Search Results (321)

A 51-year-old female presented to the emergency department with vertigo, visual disturbances, involuntary rapid repetitive eye movements, incoordination, and imbalance. Physical examination revealed opsoclonus, myoclonus, and bilateral limb and gait ataxia. Initial workup was negative for intracranial abnormalities, and no abnormalities were noted on blood work or cerebrospinal fluid analysis. Tumor markers were within normal limits. As part of her diagnostic workup, a positron emission tomography (PET) scan was performed, which showed a highly FDG-avid solitary 7 mm left axillary lymph node. Ultrasound-guided percutaneous biopsy revealed metastatic poorly differentiated carcinoma. Histopathological examination could not conclusively distinguish between adenocarcinoma and squamous cell carcinoma. She was diagnosed with seronegative opsoclonus-myoclonus ataxia syndrome of paraneoplastic origin from an occult primary malignancy and started on pulsatile corticosteroids and intravenous immunoglobulin (IVIG), with only moderate symptomatic improvement. Given the anatomic location and immunohistochemical staining pattern of the lymph node, the malignancy was considered as being of primary breast origin. A left axillary lymph node dissection was performed, with 1/12 nodes testing positive for poorly differentiated carcinoma. The patient experienced significant improvement in her neurological symptoms 2–3 days following resection of the solitary malignant lymph node, largely regaining her functional independence. She went on to receive adjuvant radiotherapy to the breast and axilla, as well as adjuvant hormonal therapy. Full article

Background and Clinical Significance: Hemophagocytic lymphohistiocytosis (HLH) and autoimmune hemolytic anemia (AIHA) are both life-threatening hematologic syndromes that rarely present together outside of malignancy. Advanced acquired immunodeficiency syndrome (AIDS) creates a milieu of profound immune dysregulation and hyperinflammation, predisposing patients to atypical overlaps of these disorders. Case Presentation: A 30-year-old woman with poorly controlled AIDS presented with three weeks of jaundice, fever, and fatigue. Initial labs revealed pancytopenia, hyperbilirubinemia, and elevated ferritin level. Direct anti-globulin testing confirmed warm AIHA (IgG⁺/C3d⁺) with transient cold agglutinins. Despite intravenous immunoglobulin (IVIG), rituximab, and transfusions, she developed hepatosplenomegaly, extreme hyperferritinemia, and sIL-2R > 10,000 pg/mL, meeting HLH-2004 criteria. Bone marrow biopsy excluded malignancy; further work-up revealed Epstein–Barr virus (EBV) viremia and cytomegalovirus (CMV) reactivation. Dexamethasone plus reduced-dose etoposide transiently reduced soluble interleukin-2 receptor (sIL-2R) but precipitated profound pancytopenia, Acute respiratory distress syndrome (ARDS) from CMV/parainfluenza pneumonia, bilateral deep vein thrombosis (DVT), and an ST-elevation myocardial infarction (STEMI). She ultimately died of hemorrhagic shock after anticoagulation despite maximal supportive measures. Conclusions: This case underscores the diagnostic challenges of HLH-AIHA overlap in AIDS, where cytopenias and hyperferritinemia mask the underlying cytokine storm. Pathogenesis likely involved IL-6/IFN-γ overproduction, impaired cytotoxic T-cell function, and molecular mimicry. While etoposide remains a cornerstone of HLH therapy, its myelotoxicity proved catastrophic in this immunocompromised host, highlighting the urgent need for cytokine-targeted agents to mitigate treatment-related mortality. Full article

Background: Parvovirus B19 (B19V) can cause severe relapsing episodes of pure red cell aplasia in immunocompromised individuals, which are commonly treated with intravenous immunoglobulins (IVIGs). Few data are available on B19V intra-host evolution and the role of humoral immune selection. Here, we report the dynamics of genomic mutations and subsequent protein changes during relapsing infection. Methods: Longitudinal plasma samples from immunocompromised patients with relapsing B19V infection in the period 2011–2019 were analyzed using whole-genome sequencing to evaluate intra-host evolution. The impact of mutations on the 3D viral protein structure was predicted by deep neural network modeling. Results: Of the three immunocompromised patients with relapsing infections for 3 to 9 months, one patient developed two consecutive nonsynonymous mutations in the VP1/2 region: T372S/T145S and Q422L/Q195L. The first mutation was detected in multiple B19V IgG-seropositive follow-up samples and resolved after IgG seroreversion. Computational prediction of the VP1 3D structure of this mutant showed a conformational change in the proximity of the antibody binding domain. No conformational changes were predicted for the other mutations detected. Discussion: Analysis of relapsing B19V infections showed mutational changes occurring over time. Resulting amino acid changes were predicted to lead to a conformational capsid protein change in an IgG-seropositive patient. The impact of humoral response and IVIG treatment on B19V infections should be further investigated to understand viral evolution and potential immune escape. Full article

