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Anti-neutrophil cytoplasmic antibodies (ANCA)-associated systemic vasculitis (AASV) is a rare systemic immunological condition that predominantly impacts small arteries, veins, and capillaries, often leading to kidney damage and pulmonary injury. It is important to note that individuals primarily presenting with peripheral neuropathy (PN) are uncommon in AASV, which can result in significant misdiagnosis or undiagnosed cases. The severity and location of PN can vary among patients. In this article, we present a case of an AASV patient initially showing signs of PN. This case highlights the significance of considering AASV as a potential cause of unexplained neurological symptoms. Timely identification and proper treatment are essential for improving the survival rate and functional prognosis of AASV patients. [ABSTRACT FROM AUTHOR]

Chronic primary systemic vasculitis (PSV) comprises a group of heterogeneous diseases that are broadly classified by affected blood vessel size, clinical traits and the presence (or absence) of anti-neutrophil cytoplasmic antibodies (ANCA) against proteinase 3 (PR3) and myeloperoxidase (MPO). In small vessel vasculitis (SVV), ANCA are not present in all patients, and they are rarely detected in patients with vasculitis involving medium (MVV) and large (LVV) blood vessels. Some studies have demonstrated that lysosome-associated membrane protein-2 (LAMP-2/CD107b) is a target of ANCA in SVV, but its presence and prognostic value in childhood MVV and LVV is not known. This study utilized retrospective sera and clinical data obtained from 90 children and adolescents with chronic PSV affecting small (SVV, n = 53), medium (MVV, n = 16), and large (LVV, n = 21) blood vessels. LAMP-2-ANCA were measured in time-of-diagnosis sera using a custom electrochemiluminescence assay. The threshold for seropositivity was established in a comparator cohort of patients with systemic autoinflammatory disease. The proportion of LAMP-2-ANCA-seropositive individuals and sera concentrations of LAMP-2-ANCA were assessed for associations with overall and organ-specific disease activity at diagnosis and one-year follow up. This study demonstrated a greater time-of-diagnosis prevalence and sera concentration of LAMP-2-ANCA in MVV (52.9% seropositive) and LVV (76.2%) compared to SVV (45.3%). Further, LAMP-2-ANCA-seropositive individuals had significantly lower overall, but not organ-specific, disease activity at diagnosis. This did not, however, result in a greater reduction in disease activity or the likelihood of achieving inactive disease one-year after diagnosis. The results of this study demonstrate particularly high prevalence and concentration of LAMP-2-ANCA in chronic PSV that affects large blood vessels and is seronegative for traditional ANCA. Our findings invite reconsideration of roles for autoantigens other than MPO and PR3 in pediatric vasculitis, particularly in medium- and large-sized blood vessels. [ABSTRACT FROM AUTHOR]

Nephrotic range proteinuria in the setting of dual-positive anti-glomerular basement membrane (AGBM) and anti-neutrophil cytoplasmic antibodies (ANCAs) is rare. Furthermore, using rituximab as a primary immunosuppressant along with steroids and plasmapheresis has not been widely studied. We present a case of dual AGBM and ANCA with nephrotic range proteinuria in a young female, where rituximab was used as a primary immunosuppressant with partial recovery. [ABSTRACT FROM AUTHOR]

Objective To investigate the clinical significance of ANCA in the disease activity of patients with SLE. Methods A total of 1 025 SLE patients were recruited and were divided into inactive and active groups according to SLEDAI score. Demographic characteristics, clinical symptoms, autoantibodies, routine laboratory tests and renal pathology were also recorded and compared between the two groups. Results All patients were divided into inactive group (n = 750) and active group (n = 250). The occurrence of renal, pulmonary, cutaneous, arthritis manifestations were significantly higher than those of the inactive group (all P < 0.05). All patients were tested for ANCA, and the most common pattern being perinuclear or p-ANCA, the percentage of p-ANCA seropositive increased greatly with the increased disease activity (P < 0.05). The autoantibodies were further analyzed between the two groups, 25 patients had reactivity to MPO, but no patient had reactivity to PR3. Also, there were significant differences in anti-dsDNA antibody, anti-nucleosome antibody between the two groups (P < 0.05). In the active group, patients with p-ANCA seropositive exhibited higher serum beta-2-microglobulin (β2-MG), titers of anti-dsDNA antibody, SLEDAI scores, lower albumin, C3, and C4 levels (P < 0.05). Meanwhile, p-ANCA was associated with IL-6, which increased significantly with the increase of SLEDAI score. In addition, patients with p-ANCA seropositive had more occurrence of lupus nephritis, but it had no association with the renal pathology. Conclusion The appearance of p-ANCA in SLE patients indicated more severe disease activity status. [ABSTRACT FROM AUTHOR]

Granulomatosis with polyangiitis (GPA) is a rare systemic disease characterized by granulomatous inflammation of the respiratory tract and necrotizing vasculitis of small and medium vessels often associated with the production of anti-neutrophil cytoplasmic antibodies (ANCA) directed mainly against leukocyte proteinase 3 (PR3). Usually, it involves upper airways, lungs, and kidneys, however any organ may be affected. The diagnosis is based on clinical, radiological, and serological findings. Biopsies, although strongly recommended, are not always feasible and often provides non-specific features. ANCA plays a crucial role in the diagnosis of GPA; nevertheless, ANCA detection is not a substitute for biopsy, which plays an important role in suspected cases, particularly when histological confirmation cannot be obtained. Significant advances have been made in classification criteria and phenotyping of the disease, particularly in determining the nuances between PR3-ANCA and myeloperoxidase (MPO)-ANCA vasculitis. This has led to better characterization of patients and the development of targeted treatment in the future. In addition, better identification of cytokine and immunological profiles may result in immuno-phenotyping becoming a new approach to identify patients with ANCA-associated vasculitis (AAV). Due to the chronic relapsing–remitting nature, strict follow-up of GPA is necessary to provide appropriate management. The search for the accurate marker of disease activity and to predict relapse is still ongoing and no predictor has been found to reliably guide therapeutic decision-making.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of systemic diseases caused by a combination of many factors, including genetics, environment, and immunity. AAV is characterized by predominantly small-vessel involvement and has a variety of clinical manifestations. Small-vessel lesions of the kidneys and lungs are common, and lesions of medium-sized arteries may also present, but the involvement of large arteries and their primary branches is very rare. This report delineates two instances of AAV with large arterial involvement, one case presenting with lesions of the aortic valve and the other with lesions of the pulmonary artery. The first case involved a 57-year-old man with no underlying diseases. Transthoracic echocardiography showed thickening of the left and right coronary valves of the aortic valve with enhanced echogenicity, moderate echogenic masses were seen on both valve leaflets, and the leaflets had restricted opening and poor closure. Blood tests showed positive perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA) and anti-myeloperoxidase (MPO) antibodies. The patient's aortic valve thickening virtually disappeared after treatment with hormones combined with immunosuppressive agents. The second case involved a 60-year-old woman whose transthoracic echocardiography and CT (computed tomography) angiography of the pulmonary arteries showed wall thickening of the main pulmonary artery and the proximal left and right pulmonary arteries, leading to luminal stenosis. Blood tests showed positive cytoplasmic anti-neutrophil cytoplasmic antibodies (c-ANCA) and anti-proteinase 3 (PR 3) antibodies. The patient's pulmonary artery wall thickening reduced after receiving hormones in combination with immunosuppression but she died of heart failure during subsequent treatment. The patient had been diagnosed with tuberculosis six months earlier and had been poorly treated with anti-tuberculosis therapy. The involvement of large arteries in AAV is a rare and critical condition with rapid progression and a high mortality rate. Early recognition of this type of AAV and aggressive immunosuppressive therapy may facilitate the reversal of the vascular lesion and a reduction in the risk of patient death.

