High-dose Immunosuppressive Therapy Research Articles

Resting state functional magnetic resonance imaging in patients with multiple sclerosis before and after high-dose immunosuppressive therapy and autologous hemopoietic stem cell transplantation

BACKGROUND: Multiple sclerosis is a chronic autoimmune disease characterized by multifocal foci of demyelination in the central nervous system, usually affecting people of working age. The disease causes damage to the blood-brain barrier, the development of multifocal inflammation, destruction of the myelin sheath of axons and various degrees of damage. It is clinically manifested by restriction of motor activity, visual acuity, as well as other symptoms leading to loss of performance and disability of the patient. AIM: determination of changes in the functional connectivity of brain neural networks in patients with multiple sclerosis before and after high-dose immunosuppressive therapy and autologous hematopoietic stem cell transplantation by performing functional magnetic resonance imaging at rest. MATERIALS AND METHODS: The data of functional magnetic resonance imaging of patients with multiple sclerosis were analyzed in dynamics before and after the use of high-dose immunosuppressive therapy followed by autologous hematopoietic stem cell transplantation. The study involved 25 patients with a verified diagnosis of multiple sclerosis. Each underwent complex magnetic resonance imaging at two time points (before and after high-dose immunosuppressive therapy followed by autologous hematopoietic stem cell transplantation) with a difference of 12 months, which included structural magnetic resonance imaging - in order to exclude the presence of pathological foci in the brain (in addition to foci of multiple sclerosis) and functional magnetic resonance imaging.-resonance imaging at rest — to assess functional connectivity. Also, according to the method generally accepted in classical neurology, a clinical neurological examination was performed. RESULTS: At the stage of comparing data on the two groups obtained using functional magnetic resonance imaging at rest, changes in functional activity were detected in various parts of the brain, presumably responsible for clinical differences in the studied groups. CONCLUSION: Currently, the links between brain structures and morphological changes that cause cognitive impairment in multiple sclerosis are being studied. To predict the progression of the disease, the development of biomarkers, including those based on functional magnetic resonance imaging, is required. Evaluating changes in the functional connectivity of brain neural networks can help personalize therapeutic and rehabilitation approaches.

Analysis of the quality of life in patients with multiple sclerosis within 3 years after high-dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation

Introduction. To date, data have been accumulated indicating the high effectiveness of the HDIT-AHSCT and the possibility of preserving and improving the quality of life of patients after its application.The objective was to analyze the dynamics of quality of life using standardized assessment tools in patients with MS for 3 years after the use of HDIT-AHSCT, who participated in the program of clinical approbation of the method.Methods and materials. The single-center observational study included 21 patients (10 women, 11 men) with a reliable diagnosis of MS, who underwent HDIT-AHSCT at the Pavlov First Saint Petersburg State Medical Universityin accordance with the protocol of clinical approbation. Distribution by type of MS course: remitting (RMS) 16 (76.2 %), secondary progressive (SPMS) 4 (19 %), primary progressive (PPMS) 1 patient (4.8 %). The assessment of quality of life (SF-36, FAMS, CSP-MS42, HADS) and severity of disability (EDSS) in all patients was performed before, 12 and 36 months after HDIT-AHSCT.Results. Three years after the HDIT-AHSCT, a significant decrease in weakness, feelings of constant fatigue and rapid fatigue during exertion was recorded. The level of anxiety decreased in more than 50 % of patients. A direct relationship between the dynamics of clinical characteristics and the data of the scales of the SF-36 questionnaire was revealed; at the same time, after 36 months, an improvement in all parameters of the scale was noted.Conclusion. The assessment of the indicators of the quality of life questionnaires allows us to confirm the effectiveness and significance of therapy not only from the point of view of objective clinical and radiation parameters necessary for the evidence base of the treatment method, but also from the patient’s position, which in conditions of a chronic progressive process is an integral factor for the appointment of therapeutic intervention.

Comparison of a voclosporin-based triple immunosuppressive therapy to high-dose glucocorticoid-based immunosuppressive therapy: a propensity analysis of the AURA-LV and AURORA 1 studies and ALMS

IntroductionHigh-dose glucocorticoid (GC)-based dual immunosuppressive treatment regimens are still frequently used in active lupus nephritis (LN) despite their known association with dose-dependent toxicities and incomplete efficacy. We hypothesised that the...

