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Purpose: While the relationship between eosinophilia and tumors has been extensively studied, eosinophilia is primarily observed clinically after tumor development, with no prior reports of eosinophilia occurring before tumor onset. This case report presents a unique instance of eosinophilia preceding the development of gastric cancer in an old male patient. Methods: The patient was evaluated after being diagnosed with gastric cancer. Investigations included physical examinations, hematological evaluations, molecular assays for genetic variations associated with eosinophilia, tumor marker assessments, staging using the AJCC system, histopathological examinations, and comprehensive sequencing of tumor tissue. Results: The patient exhibited disseminated erythematous macules and had a history of eosinophilia. Genetic testing for germline variations associated with eosinophilia was negative, and molecular assays did not detect significant genetic alterations linked to clonal eosinophilia. Staging revealed T1N0MX gastric cancer, with histopathology showing high-grade intraepithelial neoplasia and positive PD-L1 expression. Notably, sequencing identified mutations in the NOTCH1 and NOTCH2 genes, which are known to regulate eosinophil migration. After surgical intervention, pathological examinations confirmed high-grade squamous cell carcinoma in the esophagus and high-grade intraepithelial neoplasia in the stomach, without eosinophil infiltration. Surprisingly, the peripheral blood eosinophilia dramatically decreased following tumor resection. Conclusion: This case underscores the potential for eosinophilia to occur prior to tumor development, challenging the current understanding of the relationship between eosinophilia and cancer. Further research is warranted to explore the implications of eosinophilia in cancer pathogenesis and its clinical significance. [ABSTRACT FROM AUTHOR]

AbstractBackgroundCase reportConclusionsEosinophilic granulomatosis with polyangiitis (EGPA) is a multisystemic, immune-mediated disease that occurs in patients with asthma and eosinophilia. It is characterized by inflammation of small- and medium-caliber blood vessels.This report presents an unusual clinical case of EGPA with positive anti-neutrophil cytoplasmic antibodies who manifested bilateral pleural effusion. The diagnosis was confirmed through laboratory assessments and bronchial biopsies. The patient was treated with methylprednisolone showing improvement in symptoms.Our case appear interesting considering the limited evidence of pleural effusion in patients with EGPA documented in the literature. [ABSTRACT FROM AUTHOR]

Background: Rituximab (RTX) is a monoclonal antibody that has been increasingly used in the treatment of myasthenia gravis (MG). In most studies, the therapeutic protocol of RTX has been similar to that adopted for B cell lymphoma, with an increasing number of studies aimed at exploring the efficacy of low-dose RTX in MG. However, the beneficial effects of low-dose RTX in MG remain a subject of critical debate. Methods: This study was conducted following the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) guidelines. Two reviewers (Xishuai Yang and Bingxia Li) independently conducted searches across multiple databases, including PubMed, MEDLINE, EMBASE, Web of Science, Cochrane Library, and China National Knowledge Infrastructure (CNKI). A meta-analysis, utilizing representative forest plots, was performed to assess "Improved clinical status" and changes in the Quantitative Myasthenia Gravis (QMG) score before and after treatment. Results: A total of 17 studies involving 292 patients were included in the meta-analysis. A noticeable improvement in clinical status was observed in 91% of patients at the final follow-up after therapy (95% CI: 84–96%, P < 0.001). The QMG score showed a significant reduction following the treatment, with a standardized mean difference (SMD) of −1.69 (95% CI: −2.21 to −1.16, Z = 6.29, P < 0.001). In the acetylcholine receptor antibody-positive myasthenia gravis (AChR-MG) group, 90% of patients achieved improved clinical status (95% CI: 80–97%, P < 0.001) and the QMG score significantly decreased after low-dose RTX treatment, with an SMD of −1.51 (95% CI: −0.80 to −2.21, Z = 4.50, P < 0.001). In the muscle-specific kinase antibody-positive myasthenia gravis (MuSK-MG) group, 97% of patients achieved improved clinical status (95% CI: 89–100%, P < 0.001). The QMG score also significantly decreased following low-dose RTX treatment, with an SMD of −2.31 (95% CI: −2.99 to −1.62, Z = 6.60, P < 0.001). Adverse effects were reported in 29 out of 207 patients (14%, including infusion reactions in 22 patients (10.1%), infections in three patients (1.45%), cytopenia in two patients (0.96%), eosinophilia in one patient (0.48%), and hemiplegia in one patient (0.48%). Additionally, one patient (0.48%) succumbed to complications from invasive thymoma. Conclusion: Our meta-analysis shows that low-dose RTX is both effective and safe for treating MG. Systematic Review Registration: PROSPERO, identifier: CRD42024509951. [ABSTRACT FROM AUTHOR]

Fumarate hydratase (FH) mutated papillary renal cell carcinoma is an aggressive variant of kidney cancer that poorly responds to conventional targeted therapies and immunotherapy. Here, we present the 10-year follow-up of a heavily pre-treated patient with several lines of therapy, achieving a remarkable complete response to anti-PD-1 rechallenge. In addition, we highlight a common immune-related adverse event of anti-PD-1, eosinophilia, as a possible biomarker of response and using TCGA data analysis, provide proof-of-concept for tumor expression of the eosinophil-related gene SIGLEC8, as a promising powerful predictor of prognosis for papillary renal cell carcinoma patients. [ABSTRACT FROM AUTHOR]

Key points: Asian‐American (AA) patients with chronic rhinosinusitis with nasal polyps (CRSwNP) have comparable rates of tissue eosinophilia compared to Caucasians when defined as >10 eosinophils/high‐powered field (HPF).AA patients with CRSwNP have significantly higher incidence of mixed inflammation defined as >10 eosinophils/HPF and >10 neutrophils/HPF. [ABSTRACT FROM AUTHOR]

