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The recurrence of primary disease is an important cause affecting the short-term and long-term survival of transplant kidney, which receives increasing attention. Systemic disease-related renal damage may recur after kidney transplantation and cause varying degrees of damage to the transplant kidney. With an in-depth understanding of the pathogenesis of systemic disease-related renal damage, the level of diagnosis and treatment of recurrence of systemic disease-related renal damage in transplant kidney is gradually improving. Branch of Organ Transplantation of Chinese Medical Association organized organ transplantation experts to fully read, analyze, and summarize the current international and domestic literature. On the basis of "Technical Specification for Diagnosis and Treatment of Chronic Renal Allograft Dysfunction (2019 edition)", the risk factors, preventive measures, treatment measures, and prognosis of the recurrence of systemic disease-related renal damage were evaluated based on the Grading of Recommendations Assessment, Development and Evaluation for evidence quality and recommendation strength. The " Guidelines for Clinical Diagnosis and Treatment of Recurrence of Systemic Disease-Related Renal Damage in Transplant Kidney in China" were formulated, which provide recommendations for corresponding clinical issues to better ensure and promote the long-term survival of transplant kidneys and recipients. [ABSTRACT FROM AUTHOR]

Objectives: Pneumocystis jirovecii pneumonia (PJP) is a serious complication of autoimmune and inflammatory diseases. This study aimed to describe the characteristics of PJP in patients with various systemic vasculitides and explore potential prognostic factors. Method: Data on 62 enrolled PJP patients with systemic vasculitis were analyzed. Patients were stratified based on the outcomes. Prognostic factors were investigated using Cox-regression models. Characteristics of patients with and without interstitial lung disease (ILD) were compared. Results: Among 62 vasculitis-PJP patients, 48 had anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV), with microscopic polyangiitis (MPA) being the most common subtype (28 patients). MPA (HR 4.33, p = 0.001), concomitant aspergillosis (HR 2.68, p = 0.019), and higher D-dimer at PJP diagnosis (HR 1.07, p = 0.004) were independent adverse prognostic factors for overall survival. Stable disease activity of vasculitis was an independent favorable prognostic factor (HR 0.28, p = 0.027). Patients with MPA were older than non-MPA patients (median age: 69 vs. 58 years, p = 0.001); both ILD and fibrotic ILD were more prevalent in MPA patients (ILD: 78.6% vs. 35.3%, p = 0.001; fibrotic ILD: 57.1% vs. 11.8%, p < 0.001). At the diagnosis of PJP, patients with preexisting ILD had higher counts of white cells, lymphocytes, and neutrophils, as well as higher levels of immunoglobulin (Ig) G and IgA, than patients without preexisting ILD. Conclusions: MPA was associated with a higher risk of death in patients with vasculitis-PJP, possibly due to a higher prevalence of ILD. In clinical practice, we should pay more attention to the prophylaxis and management of PJP in patients with systemic vasculitis-associated ILD and/or MPA. Key Points • Data from this study showed that MPA was the most common subtype of vasculitis among vasculitis-PJP patients. • Compared with non-MPA patients in this study, patients with MPA were older, had more ILD and fibrotic ILD, and had a poorer prognosis. • In clinical practice, we should pay more attention to the prophylaxis and management of PJP in patients with systemic vasculitis-associated ILD and/or MPA. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the clinical and image characteristics of primary systemic vasculitis-associated optic neuritis patients. Methods: This is a retrospective study. The patients clinically diagnosed with primary system vasculitis-induced optic neuritis were recruited from March 2013 to December 2023. All cases received orbital magnetic resonance imaging scans were analyzed. The ocular findings, systemic manifestations, laboratory data and prognosis were reviewed retrospectively. In addition, the related literature was reviewed. Results: Fourteen patients (21 eyes), including 10 men and 4 women, were enrolled in this study. The ages ranged from 30 to 86 years in this cohort. Orbits MRI detects the enlargement and/or enhancement of the optic nerve. Cases 1–5 reported a confirmed diagnosis of Takayasu's arteritis, and cases 6–8 had giant cell arteritis. Cases 9–13 were antineutrophil cytoplasmic antibody-associated vasculitis. Case 14 was Cogan's syndrome. Mult organs and tissues, such as the kidneys, heart, paranasal sinuses, meninges, and respiratory system, were involved. In all of the 14 involved patients, the disease onset was either during the fall or winter season. There were no or only slight improvements in visual activity after conventional therapies. Conclusions: The autoantibodies' attack on the optic nerve, ischemic damage, or destruction of the blood–brain barrier may be the potential pathogenesis of vasculitis-associated optic neuritis. Even with prompt and aggressive clinical interventions, the prognosis remains unsatisfactory. [ABSTRACT FROM AUTHOR]

Objectives: To identify the optimal dose of intravenous cyclophosphamide (IVCY) for induction therapy for anti-neutrophil cytoplasmic antibody-associated vasculitis. Methods: We retrospectively assessed patients with antibody-associated vasculitis who received IVCY every 2–3 weeks during the remission induction phase. The associations of the IVCY dose with infection-free survival and relapse-free survival were analysed using a Cox regression model. We compared patients in three categories: very low-dose (VLD), low-dose (LD), and conventional dose (CD) (<7.5 mg/kg, 7.5–12.5 mg/kg, and >12.5 mg/kg, respectively). The non-linear association between IVCY dose and the outcomes was also evaluated. Results: Of the 80 patients (median age 72 years), 12, 42, and 26 underwent the VLD, LD, and CD regimens, respectively, of whom 4, 3, and 7 developed infection or died. The adjusted hazard ratios for infection or death were 4.3 (95% confidence interval (CI) 0.94–19.8) for VLD and 5.1 (95% CI 1.21–21.3) for CD, compared with LD. We found the hazard ratio for infection or death increased when the initial IVCY dose exceeded 9 mg/kg. Relapse-free survival did not differ clearly. Conclusion: Low-dose IVCY (7.5–12.5 mg/kg) may result in fewer infections and similar relapse rates compared with the conventional regimen (>12.5 mg/kg). [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to evaluate the applicability of the new 2022 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) criteria in Turkish adult patients previously diagnosed with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Patients and methods: One hundred sixty-four patients (96 males, 68 females; mean age: 49.6±14.4 years; range, 18 to 87 years) diagnosed with AAV by experienced rheumatologists between July 2016 and May 2022 were included in this retrospective cross-sectional study and reclassified based on the 1990 ACR criteria, the European Medicines Agency (EMEA) algorithm, and the 2022 ACR/EULAR criteria. For external validation, 83 patients (48 males, 35 females; mean age: 47.3±17.5 years; range, 19 to 81 years) diagnosed with immunoglobulin (Ig)A vasculitis were included. Results: One hundred twenty-six (76.8%) patients had granulomatosis with polyangiitis (GPA), 13 (7.9%) patients had eosinophilic granulomatosis with polyangiitis (EGPA), and 25 (15.2%) patients had microscopic polyangiitis (MPA). According to the criteria, the number of unclassified patients was nine (5.5%) for both the 2022 ACR/EULAR AAV classification criteria and the EMEA algorithm. The new criteria had an almost perfect agreement with the clinician's diagnosis (Cohen's kappa coefficient [k]=0.858 for GPA, k=0.820 for EGPA, and k=0.847 for MPA). The kappa statistics for agreement of 2022 ACR/EULAR classification criteria with the EMEA algorithm were found 0.794 for GPA, 0.820 for EGPA, and 0.700 for MPA. None of the 83 patients diagnosed with IgA vasculitis could be classified as GPA, EGPA, or MPA using the new ACR/EULAR AAV classification criteria. Conclusion: The 2022 ACR/EULAR classification criteria for AAV showed substantial or perfect agreement with the clinical diagnosis and the EMEA algorithm. [ABSTRACT FROM AUTHOR]

