Search Results (230)

Background and Clinical Significance: Cutaneous paraneoplastic phenomena are infrequently characterised in colorectal cancer (CRC), and chronic pruriginous inflammatory eruptions in particular have received limited attention. In older adults, persistent treatment-resistant dermatoses of unclear aetiology may represent overlooked extraintestinal diagnostic clues to occult malignancy, including potentially curable CRC. Faecal immunochemical testing (FIT) for occult bleeding is a low-cost, non-invasive tool whose role outside conventional alarm-symptom triage remains underexplored. Case presentation: A 72-year-old woman presented for outpatient evaluation with several months of pruriginous, pustular, and crusted symmetric eruption involving the dorsal aspects of the limbs, refractory to standard dermatologic treatment, and without gastrointestinal symptoms. A non-invasive systemic stool-based work-up demonstrated detectable faecal haemoglobin (iFOBT), mildly elevated faecal calprotectin (51.6 mg/kg, ULN 50 mg/kg), markedly elevated faecal alpha-1-antitrypsin (631 µg/mL; 2.3× ULN), and predominance of Escherichia coli on stool culture. Colonoscopy revealed a locally advanced rectal adenocarcinoma; staging classified the lesion as cT3N1M0. The patient received long-course neoadjuvant chemoradiotherapy (50 Gy, concurrent capecitabine) followed by low anterior resection with total mesorectal excision and pathological complete response (ypT0N0, R0), and adjuvant capecitabine. The cutaneous eruption resolved progressively in parallel with antineoplastic therapy without specific dermatologic intervention. The patient remains in remission at over 36 months. Conclusions: Persistent, unexplained, treatment-resistant pruriginous/pustular cutaneous eruptions may, in selected patients, coincide with an underlying malignancy, including colorectal cancer, and should prompt careful individualised clinical assessment, including review of age-appropriate colorectal cancer screening status. This single case raises the hypothesis that quantitative faecal immunochemical testing (FIT) may be prospectively evaluated as a low-cost, non-invasive triage tool in carefully selected patients aged ≥50 years with persistent dermatoses of unclear aetiology, even in the absence of gastrointestinal symptoms. Positive FIT results should be managed according to established local colorectal referral pathways. NICE diagnostics guidance DG56 supports FIT use in symptomatic adults with suspected lower gastrointestinal pathology; however, any extension of FIT to extraintestinal presentations remains investigational and requires formal validation through prospective studies assessing diagnostic yield, cost-effectiveness, and stage distribution. Full article

Background: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) represents a group of rare systemic autoimmune disorders marked by inflammation and damage to small- and medium-sized blood vessels. The clinical presentation of AAV is highly variable, ranging from isolated organ involvement to severe, life-threatening multisystem disease, posing significant challenges in diagnosis, treatment, and prognosis. Objective: To demonstrate the clinical heterogeneity and different outcomes in three pediatric cases of ANCA-positive disease and emphasize the importance of integrating clinical findings with laboratory and imaging investigations for accurate diagnosis. Methods: We present three pediatric patients (ages 12–15 years) with ANCA-positive results but distinct clinical presentations, evaluated at the Children’s Emergency Hospital “Louis Turcanu”, Timisoara, between 2020 and 2024. All cases were investigated according to EULAR/PRINTO/PReS criteria for pediatric vasculitis. Results: Case 1 (PR3-ANCA positive) developed severe multi-organ involvement, including granulomatosis with polyangiitis (GPA) with pulmonary hemorrhage, pericarditis, thrombotic events, and renal impairment, requiring intensive immunosuppression with cyclophosphamide, rituximab, and mycophenolate mofetil, ultimately developing chronic kidney disease stage 3a. Case 2 (BPI-ANCA positive) presented with purpuric lesions and painless joint swelling, responding favorably to corticosteroid therapy with subsequent remission. Case 3 (MPO-ANCA) manifested as polyarticular arthritis without other organ involvement and was ultimately diagnosed as seronegative juvenile idiopathic arthritis (JIA), achieving complete remission with adalimumab therapy. Conclusions: This case series highlights the diverse clinical and biological features of ANCA-positive conditions in children, emphasizing that ANCA positivity requires careful clinical correlation as it may indicate true vasculitis requiring aggressive treatment or alternative diagnoses such as JIA with incidental ANCA positivity. Tailored therapeutic strategies based on clinical presentation and continued research are essential to improve patient outcomes. Full article