Background and Clinical Significance: Hematologic malignancies, including diffuse large B-cell lymphoma (DLBCL), have been associated with the development of Guillain–Barré syndrome (GBS). Specifically, treatment with the immunomodulator rituximab, which is used in the backbone of DLBCL treatment, has increasingly been used in this patient population. Case Presentation: We present the case of a man in his 60s with DLBCL who presented to the hospital with the progressive weakness of the bilateral upper and lower extremities within 6 weeks of the completion of treatment including rituximab. The temporal relationship between the completion of rituximab and subsequent polyradiculoneuropathy, as well as a favorable response to intravenous immunoglobulin (IVIG), affirmed the diagnosis of treatment-induced GBS. Conclusions: The increased use of rituximab as part of a standard treatment regimen for hematologic malignancies demonstrates the need for an awareness of a possible association between rituximab and the subsequent paradoxical development of GBS, which will allow for expeditious evaluation for better patient outcomes. Full article

Sickle cell disease (SCD) is a prevalent genetic disorder caused by a mutation in the beta-globin gene. Hyperhemolysis (HS) is a severe complication involving the rapid destruction of both transfused and endogenous red blood cells, commonly found in SCD. This literature review explores the clinical presentation, diagnosis, pathogenesis, and management of HS in SCD. HS can manifest acutely or in a delayed manner, complicating diagnosis due to overlapping symptoms and varying reticulocyte responses. Immunohematological assessments often reveal delayed positivity in direct antiglobulin tests and antibody screens. HS typically presents severe anemia, jaundice, hemoglobinuria, and hemodynamic instability. Diagnostic markers include elevated bilirubin and lactate dehydrogenase levels alongside a reduced reticulocyte count. The management of HS is primarily empirical, with no clinical trials to support standardized treatment protocols. First-line treatments involve steroids and intravenous immunoglobulins (IVIG), which modulate immune responses and mitigate hemolysis. Refractory cases may require additional agents such as rituximab, eculizumab, tocilizumab, and, in some instances, plasma exchange or erythropoietin-stimulating agents. Novel therapeutic approaches, including bortezomib and Hemopure, have shown promise but require further investigation. Current management strategies are empirical, underscoring the need for robust clinical trials to establish effective treatment protocols that ultimately improve outcomes for SCD patients experiencing HS. Full article

Immunological factors have gained growing recognition as key contributors to recurrent pregnancy loss (RPL) after in vitro fertilization (IVF), representing a major challenge in reproductive medicine. RPL affects approximately 1–2% of women trying to conceive naturally and up to 10–15% of those undergoing IVF, where overall success rates remain around 30–40% per cycle. An imbalance in maternal immunological tolerance toward the semi-allogeneic fetus during pregnancy may lead to miscarriage and implantation failure. IVF-related ovarian stimulation and embryo modification offer additional immunological complications that can exacerbate existing immune dysregulation. Recent advances in reproductive immunology have significantly deepened our understanding of the immune mechanisms underlying RPL following IVF, particularly highlighting the roles of regulatory T cells (T regs), natural killer cells, cytokine dysregulation, and disruptions in maternal–fetal immune tolerance. In order to better customize therapies, this evaluation incorporates recently discovered immunological biomarkers and groups patients according to unique immune profiles. Beyond conventional treatments like intralipid therapy and intravenous immunoglobulin, it also examines new immunomodulatory medications that target certain immune pathways, such as precision immunotherapies and novel cytokine modulators. We also discuss the debates over immunological diagnostics and therapies, such as intralipid therapy, intravenous immunoglobulin, corticosteroids, and anticoagulants. The heterogeneity of patient immune profiles combined with a lack of strong evidence highlights the imperative for precision medicine to improve therapeutic consistency. Novel indicators for tailored immunotherapy and emerging treatments that target particular immune pathways have encouraging opportunities to increase pregnancy success rates. Improving management approaches requires that future research prioritize large-scale clinical trials and the development of standardized immunological assessments. This review addresses the immunological factors in RPL during IVF, emphasizing underlying mechanisms, ongoing controversies, and novel therapeutic approaches to inform researchers and clinicians. Full article