Vasculitic neuropathy has a broad range of etiologies, and roughly comprises nonsystemic vasculitic neuropathy and neuropathies accompanied by antineutrophil cytoplasmic antibody‐associated vasculitis (AAV). Recent morphological analyses of sural nerve specimens from patients with vasculitic neuropathy showed some distinct pathogeneses within vasculitic neuropathy. Several randomized, controlled studies and updated practice guidelines cover immunotherapies for AAV, whereas there is a paucity of evidence for vasculitic neuropathy, including neuropathies associated with AAV. Corticosteroids have been the mainstay of immunotherapy for vasculitic neuropathy, and cyclophosphamide is indispensable for refractory cases. Recent AAV guidelines are shifting their recommendations toward minimizing the harm caused by corticosteroids and cyclophosphamide with a reduced‐dose corticosteroid regimen and the recent advent of various optional drugs, especially molecular‐targeted agents. Clinicians expect the efficacy of reduced‐dose corticosteroid regimens and molecular‐targeted agents in treating vasculitic neuropathy to be verified, and clarification of the mechanism of vasculitic neuropathy might lead to the development of the best treatment based on the background pathogenesis of individual cases. [ABSTRACT FROM AUTHOR]

Background: The anti-thyroid medication propylthiouracil (PTU) is a recognised cause of drug-induced antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Pauci-immune crescentic glomerulonephritis is the characteristic feature of this condition on renal biopsy. We present a case of PTU-induced AAV with the unusual histological finding of overlap IgA nephropathy (IgAN) in a young female with treatment-resistant Graves’ disease. Case Report: A 26-year-old female presented with an acute kidney injury, macroscopic haematuria, and proteinuria 14 months after starting PTU for Graves’ disease. She had a history of established thyroid eye disease and a previous severe adverse reaction to carbimazole. Her autoantibodies were strongly positive for myeloperoxidase-ANCA (199 U/mL). Renal biopsy demonstrated both necrotising crescentic glomerulonephritis and prominent (3+) mesangial deposition of IgA. She was treated with glucocorticoids and rituximab with sustained improvement in her renal function but persisting mild proteinuria and microscopic haematuria. PTU was ceased following a dose of radioactive iodine (RAI). Twelve months post-RAI, her Graves’ orbitopathy remained stable, and her thyroid function was gradually normalising. Conclusion: This was a case of drug-induced AAV with histological features of overlap IgAN. We suggest that this patient had pre-existing subclinical IgAN and then developed AAV secondary to PTU. The management of her thyroid disease was complex given the PTU-induced vasculitis, previous reaction to carbimazole, the risks of a thyroidectomy on immunosuppression, and the possible worsening of her eye disease with RAI. The glucocorticoids and Rituximab prescribed for vasculitis may have prevented the progression of her Graves’ orbitopathy after RAI.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of rare conditions predominantly affecting small vessels of skin, musculoskeletal, pulmonary, renal, and rarely central and peripheral nervous systems. Isolated neurological manifestations of AAV are uncommon and challenging to diagnose. Cocaine has been reported as a potential trigger for the development of AAV. There are only a few case reports of isolated neurological involvement in cocaine-induced AAV with poorly characterized histopathological features. We present a unique case of AAV with isolated neurological manifestations presenting with multiple cranial neuropathies, leptomeningeal enhancement on imaging and histopathologic evidence of small-vessel vasculitis in the leptomeninges and brain and extensive dural fibrosis in a patient with cocaine abuse. The patient's progressive neurological deficits were controlled after starting immunosuppression with rituximab and prednisone. We also reviewed the literature to provide the diagnostic overview of AAV and evaluate intervention options. To our knowledge, this is the first case of AAV with isolated neurological manifestations and histopathologic evidence of small-vessel vasculitis in a patient with cocaine abuse. Patients with multiple cranial neuropathies and meningeal involvement should be screened for AAV, especially if they have a history of cocaine abuse. [ABSTRACT FROM AUTHOR]

Introduction: Immunoglobulin G4-related disease (IgG4-RD) is a systemic inflammatory disease characterized by elevated serum IgG4, tissue infiltration of IgG4-positive cells, and fibrosis. Although a number of IgG4-RD patients show sinonasal involvement, there is little known about sinonasal inflammation associated with IgG4-RD. This study aimed to describe the clinicopathological features of sinonasal inflammation associated with IgG4-RD and to compare with other inflammatory diseases, such as eosinophilic chronic rhinosinusitis (ECRS) and granulomatosis with polyangiitis (GPA). Methods: A retrospective analysis of clinicopathological features of patients with sinonasal lesions and high serum IgG4 was performed. Patient data were reviewed to determine whether they fulfilled the diagnostic criteria for other inflammatory diseases. Results: Six of 7 patients were diagnosed with IgG4-RD, while 1 patient was diagnosed with GPA. In the 6 patients with IgG4-RD, intranasal findings showed nasal polyps in 3 patients (50%) and nasal crusting in the 3 patients (50%). Computed tomography showed ethmoid sinus involvement in 5 patients (83%). Five of the 6 patients (83%) were diagnosed with IgG4-RD based on nasal biopsy, whereas 1 patient (17%) was diagnosed based on lacrimal gland biopsy. Four patients fulfilled the Japanese epidemiological survey of refractory ECRS (JESREC) criteria. However, none of the patients showed eosinophil infiltration. Although the patient with GPA showed high levels of serum IgG4 and tissue infiltration of IgG4-positive cells in the nasal biopsy, the patient showed common clinical features of GPA. Conclusion: Patients with sinonasal inflammation associated with IgG4-RD had similar clinical characteristics with ECRS and GPA. Histopathological findings of the nasal biopsy from clinically diagnosed GPA was consistent with that of IgG4-RD. Sinonasal inflammation associated with IgG4-RD should be diagnosed based not only on tissue infiltration of IgG4-positive cells but in conjunction with clinical findings such as local nasal characteristics, involvement of other organs, and serum antineutrophil cytoplasmic antibody levels. IgG4-RD should be ruled out in patients with eosinophilia without histopathological eosinophil infiltration. Plain Language Summary: Immunoglobulin 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. [ABSTRACT FROM AUTHOR]

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Hypertrophic pachymeningitis is a rare inflammatory condition that leads to the thickening of the dura mater, either due to unknown or identifiable secondary causes. Granulomatosis with polyangiitis is a notable causative agent, and hypertrophic pachymeningitis is the initial presentation in certain cases. The diagnosis of hypertrophic pachymeningitis is aided by contrast-enhanced MRI, although distinguishing between normal and abnormal dural enhancement can be challenging using contrast-enhanced T1WI. This study highlights the case of an 80-year-old woman diagnosed with hypertrophic pachymeningitis secondary to antineutrophil cytoplasmic antibody-associated granulomatosis with polyangiitis, where contrast-enhanced FLAIR played a crucial role in distinctly identifying abnormal dural enhancement and differentiating it from normal dura. In conclusion, although contrast-enhanced T1WI remains indispensable, contrast-enhanced FLAIR can serve as a valuable complementary tool in MRI study sequences for the diagnosis of hypertrophic pachymeningitis.

