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Background: Solitary fibrous tumors (SFTs) of the pleura are usually benign. We present a case of SFT of the pleura which grew rapidly after slow long-term progression. Case presentation: A 78-year-old man was referred to our hospital for left-sided back pain and shortness of breath. He was found to have a left mediastinal mass at 15 years of age. He remained asymptomatic for 60 years, and chest computed tomography (CT) during treatment of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis revealed that the mediastinal tumor was 8.0 cm in diameter. The size remained unchanged for 3 years but increased to 15.0 cm over the next 5 years. As the left main pulmonary artery was compressed by the mass, there were concerns regarding the worsening of haemodynamics and exacerbation of symptoms of respiratory distress. A sixth-rib intercostal thoracotomy with a posterolateral incision was performed to remove the large tumor. Perioperative steroid administration (methylprednisolone 125 mg/day) and positive pressure ventilation were administered to prevent re-expansion of the pulmonary oedema. The patient was discharged following an uneventful course. The tumor was pathologically diagnosed as an SFT with no malignant findings. Conclusion: SFTs require surgical intervention because of their potential for rapid growth. [ABSTRACT FROM AUTHOR]

Background: Infectious episodes contribute to morbidity and mortality in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Renal involvement, also known as ANCA-associated glomerulonephritis (AGN), is frequently observed in AAV. Little is known about whether co-infection at initial diagnosis is associated with renal outcome and prognosis in children with AGN. Methods: Clinical and prognostic data for children admitted to our center with AAV from January 2001 to August 2023 were analyzed retrospectively. We compared the incidence of end-stage renal disease (ESRD) and mortality according to infection status at initial diagnosis. Results: A total of 33 children with AGN were included in this study, 22 had an infection at the time of AGN diagnosis. A trend toward higher levels of proteinuria in the infected group than in the non-infected group was observed (p = 0.42). Patients in the infected group had higher creatinine and lower eGFR values than those in the non-infected group (p = 0.09). A significant decrease in HGB was observed in the infected group (p < 0.05). There were no significant differences in the baseline values of ALB and complement c3 between the two groups. A similar proportion of patients in both groups required dialysis at the time of diagnosis (27.3% vs. 31.8%). Patients with infection presented with significantly greater ESR and CRP levels (p < 0.05), and the most commonly infected site was the lung. After 6 months of treatment, compared with those in the non-infected group, the median levels of creatinine and proteinuria were higher in the infected group. Besides, lower levels of eGFR and ALB were also observed in the infected group. 5 (45.5%) and 13 (59.1%) patients died or progressed to ESRD, respectively, in the non-infected group and infected group at the last follow-up. Conclusions: Infection at initial diagnosis does not affect the outcomes of children with AGN, although it could lead to a reduction in kidney function. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the diversity of ocular manifestations in patients with positive perinuclear antineutrophil cytoplasmic antibody (p-ANCA). Methods: The clinical records of five patients exhibiting ocular manifestations and testing positive for serum MPO-ANCA were retrospectively reviewed. Results: Three out of five patients were female. The youngest patient was aged 26, whereas the eldest was 83 years old. 80% (n = 4) of them had purely anterior segment involvement, with the commonest manifestation being peripheral ulcerative keratitis and scleritis. Only one patient had posterior segment involvement, specifically posterior ischemic optic neuropathy. Two patients demonstrated unilateral involvement. There was only one patient diagnosed with systemic involvement, presenting as mixed nephrotic and nephritic syndrome, who required a course of intravenous methylprednisolone during the active stage. Three patients required second-line immunosuppressants throughout the course due to frequent relapse. Conclusion: Anterior segment ocular manifestations are not uncommon and can be the initial presentation of p-ANCA-associated vasculitis (AAV). Therefore, its evaluation should be considered in establishing the diagnosis of AAV, a life-threatening disease. [ABSTRACT FROM AUTHOR]

Objective: Pulmonary involvement is commonly observed in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), presenting with manifestations such as diffuse alveolar hemorrhage, inflammatory infiltrates, pulmonary nodules, and tracheobronchial disease. We aimed to identify distinct subgroups of tracheobronchial disease patterns in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) using latent class analysis (LCA), and to evaluate their clinical characteristics and outcomes. Methods: We conducted a retrospective cohort study using electronic medical records of patients aged >18 years diagnosed with AAV and tracheobronchial disease between 1 January 2002 and 6 September 2022. Patients with follow-up <6 months were excluded. LCA was employed to identify disease subtypes based on 10 pre-defined indicators. Maximum likelihood estimation with 10 repetitions per model ensured robustness in model selection, guided by the Akaike information criterion (AIC). Patient and disease characteristics were summarized and compared across predicted classes. Statistical analyses included Kruskal–Wallis and Fisher's exact tests for continuous and categorical variables, respectively. The primary outcome was time to relapse of the tracheobronchial inflammation after starting immunosuppressive medication, analyzed using the Kaplan–Meier method and log-rank tests. Secondary outcomes included severity of pulmonary disease on pulmonary function tests, endoscopic interventions, tracheostomy, or mortality during follow-up. Results: Among 136 identified AAV patients assessed for tracheobronchial involvement, 111 (81.6%) were included after excluding 25 without tracheal or bronchial disease. Predominant findings included subglottic stenosis (91.0%), lower tracheal stenosis (16.2%), and bronchial stenosis (17.1%). LCA identified a three-class model as optimal: tracheal predominant (n = 94), tracheobronchial (n = 12), and bronchial predominant (n = 5). Tracheal predominant patients showed reduced risk of ear, eye, and lower respiratory manifestations, with milder obstruction on pulmonary function testing (PFT). Tracheobronchial-class patients were prone to saddle nose deformity (50%), extensive lower respiratory involvement (91.7%), and renal disease (66.7%). Bronchial predominant patients exhibited severe obstructive disease (median forced expiratory volume in 1 s (FEV1)% predicted: 58, IQR 34–66; FEV1/forced vital capacity (FVC) ratio: 56.9, interquartile range (IQR) 43–63.3) but lacked systemic AAV manifestations. LCA classes did not predict outcomes such as endoscopic intervention, tracheostomy, recurrent tracheobronchial narrowing, or mortality. Conclusion: LCA shows promise in subtype stratification of AAV patients, yet its utility in predicting outcomes and guiding treatment remains limited based on our analysis. Future studies with enhanced phenotypic data and larger cohorts are warranted to improve predictive accuracy. [ABSTRACT FROM AUTHOR]

The article discusses autoimmune hepatitis (AIH), a condition characterized by immune-mediated inflammation affecting patients of all ages. Diagnosis of AIH involves a combination of clinical, laboratory, and histologic criteria. Treatment typically involves corticosteroids as the first-line therapy, with options for steroid-sparing agents like azathioprine or mycophenolate mofetil. In refractory cases, calcineurin inhibitors or other targeted therapies may be considered. Long-term management includes monitoring for relapse and potential withdrawal of immunosuppression in patients with complete biochemical response. Future directions in AIH treatment involve novel therapies targeting inflammatory pathways. [Extracted from the article]

