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Objective Von Willebrand factor (VWF) antigen plays a role in vascular inflammation and thrombosis, both of which are important in the pathogenesis of ANCA-associated vasculitis (AAV). Previous work found that VWF correlates with disease activity in childhood-onset primary CNS vasculitis. We sought to determine the relationship between VWF and disease activity over time in children with AAV. Methods AAV patients with more than one VWF level measured were included in this retrospective study, and the relationships between active vasculitis, VWF and other disease measures were analysed. Generalized estimating equations analysis was used to account for repeated VWF measurements within a patient. Repeated measures correlation was used to determine associations of paired laboratory observations. Diagnostic performance was evaluated using receiver operating curve analysis. Results A total of 732 total VWF measurements were collected in 33 AAV patients. VWF antigen levels were higher during active disease [median 2.03 IU/ml, interquartile range (IQR) 1.35, 2.55] compared with inactive disease (median 1.18 IU/ml, IQR 0.94, 1.53). VWF antigen was the only variable that was significantly associated with active disease (odds ratio 3.01, P  < 0.001, 95% CI 2.3, 3.93). The effect of VWF did not show a substantial difference between the disease subtypes. There was a moderate positive correlation between VWF antigen and disease activity, with an acceptable sensitivity and specificity rates. Conclusion Increased VWF antigen levels correlate with active vasculitis in this paediatric-onset AAV cohort and may be used as an additional biomarker in childhood AAV. [ABSTRACT FROM AUTHOR]

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

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) has been traditionally treated using glucocorticoids and immunosuppressants. However, these treatment modes are associated with high recurrence AAV rates and adverse reactions. Therefore, treatment strategies for AAV need to be urgently optimized. The efficacy and safety of biological agents in the treatment of vasculitis have been clinically validated. This review comprehensively summarizes the evidence-based support for the clinical use of existing biological agents in AAV. The findings reveal that multiple biological agents not only effectively reduce the adverse reactions associated with glucocorticoids and immunosuppressants but also demonstrate significant therapeutic efficacy. Notably, rituximab, an anti-CD20 antibody, has emerged as a first-line treatment option for AAV. Mepolizumab has shown promising results in relapsed and refractory eosinophilic granulomatosis with polyangiitis. Other biological agents targeting cytokines, complement, and other pathways have also demonstrated clinical benefits in recent studies. The widespread application of biological agents provides new insights into the treatment of AAV and is expected to drive further clinical research. These advancements not only improve patient outcomes but also offer more possibilities and hope in the field of AAV treatment. [ABSTRACT FROM AUTHOR]

As a group of systemic autoimmune diseases, anti-neutrophil cytoplasmic antibody-associated vasculitis （AAV） is characterized by necrotizing inflammation and fibrinoid necrosis of small blood vessels in multiple systems and positive serum antibodies to anti-neutrophil cytoplasmic antibody. Renal injury is common in this disease. Major clinical manifestations are hematuria, proteinuria and varying degrees of renal impairment. Glucocorticoids plus immunosuppressive agents are a conventional treatment for AAV. However, this regimen has a high relapse rate and numerous adverse events. Seeking a safer, more effective and comprehensive treatment, this review summarized the latest advances in the diagnosis and treatment of AAV.

Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) can occasionally trigger thrombotic microangiopathy (TMA). Cytomegalovirus (CMV) may be reactivated during intensive immunosuppressive therapy for AAV and cause TMA. Therefore, we aimed to evaluate the clinical features of and the association between vascular endothelial injury markers and TMA due to CMV in patients with AAV. A 61-year-old female was diagnosed with AAV and severe kidney injury. Immunosuppressive therapy gradually improved her symptoms and laboratory findings. However, 2 weeks after induction therapy initiation, she exhibited altered consciousness, a significant decrease in platelet count, and hemolytic anemia, resulting in a TMA diagnosis. Plasma exchange did not improve TMA findings and routine screening test revealed CMV infection. Ganciclovir injection improved the infection and TMA findings. Consequently, we diagnosed her with CMV-induced TMA. Both AAV and CMV may induce severe vascular endothelial injury, potentially leading to TMA development. CMV-induced TMA should be considered when TMA develops during induction therapy against AAV. Moreover, of the three serum markers of vascular injury—serum sulfatides, soluble thrombomodulin, and pentraxin 3—serum sulfatides may be associated with the development of TMA, and a high level of soluble thrombomodulin may be associated with the development of CMV viremia during the clinical course of AAV. [ABSTRACT FROM AUTHOR]

Involvement of the complement system is key to the pathogenesis of antineutrophil cytoplasmic antibody (ANCA)-associated renal vasculitis, but immunometabolic implications, especially on serum uric acid (UA) levels, still need to be elucidated. A total of 34 patients with biopsy-proven ANCA-associated renal vasculitis between 2015 and 2020 were retrospectively enrolled. Serum UA levels were correlated with clinical and histopathological characteristics, separated for critically ill (CI, n = 19), myeloperoxidase (MPO)-ANCA (n = 21) and proteinase 3 (PR3)-ANCA (n = 13) subgroups. We here identified inverse correlations of serum UA levels and complement C3 levels in the total cohort (p = 0.005) and the CI subgroup (p < 0.001). Intrarenal complement C4d deposition in venules correlated with serum UA levels in the total cohort (p = 0.007) and in the CI subgroup (p = 0.016). Significant associations of serum UA levels and tubulitis in areas of scarred cortex (t-IFTA) were identified in the total cohort (p = 0.008), and both subgroups of CI (p = 0.034) and MPO-ANCA (p = 0.029). In PR3-ANCA, interstitial fibrosis (ci) was observed as the strongest association with serum UA levels (p = 0.022). Our observations broaden our current understanding of contributory metabolic factors that influence the initial disease course in ANCA-associated renal vasculitis. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to compare the American College of Rheumatology/European Alliance of Associations for Rheumatology 2022 criteria with the previous classification algorithm for anti-neutrophil cytoplasmic antibody–associated vasculitis. Methods: We used data from two nationwide, prospective, inception cohort studies. The enrolled patients were classified as having eosinophilic granulomatosis with polyangiitis (EGPA), granulomatosis with polyangiitis (GPA), or microscopic polyangiitis (MPA) according to the new criteria; these criteria were compared with Watts' algorithm. Results: Among 477 patients, 10.7%, 9.9%, and 75.6% were classified as having EGPA, GPA, and MPA, respectively; 6.1% were unclassifiable. Three patients met both the EGPA and MPA criteria, and eight patients met both the GPA and MPA criteria. Of 78 patients with GPA classified using Watts' algorithm, 27 (34.6%) patients were reclassified as having MPA. Ear, nose, and throat involvement was significantly less frequent in patients reclassified as having MPA than in those reclassified as having GPA. Of 73 patients unclassifiable using Watts' algorithm, 62 were reclassified as having MPA. All patients reclassified as having MPA were myeloperoxidase-anti-neutrophil cytoplasmic antibody positive, and 46 had interstitial lung disease. Conclusion: Although the American College of Rheumatology/European Alliance of Associations for Rheumatology 2022 criteria cause overlapping multiple criteria fulfilments in some patients, those items contribute to classifying unclassifiable patients using Watts' algorithm into MPA. [ABSTRACT FROM AUTHOR]