High-dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation in crohn disease: literature review

The literature review presents the current status of the method of high-dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation in the treatment of Crohn’s disease.In recent decades, there has been an increase in Crohn’s disease. The frequency of CD the response rate to biopreparations ranges from 20 to 50%, up to 80% of patients need surgical treatment. Due to the insufficient effectiveness of therapy, an active research is underway for new therapeutic opportunities, one of which is the method of HDIT-AHSCT. In the Russian Federation, there are data on the use of mesenchymal stem cells for the treatment of CD, there are no studies on the use of HDIT-AHSCT in IBD. According to the EBMT register in the period from 1994 to 2023. more than 4000 HDIT-AHSCT were performed in patients with autoimmune diseases, the proportion of CD was 6.13% of all protocols. The HDIT-AHSCT procedure consists of the following stages: mobilization of autologous HSCs, apheresis and cryopreservation of HSCs, immunoablative conditioning and infusion of HSCs. Most of the publications on the use of HDIT-AHSCT in CD were not universal in the selection and management of patients. Currently, there is the only one completed RCT on the use of HDIT-AHSCT in CD, the results of which have not received a definite outcome. However, for a cohort of patients with refractory CD, it is necessary to consider the possibility of using this method. The review presents the indications and selection criteria for the HDIT-AHSCT protocol. Further studies of the HDIT-AHSCT in CD will help expand the therapeutic opportunities of treating patients with refractory CD to standard and biological therapy.

Вплив імуносупресивної терапії на стан імунного захисту в дітей

For the treatment of rheumatological diseases, autoimmune lymphoproliferative syndrome and nephrotic syndrome in children, glucocorticosteroid therapy with/without cytostatics is used. Immunosuppression is a serious side effect of these medications. Aim - to investigate immunological parameters in children receiving immunosuppressive therapy in order to determine vaccination tactics. Materials and methods. 50 healthy children (comparison group) and 34 children who received immunosuppressive therapy for rheumatological pathology, autoimmune lymphoproliferative syndrome or nephrotic syndrome (study group) participated in the study. Patients who received high-dose immunosuppressive therapy (n=16) made up the subgroup I, low-dose immunosuppressive therapy (n=18) - the subgroup II. Determination of subpopulations of blood lymphocytes was carried out by the method of flow cytometry, serum immunoglobulins - by the method of radial immunodiffusion. Statistical analysis was performed using the SPSS 23.0 software package. Results. In children who received immunosuppressive therapy, a significant increase in the number of T-lymphocytes (CD3+), a decrease in B-lymphocytes (CD19+) and NK cells (CD3-CD16/56+) was established, while the average levels of serum IgA, IgM, IgG did not differ from the indicators of healthy children, which demonstrates the preservation of humoral immunity. However, in children who received high-dose immunosuppressive therapy, a dose-dependent decrease in the level of serum IgA, IgM, and IgG was found, respectively, by 1.7, 1.3 times, and by 18.9%. Conclusions. It is advisable to vaccinate children before starting immunosuppressive therapy for rheumatological pathology or nephrotic syndrome. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of all participating institutions. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

High-dose immunosuppressive therapy followed by haematopoietic stem cell transplantation as a method for the treatment of refractory forms of neuromyelitis optica spectrum disorder in children

High-dose immunosuppressive therapy followed by haematopoietic stem cell transplantation as a method for the treatment of refractory forms of neuromyelitis optica spectrum disorder in children

Autologous hematopoietic stem cell transplantation as a method of immune prevention of type 1 diabetes mellitus: possibilities and prospects

Type 1 diabetes mellitus (DM) is one of the most common autoimmune disease that is treated with lifelong insulin therapy. Non-target indicators of glycemic control, which are observed in 71% of patients, lead to the formation and progression of diabetes complications, early disability and mortality. In this regard, the search for new approaches to the treatment and prevention of type 1 DM seems to be relevant. Various methods of immunological prophylaxis for the development of type 1 DM have been studied, in particular, the use of monoclonal antibodies. Thus, in November 2022, teplizumab was approved to slow down the clinical progression of the stage of type 1 DM. The prospects for the use of new options for islet cell transplantation are being studied — in June 2023, an allogeneic donor β-cell transplant obtained from the pancreas of donors after death was approved. Another pathogenetically substantiated method for the prevention and treatment of autoimmune diseases is high-dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation (HDIT-HSCT). HDIT-HSCT demonstrated its effectiveness and cost-effectiveness in various clinical trials. This review provides up-to-date information on modern methods of immunological prophylaxis of type 1 DM.

