Massive Eosinophilic Infiltration Research Articles

Eosinophilic esophagitis in children: Experience in diagnosis, clinical observation in a multidisciplinary hospital

This study presented the characteristics of seven patients with eosinophilic esophagitis from age 1 year and 2 months to age 17 years and 4 months. The follow-up duration ranged from 1 to 7.5 years.
 Disease onset was observed at different ages: aged 2 years (n=6) and 2 months (n=1). The period between the occurrences of the first symptom to diagnosis ranged from 3 months to 9 years. In one patient, the symptoms were associated with cows milk allergy, whereas the cause was not identified in other cases. Allergic diseases (i.e., atopic dermatitis, allergic rhinitis, and asthma) were observed in six patients.
 Treatment was provided according to the clinical guidelines. Six patients were prescribed topical steroids (budesonide) and an empirical elimination diet. One patient was prescribed only with an empirical elimination diet due to the steroid phobia of the parents. However, the ineffectiveness of the diet was the basis for topical steroid prescription. During the follow-up, a relapse was observed in two patients who required repeated treatments.
 A clinical case of eosinophilic esophagitis in a 6-year-old child, with 7.5 years of follow-up, was described. According to the anamnesis, the patient visited a gastroenterologist 4 years after the onset of dysphagia symptoms. Endoscopy revealed cicatricial stenosis of the upper third of the esophagus (grades 23). A morphological study of the esophageal mucosa, which was performed after repeated endoscopic bougienage and a 5-month course of antisecretory therapy was deemed ineffective, revealed massive eosinophilic infiltration. Eosinophilic esophagitis was confirmed based on the anamnesis, clinical symptoms, and endoscopic and morphological data. An elimination diet and topical corticosteroids (budesonide) were prescribed. Following the treatment, the patient showed significant improvements. Subsequently, during the follow-up, a relapse of eosinophilic esophagitis was diagnosed twice (with an interval of 2.3 and 2.5 years), which required topical steroids (case 1) and proton pump inhibitors (case 2).
 This paper highlights the importance of a multidisciplinary approach, involving an allergist-immunologist, pediatrician, gastroenterologist, endoscopist, and pathologist, in the management of eosinophilic esophagitis in children.

Macrophage Migration Inhibitory Factor in Psoroptes ovis: Molecular Characterization and Potential Role in Eosinophil Accumulation of Skin in Rabbit and Its Implication in the Host-Parasite Interaction.

Psoroptes ovis, a common surface-living mite of domestic and wild animals worldwide, results in huge economic losses and serious welfare issues in the animal industry. P. ovis infestation rapidly causes massive eosinophil infiltration in skin lesions, and increasing research revealed that eosinophils might play an important role in the pathogenesis of P. ovis infestation. Intradermal injection of P. ovis antigen invoked massive eosinophil infiltration, suggesting that this mite should contain some relative molecules involved in eosinophil accumulation in the skin. However, these active molecules have not yet been identified. Herein, we identified macrophage migration inhibitor factor (MIF) in P. ovis (PsoMIF) using bioinformatics and molecular biology methods. Sequence analyses revealed that PsoMIF appeared with high similarity to the topology of monomer and trimer formation with host MIF (RMSD = 0.28 angstroms and 2.826 angstroms, respectively) but with differences in tautomerase and thiol-protein oxidoreductase active sites. Reverse transcription PCR analysis (qRT-PCR) results showed that PsoMIF was expressed throughout all the developmental stages of P. ovis, particularly with the highest expression in female mites. Immunolocalization revealed that MIF protein located in the ovary and oviduct of female mites and also localized throughout the stratum spinosum, stratum granulosum, and even basal layers of the epidermis in skin lesions caused by P. ovis. rPsoMIF significantly upregulated eosinophil-related gene expression both in vitro (PBMC: CCL5, CCL11; HaCaT: IL-3, IL-4, IL-5, CCL5, CCL11) and in vivo (rabbit: IL-5, CCL5, CCL11, P-selectin, ICAM-1). Moreover, rPsoMIF could induce cutaneous eosinophil accumulation in a rabbit model and increased the vascular permeability in a mouse model. Our findings indicated that PsoMIF served as one of the key molecules contributing to skin eosinophil accumulation in P. ovis infection of rabbits.