To investigate the clinical features and long-term outcomes of Chinese anti-neutrophil cytoplasmic antibodies (ANCAs)-associated vasculitis (AAV) patients with different ANCA serotypes. Two hundred and twenty-four AAV patients from January 2010 to June 2021 were divided into myeloperoxidase (MPO)-ANCA and proteinase 3 (PR3)-ANCA groups. Clinical and long-term outcomes were compared. In this study, the average follow-up was 46.4 months (range 0.3–188.4 months). One hundred and seventy-seven (79.0%) patients were MPO–ANCA-positive and 47 were PR3–ANCA-positive; the mean age of MPO–ANCA positive patients at diagnosis was elder than that of PR3–ANCA positive patients (67.0 vs. 60.0 years, p =.004). Among PR3–ANCA-positive patients, ear, nose and throat symptoms were more common (p =.014). Between two ANCA serotypes, there were no differences in complement 3 (C3), Birmingham vasculitis activity score (BVAS), five-factor score (FFS) or other organ involvements. For all AAV patients, the overall survival rates at one, three and five years were 80.0%, 67.0% and 56.4%, respectively. The cumulative relapse-free rates of one, three and five years were 89.5%, 76.4% and 68.4%, respectively. The survival of AAV patients was unaffected by the ANCA serotype (p =.23). The ANCA serotype also had no effect on either disease relapse (p =.20) or remission rates (p =.10). In our study, PR3–ANCA patients showed a better long-term survival, as the 5-year survival rate and the 5-year relapse-free survival rate of PR3–ANCA patients were 60.7% and 76.9%, while that of MPO–ANCA patients were 55.2% and 65.8%, respectively. Rather than ANCA serotype, younger patients with milder kidney involvement and lower disease assessment scores (BVAS and FFS) might be more relevant to better prognosis. The likelihood of induced remission, patient survival or disease recurrence is all unaffected by ANCA serotypes. A better prognosis is seen in younger patients with milder kidney involvement and lower BVAS/FFS scores. [ABSTRACT FROM AUTHOR]

To investigate the clinical characteristics, pathological features, and outcomes of patients with antineutrophil cytoplasmic antibody (ANCA)-positive systemic lupus erythematosus (SLE) in northwest China. This retrospective study included 491 patients with SLE tested for ANCA antibodies and 171 patients with ANCA-associated vasculitis (AAV) as controls. Subgroup analysis limited to those with renal involvement, and by ANCA antibody subtype (PR3 vs MPO). To compare the proteinuria remission rates between ANCA-positive and ANCA-negative lupus nephritis (LN) groups, a logistic regression model was used for propensity score matching based on age, hemoglobin, and baseline estimated glomerular filtration rate (eGFR). Compared to ANCA-negative SLE (n = 442), ANCA-positive SLE (n = 46) occur in older patients; however, these patients were younger than those with AAV (n = 167). The eGFR of patients with ANCA-positive LN (n = 25) was higher than that of patients having AAV with renal involvement (n = 56) but lower than that of patients with ANCA-negative LN (n = 163). Patients with SLE who had MPO-ANCA (n = 16) had higher levels of serum creatinine compared to those with PR3-ANCA (n = 30) (156.5 µmol/L vs. 45.5 µmol/L, p = 0.005). During the follow-up period, the remission rate of proteinuria in patients with ANCA-positive LN was lower than that of patients with ANCA-negative LN (50% vs. 75%, p = 0.008). Patients with ANCA-positive LN may have worse baseline renal function and lower protein remission rates compared to patients with ANCA-negative LN. ANCA titers should be regularly monitored throughout the follow-up period in patients with SLE, especially in cases of renal involvement. [ABSTRACT FROM AUTHOR]

Introduction: Anti-glomerular basement membrane (anti-GBM) disease is a rare organ-specific autoimmune disease. The overall and renal outcomes of patients have mostly been reported in small-sized cohorts. We aimed to study the clinical profile, overall survival, and renal survival of anti-glomerular basement membrane disease patients at our center. Methods: We conducted a retrospective analysis of the data regarding the clinical profile and renal survival of patients diagnosed with anti-GBM disease from October 2019 to March 2022, having a minimum follow-up of 12 months. Results: There were 15 patients in the study, with the mean age of presentation being 51.6 ± 13.7 years. The median duration of symptoms onset to the nephrologist opinion was 15 (10–23) days. The extrarenal manifestations were seen in the respiratory, otorhinolaryngological, and neurological systems. The mean serum anti-GBM titers were 154.5 (14.9–263.5) U/mL. Serum anti-GBM titers were present in 13/15 (86.6%) patients, and 12/13 (92.3%) patients had above the reference range. Anti-neutrophil cytoplasm antibody (ANCA) levels were assessed in 12/15 (80%) patients, and 9/12 (75%) had higher levels. Renal biopsy was available in 14 patients with more than 50% crescents. Along with crescents, necrotizing lesions, rupture of the Bowman’s capsule, and granulomatous lesions were also seen. Among the initial therapies, the steroid pulse was given to 13 (86.6%) patients, whereas membrane plasmapheresis was given to 8 (53.3%) patients. Inj. cyclophosphamide and inj. rituximab were given to 8 (53.3%) and 4 (26.6%) patients, respectively. No difference was seen in clinical characteristics, renal biopsy features, treatment received, and outcomes with ANCA positivity except for age, where patients who were ANCA positive were older compared to patients who were ANCA negative. One-year renal and patient survival was seen in 4 (26.6%) and 6 (40%) patients, respectively. Conclusion: Most patients of anti-GBM disease have active sediments, raised creatinine, and non-specific symptomatology. There is poor renal and patient outcome as most patients present with advanced renal failure.

AbstractObjectives To investigate the clinical features and long-term outcomes of Chinese anti-neutrophil cytoplasmic antibodies (ANCAs)-associated vasculitis (AAV) patients with different ANCA serotypes.Methods Two hundred and twenty-four AAV patients from January 2010 to June 2021 were divided into myeloperoxidase (MPO)-ANCA and proteinase 3 (PR3)-ANCA groups. Clinical and long-term outcomes were compared.Results In this study, the average follow-up was 46.4 months (range 0.3–188.4 months). One hundred and seventy-seven (79.0%) patients were MPO–ANCA-positive and 47 were PR3–ANCA-positive; the mean age of MPO–ANCA positive patients at diagnosis was elder than that of PR3–ANCA positive patients (67.0 vs. 60.0 years, p = .004). Among PR3–ANCA-positive patients, ear, nose and throat symptoms were more common (p = .014). Between two ANCA serotypes, there were no differences in complement 3 (C3), Birmingham vasculitis activity score (BVAS), five-factor score (FFS) or other organ involvements. For all AAV patients, the overall survival rates at one, three and five years were 80.0%, 67.0% and 56.4%, respectively. The cumulative relapse-free rates of one, three and five years were 89.5%, 76.4% and 68.4%, respectively. The survival of AAV patients was unaffected by the ANCA serotype (p = .23). The ANCA serotype also had no effect on either disease relapse (p = .20) or remission rates (p = .10). In our study, PR3–ANCA patients showed a better long-term survival, as the 5-year survival rate and the 5-year relapse-free survival rate of PR3–ANCA patients were 60.7% and 76.9%, while that of MPO–ANCA patients were 55.2% and 65.8%, respectively. Rather than ANCA serotype, younger patients with milder kidney involvement and lower disease assessment scores (BVAS and FFS) might be more relevant to better prognosis.Conclusions The likelihood of induced remission, patient survival or disease recurrence is all unaffected by ANCA serotypes. A better prognosis is seen in younger patients with milder kidney involvement and lower BVAS/FFS scores.

