Granulomatosis With Polyangiitis Patients Research Articles

Respiratory manifestations of pediatric granulomatosis with polyangiitis: A 12-year experience from a tertiary care facility.

Pediatric granulomatosis with polyangiitis (GPA) is associated with several pulmonary manifestations. This study aims to describe these manifestations at time of diagnosis and longitudinally at a tertiary-care pediatric hospital. We performed a retrospective chart review of patients with GPA treated at our facility between 1 January 2010 through 31 December 2021. We collected baseline demographics, reported symptoms, imaging findings, pulmonary function tests (PFTs), and laboratory data at time of diagnosis. Data were collected using 6-month observation intervals to follow recurrence of respiratory manifestations, testing during recurrence, and resultant treatment modifications. Of 13 patients treated for GPA during the study period, 12 developed respiratory tract involvement. A total of 87 6-month observation periods were analyzed. At time of diagnosis, 83% (10/12) of subjects reported respiratory symptoms, 92% (11/12) had abnormal chest computed tomography (CT) imaging, and 42% (5/12) had abnormal PFTs. Fewer than half of the patients were seen by pulmonology within 6 months of diagnosis. Eight subjects (75%) had respiratory manifestations during subsequent observation periods. Chest CT or PFTs were obtained in 23/44 (52%) of observations periods with respiratory symptoms, with pulmonary consultation in only 9/44 (20%). This is the first US study to describe respiratory manifestations in pediatric GPA patients longitudinally, finding they are common and frequently recurrent. Our cohort had almost universally abnormal imaging at diagnosis regardless of respiratory symptoms. Early collaboration with pediatric pulmonology in the care of GPA patients may allow rheumatology teams to efficiently evaluate recurrent symptoms and address concomitant lung disease.

Pneumatosis cystoides intestinalis in granulomatosis with polyangiitis: a case report.

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 2months 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.

Ocular manifestations in ANCA-associated vasculitis: a comprehensive analysis from Chinese medical centers.

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. 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. 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. 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.

Impact of Rituximab on Remission Rates in Granulomatosis With Polyangiitis: A Systematic Review.

This systematic review evaluates the efficacy of rituximab in inducing and maintaining remission in patients with granulomatosis with polyangiitis (GPA). We conducted a comprehensive search across multiple databases, identifying 81 studies, of which 11 met our inclusion criteria after rigorous screening and assessment for relevance and quality. Our analysis shows that rituximab, compared to traditional treatments such as cyclophosphamide and azathioprine, significantly improves remission rates and reduces relapse frequency in GPA patients. Notably, rituximab's benefits extend across various patient demographics, including pediatric groups, and are evident in different dosing regimens, highlighting its versatility and potential as a first-line therapy. The review also underscores the importance of personalized medicine approaches in managing GPA, as rituximab's effectiveness was particularly pronounced in patients with relapsing disease forms. Future research should focus on long-term outcomes, optimal dosing strategies, and the economic implications of widespread rituximab use in clinical practice. Our findings advocate for the integration of rituximab into standard treatment protocols for GPA, offering new hope for patients afflicted with this challenging autoimmune disorder.

Distinct pulmonary patterns in ANCA-associated vasculitides: insights from a retrospective single center cohort study.

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 37months, 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 CTpatterns including GGO and pleura effusion may help to identify patients who are at higher risk for relapsing disease.

Challenges in Managing Newly Diagnosed Granulomatosis With Polyangiitis and Concurrent Respiratory Infections: A Retrospective Case Series.

