Eosinophilic gastrointestinal disorders (EGIDs) are a group of conditions characterized by an abnormal accumulation of eosinophils in the gastrointestinal tract, leading to inflammation and tissue damage. Regulatory cells are a subset of immune cells that are crucial in maintaining the balance of the immune system and preventing the occurrence of autoimmune diseases. In EGIDs, regulatory cells are believed to play a key role in controlling the immune response and overseeing the growth and activation of eosinophils in the gastrointestinal tract. There is evidence indicating that regulatory T cells (Tregs) and regulatory eosinophils may play a role in suppressing the inflammatory response in EGIDs. Regulatory eosinophils are a subgroup of eosinophils that possess an anti-inflammatory role. Recent studies have shown that enhancing the number or effectiveness of regulatory eosinophils can reduce the severity of EGIDs. Regulatory eosinophils dampen inflammation through their regulatory mediators, such as galectin-10 and growth factor beta (TGF-β), which promote Treg expansion and inhibit effector T cell function. Further research on regulatory cells in EGIDs may have significant implications for the advancement of novel therapies for these uncommon and intricate disorders. The aim of this review is to provide complete view of the immune responses connected to EGIDs, examine the regulatory cells that control these responses, and evaluate their potential as therapeutic targets for EGID treatment.

Hypereosinophilia is a rare condition, defined as a persistent elevation of absolute eosinophil count greater than 1.5x109/L and/or tissue eosinophilia. This condition can be caused by numerous different etiologies, both hematological (clonal) and non-hematological (reactive). Reactive hypereosinophilia encompasses all disorders, including infections. Patients with hypereosinophilia may experience a spectrum of clinical consequences due to multiple organ damage, including neurologic and thrombotic complications, associated with organ dysfunction and potentially life-threatening sequelae. Cerebral venous thrombosis (CVT) is the term used to describe thrombotic occlusion of veins and/or venous sinuses in the brain. This condition can occur at all ages and CVT related to hypereosinophilia is a rare disease. Diagnosis of the disease must be done quickly because thrombosis causes blockage of cerebral drainage, venous congestion, disruption of cerebrospinal fluid reabsorption, ischemic neuronal damage, cerebral edema, and hemorrhage, leading to severe neurological complications. Management of intracranial hemorrhage from CVT due to hypereosinophilia is a challenging task for clinicians, based on anticoagulation therapy, systemic corticosteroid, management of elevated intracranial pressure, and potentially progressive hemorrhage due to anticoagulant. The outcome of the patient generally relies on early detection, prompt, and appropriate treatment. In this case report, we discuss a rare case of CVT with hypereosinophilia and positive dengue serology in a child, in the context of intracranial hemorrhage, enlightening the importance of considering a personalized strategy in the management of this complex scenario.

UNASSIGNED: Eosinophilia is frequent in pediatrics and concerns regarding its etiology are often raised. Pediculosis capitis is a common ectoparasitic disease in children but is not traditionally associated with changes in laboratory parameters.
UNASSIGNED: We present the case of a healthy, 9-year-old girl who presented with abdominal pain and a history of loose stools (2-3) in the preceding week. Laboratory investigations showed leukocytosis with significant eosinophilia. A thorough investigation concerning the most common causes of eosinophilia was negative. Detailed physical examination and history revealed a persistent scalp infestation with head lice. Successful pediculosis management coincided with the gradual resolution of eosinophilia without recurrence until the most recent follow-up visit twelve months later.
UNASSIGNED: The presented case indicates a possible association between eosinophilia and pediculosis capitis, which was not previously displayed, but also highlights the importance of detailed history and clinical examination. Research focusing on the systematic effects of pediculosis capitis in children could clarify whether it can represent a frank cause of eosinophilia. HIPPOKRATIA 2023, 27 (2):112-114.