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Anti‐neutrophil cytoplasmic antibody (ANCA) ‐positive vasculitis is a small‐vessel vasculitis that affects multiple body systems. Salivary gland involvement in ANCA‐associated vasculitis is rare. When present, it mimics infection or malignancy, which might lead to misdiagnosis. In this report, we describe a 72‐year‐old man who presented with parotid and submandibular gland pain and swelling in addition to dry mouth and eyes. He had bilateral non‐tender parotid gland lumps and no lymphadenopathies. Laboratory tests were positive for ANCA, hematuria, and proteinuria but negative for Anti‐Ro and ‐La. He was treated with corticosteroids and cyclophosphamide for acute kidney injury. Unfortunately, the patient died a few months later. This case report sheds light on a rare manifestation of salivary gland involvement in ANCA‐associated vasculitis that mimics Sjögren syndrome and the challenges associated with its diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Background: Increasing evidence indicates that clinicopathologic phenotypes and ANCA serotypes may differ ethnically and geographically. This review highlights the progress in the prevalence, pathogenesis, management, and outcomes of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in China. Summary: AAV is not rare in China. Cumulative evidence has demonstrated a significant preponderance of microscopic polyangiitis (MPA) and myeloperoxidase (MPO)-ANCA AAV in China. Even in patients with granulomatosis with polyangiitis (GPA), there is a predominance of MPO-ANCA over proteinase 3 (PR3)-ANCA, presenting a unique subset. The pathogenesis of AAV is multifactorial, with the role of complement activation being highlighted during recent years. Treatment strategies for AAV in China have also been refined recently. A rapid tapering of glucocorticoids to minimize exposure has been recommended by the Chinese guidelines. Along with a better understanding of the disease, B cell-targeted therapy and complement-targeted therapy are developing. A considerable number of patients in China received rituximab treatment and achieved remission. However, infection risk and associated mortality still remain concerns. Therefore, less rituximab exposure should be considered and evaluated in Chinese AAV patients. Prognostic factors have been reviewed. Of note, along with improved outcomes, there is an increase of cardiovascular and malignant-related death, warranting specific care. Recently, a modified renal risk score model has been validated for early risk prediction in Chinese AAV patients. Moreover, emerging biomarkers for AAV, including complement components, have been identified in Chinese patients. Key Messages: There is a preponderance of MPA and MPO-ANCA in China. Treatment strategies for Chinese AAV patients generally align with those in western countries, and to some extent, less aggressive. Prognostic factors and emerging biomarkers for AAV in China have been identified. Further challenges include optimizing interventions, minimizing treatment-related comorbidities, improving disease monitoring, and enhancing life qualities of AAV patients.

Introduction: Atypical anti-neutrophil cytoplasmic antibody (a-ANCA) is characterized by a positive fluorescence staining other than typical cytoplasmic or perinuclear ANCA. ANCA is associated with increased risk of dialysis and mortality in patients with ANCA vasculitis. However, comorbidities related to a-ANCA and whether a-ANCA exhibits an increased risk for renal failure and mortality remain unclear. This study aimed to explore the comorbidities and outcome associated with a-ANCA. Materials and methods: This retrospective study enrolled 164 and 170 patients with typical ANCA and a-ANCA positivity, respectively, who visited Taichung Veterans General Hospital, Taiwan from January 2016 to March 2021. Logistic regression analysis was used to determine risk factors and the rheumatological diagnosis associated with a-ANCA. Cox proportional hazard regression and Kaplan–Meier curves were employed to identify variables associated with 5-year renal survival and mortality. Results: Patients with a-ANCA had lower chance of ANCA-associated vasculitis (OR: 0.02, 95 % CI: 0.01–0.07 p

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides are a group of diseases characterised by necrotizing inflammation of small vessels such as arterioles, venules, and capillaries. ANCA-associated vasculitides (AAV) are referred to as small vessel vasculitides. Three AAV subgroups, namely granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic GPA (EGPA), are defined according to clinical features. The most common disease with renal involvement in AAV is MPA Approximately 90% of patients with MPA have renal involvement. While this rate is 70–80% in GPA, less than half of EGPA patients have renal involvement. Untreated survival in AAVs is less than one year. With appropriate immunosuppressive therapy, the 5-year renal survival rate is 70–75%. Without therapy, the prognosis is poor but treatments, typically immunosuppressants, have improved survival, albeit with considerable morbidity from glucocorticoids and other immunosuppressive medications. Current challenges include improving the measures of disease activity and risk of relapse, uncertainty about optimal therapy duration and a need for targeted therapies with fewer adverse effects. In this review, we described the treatment of renal involvement in AAV in line with current studies. [ABSTRACT FROM AUTHOR]

