Paragonimiasis is a zoonotic disease caused by trematodes belonging to the genus Paragonimus. It is acquired by ingesting freshwater crustaceans or raw game meat. Here, we report two patients (a couple) who developed paragonimiasis and pulmonary lesions with peripheral eosinophilia after sharing and consuming previously frozen freshwater crabs (Eriocheir japonica) together at the same restaurant in Tokyo. One patient developed peripheral airspace consolidation, which was initially misdiagnosed as chronic eosinophilic pneumonia, whereas the other exhibited eosinophilic pleural effusion. Antiparasitic antibody testing of serum using enzyme-linked immunosorbent assay (ELISA) established a diagnosis of paragonimiasis. Both cases were effectively treated with praziquantel. These cases demonstrate that frozen freshwater crabs remain a potential source of paragonimiasis, underscoring the critical role of dietary history in patients with eosinophilic lung diseases.

Marine seafood-derived anisakid nematodes (e.g., Anisakis spp. and Phocanema spp. [formerly Pseudoterranova spp.]) may cause gastrointestinal and allergic manifestations. Here, we report an unusual case of persistent, asymptomatic peripheral eosinophilia following ingestion of raw or lightly marinated seafood, raising the possibility of subclinical antigenic stimulation. The patient remained entirely asymptomatic with normal total IgE levels, and parasite serology (including Angiostrongylus cantonensis IgG) was negative, yet developed marked eosinophilia. The patient had a childhood history of allergic diseases that fully resolved in adulthood, which may represent an immunologic background relevant to the unusual presentation of marked eosinophilia with persistently normal total IgE. Although the underlying mechanism could not be directly demonstrated, this pattern raises the possibility of a predominantly eosinophil-associated type 2 response without a prominent humoral allergic manifestation. The eosinophil count remained persistently elevated over several months and stayed markedly above the adult upper reference limit before treatment, while comprehensive evaluations for parasitic infection, infectious disease, and autoimmune conditions were negative. Bone marrow findings demonstrated reactive eosinophilic hyperplasia, and imaging studies were unremarkable. Following empiric albendazole therapy, the eosinophil count rapidly returned to normal. This temporal association was supportive of, but not diagnostic for, a parasite-related or antigen-mediated trigger in this otherwise unexplained case. This observation aligns with the latest UK Guideline for the Investigation and Management of Eosinophilia, which recommends considering empiric anthelmintic therapy in asymptomatic patients without an identifiable cause. This case suggests that in patients with otherwise unexplained asymptomatic eosinophilia, even a remote and limited history of consuming raw or lightly marinated seafood should not be overlooked during history taking, and that empiric anthelmintic therapy may offer practical diagnostic and therapeutic value in selected cases.

Cystic fibrosis-asthmaoverlap syndrome (CFAOS) has high incidence in people with CF (pwCF) yet remains poorly defined, hindering both diagnosis and treatment. Asthmatic type2 (T2) inflammation (eosinophilia, elevated IgE, and increased IL-4/IL-5/IL-13), identifies an endo type within the CF community with accelerated disease progression and increased mortality. However, diagnostic criteria for asthma in the general population are less useful inpwCF due to overlapping phenotypes generated by chronic inflammation and structural lung disease. Therapeutically, the lack of standardized CFAOS diagnostic criteria has led to the heterogenous use of asthma-directed therapies, with inconsistent benefits.

Asthma and chronic obstructive pulmonary disease (COPD) are the most prevalent chronic inflammatory airway diseases worldwide, significantly affecting patients' quality of life and mortality and imposing a substantial socioeconomic burden. Increasing insights into their pathophysiology have led to the recognition of both conditions as complex syndromes encompassing distinct pheno-endotypes. Asthma patients can be broadly stratified into type 2 (T2)-high and T2-low phenotypes based on biomarker expression and clinical features. More than half of asthma patients exhibit a T2-high phenotype, which includes two principal endotypes: allergic eosinophilic and non-allergic eosinophilic asthma. In COPD, traditionally associated with type 1 and type 3 immune responses and neutrophilic inflammation, around 20-30% of patients display a marked T2 signature, defining a novel T2-COPD endotype. In both diseases, epithelial and innate immune cells cooperate to orchestrate adaptive and effector T2 responses characterized by blood and airway eosinophilia and elevated fractional exhaled nitric oxide (FeNO). In asthma, 6 biologics targeting key T2 inflammatory pathways are approved as add-on treatment (omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab and tezepelumab). In T2 COPD, 2 biologics have recently been approved (dupilumab and mepolizumab) and others are under clinical evaluation. Other emerging strategies, including next-generation allergen-specific immunotherapy and trained immunity-based vaccines, offer promising new therapeutic avenues. A better understanding of the molecular mechanisms driving T2-high asthma and T2 COPD endotypes is essential to identify reliable biomarkers and novel therapeutic targets. Such advances will improve patient stratification, optimize disease management, and foster the development of preventive and precision medicine approaches in chronic airway diseases.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare but potentially life-threatening drug-induced hypersensitivity reaction characterized by delayed onset and variable multi-organ involvement, which can complicate timely diagnosis. We report the case of a 75-year-old female who developed fever, generalized pruritic maculopapular rash, facial edema, lymphadenopathy, and acute kidney injury 10 days after completing a one-week course of amoxicillin-clavulanate for a respiratory infection. Laboratory evaluation revealed leukocytosis with neutrophilia, mild eosinophilia not meeting diagnostic threshold criteria, acute kidney injury with proteinuria and hematuria, and isolated cholestatic liver injury without significant ALT or AST elevation; atypical lymphocytosis was absent. Autoimmune serology and viral hepatitis screening were negative. Based on the RegiSCAR scoring system, the patient achieved a score of 7, consistent with a definite diagnosis of DRESS. Systemic corticosteroid therapy, alongside adjunctive topical treatment and antihistamines, led to progressive clinical and laboratory improvement. This case represents an atypical presentation of DRESS with predominantly renal involvement and isolated cholestatic liver injury, where the absence of typical hematologic manifestations posed a diagnostic challenge. Although viral reactivation, particularly HHV-6, is often implicated in DRESS pathogenesis, its role here remains unconfirmed due to the lack of virological testing. The case highlights the importance of considering DRESS in patients with delayed-onset cutaneous eruptions and unexplained acute kidney injury after drug exposure, even in the absence of classic hematologic features, as early recognition and appropriate management are crucial for favorable outcomes.