Tolerability and safety of a new elimination diet for pediatric eosinophilic gastritis and duodenitis

BackgroundNon-esophageal eosinophilic gastrointestinal disorders (non-EoE EGIDs) are chronic inflammatory disorders with massive infiltration of eosinophils into the gastrointestinal tract. Food elimination diets are potentially effective treatments. But the existing dietary therapies have various weak points. We developed a new regimen to compensate for the shortcomings of the elemental diet and 6-food elimination diet. The new regimen consists of an amino-acid-based formula, potatoes, vegetables, fruits and restricted seasonings. We named it the “Rainbow Elimination Diet (ED).” The aims of this study were to evaluate the tolerability and safety of this diet. MethodsA retrospective medical record examination was conducted at the National Center for Child Health and Development covering the period from January 2010 through December 2018. The medical records of patients (age 2–17 y) with histologically diagnosed non-EoE EGIDs were reviewed. The tolerability, nutritional intake, symptoms, and blood test findings were evaluated. ResultsNineteen patients were offered several kinds of food-elimination diets. Seven patients (eosinophilic gastritis: 5; gastroenteritis: 1; duodenitis: 1) were treated with Rainbow ED. Six patients were compliant with this diet. The median duration of the diet induction phase was 15 days (range 14–30). All 5 patients who had had symptoms just before the induction phase became symptom-free. The body weight decreased in 5 patients (median −0.6 kg), probably because the serum protein increased, resulting in reduced edema. All 5 patients with hypoproteinemia had elevated serum albumin (median 2.9–3.5 g/dL). The ingested nutritional elements were calculated, and most of them were sufficient, except for fat and selenium. ConclusionsThe Rainbow ED was well-tolerated and safe for pediatric non-EoE EGIDs.

Comprehensive analysis of metabolic pathway activity subtypes derived prognostic signature in hepatocellular carcinoma.

Metabolic reprogramming is one of the hallmarks of cancer, but metabolic pathway activity-related subtypes of hepatocellular carcinoma (HCC) have not been identified. Based on the quantification results of 41 metabolic pathway activities by gene set variation analysis, the training cohort (n=609, merged by TCGA and GSE14520) was clustered into three subtypes (C1, C2, and C3) with the nonnegative matrix factorization method. Totally 1371 differentially expressed genes among C1, C2, and C3 were identified, and an 8-gene risk score was established by univariable Cox regression analysis, least absolute shrinkage and selection operator method, and multivariable Cox regression analysis. C1 had the strongest metabolic activity, good prognosis, the highest CTNNB1 mutation rate, with massive infiltration of eosinophils and natural killer cells. C2 had the weakest metabolic activity, poor prognosis, was younger, was inclined to vascular invasion and advanced stage, had the highest TP53 mutation rate, exhibited a higher expression level of immune checkpoints, accompanied by massive infiltration of regulatory T cells. C3 had moderate metabolic activity and prognosis, the highest LRP1B mutation rate, and a higher infiltration level of neutrophils and macrophages. Internal cohorts (TCGA, n=370; GSE14520, n=239), external cohorts (ICGC, n=231; GSE116174, n=64), and clinical subgroup validation showed that the risk score was applicable for patients with diverse clinical features and was effective in predicting the prognosis and malignant progression of patients with HCC. Compared with the low-risk group, the high-risk group had a poor prognosis, enhanced cancer stem cell characteristics, activated DNA damage repair, weakened metabolic activity, cytolytic activity, and interferon response. We identified HCC subtypes from the perspective of metabolism-related pathway activity and proposed a robust prognostic signature for HCC.

Impacts of eosinophil percentage on prognosis acute type A aortic dissection patients