Background: Asthma, a complex respiratory disease, presents with inflammatory symptoms in the lungs, blood, and other tissues. We investigated the relationship between DNA methylation and 35 clinical markers of asthma. Methods: The Illumina Infinium EPIC v1 methylation array was used to evaluate 742,442 CpGs in whole blood from 319 participants from 94 families. They were part of the Netherlands Twin Register from families with at least one member suffering from severe asthma. Repeat blood samples were taken after 10 years from 182 individuals. Principal component analysis on the clinical asthma markers yielded ten principal components (PCs) that explained 92.8% of the total variance. We performed epigenome-wide association studies (EWAS) for each of the ten PCs correcting for familial structure and other covariates. Results: 221 unique CpGs reached genome-wide significance at timepoint 1 after Bonferroni correction. PC7, which correlated with loadings of eosinophil counts and immunoglobulin levels, accounted for the majority of associations (204). Enrichment analysis via the EWAS Atlas identified 190 of these CpGs to be previously identified in EWASs of asthma and asthma-related traits. Proximity assessment to previously identified SNPs associated with asthma identified 17 unique SNPs within 1 MB of two of the 221 CpGs. EWAS in 182 individuals with epigenetic data at a second timepoint identified 49 significant CpGs. EWAS Atlas enrichment analysis indicated that 4 of the 49 were previously associated with asthma or asthma-related traits. Comparing the estimates of all the significant associations identified across the two time points yielded a correlation of 0.81. Conclusion: We identified 270 unique CpGs that were associated with PC scores generated from 35 clinical markers of asthma, either cross-sectionally or 10 years later. A strong correlation was present between effect sizes at the 2 timepoints. Most associations were identified for PC7, which captured blood eosinophil counts and immunoglobulin levels and many of these CpGs have previous associations in earlier studies of asthma and asthma-related traits. The results point to a robust DNA methylation profile as a new, stable biomarker for asthma. [ABSTRACT FROM AUTHOR]

We present three cases of eosinophilic granulomatosis with polyangiitis (EGPA) where patients experienced relapse of eosinophilic sinusitis without peripheral eosinophilia while on remission maintenance therapy with mepolizumab (MPZ), an anti-interleukin (IL)-5 monoclonal antibody. Despite the initial control of symptoms with high-dose prednisolone (PSL) and MPZ, patients experienced a relapse of nasal obstruction and eosinophilic infiltration in nasal mucosal biopsies. Notably, relapses occurred despite normal peripheral eosinophil counts, indicating the localized nature of eosinophilic inflammation. While IL-5 inhibitors effectively reduce peripheral blood eosinophils, eosinophilic sinusitis may persist due to local factors such as IL-4-mediated inflammation. IL-4 has been implicated in promoting eosinophil migration into nasal tissues, suggesting that IL-5 inhibitors alone may not sufficiently suppress eosinophilic infiltration in such cases. These findings highlight the importance of considering the possibility of eosinophilic sinusitis relapse in EGPA patients treated with IL-5 inhibitors and reduced glucocorticoid doses. Further research is warranted to elucidate the mechanisms underlying local eosinophilic inflammation and optimize treatment strategies for EGPA patients. [ABSTRACT FROM AUTHOR]

Kimura disease (KD) is a rare chronic inflammatory disease that typically presents with soft subcutaneous granulomas in the head and neck regions characterized by elevated blood eosinophils and immunoglobulin E (IgE) level, whose aetiology remains poorly elucidated. Minimal change disease (MCD) has been reported as one of the renal manifestations that KD can present with, indicating that they may share a common pathology. Herein we describe a case of recurrent MCD associated with KD. During a follow‐up period of 15 years, MCD recurred three times with increased disease activity of KD as reflected by flares of skin lesions and elevated peripheral eosinophils, and responded well to increased doses of prednisolone and cyclosporin. Notably, visual field defects in his right monocular vision appeared at the time of third recurrence of MCD, leading to the diagnosis of optic neuritis (ON). Optic nerve involvement associated with KD is extremely rare, and this case is noteworthy in that inflammation in the optic nerve was observed at the time of MCD recurrence with increased disease activity of KD, suggesting the existence of a common pathology between KD, MCD, and ON. In patients with KD, an imbalance of T helper (Th) cells with Th2 cells predominating over Th1 cells is observed, which results in hyperIgEemia and eosinophilia. This Th2‐predominant immunological status in KD considered to predispose to MCD may also predispose to ON. MCD with a background of Th2‐predominant immune state may require attention to the possibility of complication of ON. [ABSTRACT FROM AUTHOR]

This article discusses a case of eosinophilic angiocentric fibrosis (EAF) with atypical clinical presentation involving the skin and upper respiratory tract. EAF is a rare fibroinflammatory condition that primarily affects the orbit and upper respiratory tract. The patient in this case initially presented with a firm plaque on her thigh, which later became inflamed and coincided with upper respiratory tract infections. The diagnosis was confirmed through skin and nasal mucosa biopsies, which revealed characteristic histopathological findings, including eosinophils and IgG4+ plasma cells. The patient's symptoms improved with treatment using methotrexate and prednisone. This case highlights the importance of recognizing the diverse and atypical manifestations of EAF for accurate diagnosis and management. [Extracted from the article]