AbstractPurpose To investigate the clinical characteristics, pathological features, and outcomes of patients with antineutrophil cytoplasmic antibody (ANCA)-positive systemic lupus erythematosus (SLE) in northwest China.Methods This retrospective study included 491 patients with SLE tested for ANCA antibodies and 171 patients with ANCA-associated vasculitis (AAV) as controls. Subgroup analysis limited to those with renal involvement, and by ANCA antibody subtype (PR3 vs MPO). To compare the proteinuria remission rates between ANCA-positive and ANCA-negative lupus nephritis (LN) groups, a logistic regression model was used for propensity score matching based on age, hemoglobin, and baseline estimated glomerular filtration rate (eGFR).Results Compared to ANCA-negative SLE (n = 442), ANCA-positive SLE (n = 46) occur in older patients; however, these patients were younger than those with AAV (n = 167). The eGFR of patients with ANCA-positive LN (n = 25) was higher than that of patients having AAV with renal involvement (n = 56) but lower than that of patients with ANCA-negative LN (n = 163). Patients with SLE who had MPO-ANCA (n = 16) had higher levels of serum creatinine compared to those with PR3-ANCA (n = 30) (156.5 µmol/L vs. 45.5 µmol/L, p = 0.005). During the follow-up period, the remission rate of proteinuria in patients with ANCA-positive LN was lower than that of patients with ANCA-negative LN (50% vs. 75%, p = 0.008).Conclusion Patients with ANCA-positive LN may have worse baseline renal function and lower protein remission rates compared to patients with ANCA-negative LN. ANCA titers should be regularly monitored throughout the follow-up period in patients with SLE, especially in cases of renal involvement.

Anti-neutrophil cytoplasmic antibodies (ANCA) are mainly associated with medium and small vessel vasculitis. Two main methodologies currently available for detection of these antibodies are indirect immunofluorescence (IIF) and monospecific proteinase 3 (PR3) and myeloperoxidase (MPO) based immunoassays. However, well-defined guidelines regarding mode of testing for ANCA in laboratories still don't exist, leading to problems in diagnosis and further patient management. Anti-neutrophil cytoplasmic antibodies testing by IIF and enzyme linked immunosorbent assay (ELISA) often pose a significant challenge in diseases other than vasculitis and in overlapping autoimmune conditions. Anti-neutrophil cytoplasmic antibodies reporting by IIF can be challenging in certain circumstances. This case series aims to discuss four cases with probable interference of anti-nuclear antibodies (ANA) during ANCA testing by IIF resulting in ANCA false positivity. All four cases on subsequent reflex testing by line immunoassay (LIA) for PR3, MPO and glomerular basement membrane (GBM) antigens proved otherwise. While analysing for the presence of ANCA by IIF, the possible interference of ANA leading to a false positive ANCA result should be kept in mind and alternative methods of testing like ELISA, extended granulocyte based IIF assays with MPO and PR3 coated beads, etc., should also be advised. Probability of atypical ANCA in diseases other than vasculitis should also be considered in case of ambiguous results. [ABSTRACT FROM AUTHOR]

Abstract Background Anti-glomerular basement membrane (GBM) disease and ANCA-associated vasculitis (AAV) diseases are rare. It is associated with variable renal manifestations and increased mortality, thus requiring early aggressive treatment to minimize adverse outcomes and improve prognosis. Case presentation We present the case of a male patient with 1-month onset of asthenia, adynamia, oliguria, and weight loss. Initial laboratory findings were indicative of severe kidney dysfunction. The urinalysis showed active sediment, but the urinary tract ultrasound was unaltered. As these findings were consistent with rapidly progressive glomerulonephritis, he received steroid pulses, and given the severity of the condition, renal replacement therapy was initiated. Other diagnostic tests revealed MPO-ANCA antibody levels of 26 mg/dl, pANCAs 1/320, and anti-GBM of 8 mg/dl. Kidney biopsy evidenced necrotizing glomerulonephritis with extracapillary proliferation in 90% of the glomeruli. The patient received plasma exchange (PE) therapy and intravenous (IV) cyclophosphamide (CYC) cycles; however, he presented with severe alveolar hemorrhage requiring the completion of 21 PE sessions and 3 CYC boluses. Pulmonary symptoms resolved, but the patient persisted dependent on dialysis. During the outpatient follow-up, monthly CYC were prescribed until circulating antibody levels were normal; however, the patient did not recover full kidney function and remained dependent on renal support. Conclusions Anti-GBM and AAV diseases are rare; therefore, anti-GBM antibodies should be screened simultaneously in patients with ANCA positive, especially in older patients, due to the early morbidity and mortality typical of anti-GBM disease with comparable disease severity it represents.

Nephrotic range proteinuria in the setting of dual-positive anti-glomerular basement membrane (AGBM) and anti-neutrophil cytoplasmic antibodies (ANCAs) is rare. Furthermore, using rituximab as a primary immunosuppressant along with steroids and plasmapheresis has not been widely studied. We present a case of dual AGBM and ANCA with nephrotic range proteinuria in a young female, where rituximab was used as a primary immunosuppressant with partial recovery.

Eosinophilic granulomatosis with polyangiitis (EGPA) is an antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, mostly affecting small-sized arteries and usually occurring in patients with an allergic background. Eosinophils seem to play a significant role in the pathogenesis of the disease and, therefore, biologics targeting interleukin 5 (IL5), a cytokine tightly linked to eosinophils, have emerged as a promising therapeutic tool. A systematic review of Medline was conducted from 2007 to 2022 to search for data regarding the use of anti-IL5 therapies in patients with EGPA. Ongoing or unpublished trials were also searched in ClinicalTrials.gov and the World Health Organization trials portal. The efficacy and safety of mepolizumab, an anti-IL5 monoclonal antibody (mAb), was confirmed by a randomized controlled trial (RCT), although a significant proportion of patients did not respond to this treatment. Other studies showed that both doses of 100 mg and 300 mg of mepolizumab are almost equally effective in EGPA. Benralizumab, an anti-IL5 receptor mAb has preliminary promising results and an RCT is planned to be conducted. Apart from their clinical efficacy in EGPA, anti-IL5 therapies may have steroid-sparing properties. Anti-IL5 therapies seem to be effective and safe in patients with refractory/relapsing EGPA and can be used as a steroid-sparing treatment. Nevertheless, more research is needed to clarify the pathophysiology of the disease; this may potentially lead to the identification of biomarkers to pinpoint patients most likely to respond to anti-IL5-blockade. [ABSTRACT FROM AUTHOR]