Objectives: Despite the identification of risk factors for relapses in antineutrophil cytoplasmic antibody-associated vasculitis, the relationship between changes in C-reactive protein (CRP) levels after the initial treatment and the incidence of relapse remains unknown. This study aimed to assess the association between the time taken for normalisation of CRP levels and the incidence of relapse in Japanese adult patients with microscopic polyangiitis. Methods: This study included 85 consecutive patients with newly diagnosed microscopic polyangiitis who achieved remission after 6 months of immunosuppressive treatment at the Aichi Medical University Hospital between 2009 and 2017. The relationship between the time to normalisation of CRP after the initial immunosuppressive treatment and relapse incidences was evaluated using multivariable Cox proportional hazard models. Results: During the follow-up period, 13 (30.2%), 7 (41.2%), and 16 (64.0%) patients relapsed (P = .025) within 1–14, 15–28, and ≥29 days of normalisation, respectively. The hazard ratios [95% confidence intervals (CIs)] for the time to normalisation of CRP of 1–14, 15–28, and ≥29 days were 1.00 (reference), 2.42 (95% CI: 0.92–6.39), and 3.48 (95% CI: 1.56–7.76), respectively. Conclusions: A significant association between the time to normalisation of CRP and the relapse incidence in Japanese patients with microscopic polyangiitis was observed. [ABSTRACT FROM AUTHOR]

Objective: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) refers to a group of small vessel inflammatory disorders. Overlapping clinical phenotypes of AAV subgroups continually provoke controversies over their diagnostic and classification criteria. Methods: Using the agglomerative hierarchical clustering method, we classified 210 Korean patients diagnosed with AAV into mutually exclusive clusters according to Birmingham Vasculitis Activity Score items, ANCA specificity, sex, and age. We analyzed the resulting clusters' outcomes to investigate the clinical significance of the classification. We proposed a distance-based algorithm of patient assignment and explored its clinically relevant modification. Results: In total, 116 patients (55%) had microscopic polyangiitis, 53 (25%) had granulomatosis with polyangiitis, and 42 (20%) had eosinophilic granulomatosis with polyangiitis. Our model grouped the patients into five clusters, namely, "limited proteinase 3 (PR3)-ANCA vasculitis," "generalized PR3-ANCA vasculitis," "ANCA-negative vasculitis," "renal-limited vasculitis," and "myeloperoxidase-ANCA vasculitis." Patients clustered under "generalized PR3-ANCA vasculitis" had a higher relapse rate (hazard ratio [HR] = 2.12, P = 0.067). The incidence of end-stage renal disease was higher in patients belonging to the "renal-limited vasculitis" cluster (HR=1.50, P=0.03), and those in the "ANCA-negative vasculitis" cluster experienced a relatively milder clinical course of AAV (mortality = 0). Conclusion: Because the clusters were naturally derived from their distinguished phenotypes and have different clinical courses, our clustering method may be a more clinically relevant classification system for AAV, revealing its phenotypic diversity. We also proposed a simple and intuitive distance-based assignment algorithm, which can be easily modified according to specific clinical needs. Key Points • In this study with a single-center AAV cohort, we showed that AAV can be divided into five distinct subclasses with different disease courses based on the clinical and laboratory features of the patients. • Our study revealed ethnic differences in AAV manifestation and suggests that physicians may need to analyze their own AAV patients to assess the disease status of AAV patients. • We proposed a distance-based cluster membership assignment method that can be clinically modified to fit the specific purpose of grouping patients. [ABSTRACT FROM AUTHOR]

Background: The anti-thyroid medication propylthiouracil (PTU) is a recognised cause of drug-induced antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Pauci-immune crescentic glomerulonephritis is the characteristic feature of this condition on renal biopsy. We present a case of PTU-induced AAV with the unusual histological finding of overlap IgA nephropathy (IgAN) in a young female with treatment-resistant Graves' disease. Case Report: A 26-year-old female presented with an acute kidney injury, macroscopic haematuria, and proteinuria 14 months after starting PTU for Graves' disease. She had a history of established thyroid eye disease and a previous severe adverse reaction to carbimazole. Her autoantibodies were strongly positive for myeloperoxidase-ANCA (199 U/mL). Renal biopsy demonstrated both necrotising crescentic glomerulonephritis and prominent (3+) mesangial deposition of IgA. She was treated with glucocorticoids and rituximab with sustained improvement in her renal function but persisting mild proteinuria and microscopic haematuria. PTU was ceased following a dose of radioactive iodine (RAI). Twelve months post-RAI, her Graves' orbitopathy remained stable, and her thyroid function was gradually normalising. Conclusion: This was a case of drug-induced AAV with histological features of overlap IgAN. We suggest that this patient had pre-existing subclinical IgAN and then developed AAV secondary to PTU. The management of her thyroid disease was complex given the PTU-induced vasculitis, previous reaction to carbimazole, the risks of a thyroidectomy on immunosuppression, and the possible worsening of her eye disease with RAI. The glucocorticoids and Rituximab prescribed for vasculitis may have prevented the progression of her Graves' orbitopathy after RAI. [ABSTRACT FROM AUTHOR]

Introduction: Rheumatic diseases are associated with poor obstetric outcomes, especially in developing countries. In a multisystem disease like antineutrophil cytoplasmic antibodyassociated vasculitis (AAV), pulmonary and renal involvement may contribute to adverse pregnancy outcomes. we explored pregnancy outcomes in women with AAV and compared pregnancies after disease onset to those that occurred before it. Method: Women with AAV (Chapel Hill Criteria, 2012) registered at a tertiary care center (2001-2021) were interviewed by teleconsultation or during outpatient visits. Maternal complications and fetal complications were recorded. Results: Median age at disease onset was 48 (33-60) years, with the most common subtype being granulomatosis with polyangiitis (13, 48%) followed by microscopic polyangiitis (10, 37%). Twelve women were in the reproductive age group, of which six suffered from a premature menopause. Three pregnancies in three women after disease onset were compared with 62 pregnancies in 23 women with conception before the disease. Pregnancies before disease onset resulted in 58 (93.3%) live birth. One (33.33%) live birth was observed in the pregnancies after disease onset, and disease onset during pregnancy resulting in intrauterine death at 20 weeks period of gestation. One patient is currently in her antenatal period with no complications so far. This study suggests the absence of impact on pregnancy outcome before diagnosis of AAV. Conclusion: Pregnancy after a diagnosis of AAV is rare, and successful outcomes may be reported on occasion. [ABSTRACT FROM AUTHOR]

Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) represents one of the most challenging and potentially life-threatening conditions faced by rheumatologists. Part of the challenge has been the limited therapeutic options available and the substantial concern related to their toxicity, which are time dependent and dose dependent. Systemic glucocorticoids (GC) have been the cornerstone of AAV therapy since the 1950s; however, the extensive list of risks associated with its use are well described. Cyclophosphamide and rituximab have become the standard therapy for remission induction in organ or life-threatening AAV but not all patients achieve or sustain remission and many remain on long-term GC therapy. Recent attention focuses on achieving sustainable steroid-free induction and remission maintenance through transformative innovation of novel drug development or repurposing. This review sheds light on the significant advances made in similar or more effective novel innovative steroid-sparing or reduction strategies in AAV. [ABSTRACT FROM AUTHOR]

Microscopic polyangiitis (MPA) is an antineutrophil cytoplasmic autoantibody-associated vasculitis, usually affecting the small vessels in the form of systemic necrotizing vasculitis. It commonly manifests as diffuse alveolar hemorrhage and rapidly progressive glomerulonephritis but may present with the involvement of multiple organs. Timely diagnosis at an early localized stage is crucial for instituting an early disease-specific treatment. We report a case of a 63-year-old female who was diagnosed with MPA predominantly involving lungs and middle ears. The absence of a typical pulmonary–renal presentation and clinical features favoring obstructive airway disease and tuberculosis led to a delayed diagnosis. The presence of antimyeloperoxidase antibodies in high titer and a clinical response to monoclonal antibody therapy, thereby confirming the diagnosis of MPA prompted us to report this case. [ABSTRACT FROM AUTHOR]

