Wegener's Granulomatosis Research Articles

Cardiovascular disease and antineutrophil cytoplasmic antibodies-associated vasculitis: A systematic review

ABSTRACT Recent evidence suggests that cardiovascular disease and antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) are interconnected. This investigation aims to examine the epidemiology, potential risk, and cardiovascular events among AAV sufferers to shed light on the intricate relationship between these seemingly unrelated conditions. A systematic review following PRISMA criteria encompassed 18 relevant studies with a pooled sample size of 21,291 ANCA-associated vasculitis patients. Studies were retrieved from PubMed, Embase, and Cochrane Library. Inclusion criteria focused on longitudinal studies reporting cardiovascular events in AAV patients. Data extraction and synthesis were performed, focusing on prevalence, types of cardiovascular events, comparison with control groups, and identification of risk factors and independent predictors. The study found that patients with ANCA-associated vasculitis had a mean age of 57.5 years, with 47% being male. The mean follow-up duration was 4.77 years. Overall, 1350 cardiovascular events were reported across the studies, yielding a pooled prevalence of 6.3%. Major adverse cardiovascular events, ischemic heart disease, stroke, venous thromboembolism, and acute coronary syndromes were the specific events. Comparison with control groups demonstrated a higher cardiovascular risk in AAV patients. Age, systolic blood pressure, estimated glomerular filtration rate, and the Birmingham Vasculitis Activity Score were independent predictors. In conclusion, ANCA-associated vasculitis patients have elevated cardiovascular risk and a variety of manifestations. AAV-specific variables,such as inflammation and disease activity, and conventional risk factors, play a role in cardiovascular complications. The study challenges conventional assessment timelines by highlighting the importance of early and proactive cardiovascular risk management.

Non-Eosinophilic Granulomatosis with Polyangiitis Vasculitic Neuropathy: An Overview

Vasculitic neuropathy is commonly associated with systemic vasculitis, leading to ischemic damage to the peripheral nerves and axonal degeneration. The typical clinical manifestation of vasculitic neuropathy is a sensory-dominant multiple mononeuropathy often accompanied by pain. Although vasculitic neuropathy is caused by various systemic diseases, ANCA-associated vasculitis, secondary systemic vasculitis linked to various collagen diseases, and non-systemic vasculitic neuropathy hold particular significance. A comprehensive understanding of vasculitic neuropathy is crucial for its early diagnosis, contributing to an improved prognosis for this condition.

Myeloperoxidase-specific antineutrophil cytoplasmic antibody-associated vasculitis.

Myeloperoxidase (MPO)-specific antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (MPO-ANCA-associated vasculitis) is one of two major ANCA-associated vasculitis variants characterised by systemic necrotising vasculitis with few or no immune deposits. MPO-ANCA-associated vasculitis predominantly affects small blood vessels and, in contrast to its counterpart proteinase 3-ANCA-associated vasculitis, is generally not associated with granulomatous inflammation. The kidneys and lungs are the most commonly affected organs. The pathogenesis of MPO-ANCA-associated vasculitis is characterised by loss of tolerance to the neutrophil enzyme MPO. This loss of tolerance leads to a chronic immunopathological response where neutrophils become both the target and effector of autoimmunity. MPO-ANCA drives neutrophil activation, leading in turn to tissue and organ damage. Clinical trials have improved the therapeutic approach to MPO-ANCA-associated vasculitis. However, there remains substantial unmet need regarding relapse frequency, toxicity of current treatment, and long-term morbidity. In this Series paper, we present the current state of research regarding pathogenesis, diagnosis, and treatment of MPO-ANCA-associated vasculitis.

Peripheral Neuropathy in Eosinophilic Granulomatosis with Polyangiitis

Eosinophilic granulomatosis with polyangiitis (EGPA) is an antineutrophil cytoplasmic autoantibody-associated vasculitis secondary to inflammation of the small vessels. EGPA-induced neuropathy develops in approximately 90% of patients with peripheral blood eosinophilia and may lead to serious complications of the peripheral nervous system, necessitating emergency therapeutic intervention.

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.

The predictive performance of the ANCA renal risk score in patients over 65 years of age with renal ANCA-associated vasculitis.

