ANCA-associated Systemic Vasculitis Research Articles

Comparison of Interstitial Lung Disease Between Antineutrophil Cytoplasmic Antibodies Positive and Negative Patients: A Retrospective Cohort Study.

Positive antineutrophil cytoplasmic antibodies (ANCAs) may occur in the setting of interstitial lung disease (ILD), with or without ANCA-associated vasculitis (AAV). We aim to compare the characteristics and clinical course of patients with ILD and positive ANCA (ANCA-ILD) to those with negative ANCA. We performed a single-center retrospective cohort study from 2018 to 2021. All patients with ILD and ANCA testing were included. Patient characteristics (symptoms, dyspnea scale, and systemic AAV), test results (pulmonary high-resolution computed tomography and pulmonary function tests), and adverse events were collected from electronic medical records. Descriptive statistics and the Fisher exact test were used to compare the outcomes of patients with ANCA-ILD to those with ILD and negative ANCA. A total of 265 patients with ILD were included. The mean follow-up duration was 69.3 months, 26 patients (9.8%) were ANCA positive, and 69.2% of those with ANCA-ILD had another autoantibody. AAV occurred in 17 patients (65.4%) with ANCA-ILD. In 29.4% of patients, AAV developed following ILD diagnosis. Usual interstitial pneumonia was the most common radiologic pattern in patients with ANCA-ILD. There was no association between ANCA status and the evolution of dyspnea,diffusing capacity of the lungs for carbon monoxide, and lung imaging. Forced vital capacity improved over time in 42% of patients with ANCA-ILD and in 17% of patients with negative ANCA (P = 0.006). Hospitalization occurred in 46.2% of patients with ANCA-ILD and in 21.8% of patients with negative ANCA (P = 0.006). Both groups had similar mortality rates. Routine ANCA testing should be considered in patients with ILD. Patients with ANCA-ILD are at risk for AAV. More research is required to better understand and manage patients with ANCA-ILD.

82 Subclinical Podocytopathy in the setting of Systemic ANCA-Associated Vasculitis

82 Subclinical Podocytopathy in the setting of Systemic ANCA-Associated Vasculitis

ANCA-associated systemic vasculitis initially mimicking peripheral neuropathy in an elderly woman

Anti-neutrophil cytoplasmic antibodies (ANCA)-associated systemic vasculitis (AASV) is a rare systemic immunological condition that predominantly impacts small arteries, veins, and capillaries, often leading to kidney damage and pulmonary injury. It is important to note that individuals primarily presenting with peripheral neuropathy (PN) are uncommon in AASV, which can result in significant misdiagnosis or undiagnosed cases. The severity and location of PN can vary among patients. In this article, we present a case of an AASV patient initially showing signs of PN. This case highlights the significance of considering AASV as a potential cause of unexplained neurological symptoms. Timely identification and proper treatment are essential for improving the survival rate and functional prognosis of AASV patients.
 doi: https://doi.org/10.12669/pjms.40.5.9070
 How to cite this: He X, Wang Y, Li X. ANCA-associated systemic vasculitis initially mimicking peripheral neuropathy in an elderly woman. Pak J Med Sci. 2024;40(5):---------. doi: https://doi.org/10.12669/pjms.40.5.9070
 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Rituximab as maintenance therapy for ANCA-associated vasculitides: pooled analysis and long-term outcome of 277 patients included in the MAINRITSAN trials

ObjectiveTo compare the long-term efficacy and safety of azathioprine (AZA), 18-month fixed-schedule rituximab (RTX), 18-month tailored RTX and 36-month RTX in preventing relapses in patients with antineutrophil cytoplasmic antibody (ANCA)-associated...

