Search Results (128)

Visceral leishmaniasis (VL) is a rare but increasingly recognized parasitic infection in non-endemic European regions, including Romania. We report two cases of VL diagnosed in Timiș County, Western Romania, in 2020: a 57-year-old male presenting with fever, massive splenomegaly, and severe pancytopenia, and a 51-year-old male presenting atypically with fatigue, bicytopenia, and absence of organomegaly. Both patients were diagnosed through bone marrow aspirate examination revealing Leishmania amastigotes. Both cases were classified as imported VL, with exposure linked to endemic regions of eastern Spain (Castellón and València). These cases highlight the importance of maintaining a high index of clinical suspicion for VL in patients presenting with unexplained cytopenias and elevated inflammatory markers, even in the absence of classic features such as hepatosplenomegaly. The present report underscores the relevance of travel history in non-endemic regions such as Romania and the need for clinical awareness of imported VL in patients returning from endemic areas of southern Europe. Full article

Primary Epstein–Barr virus (EBV) infection in children exhibits substantial clinical heterogeneity, often complicating early diagnosis and leading to unnecessary antibiotic use. This retrospective study evaluated 695 children (0–18 years) diagnosed with primary EBV infection at a tertiary pediatric center between 2010 and 2015, defined by positive viral capsid antigen (VCA) IgM and negative Epstein–Barr nuclear antigen (EBNA) IgG. Clinical, laboratory, and ultrasonographic findings were compared according to age group (≤4 vs. >4 years) and clinical setting (inpatient vs. outpatient). The median age was 3.75 years (IQR: 2–6.25), and more than half of the patients were ≤4 years. Younger children more frequently presented with nonspecific respiratory and gastrointestinal symptoms, whereas older children more commonly exhibited the classic infectious mononucleosis (IM) phenotype, including sore throat, dysphagia, lymphadenopathy, and hepatosplenomegaly (p < 0.001). Antibiotics were prescribed in 64.2% of patients, while 21.7% required hospitalization. Multivariable logistic regression analyses demonstrated that age was not an independent predictor of hospitalization, classic IM phenotype, or antibiotic use. Instead, specific clinical and laboratory findings—such as lymphopenia, lymphadenopathy, vomiting, thrombocytosis, and tonsillar hypertrophy—emerged as the key determinants of clinical outcomes. To enhance diagnostic discrimination, receiver operating characteristic (ROC) analysis of ANC/ALC and AST/ALT ratios was performed, and a composite risk score (0–2) was derived. Although both markers showed modest discriminative ability (AUC 0.607 and 0.575), their high negative predictive values (>90%) suggest potential utility as rule-out tools. The composite score demonstrated a stepwise increase in the probability of classic IM presentation across age groups. In conclusion, primary EBV infection demonstrates a clear age-related clinical spectrum; however, clinical and laboratory features rather than age alone drive key outcomes. These findings highlight the need for age-specific diagnostic strategies and improved antimicrobial stewardship, while the proposed risk score provides a foundation for future validation studies. Full article

Background/Objectives: The impact of postnatal CMV infection in extremely premature newborns is poorly characterized. We aimed to determine the impact and outcomes of postnatal CMV infection in a population of extremely premature newborns of gestational age of less than 29 weeks hospitalized in the Department of Perinatology, Division of Gynecology, University Medical Center Ljubljana. Methods: We included all extremely premature newborns of gestational age of less than 29 weeks treated in the Department of Perinatology between December 2022 and December 2024. Newborns were screened for CMV infection at set timepoints and congenital infection was excluded with PCR testing. Additional PCR testing for CMV was performed if newborns developed clinical features suspect for postnatal CMV infection. Clinical characteristics and treatment outcomes of newborns were noted. Mothers of infected newborns had their CMV serostatus determined. Results: In total, 63 extremely premature newborns were included, and 14 newborns had confirmed postnatal CMV infection. Postnatal CMV infection was associated with hepatosplenomegaly and lower platelet and leukocyte counts compared to controls. We found no association between postnatal CMV infection and other neonatal comorbidities. Conclusions: In our study, postnatal CMV infection was associated with a more severe and prolonged clinical course of extremely premature newborns compared to uninfected controls; however, in multivariable analysis, the association with a prolonged length of stay was no longer statistically significant. The results suggest that preventing postnatal CMV infection in this population is important. Full article