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. 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. 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. 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.

Evolution of therapeutic management of patients with ANCA associated vasculitis in France after licensing Rituximab use

IntroductionIn 2013, rituximab was approved in France for the treatment of ANCA-associated vasculitis (AAV). The aim of the study was to compare the treatment and health events of adult incident patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), included before rituximab approval (over 2010–2012, Group 1) and those included after rituximab approval (over 2014–2017, Group 2).MethodData were extracted from the French National Health Insurance database (SNDS) including outpatient health care consumption and hospital discharge forms. Comparisons between inclusion periods were performed using Wilcoxon and χ² tests. Kaplan-Meier method was used to model the duration of treatment induction, maintenance, and off-drug periods. Fine and Gray tests were used to compare treatment phase durations.ResultsA total of 694 GPA and 283 MPA patients were included in Group 1, while 668 GPA and 463 MPA patients were included in Group 2. Between the two inclusion periods, the proportions of patients treated with rituximab increased in the induction and maintenance phases whereas treatment with azathioprine declined. These proportions remained stable in the case of methotrexate, cyclophosphamide, and glucocorticoid-treated patients. Frequency of first-time hospitalized infections, diabetes and renal failure during the first year after inclusion increased for both groups.Limitations of the studyThis is a retrospective study based on claims data including only 76% of people covered by health insurance in France. The period studied includes the learning phase of using rituximab. This study lacks biological data and precise quantitative analysis for the use of steroids, therefore the criteria for establishing diagnosis and therapeutic choice were unknown.ConclusionsIntroduction of rituximab reduced the use of azathioprine without affecting the use of glucocorticoids or cyclophosphamide.

Clinical Characteristics of EGPA Patients in Comparison to GPA Subgroup with Increased Blood Eosinophilia from POLVAS Registry.

To characterize the eosinophilic granulomatosis with polyangiitis (EGPA) population from the POLVAS registry depending on ANCA status and diagnosis onset, including their comparison with the granulomatosis with polyangiitis (GPA) subset with elevated blood eosinophilia (min. 400/μl) (GPA HE) to develop a differentiating strategy. A retrospective analysis of the POLVAS registry. The EGPA group comprised 111 patients. The ANCA-positive subset (n = 45 [40.54%]) did not differ from the ANCA-negative one in clinics. Nevertheless, cardiovascular manifestations were more common in ANCA-negative patients than in those with anti-myeloperoxidase (MPO) antibodies (46.97% vs. 26.92%, p = 0.045). Patients diagnosed before 2012 (n = 70 [63.06%]) were younger (median 41 vs. 49 years, p < 0.01), had higher blood eosinophilia at diagnosis (median 4,946 vs. 3,200/μl, p < 0.01), and more often ear/nose/throat (ENT) and cardiovascular involvement. GPA HE comprised 42 (13.00%) out of 323 GPA cases with reported blood eosinophil count. Both GPA subsets had a lower prevalence of respiratory, cardiovascular, and neurologic manifestations but more often renal and ocular involvement than EGPA. EGPA also had cutaneous and gastrointestinal signs more often than GPA with normal blood eosinophilia (GPA NE) but not GPA HE. The model differentiating EGPA from GPA HE, using ANCA status and clinical manifestations, had an AUC of 0.92, sensitivity of 96%, and specificity of 95%. Cardiovascular symptoms were more prevalent in the ANCA-negative subset than in the MPO-ANCA-positive one. Since EGPA and GPE HE share similarities in clinics, diagnostic misleading may result in an inappropriate therapeutic approach. Further studies are needed to optimize their differentiation and tailored therapy, including biologics.