Several studies have examined the utility of quadriceps femoris muscle biopsies for diagnosing antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). We aimed to investigate the effects of glucocorticoid therapy on the muscle biopsy findings of patients with AAV. Data from patients with AAV who underwent a biopsy of the bilateral vastus lateralis of the quadriceps femoris at Tokyo Metropolitan Tama Medical Center between January 2015 and December 2023 were retrospectively analyzed. In total, 126 patients with suspected small vessel vasculitis (SVV) or medium vessel vasculitis (MVV) underwent a muscle biopsy at the study center. Of these, the present study included 71 patients with a final diagnosis of AAV who received a muscle biopsy of the bilateral vastus lateralis at disease onset and began glucocorticoid therapy at the study center. Of the 71 patients, 41 (57.7%) had a positive muscle biopsy finding as defined by the presence of inflammatory infiltrates with fibrinoid necrosis in the vessels. Fifty-six and 15 patients underwent a biopsy before and after starting glucocorticoid therapy, respectively. Of the former, 33 (58.9%) had a positive finding compared to eight (53.3%) of the latter (Pearson's chi-square test: p = 0.697). Among the patients with a positive biopsy result, 22 (53.7%) and 19 (46.3%) had a unilaterally and bilaterally positive finding, respectively. Glucocorticoid therapy did not significantly affect the findings of quadriceps femoris muscle biopsies. Unilateral biopsies may have a lower diagnostic sensitivity for AAV than bilateral biopsies. Key Points • Glucocorticoid therapy does not significantly impact the results of quadriceps femoris muscle biopsies in patients with antineutrophil cytoplas¬mic antibody (ANCA)-associated vasculitis (AAV). • Unilateral biopsies may have a lower diagnostic sensitivity for AAV than bilateral biopsies. [ABSTRACT FROM AUTHOR]

Objective: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is an autoimmune disease that is challenging to treat. This study aimed to identify the effect of sodium ferulate on endothelial dysfunction mediated by neutrophil extracellular trap (NET)–platelet activation in AAV to provide potential strategies for AAV treatment. Material and Methods: An animal model of myeloperoxidase (MPO)-AAV passive immune vasculitis was established using anti-MPO immunoglobulin G and Rag2 knockout mice. The efficacy and mechanism of action of sodium ferulate in AAV were explored in cultured and isolated endothelial progenitor cells (EPCs), and messenger ribonucleic acid gene expression, relative protein expression, and protein fluorescence intensity were determined through quantitative polymerase chain reaction, Western blotting, and immunofluorescence, respectively. Serum antibody concentrations were determined by enzyme-linked immunosorbent assay, and flow cytometry was used in determining the expression levels of platelet-selectin (CD62p) and procaspase-activating compound-1 (PAC-1) on the surfaces of the platelets. The EPCs' ultramicroscopic structure was observed through transmission electron microscopy. Results: The expression levels of ANCA, histone H3 citrullinated, and MPO protein fluorescence intensity in MPO-AAV mice were inhibited by sodium ferulate, and the expression levels of CD62p and PAC-1 on the cell surface were reduced. The relative expression levels of β-trace protein (β-TG), soluble thrombomodulin, inducible nitric oxide synthase (iNOS), and tumor necrosis factor α decreased. We found that sodium ferulate inhibited NETs' free DNA and mitigated damage in EPCs. In addition, relative expression levels of von Willebrand Factor, β-TG, and iNOS and serum concentrations of PAC-1, β-TG, and iNOS were inhibited. Conclusion: Sodium ferulate can treat AAV by inhibiting NET release and platelet activation and reducing endothelial cell damage. [ABSTRACT FROM AUTHOR]

Background: Anti-ETAR (endothelin A receptor) antibodies and anti-CXCR3 (C-X-C motif chemokine receptor 3) antibodies are types of non-HLA (human leukocyte antigens) antibodies that could have some influence on the course of glomerulonephritis. The authors aimed to study the influence of these antibodies' levels on the course of specific glomerulonephritis types. Methods: We evaluated the anti-ETAR and anti-CXCR3 antibody levels in the serum of patients with membranous nephropathy (n = 18), focal and segmental glomerulosclerosis (FSGS) (n = 25), systemic lupus erythematosus (n = 17), IgA nephropathy (n = 14), mesangiocapillary glomerulonephritis (n = 6), anti-neutrophil cytoplasmic antibodies (c-ANCA) vasculitis (n = 40), and perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA) vasculitis (n = 16), and we compared their levels with the control group (n = 22). Next, we observed the patients' clinical parameters (serum creatinine, albumin, total protein) for 2 years and checked the correlation of the clinical course markers with basic receptor antibody level. Results: Our results indicate lower anti-ETAR antibody levels in patients with FSGS and IgA nephropathy compared to the control group. Both types of antibodies correlated with creatinine levels after 2 years of observation in IgA nephropathy. Both types of antibodies seemed to negatively influence the total protein and albumin levels in systemic lupus erythematosus. Conclusions: This prospective observation showed that anti-ETAR and anti-CXCR 3 antibody levels are connected with the course of IgA nephropathy and lupus nephritis. [ABSTRACT FROM AUTHOR]

PurposeMethodsResultsConclusionsTo report a complex case of serpiginous-like choroiditis (SLC) in a patient with anti-neutrophil cytoplasmic antibody (ANCA)-anti-proteinase 3 (PR3)-associated vasculitis with systemic involvement.Case report.A 40-year-old male from a tuberculosis (TB)-endemic region presented with bilateral active SLC lesions. He was diagnosed with ANCA-PR3 vasculitis with unilateral otitis media, nasopharyngeal mass, lung abscess, pleurisy, and joint pain, all of which responded well to corticosteroids and rituximab. Extensive evaluations and biopsies ruled out Mycobacterium tuberculosis infection. Despite consensus criteria recommending anti-tubercular therapy (ATT), the SLC lesions were effectively managed with an intravitreal dexamethasone implant and systemic azathioprine, showing no recurrence at 18 months without ATT.The development of SLC lesions in the context of systemic autoimmune conditions like ANCA-PR3 vasculitis is uncommon. In these cases, the need for ATT should be carefully evaluated, with close attention to systemic disease manifestations and tailored management strategies. [ABSTRACT FROM AUTHOR]

Background: The association between interstitial lung disease (ILD) and microscopic polyangiitis (MPA) has received increasing attention in recent years. However, there are still no studies comparing clinical characteristics and prognoses between MPA-ILD patients and patients with ANCA-negative ILDs. Therefore, the purpose of this study was to analyse a group of patients presenting MPA-ILD matched with patients exhibiting ANCA-negative ILDs to identify differences in their clinical characteristics and survival. Methods: This study retrospectively reviewed the data of 60 patients with MPA-ILD and 60 patients with ANCA-negative ILDs who were matched for age, sex, and patterns on chest high-resolution CT (HRCT) images. The baseline clinical information, laboratory parameters and chest CT data were collected and analysed at each patient's initial diagnosis. Results: Sixty of the 682 (8.8%) ILD patients were diagnosed with MPA-ILD. MPA-ILD patients tended to be older and have higher CRP and ESR levels. ILD antedated MPA in 61.7% (37/60) of the patients, and MPA occurred on average (45.1 ± 33.4) months after the ILD diagnosis. Compared with matched ANCA-negative ILD patients, MPA-ILD patients had higher CRP and serum creatinine levels and lower haemoglobin levels. UIP (63.3%) was the most common chest HRCT pattern, and the proportion of patients with oddly shaped cysts (P = 0.04) was significantly greater in the MPA-ILD group than in the matched ANCA-negative ILD group. The number of MPA-ILD patients was significantly shorter than that of ANCA-negative ILD patients (P = 0.005). Survival analysis revealed that acute exacerbation (AE) of ILD (HR 2.40, 95% CI 1.03–5.59, P = 0.043) and diffuse alveolar haemorrhage (HR 3.42, 95% CI 1.09–10.73, P = 0.036) were independently associated with shorter survival and that receiving glucocorticoids combined with immunosuppressants (HR 0.11, 95% CI 0.03–0.37, P < 0.001) was independently associated with prolonged survival in MPA-ILD patients. Conclusions: The proportion of MPA-ILD patients with total ILD is not low, and ANCA testing of ILD patients is necessary. Oddly shaped cysts with a UIP pattern may be a characteristic chest imaging manifestation of MPA-ILD. The prognosis of MPA-ILD is poor, especially for patients who are older, have DAH, and have experienced AEs. [ABSTRACT FROM AUTHOR]