Comparative study of virus and lymphocyte distribution with clinical data suggests early high dose immunosuppression as potential key factor for the therapy of patients with BoDV-1 infection

ABSTRACT Borna disease virus 1 (BoDV-1) was just recently shown to cause predominantly fatal encephalitis in humans. Despite its rarity, bornavirus encephalitis (BVE) can be considered a model disease for encephalitic infections caused by neurotropic viruses and understanding its pathomechanism is of utmost relevance. Aim of this study was to compare the extent and distribution pattern of cerebral inflammation with the clinical course of disease, and individual therapeutic procedures. For this, autoptic brain material from seven patients with fatal BVE was included in this study. Tissue was stained immunohistochemically for pan-lymphocytic marker CD45, the nucleoprotein of BoDV-1, as well as glial marker GFAP and microglial marker Iba1. Sections were digitalized and counted for CD45-positive and BoDV-1-positive cells. For GFAP and Iba1, a semiquantitative score was determined. Furthermore, detailed information about the individual clinical course and therapy were retrieved and summarized in a standardized way. Analysis of the distribution of lymphocytes shows interindividual patterns. In contrast, when looking at the BoDV-1-positive glial cells and neurons, a massive viral involvement in the brain stem was noticeable. Three of the seven patients received early high-dose steroids, which led to a significantly lower lymphocytic infiltration of the central nervous tissue and a longer survival compared to the patients who were treated with steroids later in the course of disease. This study highlights the potential importance of early high-dose immunosuppressive therapy in BVE. Our findings hint at a promising treatment option which should be corroborated in future observational or prospective therapy studies. ABBREVIATIONS: BoDV-1: Borna disease virus 1; BVE: bornavirus encephalitis; Cb: cerebellum; CNS: central nervous system; FL: frontal lobe; GFAP: glial fibrillary acid protein; Hc: hippocampus; Iba1: ionized calcium-binding adapter molecule 1; Iba1act: general activation of microglial cells; Iba1nod: formation of microglial nodules; IL: insula; Me: mesencephalon; Mo: medulla oblongata; OL: occipital lobe; pASS: per average of 10 screenshots; patearly: patients treated with early high dose steroid shot; patlate: patients treated with late or none high dose steroid shot; Po: pons; So: stria olfactoria; Str: striatum

379 A propensity analysis of AURA-LV plus AURORA 1 vs ALMS to compare a voclosporin-based, triple immunotherapy regimen to high-dose glucocorticoid-based immunosuppressive therapy

379 A propensity analysis of AURA-LV plus AURORA 1 vs ALMS to compare a voclosporin-based, triple immunotherapy regimen to high-dose glucocorticoid-based immunosuppressive therapy

Quality of life of patients with multiple sclerosis after high-dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation

Introduction. Multiple sclerosis (MS) is a chronic autoimmune and neurodegenerative disease of the central nervous system (CNS). High-dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation (HDIT–AHSCT) is the most eff ective method of treating MS, which has a positive eff ect on the quality of life of patients and inhibition of the progression of disability.The aim of the study was to analyze the dynamics of quality of life in patients with MS who underwent the HDIT– AHSCT method in groups with diff erent clinical effi cacy of this method.Material and methods. The single-center observational study included patients with MS (n = 21, mean age 35.5 ± 6.2 (28–50) years; men/women — 11/10; remitting MS (RMS) n = 16, secondary-progressive (SPMS) n = 4, primaryprogressive (PPMS) n = 1), after HDIT–AHSCT (cyclophosphamide-rituximab conditioning regimen). Assessment of the quality of life (SF-36, FAMS, CSP-MS42, HADS) and the degree of disability in all patients was carried out before and 12 months after HDIT–AHSCT.Results. 12 months after HDIT–AHSCT, more than 50% of patients showed signifi cant improvement in quality of life according to the scales of viability and social functioning of the SF-36 questionnaire, as well as according to the scales of general well-being and additional problems of the FAMS questionnaire. 57% of patients had a signifi cant improvement in the overall FAMS score. According to the CSP-MS42 questionnaire, a decrease in weakness (p < 0.05), feelings of constant fatigue and rapid fatigue during exercise was revealed. After transplantation, there was a slight decrease in anxiety (p = 0.91) and a signifi cant decrease in depression (p = 0.011).Conclusion. The expected dynamics was established: in patients with clinical improvement, there was an improvement in the quality of life for most indicators; in patients with stabilization, most quality of life indicators were similar before and after HDIT–AHSCT; with clinical deterioration after HDIT–AHSCT, quality of life parameters worsened. These data indicate the expediency of further optimization of patient selection criteria and various stages of the HDIT–AHSCT in order to obtain optimal clinical results and, accordingly, improve the quality of life of patients.