Granulomatosis with polyangiitis (GPA), formerly termed Wegener's granulomatosis, is an autoimmune disease marked by necrotizing granulomatous inflammation and vasculitis affecting small-sized vessels. It commonly impacts the renal and respiratory systems. This retrospective case series sampling conductedin a tertiary care hospital between May 2023 and April 2024 examined six newly diagnosed GPA patients who wereproteinase 3 cytoplasmic-antinuclear cytoplasmic antibody (PR3 c-ANCA) positive and had concurrent respiratory infections. None of them had any prior immunosuppressive conditions.The age range was 18-47 years with a mean of 35.0 (standard deviation: 11.83). All the patients had pneumonia (N=6, 100%). Out of all, five hadbacterial pneumonia (N=5, 83.3%) and one had tuberculous pneumonia (N=1, 16.7%). A high levelof PR3 c-ANCA (>150 RU/mL) was noted in four patients (N=4, 66.7%).Common symptoms included dry cough (N=5, 83.3%), loss of weight and appetite(N=2, 33.3%), and fever (N=2, 33.3%). Three patients had otitis mediaand/or nasal polyposis (N=3, 50%). Two patients (N=2, 33.3%) with life-threatening organ dysfunction were given concurrent antibiotics and steroids; the antibiotics were later modified based on culture and sensitivity results. One of these patients received antituberculosis therapy as Mycobacterium tuberculosis (MTB) was detected after 27 days of incubation in mycobacterial growth indicator tube broth. The remaining four patients (N=4, 66.7%)receivedantibiotics initially for 5-7 days until clinical resolution of pneumonia. Ultimately, they all showed clinical and radiological resolution (N=6, 100%) within 3-6 months of treatment. The patients exhibited constitutional symptoms such as fever and weight loss; lower airway disease symptoms including dry cough and hemoptysis; nasal and ear disease symptoms like epistaxis, ear pain, and ear discharge; and a renal disease symptom, hematuria.Computed tomography of the thorax revealed bilateral consolidations, most of which were cavitating. Bronchoalveolar lavagecultures grew Escherichia coli, Burkholderia cepacia, Pseudomonas aeruginosa, Klebsiella pneumoniae, and MTB, whereas pus swab cultures from otitis media grew Pseudomonas aeruginosa, Staphylococcus aureus,and coagulase-negative staphylococci. This study highlights the therapeutic challenges of GPA complicated by concurrent infections. Patients exhibited typical GPA signs, confirmed by PR3 c-ANCA levels. Concurrent infections require cautious antibiotic treatment before starting immunosuppressive therapy, except in life-threatening organ dysfunction. A unique case presented with both tuberculosis and GPA. Tailored treatment regimens combining antibiotics and immunosuppressives, including corticosteroids, methotrexate, and rituximab, resulted in clinical and radiological improvement in all the patients within 3-6 months. The addition of co-trimoxazole reduced the incidence of non-severe GPA relapses. Tailored treatment plans addressing both infectious and autoimmune aspects are essential for optimal care in GPA complicated by concurrent infections. This study highlights the need for a multidisciplinary approachinvolving pulmonologist, rheumatologist, microbiologist, and pathologistin the diagnosis and treatment of GPA, emphasizing the importance of individualized treatment plans tailored to the specific clinical scenario.

Dynamically changing antineutrophil cytoplasmic antibodies in granulomatosis with polyangiitis: A case report

BACKGROUND Granulomatosis with polyangiitis (GPA) is one of the most prevalent forms of the antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. GPA is characterized histologically by necrotizing granulomatous inflammation in addition to vasculitis. The diagnosis of GPA depends on clinical presentation, serological evidence of a positive ANCA, and/or histological evidence of necrotizing vasculitis or granulomatous destructive parenchymal inflammation. Cytoplasmic ANCA (c-ANCA) is positive in 65%-75% of GPA patients, accompanied by proteinase 3 (PR3), the main target antigen of c-ANCA, another 5% of GPA patients had negative ANCA. CASE SUMMARY The patient, a 52-year-old male, presented with unexplained nasal congestion, tinnitus, and hearing loss. After a duration of 4 months experiencing these symptoms, the patient subsequently developed fever and headache. The imaging examination revealed the presence of bilateral auricular mastoiditis and partial paranasal sinusitis, and the ANCA results were negative. The anti-infective therapy proved to be ineffective, but the patient's symptoms and fever were quickly relieved after 1 wk of treatment with methylprednisolone 40 mg once a day. However, after continuous use of methylprednisolone tablets for 3 months, the patient experienced a recurrence of fever accompanied by right-sided migraine, positive c-ANCA and PR3, and increased total protein in cerebrospinal fluid. The patient was diagnosed with GPA. After receiving a treatment regimen of intravenous methylprednisolone 40 mg/d and cyclophosphamide 0.8 g monthly, the patient experienced alleviation of fever and headache. Additionally, the ANCA levels became negative and there has been no recurrence. CONCLUSION For GPA patients with negative ANCA, there is a potential for early missed diagnosis. The integration of histopathological results and multidisciplinary communication plays a crucial role in facilitating ANCA-negative GPA.

