Congenital Immunodeficiency Research Articles

HCT in the widening spectrum of congenital immunodeficiencies.

Hematopoietic stem cell transplantation (HSCT) and inborn errors of immunity (IEI) have been closely linked since transplantation was first used to cure severe combined immunodeficiency (SCID) in 1968. Since then, novel genes and diseases have been continually added to the ongoing list of IEI, and new data on indications and outcomes have emerged. We review recent data and progress in the field of hematopoietic cell transplantation (HCT) for IEI including new diseases and complications. Emerging data from haploidentical transplants, newborn screening results, and multicentric studies reveals promising outcomes for IEI. Immune dysregulation diseases deserve special attention regarding disease control and may require additional drugs pretransplant. Female carriers of X-linked Chronic granulomatous may present with a severe phenotype warranting the need for HCT. Insights from infectious complications and long-term comorbidities should help guide decisions to treat IEI patients. From classical indications to recently described diseases, HCT for immunodeficiencies is a rapidly growing field. Novel data regarding alternative donor transplants, results from large cohorts, and long-term complications provide valuable knowledge for clinical practice.

Oral potentially malignant disorders: leukoplakia, erythroplakia, oral submucosal fibrosis. Systematic review of associated risk factors

Introduction. Oral potentially malignant disorders (OPMD) represent a heterogeneous group of oral mucosal disorders associated with an increased risk of malignant transformation. The specialty literature indicates that tobacco consumption in various forms, such as smoking products containing tobacco, reverse smoking, chewing tobacco, alcohol consumption, consumption of areca (betel) nuts, are the factors most often involved in the development of OPMD. The aim of the study. Systematic review of scientific researches and clinical trials on risk factors involved in the development of leukoplakia, erythroplakia and oral submucosal fibrosis. Material and methods. To carry out the systematic review, scientific researches and clinical studies from the last 5 years available on the platforms PubMed, Embase, Scopus and Cochrane Library were analyzed. The identification of the studies was based on the presence in them of the terms specific to the topic of the systematic review and the data analysis was carried out by 2 doctors - dento-alveolar surgeons independently. Results. 16 articles that met the inclusion criteria were analyzed, with a total of 3874 patients, 5 articles - risk factors of leukoplasia, 2 articles - risk factors of erythroplasia, 4 articles risk factors of oral submucosal fibrosis and 5 articles included studies of risk factors for two or all three forms of OPMD examined. Conclusion. The mucosa of the oral cavity is constantly subjected to external aggressions in the case of patients with harmful habits such as the consumption of tobacco, alcohol or other products with a carcinogenic effect that prove to be high risk factors in the development of oral lesions with malignant potential.Oral potentially malignant disorders (OPMD) represent a heterogeneous group of oral mucosal lesions associated with an increased risk of malignant transformation into invasive forms of oral cavity cancer. A systematic review of the prevalence of oral potentially malignant disorders by Mello FW et al. in 2018 [14], reports that approximately 4.5% of the world’s population presents OPMD, the study being based on the presence at the given stage of scientific researches from different geographical regions. Leukoplakia, erythroplakia and oral submucosal fibrosis represent 3 of the most common types of oral potentially malignant disorders [20]. At the current stage, the specialty literature assert the fact that OPMD are polyetiological, rarely being involved only on a single risk factor in their development [6]. Tobacco consumption in various forms, such as smoking products containing tobacco, reverse smoking, chewing tobacco, alcohol consumption, consumption of areca (betel) nuts, are the factors most often incriminated in the development of oral potentially malignant disorders Chewing tobacco is a major risk factor for all three previously mentioned entities, while smoking tobacco products increases the risk of predominantly developing leukoplakia, chewing areca nuts is associated with the development of oral submucosal fibrosis and the combination of alcohol consumption and smoking creates premises for the development of erythroplakia [5]. Among other risk factors associated with the occurrence of OPDM, we distinguish, sexual transmission of the human papillomavirus (HPV, with a predilection for type 16), chronic inflammation of the mucosa and trauma of the oral mucosa caused by teeth or prosthetics, the presence of various types of metals in the oral cavity with the formation of galvanic currents, poor oral hygiene, vitamin and iron deficiencies, oral candidiasis and syphilis, congenital immunodeficiencies as well as those acquired posttransplant, HIV infection, ultraviolet radiation and last but not least, genetic predisposition [12]. It is important to note that a clinical patient diagnosed with one of the entities of oral potentlly malignant disorders has an increased risk of developing oral cancer and the screening of patients and the early detection of these lesions, as well as the exclusion of risk factors, remain the most effective methods to prevent malignant transformations. The aim of this study was to make a systematic review the current scientific researches and clinical studies on the risk factors implicated in the development of leukoplakia, erythroplakia and oral submucosal fibrosis.

