Eosinophilic granulomatous polyangiitis with central nervous system involvement in children: a case report and literature review.

Objective: To explore the clinical characteristics and treatment outcomes of children with central nervous system (CNS) involvement in eosinophilic granulomatosis with polyangiitis (EGPA). Methods: A child who presented with EGPA complicated by CNS involvement was admitted to our hospital in June 2023. The clinical features were analyzed retrospectively, and relevant literatures were reviewed to provide a comprehensive overview of this condition. Results: A ten-year-old girl, who had a history of recurrent cough and asthma accompanied by peripheral blood eosinophilia for eight months, was admitted to our hospital. On admission, spotted papules were visible on her hands and feet, bilateral pulmonary rales were audible. The laboratory examination revealed that the proportion of eosinophils (EOS) exceeded 10% of white blood cells, the anti-neutrophil cytoplasmic antibody (MPO-ANCA) was positive, the immunoglobulin G level was 15.80g/L, and the immunoglobulin E level was greater than 2500.00IU/mL. The imaging examination showed multiple patchy and nodular high-density shadows in both lungs as well as sinusitis. Pulmonary function tests indicated moderate ventilation and diffusion dysfunction. Bone marrow cytology demonstrated a significant increase in the proportion of eosinophils. Skin pathology confirmed leukocytoclastic vasculitis. During the hospitalization, the child had a convulsion. The magnetic resonance imaging (MRI) scan of the brain showed multiple abnormal signal shadows in the bilateral cerebral cortex and the electroencephalogram (EEG) showed epileptic waves. Following the administration of methylprednisolone pulse therapy in combination with cyclophosphamide treatment, her cough and asthma resolved, the skin rash disappeared without any further convulsions. We found that only a young EGPA patient with CNS involvement had been previously reported. The previously reported case began with long-term fever, weight loss, and purpuric rash. Both patients responded well to treatment with glucocorticoids and cyclophosphamide, experiencing significant improvement in their clinical symptoms and normalization of their peripheral blood eosinophils. Conclusion: The diagnosis of EGPA in children can be challenging. When a child is affected by EGPA, it is essential to remain vigilant for signs of CNS involvement. The treatment with glucocorticoids and cyclophosphamide is effective in managing EGPA in children.

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

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

[Peripheral Neuropathy in Eosinophilic Granulomatosis with Polyangiitis].

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

Pathogenesis of Pulmonary Manifestations in ANCA-Associated Vasculitis and Goodpasture Syndrome.

Pulmonary manifestations of vasculitis are associated with significant morbidity and mortality in affected individuals. They result from a complex interplay between immune dysregulation, which leads to vascular inflammation and tissue damage. This review explored the underlying pathogenesis of pulmonary involvement in vasculitis, encompassing various forms such as granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), eosinophilic granulomatosis with polyangiitis (EGPA), and anti-GBM disease. Mechanisms involving ANCA and anti-GBM autoantibodies, neutrophil activation, and neutrophil extracellular trap (NETs) formation are discussed, along with the role of the complement system in inducing pulmonary injury. Furthermore, the impact of genetic predisposition and environmental factors on disease susceptibility and severity was considered, and the current treatment options were presented. Understanding the mechanisms involved in the pathogenesis of pulmonary vasculitis is crucial for developing targeted therapies and improving clinical outcomes in affected individuals.

[Clinical and electrophysiological characteristics and treatment outcomes of anti-neutrophil cytoplasmic antibody ANCA-associated vasculitic neuropathy].