#1154 Type I interferon pathway is upregulated in microscopic polyangiitis (vs granulomatosis with polyangiitis)

Abstract Background and Aims The two main types of ANCA-associated vasculitis (AAV), microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA), share common characteristics but also differ on many aspects (epidemiological, genetic, clinical, outcomes). These differences did not justify, to date, different patient management. To identify more specific targetable pathways, we characterized the kidney transcriptome of MPA vs. GPA patients with AAV-glomerulonephritis (AAV-GN). Method This retrospective study included adult patients with AAV-GN from the French Maine-Anjou Registry. Immune gene transcript analysis was performed on RNA extracted from 97 kidney biopsies using NanoString technology. Significant transcripts were examined to identify immune pathways of interest. We then used a publicly available dataset to explore these identified pathways (qPCR / ELISA). Results We compared kidney biopsies from GPA (n = 33) and MPA (n = 64) patients. There was no difference in eGFR between both groups at diagnosis. Of the 750 evaluated immune transcripts, 8 genes were found differentially expressed between MPA and GPA patients, all being upregulated in MPA (log2FC > 1, q-value < 0.05) (Fig. 1A). Seven (out of 8) genes belonged to the type I interferon (IFN-I) signaling pathway. A personal analysis of unpublished, publicly available, data1 identified a significantly more pronounced IFN-I signature in the peripheral blood mononuclear cells of patients with MPO-AAV when compared to those with PR3-AAV (Fig. 1B). Serum levels or CXCL10, a cytokine that mediates immune responses through the recruitment and activation of numerous immune cells under the regulation of IFN-I, were found higher in MPO-AAV patients (Fig. 1C). Conclusion We identified a type I interferon signature, both in kidneys and in blood, in patients with MPA (or MPO-AAV) in comparison to GPA (or PR3-AAV). This is in line with previous lines of evidence brough by Kessenbrock et al. and Kessler et al. suggesting a role for IFN-I in AAV and especially in MPO-AAV. This signature may help gain a deeper understanding of the AAV-GN pathogenesis and provide insights for developing new therapeutic options.

#581 Therapeutic management of patients with GPA and MPA: a nationwide observational study in France