CXCR4 signaling determines the fate of hematopoietic multipotent progenitors by stimulating mTOR activity and mitochondrial metabolism

Both cell-intrinsic and niche-derived, cell-extrinsic cues drive the specification of hematopoietic multipotent progenitors (MPPs) in the bone marrow, which comprise multipotent MPP1 cells and lineage-restricted MPP2, MPP3, and MPP4 subsets. Patients with WHIM syndrome, a rare congenital immunodeficiency caused by mutations that prevent desensitization of the chemokine receptor CXCR4, have an excess of myeloid cells in the bone marrow. Here, we investigated the effects of increased CXCR4 signaling on the localization and fate of MPPs. Knock-in mice bearing a WHIM syndrome–associated CXCR4 mutation ( CXCR4 1013 ) phenocopied the myeloid skewing of bone marrow in patients. Whereas MPP4 cells in wild-type mice differentiated into lymphoid cells, MPP4s in CXCR4 1013 knock-in mice differentiated into myeloid cells. This myeloid rewiring of MPP4s in CXCR4 1013 knock-in mice was associated with enhanced signaling mediated by the kinase mTOR and increased oxidative phosphorylation (OXPHOS). MPP4s also localized further from arterioles in the bone marrow of knock-in mice compared with wild-type mice, suggesting that the loss of extrinsic cues from the perivascular niche may also contribute to their myeloid skewing. Chronic treatment with the CXCR4 antagonist AMD3100 or the mTOR inhibitor rapamycin restored the lymphoid potential of MPP4s in knock-in mice. Thus, CXCR4 desensitization drives the lymphoid potential of MPP4 cells by dampening the mTOR-dependent metabolic changes that promote myeloid differentiation.

RETRACTED: Kosumi et al. Systemic Retinoids for Generalized Verrucosis Due to Congenital Immunodeficiency: Case Reports and Review of the Literature. Genes 2023, 14, 769.

The journal Genes retracts the article, "Systemic Retinoids for Generalized Verrucosis Due to Congenital Immunodeficiency: Case Reports and Review of the Literature" [...].

Intra-abdominal infection and sepsis in immunocompromised intensive care unit patients: Disease expression, microbial aetiology, and clinical outcomes

We compared epidemiology of intra-abdominal infection (IAI) between immunocompromised and non-immunocompromised ICU patients and identified risk factors for mortality.We performed a secondary analysis on the “AbSeS” database, a prospective, observational study with IAI patients from 309 ICUs in 42 countries. Immunocompromised status was defined as either neutropenia or prolonged corticosteroids use, chemotherapy or radiotherapy in the past year, bone marrow or solid organ transplantation, congenital immunodeficiency, or immunosuppressive drugs use. Mortality was defined as ICU mortality at any time or 28-day mortality for those discharged earlier. Associations with mortality were assessed by logistic regression.The cohort included 2589 patients of which 239 immunocompromised (9.2 %), most with secondary peritonitis. Among immunocompromised patients, biliary tract infections were less frequent, typhlitis more frequent, and IAIs were more frequently healthcare-associated or early-onset hospital-acquired compared with immunocompetent patients. No difference existed in grade of anatomical disruption, disease severity, organ failure, pathogens, and resistance patterns. Septic shock was significantly more frequent in the immunocompromised population. Mortality was similar in both groups (31.1% vs. 28.9 %; p = 0.468). Immunocompromise was not a risk factor for mortality (OR 0.98, 95 % CI 0.66–1.43). Independent risk factors for mortality among immunocompromised patients included septic shock at presentation (OR 6.64, 95 % CI 1.27–55.72), and unsuccessful source control with persistent inflammation (OR 5.48, 95 % CI 2.29–12.57). In immunocompromised ICU patients with IAI, short-term mortality was similar to immunocompetent patients, despite the former presented more frequently with septic shock, and septic shock and persistent inflammation after source control were independent risk factors for death.