Objective: To investigate the clinical and electrophysiological characteristics of ANCA-associated vasculitic neuropathy (VN) and analyze the predictors of treatment outcomes. Methods: Retrospective case series. In all, 652 consecutive patients with ANCA-associated vasculitis were admitted to the First Medical Center of the Chinese PLA General Hospital between January 2006 and December 2022. Peripheral neuropathy occurred in 91 patients. Patients were excluded if other known causes of neuropathy were present. Sixty-one patients were eventually enrolled, including 17 with eosinophilic granulomatosis with polyangiitis (EGPA), 11 with granulomatosis polyangiitis (GPA), and 33 with microscopic polyangiitis (MPA). Their clinical data were collected and clinical characteristics, VN manifestations, electrophysiological findings (including interside amplitude ratio [IAR]), and treatment outcomes were compared among the three subsets of AAV. Then, factors influencing the treatment outcomes were analyzed using multivariable logistic regression analysis. Results: Peripheral neuropathy occurred in 62.1%(18/29) of EGPA, 8.3%(15/180) of GPA, and 13.1%(58/443) of MPA patients. The age at onset and examination was higher in patients with MPA than those with EGPA or GPA (P<0.01). The occurrence of VN was later in patients with GPA than those with EGPA (P<0.01), and the GPA group had fewer affected nerves than the other two groups (P<0.016). The abnormal IARs of motor nerves in lower limbs were more detected in the EGPA than the MPA group (P<0.01). Logistic regression analysis suggested that higher Birmingham vasculitis activity score-version 3 (BVAS-V3) (OR=6.85, 95%CI 1.33-35.30) was associated with better treatment outcomes of VN. However, central nervous system involvement was a risk factor for poor treatment outcomes (OR=0.13, 95%CI 0.02-0.89). Conclusions: The clinical and electrophysiological characteristics of VN were slightly different among subsets of AAV. Patients with GPA often presented with polyneuropathy and had fewer nerves affected; mononeuritis multiplex was more common in EGPA than GPA and MPA. Higher BVAS-V3 and central nervous system involvement might predict the treatment outcome of VN.

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

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

Granulomatosis with polyangiitis or its mimic? A case report.

Differentiation between granulomatosis with polyangiitis (GPA) limited to the upper airways and cocaine-induced midline destructive lesion (CIMDL) may be particularly difficult because of their common histopathologic features and antineutrophil cytoplasmic antibody (ANCA) profiles. We herein present a case involving a young woman with an initial diagnosis of GPA based on upper and lower airway manifestations and constitutional symptoms, histopathologic evidence of granulomas, a positive cytoplasmic ANCA indirect immunofluorescent test result, and proteinase 3 positivity by enzyme-linked immunosorbent assay (ELISA). CIMDL was confirmed based on the appearance of a hard palate perforation, positivity for methylecgonine on urine toxicology, a positive perinuclear ANCA indirect immunofluorescent test result, and subsequent human neutrophil elastase (HNE) ANCA positivity by ELISA. Finally, based on the coexistence of CIMDL, constitutional symptoms, and lower airway manifestations, the diagnosis was modified to cocaine-induced GPA mimic. Urine toxicology for cocaine and HNE ELISA are indicated in young patients with GPA who develop limited airway disease to check for the presence of CIMDL and cocaine-/levamisole-induced ANCA-associated vasculitis. Continued abstinence from cocaine is the first-choice therapy for both CIMDL and cocaine-induced GPA mimic.

The HLA region in ANCA-associated vasculitis: characterisation of genetic associations in a Scandinavian patient population.

OBJECTIVE: The antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are inflammatory disorders with ANCA autoantibodies recognising either proteinase 3 (PR3-AAV) or myeloperoxidase (MPO-AAV). PR3-AAV and MPO-AAV have been associated with distinct loci in the human leucocyte antigen (HLA) region. While the association between MPO-AAV and HLA has been well characterised in East Asian populations where MPO-AAV is more common, studies in populations of European descent are limited. The aim of this study was to thoroughly characterise associations to the HLA region in Scandinavian patients with PR3-AAV as well as MPO-AAV. METHODS: Genotypes of single-nucleotide polymorphisms (SNPs) located in the HLA region were extracted from a targeted exome-sequencing dataset comprising Scandinavian AAV cases and controls. Classical HLA alleles were called using xHLA. After quality control, association analyses were performed of a joint SNP/classical HLA allele dataset for cases with PR3-AAV (n=411) and MPO-AAV (n=162) versus controls (n=1595). Disease-associated genetic variants were analysed for association with organ involvement, age at diagnosis and relapse, respectively. RESULTS: PR3-AAV was significantly associated with both HLA-DPB1*04:01 and rs1042335 at the HLA-DPB1 locus, also after stepwise conditional analysis. MPO-AAV was significantly associated with HLA-DRB1*04:04. Neither carriage of HLA-DPB1*04:01 alleles in PR3-AAV nor of HLA-DRB1*04:04 alleles in MPO-AAV were associated with organ involvement, age at diagnosis or relapse. CONCLUSIONS: The association to the HLA region was distinct in Scandinavian cases with MPO-AAV compared with cases of East Asian descent. In PR3-AAV, the two separate signals of association to the HLD-DPB1 region mediate potentially different functional effects.