Abstract Background and Aims Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are rare systemic necrotizing vasculitis. Treatment per rituximab was approved in 2013, and recent guidelines recommend corticosteroids sparing. A real-life pharmacoepidemiologic retrospective study was set up to describe the demographic characteristics of hospitalized GPA and MPA patients and compare the treatments of patients included before rituximab approval (over 2010–2012, Group 1) and after rituximab approval in France (over 2014–2017, Group 2). Method All adult patients hospitalized for GPA or MPA between January 1, 2010 and December 31, 2017 were included from the French National Health Insurance database (SNDS) which covers >97.5% of French population. Patients were separated in 2 groups according to their date of inclusion: (i) Over 2010-2012 for group 1 and (ii) over 2014-2017 for group 2. Descriptive analyses were performed. Kaplan-Meier method was used to model the duration of treatment induction and maintenance. Fine and Gray tests were used to compare treatment phases durations. Results The study involved 4445 prevalent GPA patients (including 1578 incident patients) and 1833 prevalent MPA patients (878 incident patients). Group 1 consisted of 694 and 283 GPA and MPA patients respectively; group 2 included 668 and 463 GPA and MPA patients respectively. Mean age and the sex ratio were stable over time. During the first year after inclusion, the proportion of patients with first-time hospitalized infections, diabetes or renal failure increased between 2010–2012 and 2014–2017. Between the two inclusion periods, the proportions of patients treated with rituximab increased both in the induction and maintenance phases whereas treatment with azathioprine declined (Table 1). As for methotrexate, cyclophosphamide and glucocorticoids, the proportions remained stable. Conclusion According to real-life, pharmacoepidemiologic data in GPA and MPA patients, the introduction of rituximab reduced the use of azathioprine without affecting the use of glucocorticoids, although corticosteroids sparing should become a standard of care with the emerging treatment regimens. No reductions in adverse events were observed with the increased use of rituximab.

LIPIDS INCREASE IN HYPERTENSIVES DURING THE FIRST YEAR STEROID TREATMENT FOR GRANULOMATOSIS WITH POLYANGIITIS (GPA)

Objective: Granulomatosis with polyangiitis (GPA) is an ANCA-associated small-vessel vasculitis. Vessel wall inflammation induces multiple vascular damages leading to accelerated atherosclerosis. Metabolic profile and cardiovascular risk are marginally known in the GPA patients. Our purpose is to evaluate lipid profile and ASCVD-risk in GPA patients. Design and method: We selected 36 patients who received GPA diagnosis (T0) and evaluated them after 1 (T1) and 2 (T2) years follow-up. All patients were treated with high-dose glucocorticoid, one-year tapered, associated with immunosuppressants. Pathological history and a complete list of drugs at different time points were recorded. Results: The study reveals noteworthy alterations in lipid profiles, with a substantial increase observed in total cholesterol during both T1 and T2 in comparison to T0. A similar trend was noted in LDLand triglycerides. Conversely, no discernible differences were identified in HDL levels. Additionally, a considerable decrease in high-sensitivity C-reactive protein was observed at T1 and T2 in relation to T0, with no significant variance between T2 and T1. Furthermore, a notable reduction in erythrocyte sedimentation rate was noted at T2 as opposed to both T1 and T0, as well as at T1 compared to T0. Moreover, an interesting observation pertains to hypertensive patients who exhibited a marked escalation in lipid levels, juxtaposed with a gradual reduction in inflammation when compared to normotensive individuals. In particular, notable distinctions emerge between the two groups at both T1 and T2 concerning total cholesterol and LDL (p=0.027), despite comparable baseline values at T0. Then, while triglyceride levels start at similar values at T0, a substantial increase is observed at T1 in hypertensive patients and, conversely, at T2, normotensive individuals experience a significant rise in triglyceride levels, accompanied by a noteworthy reduction in hypertensive subjects. Conclusions: The findings indicate that lipid profile alterations, likely influenced by glucocorticoid treatment, may not be directly linked to inflammation. Furthermore, there is a higher relation between hypertension and these alterations. Actual data doesn’t reveal increased mortality in hypertensive GPA patients but further research is required to pinpoint specific patterns characterizing cardiovascular risk and progression in this context.

