutrophil cytoplasmic antibodies associated vasculitis (ANCA-AV) is a systemic necrotizing granulomatous vasculitis affecting mainly small-caliber vessels. ANCA-AV occupy a special place among systemic vasculitis, which is characterized by a highly active life-threatening course of the disease, requiring rapid differential diagnosis and aggressive immunosuppressive therapy. The ANCA-AV group consists of 3 nosologies: granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis and microscopic polyangiitis. The “calling card” of ANCA-AV is the lesion of the upper respiratory tract, especially the ENT organs (70–100 % of patients). The nasal cavity and paranasal sinuses are the most common areas of lesion in the head and neck (85–100 %), whereas ear damage occurs in about 35% (range, 19–61 %) of cases. Lesion of the ENT organs is typical for the debut of ANCA-AV, which makes early diagnosis difficult, since diseases of the upper respiratory tract are extremely common in all age groups. Diagnosis verification occurs mainly at the stage of generalized involvement of many organs and systems, causing severe course with the development of pulmonary-cardiac and renal insufficiency, which lead to the death of the patient. The main ENT manifestations of ANCA-AV can be grouped into several groups: sinonasal, otological, tracheobronchial, oral cavity lesions and others. Pseudotumors are often found in ANCA-AV. They are characterized by the appearance of parapharyngeal, parotid, submandibular, paratracheal volumetric formations. As a rule, the appearance of tumor-like formations is observed at an early stage of the disease and is associated with the presence of antibodies to proteinase 3, systemic manifestations of vasculitis. Pseudotumor in the ENT region may be accompanied by secondary neuropathies of cranial nerves, destruction of bone tissue, which requires histological verification of the disease.

Ling Hou,1,&ast; Jinbo Zhao,2,&ast; Ting He,1,&ast; Yinhua Luo,3 Ke Su,2 Yuanhong Li,2 Ruiyang Zhu3 1Central Hospital of Tujia and Miao Autonomous Prefecture, Hubei University of Medicine, Shiyan, People’s Republic of China; 2Cardiovascular Disease Center, Central Hospital of Tujia and Miao Autonomous Prefecture, Hubei University of Medicine, Enshi, Hubei Province, People’s Republic of China; 3Center for Gene Diagnosis and Department of Clinical Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuanhong Li, Cardiovascular Disease Center, Central Hospital of Tujia and Miao Autonomous Prefecture, Hubei University of Medicine, Enshi, 445400, People’s Republic of China, Email lyh0101@vip.163.com Ruiyang Zhu, Center for Gene Diagnosis and Department of Clinical Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, People’s Republic of China, Email zhuruiyang@whu.edu.cnAbstract: Granulomatosis with polyangiitis (GPA) is a necrotizing granulomatous vasculitis classified as an autoimmune small-vessel vasculitis. Clinically, approximately 80% of affected organs in GPA involve the upper/lower respiratory tract and kidneys, with cardiovascular system involvement being rare. Here, we report a case of a 50-year-old female patient who presented with sudden-onset chest pain lasting for 1 hour. The patient had normal body temperature, and markers of infection such as C-reactive protein and erythrocyte sedimentation rate were within normal limits. Electrocardiography revealed ST-segment elevation in inferior, precordial, and posterior leads. Emergency coronary angiography showed no significant obstructive disease, prompting consideration of vasospastic angina given the patient’s recurrent chest pain symptoms and findings on laboratory and imaging studies. The patient underwent treatment including coronary vasospasm antagonists and immunomodulation, resulting in clinical improvement and subsequent discharge. During a 7-month follow-up period, the patient did not experience any further adverse cardiovascular events.Keywords: granulomatosis with polyangiitis, vasospastic angina, case report