This study is a narrative review of natural killer (NK) cells in Behcet disease (BD). BD is an inflammatory disorder with manifestations in mucosal tissues. Unlike autoimmune diseases that generate autoantibodies, BD is believed to be an autoinflammatory disease triggered by innate immune cells rather than adaptive cells. Hyperactivation of neutrophils causes vasculitis and thrombosis, and they migrate into cutaneous and ocular lesions. Dominance of M1 macrophages promotes the differentiation of Th1 cells. Moreover, the cross-reaction of bacterial heat shock proteins induces production of cytokines such as IL-4 and IFN-γ in γδT cells, which alters the balance between Th1 and Th2 phenotypes. Nevertheless, NK cells play more critical roles in BD pathogenesis than other innate immune cells because not only is their activity precisely controlled by the interaction between ligands and receptors, but NK1 shift also elicits Th1 dominance. The genetic factors associated with BD are HLA-B51 and major histocompatibility complex class I-related chain A (MICA), which stimulate NK receptors as ligands. Improperly processed peptides dysregulate their interaction with NK receptors, triggering the inflammatory response. NK1 and NK2 subsets represent cytokine production in relapse and remission periods; however, the cytotoxicity of NK cells in relapse is lower than that in remission periods. It still remains unclear how NK cells are activated recurrently and expand cytokine production. This review highlights the regulation of gene expression encoding NK receptors, tissue-resident NK cells, and adaptive NK cells to discuss their potential for relapse. Splicing variants and readthrough genes encoding NK receptors easily alter cytokine production. Moreover, tissue-resident NK cells in mucosal tissues and adaptive NK cells that memorize the virus infection have the potential to trigger hyperactivation in relapse. Full article

Background. Autoimmune sclerosing cholangitis (ASC) is a rare clinical entity characterized by overlapping features of autoimmune hepatitis and primary sclerosing cholangitis. It predominantly affects pediatric patients. Therapeutic management is often complex, requiring a multidisciplinary and individualized approach, especially in the context of associated autoimmune diseases. Case presentation. We present the case of a female patient diagnosed at the age of 10 with ASC, for which immunosuppressive therapy with prednisone, azathioprine (AZA), and ursodeoxycholic acid (UDCA) was initiated, with an initially favorable course. One year later, following a Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection, the patient experienced reactivation of liver disease and subsequently developed ulcerative pancolitis (UC), for which 5-aminosalicylic acid (5-ASA) therapy was initiated. Due to repeated hepatic flares and/or colitis relapses, therapy was escalated successively to mycophenolate mofetil, tacrolimus, and eventually infliximab (IFX). Despite treatment, the liver disease progressed, culminating in liver cirrhosis. Our patient developed portal hypertension and esophageal varices, with two episodes of upper gastrointestinal bleeding requiring endoscopic band ligation. At the age of 14, the patient developed recurrent episodes of non-infectious ulcerative stomatitis. Biopsy of the lesions revealed non-specific chronic inflammation, unrelated to colitis activity (confirmed microscopic remission of UC). By exclusion, an adverse drug reaction was suspected, with AZA being the most likely cause. Following its discontinuation, the lesions resolved. Beyond the physiological and therapeutic aspects, the patient displays marked emotional fragility due to prolonged and repeated hospitalizations (18 out of 60 months), which have impacted treatment adherence. Conclusions. This case highlights the complexity of managing pediatric patients with multiple autoimmune diseases. The necessary combination of immunosuppressive therapies may lead to significant adverse effects and further complicate disease progression. Moreover, psychological components play a crucial role in treatment compliance and therapeutic success, emphasizing the need for an integrated approach that includes specialized psychological support. Full article

Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy, with most cases arising from B-cell precursors expressing the CD19 marker. CD19 negativity in B-lineage ALL (B-ALL) is very rare de novo and poses diagnostic and therapeutic challenges. Sometimes, de novo CD19-negative B-ALL is associated with hypercalcemia, which is a potentially life-threatening metabolic disorder in children, rarely occurring in cancers. Most often it is reported in solid tumors, and few cases are reported in pediatric acute leukemia. CD19-negative B-ALL relapse is also an increasing dramatic event, secondary to immunotherapy. We describe a ten-month-old infant presenting with hypercalcemia, anemia, and osteolytic bone lesions. Bone marrow analysis revealed CD10-positive and CD19-negative B-ALL. The patient achieved complete remission but later experienced two relapses and died of respiratory failure after a second allogeneic hematopoietic stem cell transplantation (HSCT). Only nine cases of de novo CD19-negative B-ALL have been reported so far. Many are associated with hypercalcemia and osteolytic lesions. However, here we highlight the clinical impact of the more common secondary form of CD19-negative B-ALL as a relapse of CD19-positive ALL, right after the administration of targeted immunotherapy. Full article

Background and Clinical Significance: Burkitt lymphoma is an aggressive form of non-Hodgkin lymphoma of B-cell origin, caused by a MYC gene translocation on chromosome 8. There are three clinical subtypes, of which the sporadic subtype is most prevalent in the United States. Sporadic Burkitt lymphoma is diagnosed at a median age of 30 years and commonly manifests as bulky abdominal lesions, most often involving the ileocecal region. Pancreatic involvement is uncommon, and presentation as acute pancreatitis secondary to Burkitt lymphoma is exceedingly rare. Case Presentation: We present a case of a young male who presented with epigastric pain, nausea, and vomiting. He had a diffusely tender abdomen and elevated lipase levels. On imaging, he was found to have large retroperitoneal and intraperitoneal masses, contiguous with an enlarged pancreas. Burkitt lymphoma was confirmed upon biopsy of duodenal and gastric masses via endoscopic ultrasound. MRI brain and testicular ultrasound revealed unilateral fifth cranial nerve and bilateral testicular involvement, respectively. His course was complicated by bowel perforation requiring urgent surgery. However, he achieved complete remission with dose-dense systemic and intrathecal chemotherapy. Conclusions: This case highlights the diverse presentations of Burkitt’s lymphoma and a favorable prognosis with treatment. Clinicians should maintain a high index of suspicion for a malignant etiology of acute pancreatitis in patients without classic risk factors. Full article

Background: Endoscopic assessment is central to the management of inflammatory bowel disease (IBD), particularly within treat-to-target strategies. However, conventional high-definition white-light endoscopy (HD-WLE) is limited by interobserver variability and its inability to reliably reflect microscopic inflammation or predict long-term outcomes. Over the last decade, multiple technological innovations have reshaped the role of endoscopy in both disease activity monitoring and dysplasia surveillance. Methods: This narrative review provides a comprehensive and clinically oriented overview of emerging endoscopic technologies in IBD, including image-enhanced endoscopy, ultra-high-magnification techniques, artificial intelligence (AI), and molecular imaging. We discuss their diagnostic performance, prognostic implications, and potential integration into clinical practice. Results: Image-enhanced endoscopy improves visualization of subtle mucosal and vascular alterations and demonstrates stronger correlation with histological activity compared with HD-WLE alone. Confocal laser endomicroscopy and endocytoscopy enable in vivo microscopic assessment of epithelial architecture and barrier integrity, redefining remission beyond macroscopic healing. AI systems have shown expert-level performance in grading inflammatory severity in ulcerative colitis and high sensitivity in capsule endoscopy for Crohn’s disease, supporting objective and reproducible assessment. In surveillance, targeted high-definition inspection has replaced random biopsies, while adjunctive optical and AI-based tools enhance lesion detection and characterization. Molecular imaging introduces a predictive dimension by enabling visualization of drug–target engagement and dysplasia-specific pathways. Conclusions: Endoscopy in IBD is evolving from a descriptive modality toward a multimodal precision tool integrating enhanced imaging, AI-driven standardization, and molecular profiling. Although further validation and cost-effectiveness studies are required, these innovations have the potential to improve therapeutic stratification, surveillance strategies, and long-term patient outcomes. Full article