Clinicopathological Features and Outcomes of IgA Nephropathy with Serum Antineutrophil Cytoplasmic Autoantibody Positivity

Introduction: IgA nephropathy (IgAN) with serum antineutrophil cytoplasmic autoantibody (ANCA) positivity is uncommon. This study analyzed the clinicopathologic features and prognosis of IgAN patients with serum ANCA positivity. Methods: 2,864 IgAN patients were tested for ANCA by the indirect immunofluorescence assay and chemiluminescence immunoassay. Patients with serum ANCA positivity (n = 85) were identified, and their clinical, pathological, and prognostic characteristics were analyzed. They were compared with ANCA-negative IgAN patients (n = 170) and ANCA-associated systemic vasculitis (AAV) with renal involvement patients (n = 85) selected randomly. Results: 2.97% (85/2,864) of IgAN were ANCA positive, and 4 patients were diagnosed as having crescentic IgAN with ANCA positivity. The clinicopathological characteristics of ANCA-positive IgAN patients were comparable to ANCA-negative IgAN patients, but they had higher antinuclear antibody (ANA)-positive rates, lower levels of renal interstitial inflammation, and fewer immune depositions than ANCA-negative IgAN patients. Compared with AAV patients, ANCA-positive IgAN patients were younger and had fewer extrarenal manifestations, milder renal damage, and more immune complex depositions. The renal outcomes were similar between IgAN patients with and without ANCA positivity. Multivariate Cox analysis revealed that in IgAN patients with ANCA positivity, male, ANA positivity, higher serum creatinine and proteinuria, and more severe renal tubular atrophy/interstitial fibrosis were risk factors for adverse renal outcomes. Conclusion: The clinical, pathological features and prognosis of ANCA-positive IgAN patients were similar to those of ANCA-negative IgAN patients except for higher ANA-positive rate, milder renal inflammation, and fewer immune depositions. ANA positivity was an independent risk factor for adverse renal outcomes in ANCA-positive IgAN patients.

Experience with Tixagevimab and Cilgavimab (Evusheld) in 86 rheumatic patients undergoing anti-B cell therapy with rituximab

The problem of prevention of coronavirus disease 2019 (COVID-19) in patients with immune-mediated inflammatory rheumatic diseases (IMRD) remains highly relevant. The presence of IRD is associated with a high risk of disease and severe course of COVID-19 during immunosuppressive treatment, primarily anti-B cell therapy with rituximab (RTX), and a low level of post-vaccination response in such patients. A new strategy for the prevention and treatment of COVID-19 are virus-neutralizing monoclonal antibodies to coronavirus; currently, combined long-acting monoclonal antibodies tixagevimab and cilgavimab (Evusheld) are registered for prevention in the world and the Russian Federation. . Tixagevimab and cilgavimab (TC) show neutralizing activity against SARS-CoV-2, including the Omicron strain, primarily its variants BA.4, BA.5, BA.2.75 ("Centaur").Objective – to evaluate the efficacy and safety of TC for pre-exposure prophylaxis of COVID-19 in rheumatic patients receiving RTX, based on a prospective observational study.Materials and methods. The main group included 86 patients with various IMRD receiving RTX: 50 of them had ANCA-associated systemic vasculitis (AAV), 15 – rheumatoid arthritis, 9 – Sjogren’s syndrome (SS), 4 – IgG4-related disease, 3 – systemic lupus erythematosus (SLE), 3 – dermatomyositis (DM), 2 – systemic scleroderma (SSD). Median age was 59 (19–82) years; male : female ratio – 1:1,8. From March 26 to August 30 2022, patients received a single intramuscular injection of TC in a total dose of 300 mg, mainly after RTX (in 52% of cases, in 28% on the next day after RTX). The control group included 42 patients with AAV (median age – 45 (35–71) years; male : female ratio – 1:1), also treated with RTX, who did not receive pre-exposure prophylaxis of TC. The duration of observation was 7 months, until November 1 2022. At this time, 98% of confirmed cases of coronavirus in the Russian Federation were Omicron. A telephone and/or online survey of patient has been conducted to detect cases of COVID-19 and adverse reactions.Results. In the TC group, confirmed coronavirus infection have been detected in 17 (20%) patients (AAV – 10, SS – 3, SSD – 2, SLE – 1, DM – 1), with fever in 7 (8%), only in one case hospitalization was required (lung damage was not detected in computed tomography), in two cases, according to CT mild lung damage (CT 1–2), there were no deaths. Good TC’s tolerability was noted, signs not associated with COVID-19 or progression of IMRD after administration of TC were observed in 8 (9%) patients (GPA – 3 MPA – 1, RA – 2, SLE – 1, IgG4-related disease – 1), adverse reactions definitely associated with the use of TC were not found. The most serious event not associated with coronavirus infection was the progression of polyneuropathy in a patient with RA. In the control group, 3 (7%) patients were diagnosed with COVID-19, one with severe lung injury (CT 3, pulmonary embolism) and death.Conclusions. The data of clinical studies and our own clinical experience evidence the effectiveness of the use of a combination of long-acting monoclonal antibodies TC (Evusheld), registered for indications for pre-exposure prophylaxis and treatment of COVID-19. Patients with IMRD treated with RTX have a favorable safety profile of TC. The introduction of virus-neutralizing monoclonal antibodies, a new drug class for the prevention and treatment of infectious diseases, opens significant prospects for improving the prognosis of patients with IRD.

