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.

Serum concentration of dickkopf-related protein 1 (DKK1) in psoriatic arthritis in the context of bone remodelling.

Psoriatic arthritis (PsA) is a chronic inflammatory disease, characterised by the pathological occurrence of two opposite phenomena-osteoresorption and osteogenesis. Dickkopf-related protein 1 (DKK1) which inhibits the Wingless protein (Wnt) signalling pathway has been shown to be a master regulator of bone remodeling in inflammatory rheumatic diseases. However, the exact relationship between DKK1 serum level and bone remodelling is not clear. The goal of this study is to review state-of-the-art knowledge on the association of serum DKK1 with a bone remodelling in PsA. The MEDLINE-PubMed, EMBASE, Scopus, Web of Science and DOAJ databases were searched for appropriate papers. The English terms: 'DKK1', 'Dickkopf-1' 'Dickkopf related protein 1', 'psoriatic arthritis' and 'PsA' were used for search purposes. Eight original articles and two reviews were identified up to August 2023. In four out of 8 discussed studies DKK1 serum level was higher in PsA patients than in healthy controls [Dalbeth, p < 0.01; Diani, p < 0.001; Chung, p < 0.01; Abd el Hamid, p < 0.001)], it was comparable in another (Daousiss, p = 0.430) and was lower in two (Fassio2017, p < 0.05; Fassio2019, p < 0.05). In one study, the comparative groups included patients with axial spondyloarthritis, where DKK1 serum levels were lower in PsA groups [Jadon, peripheral PsA, p = 0.01]. The true relative serum concentration of DKK1 in PsA, as well as its influence on osteogenesis and osteoresorption, is still equivocal. Further studies on this matter with consistent and stringent methodology are warranted.

Functional magnetic resonance imaging for the assessment of autonomic dysfunction in patients with antineutrophil cytoplasmic antibody-associated vasculitides.

INTRODUCTION: Nervous system involvement is common in antineutrophil cytoplasmic antibody-associated vasculitides (AAV). While the involvement of the peripheral and central nervous system is well described, it is still unclear how and to what extent the autonomic nervous system (ANS) is affected. Functional magnetic resonance imaging (fMRI) can provide information on both structure and potential damage of the brain, as well as on the function of selected brain centers. OBJECTIVES: The aim of this study was to investigate the ANS dysfunction in AAV patients and its correlation with the results of fMRI performed during the Valsalva maneuver. PATIENTS AND METHODS: A total of 31 patients with AAV and 30 healthy controls were enrolled in the study. Each participant completed the Composite Autonomic Symptom Score (COMPASS)-31 questionnaire. MRI was performed using a 3T scanner. The participants were asked to perform the Valsalva maneuver according to the fixed protocol, and their airway pressure was monitored. During the maneuver, fMRI data were collected. The generalized least­ squares time series analysis and the region of interest (ROI) analysis were subsequently performed. RESULTS: The patients with AAV had a higher median COMPASS­ 31 score than the controls (12.86 vs 2.99, respectively; P <0.01). Structural MRI investigation did not reveal any significant differences between the groups. The brain centers involved in ANS function were detected during fMRI; however, the ROI analysis showed no differences between the study patients and controls. CONCLUSIONS: The patients with AAV reported symptoms related to the ANS dysfunction; however, no differences with respect to the functioning of the ANS brain centers were demonstrated between these patients and healthy controls in the fMRI study during the Valsalva maneuver.

Respiratory involvement in antineutrophil cytoplasmic antibody-associated vasculitides: a retrospective study based on POLVAS registry.