Common Characteristics of Sinonasal Inflammation Associated with IgG4-Related Disease and Other Chronic Inflammatory Diseases: A Retrospective Observational Study

Plain Language SummaryImmunoglobulin G4-related disease (IgG4-RD) is a systemic inflammatory disease characterized by elevated serum IgG4 levels and tissue IgG4-positive cells. A part of IgG4-RD patients has sinonasal lesions. Because other inflammatory diseases also have features common to IgG4-RD, accurate knowledge of IgG4-RD is required. However, very little is known about IgG4-related rhinosinusitis. This study retrospectively analyzed clinicopathological features of IgG4-related rhinosinusitis and compared IgG4-related rhinosinusitis with other inflammatory diseases. Seven patients with sinonasal lesions and high serum IgG4 levels were retrospectively reviewed. Six of 7 patients were diagnosed with IgG4-RD, while one was diagnosed with granulomatosis with polyangiitis (GPA). In the 6 patients with IgG4-RD, intranasal findings showed nasal polyps in 3 patients (50%) and computed tomography showed ethmoid sinus involvement in 5 patients (83%), which shared common features with eosinophilic sinusitis (ECRS). However, no patients showed histopathological eosinophil infiltration. Although the patient with GPA revealed tissue infiltration of IgG4-positive cells in the nasal biopsy, the patient also had saddle nose and positivity of myeloperoxidase-antineutrophil cytoplasmic antibody (ANCA), which indicated GPA. We diagnosed the patient with GPA, which is a known mimicker of IgG4-RD. In this study, the patients with IgG4-related rhinosinusitis had clinical and pathological characteristics similar to those of ECRS and GPA. IgG4-related rhinosinusitis should be diagnosed based on not only tissue infiltration of IgG4-positive cells but also systemic findings including nasal findings and serum ANCA levels. IgG4-RD should be ruled out in patients with eosinophilia without histopathological eosinophil infiltration.

E025 From risk to reward: a case of systemic antineutrophilic cytoplasmic antibody associated vasculitis

Abstract Background/Aims The background and aims of this case involve a 70-year-old female patient with a history of complex medical conditions, including bronchiectasis and dementia, who initially presented with respiratory symptoms and fever. The primary aim was to understand the underlying cause of her deteriorating condition, which did not respond to initial antibiotic treatment for suspected pneumonia. Subsequent diagnostic efforts, including extensive vasculitis workup, were undertaken to identify the source of her symptoms, which led to the discovery of positive PR3 results and elevated inflammatory markers. The key goal was to determine the most effective treatment strategy, considering the patient’s unique medical history, balancing the need for immunosuppressive therapy against the potential risks of exacerbating underlying infections. The case ultimately aimed to demonstrate the successful management of the patient’s complex clinical presentation through a multidisciplinary approach, including immunosuppressive therapy and supportive care, resulting in significant improvements in her neurological and functional status. Methods We conducted a comprehensive assessment of a 70-year-old patient with ANCA-associated vasculitis (AAV) involving the central nervous system (CNS) and cutaneous manifestations. Lab tests targeted PR3-positive ANCA, and imaging assessed disease extent. A multidisciplinary team designed a tailored treatment plan with cyclophosphamide, closely monitoring progress. Ethical considerations were adhered to, and a literature review provided context. Data analysis evaluated treatment efficacy, leading to a discussion of lessons learned in managing complex AAV cases. Results We documented the remarkable trajectory of a 70-year-old patient with ANCA-associated vasculitis (AAV) presenting with central nervous system (CNS) involvement and cutaneous manifestations. With a meticulous and tailored treatment plan involving the judicious use of cyclophosphamide, we witnessed a profound recovery marked by significant improvements in both motor and cognitive function. This case underscores the importance of balancing potent immunosuppression with the imperative to curb disease progression and mitigate treatment-associated repercussions in complex AAV presentations. The patient’s restoration to baseline functioning serves as a compelling testament to the potential of precision medicine in managing intricate clinical scenarios of AAV. Our findings emphasize the need for continued awareness and consideration of individualized treatment approaches in similar cases, offering hope and insights for improved outcomes in challenging AAV presentations. Conclusion This case offers valuable lessons on the complexities and challenges involved in diagnosing and managing a multi-faceted condition like AAV. It emphasizes the urgent need for a timely and accurate diagnosis, especially when presented with atypical cases involving the central nervous system and cutaneous manifestations. Moreover, the case enriches our understanding of AAV and contributes insights into its nuanced management. It calls for a sophisticated, patient-centered approach, informed by cutting-edge research, to optimize patient outcomes in this challenging clinical scenario. Disclosure A.J. AlZeera: None. D. Gurdeep: None.