UNASSIGNED: Hepatobiliary fascioliasis has two phases, each requiring specific management approaches. Triclabendazole has been widely effective in treating the two phases of clinical fascioliasis and endoscopic retrograde cholangiopancreatography (ERCP) in the biliary phase. We aimed to characterize presentations of hepatobiliary fascioliasis and highlight the role of ERCP in management.
UNASSIGNED: This retrospective cohort includes patients diagnosed with clinical hepatobiliary fascioliasis between January 2013 and December 2022. Demographic data, clinical presentation, laboratory and radiological investigations, treatment, and endoscopy reports were collected from the records of 62 participants. Patients were divided into two groups: acute hepatic and chronic biliary phases.
UNASSIGNED: Thirty-six patients were in the biliary phase, and 26 were in the hepatic phase. All patients were from rural areas, and females were predominant (76%). Hypereosinophilia was detected in 92% of acute cases and 58% of chronic biliary cases. In chronic biliary cases, the levels of liver biochemicals, including alanine transaminase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), and bilirubin, were higher at levels of 189 ± 76, 127 ± 47, 268 ± 77, and 2.4 ± 0.7 respectively, compared to acute hepatic cases, 35.6 ± 8.2, 32.7 ± 4.3, 69.2 ± 45.45, and 0.58 ± 0.01. The corresponding P-values were 0.003, 0.001, <0.001, and <0.001, respectively. Triclabendazole effectively cured 93.5% of patients and was used in combination with ERCP in biliary-phase cases where the fluke was extracted from the biliary system in 34 patients (94.4%). Three patients (8.8%) were diagnosed with post-ERCP pancreatitis. None of the patients experienced bleeding, perforation, or required biliary stenting.
UNASSIGNED: Clinical fascioliasis could manifest in acute hepatic or chronic biliary phases. Hypereosinophilia was more evident in the hepatic phases, while ALT, AST, GGT, and bilirubin were higher in the biliary phase. Triclabendazole is effective in the hepatic phase and when combined with ERCP in the biliary phase. ERCP is highly effective for relieving obstruction and treating biliary fascioliasis.

BACKGROUND: Hypereosinophilic syndrome can produce cardiac involvement and endomyocardial fibrosis, which have a poor prognosis. However, there is limited information regarding cardiac involvement among migrants from Latin America with eosinophilia related to helminthiasis.
METHODS: We conducted a pilot observational study where an echocardiography was performed on migrants from Latin America with both eosinophilia (>450 cells/μL) and a diagnosis of helminth infection, and on migrants from Latin America without eosinophilia or helminth infection. Microbiological techniques included a stool microscopic examination using the Ritchie\'s formalin-ether technique, and a specific serology to detect Strongyloides stercoralis antibodies.
RESULTS: 37 participants were included, 20 with eosinophilia and 17 without eosinophilia. Twenty (54.1%) were men with a mean age of 41.3 (SD 14.3) years. Helminthic infections diagnosed in the group with eosinophilia were: 17 cases of S. stercoralis infection, 1 case of hookworm infection, and 2 cases of S. stercoralis and hookworm coinfection. Among participants with eosinophilia, echocardiographic findings revealed a greater right ventricle thickness (p = 0.001) and left atrial area and volume index (p = 0.003 and p = 0.004, respectively), while showing a lower left atrial strain (p = 0.006) and E-wave deceleration time (p = 0.008). An increase was shown in both posterior and anterior mitral leaflet thickness (p = 0.0014 and p = 0.004, respectively) when compared with participants without eosinophilia.
CONCLUSIONS: Migrants from Latin America with eosinophilia related to helminthic infections might present incipient echocardiographic alterations suggestive of early diastolic dysfunction, that could be related to eosinophilia-induced changes in the endomyocardium.