Clinical and immunological variants of ANCA-associated systemic vasculitis: a look at the pulmonary fibrosis in microscopic polyangiitis with anti-myeloperoxidase antibodies and rheumatoid factor. Literature review and own observation

Depending on the epitope specificity of antineutrophil cytoplasmic antibodies (ANCA) and the presence or absence of a granulomatous inflammation. Patients with ANCA-associated vasculitis (AAV) show variability in clinical manifestations and prognosis depending on the epitope specificity of ANCA and the presence or absence of granulomatous inflammation. In this regard, it is important to identify the clinical and immunological phenotypes of AAV and a personalized approach to treatment. Microscopic polyangiitis (MPA) with antibodies to myeloperoxidase (aMPO) has a relatively high incidence of lung involvement and pulmonary fibrosis. We present our own clinical case of pulmonary fibrosis in MPA with aMPO and rheumatoid factor. Literature data are discussed. In cases of early arthritis and interstitial pneumonia, the possibility of AAV should be considered, a detailed examination is necessary to identify pathognomonic signs of AAV, including asymptomatic ones. Before prescribing immunosuppressants, the epitope specificity of ANCA should be determined. Treatment with rituximab, mycophenolate mofetil and nintedanib is discussed.

Vascular and Vasogenic Manifestations of Systemic ANCA-Associated Vasculitis with Renal Involvement in Non-Contrast Brain MRI in Patients with Acute Disease Onset.

Background. Data concerning central nervous system (CNS) alterations in ANCA-associated vasculitis with renal involvement (AAVR) are sparse. The study aimed to assess vascular and vasogenic brain alterations in patients with acute onset of AAVR and the applicability of non-contrast magnetic resonance imaging (MRI) techniques in this diagnosis. Methods. Thirty-eight patients with acute onset of AAVR were included in the study. BVAS/WG, c-ANCA, p-ANCA, renal function and perfusion, neurological assessment, and brain MRI were performed. Results. Cerebral vascular alternating narrowing and dilatation (VAND) was detected in 42.1% of patients, and the black-blood was significantly more diagnostic than the TOF technique (p < 0.001). VAND occurrence was independently associated with the concentration of p-ANCA. The vasogenic white matter lesions (VWML) were found in 94.4% of patients, and in their detection, SWAN was significantly better than the FLAIR technique (p = 0.002). The number of VWML correlated with age and cranial nerve damage. Hemosiderin deposits were found in 21.6% of patients and were associated with a gait impairment and paresthesia. Conclusions. Vascular and vasogenic alterations in the CNS are frequent in patients with acute onset of systemic ANCA-associated vasculitis with renal involvement. Non-contrast MRI is useful in the diagnosis of brain vasculitis.

Late-onset neutropenia induced by anti-B cell therapy with rituximab in patients with ANCA-associated systemic vasculitis