E078 Long term outcomes of diffuse alveolar haemorrhage in antineutrophil cytoplasmic antibody-associated vasculitis: a single centre study

Abstract Background/Aims ANCA associated vasculitis (AAV) is a heterogeneous disease with significant mortality and morbidity. Diffuse Alveolar Hemorrhage (DAH) is a life-threatening condition and presents with hemoptysis, cough, breathlessness and respiratory failure. Studies have shown a prevalence of about 25%. This study was designed to assess the clinical features, serology, efficacy of treatment and long term outcomes in DAH patients secondary to AAV. Methods This was an observational study which included adult AAV Patients diagnosed based on Revised International Chapel Hill Consensus Conference classification criteria from January 2016 to August, 2023 after IEC approval. DAH was diagnosed based on clinical symptoms, Imaging (Diffuse alveolar infiltrates), drop in hemoglobin, hypoxia and Bronchoalveolar lavage in cases where feasible. Demographic details, clinical features, laboratory data including ANCA serology, treatment, disease activity, outcomes of patients were assessed prospectively. DAH and Non DAH groups were compared using Kruskal Wallis test for median values. Student t-test for mean values and Chi square for categorical variables were used to test association between two groups with statistical significance of P-Value &amp;lt;0.05. Results 133 AAV patients were included in the study. DAH was seen in 42(31.5%) patients. The mean (± SD) age of patients was 49.4(±18.9) years. Males (52.3%) were marginally higher in number then females (47.6%). Patients presented with a median of 8 weeks after AAV diagnosis. Hemoptysis (61.9%), cough (47.6%) and breathlessness(64.3%) were the presenting complaints. Renal, Sinusitis, Gastrointestinal involvement was seen in 83.3%, 61.9% and 14.2% respectively. Musculoskeletal and Ophthalmic features were seen in 33.3% each. RPRF was seen in 42.8%. c-ANCA, p-ANCA were seen in 73.8%,21.4% while Anti PR3 antibody and Anti MPO antibody were seen in 78.5%, 21.4% patients respectively. Median (IQR) BVAS score at presentation was 20(13-24) compared to 11(7-11) in Non DAH group which was statistically significant (p &amp;lt; 0.001). 10(23.8%) patients required ventilator support. IVIg was given in 3(7.1%), while plasmapheresis was used in 7(16.7%). Induction regimen with Cyclophosphamide was used in 73.8% and Rituximab (RTX) in 8(19%) patients. Maintenance RTX was used in 42.8% and 45.2% patients received Azathioprine. 23.8% patients relapsed and 54.6% patients were in remission. 10(23.8%) required Mechanical Ventilation. No patients were on long term oxygen therapy. 7(16.6%) patients died. Morbidity was seen in 16(38%) including CKD in 8(19%) patients. Median(IQR) duration of follow up was 10(6-24) months. Conclusion DAH is a serious manifestation of AAV and an important Rheumatological emergency. DAH was present in 31.5% with majority patients in remission. Mortality was seen in 16.6% and morbidity in 38% cases. Management with combination of Pulse steroids, Cyclophosphamide /Rituximab and Plasmapheresis is the key to better outcomes. Ventilator support may be necessary in severe cases. Timely diagnosis and aggressive management is the key to survival and prevents morbidity. Disclosure J.R. Yadavalli: None. K. Telang: None. P. Khatri: None. S. Dhuria: None. G. Ekbote: None. R. Gupta: None.