Background/Objectives: Mucopolysaccharidosis type III (MPS III, Sanfilippo syndrome) is an autosomal recessive lysosomal storage disorder caused by deficiencies in enzymes required for heparan sulfate degradation. While primarily recognized for its devastating neurodegenerative course, the systemic extent of glycosaminoglycan (GAG) accumulation remains under-characterized. This study aims to provide a detailed multisystemic pathological mapping of MPS III to challenge the traditional “brain-only” disease paradigm and highlight the clinical relevance of extracerebral involvement. Methods: We present a comprehensive clinicopathological analysis of a 15-year-old female patient with a history of profound neuropsychomotor delay, refractory epilepsy, and spastic tetraplegia. Following her death due to terminal bronchopneumonia during palliative care, a complete forensic and pathological autopsy was conducted. Tissue samples from all major organ systems were processed using routine Hematoxylin–Eosin (HE) staining, immunohistochemical staining for CD68, and specialized histochemical stains to identify intracellular storage products. Results: Macroscopic evaluation revealed significant diffuse cerebral atrophy, meningoencephalic edema, cardiac valvulopathy with compensatory myocardial remodeling, and hepatosplenomegaly. Furthermore, erosive gastrointestinal lesions and degenerative renal changes were identified. Histopathological examination confirmed widespread cytoplasmic vacuolization across diverse cell populations, including neurons, hepatocytes, renal tubular cells, and the reticuloendothelial system. These findings demonstrate that GAG deposition is a generalized process affecting nearly every parenchymal structure. Conclusions: Although neurological decline dominates the clinical phenotype, our findings underscore that MPS III is a true systemic storage disorder. Significant involvement of the cardiovascular and visceral systems contributes to the disease’s complexity and mortality. This case reinforces the critical diagnostic value of a comprehensive autopsy in delineating the full morphological spectrum of Sanfilippo syndrome, providing essential insights for multidisciplinary management. Full article

Background: Infantile hepatic hemangiomas (IHH) are common benign vascular tumors in infancy with diverse presentations. Methods: We report a 7-week-old infant presenting with hepatosplenomegaly, multiple skin and hepatic hemangiomas, anemia, and recurrent lung infections. Results: Treatment included propranolol, corticosteroids, and sirolimus, along with antifungal prophylaxis with fluconazole. The patient developed pneumothorax and pulmonary aspergillosis. Despite antifungal therapy with voriconazole and liposomal amphotericin B, along with surgical intervention, her condition deteriorated, resulting in multi-organ failure and death at 8.5 months of age. Conclusions: This case illustrates the complexity of IHH management and highlights the risk of severe infections during immunosuppressive therapy even when standard prophylaxis protocols are applied. Full article

We report a diagnostically challenging case of a 79-year-old man who presented with mediastinal lymphadenopathy, hepatosplenomegaly, and renal enlargement, raising suspicion for clinical lymphoma. However, the histological evaluation of a submandibular gland excision revealed fibrosis, a dense IgG4-positive plasma cell infiltrate (>100/HPF), and an IgG4:IgG ratio > 40%, supportive of IgG4-related disease (IgG4-RD) in the appropriate clinicopathologic context. This case illustrates an important but well-recognised diagnostic pitfall in which IgG4-RD may clinically and radiologically mimic lymphoma. PET-CT demonstrated multiorgan involvement with diffuse FDG uptake, but definitive diagnosis required the integration of clinical, radiologic, serologic, and pathologic findings. The patient’s laboratory profile, including hypocomplementemia and elevated inflammatory markers, supported the proliferative phenotype of IgG4-RD—recently proposed in the literature as a clinically distinct subgroup with systemic involvement and steroid responsiveness. Rather than representing a novel presentation, this case reinforces the importance of integrated assessment in distinguishing IgG4-RD from haematolymphoid malignancy. PET-CT served as a useful adjunct for identifying multiorgan disease and guiding diagnostic evaluation, but tissue evaluation remained essential to avoid misdiagnosis and inappropriate treatment. Recognition of this entity is vital to avoid misdiagnosis and inappropriate treatment. Full article