Circulating immune profile in granulomatosis with polyangiitis reveals distinct patterns related to disease activity

Granulomatosis with polyangiitis (GPA) is an autoimmune disorder characterized by recurrent relapses that can cause severe tissue damage and life-threatening organ dysfunction. Multiple immune cells and cytokines/chemokines are involved in the different stages of the disease. Immune profiling of patients may be useful for tracking disease activity, however, reliable immune signatures for GPA activity are lacking. In this study, we examined circulating immune profiles in GPA patients during active and remission disease states to identify potential immune patterns associated with disease activity.The distribution and phenotypic characteristics of major circulating immune cells, and the profiles of circulating cytokines/chemokines, were studied on cryopreserved peripheral blood mononuclear cells from GPA patients (active, n = 20; remission, n = 20) and healthy controls (n = 20) leveraging a 40-color optimized multicolor immunofluorescence panel (OMIP-69) and in serum using a 46-plex Luminex multiplex assay, respectively.Deep phenotyping uncovered a distinct composition of major circulating immune cells in active GPA and GPA in remission, with the most significant findings emerging within the monocyte compartment. Our detailed analysis revealed circulating monocyte diversity beyond the conventional monocyte subsets. We identified eight classical monocyte populations, two intermediate monocyte populations, and one non-classical monocyte population. Notably, active GPA had a higher frequency of CD45RA+CCR5+CCR6−CCR7+/lowCD127−HLA-DR+CD2− classical monocytes and a lower frequency of CD45RA−CCR5-/lowCCR6−CCR7−CD127−HLA-DR+CD2+/− classical monocytes, which both strongly correlated with disease activity. Furthermore, serum levels of CXCL1, CXCL2, and CCL20, all linked to monocyte biology, were elevated in active GPA and correlated strongly with disease activity.These findings shed light on the circulating immune profile of GPA and may lead to immune signature profiles for assessing disease activity. Monocytes in particular may be studied further as potential markers for monitoring GPA.

Investigating the concomitance of anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitides and inflammatory bowel disease (IBD)

ObjectiveTo assess relationship between Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis and inflammatory bowel disease (IBD). MethodsThis is a retrospective study design. The patients were identified using a preset criteria of patients who have the diagnosis of ANCA associated vasculitis including a diagnosis of granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) or eosinophilic granulomatosis with polyangiitis (EGPA) with overlapping inflammatory bowel disease (Crohn's disease or ulcerative colitis) in the time period from 01/01/2020 to 08/03/2023. Subsequently data from each patient was collected that will include baseline demographics, disease characteristics, disease activity, treatment information, multiorgan involvement, and pathology findings which were then analyzed. Results39 patients were identified that met criteria. 20 patients carried a diagnosis of GPA, 6 had MPA and 4 patients had EGPA. 20 patients with GPA had inflammatory bowel disease, 13 with ulcerative colitis and 6 with Crohn's disease while 1 GPA patient had unspecified inflammatory bowel disease. 4 patients with EGPA had inflammatory bowel disease, 2 with ulcerative colitis and 2 with Crohn's disease. 6 patients with MPA had inflammatory bowel disease, 4 with ulcerative colitis and 2 with Crohn's disease. IBD diagnosis preceded the diagnosis of ANCA vasculitis in 77.8 % of the cases. ConclusionObjective observation and deductions from this study raise the concern for a possible pathogenic association of ANCA associated vasculitis and inflammatory bowel disease and more research is needed to identify any causal association or influence of the two systemic disease on each other.

Sinonasal manifestations of granulomatosis with polyangiitis: A retrospective analysis

ObjectiveThis study aimed to examine the characteristics of nasal and imaging findings of sinonasal lesions in granulomatosis with polyangiitis (GPA) patients and how these lesions change over time in both the active and remission phases of the disease. MethodsWe retrospectively reviewed GPA patients with sinonasal lesions who were followed up at our department between January 2005 and December 2020. The following data were collected: age, sex, symptoms at initial presentation, anti-neutrophil cytoplasmic antibody (ANCA) type, and histopathological, nasal (initial and follow-up), and imaging (initial and follow-up) findings. ResultsThis study included 17 patients with GPA aged 30 to 79 years. Computed tomography (CT) of the sinuses showed mucosal thickening in 16 patients, bone thickening in 12, bone destruction in 4, and an orbital invasion mass in 3 at the time of diagnosis. After initiating treatment, mucosal thickening of the sinuses improved in 3 of 16 patients and remained unchanged in 13. Bone thickening at the time of diagnosis remained unchanged in 10 of 12 patients and worsened in 2; 1 patient displayed newly developed bone thickening. Destructive nasal findings on CT were positive for proteinase 3-ANCA. ConclusionsOur study revealed that mucosal thickening, bone thickening, bone destruction, and orbital invasion mass were major CT findings in patients with GPA. Intranasal findings such as granulations, crusting, and necrosis were seen in the active phase; moreover, saddle nose, loss of turbinate, and nasal septal perforation were subsequently seen in the course of the disease. Sinonasal findings of GPA vary depending on the disease stage and period.