СИНДРОМ «ГОЛЫХ» ЛИМФОЦИТОВ (ДЕФИЦИТ МОЛЕКУЛ MHC II КЛАССА): КЛИНИЧЕСКОЕ НАБЛЮДЕНИЕ

Article represents a clinical case of severe combined immune deficiency (SCID), deficiency of MHC class II molecules which was coupled with normal levels of TREC and KREC in a pediatric patient. Simultaneous determination of TREC and KREC in dried blood spots during neonatal screening makes it possible to diagnose various forms of congenital immunodeficiency disorders. For example, a dramatic decrease in TREC is observed in most SCIDs and combined immune deficiencies. However, in some SCIDs associated with a defect primarily in T-cell function rather than T-cell differentiation, TREC levels do not exceed established threshold levels and therefore some rare forms of SCIDs may be missed by neonatal screening programs and consequently lead to its late diagnosis.

Genetic background of primary and familial HLH in Qatar: registry data and population study.

Familial hemophagocytic lymphohistiocytosis (FHLH) is an inherited life-threatening disease. Five types are identified, with the addition of congenital immunodeficiency syndromes in which HLH is a typical manifestation. The literature on this disease is very scarce in the Middle East, with only a few scattered reports. We report detailed demographic, clinical, and genomic data from 28 patients diagnosed with primary and familial HLH over the last decade in Qatar. An evaluation was performed of allele frequencies of deleterious variants from 12 primary and familial HLH causative genes on the Qatar Genome Programme (QGP) cohort of 14,669 Qatari individuals. The genetic diagnosis was obtained in 15 patients, and four novel mutations in Perforin 1 (PRF1), UNC13D, LYST, and RAB27A genes were found. We identified 22,945 low/high/moderate/modifier impact variants significantly enriched in the QGP in those 12 genes. The variants rs1271079313 in PRF1 and rs753966933 in RAB27A found in our patient cohort were significantly more prevalent in the QGP compared to the Genome Aggregation Database (gnomAD) database, with a high carrier frequency in the Qatari population. We established the first primary and familial HLH Registry in the Gulf Region and identified novel possibly pathogenic variants present at higher frequency in the Qatari population, which could be used for screening purposes. Raising awareness about primary and familial HLH and implementing screening activities in the Qatari highly inbred population could stem into more comprehensive premarital and prenatal evaluations and faster diagnosis.

Jacobsen’s syndrome: case report

Introduction. Jacobsen syndrome (JS) is a rare genetic disease associated with the deletion of chromosome 11q, characterized by multiple malformations, hematological and immune disorders. The development of immunodeficiency in JS is often underestimated, which leads to recurrent infectious complications. Presentation of a clinical case. The article presents a clinical case of a patient with a deletion of chromosome 11q and combined immunodeficiency. Our patient had recurrent infections, cytopenic syndrome, combined immunodeficiency, as well as other clinical manifestations of Jacobsen syndrome. In addition to a decrease in serum immunoglobulins, a deep deficiency of the T-cell link of immunity with a low content of T-lymphocytes, recent emigrants from the thymus, has been established. Conclusions. The peculiarity of the presented clinical case is that with a relatively small amount of deletion 11q, the child realized a complete clinical phenotype of the disease and a deep combined immunodeficiency. The article was written to improve doctors’ knowledge about this rare form of congenital immunodeficiency.