Granulomatosis of polyangiitis (GPA) is a multisystem necrotizing vasculitis, which affects small- and medium-sized blood vessels and characterized by frequent involvement of the upper and lower respiratory tract and kidneys. Altough anti-neutrophil cytoplasmic antibodies (ANCA) are higly associated with GPA and play an important role in the pathogenesis of this disease, ANCA positivity is not essential for clinical diagnosis. We describe a patient with ANCA-negative granulamatosis of polyangiitis involving cerebellum, having complaints due to sinusitis. [ABSTRACT FROM AUTHOR]

Background Kidney complications associated with anticancer drug therapy have greatly increased recently. We aimed to investigate the real-world clinical outcomes of anticancer drug therapy–associated renal complications in Japan using the national kidney biopsy database, Japan Renal Biopsy Registry (J-RBR). Methods From 2018 to 2021, 449 cases from 49 facilities identified as 'drug-induced' histopathology in the J-RBR were screened, of which a total of 135 were confirmed as anticancer drug–related cases and included in the analysis. Overall survival rates were estimated using the Kaplan–Meier method and compared by logrank test. The Cox regression model was used to evaluate the association between variables and deaths. Results The most common primary sites of malignancies were the lung (33.3%), followed by gastrointestinal (16.3%) and gynaecological (11.1%) cancers. Tubulointerstitial nephritis (TIN; 47.4%) and thrombotic microangiopathy (TMA; 35.6%) were the most frequent diagnoses. All immunoglobulin A nephropathy, minimal change disease and crescentic glomerulonephritis (CrGN) cases were immune checkpoint inhibitor related. All CrGN cases were anti-neutrophil cytoplasmic antibody negative. Antibiotics were most frequently used concomitantly with anticancer drugs in TMA cases among subgroups (TMA versus others: 62.5 versus 27.5%; P  < .001). Among TMA cases, the serum lactate dehydrogenase level tended to be higher in cytotoxic agent–associated TMA (CTx-TMA) than in other TMAs, but was not significant between groups (415.5 versus 219.0 U/l; P  = .06). Overall survival was worse in CTx-TMA than in other TMAs (P  = .007). The Cox model demonstrated proton pump inhibitor (PPI) use (hazard ratio 2.49, P  = .001) as a significant prognostic factor, as well as the presence of metastasis and serum albumin level. Conclusions Our registry analysis highlighted various presentations of biopsy-proven kidney complications associated with anticancer drug therapy. Clinicians should be aware of worse outcomes associated with CTx-TMA and the prognostic role of PPI use. [ABSTRACT FROM AUTHOR]

The article discusses a unique case of a 67-year-old woman with IgG4‐related disease (IgG4‐RD) presenting with a gingiva lesion and extensive cerebral edema, a rare manifestation of the disease. Despite normal serum IgG4 levels, the diagnosis was confirmed through biopsy results, highlighting the complexity of IgG4‐RD's clinical presentations. The patient responded well to prednisolone therapy, with a significant reduction in edema observed on follow-up MRI scans. This case underscores the importance of histopathological and immunohistochemical analyses in diagnosing IgG4‐RD and the variability in its clinical manifestations. [Extracted from the article]

Objective: To evaluate the frequency and the clinical relevance of thyroid disease in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) patients. Methods: A total of 305 AAV patients admitted to the Second Affiliated Hospital of Chongqing Medical University between October 2010 and December 2023 were analyzed. Demographic, clinical, and laboratory data were compared between AAV patients with and without thyroid disease. Univariate and multivariate logistic regression analyses were conducted to identify factors associated with thyroid disease in AAV patients. Results: Among the 305 AAV patients, 52 (17.0%) had concurrent thyroid disease. In univariate analysis, gender, coronary artery disease, renal involvement, anti-Ro/SSA antibodies, anti-Ro52 antibodies, anti-thyroglobulin antibodies (TgAb), and anti-thyroid peroxidase antibodies (TPOAb) exhibited significant differences between AAV patients with and without thyroid disease (P < 0.05). Multivariate analysis revealed that female gender (odds ratio (OR) = 2.423, 95% confidence interval (95% CI) 1.241, 4.729; P = 0.009), concurrent coronary artery disease (OR = 2.998, 95% CI 1.280, 7.019; P = 0.011), and positive anti-Ro/SSA antibodies (OR = 4.697, 95% CI 1.960, 11.257; P = 0.001) were associated with thyroid disease in AAV patients. Conclusion: AAV patients have a higher incidence of thyroid disease. Regular monitoring of thyroid function is advised for AAV patients, particularly for women, those with coronary artery disease, and those who are positive for anti-Ro/SSA antibodies. Key Points • AAV patients have a higher incidence of thyroid disease. • The potential clinical relevance of AAV patients with thyroid disease was explored. • Regular monitoring of thyroid function is advised for AAV patients. [ABSTRACT FROM AUTHOR]

Objective ANCA-negative granulomatosis with polyangiitis (GPA) remains a diagnosis of exclusion. Clinical differences between patients with ANCA-negative vs ANCA-positive GPA have not been analysed in sizable case-control studies, and the effects of ANCA-seroconversion from negative to positive are not well documented. Methods A single-centre, sex and age matched case-control study evaluated ANCA-negative vs ANCA-positive GPA from 1 January 1996 to 31 December 2015. Patients who experienced seroconversion were the subject of a case-crossover study. Clinical data and outcomes were retrieved from electronic medical records. Results ANCA-negative GPA was identified in 110 patients; 65% were female; median age was 55 (IQR 39–65) years at time of diagnosis. Disease severity was milder in ANCA-negative GPA (BVAS/WG = 2 vs 6, P  < 0.001). Mucous membranous/eye manifestations were more frequent in ANCA-negative GPA. General symptoms, pulmonary and renal involvement were more frequent in ANCA-positive GPA. Patients with ANCA-positive GPA relapsed more over 60 months (21.8% vs. 9.1%, P =  0.009) compared with ANCA-negative GPA and had shorter time to event (P =  0.043). Patients with general manifestations, BMI > 30kg/m2 and necrotizing granulomatous inflammation were more likely to relapse. The 16 patients who seroconverted into ANCA-positive during follow-up had higher mean BVAS/WG at time of diagnosis (P <  0.001) and increased incidence of relapses (P =  0.004) after seroconversion. Necrotizing granulomatous inflammation on biopsy in ANCA-negative GPA patients was identified as a risk factor for subsequent seroconversion to ANCA-positivity. Conclusion Patients with ANCA-negative GPA have milder disease and a lower frequency of relapse than those with ANCA-positive GPA. ANCA appearance portended higher disease severity and an increased frequency of relapses. [ABSTRACT FROM AUTHOR]

Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is a multisystemic, immune-mediated disease that occurs in patients with asthma and eosinophilia. It is characterized by inflammation of small- and medium-caliber blood vessels. Case report: This report presents an unusual clinical case of EGPA with positive anti-neutrophil cytoplasmic antibodies who manifested bilateral pleural effusion. The diagnosis was confirmed through laboratory assessments and bronchial biopsies. The patient was treated with methylprednisolone showing improvement in symptoms. Conclusions: Our case appear interesting considering the limited evidence of pleural effusion in patients with EGPA documented in the literature. [ABSTRACT FROM AUTHOR]