Significance of clinical-immunological patterns and diagnostic yield of biopsies in microscopic polyangiitis and granulomatosis with polyangiitis.

Microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) are the two major antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). To characterize a homogenous AAV cohort and to assess the impact of clinicopathological profiles and ANCA serotypes on clinical presentation and prognosis. Clinical differences in GPA patients according to ANCA serotype and the diagnostic yield for vasculitis of biopsies in different territories were also investigated. This retrospective study (2000-2021) included 152 patients with AAV (77 MPA/75 GPA). MPA patients (96.1% myeloperoxidase [MPO]-ANCA and 2.6% proteinase 3 [PR3]-ANCA) presented more often with weight loss, myalgia, renal involvement, interstitial lung disease (ILD), cutaneous purpura, and peripheral nerve involvement. Patients with GPA (44% PR3-ANCA, 33.3% MPO, and 22.7% negative/atypical ANCA) presented more commonly with ear, nose, and throat and eye/orbital manifestations, more relapses, and higher survival than patients with MPA. GPA was the only independent risk factor for relapse. Poor survival predictors were older age at diagnosis and peripheral nerve involvement. ANCA serotypes differentiated clinical features in a lesser degree than clinical phenotypes. A mean of 1.5 biopsies were performed in 93.4% of patients in different territories. Overall, vasculitis was identified in 80.3% (97.3% in MPA and 61.8% in GPA) of patients. The identification of GPA presentations associated with MPO-ANCA and awareness of risk factors for relapse and mortality are important to guide proper therapeutic strategies in AAV patients. Biopsies of different affected territories should be pursued in difficult-to-diagnose patients based on their significant diagnostic yield.

Cutting-Edge Strategies for Renal Tumour-like Lesions in Granulomatosis with Polyangiitis: A Systematic Review.

Granulomatosis with polyangiitis (GPA) is characterised by granulomatous inflammation and small-to-medium vessel necrotising vasculitis, mainly affecting respiratory tract and kidneys. Renal involvement presenting as tumour-like lesions poses diagnostic and treatment challenges. Following the observation of a GPA patient presenting with multiple renal tumour-like lesions, we conducted a systematic literature review on MEDLINE/PubMed, EMBASE, and Cochrane databases. Data gathered from the literature were analysed to summarise the diagnostic approach, management, and outcome of renal GPA-related tumour-like lesions. a 49-year-old female presented with persistent constitutional symptoms and multiple bilateral renal lesions. Renal biopsy showed chronic interstitial inflammation with necrotising granulomas. Laboratory tests disclosed positive anti-proteinase 3 (PR3) anti-neutrophil cytoplasmic antibody (ANCA) leading to a final diagnosis of GPA. She was effectively treated with high-dose glucocorticoids and rituximab. Literature search yielded 41 articles, concerning 42 GPA patients with renal masses, presenting bilaterally in 23.8% of the cases. Positive PR3-ANCA was observed in 86.5% of the cases. Half of 42 patients showed kidney abnormalities. Treatment with glucocorticoids (83.3%) and immunosuppressive agents (80.9%) resulted in an overall good remission rate and favourable prognosis. GPA should be considered in the differential diagnoses of kidney tumour-like lesions. The diagnosis is challenging, and histological examination greatly contributes to the diagnostic work-up.