In the last decade, anti-neutrophil cytoplasmic antibodies (ANCA)-associated systemic vasculitis (SV) has been treated with the anti-B-cell drug, rituximab (RTM) both for induction and maintenance therapy. One of the problems of the treatment with RTM in patients with ANCA-SV is the risk of late-onset neutropenia (LON), mechanisms of development of which have not been studied enough yet.Objective: to evaluate the incidence and outcomes of LON in patients with ANCA-SV treated with RTM. Patients and methods. A retrospective analysis of the register of 140 patients with ANCA-SV who received RTM treatment at the V.A. Nasonova Research Institute of Rheumatology from 2009 to 2021 years. The median duration of RTM treatment was 49 (6–121) months, the median of the total RTM dose was 3.5 (0.5–9.5) grams. The duration of follow-up exceeded 6 months after the first administration of RTM.Results and discussion. LON was detected in 16 (11.4%) patients, of which 6 suffered from Wegener's granulomatosis with polyangiitis (GPA), 4 – microscopic polyangiitis (MPA), 4 – Churg-Strauss eosinophilic granulomatosis with polyangiitis (EGPA) and 2 – undifferentiated ANCA-SV. In 8 (50%) out of 16 patients, LON developed within 2 months after the 1st course of RTM, in the remaining 8 patients, on average, after 10 (4– 15.5) months. A lethal outcome was documented in 5 (31.2%) of 16 cases of LON (1 with MPA, 3 with GPA, and 1 with EGPA) on average 2 (1.5–9) months after the 1st course of RTM, at the same time, in 4 patients LON was complicated by pneumonia, including 2 with septic shock, in another 1 case LON was combined with the development of acute myocardial infarction and progression of chronic renal failure. Overall mortality among 140 patients with ANCA-SV treated with RTM was 11.4%, while in cases with a fatal outcome, the frequency of LON reached 31.2%.Conclusion. Thus, LON induced by RTM is a common (11%) and clinically significant consequence of B-cell depletion in patients with ANCA-SV, in every 5th case it is complicated by serious infections (including sepsis in 13%) and accounts for a significant proportion in the structure of lethal outcomes (31.2%).Patients treated with RTM require careful monitoring of absolute neutrophil count both during the first months after initiation of anti-B-cell therapy and thereafter. In the combined administration of RTM with cytotoxic drugs (primarily cyclophosphamide) in patients with ANCA-SV, it is necessary to consider the risk of LON developing, secondary immunodeficiency, and infectious complications. During the coronavirus pandemic, one should remember that treatment with interleukin 6 inhibitors used in severe COVID-19 can also be accompanied by neutropenia and requires careful dynamic monitoring of the absolute number of neutrophils in patients with ANCA-SV treated with RTM. It is necessary to inform both patients and physicians of the risk of LON development during the treatment of RTM in ANCA-SV and other rheumatic diseases.

A clinical case of ANCA-associated systemic vasculitis in a nine-year-old Sakha child

A clinical case of ANCA-associated systemic vasculitis in a nine-year-old Sakha child

Cost-Effectiveness of Rituximab (Fixed Schedule vs Tailored Dose) Compared With Azathioprine Maintenance Therapy in Adults With Generalized Antineutrophil Cytoplasm Antibody-Associated Vasculitis in Colombia

ObjectivesAzathioprine has been the therapy of choice for the maintenance of remission in patients with antineutrophil cytoplasm antibody (ANCA)-associated systemic vasculitis, but recent studies show that rituximab could be more effective. To evaluate the cost-effectiveness of azathioprine, fixed-schedule rituximab, and tailored-dose rituximab for ANCA-associated systemic vasculitis. MethodsA Markov model from the perspective of the Colombian healthcare system was designed with annual cycles and a 5-year time horizon, charting the following states: remission, minor relapse, major relapse, and death. The discount rate was 5%. Transition probabilities were obtained from a systematic literature review. The costs (1 US dollar = 2956 Colombian pesos in 2018) were estimated based on national drug registries and official fee manuals for procedures, along with other resources. The main outcomes were quality-adjusted life-years (QALYs) taken from the Tufts registry. Univariate and multivariate sensitivity analyses were performed. ResultsFinal costs were $1446 for azathioprine, $4898 for tailored-dose rituximab, and $6311 for fixed-schedule rituximab. QALYs gained were 3.18, 4.08, and 3.98, respectively. Rituximab was cost-effective (cost per incremental QALY gained: $4919, and $6865), and tailored-dose administration had a lower cost. Sensitivity analyses did not affect the results. ConclusionsTailored-dose rituximab was the most cost-effective treatment for ANCA-associated vasculitis. Azathioprine presented worse effectiveness and lower cost, and fixed-schedule rituximab was dominated by tailored-dose rituximab.