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe, adverse drug reaction that is notoriously complex in both its presentation and treatment. Although early diagnosis and cessation of the causative agent are universally accepted as the initial interventions for DRESS, the subsequent management lacks a standardized approach. Historically, systemic steroids have been used as first-line treatment, but there is debate about the optimal dosing and route of administration, and evidence persists on the long-term complications associated with steroid use. Novel treatment approaches with targeted therapy, cyclosporine, intravenous immunoglobulin, and plasmapheresis have been gaining interest as alternative mono- and adjuvant therapies, but their use has yet to be supported by clinical trials. This narrative review provides a summary of the current knowledge of DRESS, with a focus on clinical management. The various mono- and adjuvant therapy options are discussed, with literature-supported suggestions for their optimal use in clinical practice. The risks for relapses, viral reactivation, and long-term complications are also considered. The PubMed and Medline databases were searched for articles on DRESS, published between January 1, 2008, and May 1, 2023. 334 articles met the inclusion criteria. Based on the literature, a DRESS management tool with step-by-step guidance is provided. Further suggestions for management are woven throughout this review, giving clinicians a toolbelt of resources with which to approach diagnosis, treatment, and follow-up. [ABSTRACT FROM AUTHOR]

Eosinophils are often encountered in the stroma and peritumoral microenvironment of squamous cell carcinomas. Because eosinophils are readily identified on routine hematoxylin and eosin stained sections, researchers have explored multiple ways in which identifying the extent of eosinophil infiltration on routine biopsy and excisional specimens might provide diagnostic and prognostic information. We review the literature on this evolving topic. [ABSTRACT FROM AUTHOR]

Simple Summary: Siglec-8 has been identified as a promising target to treat eosinophilic and mast cell disorders. However, there are currently few Siglec-8 antibodies available, and therapeutic efforts have so far primarily focused on unconjugated antibodies, which may be insufficiently effective in many patients. To address these limitations, we raised a diverse panel of fully human Siglec-8 antibodies as the basis for novel therapeutics. They were all efficiently internalized, suggesting their potential to deliver cytotoxic payloads. T cell-engaging bispecific antibodies and chimeric antigen receptor (CAR)-modified natural killer (NK) cells built from these Siglec-8 antibodies were highly potent against Siglec-8-positive cells even in cases of very low target antigen abundance. Importantly, mechanistic studies with target cells expressing either full-length Siglec-8 or an artificial smaller Siglec-8 variant demonstrated that T cell-engaging bispecific antibodies and CAR-modified NK cells were substantially more effective if they bound Siglec-8 closer to the cell membrane, indicating targeting membrane-proximal epitopes enhances effector functions of Siglec-8 antibody-based therapeutics. Indeed, tool therapeutics that bind one of the membrane-proximal C2-set domains of Siglec-8 were very effective against Siglec-8-positive target cells. Together, these data demonstrate Siglec-8-directed immunotherapies can be highly potent, supporting their further development for eosinophilic and mast cell disorders. Background/Objective: Current treatments for eosinophilic and mast cell disorders are often ineffective. One promising target to improve outcomes is sialic acid-binding immunoglobulin-like lectin-8 (Siglec-8). As limitations, there are few Siglec-8 monoclonal antibodies (mAbs) available to date, and Siglec-8-directed treatments have so far primarily focused on unconjugated mAbs, which may be inadequate, especially against mast cells. Methods: Here, we used transgenic mice to raise a diverse panel of fully human mAbs that either recognize the V-set domain, membrane-distal C2-set domain, or membrane-proximal C2-set domain of full-length Siglec-8 as a basis for novel therapeutics. Results: All mAbs were efficiently internalized into Siglec-8-expressing cells, suggesting their potential to deliver cytotoxic payloads. Tool T cell-engaging bispecific antibodies (BiAbs) and chimeric antigen receptor (CAR)-modified natural killer (NK) cells using single-chain variable fragments from Siglec-8 mAbs showed highly potent cytolytic activity against Siglec-8-positive cells even in cases of very low target antigen abundance, whereas they elicited no cytolytic activity against Siglec-8-negative target cells. Siglec-8V-set-directed T cell-engaging BiAbs and Siglec-8V-set-directed CAR-modified NK cells induced substantially greater cytotoxicity against cells expressing an artificial smaller Siglec-8 variant containing only the V-set domain than cells expressing full-length Siglec-8, consistent with the notion that targeting membrane-proximal epitopes enhances effector functions of Siglec-8 antibody-based therapeutics. Indeed, unconjugated Siglec-8C2-set mAbs, Siglec-8C2-set-directed T cell-engaging BiAbs, and Siglec-8C2-set-directed CAR-modified NK cells showed high antigen-specific cytolytic activity against Siglec-8-positive human cell lines and primary patient eosinophils. Conclusions: Together, these data demonstrate Siglec-8-directed immunotherapies can be highly potent, supporting their further development for eosinophilic and mast cell disorders. [ABSTRACT FROM AUTHOR]