Although rapidly progressive glomerulonephritis (RPGN) is the main renal phenotype of microscopic polyangiitis (MPA), we aim to clarify the clinical features of slowly progressive MPA. This retrospective observational study included 12 patients diagnosed with MPA in our hospital between January 2012 and February 2022. We investigated the differences in surrogate markers, rate of decline of estimated glomerular filtration rate (eGFR) between the slowly progressive and rapidly progressive MPA groups. Of the 12 patients with MPA, 3 (25.0%) had slowly progressive MPA: MPA within 30% decrease in eGFR 3 months pretreatment, all of whom developed RPGN during the course. Patients with slowly progressive MPA had lower levels of C-reactive protein, myeloperoxidase anti-neutrophil cytoplasmic antibodies, and interleukin-6; higher levels of sialylated carbohydrate antigen KL-6. Slowly progressive MPA is not uncommon in our hospital. A linear relationship was found between slower rate of eGFR decline and lower surrogate markers of disease activity. Some MPA cases have slowly progressive glomerulonephritis leading to RPGN, which may be clinically characterized by low disease activity. It may be useful to measure myeloperoxidase anti-neutrophil cytoplasmic antibody in chronic kidney disease with concomitant urinary abnormalities to diagnose MPA with slowly progressive glomerulonephritis. KEY LEARNING POINTS: Rapidly progressive glomerulonephritis is the main renal phenotype of microscopic polyangiitis (MPA), and slowly progressive MPA is rarely observed. Slowly progressive MPA was not rare in our hospital and was characterized clinically by low disease activity and complicated by interstitial pneumonia. When encountering patients with undiagnosed chronic kidney disease complicated by interstitial pneumonia, measuring myeloperoxidase anti-nuetrophil cytoplasmic antibody regardless of the rate of renal function decline, potentially leads to the diagnosis of slowly progressive MPA. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to evaluate the impact of the coronavirus disease-2019 (COVID-19) pandemic on the incidence and clinical characteristics of granulomatosis with polyangiitis (GPA) in patients diagnosed before and after the onset of the pandemic. Material and Methods: A retrospective analysis was conducted on 67 patients diagnosed with GPA between 2012 and 2023, categorized into pre-pandemic (n=35) and post-pandemic (n=32) cohorts. Data on sociodemographic, laboratory, and clinical characteristics were collected and statistically analysed. Results: The incidence of GPA increased from approximately 0.58 to 1.07 cases per 100,000 person-years post-pandemic. No statistically significant differences were observed in most clinical parameters, although a notable rise in alkaline phosphatase levels was identified (p=0.016). The demographic analysis revealed a higher prevalence of male patients in the post-pandemic group (p=0.020). Despite the increased incidence, mortality rates and clinical features remained stable between the two periods. Conclusion: The findings suggest a significant association between the COVID-19 pandemic and the increased incidence of GPA, potentially linked to immune dysregulation triggered by severe acute respiratory syndrome coronavirus 2 infection. While the clinical management of GPA has remained effective, the need for heightened awareness of autoimmune conditions in the context of COVID-19 is emphasized, warranting further investigation into the long-term implications of viral infections on autoimmune diseases. [ABSTRACT FROM AUTHOR]

Antineutrophil cytoplasmic antibody-associated (ANCA) vasculitis are a group of autoimmune diseases characterized by inflammation of the microvasculature, leading to life-threatening complications, including kidney disease. These diseases are associated with a high morbidity and mortality rate. Conventional treatment modalities have evolved towards personalized therapies intending to mitigate inflammation and minimize the adverse effects of traditional immunosuppressive agents. Avacopan, a novel C5a receptor inhibitor, represents a promising therapeutic option for vasculitis with renal involvement. This article provides a comprehensive review of the role of complement in the pathogenesis of vasculitis with renal involvement and the role of avacopan for its treatment, taking into account recent updates to both the EULAR and KDIGO guidelines and published experience of avacopan use in real clinical settings. [ABSTRACT FROM AUTHOR]

The article discusses a rare subtype of idiopathic multicentric Castleman disease known as the TAFRO syndrome, characterized by thrombocytopenia, anasarca, reticulin fibrosis, renal dysfunction, and organomegaly. The diagnosis of Castleman disease requires careful clinicopathological correlation, and radiographic adrenal abnormalities can serve as a diagnostic clue for TAFRO. Treatment with an interleukin-6 inhibitor is crucial to prevent morbidity and death, with rapid initiation often resulting in excellent outcomes. The case study presented in the article highlights the challenges in diagnosing and treating this rare disease, emphasizing the importance of early recognition and appropriate therapy. [Extracted from the article]

Tumor necrosis factor alpha inhibitors (TNFi) are biological drugs used worldwide to treat various autoimmune disorders. Paradoxically, TNF‐α antagonists can also induce autoimmune diseases being systemic vasculitis, systemic lupus erythematosus, and psoriasis, the most common. We present a 22‐year‐old woman with ulcerative colitis (UC) who was started on adalimumab 40 mg subcutaneously every 2 weeks. After two doses of adalimumab, she developed gangrene of all toes and acute kidney injury requiring hemodialysis. Skin biopsy showed thrombi in the small vessels of the dermis. Renal biopsy disclosed diffuse proliferative glomerulonephritis (GN) and acute tubulointerstitial nephritis. Serologic work‐up showed positive IgG anticardiolipin (ACL) antibodies and low C3 levels. Antinuclear, anti‐dsDNA, anti‐Smith, anti‐SSA, anti‐SSB, anti‐RNP, antineutrophil cytoplasmic antibodies, ACL (IgA and IgM), and anti‐β2‐glycoprotein I (IgG, IgM, and IgA) antibodies were not elevated. Lupus anticoagulant test and cryoglobulins were negative. Adalimumab was discontinued, and she was treated with enoxaparin, intravenous (IV) methylprednisolone pulse, IV cyclophosphamide, and plasmapheresis followed by maintenance therapy with warfarin, prednisone, azathioprine, and hydroxychloroquine. She did not have further thrombotic events, and the acute kidney injury completely resolved. ACL IgG antibodies decreased to normal levels, and repeated tests were negative. After 7 years, anticoagulation and immunosuppressive drugs were discontinued. During a follow‐up of 24 months, she remained in complete clinical remission. This report highlights the occurrence of autoimmune disorders induced by TNFi. Thus, careful monitoring of adverse immune reactions to TNFi is highly recommended. [ABSTRACT FROM AUTHOR]

This article from Clinical Case Reports discusses a case of a diabetic patient with focal segmental glomerulosclerosis (FSGS) and infection-related glomerulonephritis (IRGN) leading to rapid renal decline. The patient's complex condition required careful management to balance immunosuppressive treatments for FSGS with infection control strategies for IRGN. The case highlights the importance of multidisciplinary collaboration, timely histopathological assessment, and personalized treatment approaches to prevent irreversible kidney damage in high-risk patients with overlapping pathologies. [Extracted from the article]

The article discusses three cases of children diagnosed with juvenile dermatomyositis (JDM) complicated by systemic capillary leak syndrome (SCLS), a condition characterized by capillary leakage leading to anasarca, hemoconcentration, hypoalbuminemia, and hypotension. The cases highlight the severe manifestations of JDM with SCLS, including complications such as shock, acute kidney injury, and acute respiratory distress. Effective management involves aggressive immunosuppression and supportive care, with early recognition and prompt treatment being crucial for successful intervention. The study emphasizes the importance of timely immunosuppression and targeted therapy to reduce morbidity and mortality in such cases. [Extracted from the article]

The article discusses a case of neurosarcoidosis in a 54-year-old female patient with a history of sarcoidosis. The patient experienced visual hallucinations and dizziness, leading to a diagnosis of neurosarcoidosis. Treatment with low-dose methylprednisolone pulse therapy followed by oral methylprednisolone resulted in rapid remission. The case highlights the importance of prompt diagnosis, personalized treatment, and shared decision-making in managing neurosarcoidosis, with a focus on patient-centered care. The successful outcome suggests that dose de-intensification strategies could be beneficial for other neurosarcoidosis patients, potentially influencing future treatment guidelines. [Extracted from the article]

Vasculitis in children represents a diverse group of diseases characterized by inflammation of blood vessels, which can lead to significant morbidity if not promptly recognized and managed. This review explores the epidemiology, pathophysiology, classification, and management of key pediatric vasculitides. Classification based on vessel size aids in diagnosis and treatment. Understanding these conditions” clinical features and therapeutic options is critical for improving pediatric patient outcomes and preventing long-term complications. Continued research is essential for refining treatment strategies and enhancing patient care. [ABSTRACT FROM AUTHOR]