Miranti Pangastuti, Trustia Rizqandaru, Oki Suwarsa, Hartati Purbo Dharmadji, Endang Sutedja Department of Dermatology and Venereology, Faculty of Medicine, Universitas Padjadjaran - Dr. Hasan Sadikin Hospital, Bandung, IndonesiaCorrespondence: Miranti Pangastuti, Department of Dermatology and Venereology, Faculty of Medicine, Universitas Padjadjaran - Dr. Hasan Sadikin Hospital, Jl. Pasteur 38, Bandung, West Java, 40161, Indonesia, Tel +6281223114874, Email pangastuti.miranti@gmail.comAbstract: Bullous dermatoses is a heterogeneous group of blistering skin disorders that can either be inherited or acquired. Subepidermal blisters may result in ulceration and scarring following their rupture. Wegener’s granulomatosis (WG) is a granulomatous necrotizing vasculitis affecting small- to medium-sized blood vessels. It is associated with anti-neutrophil cytoplasmic antibodies (ANCA) and can be manifested cutaneously as multiple bullous and ulcers. A case of WG was reported in an 18-year-old man presented with multiple skin bullous and ulcers. The patient was diagnosed with WG based on the findings from nasopharyngoscopy examination that revealed crusts in his nasal cavity; necrotizing granulomatous appearance on chest radiograph; hematuria on urinalysis; and positive ANCA blood test. This patient received a combination of methylprednisolone and methotrexate, resulting in improvement within four weeks of therapy. His multiple skin ulcers were treated with a combination of dialkyl carbamoyl chloride, hydrocolloid, and hydrogel dressings. This patient was in complete remission state after six months of treatment, which later followed by a relapse episode that occurred within one year. WG with multiple skin bullous and ulcers can mimic other diseases. Various examinations such as histopathology, direct immunofluorescence, and ANCA blood test may aid in determining the etiology of skin bullous and ulcers.Keywords: anti-neutrophil cytoplasmic antibodies, bullous, ulcers, Wegener’s granulomatosis

Abstract Symptoms of Wilson disease (WD) vary and additional factors such as autoimmunity may play an important role in WD pathogenesis. The presence of antinuclear antibodies (ANA), anti‐neutrophil cytoplasmic antibodies, neuronal surface antibodies, and onconeural antibodies in WD was investigated using standardized indirect immunofluorescence assays and Western Blot analysis. The presence of all studied autoantibodies was higher in WD patients in comparison to healthy subjects, but there was no statistically significant difference in autoantibodies frequency according to disease manifestation. D‐penicillamine treatment was associated with a higher presence of ANA than zinc sulfate but without an increase in autoimmune diseases rate.

Background: Anti-glomerular basement membrane (GBM) disease and ANCA-associated vasculitis (AAV) diseases are rare. It is associated with variable renal manifestations and increased mortality, thus requiring early aggressive treatment to minimize adverse outcomes and improve prognosis. Case presentation: We present the case of a male patient with 1-month onset of asthenia, adynamia, oliguria, and weight loss. Initial laboratory findings were indicative of severe kidney dysfunction. The urinalysis showed active sediment, but the urinary tract ultrasound was unaltered. As these findings were consistent with rapidly progressive glomerulonephritis, he received steroid pulses, and given the severity of the condition, renal replacement therapy was initiated. Other diagnostic tests revealed MPO-ANCA antibody levels of 26 mg/dl, pANCAs 1/320, and anti-GBM of 8 mg/dl. Kidney biopsy evidenced necrotizing glomerulonephritis with extracapillary proliferation in 90% of the glomeruli. The patient received plasma exchange (PE) therapy and intravenous (IV) cyclophosphamide (CYC) cycles; however, he presented with severe alveolar hemorrhage requiring the completion of 21 PE sessions and 3 CYC boluses. Pulmonary symptoms resolved, but the patient persisted dependent on dialysis. During the outpatient follow-up, monthly CYC were prescribed until circulating antibody levels were normal; however, the patient did not recover full kidney function and remained dependent on renal support. Conclusions: Anti-GBM and AAV diseases are rare; therefore, anti-GBM antibodies should be screened simultaneously in patients with ANCA positive, especially in older patients, due to the early morbidity and mortality typical of anti-GBM disease with comparable disease severity it represents. [ABSTRACT FROM AUTHOR]

Aim: To elucidate the clinical features, long‐term survival, and prognostic factors for mortality among patients with microscopic polyangiitis (MPA), including those with anti‐neutrophil cytoplasmic antibody‐positive interstitial lung disease (ILD) (ANCA‐ILD), which could be a subset of its variant phenotype. Methods: We retrospectively included 76 consecutive patients between 2006 and 2014, diagnosed with MPA according to the European Medicines Agency algorithm using the Chapel Hill Consensus Conference definitions or ANCA‐ILD. ILD was classified as usual interstitial pneumonia (UIP) or nonspecific interstitial pneumonia pattern using chest computed tomography. Results: The mean (standard deviation) age of the patients (female, 68%) was 69 (12) years. The median (interquartile range) follow‐up period was 68 (33‐95) months. Comorbid ILD and glomerulonephritis were observed in 44 (58%) (68% UIP) and 54 (71%) patients, respectively. Comorbid ILD was associated with low survival (P =.0563). There were 17 (39%) and 5 (16%) deaths in the ILD and non‐ILD groups, respectively (P =.0404). In the ILD group, 6 and 5 of the deaths were attributed to infection and ILD progression, respectively. In the non‐ILD group, 1 and 2 patients expired from subsequently developed ILD and aspiration pneumonia, respectively. Age ≥ 70 years (hazard ratio = 2.78; 95% confidential interval 1.15‐6.70) and UIP (3.95; 1.60‐9.77) were independent risk factors for mortality. Conclusion: Age ≥ 70 years and ILD with a UIP pattern were associated with high mortality, owing to susceptibility to infection and ILD progression. A more effective and less toxic treatment is required for progressive ILD. [ABSTRACT FROM AUTHOR]

Background: The histopathological classification of ANCA-GN divides patients into four groups based on signs of glomerular injury. However, this classification did not consider age-related glomerulosclerosis. In this study, we aimed to compare the prediction of renal survival between Berden's ANCA-GN histopathological classification and ANCA-GN histopathological classification modified with age-related glomerulosclerosis. Methods: Between January 2004 and December 2019, 65 patients diagnosed with ANCA-GN were enrolled. Demographic, laboratory, and histopathologic findings were retrospectively analyzed. Renal survival analyses were compared according to classical and modified ANCA-GN histopathological classifications. Multivariate Cox regression analysis for the factors affecting renal survival was performed. Results: In Berden's ANCA-GN histopathological classification, 15 patients were in the focal group, 21 in the crescentic, 21 in the sclerotic, and 8 in the mixed group. The ANCA-GN histopathological classification model generated statistically significant predictions for renal survival (p = 0.022). When the histopathological classification was modified with age-related glomerulosclerosis, eight of the nine patients previously classified in the sclerotic group were classified in the mixed and one in the crescentic groups. Modification of histopathological classification with age-related glomerulosclerosis increases the statistical significance in renal survival analysis (p = 0.009). The multivariate Cox regression analysis showed that the disease-related global sclerotic glomeruli percentage and serum creatinine level were significant independent factors. Conclusion: Modification of Berden's ANCA-GN histopathological classification model with age-related glomerulosclerosis may increase the statistical significance of the histopathological classification model. [ABSTRACT FROM AUTHOR]

Chronic pulmonary infection is a hallmark of cystic fibrosis (CF) and requires continuous antibiotic treatment. In this context, Pseudomonas aeruginosa (Pa) is of special concern since colonizing strains frequently acquire multiple drug resistance (MDR). Bactericidal/permeability-increasing protein (BPI) is a neutrophil-derived, endogenous protein with high bactericidal potency against Gram-negative bacteria. However, a significant range of people with CF (PwCF) produce anti-neutrophil cytoplasmic antibodies against BPI (BPI-ANCA), thereby neutralizing its bactericidal function. In accordance with literature, we describe that 51.0% of a total of 39 PwCF expressed BPI-ANCA. Importantly, an orthologous protein to human BPI (huBPI) derived from the scorpionfish Sebastes schlegelii (scoBPI) completely escaped recognition by these autoantibodies. Moreover, scoBPI exhibited high anti-inflammatory potency towards Pa LPS and was bactericidal against MDR Pa derived from PwCF at nanomolar concentrations. In conclusion, our results highlight the potential of highly active orthologous proteins of huBPI in treatment of MDR Pa infections, especially in the presence of BPI-ANCA.