ОЦЕНКА ОСОБЕННОСТЕЙ ПРОЯВЛЕНИЙ ЗАБОЛЕВАНИЯ У ПАЦИЕНТОВ С ВРОЖДЕННЫМИ ДЕФЕКТАМИ ИММУНИТЕТА, ПОЛУЧАЮЩИХ АЛЛОГЕННУЮ ТРАНСПЛАНТАЦИЮ ГЕМОПОЭТИЧЕСКИХ СТВОЛОВЫХ КЛЕТОК

Congenital immunodeficiency disorders (CIDs) are a group of rare and diverse diseases that are based on dysfunction of the immune system. The only therapy that radically cures CIDs is allogeneic hematopoietic stem cell transplantation (HSCT). Despite the expansion of indications for HSCT in CIDs, making a decision on the need for HSCT in many diseases still remains a difficult task requiring an assessment of the risk for the life-threatening complications development in a patient. The purpose of this research was to assess the diseases developing in patients with CIDs who received allogeneic HSCT. Materials and methods used: the study included 312 patients with CIDs under the age of 18 y/o who had received allogeneic HSCT at the National Scientific and Practical Center for Pediatric Hematology, Oncology and Immunology named after Dmitry Rogachev (Moscow, Russia) in 2012-2020. The analysis was performed in 5 main groups of CIDs: immunodeficiencies with cellular and humoral defects (n=71), combined immune deficiency with associated or syndromic pathology (n=98), immune dysregulation defects (n=56), qualitative and quantitative defects of phagocytosis (n=57) and other CIDs nonmentioned above (n=30). Results: the presence of diseases uncontrolled by the therapy at the time of HSCT was noted in 160 (51%) patients. 73 (23%) had infection, 109 (35%) had autoimmune and/or autoinflammatory diseases, 15 (5%) showed absence of remission of an oncological disease. 33 patients had a combination of various diseases: 29 had infectious and autoinflammatory ones, two had infectious and tumor ones, another two had autoinflammatory and tumor. Active infections were observed in 48% of patients with immunodeficiencies with cellular and humoral defects and 33% of patients with other CIDs, active autoinflammatory processes in 43% of immune dysregulation defects and 63% of other CIDs, active tumors in 12% of patients with defects of phagocytosis. Conclusion: solutions have been proposed for assessing the pre-transplant status of patients with CIDs for the presence of infectious, autoimmune/autoinflammatory and oncological complications, age and nutritional status of the patient, which in tis turn underlie the choice for the optimal HSCT technique.

РАСШИРЕННЫЙ НЕОНАТАЛЬНЫЙ СКРИНИНГ ДЛЯ ВЫЯВЛЕНИЯ ВРОЖДЕННЫХ ДЕФЕКТОВ ИММУННОЙ СИСТЕМЫ: ОПЫТ МОСКОВСКОГО ЦЕНТРА НЕОНАТАЛЬНОГО СКРИНИНГА

Starting Jan., 2023 the extended neonatal screening (ENS) has been carried out in Russia that includes the determination of TREC/KREС markers, which in its turn allow suspecting severe combined immunodeficiency (SCID), phenotypical T-cell immunodeficiencies and X-linked agammaglobulinemia (XLA) prior to possible development of severe infectious complications. The purpose of the research was to evaluate the results of ENS for congenital immunodeficiency disorders (CIDs) in newborns in Moscow and to subsequently identify the most problematic issues in organizing of its implementation. Materials and methods used: the study was conducted in the Morozov Children's City Clinical Hospital (Moscow, Russia) among the 116,584 children born in Moscow in Jan. 01-Dec. 31, 2023 (this was the first year since the ENS introduction in Moscow) with a decrease in TREC/KREC below 100 copies per 105. Results: a total of 14 patients with CIDs were identified, of which 4 patients had a genetically confirmed form of SCID; 2 patients with immunophenotype of SCID; 3 patients with XLA; 2 patients with DiGeorge syndrome; single patient with a syndrome associated with a mutation in the PI4KA gene; and 2 patients with syndromic pathology without genetic confirmation. Thus, the frequency of detection of patients with the immunophenotype of SCID was a single case per 19,430 children, the frequency of patients with XLA was 1:38,861. 5 of 14 had already received hematopoietic stem cell transplantation, single patient was preparing for it at the time of the manuscript finalization. All of the patients receive regular immunoglobulin replacement therapy. Conclusion: the experience of an integrated approach to the provision of medical care based on neonatal screening in a municipal children's multidisciplinary hospital is presented; the results of the study helped identifying organizational shortcomings and determined the vector for its further development in order to improving of medical care provision to children with CIDs.