P023 A case of ANCA-associated vasculitis with possible IgG4-related disease

Abstract Background/Aims IgG4-related disease (IgG4-RD) and granulomatous polyangiitis (GPA) have apparent different pathology. There are infrequent reports of the two conditions occurring simultaneously. We add to the literature by describing a patient who appears to have both conditions. Methods A 65-year-old male presented with low back pain radiating to the perineum. His past history included T2DM, CABG and ablation for AF. Initial investigations showed a CRP of 102mg/ml and an eGFR of &amp;gt; 90ml/hr. A CT urogram revealed possible aortitis. A dedicated aortogram showed a cuff of added tissue around the infrarenal aorta and iliac arteries. A whole aortogram showed an increase in the abnormal tissue and detected a left upper lobe cavitating lesion. A PET-CT scan showed activity in the infrarenal aortic tissue, with focal uptake in the aortic arch and right superficial femoral artery. Several pleural based and parenchymal lesions showing moderate increased FDG activity were seen. A CT scan of the sinuses showed multifocal sinonasal mucosal thickening without bony erosions. C-ANCA was positive at 1/40, with raised PR3 of 32U/ml and IgG4 of 2.2g/L. Other immunoglobulin levels were normal and IGRA was negative. A biopsy of the lung lesion showed necrotising granulomatous inflammation and surrounding palisading histocytes, withno vasculitic element. Treatment with prednisolone 40mg daily and methotrexate 15mg weekly was started. A quick symptomatic improvement followed. CRP fell to 14mg/ml within two months. It was discussed in the national IgG4-RD MDT, and the consensus was that he had features of both GPA and IgG4-RD. A follow-up CT scan showed reduction in the volume of para-aortic tissue, with regression of some lesions in the chest, while others increased. However, he remains well with a normal CRP, stable renal function and normal urinalysis. His latest IgG4 level dropped to 0.67 g/L. Results The ANCA positivity and lung biopsy findings satisfy classification criteria of GPA. While aortic involvement is not commonly seen in GPA; it is typical of IgG4-RD; however, its diagnostic criteria require a confirmatory biopsy. This is challenging due to the risk of sampling around the aorta and ureters. Our case fulfils criteria for ‘possible’ IgG4-RD. In retrospect, an earlier PET CT scan may have spared the patient several CT scans. Conclusion The co-existence of IgG4-RD and ANCA-associated vasculitis may be more common than might be expected. Our case highlights the usefulness of early PET-CT scanning in rheumatic conditions. It is important to check ANCA in suspected IgG4-RD cases. It is possible that future AI programmes may help clinicians better judge the timing of investigations that may be more expensive, invasive or have increased radiation exposure in such complex cases. Finally, the usefulness of a national MDT for IgG4-RD is highlighted. Fortunately, treatment modalities are similar for both conditions. Disclosure H. Eltahir: None. M. Lloyd: None.

P184 Geographical variations in delivery of intravenous treatments for ANCA-associated vasculitis

Abstract Background/Aims Timely access to intravenous immunosuppressant therapy is essential to effectively manage systemic vasculitis; however, significant variations in care and outcomes exists across centres. We systematically evaluated access to treatment for ANCA-associated vasculitis across the UK and Ireland. Methods This multi-method study included: a survey of 87 UK and Ireland Vasculitis Society sites and 11 Scottish Health Boards between Nov 2020 and June 2021; interviews with staff and patients with systemic vasculitis. Survey data was analysed descriptively. Interviews were audio or video recorded and analysed thematically. Results 59 responses from 51 Trusts/Health Boards across Scotland (n = 11), England (n = 33), Wales (n = 2), and Ireland (n = 5) included equal numbers of rheumatology and nephrology vasculitis services across diverse healthcare settings. 67 healthcare professionals across six case studies in Scotland (n = 3) and England (n = 3) and 32 patients with systemic vasculitis were interviewed. Services faced significant challenges in prescribing and delivering high-cost drugs to manage systemic vasculitis: balancing accountability versus bureaucracy, and tensions between different specialties looking after vasculitis patients when implementing access to high-cost drugs via multi-disciplinary networks. There was significant variation in how services delivered intravenous treatments: 10%(5/51) used inpatient beds; 35% (18/51) accessed another specialty unit or shared a daycase facility; 65% (33/51) used their own specialty daycase unit. Average wait time for urgent IV treatment was 2.67 days (range 1-10 days). 18% of services had waiting times &amp;gt;7 days, and of those 67% accessed intravenous treatments via another daycase facility. Specific challenges in accessing daycase facilities included availability of slots and staff, particularly in shared units, due to competition with other services and limited awareness of the importance of timely treatment for systemic vasculitis. This could impact on timing and treatment decisions e.g., prolonged steroid prescriptions. Staff training, competencies and governance to deliver cytotoxic drugs was problematic, particularly for smaller services, and 70% of services said national training modules would be helpful. Oncology units could provide workarounds but daycase nurses with vasculitis knowledge were a valuable source of advice and support for patients attending for treatments, identifying medical issues and arranging assessment if required. Conclusion There is significant variation in access to intravenous treatment for systemic vasculitis. Healthcare organisations should ensure timely access to urgent intravenous treatment for systemic vasculitis within 7 days and appropriately trained staff. National training modules for non-cancer chemotherapy could facilitate equitable access to training. Where treatment is delivered via other units, greater awareness of systemic vasculitis would help provision of information and support for patients. Disclosure W. James: None. A. Nicoll: None. L. Locock: None. L. Harper: None. M. Little: None. N. Basu: None. R.J. Hollick: None.