Background: Autoantibodies are vital biomarkers for the diagnosis, assessment and prognostic determination of various autoimmune disorders. Objective: This study aimed to evaluate the performance of the two AtheNA Multi-Lyte® systems for the detection of various autoantibodies. Methods: A total of 105 systemic lupus erythematosus patients, 35 patients with other autoimmune diseases (diseased controls), and 30 healthy volunteers (healthy controls) at Zagazig University Hospitals, Zagazig city, Al Sharqia governorate were tested for anti-double-stranded DNA (anti-dsDNA) antibodies using indirect immunofluorescence (IIF) and the AtheNA Multi-Lyte® anti-nuclear antibodies-II system between May 2020 and April 2022. Seventy-five patients with clinically suspected autoimmune vasculitis (AIV) and 25 healthy volunteers were also tested for anti-myeloperoxidase and anti-proteinase 3 antibodies using IIF, the AtheNA Multi-Lyte® AIV system, and enzyme-linked immunosorbent assay (ELISA). Results: The AtheNA anti-dsDNA test (98.5%) was more specific than IIF (96.9%) for diagnosing systemic lupus erythematosus, but both tests had the same sensitivity (38.1%). Combining both methods increased sensitivity to 47.6%, while increasing the cut-off of the AtheNA anti-dsDNA test to 134 international units/mL increased specificity to 100%. The AtheNA Multi-Lyte AIV system exhibited substantial agreement with IIF regarding anti-myeloperoxidase testing (κ = 0.65) and almost perfect agreement with ELISA (κ = 0.85). The AtheNA Multi-Lyte® AIV system exhibited perfect agreement with IIF (κ = 1) and substantial agreement with ELISA for anti-proteinase 3 testing (κ = 0.63). Conclusion: AtheNA Multi-Lyte® systems appear to be reliable for anti-dsDNA, anti-myeloperoxidase, and anti-proteinase 3 screening and may be an optimal choice for monitoring anti-dsDNA levels. What this study adds: It is necessary to evaluate various autoantibodies detection assays to increase both sensitivity and specificity of autoimmune diseases diagnostic approaches. AtheNA Multi-Lyte® systems appear to be reliable for anti-dsDNA, anti-myeloperoxidase, and anti-proteinase 3 screening and may be an optimal choice for monitoring anti-dsDNA levels.

Background: Autoantibodies are vital biomarkers for the diagnosis, assessment and prognostic determination of various autoimmune disorders. Objective: This study aimed to evaluate the performance of the two AtheNA Multi-Lyte® systems for the detection of various autoantibodies. Methods: A total of 105 systemic lupus erythematosus patients, 35 patients with other autoimmune diseases (diseased controls), and 30 healthy volunteers (healthy controls) at Zagazig University Hospitals, Zagazig city, Al Sharqia governorate were tested for anti-double-stranded DNA (anti-dsDNA) antibodies using indirect immunofluorescence (IIF) and the AtheNA Multi-Lyte® anti-nuclear antibodies-II system between May 2020 and April 2022. Seventy-five patients with clinically suspected autoimmune vasculitis (AIV) and 25 healthy volunteers were also tested for anti-myeloperoxidase and anti-proteinase 3 antibodies using IIF, the AtheNA Multi-Lyte® AIV system, and enzyme-linked immunosorbent assay (ELISA). Results: The AtheNA anti-dsDNA test (98.5%) was more specific than IIF (96.9%) for diagnosing systemic lupus erythematosus, but both tests had the same sensitivity (38.1%). Combining both methods increased sensitivity to 47.6%, while increasing the cut-off of the AtheNA anti-dsDNA test to 134 international units/mL increased specificity to 100%. The AtheNA Multi-Lyte AIV system exhibited substantial agreement with IIF regarding anti-myeloperoxidase testing (κ = 0.65) and almost perfect agreement with ELISA (κ = 0.85). The AtheNA Multi-Lyte® AIV system exhibited perfect agreement with IIF (κ = 1) and substantial agreement with ELISA for anti-proteinase 3 testing (κ = 0.63). Conclusion: AtheNA Multi-Lyte® systems appear to be reliable for anti-dsDNA, anti-myeloperoxidase, and anti-proteinase 3 screening and may be an optimal choice for monitoring anti-dsDNA levels. What this study adds: It is necessary to evaluate various autoantibodies detection assays to increase both sensitivity and specificity of autoimmune diseases diagnostic approaches. AtheNA Multi-Lyte® systems appear to be reliable for anti-dsDNA, anti-myeloperoxidase, and anti-proteinase 3 screening and may be an optimal choice for monitoring anti-dsDNA levels. [ABSTRACT FROM AUTHOR]

Usually associated with autoimmune diseases, anti-neutrophil cytoplasmic antibodies are also detected in other conditions, such as infections, malignancies, and after intake of certain drugs. Even if the mechanisms of production and their pathogenic role have not been fully elucidated yet, ANCA are widely recognized as a clinically alarming finding due to their association with various disorders. While ANCA target several autoantigens, proteinase-3, and myeloperoxidase are the ones proved to be most frequently related to chronic inflammation and tissue damage in murine models. Albeit these autoantibodies could be present as an isolated observation without any implications, ANCA are frequently used in clinical practice to guide the diagnosis in a suspect of small vessel vasculitis. Conditions that should prompt the clinician to test ANCA status range from various forms of lung disease to renal or peripheral nervous system impairment. ANCA positivity in the presence of an autoimmune disease, especially rheumatoid arthritis, or connective tissue diseases, is frequently correlated with more clinical complications and treatment inefficacy, even in the absence of signs of vasculitis. For this reason, it has been postulated that ANCA could represent the final expression of an immune dysregulation rather than a pathogenic event responsible for organs damage. Recently, it has also been proposed that ANCA specificity (PR3 or MPO) could possibly define ANCA-associated vasculitides better than clinical phenotype. This review aims at summarizing the latest advancements in the field of ANCA study and clinical interpretation. [ABSTRACT FROM AUTHOR]

Copyright of Der Internist is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Rapidly progressive crescentic glomerulonephritis associated with anti-neutrophil cytoplasmic antibodies (ANCA-GN) is a major cause of renal failure. Current immunosuppressive therapies are associated with severe side effects, intensifying the need for new therapeutic strategies. The activation of Mas receptor/Angiotensin-(1-7) axis exerted renoprotection in chronic kidney disease. Here, we investigated the effect of adding the lanthionine-stabilized cyclic form of angiotensin-1-7 [cAng-(1-7)] to cyclophosphamide in a rat model of ANCA-GN. At the onset of proteinuria, Wistar Kyoto rats with ANCA-GN received vehicle or a single bolus of cyclophosphamide, with or without daily cAng-(1-7). Treatment with cAng-(1-7) plus cyclophosphamide reduced proteinuria by 85% vs. vehicle, and by 60% vs. cyclophosphamide, and dramatically limited glomerular crescents to less than 10%. The addition of cAng-(1-7) to cyclophosphamide protected against glomerular inflammation and endothelial rarefaction and restored the normal distribution of parietal epithelial cells. Ultrastructural analysis revealed a preserved GBM, glomerular endothelium and podocyte structure, demonstrating that combination therapy provided an additional layer of renoprotection. This study demonstrates that adding cAng-(1-7) to a partially effective dose of cyclophosphamide arrests the progression of renal disease in rats with ANCA-GN, suggesting that cAng-(1-7) could be a novel clinical approach for sparing immunosuppressants. [ABSTRACT FROM AUTHOR]