Assessing the Association Between Head and Neck Cancer and Granulomatosis with Polyangiitis.

Objective: To determine the odds of head and neck cancer (HNC) in patients with a concurrent or prior diagnosis of granulomatosis with polyangiitis (GPA). Methods and Materials: The TriNetX Analytics Network, a federated research platform that aggregates de-identified electronic health record data of over 130 million patients worldwide, was queried for patients with at least one ICD-10 encounter diagnosis of GPA. Patients within this group with an encounter diagnosis of cancer of the sinonasal, oral cavity, oropharynx, nasopharynx, and larynx concurrent or after the initial encounter diagnosis of GPA were recorded and compared to a standardized control population to determine odds ratios with a 95% confidence interval (CI). Relevant confounding variables, including human papillomavirus, Epstein Barr virus, tobacco, and alcohol exposure, were balanced between cohorts by 1:1 propensity matching. Results: Of the patients in the GPA cohort, 126 (0.48%) had an ICD-10 diagnosis of HNC. When stratifying by head and neck subsites, 20 (0.08%), 18 (0.07%), 23 (0.09%), 70 (0.27%), and 22 (0.084%) GPA patients had an ICD-10 encounter diagnosis of cancer involving the sinonasal, nasopharynx, larynx, oral cavity, and oropharynx. When comparing the experimental GPA group with the standardized control population after matching, patients in the GPA group had 1.3 times (95% CI: 1.03-1.175) greater odds of HNC when including cases diagnosed after or concurrently with the diagnosis of the vasculitis. There was no statistical difference in the odds of cancer at each anatomical subsite between the GPA and control cohort after matching. Conclusion: Our study identifies a statistically significant increase in the odds of HNC encounter diagnoses in patients with GPA.

Audiological Manifestations in Patients with Granulomatosis with Polyangiitis.

Background and Objectives: Granulomatosis with Polyangiitis (GPA) is a rare, autoimmune, multisystemic disease characterized by vasculitis and necrotizing granuloma that commonly affects the upper and lower respiratory tract and kidneys. Audiovestibular dysfunction in GPA diseases may have different clinical presentations. The aim of the present study was to evaluate hearing function in patients with GPA and to compare the results with a healthy control group. Materials and Methods: A total of 34 individuals participated in the study. The GPA group consisted of 14 participants, and the control group was composed of 20 healthy participants with no signs or symptoms of ear disease. The ages ranged from 18 to 65 years old, with a mean age of 43.8 years. The participants underwent a complete audiological evaluation using otoscopy, impedance audiometry, pure tone audiometry, speech audiometry-evaluation of speech thresholds, and speech recognition in quiet. Both ears were tested. All of the participants of the study were native Lithuanian speakers. Data were statistically analyzed using the Statistical Analysis System software SAS® Studio 3.8. A p value < 0.05 was regarded as statistically significant. Results: 92.85% of patients from the GPA group reported hearing-related symptoms: hearing loss, tinnitus, and fullness in the ears. The arithmetic means of all hearing thresholds at frequencies from 125 Hz to 8000 Hz were significantly higher in the GPA group. The results revealed statistically significant differences between the two groups in the Speech Detection Threshold, Speech Recognition Threshold, Speech Discomfort level, and Word Recognition Scores. Conclusions: The frequency of hearing loss, the average hearing thresholds, and speech thresholds were higher in GPA patients than in healthy individuals. The most common type of hearing loss was sensorineural. Audiological assessments should be considered during the routine evaluation of patients with GPA disease to prevent hearing-related disabilities.