A rare case of childhood-onset systemic lupus erythematosus associated end-stage renal disease with cerebral abscess and hemorrhage

Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease that affects multiple organs. More than half of the patients with SLE have kidney involvement, and up to 10% of patients with lupus nephritis develop end-stage renal disease (ESRD). Central nervous system (CNS) involvement in SLE occurs in 21% to 95% of patients. Severe neurological manifestations such as seizures, cerebrovascular disease, meningitis, and cerebrovascular accidents can develop in childhood-onset SLE, but cerebral infections, such as brain abscess and hemorrhage, are seldom reported in lupus nephritis, even in adults. Here, we report a rare case of childhood-onset SLE with ESRD, a cerebral abscess, and hemorrhage. A 9-year-old girl diagnosed with lupus nephritis was administered high-dose steroids and immunosuppressant therapy to treat acute kidney injury (AKI) and massive proteinuria. The AKI deteriorated, and after 3 months, she developed ESRD. She received hemodialysis three times a week along with daily peritoneal dialysis to control edema. She developed seizures, and imaging showed a brain abscess. This was complicated by spontaneous cerebral hemorrhage, and she became unstable. She died shortly after the hemorrhage was discovered. In conclusion, CNS complications should always be considered in clinical practice because they increase mortality, especially in those with risk factors for infection.

Multimodality Imaging Features of Orbital Necrobiotic Xantogranuloma: A Case Report and Literature Review

Background: Necrobiotic xanthogranuloma (NXG) is a rare non-Langerhans histiocytosis that primarily manifests as skin lesions and is often associated with hematologic disorders, particularly monoclonal gammopathy. The orbit is the most common site of extracutaneous involvement in NXG. Since its first description in 1980, the molecular pathology and dermatologic characteristics of NXG have been extensively studied. However, there is no comprehensive multimodality description of the imaging features of orbital NXG in the literature. This case report aimed to describe the imaging features of NXG and provide a brief overview of the imaging differentials. Patient presentation: A 16-year-old white young man was referred to our center for evaluation of a 6-year history of a slowly growing right orbital mass, which resulted in vision loss in his right eye. His medical history was notable for systemic juvenile rheumatoid arthritis (sJRA) and a gain-of-function (GOF) mutation in the IKAROS gene, which predisposed him to immune dysregulation. To further characterize the orbital lesion, orbital computed tomography (CT), magnetic Resonance Imaging (MRI), and Fluorodeoxyglucose Positron Emission Tomography/Magnetic Resonance Imaging (FDG PET/MRI) were performed. A biopsy of the most hypermetabolic component of the infiltrative retro-orbital mass confirmed the diagnosis of NXG. He received high-dose immunosuppressive and IVIG therapy and bone marrow stem cell transplantation, which resulted in a slight reduction in the right orbital mass. Conclusion: This paper presents the first multimodality imaging features of orbital necrobiotic xanthogranuloma in an adolescent patient.