Background/Aims This study investigated the clinical implication of proteinase 3 (PR3)-antineutrophil cytoplasmic antibody (ANCA) in Korean patients with eosinophilic granulomatosis with polyangiitis (EGPA). Methods Among the 242 patients with ANCA-associated vasculitis identified from the hospital database, 49 patients with EGPA were selected and analysed in this study. Demographic, clinical, and laboratory data at diagnosis were reviewed to compare the features of patients with PR3-ANCA and without, as well as the clinical outcomes of relapse and end-stage renal disease (ESRD) during the follow-up period. The outcomes of patients with PR3-ANCA and without were compared by using the Kaplan-Meier survival analysis. Results The median age of the patients was 54 years, 17 (34.7%) were male, and six (12.2%) patients had PR3-ANCA at baseline. The most common items of the 1990 American College of Rheumatology criteria for EGPA were sinusitis (95.9%) and asthma (or asthmatic history) (93.9%). During the follow-up, none died, eight experienced relapse and two progressed to ESRD. EGPA patients with PR3-ANCA exhibited peripheral eosinophilia less frequently than those without (50.0% vs. 88.4%, p = 0.047). On the other hand, EGPA patients with PR3-ANCA experienced relapse more often compared to those without (50.0% vs. 11.6%, p = 0.047), and the cumulative relapse-free survival rate was lower compared to those without PR3-ANCA (p = 0.012). Conclusions EGPA patients possessing PR3-ANCA at disease diagnosis had distinct clinical feature and outcome compared to those without PR3-ANCA. These results should be taken into account in the management of patients with EGPA.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) encompasses a group of potentially life-threatening disorders characterized by necrotizing small vessel vasculitis with positive serum ANCA. To date, the pathogenesis of AAV has not been fully elucidated, but remarkable progress has been achieved in the past few decades. In this review, we summarize the mechanism of AAV. The pathogenesis of AAV involves various factors. ANCA, neutrophils, and the complement system play key roles in disease initiation and progression, forming a feedback amplification loop leading to vasculitic injury. Neutrophils activated by ANCA undergo respiratory burst and degranulation, as well as releasing neutrophils extracellular traps (NETs), thus causing damage to vascular endothelial cells. Activated neutrophils could further activate the alternative complement pathway, leading to the generation of complement 5a (C5a), which amplifies the inflammatory response by priming neutrophils for ANCA-mediated overactivation. Neutrophils stimulated with C5a and ANCA could also activate the coagulation system, generate thrombin, and subsequently cause platelet activation. These events in turn augment complement alternative pathway activation. Moreover, disturbed B-cell and T-cell immune homeostasis is also involved in disease development. In-depth investigation in pathogenesis of AAV might help to offer more effective targeted therapies. [ABSTRACT FROM AUTHOR]

Involvement of the complement system is key to the pathogenesis of antineutrophil cytoplasmic antibody (ANCA)-associated renal vasculitis, but immunometabolic implications, especially on serum uric acid (UA) levels, still need to be elucidated. A total of 34 patients with biopsy-proven ANCA-associated renal vasculitis between 2015 and 2020 were retrospectively enrolled. Serum UA levels were correlated with clinical and histopathological characteristics, separated for critically ill (CI, n = 19), myeloperoxidase (MPO)-ANCA (n = 21) and proteinase 3 (PR3)-ANCA (n = 13) subgroups. We here identified inverse correlations of serum UA levels and complement C3 levels in the total cohort (p = 0.005) and the CI subgroup (p < 0.001). Intrarenal complement C4d deposition in venules correlated with serum UA levels in the total cohort (p = 0.007) and in the CI subgroup (p = 0.016). Significant associations of serum UA levels and tubulitis in areas of scarred cortex (t-IFTA) were identified in the total cohort (p = 0.008), and both subgroups of CI (p = 0.034) and MPO-ANCA (p = 0.029). In PR3-ANCA, interstitial fibrosis (ci) was observed as the strongest association with serum UA levels (p = 0.022). Our observations broaden our current understanding of contributory metabolic factors that influence the initial disease course in ANCA-associated renal vasculitis.

Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) can occasionally trigger thrombotic microangiopathy (TMA). Cytomegalovirus (CMV) may be reactivated during intensive immunosuppressive therapy for AAV and cause TMA. Therefore, we aimed to evaluate the clinical features of and the association between vascular endothelial injury markers and TMA due to CMV in patients with AAV. A 61-year-old female was diagnosed with AAV and severe kidney injury. Immunosuppressive therapy gradually improved her symptoms and laboratory findings. However, 2 weeks after induction therapy initiation, she exhibited altered consciousness, a significant decrease in platelet count, and hemolytic anemia, resulting in a TMA diagnosis. Plasma exchange did not improve TMA findings and routine screening test revealed CMV infection. Ganciclovir injection improved the infection and TMA findings. Consequently, we diagnosed her with CMV-induced TMA. Both AAV and CMV may induce severe vascular endothelial injury, potentially leading to TMA development. CMV-induced TMA should be considered when TMA develops during induction therapy against AAV. Moreover, of the three serum markers of vascular injury—serum sulfatides, soluble thrombomodulin, and pentraxin 3—serum sulfatides may be associated with the development of TMA, and a high level of soluble thrombomodulin may be associated with the development of CMV viremia during the clinical course of AAV.

Background: Anti-neutrophil cytoplasmic antibody-associated small-vessel vasculitis (AASV) is an autoimmune disease with unclear pathogenesis, which causes damage to multiple organs and systems, renal failure or even death. We aimed to explore the expression of serum soluble Klotho protein in patients with AASV-induced renal damage and influence on prognosis.

Introduction/objectives : Birmingham vasculitis activity score (BVAS) version 3 (BVAS 3.0) and BVAS/granulomatosis with polyangiitis (BVAS/GPA) are used as indicators of disease activity in anti-neutrophil cytoplasmic antibody-associated vasculitis. We evaluated the association between these indices and the significance in patients with GPA and microscopic polyangiitis (GPA/MPA). Methods: We retrospectively reviewed the records of 203 patients with GPA/MPA in our hospital. The correlation between BVAS 3.0 and BVAS/GPA with the five-factor score (FFS) and laboratory data was investigated. The episodes of all-cause mortality, end-stage renal disease, and disease relapse were counted as adverse clinical outcomes. Multivariate Cox hazard analyses were performed to assess the relationships between both indices and patient outcomes. Results: Sixty-five (32.0%) and 138 (68.0%) patients with GPA and MPA were included. The median BVAS 3.0 was significantly higher in patients with MPA than in those with GPA (13.0 vs. 11.0, p = 0.015), whereas BVAS/GPA was higher in patients with GPA (4.0 vs. 3.0, p = 0.001). BVAS 3.0 and BVAS/GPA correlated significantly (r = 0.670, p < 0.001); both BVAS 3.0 and BVAS/GPA were shown to be associated with the outcomes investigated in separate Cox models. However, the correlation between BVAS 3.0 and BVAS/GPA was especially higher in a subgroup of patients with MPA than in those with GPA (MPA: r = 0.817, p < 0.001 vs. GPA: r = 0.570, p < 0.001) and with renal involvement (r = 0.676, p < 0.001). Conclusions: Although both BVAS 3.0 and BVAS/GPA significantly correlated and predicted outcomes well in those with GPA/MPA, a discord was observed based on disease subtypes and organ involvement. Key Points • BVAS 3.0 and BVAS/GPA significantly correlated and predicted outcomes in those with GPA/MPA. • A discordance was also observed based on disease subtypes and organ involvement. [ABSTRACT FROM AUTHOR]