Background: Rituximab (RTX) is a monoclonal antibody that has been increasingly used in the treatment of myasthenia gravis (MG). In most studies, the therapeutic protocol of RTX has been similar to that adopted for B cell lymphoma, with an increasing number of studies aimed at exploring the efficacy of low-dose RTX in MG. However, the beneficial effects of low-dose RTX in MG remain a subject of critical debate. Methods: This study was conducted following the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) guidelines. Two reviewers (Xishuai Yang and Bingxia Li) independently conducted searches across multiple databases, including PubMed, MEDLINE, EMBASE, Web of Science, Cochrane Library, and China National Knowledge Infrastructure (CNKI). A meta-analysis, utilizing representative forest plots, was performed to assess "Improved clinical status" and changes in the Quantitative Myasthenia Gravis (QMG) score before and after treatment. Results: A total of 17 studies involving 292 patients were included in the meta-analysis. A noticeable improvement in clinical status was observed in 91% of patients at the final follow-up after therapy (95% CI: 84-96%, P < 0.001). The QMG score showed a significant reduction following the treatment, with a standardized mean difference (SMD) of -1.69 (95% CI: -2.21 to -1.16, Z = 6.29, P < 0.001). In the acetylcholine receptor antibody-positive myasthenia gravis (AChR-MG) group, 90% of patients achieved improved clinical status (95% CI: 80-97%, P < 0.001) and the QMG score significantly decreased after low-dose RTX treatment, with an SMD of -1.51 (95% CI: -0.80 to -2.21, Z = 4.50, P < 0.001). In themuscle-specific kinase antibody-positivemyasthenia gravis (MuSK-MG) group, 97% of patients achieved improved clinical status (95% CI: 89-100%, P < 0.001). The QMG score also significantly decreased following low-dose RTX treatment, with an SMD of -2.31 (95% CI: -2.99 to -1.62, Z = 6.60, P < 0.001). Adverse effects were reported in 29 out of 207 patients (14%, including infusion reactions in 22 patients (10.1%), infections in three patients (1.45%), cytopenia in two patients (0.96%), eosinophilia in one patient (0.48%), and hemiplegia in one patient (0.48%). Additionally, one patient (0.48%) succumbed to complications from invasive thymoma. Conclusion: Our meta-analysis shows that low-dose RTX is both effective and safe for treating MG. [ABSTRACT FROM AUTHOR]

Objective: Asthma is linked to atherosclerosis, yet the underlying mediators remain elusive. Eosinophils may contribute to both asthmatic and atherosclerotic inflammation. Hence, this study aimed to explore the potential associations of eosinophils with artery changes among patients with asthma. Methods: We assessed strain values of the common carotid arteries (CCAs) via vascular speckle tracking and compared asthma patients with low (< 300/µl) and high (≥ 300/µl) blood eosinophil counts (BEC). Results: We enrolled 100 patients, 42 with a BEC of < 300 and 58 with a BEC of ≥ 300 n/µl. Patients with high BEC exhibited more severe disease, characterized, e.g., by a higher frequency of acute exacerbations (1.3 ± 2.1 vs. 2.6 ± 2.4 n/year, p = 0.005). Both groups presented similar profiles in terms of conventional cardiovascular risk. The high BEC group demonstrated elevated arterial stiffness, reflected by reduced radial strain (mean radial strain of the right CCA: 2.7 ± 1.4% for BEC ≥ 300 n/µl vs. 3.5 ± 1.7% for BEC < 300 n/µl, p = 0.008; left CCA: 2.6 ± 1.4% vs. 4.1 ± 2.2%, p < 0.001). A weak yet statistically significant negative correlation was observed between BEC and radial strain for the right CCA (R2 = 0.131, b=-0.001, p = 0.001) and left CCA (R2 = 0.086, b=-0.001, p = 0.015). However, the prevalence of cerebrovascular disease was similar in both groups (31,0% vs. 50,0%, p = 0.057). Conclusion: We identified a correlation between BEC and vascular stiffness, which supports the hypothesis that eosinophils may promote atherosclerosis. Clinical trial number: Due to the exploratory and predominantly retrospective nature of the study, trial registration was not conducted. The only prospective procedure conducted was the angiological sonography to evaluate the current state. No ensuing health-related interventions were performed specifically for this study. [ABSTRACT FROM AUTHOR]

Background: The association between blood eosinophils and COPD exacerbation has been controversial. This study aims to investigate whether high blood eosinophils predict the risk of COPD exacerbation across different thresholds and subgroups. Methods: PubMed, Embase and Web of science were searched for randomized controlled trial (RCT) and observational studies regarding the relationship between blood eosinophils and COPD exacerbation. Pooled risk ratio (RR) for COPD exacerbation was calculated using the Mantel-Haenszel method with a random-effects model. Results: A total of 21 studies (1 RCT and 20 observational studies) with 79868 participants were included. Thresholds of high blood eosinophils including absolute counts (200, 300 and 400 cell/μL) and percentages (2%, 3% and 4%) were analyzed respectively. Pooled analyses suggested that high blood eosinophils were significantly associated with increased risk of COPD exacerbation when using the thresholds of 300 cells/μL (RR 1.21, 95%CI 1.12–1.30, P <0.001, 16 studies), 400 cells/μL (RR 1.79, 95%CI 1.41–2.28, P <0.001, 3 studies), 2% (RR 1.26, 95%CI 1.02–1.55, P = 0.030, 10 studies) and 4% (RR 1.44, 95%CI 1.05–1.96, P = 0.022, 4 studies), but not 200 cells/μL and 3% (P>0.05). Moreover, high blood eosinophils contributed to moderate-severe exacerbation of COPD by the cutoffs of 300 cells/μL (RR 1.30, 95%CI 1.16–1.45, P<0.001, 11 studies) and 2% (RR 1.33, 95%CI 1.02–1.76, P = 0.037, 8 studies). In subgroup analyses, the pooled results further showed a significant association between high blood eosinophils (especially over 300 cells/μL) and risk of COPD exacerbation among patients from Europe and Asia, and whether with stable or exacerbation phase at baseline, and regardless of the follow-up time (≤ or > 1year). Conclusions: This study demonstrates that high blood eosinophils (over 300 cells/μL or 2%) could predict the risk of moderate-severe exacerbation of COPD in specific subgroups. However, large sample-sized, prospective, and well-designed studies are required to validate the present findings. [ABSTRACT FROM AUTHOR]

The article focuses on a 15-year-old male with fever, rash, and abnormal laboratory findings, ultimately diagnosed with a viral infection. Topics include his medication history with minocycline, the broad differential diagnosis including conditions like toxic shock syndrome and Stevens-Johnson syndrome, and the positive respiratory viral panel for human metapneumovirus.