#2733 TRANSPLANTATION OF MESENCHYMAL STEM CELLS - NEW FOCUS OF IMMUNE CORRECTION IN TREATMENT OF LUPUS NEPHRITIS

Abstract Background and Aims Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterised by the production of organ-specific autoantibodies to components of cell nucleus, immune complex lesions of the connective tissue, and the development of irreversible damage of internal organs. Chronic relapsing course of SLE, resistance to steroid and immunosuppressive therapy, toxic effects of drugs determine the need of search for new therapeutic approaches. Objective To evaluate the efficacy and safety of bone marrow mesenchymal stem cell (MSC) transplantation with high-dose immunosuppressive therapy (HIST) in SLE patients. Method A total amount of 15 patients with a diagnosis of SLE (ACR criteria) refractory to classical immunosuppressive therapy was examined. Patients were divided into 2 groups: patients from the main group underwent MSCs transplantation with HIST (n = 10), while the control group was observed on the background of traditional immunosuppressive therapy without cell transplantation (n = 5). Both groups were comparable in age, gender of patients, duration and severity of the disease. The SELENA-SLEDAI was used to determine SLE activity. Cytokines were examined by ELISA (IL-1Β, IL-4, IL-10, TNF-Α), antibodies to double-stranded DNA (anti-dsDNA) and anti-nuclear antibodies (ANA) by indirect immunofluorescence. Morphological examination of kidney included Masson-trichrome histochemistry for collagen fibers, silvering reaction for elastic and reticulin fibers, immunofluorescent and immunohistochemical methods. The safety assessment included registration of various adverse events during and after transplantation. Statistical analysis was carried out by Kruskal-Wallis test using STATISTICA 6.1. Results Monitoring the effectiveness of autologous stem cell transplantation in SLE patients showed a significant 2-fold decrease in activity by SELENA-SLEDAI score from 14.67±1.15 to 7.33±1.15 points after 12 months (p = 0.03). In the control group, this indicator remained unchanged and amounted to 15.0±0.87 points despite ongoing immunosuppressive therapy. Clinical efficacy was noted in all patients receiving HIST and MSC transplantation, which was confirmed by a significant decrease in daily proteinuria from 2,48±0,77 to 1,06±0,56 g/l, a decrease in the value of antibodies to DNA (from 443,28±547,53 to 187,8±146,60) and blood cytokines (significantly for TNF-Α), and an increase in the level of complement (though insignificantly). According to kidney biopsy data, after MSC transplantation with HIST, positive dynamics consisted in an increase in the number of reticulin fibers in the vascular loops of the glomeruli, as well as a decrease in the immune inflammatory process in the vascular loops of the glomeruli by immunofluorescence analysis for the spectrum of antibodies (Figure 1). In most patients of the main group, the doses of methylprednisolone and immune suppressants were reduced. Chills during transplantation was registered in one patient; no other unwanted adverse events were identified. Conclusion MSC transplantation in combination with HIST is significantly more effective than traditional immunosuppressive therapy in SLE according to clinical and laboratory data. The method is safe, allows decreasing signs of autoimmune aggression and can be used in cases of refractoriness, low efficiency or intolerance of standard therapy for SLE.

#6660 HERPES ZOSTER IN LUPUS NEPHRITIS: AN UNDERESTIMATED COMPLICATION

Abstract Background and Aims Herpes zoster (HZ) is a known complication of lupus nephritis (LN) because of the drug-related immunosuppression. In fact, high dose corticosteroids (CS) and immunosuppressive (IS) therapy are almost always used in this setting. Our aim is to evaluate the predisposing factors for the development of HZ in patients with LN. Method Retrospective cohort study on 292 LN patients. Demographic and clinical data are expressed as numbers or percentages in case of discrete variables, whereas, in case of continuous variables, they are expressed as median and interquartile range (IQR). The demographic characteristics have been analyzed with Mann-Whitney U test and Fisher's test where appropriated. A univariate and multivariate logistic regression has been performed to identify potential risk factors. Results The incidence of HZ in our cohort is 22.6% (66/226). The patients’ characteristics are shown in Table 1. HZ patients are older (54 vs 45 yo, p<0.001). No differences were found in the clinical characteristics at LN diagnosis, except for higher chronicity index in HZ patients (2 vs 1, p = 0.03). No difference was found in the initial IS therapy. Higher cumulative dose of CS was used in patients with HZ (48.9 vs 21.5 grams, p<0.0001). At univariate and multivariate logistic regression (Table 2) age, female sex, the presence of a proliferative form at renal biopsy (class III or IV) and cumulative CS dose greater than 100 grams are linked to a higher risk for HZ. Conclusion Incidence of HZ in our LN cohort is high (22.6%). HZ patients are older, while non-significative differences in clinical presentation or initial IS therapy are present. Age, female sex, the presence of a proliferative form at biopsy and greater cumulative CS dose seems to be a risk factor for HZ development in LN patients. According to these data and to the possible evolution of HZ infection in disseminated forms, HZ vaccination should be strongly recommended in LN patients.