Proteinase 3-specific antineutrophil cytoplasmic antibody-associated vasculitis.

Proteinase 3 (PR3)-specific antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is one of two major ANCA-associated vasculitis variants and is pathogenically linked to granulomatosis with polyangiitis (GPA). GPA is characterised by necrotising granulomatous inflammation that preferentially affects the respiratory tract. The small vessel vasculitis features of GPA are shared with microscopic polyangiitis. Necrotising granulomatous inflammation of GPA can lead to PR3-ANCA and small vessel vasculitis via activation of neutrophils and monocytes. B cells are central to the pathogenesis of PR3-ANCA-associated vasculitis. They are targeted successfully by remission induction and maintenance therapy with rituximab. Relapses of PR3-ANCA-associated vasculitis and toxicities associated with current standard therapy contribute substantially to remaining mortality and damage-associated morbidity. More effective and less toxic treatments are sought to address this unmet need. Advances with cellular and novel antigen-specific immunotherapies hold promise for application in autoimmune disease, including PR3-ANCA-associated vasculitis. This Series paper describes the inter-related histopathological and clinical features, pathophysiology, as well as current and future targeted treatments for PR3-ANCA-associated vasculitis.

Investigating the concomitance of anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitides and inflammatory bowel disease (IBD).

OBJECTIVE: To assess relationship between Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis and inflammatory bowel disease (IBD). METHODS: This is a retrospective study design. The patients were identified using a preset criteria of patients who have the diagnosis of ANCA associated vasculitis including a diagnosis of granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) or eosinophilic granulomatosis with polyangiitis (EGPA) with overlapping inflammatory bowel disease (Crohn's disease or ulcerative colitis) in the time period from 01/01/2020 to 08/03/2023. Subsequently data from each patient was collected that will include baseline demographics, disease characteristics, disease activity, treatment information, multiorgan involvement, and pathology findings which were then analyzed. RESULTS: 39 patients were identified that met criteria. 20 patients carried a diagnosis of GPA, 6 had MPA and 4 patients had EGPA. 20 patients with GPA had inflammatory bowel disease, 13 with ulcerative colitis and 6 with Crohn's disease while 1 GPA patient had unspecified inflammatory bowel disease. 4 patients with EGPA had inflammatory bowel disease, 2 with ulcerative colitis and 2 with Crohn's disease. 6 patients with MPA had inflammatory bowel disease, 4 with ulcerative colitis and 2 with Crohn's disease. IBD diagnosis preceded the diagnosis of ANCA vasculitis in 77.8 % of the cases. CONCLUSION: Objective observation and deductions from this study raise the concern for a possible pathogenic association of ANCA associated vasculitis and inflammatory bowel disease and more research is needed to identify any causal association or influence of the two systemic disease on each other.

Myeloperoxidase-specific antineutrophil cytoplasmic antibody-associated vasculitis.

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

High-resolution epitope mapping of commercial antibodies to ANCA antigens by yeast surface display.

Epitope mapping provides critical insight into antibody-antigen interactions. Epitope mapping of autoantibodies from patients with autoimmune diseases can help elucidate disease immunogenesis and guide the development of antigen-specific therapies. Similarly, epitope mapping of commercial antibodies targeting known autoantigens enables the use of those antibodies to test specific hypotheses. Anti-Neutrophil Cytoplasmic Autoantibody (ANCA) vasculitis results from the formation of autoantibodies to multiple autoantigens, including myeloperoxidase (MPO), proteinase-3 (PR3), plasminogen (PLG), and peroxidasin (PXDN). To perform high-resolution epitope mapping of commercial antibodies to these autoantigens, we developed a novel yeast surface display library based on a series of >5000 overlapping peptides derived from their protein sequences. Using both FACS and magnetic bead isolation of reactive yeast, we screened 19 commercially available antibodies to the ANCA autoantigens. This approach to epitope mapping resulted in highly specific, fine epitope mapping, down to single amino acid resolution in many cases. Our study also identified cross-reactivity between some commercial antibodies to MPO and PXDN, which suggests that patients with apparent autoantibodies to both proteins may be the result of cross-reactivity. Together, our data validate yeast surface display using maximally overlapping peptides as an excellent approach to linear epitope mapping.