Context.--Eosinophilic solid and cystic renal cell carcinoma is now defined in the 5th edition of the 2022 World Health Organization classification of urogenital tumors. Objective.--To perform morphologic, immunohistochemical, and preliminary genetic studies about this new entity in China for the purpose of understanding it better. Design.--The study includes 18 patients from a regional tertiary oncology center in northern China (Tianjin, China). We investigated the clinical and immunohistochemical features of these cases. Results.--The mean age of patients was 49.6 years, and the male to female ratio was 11:7. Macroscopically, 1 case had the classic cystic and solid appearance, whereas the others appeared purely solid. Microscopically, all 18 tumors shared a similar solid and focal macrocystic or microcystic growth pattern, and the cells were characterized by voluminous and eosinophilic cytoplasm, along with coarse ampho-philic stippling. Immunohistochemically, most of the tumors had a predominant cytokeratin (CK) 20-positive feature, ranging from focal cytoplasmic staining to diffuse membranous accentuation. Initially, we separated these cases into different immunohistochemical phenotypes. Group 1 (7 of 18; 38.5%) was characterized by positive phospho-4EBP1 and phospho-S6, which can imply hyperactive mechanistic target of rapamycin complex 1 (mTORC1) signaling. Group 2 (4 of 18; 23%) was negative for NF2, probably implying a germ-line mutation of NF2. Group 3 (7 of 18; 38.5%) consisted of the remaining cases. One case had metastatic spread and exhibited an aggressive clinical course, and we detected cyclin-dependent kinase inhibitor 2A (CDKN2A) mutation in this case; other patients were alive and without disease progression. Conclusions.--Our research proposes that eosinophilic solid and cystic renal cell carcinoma exhibits prototypical pathologic features with CK20 positivity and has aggressive potential. [ABSTRACT FROM AUTHOR]

• Systematic literature review & expert consensus to identify red flags for raising EGPA suspicion. • EGPA diagnosis is tricky due to its heterogeneity and its overlap with eosinophilic disorders. • Creating an evidence-based checklist with red flags to initiate EGPA diagnosis process. Eosinophilic granulomatosis with polyangiitis (EGPA), is a rare ANCA-associated systemic vasculitis. Its overlapping features with other vasculitic or eosinophilic diseases, and the wide and heterogeneous range of clinical manifestations, often result in a delay to diagnosis. To identify red flags that raise a suspicion of EGPA to prompt diagnostic testing and to present an evidence-based clinical checklist tool for use in routine clinical practice. Systematic literature review and expert consensus to identify a list of red flags based on clinical judgement. GRADE applied to generate a strength of recommendation for each red flag and to develop a checklist tool. 86 studies were included. 40 red flags were identified as relevant to raise a suspicion of EGPA and assessed by the experts as being clinically significant. Experts agreed that a diagnosis of EGPA should be considered in a patient aged ≥6 years with a blood eosinophil level >1000 cells/µL if untreated and >500 cells/µL if previously treated with any medication likely to have altered the blood eosinophil count. The presence of asthma and/or nasal polyposis should reinforce a suspicion of EGPA. Red flags of asthma, lung infiltrates, pericarditis, cardiomyopathy, polyneuropathy, biopsy with inflammatory eosinophilic infiltrates, palpable purpura, digital ischaemia and ANCA positivity, usually anti-myeloperoxidase, among others, were identified. The identification of a comprehensive set of red flags could be used to raise a suspicion of EGPA in patients with eosinophilia, providing clinicians with an evidence-based checklist tool that can be integrated into their practice. [ABSTRACT FROM AUTHOR]

The ETV6::ABL1 fusion defines a subgroup of myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions. We report a case of extramedullary involvement and leukemic transformation in myeloproliferative neoplasm (MPN), where ETV6::ABL1 was initially overlooked but later detected in the blast phase. ETV6::ABL1 burden was very low during the MPN phase but increased substantially during the blast phase. This correlation between ETV6::ABL1 burden and disease phenotype indicated that an immature leukemic clone is the sole carrier of ETV6::ABL1, suggesting that ETV6::ABL1 is not the primary driver of the MPN phase. Moreover, only the blast phase revealed somatic mutations in RUNX1 and STAG2, or complex karyotype, while the MPN phase revealed no molecular and cytogenetic abnormalities. Therefore, it remains uncertain whether the small clone of ETV6::ABL1 influenced the manifestation of MPN or if another underlying driver was responsible for the MPN phase, necessitating further research. [ABSTRACT FROM AUTHOR]