Eosinophilic granulomatosis with polyangiitis (EGPA) is an ANCA-associated vasculitis characterized by the development of necrotizing granulomas rich in eosinophils and vasculitis of small and medium vessels, with compromise of the respiratory tract, peripheral nervous system, and least frequent ocular involvement. We report the case of a 54-year-old Caucasian man with a history of EGPA who presented ocular pain, red eye, vision loss, and evidence of scleral slimming compatible with necrotizing scleritis. The patient was treated with systemic steroids and cyclophosphamide, which reduced the ocular pain but did not improve visual acuity, needing surgical treatment of the scleral coverage defect. While necrotizing scleritis is an unusual manifestation of EGPA, it should be part of the differential diagnosis in patients with red eye or ocular pain as an accurate diagnosis and prompt treatment could reduce local complications. [ABSTRACT FROM AUTHOR]

Cutaneous leukocytoclastic vasculitis (LCV) can occur as skin-limited disease or as part a systemic vasculitis. Appropriate workup includes the evaluation of antineutrophil cytoplasmic antibodies (ANCAs), with a positive titer raising concern for the associated primary vasculitides including microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), or eosinophilic granulomatosis with polyangiitis (EGPA). In the absence of systemic findings, however, a drug etiology must also be considered. Tumor necrosis factor (TNF) inhibitors, propylthiouracil, levamisole-adulterated cocaine, hydralazine, and minocycline have been previously documented to induce ANCA-positive vasculitis (APV), which may present with conspicuously high ANCA titers. Herein we report trimethoprim-sulfamethoxazole as another culprit in drug-induced APV. Our case reinforces the need to consider drug etiology for APV and cautions against interpreting positive ANCAs as equivalent to evidence of systemic disease.

A 42-year-old man with undiagnosed Churg-Strauss syndrome (CSS) developed bilateral central retinal artery occlusion (CRAO). His medical history included bronchial asthma and irregular prednisolone usage but no atherosclerotic risk factors. At presentation, visual acuity (VA) was hand motion in the right eye and counting fingers in left eye. On fundoscopy, retinal whitening and a cherry red spot were observed in the right eye, while the fundus was normal in the left eye. After eyeball massage and systemic intraocular pressure lowering agents, his VA improved. On day 5 of treatment, he experienced right limb weakness and purpura on his right foot, and electromyography revealed mononeuritis multiplex. Laboratory tests indicated eosinophilia (52%). Based on the presence of hypereosinophilia, bronchial asthma, mononeuritis multiplex, vasculitis purpura, and sinusitis that was detected during etiological investigations, the patient was diagnosed as having CSS according to the American College of Rheumatology diagnostic criteria. Intravenous methylprednisolone 1 g/day was administrated for 3 consecutive days and 1 g cyclophosphamide was started and continued monthly for 6 months. Foot drop and vasculitic purpura improved after 7 days, but there was no further improvement in visual acuity. In conclusion, in the presence of bilateral CRAO and lack of atherosclerotic risk factors, CSS should be considered as a predisposing factor and investigations should be conducted accordingly.

The diagnosis of inflammatory bowel disease (IBD) is based on a combination of clinical, endoscopic, histological, radiological and laboratory methods. However, conventional diagnostic methods are not always sufficiently informative in IBD, especially in the case of unclassified colitis, which necessitates the extension of standard diagnostic approaches. Currently, there is an actively search for non-invasive serological markers for early and differential diagnosis of IBD and for the assessment of activity and prognosis of Crohn's disease (CD) and ulcerative colitis (UC). Among the most interesting serological markers are anti-Saccharomyces cerevisiae antibodies (ASCA), anti-neutrophil cytoplasmic antibodies (ANCA), goblet cells antibodies (GAB) and pancreatic autoantibodies (PAB). The aim of this review is to assess the diagnostic and prognostic significance of ASCA, ANCA, GAB, PAB in CD and UC. The paper presents the summary of the data on the role of ASCA, ANCA, GAB and PAB in abnormalities of the immunological tolerance mechanisms to intestinal microflora and intestinal permeability in IBD. We discuss the results of the studies on the associations of ASCA with a complicated CD phenotype, its response to genetically engineered biological therapies, and the need for surgical intervention. The article describes the data on the association of ANCA to the risk of progression of left-sided UC to widespread (total) colon lesions resistant to hormonal therapy, and that of antibodies to DNA-lactoferrin complexes and proteinase 3 to primary sclerosing cholangitis. It has been noted that PAB may be a prognostic marker for ileocolitis, perianal lesions, extraintestinal manifestations and complicated CD, and GAB a predictor of total UC with chronic persistent course. It should be emphasized that combined determination of ASCA, ANCA, GAB and PAB is highly informative, compared to the isolated detection of autoantibodies, for the differential diagnosis and prognosis of CD and UC.

Cocaine-induced midline destructive lesions (CIMDL) occur in a small subset of cocaine users, who clinically present with inflammation and necrosis of facial midline structures such as the palate, nasal septum, turbinates, and sinuses. We present a patient with CIMDL occurring concomitantly with ulcers on the cheek and upper trunk. Multiple biopsy specimens from the cutaneous and mucosal lesions consistently showed a dense dermal/submucosal infiltrate of neutrophils and plasma cells, without vasculitis or thrombosis. The ulcers resolved following cessation of cocaine use.

Myeloperoxidase (MPO) anti‐neutrophil cytoplasmic antibodies (ANCA) are often detected in association with a variety of lung pathologies, the most common being interstitial lung disease (ILD). A growing cohort of patients are being diagnosed with MPO‐ANCA in the context of ILD without ANCA‐associated vasculitis. Clinically and radiologically, there is little to differentiate this cohort from MPO‐ANCA‐negative ILD patients; however, the pathophysiology is likely different and different treatments are likely required. We present here a brief summary of the proposed pathophysiology of MPO‐ANCA‐positive ILD, and a more detailed review of the latest evidence on management, including monitoring for development of ANCA‐associated vasculitis, immunosuppression, anti‐fibrotics, and novel agents that have yet to be trialled in human experiments. [ABSTRACT FROM AUTHOR]

Abstract Vasculitis is a group of several clinical conditions in which the main histopathological finding is fibrinoid necrosis in the walls of blood vessels. This article assesses the main dermatological aspects relevant to the clinical and laboratory diagnosis of small- and medium-vessel cutaneous and systemic vasculitis syndromes. The most important aspects of treatment are also discussed.

Granulomatosis with polyangiitis (GPA) is a rare systemic disease characterized by granulomatous inflammation of the respiratory tract and necrotizing vasculitis of small and medium vessels often associated with the production of anti-neutrophil cytoplasmic antibodies (ANCA) directed mainly against leukocyte proteinase 3 (PR3). Usually, it involves upper airways, lungs, and kidneys, however any organ may be affected. The diagnosis is based on clinical, radiological, and serological findings. Biopsies, although strongly recommended, are not always feasible and often provides non-specific features. ANCA plays a crucial role in the diagnosis of GPA; nevertheless, ANCA detection is not a substitute for biopsy, which plays an important role in suspected cases, particularly when histological confirmation cannot be obtained. Significant advances have been made in classification criteria and phenotyping of the disease, particularly in determining the nuances between PR3-ANCA and myeloperoxidase (MPO)-ANCA vasculitis. This has led to better characterization of patients and the development of targeted treatment in the future. In addition, better identification of cytokine and immunological profiles may result in immuno-phenotyping becoming a new approach to identify patients with ANCA-associated vasculitis (AAV). Due to the chronic relapsing-remitting nature, strict follow-up of GPA is necessary to provide appropriate management. The search for the accurate marker of disease activity and to predict relapse is still ongoing and no predictor has been found to reliably guide therapeutic decision-making., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Potentas-Policewicz and Fijolek.)