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.

A case of granulomatosis with polyangiitis presenting as cerebritis

Background: Isolated Central Nervous System (CNS) involvement in Granulomatosis with Polyangiitis (GPA) is rare. There are limited accounts of such a presentation in the literature. Case presentation: A 61-year-old gentleman presented with right upper limb and lower limb weakness, slurred speech and confusion following two instances of mechanical falls while at home. A cerebrovascular event was suspected. He underwent Computed Tomography (CT) brain and Magnetic Resonance Imaging (MRI) brain which demonstrated leptomeningeal thickening of left frontal region with vasogenic oedema. The differential diagnosis included malignancy, infection and contusion. He initially commenced on Dexamethasone 8 mg, Keppra 250 mg and a combination of Ceftriaxone, Linezolid, Metronidazole to treat vasogenic edema and possible infectious cerebritis, respectively. His vasculitis screen demonstrated a positive p-ANCA, positive for high titer PR3-ANCA. He was diagnosed with cerebral vasculitis secondary to GPA and commenced on immunosuppressant treatment.

Analysis of risk factors associated with diffuse alveolar haemorrhage in patients with ANCA-associated vasculitis and construction of a risk prediction model using line graph.

This study aims to analyse the risk factors associated with diffuse alveolar haemorrhage (DAH) in patients with ANCA-associated vasculitis (AAV) and construct a risk prediction model using line graph. A retrospective study was conducted from January 2012 to May 2023 at the First Clinical College of Three Gorges University, focusing on patients diagnosed with AAV. Clinical and laboratory data were collected from these patients. The potential predictors subsets of high-risk AAV combined with DAH were screened by LASSO regression and 10-fold cross-validation method, and determined by using multivariate Logistic regression analysis, then were used for developing a prediction nomogram for high-risk AAV combined with DAH using the R software. ROC curve analysis was used to validate the model's stability. Internal validation was performed using a bootstrap method. The discrimination of the nomogram was determined by calculating the average consistency index(C-index). The calibration curve was used to assess the calibration of the nomogram. A total of 234 patients with AAV were included, among whom 85 developed DAH, with an incidence rate of 36%, and the average age was 63±12. Multivariable logistic regression analysis showed that Age [OR=1.037 (95%CI: 1.006, 1.071), p=0.019], platelet count (PLT) [OR=0.996 (95%CI: 0.992, 0.999), p=0.029], ESR [OR=1.028 (95%CI: 1.015, 1.042), p<0.01], HB [OR=0.978 (95%CI: 0.959, 0.996), p=0.024], and haematuria [OR=3.77 (95%CI: 1.677, 8.976), p=0.001] were found to be independent predictors of AAV combined with DAH and were used to construct a nomogram. The AUCROC values of the nomogram for DAH in AAV patients was 0.852 (95%CI: 0.801, 0.903), and the C-index could reach 0.824 after internal verification, showing good differentiation and consistency. The new nomogram, which included age, Hb, ESR, PLT and haematuria as variables, had the potential to predict the risk of AAV patients complicated with DAH.