Significance of clinical-immunological patterns and diagnostic yield of biopsies in microscopic polyangiitis and granulomatosis with polyangiitis.

BACKGROUND: Microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) are the two major antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). OBJECTIVES: To characterize a homogenous AAV cohort and to assess the impact of clinicopathological profiles and ANCA serotypes on clinical presentation and prognosis. Clinical differences in GPA patients according to ANCA serotype and the diagnostic yield for vasculitis of biopsies in different territories were also investigated. RESULTS: This retrospective study (2000-2021) included 152 patients with AAV (77 MPA/75 GPA). MPA patients (96.1% myeloperoxidase [MPO]-ANCA and 2.6% proteinase 3 [PR3]-ANCA) presented more often with weight loss, myalgia, renal involvement, interstitial lung disease (ILD), cutaneous purpura, and peripheral nerve involvement. Patients with GPA (44% PR3-ANCA, 33.3% MPO, and 22.7% negative/atypical ANCA) presented more commonly with ear, nose, and throat and eye/orbital manifestations, more relapses, and higher survival than patients with MPA. GPA was the only independent risk factor for relapse. Poor survival predictors were older age at diagnosis and peripheral nerve involvement. ANCA serotypes differentiated clinical features in a lesser degree than clinical phenotypes. A mean of 1.5 biopsies were performed in 93.4% of patients in different territories. Overall, vasculitis was identified in 80.3% (97.3% in MPA and 61.8% in GPA) of patients. CONCLUSIONS: The identification of GPA presentations associated with MPO-ANCA and awareness of risk factors for relapse and mortality are important to guide proper therapeutic strategies in AAV patients. Biopsies of different affected territories should be pursued in difficult-to-diagnose patients based on their significant diagnostic yield.

Protective effect of astaxanthin on ANCA-associated vasculitis.

OBJECTIVE: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a systemic autoimmune disease characterized by inflammation and fibrinoid necrosis of medium and small vessels, and its pathogenesis is closely related to inflammation and oxidative stress. Astaxanthin (ATX) is a carotenoid with anti-inflammatory, antioxidant, and immunomodulatory effects. We hypothesized that ATX could play a role in AAV treatment. This study aimed to investigate whether ATX has a protective effect against AAV and to elucidate its regulatory mechanism. METHODS: In vitro experiments, neutrophils isolated from healthy people were treated with ATX or not and cultured with serum from myeloperoxidase (MPO) -ANCA-positive patients and healthy persons. The levels of IL-6 and TNF-α in neutrophil culture supernatant before and after stimulation were measured. Neutrophil extracellular traps (NETs) and intracellular reactive oxygen species (ROS) in neutrophils were detected after stimulation. In vivo study, experimental autoimmune vasculitis (EAV) rat models were established and then treated with ATX via intragastric administration for 6 consecutive weeks. Urinary erythrocytes, urinary proteins, and serum creatinine were detected and HE staining was performed to assess renal injury in rats. Lung hemorrhage was observed by gross dissection and microscopic Prussian blue staining. The level of serum MPO-ANCA was detected. Serum IL-6, TNF-α, superoxide dismutase (SOD), and glutathione peroxidase (GSH-px) in rats were measured to explore the effects of ATX on oxidative stress and inflammation in EAV rats. The deposition of MPO in kidney and lung of rats was detected by immunohistochemistry. RESULTS: ATX significantly inhibited neutrophil secretion of inflammatory factors IL-6 and TNF-α. ATX reduced the elevated levels of ROS in neutrophils stimulated by serum from AAV patients and alleviated the release of NETs. ATX administration was observed to reduce the degree of hematuria, proteinuria, and glomerular crescent formation in EAV rats. The degree of pulmonary hemorrhage was significantly reduced. Besides, the serum levels of IL-6 and TNF-α were attenuated, and antioxidant SOD and GSH-px increased in serum. Pathological results showed that MPO deposition was decreased in lung and kidney tissues after ATX treatment. CONCLUSION: ATX could ameliorate the organ damages in EAV rats. It could serve as a hopeful therapy for AAV by its anti-inflammatory and anti-oxidative feature as a unique nature carotenoid.