A clinical case of disseminated BCG infection with a fatal outcome

Complications after the introduction of the tuberculosis vaccine develop extremely rarely. They become accidentally vaccinated infants with undiagnosed severe immunodeficiency. The article considers a clinical case of the course of disseminated BCG infection with multiple organ damage in congenital immunodeficiency in a 9-month-old boy. The disease manifested itself acutely, the child’s condition worsened within a week, and its outcome was the death of the baby. Primary immunodeficiency was confirmed by the results of a pathoanatomic examination. The discussion provides a classification of complications after the introduction of BCG vaccine, the algorithm of the doctor’s actions in case of a suspected complication after vaccination, and also describes the main signs of immunodeficiency.

Nijmegen syndrome in childhood: a clinical case

Nijmegen syndrome is a rare monogenic pathology with an autosomal recessive type of inheritance. The disease is manifested by congenital developmental anomalies and microcephaly, primary immunodeficiency, frequent recurrent viral and bacterial infections, retardation in physical and neuropsychic development. In the medical literature, 150 cases of the syndrome are described; pathology occurs more often among the Slavic population. Nijmegen syndrome belongs to a group of diseases with chromosomal instability. The pathogenetic feature of the syndrome is congenital immunodeficiency of the humoral (B-lymphocytes) and cellular (T-lymphocytes) components. According to statistics, 40 % of children with Nijmegen syndrome are diagnosed with malignant neoplasms. lymphoid tissue is more often affected (non-Hodgkin’s B and T-cell lymphomas, acute lymphoblastic leukemia), and the development of solid neoplasia is also possible. To diagnose Nijmegen syndrome, in addition to assessing the patient clinical status, it is necessary to conduct an extended immunological examination with the determination of immunoglobulins A, M, G and molecular genetic studies.The article presents a clinical case of diagnosis and treatment of Nijmegen syndrome in childhood.

Predictors of mortality among children at a tertiary hospital in Tanzania: a cohort study

BackgroundTanzania is among the countries in sub-Saharan Africa with the highest under-five mortality rate. The leading causes of mortality among these children include vaccine-preventable infections. Strategies for reducing under-five mortality in hospital settings require a good knowledge of driving factors, which are largely unknown in Tanzania. This study was conducted at Muhimbili National Hospital to determine mortality and its predictors among under-five admitted in the general paediatric wards.MethodsWe conducted a prospective cohort study among children aged between 1 and 59 months admitted in the paediatric wards at Muhimbili National Hospital from 2nd October 2017 to 13th April 2018. We recruited eligible children consecutively and followed them up until discharge or death. We calculated the mortality rate as the incidence density rate and determined the causes and predictors of mortality. We analyzed data to identify and quantify predictors of deaths and used Kaplan-Meir and Cox regression analyses to determine predictors of survival. A P-value of < 0.05 was considered statistically significant.ResultsWe recruited 925 children aged 1–59 months with a median age of 13 and (IQR) of (20) months, females constituted 40.8%. The overall mortality rate was 12.2% (95% CI: 10.2%-14.5%). We found septicaemia (27%), malnutrition (12%), congenital heart disease (12%), pneumonia (11%), and Human Immunodeficiency Virus infection (9%) to be leading causes of mortality. More deaths were observed at night, during the first 24 h of admission, and on weekends. Independent factors for mortality were found to be low wealth quintiles (lowest quintile (AOR = 4.0; 95% CI: 1.19–13.51), second quintile (AOR = 5.2; 95% CI: 1.65–16.69) and middle quintile (AOR = 3.6; 95% CI: 1.14–11.33), unconsciousness on admission (AOR = 18; 95% CI: 6.70–56.82), inability to feed (AOR = 5.7; 95% CI: 1.97–16.51), lethargy (AOR = 4.9; 95% CI: 2.32–10.40), severe wasting (AOR = 4.5; 95% CI: 2.49–8.10), and respiratory distress (AOR = 2.6; 95% CI: 1.40–4.97).ConclusionA high mortality rate was noted in this study and low wealth quantile, low parental education, and lack of health insurance were associated with high mortality. Patients had the highest risk of mortality within 24 h of admission, therefore it is important to raise awareness among clinicians regarding the need for improvement in the monitoring of patients, especially within 24 h of admission.