Gaucher disease (GD) is a lysosomal storage disorder caused by mutations in the glucocerebrosidase gene (GBA1), leading to acid β-glucosidase deficiency and the accumulation of glucosylceramide-derived glycosphingolipids. Its three phenotypes (non-neuronopathic, acute neuronopathic, and chronic neuronopathic) have variable clinical presentations including hepatosplenomegaly, cytopenia, bone disease, and neurological involvement. Early diagnosis and treatment are critical for improving outcomes, but GD is under-recognized due to non-specific symptoms and limited access to appropriate diagnostic testing. Glucosylsphingosine (lyso-Gb1), a deacylated metabolite of glucosylceramide, has been identified as a candidate biomarker for diagnosis and monitoring. This narrative review examines the role of biomarkers in GD, focusing on lyso-Gb1 as a potential diagnostic and prognostic biomarker. Lyso-Gb1 is markedly elevated in GD patients and correlates with disease burden, severity, and response to therapy. It is detectable in plasma and dried blood spots, making it suitable for newborn screening, diagnosis, and monitoring. Lyso-Gb1 is a sensitive and specific biomarker for GD, facilitating early detection, guiding treatment decisions, and enabling personalized disease management. Lyso-Gb1 levels reflect substrate accumulation and therapeutic response more reliably than other biomarkers such as chitotriosidase or CCL18. Ongoing research aims to refine diagnostic thresholds and integrate lyso-Gb1 monitoring into routine clinical practice for optimal patient outcomes. Full article

Background and Clinical Significance: Mantle cell lymphoma (MCL) frequently involves bone marrow, gastrointestinal tract, and hepatosplenomegaly, whereas pleural effusions are uncommon. Cases requiring invasive mechanical ventilation and thoracic drainage are rare. We report a case of MCL with persistent massive pleural effusions requiring invasive mechanical ventilation and bilateral continuous thoracic drainage. Case Presentation: A 71-year-old woman presented with dyspnea and was found to have bilateral pleural effusions and generalized lymphadenopathy. Shortly after admission, she developed acute respiratory failure due to pleural effusions and required invasive mechanical ventilation. Right-sided continuous thoracic drainage was initiated. Thereafter, more than 1 L of pleural fluid was drained each day. Flow cytometry of the pleural fluid showed CD5-positive B cells with kappa light-chain restriction. Bone marrow examination revealed abnormal lymphocyte infiltration. Cervical lymph node biopsy demonstrated diffuse proliferation of medium-sized, abnormal B lymphocytes with an immunophenotype of CD5⁺, CD19⁺, CD20⁺, cyclin D1⁺, SOX11⁺, and κ⁺, with a Ki-67 index of 20%, confirming MCL, stage IV. Immunochemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) was commenced under mechanical ventilation. Shortly thereafter, left-sided continuous thoracic drainage was also initiated. However, in response to immunochemotherapy, the bilateral pleural effusions gradually subsided, enabling extubation, and there was no reaccumulation after removal of both chest tubes. Furthermore, generalized lymphadenopathy regressed, and bone marrow examination revealed resolution of lymphoma infiltration, resulting in complete remission. Conclusions: De novo MCL complicated by persistent massive pleural effusions requiring invasive mechanical ventilation and bilateral continuous thoracic drainage is rare. A thorough diagnostic workup followed by prompt initiation of immunochemotherapy can arrest pleural output, enable extubation, and be lifesaving. Clinicians should recognize that MCL rarely presents with persistent massive pleural effusions. Full article

Background: Visceral Leishmaniasis (VL), a severe systemic parasitic disease caused by Leishmania species, can be complicated by secondary Hemophagocytic Lymphohistiocytosis (HLH). HLH is a life-threatening hyperinflammatory syndrome characterized by excessive immune activation that results in multiorgan dysfunction. The co-occurrence of VL and HLH in adults is a rare but critical diagnostic and therapeutic challenge, often leading to fatal outcomes if treatment is delayed. Case Presentation: We present two cases of adult males (60 and 72 years old) from Greece, an endemic area for L. infantum, who presented with prolonged fever, pancytopenia, hepatosplenomegaly, and impaired liver function. Both patients exhibited extremely elevated ferritin (all > 2000 ng/mL and one > 20,000 ng/mL) and hypertriglyceridemia, fulfilling key laboratory criteria for HLH. Diagnosis was confirmed by the visualization of Leishmania amastigotes in bone marrow aspirates, which also demonstrated features of hemophagocytosis. Case 1, critically ill with acute kidney injury and coagulopathy, required combined treatment with liposomal Amphotericin B and immunoglobulin therapy for HLH. Case 2, who showed rapid and “spectacular improvement” solely after receiving liposomal Amphotericin B, did not require HLH-specific immunosuppression. Conclusions: VL-associated HLH should be considered in adult patients presenting with complex systemic inflammation, fever, and cytopenias, particularly in endemic settings. Our cases illustrate that the prompt initiation of anti-leishmanial therapy with liposomal Amphotericin B can be sufficient to reverse the HLH syndrome by eliminating the infectious trigger. However, intensive immunomodulation may be necessary in patients presenting with critical multi-organ failure. Full article