Given the growing popularity of Rituximab (Rmab) treatment as a potential substitute for cyclophosphamide, we conducted this review to determine aspects related to Rmab therapy in central nervous system vasculitis (CNSV) patients, aiming to establish both the beneficial and detrimental consequences of Rmab while providing clinical guidance for managing patients' conditions. This systematic review was prepared following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The PubMed, Web of Science, and Scopus databases were utilized to investigate Rmab treatment in CNSV from January 2015 to May 2024. The research question was structured using the Population, Intervention, Comparison, Outcome, and Study Design (PICOS) criteria. Case series with only three or more unique cases, prospective or retrospective non-randomized studies, and randomized controlled trials (RCTs) were addressed. The initial evaluations were performed in PubMed, Scopus, and Web of Science. After removing duplicate entries, 177 publications were obtained, and 41 were chosen for full-text assessment. The review then incorporated information gathered from 27 studies, including 4 case series, 15 non-randomized cohorts, and 8 RCTs. Rmab is generally regarded as effective for CNSV therapy. Given its success, induction Rmab therapy is now frequently employed as maintenance therapy for CNSV patients. Rmab is a viable option for the induction of remission and maintenance treatment, with a successful reduction in relapse rates., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Alharthi et al.)

Eosinophilic granulomatosis with polyangiitis (EGPA) poses a significant diagnostic challenge due to its varied clinical presentation. Here, we present a case of a 59-year-old female with a history of asthma and sinusitis, who manifested with an extremely rare presentation of drastic tense blisters and hemorrhagic bullae alongside purpuric lesions and peripheral neuropathy. Examinations revealed eosinophilia, positive anti-neutrophil cytoplasmic antibody, and characteristic pathological findings with small vessel vasculitis in the purpura. Treatment with glucocorticoids and cyclophosphamide led to rapid improvement in peripheral eosinophilia, skin manifestations and motor neuron deficits. Although rare, our case underscores that bullous skin lesions should be recognized as a potential cutaneous hallmark of EGPA to aid timely diagnosis, since prompt treatment initiation is crucial given the potential irreversible organ damage and poor prognosis of EGPA., (© Japan College of Rheumatology 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Abstract Background Crescentic glomerulonephritis is a disease characterized by severe glomerular injuries that is classified into five different pathological types. Patients with type V disease have pauci-immune crescentic glomerulonephritis (PICGN) that is negative for anti-neutrophil cytoplasmic autoantibodies (ANCAs). There are limited clinical data on the manifestations, treatment, and prognosis of type V crescentic glomerulonephritis, especially in children. Case presentation A 13-year-old girl who had an intermittent fever for more than 10 months was admitted to our hospital. She had no gross hematuria, oliguria, edema, or hypertension, but further tests indicated a decreased glomerular filtration rate, hematuria, proteinuria, and an elevated level of IL-6. The antinuclear antibody spectrum test was positive at 1:1000, and the ANCA and anti-glomerular basement membrane antibody tests were negative. A renal biopsy confirmed the diagnosis of ANCA-negative PICGN. We administered methylprednisolone pulse therapy with intravenous cyclophosphamide and oral mycophenolate mofetil. At the 3-month follow-up, her urine protein level was significantly lower, and her serum creatinine level was in the normal range. Conclusions Fever may be an extrarenal manifestation of ANCA-negative PICGN, and IL-6 may play a role in the pathogenesis of this disease. Early methylprednisolone pulse therapy with an immunosuppressant may reduce symptoms and improve prognosis.

A 40-year-old Japanese woman, who underwent total thyroidectomy, had suffered from repeated episodes of fever and microscopic hematuria for 3 years, which had started 3 months after central venous port catheter insertion. On admission, she had malaise and low-grade fever, and was found to have microscopic hematuria, urinary red blood cell casts, multiple pulmonary nodules, and positivity of proteinase 3-anti-neutrophil cytoplasmic antibody (PR3-ANCA), which were suggestive to the presence of ANCA-associated small vessel vasculitis. However, her blood culture and subsequent gene analysis revealed the positivity of Tsukamurella pulmonis, and she was diagnosed with Tsukamurella pulmonis bacteremia accompanying PR3-ANCA positivity. Her condition improved after the removal of the catheter and antibiotic treatment. Tsukamurella species are categorized to the order Actinomycetales and can be misidentified as other Actinomycetales without genetic analyses. This case illustrates that chronic Tsukamurella pulmonis infection can cause ANCA production and nephritis, which mimics ANCA-associated vasculitis. Thus, it is critical to diagnose these cases correctly to avoid misdiagnosis and inappropriate treatment, such as immunosuppressive treatment.

Abstract Background C3 glomerulopathy (C3G) is a recent disease classification that is characterized by the presence of glomerular deposits (composed of C3) in the absence of significant amounts of immunoglobulin and comprises dense deposit disease and C3 glomerulonephritis (C3GN). Most C3GN manifests as membranoproliferative, mesangial proliferative glomerulonephritis patterns via light microscopy. Pure membranous nephropathy (MN)-like glomerular lesions are rare manifestations of C3GN. Anti-neutrophil cytoplasmic antibodies (ANCAs) are also seldomly reported to be positive in C3GN. Herein, we report the case of a C3GN patient presenting with an MN-like glomerular pattern with ANCA positivity. Case presentation A 68-year-old woman was admitted to a local hospital with elevated serum creatinine for two weeks. Laboratory tests showed a hemoglobin level of 85 g/L. Urinalysis was positive for 2 + protein and 360 RBCs/HPF. Blood biochemistry analysis revealed the following concentrations: albumin, 30.3 g/L; globulin, 46.2 g/L; blood urea nitrogen, 19.9 mmol/L; and serum creatinine, 234 µmol/L. The serum C3 level was 0.4950 g/L, and the serum C4 level was 0.1050 g/L. The direct Coombs test was positive. Serologic testing for ANCA revealed the presence of p-ANCA (1:10) by indirect immunofluorescence microscopy assay, as well as the presence of PR3 1.2 (normal range