Complications and causes of mortality in patients with primary necrotizing systemic vasculitis

The article reviews the clinical symptoms, main complications in patients with ANCA-associated systemic vasculitis (granulomatous with polyangiitis, microscopic polyangiitis, eosinophilic granulomatous with polyangiitis) and polyarteritis nodosa during the first three years of the disease. We evaluated the relationship between complications and long-term glucocorticosteroid therapy. Patients with granulomatosis had the most unfavourable course of the disease with a high risk of complications. A high incidence of ischemic strokes and chronic kidney disease in patients with microscopic polyangiitis has been identified. We also analyzed cases of lethal outcomes in patients with primary systemic vasculitis.

Гангрена языка и пальцев – редкое проявление системного АНЦА-ассоциированного васкулита

Гангрена языка и пальцев – редкое проявление системного АНЦА-ассоциированного васкулита

Incidence and clinical predictors of infections in patients treated with severe systemic ANCA-associated vasculitis.

Immunosuppressive therapy has improved the outcome of ANCA-associated vasculitis (AAV), but infectious morbidity and mortality remained high. Recognizing its risk factors seems crucial for prevention, aiming to increase survival of these patients. We investigated the incidence and types of infections and assessed predictive factors in 132 patients with severe systemic AAV. Patients with lower than median incidence of total infections/patient-year during induction had lower baseline serum creatinine, dialysis requirement and Charlson comorbidity index (CCI), compared to those with higher than median incidence (P = 0.037; P = 0.024; P = 0.001; respectively). In subgroups with below and above than median number of severe infections/patient-year during induction, differences were found in baseline creatinine (P = 0.002) and dialysis requirement (P = 0.001); comparing the same cohorts during maintenance immunosuppression, baseline dialysis requirement, diabetes, CCI, and dose of cyclophosphamide (CYC) administered as induction therapy differed significantly (P = 0.019; P = 0.015; P = 0.001; P = 0.015, respectively). Severe infections were predicted by baseline serum creatinine (OR 1.002 [CI 1.001-1.003]) and pulmonary manifestation (OR 2.153 [CI 1.017-4.560]) during induction immunosuppression. In multivariable Cox regression model all-cause mortality was independently predicted by severe infection (HR 1.998 [CI 1.214-3.287]). Among the 168 positive cultures Gram-negative bacteria were responsible for blood stream infections in 33%, and respiratory tract infections in 72%. Advanced renal failure, pulmonary involvement and high degree of comorbidities increase the risk of infection in AAV. Those who suffer infection during induction immunosuppression have worse long-term survival. Our findings indicate the need for high vigilance for infections and close follow-up of comorbidities when treating AAV.

The course and outcomes of COVID-19 in patients with ANCA-associated systemic vasculitis, receiving biological therapy (Rituximab, Mepolizumab): The results of the first 8 months of the pandemic

Objective. Currently, the issues of the effect of anti-B cell therapy or inhibitor of interleukin 5 on the risk of COVID-19 infecting and outcomes in patients with ANCA-associated vasculitis (AAV) has not been completely studied. We present an analysis of the COVID-19 course and outcomes in AAV patients treated with rituximab or mepolizumab from one rheumatology center registry. Methods. From November 11 to November 15, 2020, a cross-sectional study was conducted using telephone and online surveys, and information was collected from all 128 AAV patients treated with rituximab in V.A. Nasonova Research Institute of Rheumatology. Patients mean age was 51 (20–81) years, 61.7% were women. Granulomatosis with polyangiitis (GPA) was diagnosed in 58 patients, microscopic polyangiitis (MPA) – in 38, eosinophilic granulomatosis with polyangiitis (EGPA) – in 24 (including 54.2% of ANCA-negative cases), and AAV with uncertain nosological affiliation – in 8 patients. Due to the disease activity or a high risk of AAV recurrence during the pandemic rituximab was prescribed in 60/126 (47.6%) patients, and mepolizumab – in 6 cases. Results. In the spring of the pandemic (until May 2020), the incidence of COVID-19 in AAV patients treated with rituximab was 4.3%, the disease course was relatively favorable. All patients recovered. At month 3–6, antibodies to SARS-CoV-2 IgG persisted in only 1 out of 4 patients. Since September 2020, the incidence has increased 3-fold, with a more severe course of COVID-19. In total, in the period until November 11, 2020, COVID-19 was diagnosed in 17.2% (22/128); the mean age of patients was 55 (25–81) years; 54.5% were women. 21/22 patients were on rituximab therapy, 2 patients had mepolizumab therapy (including 1 case after previous rituximab therapy). COVID-19 incidence was lower in patients with GPA (15.5%) vs MPA and EGPA (21.1% and 20.8% respectively). The mortality rate was 13.6%, including 2 patients with MPA and 1 patient with GPA. When analyzing the 5-year survival rate according to the registry of AAV patients treated with rituximab, prognosis worsening was noted; in 2020 there were 3 deaths due to COVID-19, in the previous 5 years – only 2 deaths. Discussion. Taking into account the fact the mechanisms of AAV and severe COVID-19 are largely synergistic (primarily in the context of microvascular COVID-19 lung vessels obstructive thromboinflammatory syndrome as manifestation of the acute inflammatory syndrome), the activity of AAV can potentially contribute to the disease onset and a severe course of COVID-19. Given the previously published information on the use of rituximab during the COVID-19 pandemic for various diseases, it seems that B cell depletion, without reducing the risk of infection, may have a protective effect with regard to the risk of severe/catastrophic COVID-19, which, however, can be insufficient in AAV patients. Further analysis of COVID-19 cases in patients with AAV and other immuno-inflammatory rheumatic diseases is exceptionally important.