BACKGROUND: Eosinophilic solid and cystic renal cell carcinoma (ESC-RCC) is a novel subtype of renal cell carcinoma characterized by its relatively low incidence and indolent behavior. We report a rare case of ESC-RCC concurrent with clear cell renal cell carcinoma (ccRCC) in a single kidney.
METHODS: A 48-year-old male, was found to have a mixed echogenic mass in the left kidney during a physical examination. He has no history of hematuria and flank pain. An abdominal CT scan revealed a 3.0 * 1.9 * 2.5 cm3 mass with unclearly bordered at the lower pole of the left kidney. Abdominal MRI showed two nodules of different sizes in the left kidney, suggesting the possibility of a tumor. The patient underwent a subtotal nephrectomy, and the postoperative pathological results indicated ESC-RCC combined with ccRCC. The patient recovered well without tumor recurrence during the 12-month follow-up.
CONCLUSIONS: We reported a case of renal composite tumors, comprising the rare ESC-RCC and the more common ccRCC. Imaging combined with postoperative pathological examination is crucial for the definitive diagnosis of these rare tumors.

In recent decades, it has become clear that allergic diseases are on the rise in both Western and developing countries. The exact reason for the increase in prevalence has not been conclusively clarified yet. Multidimensional approaches are suspected in which diet and nutrition seem to play a particularly important role. Allergic diseases are characterized by a hyper-reactive immune system to usually harmless allergens, leading to chronic inflammatory diseases comprising respiratory diseases like asthma and allergic rhinitis (AR), allergic skin diseases like atopic dermatitis (AD), and food allergies. There is evidence that diet can have a positive or negative influence on both the development and severity of allergic diseases. In particular, the intake of the essential trace element zinc plays a very important role in modulating the immune response, which was first demonstrated around 60 years ago. The most prevalent type I allergies are mainly based on altered immunoglobulin (Ig)E and T helper (Th)2 cytokine production, leading to type 2 inflammation. This immune status can also be observed during zinc deficiency and can be positively influenced by zinc supplementation. The underlying immunological mechanisms are very complex and multidimensional. Since zinc supplements vary in dose and bioavailability, and clinical trials often differ in design and structure, different results can be observed. Therefore, different results are not surprising. However, the current literature suggests a link between zinc deficiency and the development of allergies, and shows positive effects of zinc supplementation on modulating the immune system and reducing allergic symptoms, which are discussed in more detail in this review.

UNASSIGNED: Achieving disease control is the goal of asthma management. Serum or sputum eosinophil counts have been known traditional means of assessing eosinophilic airway inflammation in asthma, which is vital in predicting response to corticosteroid therapy which ultimately promotes control of the disease. Evidence suggests that fraction of exhaled nitric oxide (FeNO) may be a more useful non-invasive surrogate biomarker for the assessment of eosinophilic airway inflammation and could help with the timely adjustment of inhaled corticosteroid therapy in the uncontrolled asthma patient. The relationship between FeNO and other markers of airway inflammation has been variable in literature, with limited data in sub-Saharan Africa where FeNO testing is very sparse. We sought to define the relationship between FeNO levels, serum eosinophil counts, spirometry measures and symptom control among asthma patients.
UNASSIGNED: The study was conducted at the Asthma Clinic of a large tertiary hospital. This study included 82 patients with physician-diagnosed asthma being regularly managed at the clinic. All participants were taken through the asthma control test (ACT), had FeNO and spirometry measurements taken according to the American Thoracic Society (ATS) guidelines. Blood samples were obtained from all participants for serum eosinophil counts. Correlation coefficient was used to ascertain the relationship between FeNO levels and serum eosinophil counts, ACT scores, and spirometry measurements. Logistic regression was used to examine the association between high FeNO and abnormal FEV1 percentage predicted (<80%) with adjustments for age, sex, and BMI.
UNASSIGNED: A total of 82 patients with asthma were included in the study, with higher prevalence of females (72%). Majority (40.2%) of the patients were found in the 60 and above age category. The median FeNO level and ACT score was 42.00 (26.00-52.50) parts per billion (ppb) and 20.0 (18-23) respectively. The median serum eosinophil counts was 0.25(0.90-0.38) × 109/L. The median FeNO levels were significantly higher in patients with partly and very poorly controlled asthma than in the well-controlled group (p < 0.001). A total of 47(57%) of the patients were classified as having well controlled asthma and 35 (42%) uncontrolled. FeNO correlated with serum eosinophil counts (r = 0.450, p < 0.001), ACT (r = -0.648, p < 0.001), and FEV1 percentage predicted (r = -0.353, p = 0.001). High FeNO (>50 ppb) was associated with an over fivefold increased risk of having an abnormal FEV1 percentage predicted.
UNASSIGNED: FeNO levels significantly correlated with the ACT scores, serum eosinophil counts and FEV1% predicted among the asthma patients who were on inhaled corticosteroid therapy. High FeNO was significantly associated with abnormal FEV1 percentage predicted. We suggest that the point of care assessment of FeNO is a reliable marker of eosinophilic inflammation in our cohort of patients and together with \'ACT scores\' in our asthma clinics could increase asthma control rates.