Abstract Background Patients with interstitial lung disease (ILD) are occasionally positive for anti-neutrophil cytoplasmic antibodies (ANCAs). Differences between ILDs secondary to microscopic polyangiitis (MPA) and isolated ANCA-positive idiopathic interstitial pneumonia (IIP) remain unclear. The aim of this study was to explore the differences in clinical features and outcomes between MPA-associated ILDs and isolated ANCA-positive IIPs. Methods We reviewed 1338 ILDs patients with available ANCA results and retrospectively analysed 80 patients who were ANCA-positive. MPA-associated ILDs (MPA-ILDs group) and isolated ANCA-positive IIPs (ANCA-IIPs group) were compared. Results Among 80 patients with ANCA-positive ILDs, 31 (38.75%) had MPA-ILDs, and 49 (61.25%) had isolated ANCA-positive IIPs. Compared with ANCA-IIPs group, patients in MPA-ILDs group had a higher proportion of fever (p = 0.006) and higher neutrophil count (p = 0.011), erythrocyte sedimentation rate (ESR) (p

Newly identified PD-1hiCXCR5–CD4+ T-cells, termed as peripheral helper T-cells (Tph), have been found elevated and playing a pathogenic role in some autoimmune diseases like systemic lupus erythematosus (SLE) and rheumatic arthritis (RA). However, the potential role of Tph-cells in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) remains unclear. Here, we explored the potential clinical significance of circulating Tph-cells in the pathogenesis of AAV. Comparing 32 active AAV patients and 18 age- and sex-matched healthy controls (HCs), we found that the frequency of circulating Tph-cells was significantly expanded in active AAV patients. Besides, programmed death 1 (PD-1) expression on the surface of Tph-cells was significantly up-regulated in active AAV patients. Importantly, the frequency of circulating Tph-cells was greatly decreased in AAV patients after receiving treatment. Tph-cells frequency was positively correlated with the Birmingham Vasculitis Activity Score (BVAS), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), neutrophil lymphocyte ratio (NLR), and cellular crescent in active AAV patients, but negatively correlated with fibrosus crescent. Tph-cells frequency was also positively correlated with naïve B-cells, serum concentration of MPO-ANCAs, serum tumor necrosis factor-α (TNF-α), IL-4, IL-21, and IL-12. However, serum IL-10 exhibited a negative correlation with circulating Tph-cells in active AAV patients. These results demonstrate that circulating Tph-cells are greatly expanded in active AAV patients and are positively associated with serum MPO-ANCAs and disease activity, thus contributing to the pathogenesis of AAV. The role of newly identified peripheral helper T cells (Tph) in ANCA-associated vasculitis (AAV) remains largely unknown, although they have been found elevated and playing pathogenic role in some autoimmune disease including SLE and RA. In this study, Liu et al found that Tph cells were greatly expanded in active AAV patients and decreased after treatment with methylprednisolone and cyclophosphamide, and they were positively correlated with vasculitis activity index, serum concentration of MPO-ANCA, IL-4 and IL-21. These results indicate that Tph cells may play a pathogenic role in AAV through promoting plasma cell activation possibly by secreting IL-4 and IL-21. [ABSTRACT FROM AUTHOR]

A significant proportion of patients with infective endocarditis presents with acute renal failure related to infective endocarditis-associated glomerulonephritis (IEAGN). However, the clinical presentation of IEAGN differs from that of other infection-related glomerulonephritis (IRGN) with anti-neutrophil cytoplasmic antibody (ANCA) positivity occurring in almost onethird of cases; therefore, it may be difficult to establish a definitive diagnosis and provide appropriate treatment. This review article provides a comprehensive understanding of the clinical presentation, investigations, histopathology, and treatment/management of IEAGN so that clinicians can keep this differential in mind for patients with fever of unknown origin accompanied by signs and symptoms of acute renal failure. [ABSTRACT FROM AUTHOR]

Abstract Background Anti-glomerular basement membrane (anti-GBM) disease is an organ-specific autoimmune disease that involves the lung and kidneys and leads to rapid glomerulonephritis progression, with or without diffuse alveolar hemorrhage, and even respiratory failure. Classic cases of anti-GBM disease are diagnosed based on the presence of the anti-GBM antibody in serum samples and kidney or lung biopsy tissue samples. However, atypical cases of anti-GBM disease are also seen in clinical practice. Case presentation We herein report the rare case of a patient with atypical anti-GBM disease whose serum was negative for the anti-GBM antibody but positive for the myeloperoxidase (MPO) anti-neutrophil cytoplasmic antibody (p-ANCA) and another atypical ANCA. Laboratory test results showed severe renal insufficiency with a creatinine level of 385 μmol/L. Renal biopsy specimen analysis revealed 100% glomeruli with crescents; immunofluorescence showed immunoglobulin G (IgG) linearly deposited alongside the GBM. Finally, the patient was discharged successfully after treatment with plasmapheresis, methylprednisolone and prednisone. Conclusion This patient, whose serum was negative for the anti-GBM antibody but positive for p-ANCA and another atypical ANCA, had a rare case of anti-GBM disease. Insights from this unusual case might help physicians diagnose rare forms of glomerulonephritis and treat affected patients in a timely manner.

Rationale: Coexistence of anti-glomerular basement membrane (anti-GBM) disease with anti-neutrophil cytoplasmic antibody (ANCA) in a case of glomerulonephritis is often identified as a “double-positive” disease. Interestingly, the majority of “double positive” ANCA is myeloperoxidase (MPO)-ANCA and some of the MPO-ANCA positive cases showed intrarenal arteritis, suggesting an ANCA-associated kidney lesion. Proteinase 3-ANCA positive diseases are also rarely reported. Patients positive for all three antibodies, i.e., triple-positive patients, are extremely rare. Patient’s Concern: A 53 year-old female presented with anasarca and oliguria of 2 months’ duration. Diagnosis: Pauci-immune type renal limited crescentic glomerulonephritis positive for MPO-ANCA, proteinase 3-ANCA, and anti-GBM antibody (triple-positive). Interventions: Intravenous high dose cyclophosphamide, oral azathioprine, intravenous methylprednisolone, and plasma exchange as per British Health Professionals in Rheumatology Guidelines. Outcomes: After one-month follow-up, anasarca and proteinuria were lessened, serum creatinine was normalized, titers of MPO-ANCA levels were decreased, and anti-GBM antibody levels were normalized. Lessons: Triple-positive renal limited vasculitis is rare and response to combined immunosuppressive therapy and plasma exchange can contribute to successful remission.