OBJECTIVES: The study aimed to characterise the Polish population of (ANCA)-associated vasculitides (AAV) with respiratory involvement (RI), in comparison to the subgroup without lung manifestations and the other cohorts. METHODS: Retrospective analysis of the Polish population of AAV with RI was conducted, based on data from the POLVAS registry. Standard descriptive statistics, χ2 test, and Mann-Whitney U test were used to perform comparisons. RESULTS: Among 461 cases qualified to this study, there were 316 cases with RI (68.5%), 206 with granulomatosis with polyangiitis (GPA) (65.2%), 80 with eosinophilic granulomatosis with polyangiitis (EGPA) (25.3%) and 30 with microscopic polyangiitis (MPA) (9.5%). Proportion of RI in GPA, MPA, and EGPA accounted for 67.8%; 40.0%; 97.6%, respectively. The number of relapses was higher in the RI group (median 1.0 vs. 0.0; p=0.01). In the subgroup of combined GPA and MPA with RI, the trends toward higher proportion of deaths (11.7% vs. 5.7%; p=0.07), relapses requiring hospitalisation (52.2% vs. 42.4%, p=0.07) and relapses requiring admission to the intensive care unit (5.6% vs. 1.4%, p=0.09) were observed, median maximal concentration of CRP was higher (46 vs. 25 mg/l; p=0.01) and more aggressive treatment was administered. CONCLUSIONS: Prevalence of RI in the Polish population of AAV is similar to the values reported in the literature, however, the proportion observed in GPA is closer to those presented in Asian than Western European cohorts. RI seems to be associated with a more severe course of disease and its presence prompts more aggressive treatment.

Subphenotypes of ANCA-associated vasculitis identified by latent class analysis.

OBJECTIVES: ANCA-associated vasculitides (AAV) are a heterogeneous group of rare diseases with unknown aetiology and the clinical spectrum ranging from life-threatening systemic disease, through single organ involvement to minor isolated skin changes. Thus, there is an unmet need for phenotype identification, especially among patients with granulomatosis with polyangiitis (GPA). Patients with microscopic polyangiitis (MPA) seem to be clinically much more uniform. Recently, three subcategories of AAV have been proposed and described as non-severe AAV, severe PR3-AAV, and severe MPO-AAV. METHODS: In line with these attempts, we decided to use an unbiased approach offered by latent class analysis (LCA) to subcategorise GPA and MPA in a large cohort of Polish AAV patients included in a multicentre POLVAS registry. RESULTS: LCA of our AAV group identified a four-class model of AAV, including previously proposed three subphenotypes and revealing a fourth (previously not described) clinically relevant subphenotype. This new subphenotype includes only GPA patients, usually diagnosed at a younger age as compared to other groups, and characterised by multiorgan involvement, high relapse rate, relatively high risk of death, but no end-stage kidney disease. CONCLUSIONS: Based on multiple clinical and serological variables, LCA methodology identified 4-class model of AAV. This newly described fourth class of AAV may be of clinical relevance and may require prompt diagnosis and aggressive treatment due to the multiorgan involvement, high risk of relapse and marked mortality among these relatively young GPA subjects.

ANCA-associated vasculitis patients treated in Polish intensive care units - retrospective characteristics based on the POLVAS registry.

INTRODUCTION: ANCA-associated vasculitides (AAV) is a group of rare disorders where inflammation and damage of the small blood vessels lead to dysfunction of the supplied organs. In severe flares of the disease patients may require intensive care unit (ICU) admission and treatment. The study aims to characterize Polish patients with AAV who were admitted to the ICU and compare them to the others. MATERIAL AND METHODS: An observational, retrospective study based on the POLVAS - registry of Polish adult patients with AAV was carried out. Patients admitted to the ICU (ICU group) were identified and compared with the patients who did not require ICU admission (non-ICU group). Characteristics and comparison between groups were made using standard statistic descriptive methods. RESULTS: 30 patients admitted to the ICU were identified among 573 cases included in the registry. All patients in the ICU group with available data were ANCA positive. The clinical manifestations related to the ICU admission were respiratory, renal and central nervous system involvement. The treatment regimen for remission induction was similar in both groups. Almost half of the patients in the ICU-group (48.3%) required dialysis, whereas in the non-ICU group it was 21.8% (P = 0.01). Infections were also more frequent in the ICU group (72.4% vs. 36.9% P < 0.001). The mortality rate among patients who needed ICU treatment was significantly higher when compared to the rest of the patients (53.6% vs. 7.8%; P < 0.001). CONCLUSIONS: In the Polish AAV cohort one in twenty patients required ICU admission. This group was characterized by multiple organ involvement and high mortality.

Treatment and its side effects in ANCA-associated vasculitides - Study based on POLVAS registry data.