BackgroundEosinophils are pro-inflammatory cells involved in thrombosis and have been proposed as a prognosis marker in acute ischemic stroke and ST-elevation myocardial Infarction. Here, we sought to clarify the prognostic value of eosinophil percentage (EOS%) in patients with acute type A aortic dissection (AAAD).MethodsWe examined 183 consecutive AAAD patients. Based on the optimum cut-off value of EOS% determined by X-tile software, patients were classified into the low EOS% (EOS% ≤ 0.1) and high EOS% groups (EOS% > 0.1). We performed multivariate regression analysis and Kaplan–Meier (KM) survival curves to assess the association between EOS% and mortality. Eosinophil accumulation in aortic dissection intraluminal thrombus was confirmed using hematoxylin–eosin (H&E) staining. An external cohort from Medical Information Mart for Intensive Care IV was performed to validate the results.ResultsRelative to surviving patients, those who died during hospitalization had significantly lower EOS% (p = 0.001) but significantly higher WBC (p = 0.002) and neutrophil (p = 0.001) counts. Multivariate regression analysis identified EOS% as an independent predictor of in-hospital and 1-year mortality. KM curves revealed that 1-year cumulative mortality was significantly higher in the low EOS% group, although it was mainly attributed to the higher 30-day mortality. H&E staining revealed massive infiltration of eosinophils in all 20 thrombus specimens. The external validation confirmed that relative to survivors, patients with in-hospital mortality (p = 0.010) had significantly lower EOS%. Moreover, multivariate regression analyses identified that decreased EOS% was independently significantly associated with in-hospital mortality.ConclusionsLow EOS% is significantly related to increased mortality rates in AAAD patients.

The clinicopathologic features and differential diagnosis of ocular Kimura disease and epithelioid hemangioma

Objective: To investigate the clinicopathologic features and differential diagnosis of ocular Kimura disease (KD) and epithelioid hemangioma. Methods: It was a retrospective case series study. The data of 10 patients with ocular KD and 3 patients with ocular epithelioid hemangioma from the Pathology Department of Eye & ENT Hospital of Fudan University from January 2010 to December 2019 were retrospectively analyzed, including clinical manifestations, morphology and immunophenotypes. Results: Among patients with ocular KD, there were 9 males and 1 female with an age from 7 to 75 years (mean, 30 years). There were 6 unilateral cases and 4 bilateral cases. The disease mainly involved the orbit in 3 patients, the lacrimal gland in 5 patients and the eyelid in 2 patients. The ophthalmic presentation included a palpable periorbital or eyelid mass with eyelid swelling and ptosis, proptosis and displacement of the eyeball, and ocular dysmotility. Three patients had a history of lymphadenopathy. The disease course ranged from 6 months to 7 years (mean, 34 months). All the patients had elevated peripheral blood eosinophilia. Three patients of ocular epithelioid hemangioma were all males with age from 25 to 60 years old. They were all unilateral cases with 1 right eye and 2 left eyes. The disease respectively involved eyelid and orbit, the eyebrow skin and the inner canthus skin. They presented with eyelid swelling, orbital mass or subcutaneous nodule for 5 months to 2 years. All patients (11 eyes) with KD underwent incisional or excisional biopsy. The histopathology revealed follicular hyperplasia of lymphoid tissue with active germinal centers in orbital fibroadipose tissue. There were massive interfollicular eosinophils with eosinophilic microabscesses. Some swelling endothelial cells of proliferating vessels were seen. All the 3 patients (3 eyes) with ocular epithelioid hemangioma underwent excision of the lesions. Histopathological examination showed proliferation of small and medium blood vessels. The vessels were lined by endothelial cells with abundant eosinophilic cytoplasm which protruded into the lumen. The endothelial cells were positive for CD31, factor Ⅷ-related antigen and E26 transformation-specific related gene immunohistochemically. There was a moderate amount of lymphocytes, plasma cells and eosinophils surrounding blood vessels without eosinophilic microabscess. Conclusions: Both ocular KD and epithelioid hemangioma are more commonly seen in males and share the common histopathological features of vascular proliferation, swelling endothelial cells and eosinophilic infiltration. KD is an allergic benign lymphoid tissue proliferation characteristic of massive eosinophilic infiltration, whereas epithelioid hemangioma is a benign neoplasm of blood vessels with plump and epithelioid endothelial cells. (Chin J Ophthalmol, 2021, 57: 689-695).

Natural nodular worm infection in goats induces eosinophil extracellular DNA trap (EET) formation.

Extracellular DNA Trap (ET) formation by granulocyte is a strong innate immune machinery that plays crucial roles in trapping and killing of pathogens. Here, we show Eosinophil Extracellular DNA Trap (EET) formation in goats naturally infected with nodular worms (Oesophagostomum columbianum, Strongyloidae: Nematoda). By a slaughterhouse based survey, we found that 60% goats were infected with nodular worms. We detected numerous, hard and pale yellow to dark black nodules of variable sizes (0.25-2cm) in the large intestine and the number of nodules were significantly (p<.05) higher in the cecum (21.7±17.9) than in the colon (10.1±9.9). Histologically, pink colored circumscribed caseous mass was surrounded by a dense zone of infiltration and fibrous proliferation along with massive infiltration of eosinophils in and around the necrotic mass. DAPI staining revealed huge accumulation of extracellular DNA, which formed wide ridge like structure surrounding the necrotic zone. Massive release of eosinophils cationic proteins (ECP), a helmintho-toxic substance, was found into the lesions. Collectively, our results suggest that nodular worm infection induces EETosis and ECP release, and is one of the major parasitic problem affecting Black Bengal goats that causes distortion of normal architecture of the gut wall.