Oral mucositis and microbial status in acute lymphoblastic leukemia subjects undergoing high-dose chemotherapy

Aim: To assess oral microbial status in patients with acute lymphoblastic leukemia (ALL) undergoing high-dose chemotherapy and to unravel possible associations between nosocomial pathogens and the establishment of chemotherapy-induced oral mucositis (CIOM). Methods: Oral mucosa, saliva, and peripheral blood samples were collected from 46 ALL subjects one day prior to chemotherapy (D0) and 2 weeks after treatment initiation (D14). Clinical intraoral inspection was performed by a single practitioner, with mucositis classification performed according to the WHO oral toxicity scale. Blood components were quantified by automatic flow cytometry, while oral Staphylococcus aureus and Pseudomonas aeruginosa were detected by Polymerase Chain Reaction with species-specific primers. Associations among bacteria and clinical findings were determined by Fisher’s Exact test, longitudinal bacterial changes by paired Macnemar, and correlations among blood parameters and mucositis status or bacteria via Mann-Whitney. Results: S. aureus displayed higher detection rates at D14 (p < 0.05) and was positively associated with mucositis, adoption of a non-solid diet (all p < 0.001), nausea and fever (all p < 0.05). Conversely, P. aeruginosa did not correlate to CIOM clinical parameters. At the systemic standpoint, lower hemoglobin levels associated with CIOM and fever events (all p < 0.01). Conclusion: The study evidences S. aureus as a potential pathogen in ALL-CIOM, reaffirming microbial control as an important preventive measure during high-dose immunosuppressive therapy. The weight of non-white-blood-cell parameters should be validated as novel CIOM biomarkers in prospective research.

What Is New in Pulmonary Mucormycosis?

Mucormycosis is a rare but life-threatening fungal infection due to molds of the order Mucorales. The incidence has been increasing over recent decades. Worldwide, pulmonary mucormycosis (PM) presents in the lungs, which are the third main location for the infection after the rhino-orbito-cerebral (ROC) areas and the skin. The main risk factors for PM include hematological malignancies and solid organ transplantation, whereas ROC infections classically are classically favored by diabetes mellitus. The differences between the ROC and pulmonary locations are possibly explained by the activation of different mammalian receptors-GRP78 in nasal epithelial cells and integrin β1 in alveolar epithelial cells-in response to Mucorales. Alveolar macrophages and neutrophils play a key role in the host defense against Mucorales. The diagnosis of PM relies on CT scans, cultures, PCR tests, and histology. The reversed halo sign is an early, but very suggestive, sign of PM in neutropenic patients. Recently, the serum PCR test showed a very encouraging performance for the diagnosis and follow-up of mucormycosis. Liposomal amphotericin B is the drug of choice for first-line therapy, together with correction of underlying disease and surgery when feasible. After a stable or partial response, the step-down treatment includes oral isavuconazole or posaconazole delayed release tablets until a complete response is achieved. Secondary prophylaxis should be discussed when there is any risk of relapse, such as the persistence of neutropenia or the prolonged use of high-dose immunosuppressive therapy. Despite these novelties, the mortality rate from PM remains higher than 50%. Therefore, future research must define the place for combination therapy and adjunctive treatments, while the development of new treatments is necessary.

A Case of Relapsing Polychondritis with Tracheobronchial Involvement

Relapsing Polychondritis (RPC) is a rare systemic inflammatory disorder of unknown etiology and characterized by recurrent and progressive inflammation of the cartilaginous structures, particularly involving the auricles, nose and respiratory tract as well as extra-cartilaginous tissues, including eyes, heart, skin, central nervous and hematological systems. Its diagnosis can be difficult when the typical clinical features such as auricular chondritis are absent. Here, we report on a case of 43-year-old woman who presented with recurrent sore thorat, dysphagia, extertional dyspnea, cough and noisy breathing initially misdiagnosed as acute laryngitis who was eventually diagnosed as Relapsing polychondritis with tracheobronchial involvement. Chest computed tomography showed the diffuse involvement of tracheobronchial cartilage. Based on the, Damiani’s criteria, she was diagnosed as relapsing polychondritis even though there was no unique involvement of auricular cartilage, and high dose steroid and immunosuppressive therapy were then started. This case indicated that patients who have tracheobronchial cartilage involvement without definite auricular chondritis should be considered for relapsing polychondritis as a differential diagnosis. This case is reported to raise awareness of airway involvement in RPC and discuss its current management.