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Simple Summary: Insect bite hypersensitivity (IBH) is a common skin allergic condition in horses caused by insect bites, mainly of Culiocides species. Affected horses develop severe itchy lesions, up to traumatic skin injuries. Eosinophils are known to play a crucial role in the pathogenesis of IBH. Recently, we described two subsets of eosinophils: inflammatory eosinophils (iEos) dominant in blood of IBH-affected horses, and resident eosinophils (rEos) present in blood of healthy horses. iEos and rEos were distinguishable by size, granularity, and proteins present on their cell surface. Interleukin (IL)-5, the main activator and regulator of eosinophils, is our vaccine target. Vaccinated horses showed a significant reduction of total eosinophils, in particular iEos, where the very few remaining eosinophils still showed iEos phenotype. In the present study, we followed the phenotype of eosinophil subsets in the 2nd year of vaccination in IBH-affected horses. Our results showed comparably lower levels of iEos and a significant increase of rEos in 2nd compared to 1st year vaccinated and unvaccinated horses. This suggests a shift from iEos to the rEos phenotype, the dominant eosinophil type of healthy horses. The change in size, granularity and migration properties suggests a benefit of long term vaccination of IBH-affected horses. Eosinophils play a key role in allergic diseases such as insect bite hypersensitivity (IBH). Together with Th2 cells, they shape the course of inflammation in associated type I/IVb allergies. Therefore, a virus-like particle (VLP)-based vaccine targeting equine interleukin-5 (eIL-5), eIL-5-CuMV-TT, was developed to interfere with the IL-5 dependency of eosinophils by inducing the production of anti-self-IL-5 antibodies and alleviating clinical signs in IBH-affected horses. A previous study highlighted the presence of two eosinophil subsets, steady-state resident eosinophils (rEos) and inflammatory eosinophils (iEos), circulating in the blood of healthy and IBH-affected horses, distinguishable by the expression of integrin CD49f. Furthermore, eIL-5-CuMV-TT 1st year vaccination showed a significant decrease of total eosinophils and, in particular, iEos. Nevertheless, the very few remaining eosinophils still shared an iEos phenotype, reflected by bigger size and higher granularity. The aim of this study was to follow up on the phenotype of eosinophils in the 2nd year of vaccination of IBH-affected horses with eIL-5-CuMV-TT. Using flow cytometry analysis of the blood of healthy, IBH, IBH-placebo, and IBH-vaccinated horses, the percentage and count of cells were compared between groups with a focus on pair analysis of eosinophils in 1st and 2nd year vaccinated horses. Our data showed comparably low levels of iEos and a significant increase of rEos in 2nd year compared to 1st year vaccinated horses, suggesting a phenotypic shift toward a resident-like eosinophil population, primarily associated with the phenotype of healthy horses. The reduction of size, granularity, and expression of integrin CD49f in the 2nd year suggests a benefit of long-term treatment with the eIL-5-CuMV-TT vaccine. [ABSTRACT FROM AUTHOR]

Purpose of Review: In this review, we aim to explore the optimal approach to patients presenting with eosinophilia, considering recent advances in diagnostic and therapeutic strategies. Specifically, we focus on the integration of novel therapies into clinical practice to improve patient outcomes. Recent Findings: Advanced insights into the clinical and genetic features of eosinophilic disorders have prompted revisions in diagnostic criteria by the World Health Organization classification (WHO-HAEM5) and the International Consensus Classification (ICC). These changes reflect a growing understanding of disease pathogenesis and the development of targeted treatment options. The therapeutic landscape now encompasses a range of established and novel therapies. For reactive conditions, drugs targeting the eosinophilopoiesis, such as those aimed at interleukin-5 or its receptor, have demonstrated significant potential in decreasing blood eosinophil levels and minimizing disease flare-ups and relapse. These therapies have the potential to mitigate the side effects commonly associated with prolonged use of oral corticosteroids or immunosuppressants. Myeloid and lymphoid neoplasms with eosinophilia and tyrosine kinase (TK) gene fusions are managed by various TK inhibitors with variable efficacy. Summary: Diagnosis and treatment rely on a multidisciplinary approach. By incorporating novel treatment options into clinical practice, physicians across different disciplines involved in the management of eosinophilic disorders can offer more personalized and effective care to patients. However, challenges remain in accurately diagnosing and risk-stratifying patients, as well as in navigating the complexities of treatment selection. [ABSTRACT FROM AUTHOR]

Estrogens regulate eosinophilia in asthma and other inflammatory diseases. Further, peripheral eosinophilia and tumor-associated tissue eosinophilia (TATE) predicts a better response to immune checkpoint blockade (ICB) in breast cancer. However, how and if estrogens affect eosinophil biology in tumors and how this influences ICB efficacy has not been determined. Here, we report that estrogens decrease the number of peripheral eosinophils and TATE, and this contributes to increased tumor growth in validated murine models of breast cancer and melanoma. Moreover, estrogen signaling in healthy female mice also suppressed peripheral eosinophil prevalence by decreasing the proliferation and survival of maturing eosinophils. Inhibiting estrogen receptor (ER) signaling decreased tumor growth in an eosinophil-dependent manner. Further, the efficacy of ICBs was increased when administered in combination with anti-estrogens. These findings highlight the importance of ER signaling as a regulator of eosinophil biology and TATE and highlight the potential near-term clinical application of ER modulators to increase ICB efficacy in multiple tumor types. [ABSTRACT FROM AUTHOR]