Objective: Antineutrophil cytoplasmic antibody (ANCA)‐associated vasculitis (AAV) is divided into granulomatosis with polyangiitis (GPA), microscopic polyangiitis, and eosinophilic GPA. It is one of the most severe and potentially fatal autoimmune inflammatory conditions. The etiology and pathology of AAV are complex and poorly understood. Since the onset of the Coronavirus Disease 2019 (COVID‐19) pandemic, numerous reports have documented GPA cases following COVID‐19, suggesting a potential link between COVID‐19 and the development of GPA. This case report discusses a 16‐year‐old East Asian boy who developed GPA with diffuse alveolar hemorrhage after contracting COVID‐19. Additionally, a literature review was conducted to gain a deeper understanding of this disorder. Methods: The study involved a retrospective analysis of the data of a case of GPA post‐COVID‐19 infection, aiming to summarize the clinical characteristics of GPA post‐COVID‐19 infection through a search of databases (PubMed, Wanfang Data, and CNKI), supplemented by standard searches in Google Scholar, Cochrane, Scopus, and LitCovid, and to conduct a comprehensive analysis of the literature. Results: A total of 12 cases were identified and, when combined with the present case, yielded 13 cases of GPA post‐COVID‐19 infection, comprising 5 males and 8 females with an average age of (40.6 ± 19.5) years. The interval between COVID‐19 infection and the diagnosis of GPA varied from 1 day to 3 months across all cases. Mortality was reported at 7.7% (1/13). The most common clinical manifestations included cough (69.2%) and dyspnea (46.1%). Computed tomography scans revealed ground‐glass opacities and multifocal pulmonary nodules. In all cases, positive findings for c‐ANCA and protease 3‐antibody were observed. Renal involvement was observed in more than half of the patients. [ABSTRACT FROM AUTHOR]

Objective Granulomatosis with polyangiitis (GPA) is an ANCA-associated vasculitis. The 2022 ACR/EULAR-endorsed classification criteria for GPA was derived using data only from adult patients. We aimed to assess the performance of the ACR/EULAR classification criteria for GPA in paediatric patients and compare it with the EULAR/Pediatric Rheumatology International Trials Organization (PRINTO)/Pediatric Rheumatology European Society (PReS)-endorsed Ankara 2008 criteria for GPA. Methods Retrospective data of paediatric patients with GPA in 20 centres from 9 countries were evaluated. The diagnosis of GPA was made according to the expert opinion. The sensitivity, specificity, positive predictive value, and negative predictive value of the criteria sets were evaluated. Results The study included 77 patients with GPA and 108 controls [IgA vasculitis (n  = 44), Takayasu's arteritis (n  = 20), microscopic polyangiitis (n  = 16), polyarteritis nodosa (n  = 14), Behçet's disease (n  = 12), eosinophilic granulomatosis with polyangiitis (n  = 1) and Cogan's syndrome (n  = 1)] with a median age of 17.8 and 15.2 years, respectively. Among patients with GPA, constitutional symptoms (85.7%) and ENT involvement (79.2%) were the most common presentations. In the GPA group, 73 patients fulfilled the Ankara 2008 criteria and 69 the ACR/EULAR classification criteria. Sensitivities of the Ankara 2008 criteria and the ACR/EULAR classification criteria were 94.8% and 89.6%, while specificities were 95.3% and 96.3%, respectively. No significant difference was found between sensitivities and specificities of both classification criteria (P  = 0.229 and P  = 0.733, respectively). Conclusion In children, both the ACR/EULAR and EULAR/PRINTO/PReS Ankara 2008 classification criteria for GPA perform well and similarly. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the effectiveness and safety of two different intravenous methylprednisolone (IVMP) pulse doses in patients with severe microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). Methods We emulated a target trial using observational data from the nationwide registry in Japan. Patients with severe glomerulonephritis or diffuse alveolar haemorrhage were selected and pseudo-randomized into three groups using propensity score-based overlap weighting as follows: non-IVMP, IVMP 0.5 g/day and IVMP 1.0 g/day. The primary outcome was all-cause mortality, and the secondary outcomes were composite all-cause mortality and kidney failure, severe relapse and serious infection from 2 to 48 weeks after treatment initiation. To estimate the treatment effects, the Cox proportional hazard model and Fine–Gray subdistribution hazard model were used. Results In this emulated target trial, of 201 eligible patients (MPA, 175; GPA, 26), 6 (3%) died, 4 (2.0%) had kidney failure, 11 (5.5%) had severe relapse, and 40 (19.9%) had severe infections. Hazard ratios (HR) for IVMP 0.5 g/day and IVMP 1.0 g/day pulse groups compared with non-IVMP pulse were as follows: all-cause mortality 0.46 (95% CI: 0.07, 2.81) and 0.07 (95% CI: 0.01, 0.41), respectively; all-cause mortality/kidney failure 1.18 (95% CI: 0.26, 5.31) and 0.59 (95% CI: 0.08, 4.52), respectively; subdistribution HRs for severe relapse were 1.26 (95% CI: 0.12, 13.70) and 3.36 (95% CI: 0.49, 23.29), respectively; and for serious infection 1.88 (95% CI: 0.76, 4.65) and 0.94 (95% CI: 0.28, 3.13), respectively. Conclusion IVMP 1.0 g/day pulse may improve 48-week mortality in patients with severe MPA/GPA. [ABSTRACT FROM AUTHOR]