Pneumocystis jirovecii Infections Among COVID-19 Patients: A Case Series and Literature Review.

Pneumocystis jirovecii pneumonia (PCP) is a serious, emerging complication of coronavirus disease 2019 (COVID-19). We performed a systematic review of published cases. We describe 6 new cases of PCP/COVID-19 coinfection. Among our cases (n = 6) and those in the literature (n = 69) with available data, the median age (interquartile range [IQR]) was 59 (44-77) years (n = 38), 72% (47/65) were male, and the mortality rate was 30.9% (21/68). Long-term corticosteroid use was noted in 45.1% (23/51), advanced HIV infection (defined as a CD4 count <200 cells/μL) in 17.6% (9/51), and antineoplastic chemotherapy in 13.7% (7/51), consistent with known PCP risk factors. Notably, 56.7% (38/47) had verifiable risk factors for PCP (high-dose corticosteroids, immunosuppressive therapy, and HIV infection) before COVID-19 infection. A median absolute lymphocyte count (IQR) of 0.61 (0.28-0.92) ×103 cells/mm3 (n = 23) and CD4 count (IQR) of 66 (33-291.5) cells/mm3 (n = 20) were also discovered among the study population. These findings suggest a need for greater attention to PCP risk factors among COVID-19 patients and consideration of PCP prophylaxis in these high-risk populations.

ВОЛЧАНОЧНЫЙ НЕФРИТ: КЛИНИЧЕСКИЙ СЛУЧАЙ С ДВОЙНОЙ ТРАНСПЛАНТАЦИЕЙ. ВКЛАД Ар.А. ДЕМИНА В ИЗУЧЕНИЕ ЗАБОЛЕВАНИЯ

Introduction. Lupus nephritis (LN) is common in systemic lupus erythematosus (SLE), a severe autoimmune disease with a poor prognosis. Restoring the immune system and self-tolerance using high-dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation (AHSCT) is a new approach in the treatment of refractory SLE. The effectiveness of SLE with LN treatment in the long-term follow-up should be the subject for study. Methods. Patient I., 25 years old, with refractory SLE and LN is described. Standard therapy was ineffective, the SLEDAI score remained 22 points, so the patient underwent high-dose immunosuppressive therapy (HIT) with ASCT, and she was included in the registry of the European Group for Blood and Marrow Transplantation of the European League Against Rheumatism (EBMT/EULAR). Results. As a result of ASCT, complete clinical and serological remission was achieved (score on the SLEDAI scale – 0 points) for 3 years. Then there was a relapse with nephrotic syndrome and anti-DNA positivity which led to the end-stage renal failure. Despite therapy, the disease activity persisted, and the patient was on regular hemodialysis for 1 year, then underwent allogeneic kidney transplantation. Currently, 18 years have passed since HIT and AHSCT and 11 years since renal transplantation. The patient receives standard post-transplant immunosuppression, and her condition remains stable, the renal allograft is functioning, the SLEDAI score is 2 points (low titer anti-DNA positivity). Discussion. Modern standards of chemotherapy (hydroxychloroquine, mycophenolate mofetil, cyclophosphamide, corticosteroids), bioactive immunotherapy (rituximab, belimumab, obinituzumab, anifrolumab), “multi-target therapy” (standard + tacrolimus, voclosporin, mycophenolate mofetil), and new approaches (immuno- and nephrotransplantation) for lupus nephritis. Conclusion. The successful long-term results of the first case of immunoablation with high-dose immunosuppressive therapy and double autologous stem cell and allogeneic kidney transplantation for SLE with refractory lupus nephritis and an analysis of the effectiveness of modern treatment approaches are presented.

Эндокринные осложнения в ходе проведения высокодозной иммуносупрессивной терапии с аутологичной трансплантацией гемопоэтических стволовых клеток при аутоиммунных заболеваниях

Эндокринные осложнения в ходе проведения высокодозной иммуносупрессивной терапии с аутологичной трансплантацией гемопоэтических стволовых клеток при аутоиммунных заболеваниях