Infantile-onset lysosomal acid lipase deficiency (LAL-D) (Wolman disease, historically) is a rare inherited, rapidly progressive disorder caused by pathogenic variants in the LIPA gene, which encodes the enzyme LAL. LAL is essential for the metabolism of cholesteryl esters and triglycerides. LAL deficiency leads to the accumulation of cholesteryl esters and triglycerides within the lysosomes, macrophages, and parenchymal cells in most tissue types, including those in the liver, gastrointestinal tract, and lymph nodes but excluding the central nervous system. Infants with rapidly progressive LAL-D present with gastrointestinal disturbance, adrenomegaly with calcification, hepatosplenomegaly, growth failure due to malabsorption, and systemic inflammation. If untreated, rapidly progressive LAL-D typically leads to death within the first year of life. Treatment takes the two-pronged approach of sebelipase alfa, a human lysosomal acid lipase enzyme replacement therapy (ERT) that improves lipid metabolism, combined with nutritional management. Dietary substrate (lipid) reduction, known as substrate reduction therapy, is essential for optimal management in LAL-D. Following a nutritional plan and managing gastrointestinal disturbances together reduce systemic inflammation and improve growth, gut function, liver health, quality of life, and survival in patients with infantile-onset LAL-D. A multidisciplinary specialized team is necessary to manage the highly complex, multisystemic conditions in these patients. Nutritional management of LAL-D has evolved with increasing experience with the clinical management of ERT-treated infantile-onset LAL-D. A review of guidance for best practice nutritional management is needed. This narrative review aims to provide updated recommendations and guidance for the optimal nutritional management of infantile-onset LAL-D. Full article

This study documents an outbreak of Salmonella enterica serovar Enteritidis (SE) on a commercial meat rabbit farm in Italy. Following the observation of increased mortality in kits and severe enteric symptoms across all age groups, SE was first isolated in early March 2024. A diagnostic and epidemiological investigation was subsequently undertaken to characterize the anatomo-histopathological features in deceased rabbits and to identify the source and transmission dynamics of the infection. Between March and December 2024, a total of 1550 rectal swabs from live rabbits, 60 environmental samples, and 168 carcasses were collected and subjected to microbiological analysis. SE-positivity rates ranged from 8.4% to 36.3%, depending on the sample type considered. Co-infections with Pasteurella multocida, Escherichia coli, and Staphylococcus spp. were also detected. Gross and histological lesions in SE-positive rabbits included fibrinonecrotizing enterocolitis, hepatosplenomegaly, and renal damage such as suppurative nephritis and tubulorrhexis. Despite the implementation of enhanced biosecurity protocols, SE re-emerged over time and across different pens. Given the zoonotic potential of SE, the outbreak described underscores the need for rabbit-specific Salmonella control programs to safeguard both animal and public health. Full article

Visceral leishmaniasis (VL) is a neglected vector-borne disease caused by obligate intracellular protozoa of the genus Leishmania. In immunocompromised patients, VL may present atypically, progress more aggressively, and respond less favorably to treatment. We present the case of a 62-year-old male with chronic inflammatory demyelinating polyneuropathy (CIDP) receiving long-term corticosteroids and azathioprine who developed relapsing VL complicated by post-kala-azar dermal leishmaniasis (PKDL). The patient initially presented with prolonged fever, pancytopenia, hepatosplenomegaly, and weight loss. Bone marrow aspirate revealed Leishmania amastigotes. Intravenous lyposomal amphotericin B (L-AMB) achieved temporary remission; however, PKDL and VL recurred one year later. Despite receiving sequential therapy with L-AMB and miltefosine, the patient experienced further relapses, likely due to severe T- and B-cell lymphopenia and marasmic-like malnutrition. VL should be considered in the differential diagnosis of prolonged fever and cytopenias in immunosuppressed patients in Mediterranean Europe, even in the absence of travel history. Chronic immunosuppression, secondary immunodeficiency, and malnutrition can significantly impair treatment response and favor recurrence, highlighting the need for integrated clinical, nutritional, and epidemiological management strategies. Full article