Waldenstrom macroglobulinaemia (WM), the predominant subtype of lymphoplasmacytic lymphoma with bone marrow involvement and serum IgM paraprotein, is a haematological condition commonly associated with renal parenchymal involvement. However, antineutrophil cytoplasmic antibody (ANCA)‐negative pauci‐immune crescentic glomerulonephritis (PICGN) in kidney infiltrated by lymphoma is very rare, with only two cases described in chronic lymphocytic leukaemia in English literature so far. We herein report the first patient with WM developing ANCA‐negative PICGN. He was a 76‐year‐old male who presented with elevated serum globulin level and bilateral groin lymph node enlargement, subsequently diagnosed to have WM after pathologic examination of the bone marrow and groin lymph node. One month later, he was found to have acute kidney injury and proteinuria. Renal biopsy confirmed the presence of parenchymal involvement by WM accompanied by PICGN; while ANCA testing was negative. He was treated with pulse methylprednisolone followed by oral prednisolone. In addition, six courses of intravenous rituximab and oral cyclophosphamide were given. There was significant improvement in both his renal and haematological conditions. The clinical course of this case suggested that ANCA‐negative PICGN may represent a paraneoplastic syndrome and a rare manifestation of WM‐associated renal lesion. Early kidney biopsy and prompt treatment may improve the outcome of patients. [ABSTRACT FROM AUTHOR]

A 71-year-old woman presented with a 30-year history of recurrent oral and nasopharyngeal ulcers, facial erythema, vesicles, and scars, along with pancytopenia and elevated ferritin levels. Laboratory tests revealed positive Epstein–Barr virus (EBV) DNA in the blood, leading to a diagnosis of Chronic active EBV disease (CAEBV) of T-cell type. Treatment with oral methylprednisolone and ganciclovir resulted in the resolution of symptoms, highlighting the challenges in diagnosing and treating CAEBV. The study was supported by the Science Foundation of Yunnan Province and the patients provided consent for participation and publication of their case details. [Extracted from the article]

Objective: Infections are a critical concern for patients with microscopic polyangiitis (MPA). This study aimed to identify the risk factors associated with serious infections (SIs) and infection-related mortality in patients with MPA, as well as the effect of glucocorticoid (GC) dose tapering on these outcomes. Methods: This multicentre, retrospective, and observational study utilised data from a cohort of patients with MPA in Japan [Registry of Vasculitis Patients to Establish REAL World Evidence (REVEAL) cohort]. Patients were categorised based on the occurrence of SIs or infection-related deaths, and various characteristics were compared among the groups. Results: Among 182 patients, 66 (36.2%) experienced 129 SIs and 27 (14.8%) developed infection-related deaths. Advanced age, elevated C-reactive protein (CRP) levels, and higher ratio of the GC dose at 3 months to the initial dose were identified as independent risk factors for SIs. Older age was also associated with infection-related deaths. Furthermore, the cumulative incidence of infection-related deaths was significantly higher in patients with a higher ratio of the GC dose at 24 months to the initial dose. Conclusion: Older age, elevated CRP levels, and slower GC dose tapering predispose patients to SIs and infection-related deaths. Strategies, such as rapid GC dose tapering, are anticipated to mitigate the risk of infections. [ABSTRACT FROM AUTHOR]

Background: Hashimoto's thyroiditis (HT) is a common autoimmune thyroid disorder characterized by elevated anti-thyroid peroxidase (A-TPO) antibodies. HT frequently coexists with other autoimmune conditions, which are marked by organ-specific and non-organ-specific autoantibodies, reflecting a deregulated immune response. However, the burden and clinical significance of these circulating autoantibodies in adult patients with HT remains unclear. Methods: A cross-sectional study was conducted at the University Hospital "R. Dulbecco" in Catanzaro, Italy, from November 2023 to May 2024, involving 200 euthyroid adults. The study population comprised 100 A-TPO-positive HT patients and 100 A-TPO-negative controls, matched for age and sex. Laboratory assessments included thyroid function tests and detection of autoantibodies [e.g., antinuclear antibodies (ANA), anti-parietal cell antibodies (APCA), and anti-neutrophil cytoplasmic antibodies (ANCA)]. Cytokine profiles were also measured using sensitive chemiluminescent multi-array technology. Results: HT patients were predominantly female (77.0%) with a median age of 56 years. Compared to controls, HT patients had higher median thyroid stimulating hormone (TSH) levels (2.215 vs. 1.705 μIU/mL, p = 0.025). Circulating autoantibodies were more prevalent in the HT group, with higher rates of APCA positivity (16.3% vs. 4.1%, p = 0.008) and atypical ANCA positivity (27.3% vs. 10.2%, p = 0.003). This suggests an increased risk for autoimmune gastritis and systemic inflammation. Additionally, HT patients with positive atypical ANCA showed elevated inflammatory cytokines, particularly interleukin-1 alpha (IL-1α), in female patients (p = 0.035). Conclusions: HT is significantly associated with a higher prevalence of circulating autoantibodies, such as APCA and atypical ANCA, which may indicate a heightened risk for autoimmune gastritis and broader autoimmune involvement. Detecting these autoantibodies in HT patients could serve as markers for more severe autoimmune dysfunction. These findings emphasize the need for proactive screening, especially in older patients and those with elevated A-TPO levels. Further research is essential to better understand the clinical implications and develop targeted management strategies for these patients. [ABSTRACT FROM AUTHOR]

Background: The incidence of monoclonal gammopathy of undetermined significance (MGUS) in the population of over 50-year-olds is approximately 3% and increases with age. The association between MG and neuropathy has been of interest for several years, but the causal relationship has not yet been clarified. Methods: For 682 patients who visited the Department of Neurology and requested tests for MG work-up, we retrospectively collected demographic and clinical information, such as age, gender, diagnosis, and neurologic and laboratory test results, from their medical records. Results: Out of a total of 682 patients who were suspected of neuropathy and tested for monoclonal gammopathy (MG), twelve (1.76%) showed MG on their serum protein electrophoresis. The most common form was IgM-κ with five patients, followed by IgG-κ, IgG-λ, and biclonal IgG-λ and IgA-κ. The results of the immunoglobulin quantitation test and free light chain assay showed that involved M-protein values in these patients were increased. Some patients were positive for anti-myelin-associated glycoprotein (MAG) antibody, anti-GD1b IgM antibody, anti-GM1 IgG & IgM antibody, and anti-cardiolipin IgM antibody. Also, some had antinuclear antibody (ANA) or antineutrophil cytoplasmic antibody (ANCA). Conclusions: In the future, it is necessary to investigate the pathogenic relationship between M-protein and autoantibodies in patients with neuropathies. [ABSTRACT FROM AUTHOR]