Objective: We investigated the prevalence of metabolic syndrome (MetS) in all or nonobese patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and compared it with age- and gender-matched controls. Also, we assessed the effect of variables at diagnosis on the risk of cardiovascular disease (CVD) in all or nonobese AAV patients. Methods: In this study, 173 AAV patients and 344 controls were included and MetS was defined by the National Cholesterol Education Program Adults Treatment Panel III criteria. The obesity based on body mass index (BMI) was defined as BMI ≥ 25 kg/m2. The follow-up duration was defined as the period from diagnosis to the last visit or to each poor outcome occurrence. Results: The median age of AAV patients was 58.7 years and 57 patients were men. The prevalence of MetS was 50.9% in all AAV patients and 46.5% in nonobese AAV patients, which were significantly higher than 37.8% in all controls and 28.2% in nonobese controls. In Kaplan–Meier survival analysis, Mets at diagnosis significantly reduced the cumulative CVD-free survival rate in both all and nonobese AAV patients. In the multivariable Cox hazards model analysis, CVD during follow-up was significantly associated with both Birmingham vasculitis activity score (BVAS) (HR 1.159) and MetS at diagnosis (HR 9.036) in nonobese AAV patients. Conclusions: The prevalence of MetS at diagnosis in all or nonobese AAV patients was significantly higher than those in all or nonobese controls. Furthermore, both BVAS and MetS at diagnosis increased the risk of CVD in nonobese AAV patients. [ABSTRACT FROM AUTHOR]

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) affects small blood vessels and causes severe systemic organ injury commonly affecting the lungs and kidney. However, gastrointestinal, especially pancreatic, lesions are rare. We report the case of a 67-year-old Japanese man diagnosed with myeloperoxidase (MPO) AAV who developed pancreatic lesions and diabetes mellitus. The patient was admitted to our hospital due to fever, cough, and weight loss. He developed progressive glomerulonephritis, lung nodules, and pancreatic swelling and mass. Additionally, laboratory examination revealed positive MPO-ANCA and elevated glycated hemoglobin A1c, which were suggestive of diabetes mellitus. Renal biopsy revealed necrotizing crescentic glomerulonephritis and vasculitis in the small arteries. Endoscopic ultrasound-guided fine needle aspiration of the pancreas was performed, and histological findings suggested the possibility of pancreatic vasculitis and parenchymal injury. The patient was diagnosed with AAV, which was managed with glucocorticoids. This improved the renal function and pancreatic lesions. Furthermore, blood glucose levels improved despite treatment with glucocorticoids. These findings suggest that AAV-related pancreatic lesions worsened glycemic control. However, glucocorticoid therapy improved vasculitis and pancreatic lesions, which resulted in improved glycemic control. [ABSTRACT FROM AUTHOR]

The management of anti-neutrophil cytoplasmic antibody-associated vasculitis has substantially improved in the last decade. For the induction of remission, rituximab is increasingly used in place of cyclophosphamide, particularly for patients with proteinase 3 (PR3)-associated vasculitis or relapsing disease, and those wishing to preserve their fertility. A lower dose regimen of glucocorticoids, with a more rapidly tapering schedule, is preferable and is as effective and safer than the standard-dose regimen. Avacopan, the complement C5a receptor inhibitor, is effective in the treatment of associated vasculitis and may replace glucocorticoids in the future. Plasma exchange provides no additional benefit for patients with severe anti-neutrophil cytoplasmic antibody-associated vasculitis, although it is still used in selected patients on a case-by-case basis. Rituximab is preferred for the maintenance of remission, repeated at fixed time intervals. The duration for which immunosuppressive therapy should be given is uncertain, but is generally longer for patients with PR3 disease or persistent anti-neutrophil cytoplasmic antibody positivity. The anti-interleukin 5 monoclonal antibody, mepolizumab, is effective for the treatment of non-severe eosinophilic granulomatosis with polyangiitis. Several other targeted therapies are in the pipeline and further progress is expected in the coming years. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the positive detection rate and clinical application value of anti-parietal cell antibody (PCA), anti-neutrophil cytoplasmic antibody (ANCA), anti-Saccharomyces cerevisiae antibody (ASCA), anti-gliadin antibody (AGA) and anti-nuclear antibody (ANA) in patients visiting the Department of Gastroenterology. Methods: From January 2015 to June 2018, 1,083 patients receiving detection of PCA and other autoantibodies were selected from the Department of Gastroenterology of Baoding First Central Hospital. The positive detection rate of autoantibodies was statistically analyzed. The enumeration data were expressed as rate or constituent ratio, and the rates were compared between groups using the x2 test. Results: Among the 1,083 patients, the positive detection rate of ANA, ASCA, AGA, PCA and ANCA was 33.52%, 16.71%, 15.51%, 13.66% and 7.66%, respectively. The total positive detection rate was 62.8% (n = 680). Conclusion: The population with abdominal distension, chronic abdominal pain, diarrhea and other digestive system symptoms should be timely treated with combined detection of PCA, ANCA, ASCA, AGA and ANA, which is of important clinical application value for early diagnosis of gastrointestinal diseases and prevention of missed diagnosis and misdiagnosis. [ABSTRACT FROM AUTHOR]

Abstract Background Ulcerative colitis (UC) is a chronic, non-specific inflammatory bowel disease (IBD) with unknown etiology. The lack of specific clinical manifestations, standard diagnostic criteria, objective and accurate indicators to the severity of the disease and the efficacy of the treatment, often results in difficulties in diagnosis and timely treatment of UC. Therefore, there is a need to develop a clinically suitable serum biomarker assay with high specificity and sensitivity. Objective and methods To explore the significance of anti-neutrophil cytoplasmic antibodies (ANCA) and anti-saccharomyces cerevisiae antibodies (ASCA) in the diagnosis, differential diagnosis and treatment assessment in patients with ulcerative colitis (UC). Serum levels of ANCA-IgG, ASCA-IgA and ASCA-IgG were measured by an enzyme-linked immunosorbent assay (ELISA) in 105 UC patients, 52 non-UC patients and 100 healthy controls. Results (1) Both the ANCA-IgG level and its positive rate in UC patients were significantly higher than those in non-UC controls and healthy controls (p 0.05). (2) The sensitivity of ANCA+ and ANCA+/ASCA− in detecting UC patients was 61.90% and 55.24%, respectively, whereas the specificity was 91.45% and 94.08%, respectively. The sensitivity of ASCA+ and ASCA+/ANCA− in non-UC disease controls was 5.33% and 3.85%, respectively, and specificity was 83.9% and 88.78%, respectively. (3) When UC patients were grouped into mild, moderate or severe subtypes, the ANCA-IgG levels were correlated with the severity of UC, and the differences of the ANCA-IgG levels were statistically different among the three subtypes (p