Possible Mechanisms of Eosinophil Accumulation in Eosinophilic Pneumonia.

Eosinophilic pneumonia (EP), including acute EP and chronic EP, is characterized by the massive pulmonary infiltration of eosinophils into the lung. However, the mechanisms underlying the selective accumulation of eosinophils in EP have not yet been fully elucidated. We reported that bronchoalveolar lavage fluid (BALF) from EP patients induced the transmigration of eosinophils across endothelial cells in vitro. The concentrations of eotaxin-2 (CCL24) and monocyte chemotactic protein (MCP)-4 (CCL13), which are CC chemokine receptor (CCR) 3 ligands, were elevated in the BALF of EP patients, and anti-CCR3 monoclonal antibody inhibited the eosinophil transmigration induced by the BALF of EP patients. The concentration of macrophage inflammatory protein 1β (CCL4), a CCR5 ligand that induces eosinophil migration, was increased in the BALF of EP patients. Furthermore, the concentration of interleukin (IL) 5 was increased in the BALF of EP patients, and it has been reported that anti-IL-5 antibody treatment resulted in remission and the reduction of glucocorticoid use in some cases of chronic EP. The concentrations of lipid mediators, such as leukotriene (LT) B4, damage-associated molecular pattern molecules (DAMPs), such as uric acid, or extracellular matrix proteins, such as periostin, were also increased in the BALF of EP patients. These findings suggest that chemokines, such as CCR3/CCR5 ligands, cytokines, such as IL-5, lipid mediators, such as LTB4, DAMPs, and extracellular matrix proteins may play roles in the accumulation or activation of eosinophils in EP.

Diagnosis and surgical management of pericardial effusion due to paragonimiasis

ObjectivesThe pericardial effusion (PE) caused by paragonimiasis is rarely reported. This study aims to present experience in the diagnosis and surgical management of PE due to paragonimiasis. MethodsMedical records of 57 children who were diagnosed with PE due to paragonimiasis and underwent surgery at Children’s Hospital of Chongqing Medical University between January 2012 and August 2018 were retrospectively reviewed. ResultsThe average age of this group was 7.6 ± 3.0 years. Patients were mainly from Chongqing and Sichuan areas. ELISA for Paragonimus skrjabini in all 57 patients showed positive results. Moderate or large PE were identified in 12 and 45 patients, respectively. All patients underwent surgery either by pericardectomy or thoracoscopic surgery. Pathological exams indicated massive eosinophil infiltration in all 57 specimens. After 3–4 courses of praziquantel therapy, the clinical outcomes were satisfactory. ConclusionsTypical endemic history, eosinophilia and multiple serous effusion raise suspicions of paragonimiasis. Once moderate to large PE is identified in patients with paragonimiasis, surgical treatment is necessary.

Large Pericardial Effusion Due to Paragonimiasis in a 4-Year-Old Chinese Boy.

Large pericardial effusion (PE) and bilateral pleural effusion were found in a 4-year-old Chinese boy. An emergent surgery was performed. The biopsy showed massive eosinophil infiltration. Serologic test for Paragonimus skrjabini was positive. Postoperative praziquantel therapy was effective.

Hypereosinophilic syndrome manifested as eosinophilic gastroenteritis and colitis in a patient undergoing hemodialysis