Objective. This study aimed to compare the 2022 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) classification criteria with the European Medicines Agency (EMA) algorithm for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Methods. All consecutive, newly diagnosed patients with AAV according to the 2012 Chapel Hill Consensus Conference who visited Keio University Hospital between March 2012 and May 2022 were retrospectively reviewed. Patients were reclassified according to the EMA algorithm and the 2022 ACR/EULAR criteria, and their clinical characteristics were statistically analyzed. Results. A total of 114 patients with AAV were included in the analyses. Using the EMA algorithm as a reference, reclassification of the patients revealed sensitivity and specificity of the 2022 ACR/EULAR criteria of 100% and 96% for eosinophilic granulomatosis with polyangiitis, 40% and 97% for granulomatosis with polyangiitis (GPA), and 90% and 49% for microscopic polyangiitis (MPA), respectively. Approximately half of patients classified as EMA-GPA or EMA-unclassifiable were reclassified as 2022-MPA; these patients were older, were more disposed to be positive for myeloperoxidase (MPO)-ANCA, and had interstitial lung disease (ILD) more frequently than patients with 2022-GPA or non--2022-MPA. Further, some patients positive for MPO-ANCA with biopsy-proven granulomatous inflammation were also reclassified from EMA-GPA to 2022-MPA. Over the mean observation period of 4.0 years, 16 patients died. Overall survival for each classification group differed significantly from the 2022 ACR/EULAR criteria (P = 0.02), but not with the EMA algorithm (P = 0.21). Conclusion. Among the patients classified as EMA-GPA or EMA-unclassifiable, older patients with MPO-ANCA and ILD tended to be reclassified as 2022-MPA. The 2022 ACR/EULAR criteria were more useful in prognostic prediction than the EMA algorithm. [ABSTRACT FROM AUTHOR]

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

Here, we report a case of antineutrophil cytoplasmic antibody (ANCA)‐associated central nervous system (CNS) vasculitis that mimicked a brain tumor. The patient presented with progressive right upper arm weakness. Brain magnetic resonance imaging (MRI) revealed large tumor‐like lesions in the left frontal and parietal lobes, with patchy and irregular enhancement with gadolinium and edema. Based on the clinical course and radiological findings, a brain tumor was suspected, and stereotactic brain biopsy was performed. Brain histopathology revealed necrotic tissue and lymphocyte infiltration around small vessels and blood vessel walls. Although the patient's clinical course and pathological findings suggested primary angiitis of CNS (PACNS), double staining for myeloperoxidase (MPO) and CD31 (a neutrophil marker) revealed infiltration of MPO‐positive neutrophils in the blood vessel walls. Therefore, we diagnosed the patient with ANCA‐associated CNS vasculitis. Because CNS vasculitis, including PACNS, presents nonspecific clinical findings and can depict brain tumor‐like MRI findings, CNS vasculitis should be carefully differentiated from brain tumors. Additionally, double staining for MPO and CD31 might be useful for evaluating the pathogenesis of CNS vasculitis. [ABSTRACT FROM AUTHOR]

Background: Mepolizumab (MPZ) has demonstrated efficacy in clinical trials for eosinophilic granulomatosis with polyangiitis (EGPA); however, few studies compare the disease course between patients treated with MPZ (MPZ group) and those who were not treated with MPZ (non-MPZ group) in real-world settings. Objectives: This study aimed to compare the disease course and outcomes between the two groups and assess the long-term efficacy of MPZ in a multicenter cohort in Japan. Methods: We enrolled 113 EGPA patients registered in the cohort until June 2023. Data on clinical characteristics, disease activity, organ damage, treatments, and outcomes were retrospectively collected. To minimize potential confounding factors, we conducted propensity score matching (PSM). Results: After PSM, 37 pairs of matched patients were identified. Clinical characteristics, including age at disease onset, sex, disease duration at last observation, antineutrophil cytoplasmic antibody positivity at disease onset, Birmingham Vasculitis Activity Score (BVAS) at disease onset, and Five-factor score at disease onset, were comparable between the groups. The median BVAS at the last observation was 0 in both groups; however, more cases in the non-MPZ group exhibited elevated BVAS, resulting in a significantly higher BVAS in the non-MPZ group at the last observation (median; MPZ group: 0, non-MPZ group: 0, p=0.028). The MPZ group had significantly lower glucocorticoid (GC) doses at the last observation (median; MPZ group: 4 mg/day, non-MPZ group: 5 mg/day, p=0.011), with a higher proportion achieving a GC dose ≤ 4 mg/day at the last observation (MPZ group: 51.4%, non-MPZ group: 24.2%, p=0.027). Three models of multivariable logistic regression analyses were performed to identify factors associated with GC doses ≤ 4 mg/day at the last observation. In all models, achieving a GC dose ≤ 4 mg/day was positively associated with MPZ administration and inversely associated with asthma at disease onset. Finally, we evaluated the survival rates between the groups, and the 5-year survival rates were significantly higher in the MPZ group compared to the non-MPZ group (MPZ group: 100%, non-MPZ group: 81.3%, p=0.012). Conclusion: Mepolizumab not only contributes to disease activity control but also reduces the GC dose, which may lead to improved survival in EGPA patients. [ABSTRACT FROM AUTHOR]

The article provides an in-depth analysis of the immune and non-immune mediators involved in the fibrosis pathogenesis of salivary glands in Sjögren's syndrome. It explores the impact of chronic inflammation, immune cell interactions, viral infections, and molecular mechanisms on the development of fibrosis. The document also discusses therapeutic strategies targeting immune cells and fibroblasts to alleviate fibrosis in Sjögren's syndrome, emphasizing the need for further research to understand the complex pathogenesis and develop effective treatments. Additionally, it delves into the correlation of T follicular helper cells with immunopathology, therapeutic options for systemic sclerosis, and the unique expansion of IL-21+ Tfh and Tph cells in Sjögren's syndrome with ectopic germinal centers and malt lymphoma. [Extracted from the article]

Introduction: Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection, the causative agent of coronavirus disease 2019 (COVID-19), causes post-acute infection syndrome in a surprisingly large number of cases worldwide. This condition, also known as long COVID or post-acute sequelae of COVID-19, is characterized by extremely complex symptoms and pathology. There is a growing consensus that this condition is a consequence of virusinduced immune activation and the inflammatory cascade, with its prolonged duration caused by a persistent virus reservoir. Methods: In this cross-sectional study, we analyzed the SARS-CoV-2-specific T cell response against the spike, nucleocapsid, and membrane proteins, as well as the levels of spike-specific IgG antibodies in 51 healthcare workers, categorized into long COVID or convalescent control groups based on the presence or absence of post-acute symptoms. Additionally, we compared the levels of autoantibodies previously identified during acute or critical COVID-19, including anti-dsDNA, anti-cardiolipin, anti-b2-glycoprotein I, anti-neutrophil cytoplasmic antibodies, and anti-thyroid peroxidase (anti-TPO). Furthermore, we analyzed the antibody levels targeting six nuclear antigens within the ENA-6 S panel, as positivity for certain anti-nuclear antibodies has recently been shown to associate not only with acute COVID-19 but also with long COVID. Finally, we examined the frequency of diabetes in both groups. Our investigations were conducted at an average of 18.2 months (convalescent control group) and 23.1 months (long COVID group) after confirmed acute COVID-19 infection, and an average of 21 months after booster vaccination. Results: Our results showed significant differences between the two groups regarding the occurrence of acute infection relative to administering the individual vaccine doses, the frequency of acute symptoms, and the T cell response against all structural SARS-CoV-2 proteins. A statistical association was observed between the incidence of long COVID symptoms and highly elevated anti-TPO antibodies based on Pearson's chi-squared test. Although patients with long COVID showed moderately elevated anti-SARS-CoV-2 spike IgG serum antibody levels compared to control participants, and further differences were found regarding the positivity for anti-nuclear antibodies, anti-dsDNA, and HbA1c levels between the two groups, these differences were not statistically significant. Disscussion: This study highlights the need for close monitoring of long COVID development in patients with elevated anti-TPO titers, which can be indicated by strongly elevated SARS-CoV-2-specific T cell response and moderately raised anti-spike IgG levels even long after the acute infection. However, our results do not exclude the possibility of new-onset thyroid autoimmunity after COVID-19, and further investigations are required to clarify the etiological link between highly elevated anti-TPO titers and long COVID. [ABSTRACT FROM AUTHOR]