Our study demonstrates that IVIG lots manufactured in 2023–2024 contain neutralizing antibodies against circulating Omicron variants, including KP.3 and XEC. These variants are resistant to all convalescent plasma and IVIG preparations produced prior to 2023. Therefore, recent IVIG lots may provide some protection against COVID-19 caused by circulating SARS-CoV-2 variants. Full article

Objectives: Our objective was to investigate the clinical characteristics, complications, and treatment outcomes of Epstein–Barr virus (EBV)-related infectious mononucleosis (IM) in children and to identify risk factors associated with prolonged fever and abnormal liver function. Methods: This retrospective study included 3006 children admitted to Shenzhen Children’s Hospital from May 2009 to April 2024 with suspected EBV-related IM. After excluding cases without etiological evidence and those with underlying diseases, 2660 cases were analyzed. Data on demographics, clinical manifestations, laboratory findings, complications, and treatment outcomes were collected. Logistic regression was used to identify risk factors for prolonged fever and abnormal liver function. Results: Among the 2660 confirmed cases, patients ranged from 8 months to 17 years of age, with a median age of 4 years and a male-to-female ratio of 1.46:1. Co-infections were identified in 369 (13.9%) patients, predominantly with Group A Streptococcus. Complications occurred in 560 (24.46%) of the 2289 patients without co-infections, with bronchitis being the most common (42.68%). Elevated ferritin and atypical lymphocyte percentage were associated with prolonged fever (p < 0.001), while elevated lactate dehydrogenase (LDH) and a lower CD4% predicted abnormal liver function (p < 0.001). Antiviral therapy did not shorten fever duration or hospital stay but prolonged both when combined with corticosteroids or intravenous immunoglobulin (IVIG) (p < 0.001). Conclusions: Specific laboratory markers such as ferritin, atypical lymphocyte percentage, LDH, and CD4% are important predictors of prolonged fever or liver dysfunction in EBV-IM. Our findings suggest that antiviral therapy may not be beneficial in uncomplicated cases and highlight the need for tailored treatment strategies to optimize patient outcomes. Full article

Objectives: Kawasaki Disease (KD) is an acute vasculitis associated with systemic inflammation. This study aimed to investigate the level and clinical significance of soluble ST2 (sST2) in children with KD. Methods: A retrospective analysis was conducted on 287 pediatric KD patients treated at the Pediatric Cardiology Department of Shengjing Hospital, China Medical University, from November 2021 to December 2022. Patients were stratified into subgroups based on the presence of myocardial damage (MD), coronary artery lesions (CAL), multi-organ involvement (MOD; ≥3 organs) and/or intravenous immunoglobulin-resistant KD (IVIG-R KD). In each group, we analyzed the correlation between sST2 levels and various laboratory parameters, including white blood cell count (WBC), hemoglobin (HB), platelet count (PLT), C-reactive protein (CRP), interleukin-6 (IL-6), erythrocyte sedimentation rate (ESR), N-terminal pro-brain natriuretic peptide (NT-pro BNP), D-dimer, and albumin (ALB). Results: Patients in the CAL group were significantly younger and predominantly male (p < 0.05). In the MD, CAL, MOD, and IVIG-R KD groups, levels of sST2, CRP, NT-pro BNP, and D-dimer were significantly higher than in their respective comparison groups (p < 0.05). sST2 showed weak positive correlations with WBC, CRP, IL-6, NT-pro BNP, and D-dimer, and weak negative correlations with HB and ALB (p < 0.05). sST2, HB, and IL-6 were identified as independent risk factors for MOD (p < 0.05). sST2 and HB were independent risk factors for IVIG-R KD (p < 0.05). Among acute-phase patients, four cases had sST2 levels > 200 ng/mL—all were classified as IVIG-R KD and MOD; three of these also developed coronary artery aneurysms (CAA). Conclusions: Elevated sST2 levels in the acute phase of KD may serve as a clinical indicator of IVIG-R KD, CAA, MOD, and MD. Full article