BackgroundHypereosinophilic syndrome (HES) consists of a group of disorders characterized by abnormal accumulation of eosinophils in the blood or peripheral tissues, independent of known secondary causes of eosinophilia. Clinical manifestations of HES are highly variable, ranging from asymptomatic eosinophilia to severe tissue damage and end-organ failure.Case presentationWe herein present the case of a 65-year-old female with a 38-year history of hemodialysis who presented with lower leg pain, fever, skin eruption with leg edema, and diarrhea. Two months before admission, she underwent placement of a stent made of nickel and titanium for abdominal aortic stenosis. Lower leg pain occurred during hemodialysis, followed by fever, pedal edema with skin eruption, and diarrhea. Gastrointestinal endoscopy, colonoscopy, and biopsy histopathology revealed colitis with massive infiltration of eosinophils, compatible with eosinophilic gastroenteritis and colitis. The patient was treated with prednisolone at an initial dose of 40 mg daily and later reduced to 10 mg daily, after which her symptoms improved and her laboratory parameters normalized. She has not experienced a relapse after 1 year of follow-up.ConclusionsOur case of HES manifested as eosinophilic gastroenteritis and colitis and was successfully treated with corticosteroids. Clinicians should consider the differential diagnosis of HES when faced with similar cases in order to effect timely and appropriate treatment.

Treating insect-bite hypersensitivity in horses with active vaccination against IL-5

Insect-bite hypersensitivity is the most common allergic dermatitis in horses. Excoriated skin lesions are typical symptoms of this seasonal and refractory chronic disease. On a cellular level, the skin lesions are characterized by massive eosinophil infiltration caused by an underlying allergic response. To target these cells and treat disease, we developed a therapeutic vaccine against equine IL-5 (eIL-5), the master regulator of eosinophils. The vaccine consisted of eIL-5 covalently linked to a virus-like particle derived from cucumber mosaic virus containing the tetanus toxoid universal T-cell epitope tt830-843 (CMVTT). Thirty-four Icelandic horses were recruited and immunized with 400μg of eIL-5-CMVTT formulated in PBS without adjuvant (19 horses) or PBS alone (15 horses). The vaccine was well tolerated and did not reveal any safety concerns but was able to induce anti-eIL-5 autoantibody titers in 17 of 19 horses. This resulted in a statistically significant reduction in clinical lesion scores when compared with previous season levels, as well as levels in placebo-treated horses. Protection required a minimal threshold of anti-eIL-5 antibodies. Clinical improvement by disease scoring showed that 47% and 21% of vaccinated horses reached 50% and 75% improvement, respectively. In the placebo group no horse reached 75% improvement, and only 13% reached 50% improvement. Our therapeutic vaccine inducing autoantibodies against self IL-5 brings biologics to horses, is the first successful immunotherapeutic approach targeting a chronic disease in horses, and might facilitate development of a similar vaccine against IL-5 in human subjects.

Changes in expression of neurotrophins and neurotrophic factors in the model of eosinophilic inflammation of the esophageal mucosa

AbstractEsophageal sensory and motor nerves contribute to the symptoms of eosinophilic esophagitis, however, the mechanisms of this neural dysfunction are essentially unknown. We addressed the hypothesis that eosinophilic inflammation in the esophagus alters production of the key regulators of neural function neurotrophins and neurotrophic factors. We developed and optimized the model of allergic eosinophilic inflammation of esophageal mucosa induced by localized administration of allergen ovalbumin into the esophagus in ovalbumin-sensitized guinea pigs. We evaluated changes in expression of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial cell-derived neurotrophic factor (GDNF) and artemin in esophageal mucosa by quantitative RT-PCR. We found that the administration of ovalbumin into the esophageal wall of sensitized animals induced a massive eosinophilic infiltration restricted to esophageal mucosa (3 ± 1 vs. 97 ± 23 eosinophils per high power filed). This inflammatory response altered the expression profile of selected neurotrophic factors. The BDNF mRNA was increased (to 200%), artemin mRNA was decreased (to 50%) while NGF and GDNF was not changed. We conclude that a strong eosinophilic inflammation can be induced in guinea pigs and alters the expression of neurotrophins and neurotrophic factors. Our findings will aid mechanistic studies of neural dysfunction in eosinophilic esophagitis.

Case: Eosinophilic cystitis presenting as a bladder mass in an 11-year-old girl

We report the case of an 11-year-old girl who presented with acute urinary retention and microscopic hematuria. Pelvic imaging revealed a bladder mass for which sarcoma was initially suspected. Surgical biopsies revealed a massive eosinophilic infiltration of the submucosa confirming a diagnosis of eosinophilic cystitis. Clinical evolution was favourable without treatment. Eosinophilic cystitis prognosis is usually benign, but rare severe complications, such as complete bladder fibrosis requiring bladder augmentation or cystectomy, may occur.