Objectives: We applied the 2022 American College of Rheumatology/ European Alliance of Association for Rheumatology (ACR/EULAR) criteria for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) to patients histologically diagnosed with lupus nephritis (LN) to investigate the overall rate of and initial contributing factors to the reclassification of overlap syndrome of LN with AAV (OS-LN-AAV). Methods: We retrospectively reviewed the medical records of 1292 patients with systemic lupus erythematosus (SLE) and included 164 patients with LN in this study. Patient demographics, SLE manifestations, LN classes, and laboratory data, including ANCA levels, were recorded. All-cause mortality and end-stage kidney disease (ESKD) were evaluated as poor outcomes. Results: The median age of the 164 patients was 37.0 years, and 12.2% were men. The overall reclassification rate was 37.8%, of which 34.1% and 3.7% of the patients were reclassified as having OS-LN-microscopic polyangiitis and OS-LN-granulomatosis with polyangiitis (GPA), respectively, but none as having eosinophilic GPA. ANCA positivity and AAV-suggesting lung lesions were major contributors to OS-LN-AAV reclassification. When patients were compared based on OS-LN AAV reclassification, ANCA positivity and myeloperoxidase-ANCA (or P-ANCA) positivity favoured for OS-LN-AAV reclassification, whereas oral ulcers did not. However, OS-LN-AAV reclassification did not affect all-cause mortality or ESKD. Conclusions: This is the first study demonstrating a 37.8% reclassification rate in patients histologically diagnosed with LN using the 2022 ACR/EULAR criteria for AAV. Furthermore, it was also the first to reveal ANCA positivity and AAV-suggesting lung lesions as major contributors to OS-LN-AAV reclassification. [ABSTRACT FROM AUTHOR]

Purpose: To report an uncommon, isolated presentation of bilateral choroidal detachments in a patient diagnosed with P-ANCA-associated vasculitis and to highlight the importance of an inflammatory work-up in such cases. Methods: Case report. Results: A 70-year-old male with a past medical history of autoimmune hepatitis presented with a sudden decrease in vision in both eyes. Over the course of the previous decade, he had experienced recurrent attacks of episcleritis, which were successfully managed with topical corticosteroid eye drops. The patient was diagnosed with bilateral detachments without accompanying scleritis or intraocular inflammation. Inflammatory markers revealed high P-ANCA and anti-MPO levels, confirming the diagnosis of P-ANCA-associated vasculitis. Treatment with systemic rituximab and corticosteroids led to the resolution of the choroidal detachment in both eyes. A 40-month follow-up confirmed the sustained resolution of the detachments. Conclusion: Choroidal detachment without other extraocular/intraocular inflammation can be associated with P-ANCA-associated vasculitis, a previously under-reported link. It is important to consider an inflammatory work-up for patients presenting with choroidal detachment to rule out conditions like P-ANCA-associated vasculitis. [ABSTRACT FROM AUTHOR]

The article discusses a case study of a 1-year-old girl with diffuse alveolar hemorrhage (DAH) as the initial presentation of hypomorphic RAG1 deficiency, a combined immunodeficiency disorder. The patient experienced severe respiratory symptoms, anemia, and abnormal immune cell counts, leading to a diagnosis of leaky severe combined immunodeficiency. Treatment with corticosteroids and immunoglobulins showed improvement, but the patient later died due to acute respiratory failure. The study highlights the importance of considering RAG1 deficiency in DAH cases and expanding autoantibody testing to anti-cytokine antibodies for diagnosis. [Extracted from the article]

Background: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis and glomerulonephritis is uncommon in children. We sought to characterize the histological and clinical features of the disease and report on risk factors for adverse outcomes in a pediatric cohort. Methods: Retrospective single-center cohort of all pediatric (< 20 years) patients diagnosed with ANCA-associated glomerulonephritis (AAGN) by kidney biopsy between 2002 and 2022 at Johns Hopkins University. Histological and clinical features were extracted from the medical record. Clinical, laboratory, and histological findings were analyzed to determine the association with kidney failure (KF) and/or death. Results: A total of 17 patients were identified (GPA n = 7, MPA = 10) with a median age of 15 years (IQR 12–17) at presentation, a slight female predominance (59%), with seven patients reaching the composite outcome of death (n = 1) or kidney failure (n = 6). There was no difference in presenting clinical symptoms or extra-renal manifestations between the two groups. Univariable Cox regression identified several factors associated with an increased hazard of endpoint including the degree of global or segmental sclerosis, interstitial fibrosis and tubular atrophy (IFTA), C3 and C1q staining, presence of subendothelial deposits, and proteinuria. Multivariable regression was not performed due to the small sample size. We saw a trend towards increased utilization of plasma exchange and a decrease in cyclophosphamide utilization in the more recent era. There was no association between treatment modality and outcome. Conclusions: Pediatric AAGN is a rare disease associated with significant morbidity. We identified glomerulosclerosis and IFTA on histology, and proteinuria on initial presentation as risk factors for KF/death. [ABSTRACT FROM AUTHOR]

Children with anti-neutrophil cytoplasmic antibody-associated vasculitis benefit immensely from avacopan as it reduces the requirement for steroids. However, descriptions of adverse drug reactions in children are lacking, and the dosage and follow-up intervals are unclear. A 10-year-old boy with initial granulomatosis and polyangiitis presented with diffuse pulmonary hemorrhage. Rituximab and 30 mg avacopan were administered twice daily as induction therapy following methylprednisolone pulse therapy. However, sudden liver function test abnormalities were observed on day 31 of avacopan treatment, despite liver enzyme levels being within the normal range 5 days earlier. A drug-induced lymphocyte stimulation and various infectious disease tests yielded negative results. Discontinuation of rituximab and avacopan resulted in improved liver function; no change in the Birmingham Vasculitis Activity Score during liver function test abnormalities was observed. Avacopan-associated abnormalities in liver function tests suggest that drug-induced liver injury may occur rapidly in children, and appropriate dosing strategies should be reconsidered. [ABSTRACT FROM AUTHOR]

Immunoglobulin glycosylation is a pivotal mechanism that drives the diversification of antibody functions. The composition of the IgG glycome is influenced by environmental factors, genetic traits and inflammatory contexts. Differential IgG glycosylation has been shown to intricately modulate IgG effector functions and has a role in the initiation and progression of various diseases. Analysis of IgG glycosylation is therefore a promising tool for predicting disease severity. Several autoimmune and alloimmune disorders, including critical and potentially life-threatening conditions such as systemic lupus erythematosus, anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis and antibody-mediated kidney graft rejection, are driven by immunoglobulin. In certain IgG-driven kidney diseases, including primary membranous nephropathy, IgA nephropathy and lupus nephritis, particular glycome characteristics can enhance in situ complement activation and the recruitment of innate immune cells, resulting in more severe kidney damage. Hypofucosylation, hypogalactosylation and hyposialylation are the most common IgG glycosylation traits identified in these diseases. Modulating IgG glycosylation could therefore be a promising therapeutic strategy for regulating the immune mechanisms that underlie IgG-driven kidney diseases and potentially reduce the burden of immunosuppressive drugs in affected patients. Here, the authors review the impact of IgG glycosylation in kidney diseases, particularly autoimmune diseases and antibody-mediated rejection. They also discuss the signalling pathways that govern antibody glycosylation, the impact of glycosylation on antibody functions and implications for therapy. Key points: Aberrant glycosylation of IgG is influenced by antibody subclass and antigen specificity and is established during B cell differentiation and maturation within germinal centres. Hypogalactosylation of the fragment crystallizable (Fc) of anti-PLA2R1 is a key feature of primary membranous nephropathy. Hypogalactosylation and hyposialylation of the Fc portion of anti-neutrophil cytoplasmic antibodies and total IgG in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis are associated with more severe disease and disease relapse. Among patients with systemic lupus erythematosus, those with lupus nephritis have reduced levels of galactosylation of the Fc portion of total IgG. In patients with IgA nephropathy, hypogalactosylated IgA1 triggers the generation of anti-hypogalactosylated IgA1 autoantibodies, leading to the formation of immune complexes. Aberrant hyposialylation and hypofucosylation of donor-specific antibodies are associated with antibody-mediated rejection of kidney grafts. [ABSTRACT FROM AUTHOR]