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of systemic diseases caused by a combination of many factors, including genetics, environment, and immunity. AAV is characterized by predominantly small-vessel involvement and has a variety of clinical manifestations. Small-vessel lesions of the kidneys and lungs are common, and lesions of medium-sized arteries may also present, but the involvement of large arteries and their primary branches is very rare. This report delineates two instances of AAV with large arterial involvement, one case presenting with lesions of the aortic valve and the other with lesions of the pulmonary artery. The first case involved a 57-year-old man with no underlying diseases. Transthoracic echocardiography showed thickening of the left and right coronary valves of the aortic valve with enhanced echogenicity, moderate echogenic masses were seen on both valve leaflets, and the leaflets had restricted opening and poor closure. Blood tests showed positive perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA) and anti-myeloperoxidase (MPO) antibodies. The patient's aortic valve thickening virtually disappeared after treatment with hormones combined with immunosuppressive agents. The second case involved a 60-year-old woman whose transthoracic echocardiography and CT (computed tomography) angiography of the pulmonary arteries showed wall thickening of the main pulmonary artery and the proximal left and right pulmonary arteries, leading to luminal stenosis. Blood tests showed positive cytoplasmic anti-neutrophil cytoplasmic antibodies (c-ANCA) and anti-proteinase 3 (PR 3) antibodies. The patient's pulmonary artery wall thickening reduced after receiving hormones in combination with immunosuppression but she died of heart failure during subsequent treatment. The patient had been diagnosed with tuberculosis six months earlier and had been poorly treated with anti-tuberculosis therapy. The involvement of large arteries in AAV is a rare and critical condition with rapid progression and a high mortality rate. Early recognition of this type of AAV and aggressive immunosuppressive therapy may facilitate the reversal of the vascular lesion and a reduction in the risk of patient death., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Zhang, Yan, Wei, He, Chang and Zhang.)

Background: Granulomatosis with polyangiitis (GPA) is one of the most prevalent forms of the antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. GPA is characterized histologically by necrotizing granulomatous inflammation in addition to vasculitis. The diagnosis of GPA depends on clinical presentation, serological evidence of a positive ANCA, and/or histological evidence of necrotizing vasculitis or granulomatous destructive parenchymal inflammation. Cytoplasmic ANCA (c-ANCA) is positive in 65%-75% of GPA patients, accompanied by proteinase 3 (PR3), the main target antigen of c-ANCA, another 5% of GPA patients had negative ANCA., Case Summary: The patient, a 52-year-old male, presented with unexplained nasal congestion, tinnitus, and hearing loss. After a duration of 4 months experiencing these symptoms, the patient subsequently developed fever and headache. The imaging examination revealed the presence of bilateral auricular mastoiditis and partial paranasal sinusitis, and the ANCA results were negative. The anti-infective therapy proved to be ineffective, but the patient's symptoms and fever were quickly relieved after 1 wk of treatment with methylprednisolone 40 mg once a day. However, after continuous use of methylprednisolone tablets for 3 months, the patient experienced a recurrence of fever accompanied by right-sided migraine, positive c-ANCA and PR3, and increased total protein in cerebrospinal fluid. The patient was diagnosed with GPA. After receiving a treatment regimen of intravenous methylprednisolone 40 mg/d and cyclophosphamide 0.8 g monthly, the patient experienced alleviation of fever and headache. Additionally, the ANCA levels became negative and there has been no recurrence., Conclusion: For GPA patients with negative ANCA, there is a potential for early missed diagnosis. The integration of histopathological results and multidisciplinary communication plays a crucial role in facilitating ANCA-negative GPA., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Copyright of Die Nephrologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The classification of vasculitis according to a schema with universal acceptance is challenging, given the heterogeneous and protean nature of these diseases. Formal nomenclature and classification criteria for anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) have suffered several changes since their first description; none provides comprehensive diagnostic and classification criteria. Different factors account for the difficulties in the classification of vasculitis, including the incomplete understanding of the pathogenesis, the multisystemic nature of the disease, the non-specific patterns of vascular involvement, the overlap between entities, and the presence of various classification systems. The present article reviews the classification of AAV considering different points of view, including clinical, serologic, pathogenetic, organ predilection, therapeutic, and prognostic factors, and provides perspectives on future challenges in the understanding of AAV. There is an unmet need for a unifying view of the disease spectrum that considers the constantly evolving paradigms. [ABSTRACT FROM AUTHOR]

ABSTARCTPurpose: To investigate ocular manifestations in patients positive for serum anti-neutrophil cytoplasmic antibodies (ANCAs) in Japan.Methods: The clinical records of patients who had ocular manifestations and who were serum ANCA positive between 2011-2017 at Tokyo Medical and Dental University Hospital were retrospectively reviewed.Results: Eighteen patients were identified to be positive for serum ANCA and had ocular manifestations, including optic nerve involvement (50%), scleritis (27.8%), iritis (27.8%), retinal vasculitis (16.7%), oculomotor disorder (16.7%), and peripheral ulcerative keratitis (11.1%). Six patients had ANCA-associated vasculitis (AAV), including 5 patients with granulomatosis with polyangiitis and 1 patient with microscopic polyangiitis. Most patients with optic nerve involvement were myeloperoxidase-ANCA positive. Contrastingly, most patients with anterior segment involvement were proteinase-3-ANCA positive.Conclusion: Ocular manifestations were observed in some patients positive for serum ANCAs. Serum ANCA evaluation is useful for identifying the etiology of ocular inflammation and for diagnosing AAV, a life-threatening disease. [ABSTRACT FROM AUTHOR]

Abstract Introduction Granulomatosis with Polyangiitis (GPA) is a small vessel vasculitis characterized by a necrositing granulomatous inflammation of the upper and lower respiratory tracts and focal/proliferative glomerulonephritis. In more than 70% of the cases, the presenting symptoms are head and neck manifestations that are often misdiagnosed as infectious or allergic in etiology. Objective The present study provides an analysis of head and neck manifestations in a series of patients diagnosed with GPA. It also evaluates their medical and surgical treatment and provides a review of the relevant literature. Methods A retrospective analysis of 19 patients diagnosed with GPA at a public tertiary care hospital between 2006 and 2017 was performed. Results A total of 19 patients were included in the present study, and 16 of them presented head and neck manifestations. Sinonasal symptoms were the most common, affecting 56% of the patients, followed by laryngotracheal (31.25%) and ear (25%) symptoms. In 7 patients, sinonasal symptoms were the first manifestation of the disease (43.75%). Four patients underwent surgery at some stage of the disease. Conclusions Head and neck involvement is common in GPA and may stand for the first or the only manifestation of the disease. The otolaryngologists play a central role in the diagnosis and long-term treatment of these patients, and they have to keep this pathology in mind when treating patients with ENT symptoms that do not respond as expected to the treatment.