Kawasaki disease (KD) is a systematic inflammatory condition that results in vasculitis and possible progression to the development of coronary artery lesions if left untreated. Disease pathogenesis is not fully understood, and diagnosis is based on clinical symptoms, with limited reliability considering that KD progression is time sensitive. This is further complicated by the shared clinical characteristics with other febrile diseases. Early diagnosis and prompt treatment start are associated with good prognosis in most patients. However, up to 20% of patients are resistant to available therapeutic agents and would benefit from alternative regimens. Therefore, identification of biomarkers that can provide insights on disease pathogenesis are necessary to enable early diagnosis and initiation of treatment, as well as to predict treatment responses. To this end, immunophenotyping, most commonly by flow cytometry, has been crucial in identifying central factors in KD pathogenesis. The available literature on such factors is vast and may include contradictory findings. Therefore, we aimed to summarize the available literature of the last decade on the immunophenotype of KD, focusing on biomarkers associated with disease pathogenesis and those associated with treatment response. Our review highlights the role of cells of both the innate and adaptive immune system in disease pathogenesis, as well as the role of various secreted and cell surface proteins, including inflammatory cytokines, chemokines, complement receptors, and chemoattractants both in KD pathogenesis and in treatment response. Full article

Necrotizing soft tissue infections (NSTIs) are serious and aggressive infections which can result in significant morbidity and mortality. Both prompt surgical intervention and early antibiotics can decrease patient mortality. Based on microbiology, NSTIs can be categorized into four different types. Type I is polymicrobial, caused by a mix of both anaerobic and aerobic bacteria. Type II is monomicrobial, usually caused by either Streptococcus or Staphylococcus. Type III infections are caused by Gram-negative bacteria, often marine-related organisms, such as Vibrio. Lastly, Type IV infections are caused by fungi, and they are often associated with trauma. Despite the possibility of all these different pathogens in NSTI, early therapy often consists of a broad Gram-positive antimicrobial such as linezolid or vancomycin, and a broad Gram-negative agent such as piperacillin/tazobactam. Multiple factors including patient comorbidities, environmental exposures, and clinical presentation must also be considered when choosing antimicrobial agents and dosing. Adjunct medical therapies such as intravenous immunoglobulin (IVIG) and the antibiotics clindamycin and linezolid that are aimed at toxin suppression may be utilized to improve outcomes. Microbiological data are critical for optimizing the antimicrobial regimen. Full article

Background/Objectives: Pregnancies complicated by red cell alloimmunization can progress to hemolytic disease of the fetus and newborn (HDFN), requiring close monitoring and timely intervention to prevent fetal/neonatal morbidity and mortality. This study investigated disease presentation, interventions, and outcomes in respondents with a history of alloimmunized pregnancy. Methods: This was a retrospective cross-sectional survey study administered online to alloimmunized patients between November 2022–February 2023. A total of 127 participants reported on 200 alloimmunized pregnancies. Distribution of pregnancy characteristics, antibodies and titers, monitoring, treatments and fetal outcomes were described and stratified where appropriate by fetal antigen status and disease severity. Outcomes and management practices in subsequent pregnancies following fetal loss to HDFN are reported. Results: Multiple antibodies were present in 42% of pregnancies with known antibody type (80/192). Titers reached critical levels (any titer for Anti-K; ≥16 for all other antibodies) in 71% (125/176) of pregnancies where titer was reported. Among fetal antigen positive pregnancies with critical titers, intrauterine transfusions were conducted in 40% (42/106), intravenous immunoglobulin was administered in 14% (15/106), plasmapheresis in 7% (7/106), and phenobarbital in 9% (9/106). Complications from transfusion were reported in 38% of pregnancies receiving intrauterine transfusion (17/45). Fetal death due to HDFN or complications from intrauterine transfusion was reported in 9% of antigen positive pregnancies with critical titers (10/106) and 16% of pregnancies receiving intrauterine transfusion (7/45). Conclusions: Disease presentation and severity complements previous research in this disease population, however, monitoring practices were diverse. Fetal death and intrauterine complication rates were higher than those previously reported in large international referral centers. Development of best practices and centralized referral centers may improve disease outcomes. Full article