Proteomic Data Analysis for Differential Profiling of the Autoimmune Diseases SLE, RA, SS, and ANCA-Associated Vasculitis.

Early and correct diagnosis of inflammatory rheumatic diseases (IRD) poses a clinical challenge due to the multifaceted nature of symptoms, which also may change over time. The aim of this study was to perform protein expression profiling of four systemic IRDs, systemic lupus erythematosus (SLE), ANCA-associated systemic vasculitis (SV), rheumatoid arthritis (RA), and Sjögren’s syndrome (SS), and healthy controls to identify candidate biomarker signatures for differential classification. A total of 316 serum samples collected from patients with SLE, RA, SS, or SV and from healthy controls were analyzed using 394-plex recombinant antibody microarrays. Differential protein expression profiling was examined using Wilcoxon signed rank test, and condensed biomarker panels were identified using advanced bioinformatics and state-of-the art classification algorithms to pinpoint signatures reflecting each disease (raw data set available at https://figshare.com/s/3bd3848a28ef6e7ae9a9.). In this study, we were able to classify the included individual IRDs with high accuracy, as demonstrated by the ROC area under the curve (ROC AUC) values ranging between 0.96 and 0.80. In addition, the groups of IRDs could be separated from healthy controls at an ROC AUC value of 0.94. Disease-specific candidate biomarker signatures and general autoimmune signature were identified, including several deregulated analytes. This study supports the rationale of using multiplexed affinity-based technologies to reflect the biological complexity of autoimmune diseases. A multiplexed approach for decoding multifactorial complex diseases, such as autoimmune diseases, will play a significant role for future diagnostic purposes, essential to prevent severe organ- and tissue-related damage.

Cutaneous manifestations of ANCA-associated vasculitis and immunosuppressive therapy: cause-effect relationships (a case report)

Granulomatosis with polyangiitis, formerly known as Wegeners granulomatosis, is an autoimmune ANCA-associated systemic vasculitis characterized by extensive damage to multiple organs and systems. Besides a typical clinical triad of ENT, lungs, and kidneys injury, various types of skin lesions can be found in 1050% of cases. A severe course of the disease and low survival of patients often requires using aggressive treatment in a form of combined immunosuppressive therapy. On the one hand, it generally improves the prognosis, and on the other is itself associated with numerous complications. One of them is a secondary infection. Skin is the second most common localization of infection after the respiratory system. Preceding skin lesions caused by vasculitis may increase the risk of infection. Thus, patients with ANCA-associated vasculitis should be carefully observed for cutaneous manifestation, both before and during the immunosuppressive therapy.

Seizures in steroid-responsive encephalopathy.