• Observational study of a Single center of patients with AAV with at least one cycle of IVIG since January of 2000 to December of 2020. • IVIG represents have a clinical improvement classified according to BVAS score, clinical and laboratory parameters. • IVIG represents an effective and relative safe therapeutic alternative in relapsing/refractory AAV. • IVIG treatment may be useful to achieve and maintain the remission in certain patients with this type of vasculitis, being an advantageous therapeutic alternative in cases of concomitant infection or in patients who cannot receive conventional therapy. Anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) includes three heterogeneous and difficult to treat clinical entities. Intravenous immunoglobulins (IVIG) may constitute a good therapeutic option, although data hitherto are scarce. The aim of this study was to assess the effectiveness and safety of IVIG in AAV in a real-world setting. Single center observational study of patients with AAV with at least one cycle of IVIG since January of 2000 to December of 2020. AAV diagnosis was based on a compatible clinical presentation and positive ANCA serology and/or compatible histology. Disease activity was assessed by the Birmingham Vasculitis Activity Score (BVAS). The effectiveness was evaluated by clinical and laboratory parameters (CRP, ESR) and its glucocorticoid-sparing effect. These variables were measured at one, six, twelve and twenty-four months of IVIG treatment. The doses of IVIG were 2g/kg in the following cycles of administration: 1 g/kg/day in 2 days (n=12); 0.5 g/kg/day in 4 days (n=11); 0.4 g/kg/day in 5 days (n=5). The clinical improvement was classified according to BVAS categories in remission, partial response and no response. Twenty-eight patients (15 granulomatosis-polyangiitis, 10 microscopic polyangiitis and 3 eosinophilic granulomatosis with polyangiitis) were included. Reasons for using IVIG were relapse/refractory disease (n=25), active or suspected infection (n=3), and both (n=5). We observed a rapid and maintained BVAS score improvement, increasing from 34.6% at 1 month to 56.5% at 2 years of follow-up (p=0.12), and a reduction of glucocorticoids dose. Therapy was well tolerated and adverse events mild and scarce. IVIG represents an effective and relative safe therapeutic alternative in relapsing/refractory AAV or in presence of a concomitant active infection. [ABSTRACT FROM AUTHOR]

Introduction: We present a case of drug‐induced vasculitis secondary to low‐dose hydralazine with overlapping features of antineutrophil cytoplasmic antibody‐associated vasculitis and drug‐induced lupus nephritis. Case presentation: A 52‐year‐old Hispanic woman with a medical history of resistant hypertension treated with hydralazine 10 mg twice daily for 1 year presented with generalized weakness, dizziness, nausea, vomiting, and gross hematuria. There was fever, tachycardia, leukocytosis, lactic acidosis, hyperkalemia, renal failure, and anemia. Chest computed tomography and bronchoscopy revealed a left lower lobe infiltrate and diffuse alveolar hemorrhage. Serologic testing was positive for anti‐double‐stranded DNA, anti‐Smith, lupus anticoagulant, anti‐histone, anti‐cardiolipin IgM antibodies, and antineutrophil cytoplasmic antibodies (myeloperoxidase and proteinase 3). A kidney biopsy revealed crescentic glomerulonephritis with an overlapping finding of membranous nephropathy. Broad‐spectrum antibiotics, immunosuppressants, corticosteroids, and plasmapheresis were initiated. The patient survived but required continuous hemodialysis. Conclusions: Although a few cases of simultaneous antibody‐associated vasculitis and drug‐induced lupus nephritis secondary to hydralazine use have been reported, this case is singular. Similar findings were previously reported with doses of 50–100 mg two to three times daily over 1–5 years. In our patient, a dose of only 10 mg twice daily for a year caused a severe disease presentation. This brings to light the combination of different vasculitides that can coexist and the potentially life‐threatening adverse effects of low‐dose hydralazine that should be kept in mind. [ABSTRACT FROM AUTHOR]

Purpose: The value of monoclonal protein (M-protein) in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) patients with renal involvement has not been investigated. Methods: We analyzed AAV patients with renal involvement from 2013 to 2019 in our center. Patients with immunofixation electrophoresis were divided into M-protein positive group and M-protein negative group. The clinicopathological features and outcomes of the two groups were compared. Results: Ninety-one AAV patients with renal involvement were enrolled for analysis, and 16 patients (17.6%) had a positive test for M-protein. Compared with M-protein negative patients, M-protein positive patients had lower hemoglobin (77.6 vs 88.4 g/L, p = 0.016), mean corpuscular hemoglobin concentration (313 vs 323 g/L, p = 0.002),serum albumin (29.4 vs 32.5 g/L, p = 0.026) and complement 3 (C3) (0.66 vs 0.81 g/L, p = 0.047), while higher platelets (252 vs 201 109/L, p = 0.048) and incidence of pulmonary infection (62.5% vs 33.3%, p = 0.029). However, renal pathological features between the two groups had no significant difference. In addition, during a median follow-up of 33 months, Kaplan–Meier survival analysis showed that, compared with M-protein negative patients, M-protein positive patients had a higher risk of all-cause mortality (log-rank test, p = 0.028), especially for patients who were not dialysis-dependent at the time of admission (log-rank test, p = 0.012). Conclusion: Our results indicate that M-protein is associated with different clinicopathological features and increased all-cause mortality in AAV patients with renal involvement. Testing M-protein and rigorous diagnosing of the significance of the presence of M-protein may be helpful for assessing the survival of AAV patients with renal involvement. [ABSTRACT FROM AUTHOR]

Background and Objectives: Treatment for antineutrophil cytoplasmic antibody-associated vasculitis (AAV) must deal with immunosuppression, as well as infections associated with a compromised immune system, such as tuberculosis (TB). Our aim was to examine the risk of incidental TB after diagnosis of AAV. Materials and Methods: This retrospective population-based cohort study was based on the data from the National Health Insurance Research Database in Taiwan. Patients with newly diagnosed granulomatous polyangiitis or microscopic polyangiitis were identified between 1 January 2000 and 31 December 2012. The primary outcome was risk of incidental TB. Cox proportional hazard models were used to evaluate the association between AAV and incidental TB. Results: A total of 2257 patients with AAV and a propensity-score matched cohort of 9028 patients were studied. Overall, patients with AAV were at a 1.48× higher risk of contracting incidental TB than the patients in the matched cohort (adjusted HR 1.48; 95% confidence interval [CI], 1.02–2.15). Note that the highest risk of contracting incidental TB was in the first two years following a diagnosis of AAV, with a nearly 1-fold increase in risk (adjusted HR, 1.91; 95% CI, 1.01–3.60). Female AAV patients were 3.24× more likely than females without AAV to develop TB (adjusted HR 3.24; 95% CI, 1.85–5.67). Conclusions: Patients with AAV exhibit a 48% elevated TB risk, notably, a 91% increase within the first two years postdiagnosis. Female AAV patients face a 3.24 times higher TB risk compared to females without AAV. This study is limited by potential misclassification and overestimation of AAV cases. Clinicians should closely monitor TB risk in AAV patients, especially in females and the initial two years following diagnosis. [ABSTRACT FROM AUTHOR]

Objective: Despite recent scientific inquiry, idiopathic subglottic stenosis (iSGS) remains an enigmatic disease. The consistent demographics of the affected population suggest genetic factors may contribute to disease susceptibility. Given the inflammation observed in the affected proximal airway mucosa, we interrogated disease association with human leukocyte antigen (HLA) polymorphisms. Polymorphisms in the HLA locus have previously been shown to influence individuals' susceptibility to distinct inflammatory diseases. Methods: High‐resolution HLA typing of 37 iSGS patients was compared with 1,242,890 healthy Caucasian controls of European ancestry from the USA National Marrow Donor Program and 281 patients with granulomatosis with polyangiitis (GPA). Results: Complete HLA genotyping of an iSGS population showed no significant associations when compared to a North American Caucasian control population. Unlike GPA patients, iSGS was not associated with allele DPB1*04:01 nor did allele homozygosity correlate with disease severity. Conclusions: There was not a detectable HLA association observed in iSGS. These results support the concept that iSGS possesses a distinct genetic architecture from GPA. If genetic susceptibility exists in iSGS, it likely lies outside the HLA locus. Level of Evidence: NA, basic science Laryngoscope, 133:2533–2539, 2023 [ABSTRACT FROM AUTHOR]