Clinical and genetic analysis of trichohepatoneurodevelopmental syndrome caused by a CCDC47 variant

Trichohepatoneurodevelopmental syndrome is an extremely uncommon autosomal recessive disorder resulting from variants in the CCDC47 gene, which encodes a Ca2+-binding endoplasmic reticulum (ER) transmembrane protein. To date, only four patients with CCDC47 deficiency have been reported, all of them with homozygous truncating CCDC47 variants. For this study, a Chinese family was recruited, which included a patient diagnosed with trichohepatoneurodevelopmental syndrome. Whole exome sequencing (WES) identified the proband's novel homozygous CCDC47 variation (NM_020198: c.634C > T(p.Arg212*). The variant was confirmed to be segregating in the proband and her unaffected relatives through Sanger sequencing. The patient described exhibited a clinical phenotype similar to that of patients with the CCDC47 variant. Compared to reported cases with CCDC47 pathogenic variants, our patients showed a novel complication of hearing impairment. In addition, brain abnormalities, small feet, bilateral hip dislocation, hip dysplasia, overlapping toes, pectus excavatum, scoliosis and narrow chest were not observed in our patient. We also examined five different variations and their corresponding phenotypes from five patients, both in current and previous research. Although some clinical manifestations of trichohepatoneurodevelopmental syndrome were highly variable, the most common phenotypes observed in these patients include microcephaly, profound intellectual disability, severe global development delay, pronounced growth restriction, hypotonia, woolly hair, facial dysmorphism, respiratory and visual abnormalities, gastrointestinal abnormalities, liver dysfunction, pruritus, skeletal and limb abnormalities, congenital heart defects and immunodeficiency. The present report is the first of a Chinese infant with homozygous variant in the CCDC47 gene. We expanded the genetic and phenotypic spectrum associated with trichohepatoneurodevelopmental syndrome.

Ustekinumab for pyoderma gangrenosum–like skin ulcerations in late-onset leukocyte adhesion deficiency

BackgroundLeukocyte adhesion deficiency type 1 (LAD-1) is a congenital immunodeficiency leading to impaired trafficking of neutrophils to inflammation sites. Solitary or multiple pyoderma-gangrenosum (PG)-like skin ulcers (PGLU) have been reported previously in 13 children (aged 0.5-19 years) with LAD-1. ObjectiveTo report the case of a 10-year-old boy presenting with PGLU as the first manifestation of LAD-1, treated with ustekinumab. MethodsIn-situ cytokine profiles. ResultsPGLU was triggered by cutaneous ringworm infection (Trichophyton tonsurans). Skin biopsies showed increased intralesional expression of interleukins 17A, 23 and 1β as compared with healthy controls. After an unsuccessful attempt with oral methylprednisolone, ustekinumab induced regression of the ulcerations, associated with complete normalization of the cytokine profile. ConclusionsPG-like skin ulcers, triggered by ringworm infection, can be a late harbinger of LAD-1. Ustekinumab is a safe and effective therapeutic option for LAD-1-patients with PGLU whilst bridging the time until stem-cell transplantation.

