Nonesophageal Eosinophilic Gastrointestinal Disorders: Clinical Care and Future Directions

Eosinophilic gastrointestinal disorders are a set of conditions with a wide range of clinical manifestations and treatment modalities. The disorders are suspected to result from an abnormal inflammatory response to allergen(s), and individuals may develop a relapsing or chronic disease, if the allergen is not eliminated. Mechanisms of disease pathogenesis, including the humoral immune response, need to be fully elucidated. A variety of therapies are used, though there is a lack of well-defined randomized, prospective studies. Other therapeutic options are needed as the current treatments have potential concerns; elimination diets may impair a child’s quality of life, and corticosteroids have adverse risks with long-term use. We review what is known about non-esophageal eosinophilic gastrointestinal disorders, and discuss research investigations which need to be conducted to facilitate diagnosis and enhance treatment methods

Electrochemical detection of Toxocara canis excretory-secretory antigens in children from rural communities in Esmeraldas Province, Ecuador: association between active infection and high eosinophilia.

BACKGROUND: The diagnosis of active Toxocara canis infections in humans is challenging. Larval stages of T. canis do not replicate in human tissues and disease may result from infection with a single T. canis larva. Recently, we developed a nanobody-based electrochemical magnetosensor assay with superior sensitivity to detect T. canis excretory-secretory (TES) antigens. Here, we evaluate the performance of the assay in children from an Ecuadorian birth cohort that followed children to five years of age. METHODS: Samples were selected based on the presence of peripheral blood eosinophilia and relative eosinophil counts. The samples were analyzed by the nanobody-based electrochemical magnetosensor assay, which utilizes a bivalent biotinylated nanobody as capturing agent on the surface of streptavidin pre-coated paramagnetic beads. Detection was performed by a different nanobody chemically labelled with horseradish peroxidase. RESULTS: Of 87 samples tested, 33 (38%) scored positive for TES antigen recognition by the electrochemical magnetosensor assay. The average concentration of TES antigen in serum was 2.1 ng/ml (SD = 1.1). The positive result in the electrochemical assay was associated with eosinophilia > 19% (P = 0.001). Parasitological data were available for 57 samples. There was no significant association between positivity by the electrochemical assay and the presence of other soil-transmitted helminth infections. CONCLUSIONS: Our nanobody-based electrochemical assay provides highly sensitive quantification of TES antigens in serum and has potential as a valuable tool for the diagnosis of active human toxocariasis

Nasal histamine responses in nonallergic rhinitis with eosinophilic syndrome

Background: Nonallergic rhinitis with eosinophilic syndrome (NARES) is persistent, without atopy, but with ≥25% nasal eosinophilia. Hypereosinophilia seems to contribute to nasal mucosa dysfunction. Objectives: This analytical case-control study aimed at assessing the presence and severity of nonspecific nasal hyperactivity and at finding out whether eosinophilia may be correlated with the respiratory and mucociliary clearance functions. Materials: The symptom score was assessed in 38 patients and 15 controls whose nasal smear was also tested for eosinophils and mucociliary transport (MCT). Nonspecific nasal provocation tests (NSNPT) with histamine were also carried out, and total nasal resistance (TNR) was determined. Results: The symptom score of NARES after NSNPT were not significantly different from the control group, and there was poor or no correlation among the single symptoms and the differences studied for every nasal reactivity class. This correlation improved when using the composite symptom score. The most severe eosinophilia was observed in high reactivity groups, and it was correlated with an increase in TNR. MCT worsened as eosinophilia and nasal reactivity increased. Unlike controls, a significant correlation was observed between the increase in MCT and TNR. Conclusions: In NARES, nonspecific nasal hyperreactivity is the result of epithelial damage produced by eosinophilic inflammation, which causes MCT slow down, an increase in TNR, and nasal reactivity classes, with possible impact on classification, prognosis, and treatment control

Eosinophilic bronchitis, eosinophilic granuloma, and eosinophilic bronchopneumopathy in 75 dogs (2006-2016).

BackgroundEosinophilic lung disease is a poorly understood inflammatory airway disease that results in substantial morbidity.ObjectiveTo describe clinical findings in dogs with eosinophilic lung disease defined on the basis of radiographic, bronchoscopic, and bronchoalveolar lavage fluid (BAL) analysis. Categories included eosinophilic bronchitis (EB), eosinophilic granuloma (EG), and eosinophilic bronchopneumopathy (EBP).AnimalsSeventy-five client owned dogs.MethodsMedical records were retrospectively reviewed for dogs with idiopathic BAL fluid eosinophilia. Information abstracted included duration and nature of clinical signs, bronchoscopic findings, and laboratory data. Thoracic radiographs were evaluated for the pattern of infiltrate, bronchiectasis, and lymphadenomegaly.ResultsThoracic radiographs were normal or demonstrated a bronchial pattern in 31 dogs assigned a diagnosis of EB. Nine dogs had intraluminal mass lesions and were bronchoscopically diagnosed with EG. The remaining 35 dogs were categorized as having EBP based on radiographic changes, yellow green mucus in the airways, mucosal changes, and airway collapse. Age and duration of cough did not differ among groups. Dogs with EB were less likely to have bronchiectasis or peripheral eosinophilia, had lower total nucleated cell count in BAL fluid, and lower percentage of eosinophils in BAL fluid compared to dogs in the other 2 groups. In contrast to previous reports, prolonged survival (>55 months) was documented in dogs with EG.Conclusions and clinical importanceDogs with eosinophilic lung disease can be categorized based on imaging, bronchoscopic and BAL fluid cytologic findings. Further studies are needed to establish response to treatment in these groups