Latent class analysis of chest CT abnormalities to define subphenotypes in patients with MPO-ANCA-positive microscopic polyangiitis.

BACKGROUND: Patients with microscopic polyangiitis (MPA) and positive myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) may present with various abnormalities in chest computed tomography (CT). This study aimed to identify subphenotypes using latent class analysis (LCA) and to explore the relationship between the subphenotypes and clinical patterns, as well as compare the clinical characteristics of these subphenotypes in patients with MPO-ANCA-positive MPA (MPO-MPA). METHODS: The study identified subphenotypes using LCA based on chest CT findings in 178 patients with MPO-MPA and pulmonary involvement from June 2014 to August 2022. RESULTS: LCA identified 27 participants (15.2%) in class 1, 43 (24.1%) in class 2, 35 (19.7%) in class 3, and 73 (41.0%) in class 4. Class 1 was characterized by prominent inflammatory exudation, class 2 by fibrosis and architectural distortion, class 3 by predominantly bronchiectasis, and class 4 by lesions mixed with inflammation and fibrosis. Class 1 had the highest level of extrapulmonary disease activity, with 77.8% of patients experiencing diffuse alveolar hemorrhage. Class 2 had the lowest level of extrapulmonary disease activity, with 41.9% of patients showing usual interstitial pneumonia. Class 3 patients were more likely to have complications involving the ear, nose, and throat, as well as pulmonary infections before treatment, and they exhibited the best outcomes. The characteristics and outcomes of class 4 were intermediate among the four classes. CONCLUSIONS: These findings suggest that bronchiectasis may represent a unique pattern of pulmonary involvement in MPO-MPA, highlighting the importance of screening for bronchiectasis in MPO-MPA and identifying optimal management strategies.

[Clinical analysis of ear symptoms of 40 patients with ANCA-associated vasculitis].

Objective:To analyze the clinical feature, diagnosis and treatment of Anca-associated vasculitis with ear symptoms. Methods:In this retrospective study, we summarized the clinical and laboratory examination, pure tone audiometry, aural immittance measurement, CT scan of temporal bone and treatment of 40 patients in the First Medical Center of the PLA General Hospital. Results:A total of 11 cases（27.5%） had the initial symptom in the ear. The most common symptoms were hearing loss, and the other symptoms included a sense of ear fullness, otorrhea and tinnitus. There were 35 cases with hearing loss: 19 cases with conductive hearing loss（47.5%）, 9 cases with sensorineural hearing loss（22.5%）, and 7 cases with mixed hearing loss（17.5%）. 5 cases had a sense of ear fullness or tinnitus, and the results of the hearing test were normal（12.5%）. All of the 40 patients had multi-system involvement, and respiratory system accounted for the most. All patients had a positive result of Anti-neutrophil cytoplasmic antibody（ANCA）. Treatment included systemic hormonal, immunosuppressive, or biologic therapy. There were 3 cases recovered（7.5%）, 22 cases with alleviated ear symptoms（55.0%）, 6 cases with recurrent hearing loss（15%） and 9 cases had no significant improvement（22.5%）. Conclusion:Conductive deafness（secretory otitis media） can be the first manifestation in the early stage of otitis media with AAV（OMAAV）, later it may turn to binaural mixed deafness. Otolaryngologists need to consider OMAAV diagnosis when diagnosing and treating patients with recurrent secretory otitis media. Multi-system symptom consultation and ANCA examination can help identify. Early systemic medication and the application of immunosuppressants or biological agents can help relieve the ear symptoms.

[ANCA-negative granulomatosis with polyangiitis: a case report].