Objectives: We conducted a descriptive study of the physicians' evidence-practice gap for adults covered by the 2017 clinical practice guidelines for the management of antineutrophil cytoplasmic antibody-associated vasculitis in Japan. Methods: This web-based survey, conducted between January and February 2021, involved physicians who had treated at least five patients in the preceding year at a regional core hospital. The outcome was the physicians' experience in treating patients with microscopic polyangiitis or granulomatosis with polyangiitis [prevalence with 95% confidence intervals (CIs)], defined as treating at least 60% of their patients with the recommended therapy during the year. A modified Poisson regression analysis was performed to explore the factors associated with concordance. Results: The 202 participants included 49 pulmonologists, 65 nephrologists, 61 rheumatologists, and other physicians. The concordance was 31.5% (95% CI, 25.1-38.5) of physicians who used cyclophosphamide or rituximab for the induction of remission. Rheumatology showed the highest concordance with published evidence (risk ratio =2.4; 95% CI, 1.10-5.22, p =.03). Conclusions: These results suggest an evidence-practice gap, which varies substantially among subspecialties. Further studies and a new promotional initiative are necessary to close this gap in clinical practice. [ABSTRACT FROM AUTHOR]

Objective. To clarify seasonal and other environmental effects on the onset of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Methods. We enrolled patients with new-onset eosinophilic granulomatosis with polyangiitis (EGPA), microscopic polyangiitis (MPA), and granulomatosis with polyangiitis (GPA) registered in the database of a Japanese multicenter cohort study. We investigated the relationship between environmental factors and clinical characteristics. Seasons were divided into 4 (spring, summer, autumn, and winter), and the seasonal differences in AAV onset were analyzed using Pearson chi-square test, with an expected probability of 25% for each season. Results. A total of 454 patients were enrolled, with a mean age of 70.9 years and a female proportion of 55.5%. Overall, 74, 291, and 89 patients were classified as having EGPA, MPA, and GPA, respectively. Positivity for myeloperoxidase (MPO)-ANCA and proteinase 3 (PR3)-ANCA was observed in 355 and 46 patients, respectively. Overall, the seasonality of AAV onset significantly deviated from the expected 25% for each season (P = 0.001), and its onset was less frequently observed in autumn. In ANCA serotypes, seasonality was significant in patients with MPO-ANCA (P < 0.001), but not in those with PR3-ANCA (P = 0.97). Additionally, rural residency of patients with AAV was associated with PR3-ANCA positivity and biopsy-proven pulmonary vasculitis. Conclusion. The onset of AAV was influenced by seasonal variations and was less frequently observed in autumn. In contrast, the occurrence of PR3-ANCA was triggered, not by season, but by rural residency. [ABSTRACT FROM AUTHOR]

Abstract Background Rituximab (RTX) is a standard therapy for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). However, the most frequently used dose may lead to severe adverse effects (SAEs). We explored the efficacy and safety of low-dose RTX in Chinese patients with AAV. Methods A total of 22 Chinese patients diagnosed with AAV with renal involvement, including 8 treated with low-dose RTX (400 mg of RTX total over 4 weeks) and 14 treated with cyclophosphamide (CYC), were evaluated. The baseline clinical and pathological data and laboratory parameters during follow-up at months 1, 3, 6, and 12 were collected retrospectively. Results The baseline data showed no significant differences between the two groups. The median peripheral CD19+ cell counts in the RTX group decreased from 315.0/μL to 1.5/μL at 2 weeks, and to 2.5/μL at 1 month after the first dose. The median SCr level decreased from 267.8 μmol/L before treatment to 151.45 μmol/L at 1 month, 132.75 μmol/L at 3 months, 123.2 μmol/L at 6 months, and 151.9 μmol/L at 12 months in RTX-treated patients. The improvements in renal function, proteinuria, and ANCA titre were not significantly different between the two groups. The SAE rate was significantly lower in the RTX group (one SAE of pneumonia) compared with the CYC group. Conclusions This is the first report that low-dose RTX could be effective for the treatment of Chinese patients with AAV with renal involvement.

We present a case of granulomatosis with polyangiitis (GPA) presenting with salivary gland enlargement and right parotid abscess, left-sided facial palsy, Lacrimal Gland, extraocular muscle involvement and rapidly progressive necrotizing keratitis. Followed by review of available literature on salivary gland involvement in GPA and how salivary gland involvement may be a good prognostic factor with less renal and central nervous system involvement and argue for greater vigilance in diagnosing salivary gland involvement in GPA. An approach to a patient with salivary gland involvement and suspected autoimmune disease wtih Sjögren's Syndrome, IgG4 disease,Antineutrophil cytoplasmic antibodies (ANCA) associated vasculitis and Sarcoidosis is discussed.

The antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a systematic of relatively rare autoimmune diseases with unknown cause. Kidney involvement is one of the most common clinical manifestations, and the degree of renal damage is closely associated with the development and prognosis of AAV. In this study, we utilized the Robust Rank Aggreg (RRA) method in R to integrate GSE104948, GSE104954, GSE108109, GSE108112, and GSE108113 profile datasets loaded from Gene Expression Omnibus (GEO) database and identified a set of differentially expressed genes (DEGs) in kidney between AAV patients and living donors. Then, the results of gene ontology (GO) functional annotation showed that immunity and metabolism involved process of AAV both in glomerulus and tubulointerstitial. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that following pathways, such as complement and coagulation cascades pathway; Staphylococcus aureus infection; disease-COVID-19; and systemic lupus erythematosus (SLE) pathway play a crucial role in AAV. Next, the results analyzed by protein–protein interaction (PPI) network and Cytoscape software exhibited the hub genes ALB, TYROBP, and CYBB existed in both glomerular and tubulointerstitial compartments datasets. Finally, KEGG analysis using genes of two most important modules also further validated complement and coagulation cascades pathway and S. aureus infection existed both in glomerulus and tubulointerstitial compartments datasets. In conclusion, this study identified key genes and pathways involved in kidney of AAV, which was benefit to further uncover the mechanisms underlying the development and progress of AAV, biomarkers, and potential therapeutic targets as well.

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BackgroundThis study investigated whether the non-alcoholic fatty liver disease fibrosis score (NFS) could predict all-cause mortality during follow-up among patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV).MethodsThe medical records of 256 AAV patients were retrospectively reviewed. AAV patients with clinically critical chronic liver diseases were excluded. NFS was calculated using the following equation: NFS = −1.675 + 0.037 - age + 0.094 – body mass index +1.13 × impaired fasting glucose/diabetes mellitus +0.99 × aspartate aminotransferase/alanine aminotransferase ratio - 0.013 × platelet count - 0.66 × serum albumin.ResultsThe median age was 59.0 years, and 35.2% of the patients were male. The median Birmingham Vasculitis Activity Score (BVAS), five-factor score (FFS), and NFS were 12.0, 1.0, and − 4.7, respectively. Of the 256 patients, 33 (12.9%) died. Using the receiver operating characteristic curve, the optimal cut-off of NFS for all-cause mortality was obtained as-3.97. AAV patients with NFS at diagnosis ≥ − 3.97 exhibited a lower cumulative patients’ survival rate than those with NFS at diagnosis

BackgroundThis study aimed to investigate whether triglyceride glucose-body mass index (TyG-BMI) and a new index using TyG-BMI (NITGB) could predict all-cause mortality in non-obese patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).MethodsThe medical records of 78 non-obese AAV patients (BMI < 23.0 kg/m2 for Asians) were retrospectively reviewed. TyG-BMI was calculated by the equation: Ln (triglyceride × fasting glucose/2) × BMI. To develop NITGB, we assigned a weight of a number close to an 0.1 decimal integer to each variable according to the slopes for independent variables with P-value < 0.1 in the multivariable Cox analysis.ResultsThe median age was 54.3 years and five patients died. When non-obese AAV patients were divided into two groups based on TyG-BMI ≥ 187.74, those with TyG-BMI ≥ 187.74 exhibited a significantly higher risk for all-cause mortality than those without (RR 9.450). Since age (HR 1.324), Birmingham vasculitis activity score (BVAS; HR 1.212), and TyG-BMI ≥ 187.74 (HR 12.168) were independently associated with all-cause mortality, NITGB was developed as follows: age + 0.2 × BVAS + 2.5 × TyG-BMI ≥ 187.74. When non-obese AAV patients were divided into two groups based on NITGB ≥ 27.36, those with NITGB ≥ 27.36 showed a significantly higher risk for all-cause mortality than those without (RR 284.000). Both non-obese AAV patients with TyG-BMI ≥ 187.74 and those with NITGB ≥ 27.36 exhibited significantly higher cumulative rates of all-cause mortality than those without.ConclusionNITGB along with TyG-BMI could predict all-cause mortality in non-obese AAV patients.

