Case Report: Autoimmune Lymphoproliferative Syndrome vs. Chronic Active Epstein-Barr Virus Infection in Children: A Diagnostic Challenge

Autoimmune lymphoproliferative syndrome (ALPS) is a disorder characterized by a disruption of the lymphocyte apoptosis pathway, self-tolerance, and immune system homeostasis. Defects in genes within the first apoptosis signal (FAS)-mediated pathway cause an expansion of autoreactive double-negative T cells leading to non-malignant lymphoproliferation, autoimmune disorders, and an increased risk of lymphoma. The aim of the study was to show the diagnostic dilemmas and difficulties in the process of recognizing ALPS in the light of chronic active Epstein-Barr virus (CAEBV) infection. Clinical, immunological, flow cytometric, biomarkers, and molecular genetic approaches of a pediatric patient diagnosed with FAS-ALPS and CAEBV are presented. With the ever-expanding spectrum of molecular pathways associated with autoimmune lymphoproliferative disorders, multiple genetic defects of FAS-mediated apoptosis, primary immunodeficiencies with immune dysregulation, malignant and autoimmune disorders, and infections are included in the differential diagnosis. Further studies are needed to address the issue of the inflammatory and neoplastic role of CAEBV as a triggering and disease-modifying factor in ALPS.

Diffuse B-cell lymphoma in a child with HIV infection

Objective. To describe the case of diffuse B-cell lymphoma in a child with HIV infection.Results. A 16-year-old child with HIV infection and generalized lymphadenopathy was diagnosed with diffuse large B-cell lymphoma, stage III, negative central nervous system. The patient was diagnosed on the basis of the results of immunohistochemical study of biopaths of the tissue of the lymph nodes of the submandibular and right axillary region. The study in order to identify markers of active infection caused by the Epstein-Barr virus, cytomegalovirus and human herpesvirus type 6, made it possible to exclude the active phase of diseases that are the main infectious causes of lymphoproliferative syndrome. At the time of hospitalization, the patient was treated with antiretroviral therapy of the combined drug Eviplera. There was no HIV RNA in the blood, the level of CD4 lymphocytes was 0.4·109/l. The BFM chemotherapy regimen was used, which was accompanied by positive dynamics in the form of normalization of body temperature, reduction in the size of lymph nodes.Conclusion. This case shows that immunohistochemical examination of tissue biopsies of enlarged lymph nodes is of decisive importance in the diagnosis of lymphoma, the main non-infectious cause of lymphoproliferative syndrome in patients with HIV infection.

Predictive risk factors for the development of diseases with lymphoproliferative syndrome in children

Background. Harmful environmental factors and negative social trends have an adverse effect on the adaptive resources of the child’s body, which in combination reduces the health index in the child population. An ambiguous epidemiological situation, an increase in morbidity rates in children, a variety of clinical manifestations of Epstein – Barr viral infection, recurrent respiratory diseases, adenovirus infection complicate their differential diagnosis in the early stages. In this regard, the assessment of risk factors and early prognosis of the development of primary form of Epstein – Barr viral infection (EBVI), recurrent respiratory diseases (RRD), adenovirus infection (ADVI) in children is an urgent task.The aim: to study the significance of risk factors influencing the development of diseases with lymphoproliferative syndrome in children.Materials and methods. Clinical and laboratory examination and analysis of case histories of 336 children and adolescents held with diseases with lymphoproliferative syndrome. Data from 30 apparently healthy children and adolescents of the same age were used as a comparison group. The Bayesian method with sequential Wald analysis was used to assess risk factors. ROC-analysis was used to check the adequacy of the forecasting models. The quality of the built models was evaluated by their sensitivity and specificity.Results. It has been established that predictors of diseases with lymphoproliferative syndrome in children are intrauterine fetal hypoxia, low or, on the contrary, high birth weight, neonatal jaundice, low Apgar score, as well as maternal factors (somatic pathology and SARS during pregnancy, gestosis, gestational anemias, young or mature age of the pregnant women). Additional predictors of the development of this pathology can be considered a decrease in the indicator of the cell-phagocytic potential to 337.1 ± 2.3 CU, a decrease in the immune-lymphocytic potential to 237.0 ± 8.2 CU, an increase in the load-erythrocyte coefficient to 0.67 ± 0.03 CU and a decrease in the leukocyte index of intoxication to 0.40 ± 0.05 CU.Conclusion. The combination of clinical and anamnestic factors with indicators of general reactive potential increases the integral general informative value of the prognostic model. The accounting by specialists of the general medical and preventive network of the identified predictors of the development of diseases with lymphoproliferative syndrome will contribute to the timely diagnosis of the primary form of Epstein – Barr viral infection, recurrent respiratory diseases and adenovirus infection in children.

Case Report: Deficiency of Adenosine Deaminase 2 Presenting With Overlapping Features of Autoimmune Lymphoproliferative Syndrome and Bone Marrow Failure

Deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessive disease associated with a highly variable clinical presentation, such as vasculitis, inflammation, and hematologic manifestations. Some associations of clinical features can mimic autoimmune lymphoproliferative syndrome (ALPS). We report a case of a female patient who fulfilled the 2009 National Institute of Health revised criteria for ALPS and received a delayed diagnosis of DADA2. During her childhood, she suffered from autoimmune hemolytic anemia, immune thrombocytopenia, and chronic lymphoproliferation, which partially responded to multiple lines of treatments and were followed, at 25 years of age, by pulmonary embolism, septic shock, and bone marrow failure with myelodysplastic evolution. The patient died from the progression of pulmonary disease and multiorgan failure. Two previously unreported variants of gene ADA2/CECR1 were found through next-generation sequencing analysis, and a pathogenic role was demonstrated through a functional study. A single somatic STAT3 mutation was also found. Clinical phenotypes encompassing immune dysregulation and marrow failure should be evaluated at the early stage of diagnostic work-up with an extended molecular evaluation. A correct genetic diagnosis may lead to a precision medicine approach consisting of the use of targeted treatments or early hematopoietic stem cell transplantation.

Increased double-negative αβ+ T-cells reveal adult-onset autoimmune lymphoproliferative syndrome in a patient with IgG4-related disease

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