Background/Objectives: Mild encephalitis/encephalopathy with reversible splenial lesion (MERS) is a rare neurological disorder primarily affecting pediatric patients but also observed in adults. The radiological hallmark of MERS is a reversible lesion in the splenium of the corpus callosum. Although MERS generally has a favorable prognosis, its variable presentation poses diagnostic challenges. This study examines the clinical variability, diagnostic hurdles, and outcomes of pediatric MERS cases. Methods: Our retrospective study included 19 pediatric patients (11 female and 8 males with an average age of 8.41 years) diagnosed with MERS between 2016 and 2024. Clinical data, including demographic characteristics, prodromal symptoms, neurological features, MRI findings, laboratory results, treatments, and outcomes, were analyzed. Results: Among the 19 patients, 84% were previously healthy, with the remaining 16% having pre-existing medical conditions. The most common prodromal symptoms were fever (68%), vomiting (47%), and diarrhea (32%). Neurological manifestations included seizures (26%), headache (21%), and drowsiness (21%), among others. In terms of etiology, infections were identified in 52% of the patients, with viral agents, particularly rotavirus, being the most common (40%). Hyponatremia was present in 63% of the cohort. The typical MRI splenial lesion underwent complete resolution in all patients. Treatment varied, with 53% of patients receiving electrolyte rehydration, and 21% receiving intravenous immunoglobulin or corticosteroids. All patients, but one, achieved full recovery. Discussion: This study reinforces the clinical heterogeneity of MERS in pediatric patients, emphasizing its favorable prognosis independently of presentation. Viral infections and hyponatremia were the most frequent etiologies. Full article

This case report describes a fetus diagnosed with complete atrioventricular block (CAVB) associated with positive maternal anti-Ro and anti-La antibodies, referred to our fetal cardiology unit at 25 weeks of gestation. The diagnosis of systemic lupus erythematosus (SLE) was established during the investigation of the fetal condition. Oral dexamethasone was initiated and well tolerated, with no adverse effects reported throughout the remainder of the pregnancy. The fetal heart rate (HR) remained above 50 bpm, and, therefore, no beta-sympathomimetic agents were administered. Due to progressive reduction in myocardial contractility and the appearance of early signs of endocardial fibroelastosis, intravenous immunoglobulin (IVIG) therapy was initiated. The patient was hospitalized for the infusion, which was well tolerated without complications, and a second IVIG cycle was administered four weeks later. Significant improvement in ventricular contractility and reduction in fibroelastosis were observed. As reported in the literature, no chronotropic effect was noted, and fetal HR remained stable after treatment. Weekly monitoring of cardiovascular profile score and fetal HR was maintained, with the score consistently remaining at 8 throughout gestation, supporting continued outpatient management. Delivery occurred at 36 weeks and 3 days due to spontaneous preterm labor. A male neonate weighing 3025 g was delivered with Apgar scores of 8 and 9, and an initial heart rate of 84 bpm. Neonatal electrocardiography confirmed persistent CAVB, and the newborn was monitored in the neonatal intensive care unit. At follow-up, the infant remains clinically stable and has not required permanent pacemaker implantation. Full article

Macrophage activation syndrome (MAS) is a complex, life-threatening, hyperinflammatory condition occurring as a form of hemophagocytic lymphohistiocytosis (HLH), commonly associated with several autoimmune and autoinflammatory diseases, and certain infections such as Parvovirus B19 (P19V). The onset of systemic lupus erythematosus (SLE) presenting as MAS during pregnancy is uncommon, posing significant diagnostic and therapeutic challenges. We present a case of a 30-year-old woman at the 12th gestational week with fever, arthralgia, rash, cervical lymphadenopathy, cytopenia, and elevated liver enzyme. Bone marrow biopsy revealing hemophagocytosis, elevated ferritin and triglycerides, high interleukin-2, fever and cytopenia, confirmed the diagnosis of HLH. Further evaluation revealed the diagnosis of SLE. Treatment was initiated with intravenous immunoglobulin and corticosteroids. Given the deterioration in the patient’s clinical condition, a decision was made to terminate the pregnancy. She continued in the following months to receive SLE treatment with corticosteroids, cyclophosphamide, hydroxychloroquine, and later with mycophenolate mofetil due to the development of Class IV of lupus nephritis. P19V IgM antibodies were initially positive, later seroconverted to IgG, indicating that infection may have acted as a trigger for the onset of SLE and MAS development during pregnancy. The overlapping clinical features of P19V infection, SLE, and MAS pose significant diagnostic and therapeutic challenges. Early recognition and comprehensive diagnostic evaluation are crucial for the management of these conditions, especially during pregnancy, where both maternal outcomes are at risk. Full article