Objective: Cardiovascular diseases are the main causes of mortality in the anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) patients. Carotid intima-media thickness (CIMT) measurement and pulse wave velocity (PWV) were performed to determine atherosclerosis and arterial stiffness as cardiovascular risk markers. Patients and Methods: The data of 31 patients with AAV were compared with 21 healthy controls. Demographic and laboratory findings were recorded. Results: Seventeen patients (54.8%) were male. Mean age was 52.6±11.5 years. CIMT was higher in the patient group [0.74 (0.65 -- 0.84) vs 0.63 (0.57-0.74) mm; p=0.048]. PWV [7.9 (6.7-9.3) vs 7.8 (6.8-8.5) m/s; p=0.295] and augmentation index (AI) [22.5 (11.0-30.0) vs. 23 (9.5-30.5) mm/Hg, p=0.801] were similar in both groups. CIMT was correlated with age (r: 0.538, p<0.001) and PWV (r: 0.554 p< 0.001) while there was no correlation with AI (r: 0.047, p= 0.764). Conclusion: The present study showed that CIMT is significantly increased and correlated with age and PWV in patients with AAV compared to controls. CIMT can be used as a screening tool as part of patient follow-up to identify patients at cardiac risk. [ABSTRACT FROM AUTHOR]

Objective: Patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV) and systemic lupus erythematosus (SLE) are prone to infections. This study aims to clarify infectious complications in terms of both the disease and the specific treatments used. Patients and Methods: Sixty-three patients with SLE and AAV with kidney involvement treated with rituximab or cyclophosphamide were included. Patients were examined regarding infections, comorbidities, immunosuppressives, estimated glomerular filtration rate (eGFR), use of prophylactic antibiotics, hospitalization, and death. Results: Patients with SLE experienced more genitourinary infections in general (p=0.009). In the rituximab group, SLE patients had a higher incidence of genitourinary infections, septicemia, and intensive care unit admissions. Furthermore, lupus patients with serious infections were all treated with rituximab and had a higher incidence of low respiratory tract infections (p=0.003). On the contrary, treatment with rituximab did not cause an increased risk of infection among AAV patients compared to cyclophosphamide. In general, patients with serious infections had lower IgG and total Ig levels (p<0.05). Conclusion: Patients with SLE had a higher risk of genitourinary infections and also a higher risk of sepsis, serious infections, and hospitalizations when treated with rituximab. Immunoglobulin levels are associated with serious infections. [ABSTRACT FROM AUTHOR]

The article discusses a case of erythema nodosum (EN) induced by a tumor necrosis factor‐alpha (TNF‐α) inhibitor in a 60‐year‐old female patient with peripheral spondyloarthritis. The patient developed painful nodules on her legs after treatment with adalimumab and later etanercept. The article provides a comprehensive literature review of similar cases and highlights the importance of considering EN as a potential side effect of anti‐TNF therapy. The authors emphasize the need for a thorough diagnostic workup to rule out other causes of EN and suggest collaborative management with a dermatologist while maintaining anti‐TNF therapy if it effectively controls the underlying autoimmune condition. [Extracted from the article]

We aimed to clarify the long-term safety and efficacy of rituximab (RTX) as a remission induction therapy following severe relapse in patients with antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV). We retrospectively collected the data of patients with severely relapsed AAV from a Japanese multicentre cohort. The primary exposure was RTX use; the primary outcome was complete remission (CR) proportions at week 24. Baseline characteristics were compared between the RTX and non-RTX groups. We performed multivariate logistic regression analysis and one-to-one propensity score matching analysis as a sensitivity analysis. Totally, 100 patients were enrolled: 52 in the RTX group and 48 in the non-RTX group. Baseline characteristics were comparable between the two groups, except for age, AAV subtype and ANCA serotype. The median age was 71 vs. 75 years, and the PR3-ANCA positivity rate was 44.2% vs. 18.8% in the RTX and non-RTX groups, respectively. No significant difference was observed in CR proportions at week 24 between the two groups (79.2% vs. 68.1%, p = 0.321), with an adjusted odds ratio of 1.27 (95% confidence interval [CI] 0.47–3.51). At week 48, CR proportions were significantly higher in the RTX group (91.7% vs. 64.9%, p = 0.005), with an adjusted odds ratio of 2.95 (95% CI 0.97–9.91). Serious infection rates were lower in the RTX group than in the non-RTX group, with no statistically significant difference. RTX was not superior to conventional immunosuppressive therapies at week 24 but showed significantly favourable results at week 48 for severely relapsed AAV. Key Points • RTX might be superior to traditional treatments as an induction therapy for severely relapsed AAV. • RTX has the potential to sustain long-term remission with fewer occurrences of infections in the treatment of severely relapsed AAV. [ABSTRACT FROM AUTHOR]

This article discusses a study that examined the frequency of positive antineutrophil cytoplasmic antibody (ANCA) tests during the COVID-19 pandemic compared to before the pandemic. The study found that both PR3-ANCA and MPO-ANCA tests were more commonly ordered during the pandemic. Positive results for PR3-ANCA were more frequently detected during the pandemic, while positive results for MPO-ANCA were more commonly detected before the pandemic. The study suggests a potential link between COVID-19 and the development of autoimmune diseases, but further research is needed to understand the underlying mechanisms. The study also emphasizes the importance of educating physicians about ANCA and autoimmune vasculitis. [Extracted from the article]

Introduction: Nephrotic syndrome (NS) is a common childhood glomerular disease. The most common presentation in paediatric population is the idiopathic syndrome (INS). Treatment with levamisole is effective in frequent re- lapsing and corticosteroid-dependent NS. Studies have reported mild and rarely severe side effects, which subside after treatment withdrawal. Results: We describe two clinical cases of frequently relapsing INS treated with levamisole that presented with cutaneous vasculitis with positive anti-neutrophil cytoplasmic antibodies. Both cases had skin lesions that disappeared after withdrawal of the drug, avoiding the use of other treatments with corticosteroids, immunomodulators and even amputations due to skin necrosis. Conclusions: It is important to know the possible complications of levamisole treatment in paediatric patients with INS to proceed with drug withdrawal for resolution. [ABSTRACT FROM AUTHOR]

Objectives ANCA-associated vasculitis (AAV) is associated with significant morbidity, fatigue, pain and poor health-related quality of life (HRQoL). This review aims to assess the comprehensiveness of existing patient reported outcome measures (PROMs) used in AAV and identify associations with poorer HRQoL outcomes. Methods A literature review of studies using PROMs, including those labelled HRQoL in people with AAV as a primary or secondary study outcome were screened and reviewed up to July 2023. Quality was assessed using the Critical Appraisal Skills Programme. Results A total of 30 articles were included which utilised 22 different PROM tools, 76.7% (n  = 23) used the SF-36 or a variation as a generic measure of health status and or HRQoL. Two studies developed a disease-specific PROM. The AAV-PRO showed good psychometric properties but potential limitations in capturing all relevant aspects of the disease experience for AAV patients. Factors associated with poorer HRQoL included: neurological and sinonasal involvement, women and younger patients. A total of 86.6% of studies showed no meaningful relationships between the SF-36 and BVAS, VDI or disease duration. Depression and anxiety were common and socioeconomic factors such as unemployment were significantly associated with poorer mental health outcomes. Glucocorticoids were found to be independently associated with worse SF-36 scores. Conclusion Generic PROMs are useful in measuring significant changes but lack sensitivity to specific symptoms and unique AAV-related issues, while existing disease-specific PROMs have some limitations and may not fully capture the AAV patient's perspective on disease and treatment burden. [ABSTRACT FROM AUTHOR]