Aims The aim was to determine whether anti-neutrophil cytoplasmic antibody (ANCA)-positive serology in patients with lupus nephritis (LN) is associated with different clinicopathologic features and outcomes. Methods In our retrospective analysis, 283 patients were enrolled between 2013 and 2018. Thirty-six patients were ANCA-positive, and this group was compared with the remaining 247 patients who were confirmed as ANCA-negative at the time of biopsy. Results ANCA-positive LN patients exhibited higher anti-dsDNA antibody titers and serum creatinine levels and lower serum hemoglobin concentrations than ANCA-negative LN patients. On pathological evaluation, segmental endocapillary hypercellularity observed by light microscopy was significantly more common in the ANCA-positive group. This feature was not significantly different in the treatment group, but the response to treatment was significantly different, as was remission (76.1% vs 69.4%, p

Background Glycosuria is one of the manifestations of acute tubulointerstitial nephritis (ATIN), but may also be observed in other renal diseases. In this study, we investigated the value of non-diabetic glycosuria as a diagnostic clue for ATIN. Methods We retrospectively reviewed the medical records of adult patients who underwent a kidney biopsy as an evaluation for serum creatinine > 1.4 mg/dL. Patients with proteinuria in the nephrotic range, diabetes mellitus, or transplanted kidney were excluded. The laboratory abnormalities suggestive of tubular injury were compared between 28 patients (14 men and 14 women, mean age 48.5 ± 14.1 years) with ATIN and 116 patients (76 men and 40 women, mean age 53.1 ± 15.0 years) with other diagnoses. Results In ATIN, glycosuria (≥ 1+ on dipstick; 68%) was more frequent than hypophosphatemia (18%), hypouricemia (18%), hypokalemia (18%), and tubular proteinuria (40%). In other diagnoses, glycosuria (≥ 1+) was detected in 7 (6%) patients; 6 of them had the histological diagnosis of antineutrophil cytoplasmic antibody-associated glomerulonephritis. The presence of glycosuria (≥ 1+) had 68% sensitivity and 94% specificity for ATIN, with the positive likelihood ratio of 11.24 and the negative likelihood ratio of 0.34. Pyuria and low total CO2 were equally and more sensitive (68% and 71%, respectively) than glycosuria (≥ 1+), but had no diagnostic value due to low specificities (58% and 60%, respectively). Conclusion In non-diabetic, non-nephrotic patients undergoing a kidney biopsy for azotemia, 1+ or higher glycosuria, if present, was a good predictor of the diagnosis of ATIN.

A 78-year-old woman with severe auditory disturbance was referred to our hospital and was diagnosed with otitis media with anti-neutrophil cytoplasmic antibody -associated vasculitis (OMAAV). The auditory disturbance improved moderately with prednisolone 40 mg/day, but multiple pulmonary masses were detected on chest computed tomography six months later. Transbronchial lung biopsy revealed granulomatosis with polyangiitis (GPA). Administration of prednisolone 50 mg/day and cyclophosphamide 500 mg once every two weeks for 12 weeks improved the lung lesions, but no further improvement in the hearing ability was observed. Prednisolone monotherapy was not able to prevent progression of OMAAV to GPA.

Anti-neutrophil cytoplasmic antibody (ANCA)- associated vasculitis (AAV) is a group of systemic autoimmune diseases characterized by inflammation of small- and medium-sized vessels. The three main types of AAV are granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). A growing number of studies focus on natural killer (NK) cells in AAV. NK cells are innate lymphoid cells with important roles in anti-viral and anti-tumor defense, but their roles in the pathogenesis of autoimmunity is less well established. In this review, we will present a summary of what is known about the number, phenotype and function of NK cells in patients with AAV. We review the literature on NK cells in the circulation of AAV patients, studies on tissue resident NK cells and how the treatment affects NK cells.

Background: Increasing evidence indicates that clinicopathologic phenotypes and ANCA serotypes may differ ethnically and geographically. This review highlights the progress in the prevalence, pathogenesis, management, and outcomes of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in China., Summary: AAV is not rare in China. Cumulative evidence has demonstrated a significant preponderance of microscopic polyangiitis (MPA) and myeloperoxidase (MPO)-ANCA AAV in China. Even in patients with granulomatosis with polyangiitis (GPA), there is a predominance of MPO-ANCA over proteinase 3 (PR3)-ANCA, presenting a unique subset. The pathogenesis of AAV is multifactorial, with the role of complement activation being highlighted during recent years. Treatment strategies for AAV in China have also been refined recently. A rapid tapering of glucocorticoids to minimize exposure has been recommended by the Chinese guidelines. Along with a better understanding of the disease, B cell-targeted therapy and complement-targeted therapy are developing. A considerable number of patients in China received rituximab treatment and achieved remission. However, infection risk and associated mortality still remain concerns. Therefore, less rituximab exposure should be considered and evaluated in Chinese AAV patients. Prognostic factors have been reviewed. Of note, along with improved outcomes, there is an increase of cardiovascular and malignant-related death, warranting specific care. Recently, a modified renal risk score model has been validated for early risk prediction in Chinese AAV patients. Moreover, emerging biomarkers for AAV, including complement components, have been identified in Chinese patients., Key Messages: There is a preponderance of MPA and MPO-ANCA in China. Treatment strategies for Chinese AAV patients generally align with those in western countries, and to some extent, less aggressive. Prognostic factors and emerging biomarkers for AAV in China have been identified. Further challenges include optimizing interventions, minimizing treatment-related comorbidities, improving disease monitoring, and enhancing life qualities of AAV patients., Competing Interests: The authors declare that they have no competing interests., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Renal medullary angiitis is characterized by interstitial hemorrhaging in the medulla with neutrophil infiltration. An 81-year-old man presented with a fever, kidney dysfunction, and purpura of the legs, which was diagnosed as leukocytoclastic vasculitis. Proteinase 3 antineutrophil cytoplasmic antibodies were weakly positive. A kidney biopsy showed severe tubulointerstitial hemorrhaging with neutrophilic infiltration in the perivascular areas surrounding the vasa recta in the medulla without crescent formation in the glomeruli. An immunofluorescence analysis was negative, and electron microscopy revealed no immune-dense deposits, ruling out immunoglobulin A vasculitis. Intravenous methylprednisolone for three days and plasma exchange followed by oral prednisolone improved his general condition.