Introduction: Because the prognosis of patients with peripheral T-cell lymphoma is poor compared to that of patients with B-cell lymphoma, we want to avoid further organ damage by eosinophilia. Moreover, in patients with some types of lymphoma, blood eosinophilia is implicated in a worse prognosis. To study the risk factors of eosinophilia, the association between lymphoma type, immunophenotypic features, and peripheral blood eosinophil counts were examined in the patients with mature T-cell lymphoma. Methods: We retrospectively examined 28 patients with mature T-cell lymphoma who were admitted to our hospital and whose immunophenotypic features were confirmed using flow cytometric, immunohistochemical analysis, or both between December 2012 and November 2023. Results: We report a possible association between peripheral eosinophilia and peripheral T-cell lymphoma – not otherwise specified and CD3+CD4−D8− (double-negative) phenotypes. Mild eosinophilia was observed in various types, but moderate and severe eosinophilia were observed in patients with peripheral T-cell lymphoma – not otherwise specified. Double-negative phenotype was rarely observed; however, all patients with double-negative phenotype exhibited peripheral blood eosinophilia. In addition, four of the five cases of the double-negative type were peripheral T-cell lymphoma – not otherwise specified. Conclusion: Here, we retrospectively examined patients with peripheral T-cell lymphoma whose immunophenotypic features were confirmed and report a possible association between peripheral eosinophilia and peripheral T-cell lymphoma – not otherwise specified and CD3+CD4−CD8− (double-negative) phenotypes. In addition, clinicians should be aware of the possible risk that patients with lymphocytic hypereosinophilic syndrome of the double-negative phenotype may develop peripheral T-cell lymphoma. [ABSTRACT FROM AUTHOR]

Background: The potential link between alopecia areata (AA) and eosinophilia is unclear, as well as its clinical manifestations in these patients' subsets. Methods: This is a monocentric retrospective observational study in which clinical and laboratory data were summarized and evaluated the AA subset with concurrent eosinophilia. Results: In a sample of 205 AA patients, 38 (18.5%) were classified as AA with eosinophilia. Interestingly, this subset of patients had a statistically higher prevalence of atopia and nail abnormalities (p < 0.05) than AA without eosinophilia. AA patients with eosinophilia had a 3.70 higher odds of more severe hair loss versus age‐ and gender‐matched AA without eosinophilia. Conclusions: AA patients with eosinophilia had distinctive clinical and laboratory characteristics, so future studies may potentially explore the use of IL‐5 inhibitors. [ABSTRACT FROM AUTHOR]

Aims Methods Results Conclusions The aim of this study was to explore the clinical characteristics and risk factors for hypersensitivity reactions induced by antituberculosis drugs.A retrospective analysis was conducted on the medical records of patients with active tuberculosis (TB) treated in the TB ward at West China Hospital, Sichuan University, from November 2010 to April 2020.Out of 7106 patients with active tuberculosis, 205 experienced hypersensitivity reactions to antituberculosis drugs; the incidence of hypersensitivity was 2.9%. The predominant clinical manifestation was a rash, observed in 57.1% (117/205) of these cases. Additionally, 19.0% (39/205) of patients presented with concurrent liver injury. The laboratory parameters white blood cell count, total lymphocyte count, monocyte count, eosinophil count, basophil count, alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase were significantly elevated in patients with hypersensitivity compared to those without. In 38 patients who tested positive for oral antituberculosis drug provocation, 14 (36.8%) were allergic to more than two antituberculosis drugs. Significant risk factors included being female (odds ratio [OR] = 1.387, 95% confidence intervals [CI]: 1.016–1.894), under 65 years of age (OR = 1.826, 95% CI: 1.145–2.913), existing liver disease (OR = 2.464, 95% CI: 1.822–3.333) and a history of allergic diseases (OR = 6.633, 95% CI: 2.681–16.406) and were significantly correlated with hypersensitivity to antituberculosis drugs.Hypersensitivity reactions to antituberculosis drugs primarily affect the skin, with significant associations observed with liver injury. Females, individuals younger than 65 years, those with pre‐existing liver disease and patients with a history of allergic diseases are at elevated risk for hypersensitivity. [ABSTRACT FROM AUTHOR]

This study reported a woman with drug reaction with eosinophilia and systemic symptom (DRESS) syndrome induced by phloroglucinol who developed fulminant type 1 diabetes as sequelae. The literature review emphasized the necessity of at least seven months of follow‐up for better management of DRESS syndrome. [ABSTRACT FROM AUTHOR]

Kimura's disease (KD) is a rare, chronic inflammatory disorder characterized by angiolymphoid hyperplasia, peripheral eosinophilia, and elevated serum immunoglobulin E levels. It primarily affects young Asian males and typically involves the head and neck region, especially near the mandible and postauricular regions. Orbital involvement is unusual and extraocular muscle (EOM) involvement is exceedingly rare, with only a few cases reported in the literature. The present report describes a case of surgically confirmed KD in a 16-yearold male, involving the bilateral EOM, lacrimal gland, and left parotid gland. [ABSTRACT FROM AUTHOR]

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe and potentially life‐threatening hypersensitivity reaction. Although commonly associated with specific drugs, there have been no reports of DRESS syndrome caused by medical devices. We report a unique case of DRESS syndrome linked to a particular hemodialysis membrane during treatment. An 83‐year‐old man on hemodialysis exhibited fever, rash, and elevated eosinophils. Despite medication changes and consultations with specialists, his condition persisted. A drug‐induced lymphocyte stimulation test revealed a positive response to the dialysis membrane. His symptoms and lab results met DRESS syndrome diagnostic criteria. After substituting the membrane and administering glucocorticoids, the patient displayed early improvement. Diagnosing DRESS syndrome is complex due to its varied presentation and lack of specific benchmarks. This instance underscores the need to consider medical devices as potential DRESS syndrome triggers. Enhanced physician awareness can facilitate prompt detection and proper management, ultimately refining patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Our aim is to investigate cardiovascular risk factors, chronic graft-versus-host disease (CGvHD), and vitamin D metabolism in very long-term survivors of adult allogeneic stem cell transplantation (alloSCT). Methods: This study is a prospective unicentric, non-interventional trial. The detailed study protocol is available via the WHO Clinical Trial Registry. Results: We were able to include 33 patients with a mean age of 60.5 years (SD 11.1). Acute myeloid leukemia (AML) was the most frequent underlying disease (n = 12; 36.4%). The median survival time was 9.0 years (IQR 8.5–13.0). Relevant cardiovascular risk factors in the study population are the body mass index, cholesterol, LDL cholesterol, and lipoprotein(a). Cardiovascular risk factors have no significant impact on HRQoL. CGvHD of the skin as a limited disease was present in six patients (18.2%), and it has no impact on HRQoL. CGvHD was significantly associated with eosinophilia in peripheral blood (p = 0.003). Three patients (9.1%) had a shortage of calcitriol, and one patient (3.0%) took calcium substitution. The shortage is significantly associated with increased infection rates (p = 0.038). Conclusions: Cardiovascular risk factors and CGvHD need to be closely monitored. Eosinophilia might be a good and convenient monitoring parameter for CGvHD. [ABSTRACT FROM AUTHOR]