Disease Activity and Tendency to Relapse in ANCA-Associated Vasculitis Are Reflected in Neutrophil and Intermediate Monocyte Frequencies.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of autoimmune diseases with inflammation affecting small blood vessels and includes granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). In this study, we investigated granulocyte and monocyte subsets in a large cohort of AAV patients with emphasis on disease activity and tendency to relapse. A cohort of 105 patients with GPA or MPA and 126 healthy controls (HCs) were included. Clinical and laboratory data were collected for all patients, including disease activity, tendency to relapse, and pharmacological treatment. Using flow cytometry, circulating eosinophils, basophils, neutrophils, and monocytes were assessed. The monocytes were subdivided into classical (CD14++CD16-), intermediate (CD14++CD16+), and nonclassical (CD14-CD16+) monocytes. Mature (CD16high) or newly released (CD16dim) neutrophils were defined, as well as the frequency of CD177+ neutrophils. AAV patients displayed increased frequencies of intermediate monocytes, mature and newly released neutrophils, and an expanded population of CD177+ neutrophils compared to HC. MPA patients differed from GPA patients in terms of lower frequency of classical monocytes. No differences in cell frequencies regarding ANCA phenotype were observed. Paired data from 23 patients demonstrated that active disease was associated with an increased frequency of mature neutrophils and a decreased frequency of monocytes, in particular intermediate monocytes. Moreover, GPA patients with a tendency to relapse displayed an increased frequency of mature neutrophils with increased expression of CD177+. Relapsing MPA patients, on the other hand, showed decreased frequency of intermediate monocytes. Finally, rituximab treatment was associated with increased frequencies of classical and intermediate monocytes. In conclusion, AAV patients exhibit a skewing of different neutrophil and monocyte subpopulations that are associated with disease subtypes, disease activity, rituximab treatment, and propensity to relapse. These changes may contribute to the inflammatory process and could potentially be used as biomarkers for relapse prediction.

Clinical characteristics of hypertrophic cranial pachymeningitis in granulomatosis with polyangiitis: a retrospective single-center study in China.

Hypertrophic cranial pachymeningitis (HCP) is uncommon but a poorly understood complication of granulomatosis with polyangiitis (GPA). We conducted this retrospective study to elucidate the clinical characteristics and factors independently associated with granulomatosis with polyangiitis (GPA) complicated by hypertrophic cranial pachymeningitis (HCP) in China. We collected the medical records of 78 patients diagnosed with GPA who were admitted to the inpatient department of Peking Union Medical College Hospital between January 2003 and September 2021. Clinical features, laboratory and radiological findings, and Birmingham Vasculitis Activity Scores (excluding meningitis score) were recorded. A binary logistic regression analysis was performed to analyze factors independently associated with GPA-related HCP. Headache (100%) and cranial nerve palsy (61.5%) were common manifestations of HCP. Compared to 52 GPA patients without HCP, 26 patients with HCP required more time from initial symptoms to diagnosis, with a lower ratio of pulmonary and renal involvement, a higher ratio of myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) positivity, conductive or sensorineural hearing loss, mastoiditis, and decreased vision or sudden visual loss. Binary logistic regression analysis indicated that proteinase 3-antineutrophil cytoplasmic antibody (PR3-ANCA) negativity (OR 10.698, p = 0.001), conductive or sensorineural hearing loss (OR 10.855, p = 0.005), and decreased vision or sudden visual loss (OR 8.647, p = 0.015) were significantly associated with GPA-related HCP. Of the 26 patients, 18 received methylprednisolone pulse treatment, and 18 received intrathecal injections of dexamethasone and methotrexate. HCP was a severe manifestation of GPA in our study. Independent factors associated with the occurrence of HCP in patients with GPA included PR3-ANCA negativity, conductive or sensorineural hearing loss, and decreased vision or sudden visual loss. Furthermore, GPA-related HCP was associated with higher disease activity, requiring more intensive treatments.

Serum Soluble Receptors for Advanced Glycation End-Products May Predict Mortality in Microscopic Polyangiitis and Granulomatosis with Polyangiitis.

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). 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 shrinkage and selection operator regression was adopted to select variables included in the multivariable Cox proportional hazards (PH) regression model. 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). 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.