Steroid-responsive encephalopathy is a general term for diseases that are characterized by diffuse brain injury and respond well to corticosteroids or immunosuppressive agents, including Hashimoto's encephalopathy (HE), limbic encephalitis (LE), systemic lupus erythematosus encephalopathy (SLEE), antineutrophil cytoplasmic antibodies (ANCA)-associated systemic vasculitis encephalopathy (AASV), viral encephalitis (VE), and primary central nervous system lymphoma (PCNSL). Epilepsy and status epilepticus are the main manifestations of steroid-responsive encephalopathy. The spectrum of "autoimmune epilepsy" diseases, which has been approved by the epilepsy diagnostic recommendations of the International Antiepileptic League, is characterized by a high prevalence of epilepsy in central nervous system (CNS) autoimmune diseases and a variety of neuron-specific autoantibodies. Steroid-responsive encephalopathy with different causes may have different pathogeneses and has been suggested to be associated with some internal commonality producing seizure as the main symptom. Determining the regularity of seizures caused by steroid-responsive encephalopathy and implementing appropriate measures will help us improve the prognosis of patients. This paper summarizes the epidemiology, seizure onset, seizure type, and other characteristics of seizures in steroid-responsive encephalopathy (including HE, LE, SLEE, ANCA-associated systemic vasculitis encephalopathy, VE, and PCNSL) and then discusses the use of antiepileptic drugs to treat steroid-responsive encephalopathy.

Clinical and immunological variants of ANCA-associated systemic vasculitis: a look at the phenomenon of IgG4 overproduction. Literature review and own observations

Systemic vasculitis (SV) associated with anti-neutrophilic cytoplasmic antibodies is a multifactorial process characterized by the variability of the epitope specificity of anti-neutrophilic cytoplasmic antibodies and the diversity of clinical phenotypes of the disease. In recent years, there has been an increasing interest in the combination of AAV and the phenomenon of IgG4 hyperproduction, which varies widely within AAV, from anti-neutrophilic cytoplasmic antibodies products of IgG4 subclass of undetermined significance, the presence of IgG4 positive plasma cells in the foci of immunoinflammatory lesions in patients with a definite diagnosis of AAV, to the typical clinical manifestations of an IgG4-related disease (IgG4-RD). We introduce own clinical case and analyze the combined data of the literature, which included 35 cases of a combination of AAV and IgG4-related pathology, indicating existing differences in the clinical manifestations of classical IgG4-RD and when combined with AAV. The currently accumulated data allows us to discuss the allocation of a specific clinical and immunological variant of AAV with IgG4 hyperproduction, characterized by a combination of clinical manifestations of AAV and clinical and / or histological signs of IgG4-related pathology. It is important to emphasize that the allocation of phenotypes of AAV in the future may be important for the personalized choice of treatment tactics for patients.

ANCA-associated vasculitis in a 14 years-old patient: a clinical case

Background. ANCA-associated systemic vasculitis is a rare childhood disease. Antineutrophil cytoplasmic autoantibodies (ANCA)-related vasculitises include microscopic polyangiitis, granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis. Their rarity often leads to a late diagnosis, rapid disability and high mortality in patients due to aggressive respiratory, pulmonary lesion and renal failure.Clinical Case Description. The patient suffered from a recurrent bronchoobstructive syndrome with signs of respiratory failure, obscure origin fever and chronic rhinitis with nasal bleeding for 6 months. The patient was diagnosed with obstructive bronchitis (putative bronchial asthma debut), received antibacterial therapy and inhalation bronchodilators without stable improvement during the entire period. Skin haemorrhages and arthralgia stimulated diagnostic research to establish ANCA-associated systemic vasculitis (presence of proteinase 3-specifi c ANCAs in titre 1/80). CT lung scanning revealed frosted glass foci of reduced pulmonary pneumatisation and signs of bilateral bronchoobstruction. Immunosuppressive therapy with glucocorticosteroids (methylprednisolone pulse therapy No. 3, 1000 mg intravenously on alternate days, subsequent per os administration of 1 mg/kg/day) and cyclophosphamide (500 mg intravenously once per 28 days) was prescribed. This led to the positive dynamics with eliminated fever and skin haemorrhages, as well as essentially reduced signs of respiratory failure.Conclusion. Diagnosis of systemic vasculitis is often complicated and long-term due to commonly non-specifi c debut symptoms of autoimmune disorders. In the described case, the fi rst 6 months of illness displayed intoxication and bronchoobstruction with signs of respiratory failure. Haemorrhagic rashes, arthralgias and the presence of ANCAs are proxy to vasculitis. Standard immunosuppressive therapy for ANCA-associated vasculitis improved the patient’s condition.