Multicentric reticulohistiocytosis (MRH) is a rare systemic histiocytic disorder of uncertain etiology characterized by papulonodular cutaneous lesions and potentially destructive polyarthritis, with variable multisystem involvement. Owing to its low prevalence, evidence for optimal management remains limited, and treatment responses are heterogeneous. Emerging reports suggest that Janus kinase (JAK) inhibition may provide benefit in refractory disease. We report a 60-year-old woman with MRH presenting with papulonodular skin lesions, symmetric polyarthritis, constitutional symptoms, and interstitial lung disease (nonspecific interstitial pneumonia pattern) in the context of co-existing primary biliary cholangitis and no evidence of malignancy. Prior therapies (glucocorticoids, methotrexate, leflunomide) achieved suboptimal control. Upadacitinib, a selective JAK1 inhibitor, induced rapid and complete remission of cutaneous and articular disease with improvement of pulmonary involvement. Secondary weight gain and incident diabetes were managed with tirzepatide. This case adds to the limited literature supporting JAK inhibition as a targeted option for refractory MRH, including multisystem disease with pulmonary involvement. Systematic evaluation of efficacy, durability, and safety is warranted. Full article

Psoriasis is classically defined as an immune-mediated disease. However, many patients do not achieve durable remission after immune-targeted therapies, suggesting that further pathogenic mechanisms may contribute to the persistence of psoriasis. Here, we propose ferroptosis, an iron-dependent regulated cell death driven by lipid peroxidation and failure of lipid repair, as a potential link between metabolic stress and immune-mediated inflammation in psoriasis. We summarize experimental evidence showing that membrane lipids remodeling, antioxidant suppression, lipid peroxidation, and dysregulated iron handling together define ferroptosis-permissive niches within psoriatic lesions. We also discuss functional studies demonstrating that ferroptosis modulation can reshape psoriasiform inflammation and explore how ferroptotic stress may amplify inflammatory signaling at the immune-epidermal interface, reinforcing IL-17/TNF/IFN-γ pathways. Finally, we discuss ferroptosis-related transcriptomic signatures as a potential approach to stratify psoriasis, capturing metabolic features that are not reflected by cytokine profiling. The translational opportunities and constraints for ferroptosis-targeted interventions are outlined, highlighting epidermal redox homeostasis as a new therapeutic frontier in psoriasis. Full article

Background and Clinical Significance: Diffuse Large B-Cell Lymphoma (DLBCL) is a morphologically and molecularly heterogeneous lymphoproliferative disorder that originates from a clonal B-cell ancestor. Patients usually present with rapidly enlarging lymph nodes or mass(es) at single or multiple sites. Generally, 18F-Fluorodeoxyglucose (18F-FDG) positron emission tomography with computed tomography (PET-CT) is performed post-treatment to evaluate remission status, especially in radiologically residual tumors. Myofibroblastoma (MFB) is a benign mesenchymal tumor of the mammary stroma composed of fibroblasts and myofibroblasts. These entities do not often present concurrently. Case presentation: The patient was an 80-year-old man with a history of stage IV-BS Diffuse Large B-Cell Lymphoma (DLBCL) with a high-risk International Prognostic Index (IPI). The patient underwent treatment with a six-cycle R-CHOP regimen. Immediately after the last cycle, an 18F-Fluorodeoxyglucose (18F-FDG) positron emission tomography with computed tomography (PET-CT) scan revealed a nodular solid lesion with a faintly increased metabolic standardized uptake value (SUVmax) of 3 in the upper outer quadrant of his left breast. A biopsy of the breast lesion was performed, and it revealed a benign mesenchymal tumor, specifically a Myofibroblastoma. The patient has not presented any symptoms or complications since surgery (12 months) and remains in complete remission (CR). Conclusions: Given the potential diagnostic pitfalls and therapeutic implications of residual tumors in the context of DLBCL, a conscientious evaluation by a multidisciplinary team (MDT) is highly recommended. Full article