PURPOSE: The aim of this study is to present the treatment modalities and associated side effects in a Polish nation-wide ANCA-associated vasculitides (AAV) patients' cohort. MATERIALS AND METHODS: Retrospective analysis of patients diagnosed with AAV between 1990 and 2016, included in the POLVAS registry was performed. Standard descriptive statistic methods were used with an emphasis on the treatment modalities. RESULTS: There were 625 patients diagnosed with AAV included in this study: 417 cases of granulomatosis with polyangiitis (GPA; 66.7%), 106 cases of microscopic polyangiitis (MPA; 17.0%) and 102 cases of eosinophilic granulomatosis with polyangiitis (EGPA; 16.3%). The mean age at the date of diagnosis was 50.4 (±15.7) years and the median observational period amounted to 4.0 (2.0-8.0) years. Glucocorticosteroids (GCs) were the medicaments most frequently used for remission induction (593/622; 95.3%), followed by cyclophosphamide (487/622; 78.3%), rituximab (44/622; 7.1%), and methotrexate (39/622; 6.3%). GCs were also most frequently administered for maintenance therapy (499/592; 84.3%), followed by azathioprine (224/592; 37.8%), methotrexate (136/592; 23.0%) and mycophenolate mofetil (99/592; 16.7%). The median cumulative doses of cyclophosphamide and rituximab equalled 7.99 g (4.18-14.0) and 2000 mg (1500-2800), respectively. The most commonly observed adverse events included: infections - 214/551 cases (38.8%), which were associated with the time of observation (OR = 1.05; 95% CI 1.01-1.10), the use of GCs intravenous pulses (OR = 2.76; 95% CI 1.68-4.54) and need for haemodialysis (OR = 1.73; 95% CI 1.10-2.71). CONCLUSIONS: Polish patients with AAV were predominantly treated according to appropriate guidelines. The most frequent adverse events were typical for usually administered immunosuppressive treatment.

Patients with small-vessel vasculitides have the highest mortality among systemic autoimmune diseases patients treated in intensive care unit: A retrospective study with 5-year follow-up.

PURPOSE: Systemic autoimmune diseases are a heterogeneous group of disorders associated with dysfunction of multiple organs and unpredictable course. Complicated management and treatment become even more challenging when patients require critical care. This study aims to compare outcomes of small-vessel vasculitides (SVV) and other systemic autoimmune diseases (SAD) patients admitted to the intensive care unit (ICU). MATERIALS AND METHODS: Retrospective, observational study conducted in the ICU of Allergy and Immunology Department at the University Hospital in Krakow, Poland, between years 2001-2014, with 5-years follow-up and no lost to follow-up patients. RESULTS: 74 patients with autoimmune diseases were enrolled in the study - 23 with SVV and 51 with SAD. Patients in the SVV group achieved higher scores in APACHE II and III SAPS II and SOFA at ICU admission. The SVV patients required renal replacement techniques, blood products transfusion and immunosuppressive treatment more often. SVV patients had higher ICU mortality (60.9% vs. 35.3%, p = .04), however after discharge from ICU, in long term follow-up (1 year and 5 years) mortality was similar in both studied groups. CONCLUSIONS: Among systemic autoimmune diseases small vessel vasculitides appear to be associated with the highest ICU mortality, higher requirement for advanced procedures and aggressive immunosuppressive therapy.

Evaluation of factors that influence anxiety and satisfaction in patients undergoing bronchofiberoscopy with analgosedation.

INTRODUCTION: Bronchofiberoscopy (BF) is a key tool used in the management of patients with respiratory diseases. Describing factors that contribute to patient anxiety surrounding BF has the potential to influence patient management and willingness to undergo the procedure again in the future if needed. OBJECTIVES: This study sought to understand what factors influence anxiety and satisfaction experienced by patients undergoing BF under conscious sedation. METHODS: This study had a prospective observational character and evaluated 463 consecutive patients undergoing BF. Participants were divided into two groups, those undergoing BF for the first time and those who had undergone the procedure at least once in the past. Data were collected from three questionnaires prepared by the research team. RESULTS: Patients who had undergone multiple bronchoscopies were more satisfied with their physician's explanation of the procedure (P < 0.0001), had a better understanding of the indications (P < 0.0001) and potential complications (P < 0.0001) of BF and knew what specific procedure was planned (P < 0.001). Patients undergoing BF for the first time experienced anxiety before the procedure more frequently (P < 0.001). No significant difference in satisfaction was observed between patient groups and 89% would agree to BF in the future. CONCLUSIONS: Patients who had previously undergone BF were better prepared for their procedure; however, satisfaction levels after the procedure were similar in both groups. Results suggest that medical staff should target patients who have not undergone BF previously to relieve anxiety.