Patient-Reported Sinonasal Symptoms and Risk of Relapse in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

Relapses are frequent and difficult to predict in antineutrophil cytoplasmic antibody-associated vasculitis (AAV), resulting in long-term use of immunosuppression. Although sinonasal disease is associated with relapse of AAV, detailed characterization of sinonasal symptoms is lacking. Using a patient-reported outcome, the 22-item SinoNasal Outcome Test (SNOT-22), we investigated the relationship between sinonasal symptoms and disease activity in AAV. This was a prospective, longitudinal study of individual with AAV and healthy individuals. Relapse was defined as a Birmingham Vasculitis Activity Score for Wegner's Granulomatosis score >0. Higher SNOT-22 scores indicate worse symptoms. Generalized estimating equation and Cox proportional hazard models evaluated the association between SNOT-22 and relapse. There were 773 visits (106 active disease visits) from 168 patients with AAV and 51 controls. Median SNOT-22 at remission was higher in AAV versus controls (20 vs 5; P < 0.001) and higher during active disease versus remission (P < 0.001). In all AAV, and particularly within granulomatosis with polyangiitis, higher SNOT-22 scores were observed months to years before relapse and were associated with increased risk of relapse (hazard ratio 2.7, 95% confidence interval 1.2-6.2; P = 0.02). Similar findings were seen when examining patients with versus without sinonasal disease and after removing relapses limited to the ear, nose, and throat. A patient-reported outcome measure of sinonasal disease, the SNOT-22, not only changes with disease activity in AAV, but also is associated with a higher risk of relapse within two years. These findings support the possibility that the SNOT-22 score may enhance prediction of relapse and that persistent sinonasal disease may be important in the pathophysiology of relapse.

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.

Chemokine expression in sera of patients with microscopic polyangiitis and granulomatosis with polyangiitis

We evaluated chemokine expression and its correlation with disease activity in patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) (MPA/GPA). Serum CCL2, CCL4, CCL19, CXCL1, CXCL2, and CX3CL1 level in 80 patients were analysed using multiple enzyme-linked immunosorbent assays. Correlations between variables were investigated using Pearson’s correlation analysis, and receiver operator curve analysis was performed to identify optimal CX3CL1 values in determining active disease. Multivariate logistic regression analysis was done to evaluate predictors of active disease. CCL4 (r = 0.251, p = 0.025), CXCL1 (r = 0.270, p = 0.015), and CX3CL1 (r = 0.295, p = 0.008) significantly correlated with BVAS, while CX3CL1 was associated with five-factor score (r = − 0.290, p = 0.009). Correlations were revealed between CCL2 and CCL4 (r = 0.267, p = 0.017), CCL4 and CXCL1 (r = 0.368, p < 0.001), CCL4 and CXCL2 (r = 0.436, p < 0.001), and CXCL1 and CXCL2 (r = 0.518, p < 0.001). Multivariate analysis revealed serum CX3CL1 levels > 2408.92 pg/mL could predict active disease (odds ratio, 27.401, p < 0.001). Serum chemokine levels of CCL4, CXCL1, and CX3CL1 showed association with disease activity and especially, CX3CL1 > 2408.92 pg/mL showed potential in predicting active MPA/GPA.

The clinical complexity among patients with systemic, chronic diseases

ObjectivesThis study aimed to assess the clinical complexity of patients with chronic systemic diseases (systemic lupus erythematosus [SLE] and ANCA-associated vasculitis [AAV]) using the INTERMED Self-Assessment questionnaire (IMSA) to determine the most important factors responsible for this phenomenon in these patients. MethodsThis was a cross-sectional, observational study. Questionnaires were used to evaluate biopsychosocial complexity (IMSA), quality of life (Short Form Survey [SF-36]), mental state (General Health Questionnaire – 28 [GHQ-28] and Hospital Anxiety and Depression Scale [HADS]), and acceptance of illness (Acceptance of Illness Scale [AIS]). ResultsThe final analysis included 81 patients. There was a moderate correlation between clinical complexity (total IMSA score) and quality of life related to mental health (SF-36) and mental state (GHQ-28) in patients with SLE. However, in patients with AAV, clinical complexity had a strong relationship with physical health-related quality of life and a moderate relationship with mental health-related quality of life. Stepwise regression analysis showed that low mental health-related quality of life is a predictor of higher complexity in SLE. The predictors of high clinical complexity in AAV were low physical and mental health-related quality of life and aggravated depressive symptoms (HADS). Other principal factors of clinical complexity were employment status, place of residence, social functioning, and illness duration. ConclusionThis study confirmed the importance of holistic attitudes and complex healthcare among patients with chronic diseases.