The nature and origin of immunosuppressive disorders

This publication reflects modern ideas about the main aspects of etiology, pathogenesis and the latest achievements of clinical practice in the field of the most common primary and secondary immunodeficiency. The features of laboratory diagnostics of congenital immunodeficiency, risk factors and early clinical guidelines that allow the patient to suspect an immunosuppressive state are considered. Special attention is paid to the problem of secondary immunodeficiency, their prevalence and polyetiology. When covering immunopathogenesis, infection caused by the human immunodeficiency virus (HIV), attention is paid to the multimorbidity of clinical manifestations of HIV-associated immunosuppression and concomitant diseases, the importance of timely administration of antiretroviral therapy (ART) and its role in the development of immune reconstitution syndrome (IRS). The criteria for the diagnosis of SVI based on their own experience and the opinion of foreign colleagues, the tactics of patient management are presented in detail.

Diagnosis and management of erythroderma; a systematic review

Erythroderma, a condition characterized by diffuse erythema and scaling covering at least 90 percent of the skin\&amp;apos;s surface, poses a serious and potentially life-threatening threat. This systematic study aimed to establish diagnosis and management guidelines for erythroderma. Following PRISMA guidelines, a comprehensive review was conducted using PubMed/Medline, Scopus, and Embase databases focusing on English-language articles from 2010 to 2023. From 279 studies, seven articles were included, mainly comprising surveys and analyses of national databases. Erythroderma, as a clinical sign, can manifest as a consequence of various cutaneous and systemic diseases, drug hypersensitivity reactions, and rarely, Sezary syndrome. In pediatric patients, the clinical presentation encompasses a spectrum of acquired and inherited diseases, including infections, inflammatory skin conditions, ichthyoses, and congenital immunodeficiencies. Diagnosing erythroderma proves challenging due to its syndromatic nature, presenting with nonspecific clinical features. Dermatologists must diligently seek cause-oriented clues, employing multiple biopsies to enhance diagnostic accuracy. Initial management should include nutritional expert evaluation, assessment of fluid imbalance, skin barrier maintenance, sedative anti-histamines, and exclusion of secondary bacterial infection. Given its life-threatening potential, erythroderma might necessitate hospitalization. This study provides valuable insights into the complexities of erythroderma diagnosis and highlights essential considerations for effective management.

Re-Melody mitral valve replacement during infective endocarditis after multi-stage hybrid surgical treatment in a 2-year-old child with congenital immunodeficiency.

Re-Melody mitral valve replacement during infective endocarditis after multi-stage hybrid surgical treatment in a 2-year-old child with congenital immunodeficiency.

IMMUNOLOGICAL STATUS OF THE CALVES BORN FROM THE COWS WITH CHRONIC SYSTEMIC INFLAMMATION SYNDROME

This article presents the results of a study of the effect of chronic systemic inflammation syndrome in pregnant cows on the immunological status of newborn calves. It has been established that the calves obtained from the cows with this syndrome have intense colostral immunity against the background of congenital immunodeficiency, which is characterized by a decrease in the number of T- and B-lymphocytes, the activity of phagocytes, lysozyme and the complement system. The identified abnormalities in this group of animals increase the risk of early neonatal infection and comorbid pathology.

An interdisciplinary approach to the management of oncohematological patients with immunodeficiency: clinical cases. A review

Immunodeficiency occurs when one or more immune system components do not function properly, resulting in the body's inability to resist mostly infectious agents. Most cases of immunodeficiency in adults are acquired (secondary), but congenital immunodeficiencies are not uncommon. Primary immunodeficiencies are a heterogeneous group of innate immune errors that result in various clinical and laboratory manifestations. In contrast, secondary immunodeficiencies involve an acquired decrease in immune cell count and/or impairment of their function, commonly associated with an antibody level decrease. Secondary immunodeficiency in patients with B-cell hematological malignancies is a common condition attributed to both hematological malignancy and secondary antitumor therapy-related causes. Paradoxically, immunodeficiency, initially attributed to secondary causes, may be due to a previously undiagnosed primary immunodeficiency. Early diagnosis of immunodeficiency and optimization of management strategies with a multidisciplinary approach are critical to providing the most effective specific treatments and reducing the incidence of infection-related complications and mortality. The article addresses clinical practice, recommendations, and problems of immunodeficiency diagnosis and the effectiveness of immunoglobulin replacement therapy illustrated by clinical cases.