Background: Studies involving chronic rhinosinusitis with nasal polyps (CRSwNP) have mostly focused on bilateral cases, making unilateral CRSwNP inadequately recognized. This study examined the differences in clinical characteristics, outcomes, and risk factors for poor outcomes between unilateral and bilateral CRSwNP to facilitate a better assessment in the two groups. Methods: Demographic information, tissue and blood cells, endoscopic scores, Lund‐Mackay scores, recurrence rates, and disease control conditions were compared between 310 unilateral and 596 bilateral CRSwNP patients. Furthermore, the stepwise regression multivariate Cox proportional hazard models were performed to generate risk factors for poor outcomes in the two groups. Results: Bilateral cases exhibited higher rates of smoking, AR, and asthma comorbidities, along with higher numbers of tissue eosinophils and blood inflammatory cells when compared to unilateral patients. Endoscopic nasal polyp score, total computed tomography (CT) score (with scores for each sinus cavity), and adjusted CT scores were significantly higher in the bilateral group, except for a markedly higher adjusted maxillary score in the unilateral group. Furthermore, significantly higher proportions of bilateral patients experienced nasal polyp recurrence, uncontrolled status, and most disease control‐related symptoms at follow‐up. The primary risk factors for poor outcomes were asthma, tissue eosinophils, and total CT score in the bilateral group and blood basophils in the unilateral group. Conclusions: Bilateral CRSwNP patients experience worse disease severity and outcomes than their unilateral counterparts. Primarily, asthma, tissue eosinophils, and total CT score were risk factors for poor outcomes in bilateral CRSwNP patients, with blood basophils in unilateral cases. [ABSTRACT FROM AUTHOR]

Angiolymphoid hyperplasia with eosinophilia (ALHE) is a benign vascular proliferative condition, typically presenting as subcutaneous nodules in the head and neck region of middle‐aged women. Kimura disease (KD) is a benign condition that presents with subcutaneous nodules in a similar distribution with lymphadenopathy and eosinophilia, typically in Asian adult males. These diseases are often discussed together, including whether they exist on a spectrum or if they represent separate disease entities. Both are very rare in the pediatric population; in this report we highlight the case of a 10‐year‐old Caucasian male presenting with ALHE and KD. [ABSTRACT FROM AUTHOR]

Background/Aim. The cause of eosinophilia often remains unelucidated. The aim of the study was to analyze causes and treatment approaches in children with eosinophilia in pediatric tertiary care hospital. Methods. The medical records of children investigated for eosinophilia (based on the International Classification of Diseases code D72.1) were retrospectively reviewed in the University Children's Hospital, Belgrade, Serbia, from December 2011 to December 2022. A total of 105 children (62 boys; male:female ratio was 1:4) aged one month to 16.5 years (median 7.7 years) were diagnosed with eosinophilia. After excluding 15 of them due to incorrectly assigned diagnosis based on relative eosinophil number only, the remaining 90 children were grouped according to the severity of eosinophilia (mild, moderate or severe). Results. Serological analysis confirmed toxocariasis in six (6.7%) patients, while two (2.2%) had a confirmed nematode infestation (Ascaris lumbricoides and Enterobius vermicularis, respectively). Thirty-two (35.6%) children with eosinophilia and three with no true eosinophilia were diagnosed with helminthiasis ex juvantibus. Eosinophilia was ultimately explained by allergic/atopic conditions [19 (21.1%)], drug reactions [four (4.4%)], bacterial infections [nine (8.9%)], hematological problems [five (5.5%)], autoimmune disorders [three (3.3%)], unrelated congenital disorders (one), or as an isolated finding [seven (7.8%)]. In addition, one of the children without an increased absolute eosinophil number was diagnosed with eosinophilic esophagitis. A total of 56 (53.3%) children received anthelminthic treatment: 9 (90.0%) with severe eosinophilia, 19 (51.4%) with moderate, 23 (53.5%) with mild, and 5 (33.3%) children with no true eosinophilia. Most (42) of the children were given mebendazole only, while the remaining 14 (eight with severe, three with moderate, and three with mild) were also initially treated with mebendazole but subsequently shifted to albendazole due to the persistence of eosinophilia. In all treated children, eosinophilia and other relevant findings (if any) subsided in a matter of a few days to a few weeks after initializing treatment. Conclusion. Our results support the recommendation that unexplained eosinophilia of all levels of severity requires a standardized diagnostic approach. The results also provide some support for a potential rational basis for ex juvantibus administration of anthelminthic drugs in a fraction of children with eosinophilia without an obvious etiological explanation. [ABSTRACT FROM AUTHOR]