We reported a case of 73-year-old male with multiple pulmonary nodules and cavities. The patient was admitted with a chief complaint of "dry cough with shortness of breath for 3 months". Chest CT showed multiple irregular masses, nodules, and patchy lesions in both lungs, accompanied by the formation of cavities. He also had anemia and renal dysfunction. Despite given empirical anti-infective and anti-tuberculosis treatments, the pulmonary nodules progressed, and the cavities enlarged. Anti-neutrophil cytoplasmic antibodies (ANCA) were negative twice. Bronchoscopic biopsy was performed. The mucosal pathology of the right middle lobe lesion showed little necrosis, focal granulomatous structure formation, and relevant vasculitis and remaining vessel wall structure in the necrosis lesions by elastic fiber staining. A clinical diagnosis of ANCA-negative necrotizing granulomatous polyangiitis was made and the patient was treated with glucocorticoids and cyclophosphamide. The nodules and cavities shrank, and some lesions were absorbed.

Prospective study of complications and sequelae of glucocorticoid therapy in ANCA-associated vasculitis.

OBJECTIVE: Glucocorticoids (GC) are a cornerstone in treating antineutrophil cytoplasmic antibodies-associated vasculitides (AAV), however, they add to morbidity and mortality. To date, GC toxicity in AAV has rarely been systematically investigated. METHODS: Patients with a confirmed AAV were included in this monocentric prospective study. GC toxicity was assessed by structured interviews, clinical examination and electronic medical record analysis. The Glucocorticoid Toxicity Index (GTI) consisting of the Aggregate Improvement Score (GTI-AIS) and the Cumulative Worsening Score (GTI-CWS) was assessed at two time points (t1 baseline, t2 6 months later). We used regression analyses to assess the relationship between GTI and GC exposure, toxicity, and disease activity, and a receiver operating characteristic analysis to calculate a GC threshold dose beyond which toxicity is expected to occur. RESULTS: We included 138 patients with AAV. The median cumulative GC dose was 9014.0 mg. The most frequent adverse events were skin atrophy, osteoporosis and myopathy. GC exposure and toxicity were significantly correlated (p<0.001). GTI-AIS was significantly higher in active disease compared with patients in remission (p<0.001). GTI-CWS scored significantly higher in long-standing diseases (p=0.013) with high cumulative GC doses (p=0.003). Patients with a cumulative GC dose of 935 mg or more showed an 80% likelihood for a clinically meaningful change in GTI scoring. CONCLUSION: The GTI is capable of capturing GC toxicity in AAV and identifies patients at increased risk for GC side effects. Our data support efforts to limit GC exposure in patients with AAV.

Prevalence of a large panel of systemic autoantibodies in the Bavarian adult population.

Objective: Autoimmune diseases commonly feature the presence of specific humoral autoantibodies. However, the prevalence of a large panel of systemic autoantibodies has never been assessed in the general population. We, therefore, described the prevalence of about 50 humoral systemic autoantibodies in a sample of the general Bavarian adult population. Methods: Non-fasting venous serum samples from 331 participants were analyzed for 7 autoantibody screening tests (nuclear, cytoplasmic, and mitotic ANA, ANCA, cANCA and pANCA, anti-ENA autoantibodies) and 44 different monospecific humoral non-organ specific/systemic autoantibodies using indirect immunofluorescence tests, ELISAs, and line blots. In order to assess associations between sex, age, BMI, education level, smoking status and the presence of systemic autoantibodies, logistic regression analyses were conducted. Results: At least one screening test was positive in 29.9% of the participants, and 42.3% of the participants were seropositive for at least one monospecific autoantibody. The most frequently found monospecific autoantibodies were rheumatoid factor (35.6%), ß2-glycoprotein 1 IgM (4.8%), and cardiolipin IgG (1.8%). Only few associations between sex, age, BMI, education, smoking status and autoantibody frequencies were observed. Conclusion: Systemic autoantibodies are common in the general Bavarian population, and largely independent of sex, age, BMI, education, or smoking status. The study results may give orientation to clinicians about the occurrence of autoantibodies in the population, not (yet) associated with clinical symptoms.