Avacopan 30 mg twice daily (BID) is approved for the treatment of severe active antineutrophil cytoplasmic autoantibody–associated vasculitis (granulomatosis with polyangiitis and microscopic polyangiitis). Food effect on avacopan pharmacokinetics (PKs) and PK bridging in Japanese participants were examined through 2 phase 1 studies involving healthy adult participants. In Study 1, an open‐label, crossover trial, participants received oral administration of a single 30‐mg dose of avacopan under fasted and fed conditions. Study 2 was a randomized, single‐blind, placebo‐controlled trial in Caucasian and Japanese participants: Part A investigated single doses of 10 and 30 mg of avacopan under fasted and fed conditions and Part B investigated 30 and 50 mg BID avacopan. The PKs of single‐dose administrations of 10 and 30 mg in Japanese participants was compared with that in Caucasian participants under fasted conditions. Food substantially increased plasma avacopan area under the plasma concentration‐time curve from time 0 to time infinity (AUC0‐inf) by 1.72‐fold, supporting the recommendation of taking avacopan with food. Maximum plasma concentration (Cmax) remained relatively unchanged. The median time to reach Cmax (tmax) was delayed by 3 hours. No significant food effect was observed on the active metabolite CCX168‐M1 (M1) AUC. Avacopan and M1 exposures were <1.5‐fold higher in Japanese participants than in Caucasian participants following multiple‐dose administration of avacopan. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to explore ocular manifestations in ANCA-associated vasculitis (AAV), focusing on granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (EGPA), and microscopic polyangiitis (MPA) and to examine the associations with laboratory parameters and other systemic manifestations. Methods: This retrospective study reviewed data from 533 AAV patients across two major Chinese medical centers from January 2016 to November 2023. Data including diagnosis, cranial manifestations of disease, ocular complications, and laboratory parameters were analyzed. Univariate and multivariable logistic regression analyses assessed associations across disease manifestations. Machine learning models were also utilized to predict the risk of retinal/eye involvement in AAV patients. Results: Among 533 patients (210 GPA, 217 MPA, 99 EGPA, and 7 unclassified AAV), ocular complications were observed in 20.64% of them, with a distribution of 36.67% in GPA, 7.37% in MPA, and 18.18% in EGPA. The most common ocular manifestations included scleritis and retro-orbital mass/dacryocystitis, which were notably prevalent in GPA patients. Retinal involvement was observed in 9.09% of EGPA cases. The machine learning models yielded that eosinophil percentage (EOS%), high-sensitivity C-reactive protein (hsCRP), and CD4 + T cell/CD8 + T cell ratio (T4/T8) can predict retinal involvement. Furthermore, the white blood cell, EOS%, APTT, IgA, hsCRP, PR3-ANCA, and T4/T8 can predict eye involvement. Conclusion: Ocular manifestations are a prevalent complication across all forms of AAV. Predictive models developed through machine learning offer promising tools for early intervention and tailored patient care. This necessitates a multidisciplinary approach, integrating rheumatology and ophthalmology expertise for optimal patient outcomes. Key Points • This study provides new insights into the ocular manifestations of ANCA-associated vasculitis across different subtypes, revealing a notable prevalence of ocular complications. • A machine learning model is built to predict eye/retinal involvement, enhancing early diagnostic capabilities. • The findings could guide more systematic ocular screenings in ANCA-associated vasculitis patients and influence treatment protocols. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 15-year-old girl with migratory joint pain, rash, and respiratory symptoms, ultimately diagnosed with granulomatosis with polyangiitis (GPA). Topics discussed include the diagnostic challenges of pulmonary hemorrhage, the role of Antineutrophil Cytoplasmic Antibody (ANCA)-associated vasculitides in such presentations, and the management strategies involving corticosteroids and immunosuppressants.