Concomitant suppression of TH2 and TH17 cell responses in allergic asthma by targeting retinoic acid receptor–related orphan receptor γt

Allergic asthma is a heterogeneous chronic inflammatory disease of the airways with a massive infiltration of eosinophils or neutrophils mediated by allergen-specific TH2 and TH17cells, respectively. Therefore successful treatment of allergic asthma will require suppression of both TH2 and TH17cells. We sought to investigate the role of the TH17cell pathway in regulating TH2 cell responses in allergic asthma. Allergic asthma was induced by intranasal challenge with proteinase allergens in C57BL/6, Il17a-/-Il17f-/-, and retinoic acid receptor-related orphan receptor γt (RORγt)gfp/gfp mice. Apharmacologic RORγt inhibitor was used to evaluate its preventive and therapeutic effects in allergic asthma. Characteristics of allergic airway inflammation were analyzed by using flow cytometry, histology, quantitative real-time PCR, and ELISA. Mixed bone marrow chimeric mice, fate mapping analysis, short hairpin RNA transduction, and invitro T-cell differentiation were used for mechanistic studies. Mice deficient in IL-17A and IL-17F, as well as RORγt, exhibited a significant reduction not only in TH17cell responses but also in TH2 cell responses in an animal model of allergic asthma. Similarly, mice treated with an RORγt inhibitor had significantly diminished TH17 and TH2 cell responses, leading to reduced neutrophil and eosinophil numbers in the airway. RORγt-deficient T cells were intrinsically defective in differentiating into TH2 cells and expressed increased levels of B-cell lymphoma 6 (Bcl6). Bcl6 knockdown resulted in a remarkable restoration of TH2 cell differentiation in RORγt-deficient T cells. Blockade of RORγt also significantly hampered the differentiation of human TH2 and TH17cells from naive CD4+ T cells. RORγt in T cells is required for optimal TH2 cell differentiation by suppressing Bcl6 expression; this finding suggests that targeting RORγt might be a promising approach for the treatment of allergic asthma by concomitantly suppressing TH17 and TH2 cell responses in the airway.

Eosinophil transendothelial migration induced by the bronchoalveolar lavage fluid of acute eosinophilic pneumonia.

Acute eosinophilic pneumonia (AEP) is characterized by a massive pulmonary infiltration of eosinophils. Mechanisms regulating the selective accumulation of eosinophils in AEP have not been fully established. The objective of this study was to evaluate the mechanisms of eosinophil accumulation in alveolar spaces through examination of bronchoalveolar lavage fluid (BALF) from AEP patients (AEP-BALF). Eosinophils were isolated from the blood of healthy subjects and were placed on a human pulmonary microvascular endothelial cell monolayer cultured on Transwell filters (Coster, Cambridge, MA, USA). A saline control solution or BALF from patients with AEP, sarcoidosis or hypersensitivity pneumonitis was applied to the lower compartment, and the transendothelial migration of the eosinophils was evaluated. The concentrations of cytokines and chemokines in BALF were also measured. Transmigration of eosinophils across endothelial cells was only induced by the AEP-BALF. This transmigration was blocked by anti-β2 integrin mAb. The concentrations of eotaxin-2 and monocyte chemotactic protein (MCP)-4, which are CC chemokine receptor (CCR) 3 ligands, were elevated in the AEP-BALF, and anti-CCR3 mAb or anti-MCP-4 mAb inhibited the AEP-BALF-induced transmigration of eosinophils. Furthermore, the concentration of leukotriene (LT) B4 was increased in the AEP-BALF, and an LTB4 receptor antagonist partially suppressed the AEP-BALF-induced transmigration of eosinophils. These findings suggest that CCR3 ligands including eotaxin-2 and MCP-4, and LTB4 play a role in the accumulation of eosinophils in AEP.

Pathogenic Potential of Fresh, Frozen, and Thermally Treated Anisakis spp. Type II (L3) (Nematoda: Anisakidae) after Oral Inoculation into Wistar Rats: A Histopathological Study