Rapidly progressive crescentic glomerulonephritis associated with anti-neutrophil cytoplasmic antibodies (ANCA-GN) is a major cause of renal failure. Current immunosuppressive therapies are associated with severe side effects, intensifying the need for new therapeutic strategies. The activation of Mas receptor/Angiotensin-(1-7) axis exerted renoprotection in chronic kidney disease. Here, we investigated the effect of adding the lanthionine-stabilized cyclic form of angiotensin-1-7 [cAng-(1-7)] to cyclophosphamide in a rat model of ANCA-GN. At the onset of proteinuria, Wistar Kyoto rats with ANCA-GN received vehicle or a single bolus of cyclophosphamide, with or without daily cAng-(1-7). Treatment with cAng-(1-7) plus cyclophosphamide reduced proteinuria by 85% vs. vehicle, and by 60% vs. cyclophosphamide, and dramatically limited glomerular crescents to less than 10%. The addition of cAng-(1-7) to cyclophosphamide protected against glomerular inflammation and endothelial rarefaction and restored the normal distribution of parietal epithelial cells. Ultrastructural analysis revealed a preserved GBM, glomerular endothelium and podocyte structure, demonstrating that combination therapy provided an additional layer of renoprotection. This study demonstrates that adding cAng-(1-7) to a partially effective dose of cyclophosphamide arrests the progression of renal disease in rats with ANCA-GN, suggesting that cAng-(1-7) could be a novel clinical approach for sparing immunosuppressants.

A 42-year-old man with undiagnosed Churg-Strauss syndrome (CSS) developed bilateral central retinal artery occlusion (CRAO). His medical history included bronchial asthma and irregular prednisolone usage but no atherosclerotic risk factors. At presentation, visual acuity (VA) was hand motion in the right eye and counting fingers in left eye. On fundoscopy, retinal whitening and a cherry red spot were observed in the right eye, while the fundus was normal in the left eye. After eyeball massage and systemic intraocular pressure lowering agents, his VA improved. On day 5 of treatment, he experienced right limb weakness and purpura on his right foot, and electromyography revealed mononeuritis multiplex. Laboratory tests indicated eosinophilia (52%). Based on the presence of hypereosinophilia, bronchial asthma, mononeuritis multiplex, vasculitis purpura, and sinusitis that was detected during etiological investigations, the patient was diagnosed as having CSS according to the American College of Rheumatology diagnostic criteria. Intravenous methylprednisolone 1 g/ day was administrated for 3 consecutive days and 1 g cyclophosphamide was started and continued monthly for 6 months. Foot drop and vasculitic purpura improved after 7 days, but there was no further improvement in visual acuity. In conclusion, in the presence of bilateral CRAO and lack of atherosclerotic risk factors, CSS should be considered as a predisposing factor and investigations should be conducted accordingly. [ABSTRACT FROM AUTHOR]

Granulomatosis with polyangiitis (GPA) is a rare but serious necrotizing auto-immune vasculitis. GPA is mostly associated with the presence of Anti-Neutrophil Cytoplasmic Antibody (ANCA) targeting proteinase 3 (PR3-ANCA), a serine protease contained in neutrophil granules but also exposed at the membrane. PR3-ANCAs have a proven fundamental role in GPA: they bind neutrophils allowing their auto-immune activation responsible for vasculitis lesions. PR3-ANCAs bind neutrophil surface on the one hand by their Fab binding PR3 and on the other by their Fc binding Fc gamma receptors. Despite current therapies, GPA is still a serious disease with an important mortality and a high risk of relapse. Furthermore, although PR3-ANCAs are a consistent biomarker for GPA diagnosis, relapse management currently based on their level is inconsistent. Indeed, PR3-ANCA level is not correlated with disease activity in 25% of patients suggesting that not all PR3-ANCAs are pathogenic. Therefore, the development of new biomarkers to evaluate disease activity and predict relapse and new therapies is necessary. Understanding factors influencing PR3-ANCA pathogenicity, i.e. their potential to induce auto-immune activation of neutrophils, offers interesting perspectives in order to improve GPA management. Most relevant factors influencing PR3-ANCA pathogenicity are involved in their interaction with neutrophils: level of PR3 autoantigen at neutrophil surface, epitope of PR3 recognized by PR3-ANCA, isotype and glycosylation of PR3-ANCA. We detailed in this review the advances in understanding these factors influencing PR3-ANCA pathogenicity in order to use them as biomarkers and develop new therapies in GPA as part of a personalized approach.

Granulomatosis with polyangiitis (GPA) is a rare but serious necrotizing auto-immune vasculitis. GPA is mostly associated with the presence of Anti-Neutrophil Cytoplasmic Antibody (ANCA) targeting proteinase 3 (PR3-ANCA), a serine protease contained in neutrophil granules but also exposed at the membrane. PR3-ANCAs have a proven fundamental role in GPA: they bind neutrophils allowing their auto-immune activation responsible for vasculitis lesions. PR3-ANCAs bind neutrophil surface on the one hand by their Fab binding PR3 and on the other by their Fc binding Fc gamma receptors. Despite current therapies, GPA is still a serious disease with an important mortality and a high risk of relapse. Furthermore, although PR3-ANCAs are a consistent biomarker for GPA diagnosis, relapse management currently based on their level is inconsistent. Indeed, PR3-ANCA level is not correlated with disease activity in 25% of patients suggesting that not all PR3-ANCAs are pathogenic. Therefore, the development of new biomarkers to evaluate disease activity and predict relapse and new therapies is necessary. Understanding factors influencing PR3-ANCA pathogenicity, i.e. their potential to induce auto-immune activation of neutrophils, offers interesting perspectives in order to improve GPA management. Most relevant factors influencing PR3-ANCA pathogenicity are involved in their interaction with neutrophils: level of PR3 autoantigen at neutrophil surface, epitope of PR3 recognized by PR3-ANCA, isotype and glycosylation of PR3-ANCA. We detailed in this review the advances in understanding these factors influencing PR3-ANCA pathogenicity in order to use them as biomarkers and develop new therapies in GPA as part of a personalized approach. [ABSTRACT FROM AUTHOR]

Summary: Long‐term observation of patients with ANCA‐associated vasculitis (AAV) allows the identification of different longitudinal patterns of ANCA levels during follow‐up. This study aimed to characterize these patterns and to determine their prognostic significance. All ANCA determinations performed in two university hospitals during a 2‐year period were retrospectively reviewed. Patients were included in the analysis if they had high titers of anti‐myeloperoxidase (anti‐MPO) or anti‐proteinase 3 (anti‐PR3) antibodies at least once, ≥ 5 serial ANCA determinations and AAV diagnosed by biopsy or American College of Rheumatology (ACR) classification criteria. Patients' time–course ANCA patterns were classified as monophasic, remitting, recurrent or persistent. Associations between ANCA patterns and prognostic variables (relapse rate and renal outcome) were analysed by univariate and multivariate statistics. A total of 99 patients [55 with microscopic polyangiitis (MPA), 36 with granulomatosis with polyangiitis (GPA) and eight with eosinophilic granulomatosis with polyangiitis (EGPA)] were included. Median follow‐up was 9 years. Among patients diagnosed with MPA or GPA, recurrent or persistent ANCA patterns were associated with a higher risk of clinical relapse [hazard ratio (HR) = 3·7, 95% confidence interval (CI) = 1·5–9·1 and HR = 2·9, 95% CI = 1·1–8·0, respectively], independently of clinical diagnosis or ANCA specificity. In patients with anti‐MPO antibodies, the recurrent ANCA pattern was associated with worsening renal function [odds ratio (OR) = 5·7, 95% CI = 1·2–26·0]. Recurrent or persistent ANCA patterns are associated with a higher risk of clinical relapse. A recurrent ANCA pattern was associated with worsening renal function in anti‐MPO‐associated vasculitis. [ABSTRACT FROM AUTHOR]