BACKGROUND: Loiasis is one of the significant filarial diseases for people living in West and Central Africa with wide endemic area but is not seen in China. As economy booms and international traveling increase, China faces more and more imported parasitic diseases that are not endemic locally. Loiasis is one of the parasitic diseases that enter China by travelers infected in Africa. The better understanding of the clinical and laboratory features of loa loa infection will facilitate the diagnosis and treatment of loiasis in China.
METHODS: The study targeted travelers who were infected with L. loa in endemic Africa regions and returned to Beijing between 2014 and 2023. Epidemiological, clinical, and biological data as well as treatment of these patients were collected.
RESULTS: Total 21 cases were identified as L. loa infection based on their typical clinical manifestations and parasite finding. All cases had a history of travel to Africa for more than 6 months, most of them are the construction workers dispatched to West Africa with outdoor activities. Calabar swelling (n = 19; 90.5%) and pruritus (n = 11; 52.4%) were among the most common clinical symptoms followed by muscle pain (n = 7; 33.3%) and skin rash (n = 2; 9.5%). The adult worms were observed in the eyelid or subconjunctiva (n = 2; 9.5%) and subcutaneous tissues (n = 2; 9.5%). Although all patients presented with a high eosinophil count (> 0.52 × 109/L), only two cases displayed microfilariae in fresh venous blood and positive for filarial antigen. A cut section of adult worm was observed through biopsy on a skin nodule surrounded by lymphocytes, plasma cells and eosinophils. All subjects were positive in PCR targeting L. loa ITS-1. The constructed phylogenetic tree based on the amplified ITS-1 sequences identified their genetical relation to the L. Loa from Africa. All patients treated with albendazole and diethylcarbamazine were recovered without relapse.
CONCLUSIONS: This study provides useful information and guideline for physicians and researchers in non-endemic countries to diagnose and treat loiasis and L. loa infections acquired from endemic regions.

Current treatments of eosinophilic chronic rhinosinusitis (ECRS) involve corticosteroids with various adverse effects and costly therapies such as dupilumab, highlighting the need for improved treatments. However, because of the lack of a proper mouse ECRS model that recapitulates human ECRS, molecular mechanisms underlying this disease are incompletely understood. ECRS is often associated with aspirin-induced asthma, suggesting that dysregulation of lipid mediators in the nasal mucosa may underlie ECRS pathology. We herein found that the expression of microsomal PGE synthase-1 (encoded by PTGES) was significantly lower in the nasal mucosa of ECRS patients than that of non-ECRS subjects. Histological, transcriptional, and lipidomics analyses of Ptges-deficient mice revealed that defective PGE2 biosynthesis facilitated eosinophil recruitment into the nasal mucosa, elevated expression of type-2 cytokines and chemokines, and increased pro-allergic and decreased anti-allergic lipid mediators following challenges with Aspergillus protease and ovalbumin. A nasal spray containing agonists for the PGE2 receptor EP2 or EP4, including omidenepag isopropyl that has been clinically used for treatment of glaucoma, markedly reduced intranasal eosinophil infiltration in Ptges-deficient mice. These results suggest that the present model using Ptges-deficient mice is more relevant to human ECRS than are previously reported models and that eosinophilic inflammation in the nasal mucosa can be efficiently blocked by activation of the PGE2-EP2 pathway. Furthermore, our findings suggest that drug repositioning of omidenepag isopropyl may be useful for treatment of patients with ECRS.