Background: Interstitial lung disease (ILD) is a common pulmonary manifestation of antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Objectives: We aimed to clarify the clinical predictors of mortality in a cohort of patients with AAV-related ILD (AAV-ILD). Method: We retrospectively identified AAV-ILD patients seen at Peking University First Hospital from January 2010 to June 2020 and manually screened for study inclusion. Baseline computed tomography (CT) images were further classified as nonspecific interstitial pneumonia (NSIP), usual interstitial pneumonia (UIP), organizing pneumonia (OP), and unclassified ILD. Disease characteristics and other pulmonary findings including pulmonary function test and bronchoalveolar lavage (BAL) were also evaluated. Multivariable Cox regression analysis was performed to identify clinical predictors of mortality. Results: The cohort included 204 patients with AAV-ILD, 152 had UIP on CT (AAV-UIP), 39 had NSIP on CT (AAV-NSIP), 3 had OP, and 10 had unclassified ILD. Microscopic polyangiitis was more prevalent in patients with UIP, while granulomatosis with polyangiitis was more common in the NSIP and OP groups, and eosinophilic granulomatosis with polyangiitis was more frequent in patients with unclassified ILD. ILD diagnosis before AAV was more common in patients with either UIP or NSIP patterns. During the median follow-up of 40 months, 44 (21.6%) patients died. One- and 5-year overall survival rates were 88.2% (95% CI, 83.7–92.7%) and 81.0% (95% CI, 74.9–87.1%) for the entire cohort. Patients with UIP patterns had the worst prognosis, while those with NSIP patterns had the best long-term outcome. Specifically, patients with UIP patterns had an approximately 5-fold risk of death compared to those with NSIP. After controlling for potential confounding factors, we observed that each 10% increase in the BAL fluid neutrophil percentage was associated with nearly a 20% increased risk of death (HR 1.195, 95% CI 1.018–1.404). Conclusions: Clinical characteristics and survival differ between subgroups defined by CT patterns. BAL fluid neutrophilia is an independent predictor of mortality among AAV-ILD patients, and therefore, the clinical utility of BAL at the time of AAV diagnosis should be considered. [ABSTRACT FROM AUTHOR]

Objectives: This subgroup analysis of the randomized, double-blind, Phase 3 ADVOCATE study evaluated the efficacy and safety of avacopan compared with tapered prednisone in Japanese patients with antineutrophil cytoplasmic antibody-associated vasculitis. Methods: Patients with microscopic polyangiitis (MPA) or granulomatosis with polyangiitis (GPA) received either avacopan 30 mg twice daily for 52 weeks plus prednisone-matching placebo or tapered prednisone over 20 weeks plus avacopan-matching placebo for 52 weeks. The two primary efficacy endpoints were clinical remission at Week 26 and sustained remission at Week 52. Results: Compared with the overall population (N = 330), Japanese patients (N = 21) were older and had worse renal function, and a higher proportion were female and had MPA. The proportion of Japanese patients with clinical remission at Week 26 was 9/11 (81.8%) with avacopan vs. 7/10 (70.0%) with prednisone (overall population: 72.3% vs. 70.1%) and with sustained remission at Week 52 was 8/11 (72.7%) vs. 4/10 (40.0%), respectively (overall population: 65.7% vs. 54.9%). The safety profile of avacopan was similar in Japanese patients and the overall study population. Conclusions: The efficacy and safety of avacopan in Japanese patients with MPA or GPA were comparable to that observed in the overall ADVOCATE study population. [ABSTRACT FROM AUTHOR]

We present a case of granulomatosis with polyangiitis (GPA) presenting with salivary gland enlargement and right parotid abscess, left-sided facial palsy, Lacrimal Gland, extraocular muscle involvement and rapidly progressive necrotizing keratitis. Followed by review of available literature on salivary gland involvement in GPA and how salivary gland involvement may be a good prognostic factor with less renal and central nervous system involvement and argue for greater vigilance in diagnosing salivary gland involvement in GPA. An approach to a patient with salivary gland involvement and suspected autoimmune disease wtih Sjögren's Syndrome, IgG4 disease,Antineutrophil cytoplasmic antibodies (ANCA) associated vasculitis and Sarcoidosis is discussed. [ABSTRACT FROM AUTHOR]

Background: Rituximab (RTX) is a standard therapy for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). However, the most frequently used dose may lead to severe adverse effects (SAEs). We explored the efficacy and safety of low-dose RTX in Chinese patients with AAV. Methods: A total of 22 Chinese patients diagnosed with AAV with renal involvement, including 8 treated with low-dose RTX (400 mg of RTX total over 4 weeks) and 14 treated with cyclophosphamide (CYC), were evaluated. The baseline clinical and pathological data and laboratory parameters during follow-up at months 1, 3, 6, and 12 were collected retrospectively. Results: The baseline data showed no significant differences between the two groups. The median peripheral CD19+ cell counts in the RTX group decreased from 315.0/μL to 1.5/μL at 2 weeks, and to 2.5/μL at 1 month after the first dose. The median SCr level decreased from 267.8 μmol/L before treatment to 151.45 μmol/L at 1 month, 132.75 μmol/L at 3 months, 123.2 μmol/L at 6 months, and 151.9 μmol/L at 12 months in RTX-treated patients. The improvements in renal function, proteinuria, and ANCA titre were not significantly different between the two groups. The SAE rate was significantly lower in the RTX group (one SAE of pneumonia) compared with the CYC group. Conclusions: This is the first report that low-dose RTX could be effective for the treatment of Chinese patients with AAV with renal involvement. [ABSTRACT FROM AUTHOR]

Background We aimed to investigate the clinical characteristics and outcomes of patients aged ≥65 years with antineutrophil cytoplasmic autoantibody (ANCA)-positive ANCA-associated vasculitis (AAV) in Korea. Methods Seventy patients diagnosed with ANCA-positive AAV from 2006 to 2019 at a single center were analyzed and categorized into younger (aged

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) comprises group of small vessel vasculitides, including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). In 2022, the American College of Rheumatology (ACR) and the European Alliance of Associations for Rheumatology (EULAR) jointly proposed new classification criteria for AAV (the 2022 ACR/EULAR criteria). In this review, we briefly summarize the 2022 ACR/EULAR criteria for GPA, MPA, and EGPA, and introduce our clinical experience with applying them to patients who were previously diagnosed with AAV based on three criteria: firstly, the classification criteria for GPA and EGPA proposed by the ACR in 1990; secondly, the algorithm for the classification of AAV and polyarteritis nodosa proposed by the European Medicines Agency algorithm in 2007 (the 2007 EMA algorithm); and thirdly, the revised International Chapel Hill Consensus Conference nomenclature of vasculitides in 2012 (the 2012 CHCC definitions). We found that concordance rate was highest in patients with MPA (96.6%), followed by those with EGPA (86.3%) and GPA (73.8%). In addition, compared to previous criteria, we noted several issues of the undervalued or overvalued items in the 2022 ACR/EULAR criteria for classifying AAV and provided several suggestions. To increase the diagnostic accuracy and reduce the discordance rate among the new and previous criteria for AAV, we suggest that the previous criteria should be considered together with the 2022 ACR/EULAR criteria when applying the classification criteria for AAV to patients suspected of AAV. [ABSTRACT FROM AUTHOR]