Background and Clinical Significance: Foreign body ingestion represents an endoscopic emergency, with a risk of organ perforation of up to 35%, where increased prevalence was noticed among people with mental disorders and institutionalized patients. Case Presentation: The patient—male, 23 years old, and institutionalized for sequelae of infantile encephalopathy—was admitted for epigastric pain and hyperemetic syndrome that began 10 days earlier. Endoscopically, 12 hard plastic foreign bodies with sharp edges and sizes of 6–7 cm were identified, followed by extraction that was successfully performed in two sessions using a polypectomy snare and a Foreign Body Hood Protector. Additionally, multiple sessile exulcerated polypoid lesions were observed, measuring around 1–3 cm each, occupying the entire antrum. Histological examination showed inflammatory/regenerative elements, with features of moderate-to-high-grade dysplasia, while a rapid urease test for Helicobacter pylori infection was positive. As a consequence, the patient was administered triple eradication therapy. In addition, the patient presented marked features of hypereosinophilia and splenomegaly. Upon endoscopic reevaluation after 3 years and 8 months, no polyps were present and the H. pylori test was negative, while a complete and spectacular remission of both the hypereosinophilia and splenomegaly was observed. Conclusions: This case illustrates that the development and progression of gastric polyposis may be caused by the coexistence of chronic mucosal irritation from foreign bodies and H. pylori infection, which is a rare association. H. pylori eradication and endoscopic removal of the foreign bodies resulted in significant mucosal improvement. Full article

Introduction: Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating disease of the central nervous system with a highly heterogeneous clinical course. Early identification of patients at risk of aggressive disease progression is crucial for optimizing therapeutic strategies, including eligibility for highly effective treatments. Objective: The aim of this review was to synthesize current data on prognostic factors in multiple sclerosis, with particular emphasis on their significance in the early stages of the disease and potential clinical implications. Methods: A narrative systematic review of the literature was conducted, including observational studies, cohort studies, meta-analyses, and systematic reviews on the natural course of MS, prognostic factors, and clinical, neuroimaging, and laboratory biomarkers. We comprehensively reviewed PubMed and Scopus databases, focusing on English-language publications. Study selection prioritized longitudinal studies and meta-analyses with clear outcome definitions and sufficient follow-up. Formal quality scoring was not applied due to the narrative design of the review. Results: Key adverse prognostic factors include older age at onset, polysymptomatic onset, high relapse activity in the first years, incomplete remission after relapses, and the primary progressive form. Magnetic resonance imaging features, including the number and location of T2 lesions, contrast activity, the presence of spinal cord lesions, PRLs and SELs, and severe brain atrophy, also have significant predictive value. Increasing importance is being attached to laboratory biomarkers, such as oligoclonal bands, light neurofilaments, free kappa light chains, and GFAP. Conclusions: An integrated assessment of clinical, neuroimaging, and laboratory factors enables more effective risk stratification in patients with newly diagnosed MS. Early identification of an unfavorable prognostic profile may provide a basis for individualizing treatment and considering the use of highly effective therapies early in the course of the disease. Full article