Angiolymphoid hyperplasia with eosinophilia treated with Mohs micrographic surgery

A 60-year-old healthy man presented with several enlarging, tender, spontaneously bleeding, and episodically pruritic nodules on his ear. Five agminated pink-red papulonodules of the superior postauricular sulcus were noted on examination. Pathological examination revealed a lobular dermal vascular proliferation with plump endothelial cells protruding into the lumen in a hobnail pattern, along with a dense perivascular inflammatory infiltrate composed of plasma cells, lymphocytes, and numerous eosinophils. The diagnosis of angiolymphoid hyperplasia with eosinophilia was confirmed. After discussing treatment modalities, the patient opted for Mohs micrographic surgery (MMS). Three stages of MMS were able to remove all large vessel involvement and clear the peripheral margins, but the tumor had a complex branching pattern of growth in the deep bed of the wound with numerous tiny foci remaining. Owing to risk of disfigurement, no further excision was undertaken. The area was reconstructed with a temporalis fascia flap and a full-thickness skin graft. Despite remaining microscopic disease, the patient remained without recurrence or symptoms at one year of follow up

Tissue eosinophilia and eosinophil degranulation in Riedel's invasive fibrous thyroiditis.

The etiology of Riedel's invasive fibrous thyroiditis (IFT) has remained obscure. This rare disorder has been confused in the past with the more common fibrous variant of Hashimoto's disease. The typical histological features of IFT, in particular the presence of an invasive fibrosclerotic process in conjunction with a prominent chronic inflammatory infiltrate, suggest that the release of fibrogenic cytokines and other factors from these cellular infiltrates may play an important role in the pathogenesis of this condition. Our observations in routinely processed tissue sections obtained from patients with documented IFT of striking tissue eosinophilia led us to hypothesize that eosinophils and their products may play a role in the evolution of this disease. Immunofluorescence staining with affinity-purified polyclonal rabbit antibody directed against human eosinophil granule major basic protein revealed marked tissue eosinophilia and abundant extracellular deposition of major basic protein in all specimens from 16 patients with IFT. By contrast, only occasional eosinophils and no extracellular major basic protein were detected in control thyroid tissues obtained from patients with multinodular goiter, Graves' disease, Hashimoto's disease, and normal thyroid tissue. The presence of marked eosinophil infiltration and extracellular major basic protein deposition in IFT and other associated fibrosclerotic conditions suggests a role for eosinophils and their products in propagating the fibrogenesis seen in IFT

Diagnosis and management of eosinophilic asthma: a US perspective.

Eosinophilic asthma is now recognized as an important subphenotype of asthma based on the pattern of inflammatory cellular infiltrate in the airway. Eosinophilic asthma can be associated with increased asthma severity, atopy, late-onset disease, and steroid refractoriness. Induced sputum cell count is the gold standard for identifying eosinophilic inflammation in asthma although several noninvasive biomarkers, including fractional exhaled nitric oxide and periostin, are emerging as potential surrogates. As novel therapies and biologic agents become increasingly available, there is an increased need for specific phenotype-directed treatment strategies. Greater recognition and understanding of the unique immunopathology of this asthma phenotype has important implications for management of the disease and the potential to improve patient outcomes. The present review provides a summary of the clinical features, pathogenesis, diagnosis, and management of eosinophilic asthma

Diagnostic and therapeutic considerations in idiopathic hypereosinophilia with warm autoimmune hemolytic anemia.

Hypereosinophilic syndrome (HES) encompasses numerous diverse conditions resulting in peripheral hypereosinophilia that cannot be explained by hypersensitivity, infection, or atopy and that is not associated with known systemic diseases with specific organ involvement. HES is often attributed to neoplastic or reactive causes, such as chronic eosinophilic leukemia, although a majority of cases remains unexplained and are considered idiopathic. Here, we review the current diagnosis and management of HES and present a unique case of profound hypereosinophilia associated with warm autoimmune hemolytic anemia requiring intensive management. This case clearly illustrates the limitations of current knowledge with respect to hypereosinophilia syndrome as well as the challenges associated with its classification and management

Validation of a food frequency questionnaire for children and adolescents aged 4 to 11 years living in Salvador, Bahia.

OBJECTIVE: To assess the validity of a food frequency questionnaire (FFQ) by applying it to children and adolescents living in Salvador, Bahia. METHODS: The validity of this FFQ with 98 food items was investigated among 108 children and adolescents who were selected from a sample of 1445 that had been planned for a study on the risk factors for asthma and other allergic diseases. The adults responsible for these children and adolescents gave responses for a 24-hour recall (R24h) and an FFQ. The average energy and nutrient values from the FFQ were compared with those from the R24h by means of the paired t test and Pearson correlation coefficients. The concordance was evaluated using the Bland-Altman method and kappa statistics. RESULTS: The energy and nutrient intake estimated using the FFQ was significantly higher than what was obtained using the R24h. The correlation coefficients adjusted for energy were statistically significant for protein, fat, vitamin C and zinc. The weighted kappa values ranged from 0.06 for vitamin A (p = 0.24) to 0.34 for energy (p < 0.00). The results from the Bland-Altman plots for lipid, protein and zinc showed the most significant validity parameters, and zinc was found to show the best concordance. CONCLUSION: The results suggest that the FFQ showed satisfactory validity for use in studies involving children and adolescents