Background: Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is a cluster of potentially life-threatening disorders, often involving the kidney with a necrotizing crescentic glomerulonephritis with scanty deposition of immunoglobulins and complement. Historically the role of complement has been considered ancillary. Recently, an anti-myeloperoxidase (MPO) AAV model in complement-deficient mice has shown an involvement for the complement cascade in the development of the renal injuries. Further animal studies showing that in contrast to mice deficient for factor B and C5 animals deficient for C4 were susceptible to AAV development by injection of anti-MPO antibodies emphasized the specific involvement of the alternative pathway. Consonantly, the C5a receptor (Cd88) blockade was found to protect mice from MPO-AAV. CCX168, i.e., avacopan, a powerful inhibitor of C5a receptor that can be administered orally, was shown to reduce the proinflammatory effects of C5a and abolish the activation of neutrophils, their migration and adherence to endothelium, and the vascular endothelial cell retraction that increases permeability. Summary: Avacopan was found to be safe in healthy volunteers given a wide range of doses in a phase 1 clinical trial. The phase 2 trial CLEAR assessed the possibility to decrease dose or entirely replace glucocorticosteroids in the standard-of-care therapy of AAV. Avacopan, added to CYC or RTX either in combination with GCs or not, shortened the time to remission in patients with either newly diagnosed or relapsing AAV. The phase 3 ADVOCATE study compared the ability of an avacopan-associated regimen to induce and sustain remission in AAV patients versus a conventional GC-associated scheme. Remission at week 26 was observed in 72.3% of patients given avacopan and in 70.1% of those given prednisone. Sustained remission at week 52 (second primary endpoint) was obtained in 65.7% of patients given avacopan and in 54.9% receiving prednisone. The avacopan-associated regimen was noninferior at week 26 and superior at week 52 in sustaining remission as compared to the GC-based scheme. Key Messages: The results of the ADVOCATE trial opened new prospects for the treatment of AAV and also other immune-mediated diseases with renal involvement. The possible position of avacopan in a routine clinical setting and its possible indications in specific subsets of patients with AAV are extensively discussed. [ABSTRACT FROM AUTHOR]

Patients with antineutrophil cytoplasmic antibody‐associated vasculitis (AAV) are vulnerable to opportunistic infections, including cytomegalovirus (CMV) infection. This narrative review aims to identify factors associated with CMV infection in patients with AAV. The literature review was conducted on Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane, PubMed, Scopus, and Web of Science. The start date of the literature search was unrestricted and the end date was February 2022. CMV infection was defined as (a) CMV pp65 antigenemia or positive CMV DNA viral load by polymerase chain reaction or CMV detection on histological specimens, with associated signs and symptoms compatible with CMV infection; (b) presence of CMV clinical syndrome (defined as presence of compatible symptoms and signs and documentation of CMV by biopsy by virus isolation, rapid culture, immunohistochemistry, or DNA in biopsy material as defined by the CMV Drug Development Forum); and (c) CMV infection as coded by the International Statistical Classification of Diseases and Related Health Problems, 10th revision with at least one prescription for CMV treatment. We identified 4505 articles, of which three (2327 patients with AAV) were included. All studies were retrospective and only one of the three studies included only patients with AAV. Low or decreasing lymphocyte counts and higher prednisolone usage were associated with CMV infection in patients with AAV. Patients with AAV with lymphopenia and on high doses of prednisolone should be monitored closely for signs and symptoms of CMV infection, and might benefit from CMV prophylaxis. Prospective studies are urgently needed to better identify causes of CMV infections in patients with AAV. [ABSTRACT FROM AUTHOR]

The antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a systematic of relatively rare autoimmune diseases with unknown cause. Kidney involvement is one of the most common clinical manifestations, and the degree of renal damage is closely associated with the development and prognosis of AAV. In this study, we utilized the Robust Rank Aggreg (RRA) method in R to integrate GSE104948, GSE104954, GSE108109, GSE108112, and GSE108113 profile datasets loaded from Gene Expression Omnibus (GEO) database and identified a set of differentially expressed genes (DEGs) in kidney between AAV patients and living donors. Then, the results of gene ontology (GO) functional annotation showed that immunity and metabolism involved process of AAV both in glomerulus and tubulointerstitial. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that following pathways, such as complement and coagulation cascades pathway; Staphylococcus aureus infection; disease-COVID-19; and systemic lupus erythematosus (SLE) pathway play a crucial role in AAV. Next, the results analyzed by protein–protein interaction (PPI) network and Cytoscape software exhibited the hub genes ALB, TYROBP, and CYBB existed in both glomerular and tubulointerstitial compartments datasets. Finally, KEGG analysis using genes of two most important modules also further validated complement and coagulation cascades pathway and S. aureus infection existed both in glomerulus and tubulointerstitial compartments datasets. In conclusion, this study identified key genes and pathways involved in kidney of AAV, which was benefit to further uncover the mechanisms underlying the development and progress of AAV, biomarkers, and potential therapeutic targets as well. [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., (Copyright © 2024 by the Journal of Rheumatology.)

Abstract Background Dysthyroid optic neuropathy is the most commonly suspected diagnosis of optic neuropathy in Graves’ patients; however, other causes need to be ruled out. We present a unique case of optic neuropathy secondary to hypertrophic pachymeningitis with antineutrophil cytoplasmic antibody-associated vasculitis, which was suspected to be antithyroid drug related. Case presentation A 79-year-old Japanese male presented with acute visual loss in the left eye. He had a 24-year history of Graves’ disease and was taking methimazole. Best-corrected visual acuity was 0.8 in the right eye and light perception in the left eye, and relative afferent pupillary defect in the left eye was seen. Ocular movement was normal, and there were no findings explaining visual loss in intermediate optic media and fundus in the left eye. Contrast-enhanced magnetic resonance imaging demonstrated thickened dura mater. Tests for myeloperoxidase-antineutrophil cytoplasmic antibody, proteinuria, and hematuria were positive; pulmonary nodule lesions and a blood clot in the left lower leg were also found. After excluding the presence of diseases that could lead to hypertrophic pachymeningitis, we diagnosed optic neuropathy due to hypertrophic pachymeningitis with granulomatosis with polyangiitis—a subtype of antineutrophil cytoplasmic antibody-associated vasculitis. Since he had history of using methimazole, antineutrophil cytoplasmic antibody-associated vasculitis was considered as drug related. We started high-dosage steroid pulse therapy followed by 1 mg/kg body weight daily of oral prednisolone, and subsequently tapered. Methimazole was stopped. Best-corrected visual acuity recovered to 0.9, 2 weeks after starting treatment. Though myeloperoxidase-antineutrophil cytoplasmic antibody remained negative, the symptom relapsed 6 months after treatment initiation. We gave a second high-dose steroid pulse therapy followed by prednisolone tapered together with methotrexate. Remission remained, and using 4 mg/week methotrexate without prednisolone, myeloperoxidase-antineutrophil cytoplasmic antibody was kept within the normal limit until now, 4 years after onset. Conclusion We present a case of optic neuropathy with hypertrophic pachymeningitis related to antineutrophil cytoplasmic antibody-associated vasculitis, which was suspected to be drug related. The patient had good visual recovery after quitting the drug and receiving immunosuppressive therapy with systemic steroids. Hypertrophic pachymeningitis with antineutrophil cytoplasmic antibody-associated vasculitis related to antithyroid drugs should be considered as a differential diagnosis for optic neuropathy in Graves’ patients in whom optic nerve compression is not obvious.