Necrotizing scleritis is the most destructive and vision-threatening form of scleritis. Necrotizing scleritis can occur in systemic autoimmune disorders and systemic vasculitis, as well as following microbial infection. Rheumatoid arthritis and granulomatosis with polyangiitis remain the commonest identifiable systemic diseases associated with necrotising scleritis. Pseudomonas species is the most common organism causing infectious necrotizing scleritis, with surgery the most common risk factor. Necrotizing scleritis has the highest rates of complications and is more prone to secondary glaucoma and cataract than other phenotypes of scleritis. The differentiation between non-infectious and infectious necrotizing scleritis is not always easy but is critical in the management of necrotizing scleritis. Non-infectious necrotizing scleritis requires aggressive treatment with combination immunosuppressive therapy. Infectious scleritis is often recalcitrant and difficult to control, requiring long-term antimicrobial therapy and surgical debridement with drainage and patch grafting due to deep-seated infection and the avascularity of the sclera. [ABSTRACT FROM AUTHOR]

Purpose of Review: This review aims to summarize the evolution and recent developments in the classification of ANCA associated vasculitis (AAV) and to summarize evaluations of the 2022 ACR/EULAR classification criteria of AAV in several cohorts. Recent Findings: The classification of AAV has been a field of controversy for some time. The parallel existence of classification criteria and disease definitions produced some overlap in classification, leading to challenges when comparing different cohorts. The 2022 ACR/EULAR classification criteria derived from the largest study ever conducted in vasculitis account for significant changes in vasculitis classification with the integration of ANCA and modern imaging. These criteria show good performance compared to previous ones but also raise questions as ANCA serotypes have substantial impact on classification. In addition, there are some discrepancies with earlier agreed histopathological features of AAV disease phenotypes. Summary: During the last 35 years, several sets of classification criteria have evolved to facilitate epidemiologic studies and clinical trials in AAV. While some of these criteria have been in use for many years, they were criticized due to either not using ANCA or not integrating surrogate markers for vasculitis but also due to overlapping when used in parallel. The long-awaited new ACR/EULAR criteria for AAV were published in 2022 and are the result of a large international study, introducing for the first time ANCA and modern imaging in the classification of AAV. Though the criteria show good performance, they bring several other challenges with practical application. [ABSTRACT FROM AUTHOR]

Background and objectives: The initial symptom that triggers granulomatosis with polyangiitis (GPA) diagnosis is rarely ocular. We describe a case with a single ocular lesion identified as probable GPA due to proteinase 3 (PR3)-antineutrophil cytoplasmic antibody (ANCA)-positivity according to the diagnostic criteria of the Ministry of Health in Japan; the lesion repeatedly worsened. Materials and methods: A 25-year-old female visited the Department of Ophthalmology, Asahi General Hospital, with upper eyelid swelling and conjunctival and episcleral hyperemia of the left eye. Both hordeolum and eyelid cellulitis were suspected, as the condition was resistant to treatment with antibiotic eye drops. Episcleritis was suspected due to localized hyperemia in the upper part of the eye. Upon treatment with antibacterial agents and steroid eye drops, the swelling and the hyperemia repeatedly worsened every week. Results: Blood samples were positive for PR3-ANCA, and GPA with an isolated ocular lesion was considered. After oral steroid treatment, the patient had no recurrence for 4 years. There was no systemic involvement in the upper respiratory tract, lungs, or kidneys. Conclusions: Diagnosing GPA with ocular symptoms as initial manifestations is challenging. GPA should be considered in treatment-resistant eyelid, orbital, and episcleral lesions, even at a young age. [ABSTRACT FROM AUTHOR]