Abstract Systemic sclerosis (SSc) is a multi‐system autoimmune disease. Anti‐neutrophil cytoplasmic antibodies (ANCA) are autoantibodies directed against enzymes found within primary granules of neutrophils and lysosomes in monocytes. Although up to 12% of SSc patients have ANCA, only a minority of these patients develop an overlap syndrome with ANCA‐associated vasculitis. We summarize previous reports on SSc patients with ANCA‐associated neuropathy. In all the reported cases, the SSc diagnosis preceded the ANCA‐associated neuropathy diagnosis. Seven of the eight patients with limited cutaneous SSc had interstitial lung disease (ILD). Thus, patients with ANCA‐associated neuropathy in lSSc may be prone to complication with ILD.

Anti-neutrophil cytoplasmic antibodies-associated vasculitis (AAV) occurs in elderly people, and patients with anti-myeloperoxidase autoantibodies (MPO-ANCA)-positive AAV are often complicated with interstitial lung disease (ILD). This study aimed to evaluate the age-related clinical features of elderly patients with MPO-ANCA-positive AAV-ILD. This study retrospectively investigated 63 patients with MPO-ANCA-positive AAV-ILD, all of whom were 65 years or older at diagnosis. Clinical characteristics, causes of death and survival rates among three groups stratified by age (65–74 years, n = 29; 75–79 years, n = 18; over 80 years, n = 16) were compared. This study also examined the association with severe infections in these patients. Among the three age groups, there were significant differences in sex (P = 0.032), serum Krebs von den Lungen-6 (P < 0.01), and total ground-glass opacity score (P = 0.011). The causes of death were mainly severe infections and complications of ILD. Kaplan–Meier curve analysis showed a significantly lower 5-year survival rate in the oldest group (P < 0.01). Regarding severe infections in these patients, the 5-year cumulative incidence of severe infections was higher in the patients receiving steroid pulse therapy (P = 0.034). The clinical characteristics of MPO-ANCA-positive AAV-ILD differ with age in elderly patients, with age being an important poor prognostic factor in these patients. The administration of steroid pulse therapy is a significant risk factor of severe infection in MPO-ANCA-positive elderly patients with AAV-ILD. [ABSTRACT FROM AUTHOR]

A 40-year-old Japanese woman, who underwent total thyroidectomy, had suffered from repeated episodes of fever and microscopic hematuria for 3 years, which had started 3 months after central venous port catheter insertion. On admission, she had malaise and low-grade fever, and was found to have microscopic hematuria, urinary red blood cell casts, multiple pulmonary nodules, and positivity of proteinase 3-anti-neutrophil cytoplasmic antibody (PR3-ANCA), which were suggestive to the presence of ANCA-associated small vessel vasculitis. However, her blood culture and subsequent gene analysis revealed the positivity of Tsukamurella pulmonis, and she was diagnosed with Tsukamurella pulmonis bacteremia accompanying PR3-ANCA positivity. Her condition improved after the removal of the catheter and antibiotic treatment. Tsukamurella species are categorized to the order Actinomycetales and can be misidentified as other Actinomycetales without genetic analyses. This case illustrates that chronic Tsukamurella pulmonis infection can cause ANCA production and nephritis, which mimics ANCA-associated vasculitis. Thus, it is critical to diagnose these cases correctly to avoid misdiagnosis and inappropriate treatment, such as immunosuppressive treatment. [ABSTRACT FROM AUTHOR]

UnlabelledRheumatic manifestations of cocaine have been well described, but more recently, a dramatic increase in the levamisole-adulterated cocaine supply in the United States has disclosed unique pathologic consequences that are distinct from pure cocaine use. Most notably, patients show skin lesions and renal dysfunction in the setting of extremely high perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA). Unexpectedly, antibodies to myeloperoxidase, the typical target of p-ANCA, are relatively low if at all present. This discrepancy is due to the fact that p-ANCA seen in association with levamisole-adulterated cocaine exposure is often directed against atypical p-ANCA-associated antigens within the neutrophil granules such as human neutrophil elastase, lactoferrin, and cathepsin G. Biopsies of the skin lesions reveal leukocytoclastic vasculitis often involving both superficial and deep dermal vessels. Renal injury most typically manifests as crescentic and necrotizing pauci-immune glomerulonephritis. In this review, the manifestations of levamisole-adulterated cocaine-induced vasculitis are discussed with an emphasis on the typical histomorphologic findings seen on biopsy.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1764738711370019 .

Background: Crescentic glomerulonephritis is a disease characterized by severe glomerular injuries that is classified into five different pathological types. Patients with type V disease have pauci-immune crescentic glomerulonephritis (PICGN) that is negative for anti-neutrophil cytoplasmic autoantibodies (ANCAs). There are limited clinical data on the manifestations, treatment, and prognosis of type V crescentic glomerulonephritis, especially in children.Case Presentation: A 13-year-old girl who had an intermittent fever for more than 10 months was admitted to our hospital. She had no gross hematuria, oliguria, edema, or hypertension, but further tests indicated a decreased glomerular filtration rate, hematuria, proteinuria, and an elevated level of IL-6. The antinuclear antibody spectrum test was positive at 1:1000, and the ANCA and anti-glomerular basement membrane antibody tests were negative. A renal biopsy confirmed the diagnosis of ANCA-negative PICGN. We administered methylprednisolone pulse therapy with intravenous cyclophosphamide and oral mycophenolate mofetil. At the 3-month follow-up, her urine protein level was significantly lower, and her serum creatinine level was in the normal range.Conclusions: Fever may be an extrarenal manifestation of ANCA-negative PICGN, and IL-6 may play a role in the pathogenesis of this disease. Early methylprednisolone pulse therapy with an immunosuppressant may reduce symptoms and improve prognosis. [ABSTRACT FROM AUTHOR]