Concomitant lupus nephritis and antineutrophil cytoplasmic antibody-positive crescentic glomerulonephritis is rare, and there is little guidance on the management and outcomes of these patients. A Hispanic woman in her early 40s with no contributory medical history presented with 3 weeks of cough, shortness of breath, fever, and malaise. Laboratory test results were notable for serum creatinine level of 17.4 mg/dL (previously normal), urinalysis with a high hemoglobin level, >182 red blood cell count, and urinary protein-creatinine ratio of 5.72 g/g. Serologies showed elevated dsDNA, ribonucleoprotein antibody, Smith antibody, myeloperoxidase antibody, positive antinuclear antibody, and low complement levels. She was urgently started on hemodialysis and solumedrol 1 g for 3 days. On day 2, she had a kidney biopsy, which showed necrotizing crescentic glomerulonephritis and immunofluorescence with “full house” pattern, immune complex deposits, and strong antinuclear antibody staining of nuclei. She developed diffuse alveolar hemorrhage and was initiated on plasmapheresis and cyclophosphamide. She improved and was discharged without needing further dialysis. Clinicians should consider systemic lupus erythematosus and antineutrophil cytoplasmic antibody disease overlap syndrome when a young, female patient presents with new kidney failure and alveolar hemorrhage. Early biopsy and aggressive treatment are essential in preserving kidney function, and plasmapheresis should be considered in severe cases. This is a severe case with a positive outcome.

Background and Objectives: Treatment for antineutrophil cytoplasmic antibody-associated vasculitis (AAV) must deal with immunosuppression, as well as infections associated with a compromised immune system, such as tuberculosis (TB). Our aim was to examine the risk of incidental TB after diagnosis of AAV. Materials and Methods: This retrospective population-based cohort study was based on the data from the National Health Insurance Research Database in Taiwan. Patients with newly diagnosed granulomatous polyangiitis or microscopic polyangiitis were identified between 1 January 2000 and 31 December 2012. The primary outcome was risk of incidental TB. Cox proportional hazard models were used to evaluate the association between AAV and incidental TB. Results: A total of 2257 patients with AAV and a propensity-score matched cohort of 9028 patients were studied. Overall, patients with AAV were at a 1.48× higher risk of contracting incidental TB than the patients in the matched cohort (adjusted HR 1.48; 95% confidence interval [CI], 1.02–2.15). Note that the highest risk of contracting incidental TB was in the first two years following a diagnosis of AAV, with a nearly 1-fold increase in risk (adjusted HR, 1.91; 95% CI, 1.01–3.60). Female AAV patients were 3.24× more likely than females without AAV to develop TB (adjusted HR 3.24; 95% CI, 1.85–5.67). Conclusions: Patients with AAV exhibit a 48% elevated TB risk, notably, a 91% increase within the first two years postdiagnosis. Female AAV patients face a 3.24 times higher TB risk compared to females without AAV. This study is limited by potential misclassification and overestimation of AAV cases. Clinicians should closely monitor TB risk in AAV patients, especially in females and the initial two years following diagnosis.

Abstract Background Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis usually induces rapidly progressive glomerulonephritis, including pauci-immune necrotizing crescentic glomerulonephritis. Acute tubulointerstitial nephritis (ATIN), which is often drug-induced, is a frequent cause of kidney injury. However, ATIN associated with ANCA without any glomerular lesions has been rarely reported, and drug-induced ATIN associated with ANCA is not well recognized. Here we present a case of an older woman with ATIN associated with myeloperoxidase-ANCA (MPO-ANCA) following cimetidine treatment. Case presentation A 70-year-old woman was admitted to our hospital due to acute kidney injury and mild proteinuria. She had a one-year history of chronic thyroiditis and dyslipidemia, for which she was taking levothyroxine sodium and atorvastatin, respectively. Two weeks before admission she had started cimetidine, methylmethionine sulfonium chloride, and itopride hydrochloride for gastric discomfort persistent since a month. She had experienced fatigue for two weeks and later appetite loss. The patient demonstrated a positive titer for MPO-ANCA (192 IU/mL) and a positive drug-induced lymphocyte stimulation test for cimetidine. She underwent two kidney biopsies that revealed ATIN without any glomerular lesions. Despite discontinuation of cimetidine on admission, renal injury continued with the presence of high MPO-ANCA titer. Oral steroid treatment was closely related with the recovery of her renal function and disappearance of MPO-ANCA. Conclusions In this case, ATIN presented as sustained renal insufficiency and high MPO-ANCA titer despite withdrawal of cimetidine. Therefore, we reason that the development of ANCA-associated ATIN was caused by cimetidine. Serologic follow-up with measurement of MPO-ANCA titers and renal biopsy are recommended when the clinical history is inconsistent with the relatively benign course of drug-induced ATIN.

Many reports have described a high incidence of acute kidney injury (AKI) among patients with COVID-19. Acute tubular necrosis has been reported to be the most common damage in these patients, probably due to hemodynamic instability. However, other complex processes may be involved, related to the cytokine storm and the activation of innate and adaptive immunity. Here, we describe a patient who developed an antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis with rapidly progressive glomerulonephritis and lung involvement and an antiphospholipid syndrome soon after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. After viral pneumonia was excluded by bronchoalveolar lavage, the patient has been treated with rituximab for amelioration of kidney function and resolution of thrombosis without any adverse event. We conclude that COVID-19 may trigger autoimmune diseases including ANCA-associated vasculitis. Thus, this diagnosis should be taken in consideration in COVID-19 patients, especially when they develop AKI with active urinary sediment. In addition, considering the relationship between these 2 diseases, SARS-CoV-2 infection should be excluded in all patients with a new diagnosis ANCA-associated vasculitis before starting immunosuppressive therapy.

Background/Aims We compared the clinical and laboratory data between elderly and non-elderly patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) at diagnosis; further, we investigated the predictors at diagnosis for all-cause mortality and end-stage renal disease (ESRD) occurrence during follow-up in Korean elderly patients with AAV. Methods We reviewed the medical records of 191 AAV patients regarding clinical manifestations and laboratory results at diagnosis and during follow-up. The follow-up duration was defined as the period from diagnosis to death for deceased patients or to the time of dialysis for ESRD patients, or to the last visit. Elderly (n = 67) and non-elderly (n = 124) patients were grouped based on an age threshold of 65 years. Results At diagnosis, elderly patients exhibited higher median Birmingham Vasculitis Activity Score (BVAS) and higher frequencies of ANCA positivity and pulmonary manifestations than non-elderly patients. Furthermore, elderly patients exhibited increased median white blood cell count, blood urea nitrogen (BUN), alkaline phosphatase, erythrocyte sedimentation rate, and C-reactive protein and decreased median hemoglobin. However, there were no significant differences in all-cause mortality and ESRD occurrence between elderly and non-elderly patients. Meanwhile, elderly patients exhibited lower cumulative patients’ and ESRD-free survival rates than non-elderly patients. In the multivariable Cox hazards model, BUN, creatinine and serum albumin at diagnosis were independent predictors for ESRD occurrence, whereas there were no independent predictors at diagnosis for all-cause mortality. Conclusions Elderly AAV patients exhibited substantially higher rates of all-cause mortality and ESRD occurrence during follow-up compared than non-elderly AAV patients.

The microbiome has been implicated in small-, medium-, large-, and variable-vessel vasculitis. Dysbiosis can frequently be found in vasculitis patients with altered microbial diversity and abundance, compared with those with other diseases and healthy controls. Dominant bacteria discovered in different studies vary greatly, but in general, the intestinal microbiome in vasculitis patients tends to contain more pathogenic and less beneficial bacteria. Improvement or resolution of dysbiosis has been observed after treatment in a few longitudinal studies. In addition, some molecular changes in intestinal permeability and immune response have been found in animal models of vasculitis diseases. [ABSTRACT FROM AUTHOR]