Objectives Rituximab is used for remission induction and the prevention of relapse in anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). This study evaluated the incidence of safety events and compared time to first serious adverse event (SAE) between a rituximab cohort and a cohort treated with non-rituximab therapies in a real-life setting. Methods Rituximab surveillance study in vasculitis was a retrospective observational study of patients with AAV who received rituximab (MabThera) or other treatments between 2003 and 2017 at a specialist vasculitis clinic. The primary endpoint was time to first SAE. Results 392 patients were enrolled: 247 in the rituximab and 145 in the control cohorts with a total follow up of 2217 person-years (mean study duration 5.7 years). Mean age was 61 years, 77% had granulomatosis with polyangiitis (GPA). There were differences in baseline characteristics (disease duration and prior immunosuppressive use) between groups. 134/247 patients (54%) in the rituximab and 58/145 (40%) of controls experienced at least one SAE. Time to first SAE was shorter in the rituximab group (hazard ratio (HR) 1.55, 95% CI 1.07–2.26, P  = 0.022). Predictors of first SAE were higher vasculitis damage index and the presence of chronic pulmonary or kidney disease. The risk of serious infection was higher in the rituximab group (relative risk (RR) 2.12, 95% CI 1.31–3.43). Conclusion Over 40% of patients with AAV experienced at least one SAE. Although shorter time to first SAE and higher risk of infection were observed in the rituximab group, baseline imbalances necessitate a careful interpretation of these results. [ABSTRACT FROM AUTHOR]

Patients with granulomatosis with polyangiitis occasionally present with cutaneous manifestations, which are important clues for the early diagnosis. Although pyoderma gangrenosum-like ulcers are rarely observed, a unique case with unusual clinical features is presented herein. A 75-year-old woman with positive proteinase 3-antineutrophil cytoplasmic antibody (PR3-ANCA) repeatedly developed aseptic abscesses on the abdomen, buttock, lower legs, and forearms. Histopathological features of biopsy taken from ulcers showed necrotizing granulomatous inflammation with multinucleated giant cells without leukocytoclastic vasculitis. The present case was initially diagnosed as limited granulomatosis with polyangiitis without renal and lung involvement. However, two years later, she died of cerebral hemorrhage. [ABSTRACT FROM AUTHOR]

Observational data suggest a link between gut microbiota and immune-related vasculitis, but causality remains unclear. A bidirectional mendelian randomization study was conducted using public genome-wide data. The inverse-variance-weighted (IVW) method identified associations and addressed heterogeneity.Families Clostridiaceae 1 and Actinomycetaceae correlated positively with granulomatosis with polyangiitis risk, while classes Lentisphaeria and Melainabacteria, and families Lachnospiraceae and Streptococcaceae showed negative associations. Behçet's disease was positively associated with the risk of family Streptococcaceae abundance. And other several gut microbiota constituents were identified as potential risk factors for immune-related vasculitis. Furthermore, combining positive association results from the IVW analysis revealed numerous shared gut microbiota constituents associated with immune-related vasculitis. MR analysis demonstrated a causal association between the gut microbiota and immune-related vasculitis, offering valuable insights for subsequent mechanistic and clinical investigations into microbiota-mediated immune-related vasculitis. [ABSTRACT FROM AUTHOR]

Friedrich Wegener was the author of a comprehensive description of a disease that was named Wegener's granulomatosis. In 2010, its name was changed to granulomatosis with polyangiitis (GPA), the reason being that Wegener's links to Nazism were revealed. The research was conducted between May 2021 and August 2023 and was based on the historical method (understood as defining the subject of research, critical analysis of collected historical source materials, and historiographical synthesis) using the methods of direct and indirect inference ascribed to the historical method. Wegener and his wife were members of numerous Nazi organizations. He was rewarded for his stance by the German Reich. Together with his family, he lived in very comfortable conditions for the standards of the time, unattainable for the average person. He described himself as a frontline combatant in the Nazi invasion of Poland. Friedrich Wegener's links with Nazism were more extensive than has hitherto been known. The links involved his professional and private life. They testify to his membership in numerous Nazi organizations, as well as his active involvement in the activities of various institutions and communities of the German Reich and his overt expression of support for Hitler. Wegener's numerous accolades from the German Reich providing him with professional, material and personal benefits were proof of his links with the Nazi movement. Wegener's association with Nazism helped him to advance his career, and to attain a high social status and quality of life, both before the outbreak and during the Second World War. [ABSTRACT FROM AUTHOR]