Reactive intralymphovascular immunoblastic proliferation (ILVIP) is a rare and diagnostically challenging entity that can closely mimic intravascular large B-cell lymphoma (IVLBCL). We report the comprehensive clinicopathologic features of two patients with B-cell lineage ILVIP identified in bowel resection specimens. Both patients presented with small bowel obstruction requiring surgical intervention, and one patient was initially erroneously diagnosed with IVLBCL. Neither patient had systemic findings suggestive of lymphoma, such as lymphadenopathy, hepatosplenomegaly, or B symptoms. Histologic evaluation demonstrated focal ILVIP composed of intermediate-to-large B-lineage immunoblasts positive for CD45, CD79a, and MUM1 with polytypic light-chain expression, and negative for CD20, PAX5, CD138, Epstein–Barr virus, and HHV8. The immunoblasts showed a high proliferation index (80–100%) in both cases. Recognition of ILVIP in specimens resected for bowel obstruction in otherwise healthy patients is essential to avoid misinterpretation as intravascular lymphoma and prevent unnecessary treatment. Full article

Background: Pyruvate kinase deficiency (PKD) is the most prevalent enzymatic defect of the glycolytic pathway, causing chronic congenital non-spherocytic hemolytic anemia. Clinical severity ranges from mild anemia to transfusion-dependent diseases. Severe neonatal presentations, including liver failure, have rarely been reported. Case presentation: We report a preterm female neonate with PKD who developed early-onset hemolytic anemia, conjugated hyperbilirubinemia, hepatosplenomegaly, coagulopathy, and progressive transaminitis. Imaging demonstrated hepatomegaly with diffuse parenchymal involvement. Whole-genome sequencing identified compound heterozygous pathogenic mutations in the PKLR gene, confirming the diagnosis of PKD. The patient required continuous transfusion support and was discharged following clinical stabilization. Discussion: Although PKD most often manifests as isolated hemolytic anemia, this case illustrates a rare neonatal phenotype with concurrent liver dysfunction. We investigated the potential underlying mechanism. Recognition of hepatic involvement in PKD is essential because liver failure is associated with considerable morbidity and mortality, and it may necessitate interventions such as liver transplantation. Conclusions: This case highlights the importance of considering PKD in neonates presenting with hemolysis and liver failure. Early genetic confirmation enables timely management, including transfusion support, iron overload surveillance, and anticipatory guidance for potential hepatic complications. Full article

Background: Noninfectious complications of peritoneal dialysis (PD) are common in infants. Mechanical dysfunctions with abdominal compartment syndrome, hydrothorax with respiratory failure, and medication-induced chyloperitoneum are rare during PD. In this case report, we aim to present several life-threatening events and the timely management of a PD infant. Case Presentation: This male infant is a case of infantile nephronophthisis, NPHP3/renal-hepatic–pancreatic dysplasia type 1, with end-stage kidney disease, and he received PD therapy at 4 months of age. Because of the young age with low body weight and hepatosplenomegaly with a limited abdominal cavity, intra-abdominal pressure-associated noninfectious complications frequently occurred. Acute respiratory failure with abdominal dullness was detected at 5 months of age. Abdominal compartment syndrome caused by PD catheter outflow obstruction from omental wrapping was diagnosed via laparoscopic revision surgery. Hyperkalemia, decreased PD drainage volume, and sudden respiratory distress occurred at 10 months old. Hydrothorax due to pleuroperitoneal communication was confirmed by scintigraphy. After thoracoscopic diaphragmatic bleb repair and plication surgery were performed, no recurrence of hydrothorax was observed. Calcium channel blocker-induced chyloperitoneum was observed at 13 months of age. Chylous ascites disappeared after tapering off the calcium channel blocker in 3 days. After the patient grew up with a larger peritoneal cavity, no more pressure-associated complications of PD occurred. Conclusions: The key to successful treatment of rare and life-threatening noninfectious complications of PD in young infants lies in early detection and timely intervention. A limited abdominal cavity is not a contraindication for PD therapy, especially in very young infants with low body weight, because hemodialysis is not a choice of long-term dialysis modality. Full article