The third-stage (L3) larvae of Anisakis are the etiological agents of human anisakiasis caused by consumption of raw or undercooked seafood infected with anisakid nematodes. Infection with these worms is associated with abdominal pain, nausea, and diarrhea and can lead to massive infiltration of eosinophils and the formation of granulomas in the gastrointestinal tract if the larvae are not removed. Food allergy affects populations worldwide, and despite several reports on the presence of the potentially zoonotic nematodes among edible fishes in Egypt, there are few immunological and molecular studies investigating the epidemiology of these parasites. Anisakidosis, a human infection with nematodes of the family Anisakidae, is caused most commonly by Anisakis spp. In the present study, seventy specimens of the European seabass Dicentrarchus labrax commercialized in Alexandria city along the Mediterranean Sea were acquired during the period from July to December, 2015. Fish were necropsied and dissected to investigate the presence of nematode larvae. Thirty fish (42.9%) of the total were parasitized by nematode larvae which were morphologically identified as Anisakis spp. Type II (L3) according to light and scanning electron microscopy. The pathogenic potential of oral inoculation of fresh, frozen, and thermally treated larvae into Wistar rats was elucidated by histological examination of their thymus and spleen. Results obtained indicated that neither cooling nor freezing of the parasite could destroy their allergenic capacity. So, it is important to create a wider awareness of this potential risk to human health. It is becoming increasingly likely that the impact of Anisakis spp. on human health has been underestimated, and it is perhaps time to consider more sweeping measures than those currently enforced to protect the public health.

Anisakis - immunology of a foodborne parasitosis.

Anisakis species are marine nematodes which can cause zoonotic infection in humans if consumed in raw, pickled or undercooked fish and seafood. Infection with Anisakis is associated with abdominal pain, nausea and diarrhoea and can lead to massive infiltration of eosinophils and formation of granulomas in the gastrointestinal tract if the larvae are not removed. Re-infection leads to systemic allergic reactions such as urticarial or anaphylaxis in some individuals, making Anisakis an important source of hidden allergens in seafood. This review summarizes the immunopathology associated with Anisakis infection. Anisakiasis and gastroallergic reactions can be prevented by consuming only fish that has been frozen to -20°C to the core for at least 24hours before preparation. Sensitization to Anisakis proteins can also occur, primarily due to occupational exposure to infested fish, and can lead to dermatitis, rhinoconjunctivitis or asthma. In this case, exposure to fish should be avoided.

A Patient with a Solitary Lump in the Sigmoid Colon

Question: A 73-year-old male underwent screening colonoscopy. He has lived for a couple of years in Namibia on his farm and has gone several times on hunting safaris in other African countries. He was not aware of any serious diseases in the past except for fever for 2–3 days and a rash on his back and chest during one of his safaris in Zambia. Colonoscopy was performed on an outpatient basis and documented normal findings except for a 2-cm mass in the distal sigmoid with a normal-appearing mucosa on narrow band imaging (Figure A, B). The mass felt quite firm on touch with a biopsy forceps. Histology showed massive subepithelial eosinophilic cell infiltration (Figure C) as well as granuloma (Figure D). Considering the patient’s history, what is your diagnosis? See the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI.

Natural helper cells contribute to pulmonary eosinophilia by producing IL-13 via IL-33/ST2 pathway in a murine model of respiratory syncytial virus infection.

It has been reported that natural helper cells, which are a non-T, non-B innate lymphoid cell type expressing c-Kit and ST2, mediate influenza-induced airway hyper-reactivity by producing substantial IL-13. However, little is known about natural helper cells for the development of RSV-induced airway inflammation, particularly eosinophilic infiltration. By using BALB/c mice that were infected intranasally with RSV, it became clear that infection with RSV can induce an increase in the absolute number of natural helper cells in the lungs of mice. It seems likely that these natural helper cells contribute to the massive eosinophilic infiltration in an IL-13-dependent manner. In fact, the number of IL-13-producing natural helper cells as well as the expression of IL-13 mRNA in natural helper cells was enhanced significantly during RSV infection, suggesting that natural helper cells might be cellular source of the Th2-type cytokine IL-13. Indeed, adoptive transfer of pulmonary natural helper cells augmented not only the production of IL-13 but also the infiltration of eosinophils in the lungs of transferred mice. Pulmonary natural helper cells can produce IL-13 following response to IL-33, which was increased markedly in the lungs of mice after intranasal RSV infection. The expression of IL-13 mRNA in pulmonary natural helper cells was up-regulated by in vitro IL-33 stimulation. Furthermore, blockade of IL-33 receptor subunit, ST2, diminished the frequency of IL-13-producing natural helper cells. Taken together, these results demonstrate that natural helper cells may play an important role in RSV-induced pulmonary eosinophilia by producing IL-13 via the IL-33/ST2 pathway.