Introduction: Whipple disease is a rare infectious disease caused by the bacterium Tropheryma whipplei. The classic form affects gastrointestinal and musculoskeletal systems; but other forms may damage the heart, brain, or lungs. Due to non-specific and diverse clinical symptoms, diagnosis of Whipple disease is challenging and often late. Adequate and timely antibiotic treatment is essential for favorable outcome. Case presentation: Here we present a case of a young woman admitted to the gynecological clinic for diagnostic laparoscopy for suspected haemato-/hydro- salpinx and peritoneal endometriosis. Macroscopic findings during laparoscopy revealed miliary whitish lesions in the pelvis and histopathology reported granulomatous salpingitis and peritonitis. She was complaining of intermittent abdominal pain, bloating and weight loss. Subsequently, the laparoscopy symptoms worsened and her general condition deteriorated. Differential diagnosis included infective agents such as Mycobacterium tuberculosis; in addition to sarcoidosis, granulomatosis with polyangiitis, and malignancies; all of which were excluded. Finally, Tropheryma whipplei was suspected, and after esophagogastroduodenoscopy with duodenal biopsy, long-term antibiotic treatment was initiated and the patient fully recovered. Conclusions: Although Whipple disease is rare, it is important to have a high level of awareness for Tropheryma whipplei infection. The localization and course of Whipple’s disease may be unpredictable, but a favorable outcome is expected with adequate antibiotic treatment. [ABSTRACT FROM AUTHOR]

Background The anti-neutrophil cytoplasmic antibody (ANCA) renal risk score (ARRS) for predicting renal survival in ANCA-associated vasculitis (AAV) had not previously been validated in adults over 65 years of age and presenting impairments associated with an aging kidney, a high cardiovascular comorbidity burden and prevalent microscopic polyangiitis. Methods We retrospectively studied a cohort of 192 patients over 65 years of age [median (interquartile range) age: 73 (68–78) years], including 17.2% with renal-limited vasculitis, 49.5% with microscopic polyangiitis and 33.3% with granulomatosis with polyangiitis, at six centres in northern France. The primary study endpoint was the cumulative incidence of end-stage kidney disease (ESKD, maintenance of dialysis for at least 3 months) at 12 months, with death considered as a competing event. Results The median serum creatinine concentration at diagnosis was 300 (202–502) µmol/L, and 48 (25.0%) patients required dialysis at presentation. The ARRS was high in 43 (22.4%) patients, medium in 106 (55.2%) and low in 43 (22.4%). The cumulative incidence of ESKD at 12 months was 0% in the low-risk group, 13.0% (interquartile range 7.6–20.0) in the medium-risk group and 44.0% (29.0–58.0) in the high-risk group (P <.001). In the subgroup of 149 patients presenting a medium or high score, the ARRS had a C-index of 0.66 (0.58–0.74) for the prediction of ESKD at 12 months; this rose to 0.86 (0.80–0.90) when dialysis status at diagnosis was included. Conclusion The ARRS was a poor predictor of kidney survival at 12 months among patients over 65 years of age with renal AAV involvement—especially in the high ARRS group. The addition of dialysis status at diagnosis as an additional clinical parameter might improve the predictive performance of the ARRS. [ABSTRACT FROM AUTHOR]

Objectives Neutrophils play a key role in ANCA-associated vasculitis, both as targets of autoimmunity and as facilitators of vascular damage. In granulomatosis with polyangiitis (GPA), the data regarding the production of reactive oxygen species (ROS) in neutrophils are unclear. Further, recent data suggests that ROS production could have an anti-inflammatory effect through the regulation of inflammasomes and IL-1–related cytokines. We aimed to analyse ROS production in neutrophils from patients with GPA and investigate its association with IL-1–related cytokines and the autoantigen PR3. Methods Seventy-two GPA patients with disease flare were included in the NEUTROVASC prospective cohort study. ROS production in whole blood of patients with active GPA was evaluated and compared with that in the same patients in remission or healthy controls. Associations between ROS production, PR3 membrane expression on neutrophils, serum levels of IL-1–related cytokines as well as inflammasome-related proteins were analysed. Results We observed a robust defect in ROS production by neutrophils from patients with active GPA compared with healthy controls, independent of glucocorticoid treatment. Serum levels of IL-1–related cytokines were significantly increased in GPA patients, particularly in patients with kidney involvement, and levels of these cytokines returned to normal after patients achieved remission. Further, inflammasome-related proteins were significantly dysregulated in the cytosol of neutrophils as well as the serum from GPA patients. Conclusion Our data suggests that ROS production and regulation of inflammasomes in neutrophils from patients with GPA are disturbed and may be a potential therapeutic target. Trial registration ClinicalTrials.gov, https://www.clinicaltrials.gov , NCT01862068. [ABSTRACT FROM AUTHOR]