Clozapine remains an unparalleled antipsychotic nearly seven decades after its synthesis, distinguished by superior efficacy in treatment-resistant schizophrenia and a unique anti-suicidal effect, alongside a complex profile of adverse events and persistent underutilization. Traditional explanations based on receptor-binding broad variety and active metabolites fail to fully account for its singular clinical impact, particularly given that other compounds share similarly broad pharmacodynamics profiles without comparable efficacy. This editorial proposes that clozapine's three-dimensional molecular geometry represents a critical, yet underexplored, determinant of its biological activity. Beyond receptor affinity tables, clozapine's tricyclic dibenzazepine scaffold, subtle non-planarity, flexible substituents, and electronic distribution appear to enable qualitatively distinct interactions with neurotransmitter receptors, immune pathways, and intracellular signaling systems. Structural analyses seem to suggest that clozapine preferentially exploits less polar binding pockets and stabilizes unique receptor conformations, potentially facilitating biased signaling and modulation of receptor heteromers. These geometric properties may also underpin idiosyncratic immune-mediated adverse reactions, such as drug reaction with eosinophilia and systemic symptoms syndrome, linking therapeutic efficacy and toxicity through shared structural determinants. The overlap of clozapine's chemical scaffold with antiseizure medications and tricyclic antidepressants further supports the relevance of molecular architecture in shaping both pharmacological and immunological outcomes. Reframing clozapine as a structurally complex, biologically polyvalent molecule, rather than a collection of receptor targets, may resolve longstanding uncertainties surrounding its mechanism of action. Emphasizing molecular geometry may inform a new paradigm in psychiatric drug development, prioritizing structural complexity and multidimensional biological engagement over narrow target selectivity.

Enterobius vermicularis is a common intestinal helminth, whereas extraintestinal disease is rare and may present as a tumor-like lesion. We report a 50-year-old man with common variable immunodeficiency (CVID) and prior right hemicolectomy with adjuvant chemotherapy for cecal adenocarcinoma (pT3N1bM0) who developed a slowly enlarging left-sided cervical mass during oncologic follow-up. The lesion was painless and showed no overlying skin changes. Neck ultrasonography demonstrated a hypoechoic, round mass over the sternothyroid muscle with an elongated hyperechoic compartment and no Doppler flow. Surgical excision was performed; macroscopy suggested a lymph node. Histopathology excluded malignancy and unexpectedly revealed adult Enterobius vermicularis containing eggs embedded within inflammatory stroma. C-reactive protein was mildly elevated without leukocytosis or eosinophilia. Stool examination was negative. Whole-body MRI revealed no other extraintestinal foci. Albendazole was administered in two doses separated by two weeks with clinical resolution; the patient remains under outpatient surveillance. This case highlights that ectopic enterobiasis can mimic cervical lymphadenopathy and metastatic disease, particularly in immunocompromised patients, and that histopathology is critical for diagnosis and management.

Background and objective Vitamin D contributes to immune regulation and the control of inflammatory signaling. Deficient vitamin D status has been linked to greater systemic inflammatory activity, but its relationship with routinely used clinical markers such as erythrocyte sedimentation rate (ESR) and absolute eosinophil count (AEC) remains insufficiently characterized. The objective of this study is to assess whether low vitamin D status is associated with elevated ESR and eosinophilia in an internal medicine outpatient population. Methods This retrospective cross-sectional study included 200 patients evaluated at the Internal Medicine Clinic of Al-Ahli Hospital, Doha, Qatar, between January 1, 2022, and April 1, 2026. Participants were assigned to two equal groups according to serum 25-hydroxyvitamin D level: low vitamin D (n = 100) and normal (n = 100). For the purposes of this study, low vitamin D status was defined as serum 25-hydroxyvitamin D <30 ng/mL, combining deficiency and insufficiency categories, while normal vitamin D status was defined as 30-100 ng/mL. Elevated ESR was determined using age- and sex-specific thresholds, and eosinophilia was defined as an AEC >0.5 × 10⁹/L. Categorical comparisons were performed with Fisher's exact test. Results Vitamin D deficiency was associated with a higher prevalence of elevated ESR, identified in 23% of the low vitamin D group compared with 10% of the normal vitamin D group (relative risk (RR) 2.3; p = 0.021). Eosinophilia was also more frequent in the low vitamin D group, observed in 14% of patients versus 4% in those with normal vitamin D status (RR 3.5; p < 0.05). These findings demonstrate a significant association between low vitamin D levels and increased systemic inflammatory activity. Additionally, the higher prevalence of eosinophilia suggests a potential link between vitamin D deficiency and immune dysregulation. Conclusions Low vitamin D status was significantly associated with elevated ESR, supporting an association with systemic inflammatory activity. Eosinophilia was more frequent in the low vitamin D group, and this difference was statistically significant. Overall, these findings suggest that low vitamin D status may accompany broader inflammatory and immunologic imbalance.