Background: Congenital renal masses in neonates are most commonly congenital mesoblastic nephroma or, less frequently, or Wilms tumor. We describe a neonate with an apparent primary renal tumor that proved to be adrenal neuroblastoma infiltrating the kidney, highlighting diagnostic pitfalls in this subgroup of patients. Methods: We retrospectively reviewed the diagnostic work-up, histopathology, genomic profiling, treatment, and outcome of a term neonate in whom a renal mass was detected incidentally on ultrasound. Results: Ultrasound and MRI showed a 2 cm solid lesion centered in the upper pole of the left kidney, interpreted as nephroblastomatosis/early Wilms tumor. Left nephrectomy with adrenalectomy revealed stroma-poor, undifferentiated neuroblastoma with regional node involvement and multiple segmental chromosomal aberrations, including 1p and 3p loss, but no MYCN or ALK alterations. Initial management consisted of surgery alone with close surveillance. Within weeks, early disseminated relapse with bone and soft-tissue metastases occurred, necessitating escalation to high-risk, COJEC-based chemotherapy; resection of residual mass; and modified consolidation without high-dose chemotherapy or radiotherapy. The child remains in complete remission with preserved renal function. Conclusions: Neuroblastoma should be considered in the differential diagnosis of congenital “renal” masses. Imaging-driven provisional diagnoses may be misleading, and genomic risk profiling may help lower the threshold for systemic therapy in selected cases. Full article

Background/Objectives: This study aims to fill certain knowledge gaps by assessing the clinical effectiveness of PDT in a large group of women with HPV-related cervical lesions and examining how different patient factors affect treatment results. Methods: A total of 811 women aged from 19 to 76 were retrospectively analyzed who were treated by PDT of HPV infection with atypical squamous cells and HPV-related cervical lesions. PDT was performed using chlorin e6-based systemic photosensitizers. Irradiation was carried out at 662 nm. The endocervical dose was 334 J/cm², and the ectocervical dose was 291 J/cm². Results: Overall HPV clearance was 91.1%, lesion remission was 95.3%, and complete response was 88.3%, with the highest complete response observed in the HSIL group compared with HPV-positive ASCs. Multivariable models showed that multiple HPV infection (especially >3 genotypes) and pregnancy history were associated with lower odds of complete response, while younger age (18–25 years) and TZ2 were associated with higher odds of complete response. Conclusions: PDT using chlorin e6-based photosensitizers demonstrated high clinical and virological effectiveness across HPV-related cervical abnormalities, including HSIL, supporting its role as an organ-preserving treatment option. Multiple HPV genotypes and pregnancy history may identify patients at increased risk of partial response and warrant closer follow-up or tailored treatment strategies. Full article

Background and Clinical Significance: We report a rare case of a 66-year-old male with malignant non-germinal center-type large B-cell lymphoma involving the thoracic epidural, cauda equina, and filum terminal simultaneously. Case Presentation: The patient complained of back pain, rapid progressive numbness, and motor palsy in both legs in one month. Neurological examination revealed grade 2 muscle power in both lower limbs, hypesthesia below the T8 dermatome, and bladder and bowel dysfunctions. Magnetic resonance imaging (MRI) with contrast showed a well-defined extradural lesion extending from the T7 to T9 level, with severe spinal cord compression. Additionally, it revealed enlargement of the cauda equina occupying the extradural space from the L1-S1 level. The lesion appeared isointense on T1, mildly hyperintense on T2-weighted images, and exhibited homogeneous enhancement on post-contrast images. To relieve the patient’s spinal cord compression as soon as possible and allow the patient to recover quickly after surgery, we performed unilateral biportal endoscopy (UBE) to completely remove the T7-9 epidural lesion. The immunohistochemical assessment confirmed a histological diagnosis of diffuse large B-cell lymphoma, a non-germinal center type. The patient received radiotherapy to the thoracic and lumbosacral areas (50 Gy) and chemotherapy with six cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) after surgery. Follow-up positron emission tomography (PET) scan and MRI performed 4 months after surgery revealed complete remission of the lesion. The patient was able to walk using a walker after therapy. Conclusions: UBE is a favorable option for selected patients requiring immediate chemotherapy or radiotherapy owing to its reduced tissue trauma compared to traditional open surgery. Full article