Lupus Nephritis Disguised: The Diagnostic Challenge of Eosinophilic Enteritis - A Case Report.

Systemic lupus erythematosus (SLE) is a multi-systemic disorder affecting almost all systems of the body. Involvement of the kidney in this condition is known as lupus nephritis (LN). LN is one of the important disease manifestations of SLE with considerable influence on patient outcomes in terms of morbidity and mortality. A 33-year-old female came to the OPD with complaints of abdominal pain, infrequent loose stools since 4 months. The patient also had joint pain, predominantly small joints, since 2 months. Patient was admitted and all routine investigations were done. Patient underwent an oesophagogastroduodenoscopy (OGD) and colonoscopy for her abdominal pain and loose stools which did not respond to routine medication. Grossly there was edema present in the oesophagus and colon which on microscopy showed eosinophilic infiltration. Urine routine of the patient showed protein 1+and 24-hour urine protein quantification of 1427 mg/24 h. On further evaluation patient was found to have a positive ANA blot (dsDNA, AMAM2, Ro52 and Sm). The patient was planned for a renal biopsy in view of the proteinuria and positive ANA blot. The patient underwent a renal biopsy under USG guidance and was found to have Lupus nephritis Class 3 (ISN RPS staging). SLE is a multi-organ involving disease which if not diagnosed at the earliest can have serious complications and lead to end stage organ failure and even death. Atypical presentations often pose a diagnostic dilemma and may delay diagnosis and treatment. Early diagnosis and treatment can give patients of SLE a long and normal life. Diagnostic guidelines have helped in the diagnosis of such atypical presentations.

Dietary Management of Non-EoE Eosinophilic Gastrointestinal Diseases.

Patients with non-eosinophilic esophagitis eosinophilic gastrointestinal diseases (non-EoE EGIDs) are prone to nutritional deficiencies due to food-avoidant behaviors, malabsorption, and high nutrition impact symptoms. Nutrient deficiencies correspond to the segment, depth, and extent of the gastrointestinal tract involved and can impact organs distant from the gut. Patients with non-EoE EGIDs are often atopic, and some appear to respond to dietary avoidance of specific food allergens. Tests to identify food triggers other than response to elimination diets are lacking. Dietary restriction therapy should be considered in such patients and is best implemented through a multidisciplinary approach to avoid nutritional complications.

Clinical Presentation of Patients with Eosinophilic Gastrointestinal Diseases beyond Eosinophilic Esophagitis.

The clinical presentation of eosinophilic gastrointestinal diseases beyond eosinophilic esophagitis (non-EoE EGIDs) varies depending on the gastrointestinal segments affected by the eosinophilic inflammation, the extent of eosinophilic inflammation within the gastrointestinal tract and its depth through the bowel wall. Non-EoE EGIDs with mucosal involvement tend to present with diarrhea, malabsorption, and sometimes bleeding, those with muscular involvement may present with symptoms of obstruction or pseudo-obstruction, intussusception, and even perforation, whereas those with serosal involvement may present with eosinophilic ascites. Here we describe the differences in symptoms experienced by children with non-EoE EGIDs with varying degrees of eosinophilic inflammation through the bowel wall.

Pathophysiology of Non-Esophageal Eosinophilic Gastrointestinal Disorders.

Eosinophilic gastrointestinal disorder (EGID) is an umbrella term encompassing a group of chronic, immune-mediated disorders characterized by eosinophil-rich inflammation affecting one or more segments of the gastrointestinal tract. A recent consensus in nomenclature and emerging data made possible through multi-center consortia are beginning to unravel the molecular and cellular underpinnings of EGIDs below the esophagus. These emerging findings are revealing both overarching commonalities related to a food allergen-driven, chronic, Th2-mediated immune response as well as location-specific nuances in the pathophysiology of the collective EGIDs. Altogether, these advances offer promise for improved diagnoses and more efficacious interventional strategies.

Challenges in Diagnosis and Management of Unusual Cases of Eosinophilic Enteritis in Rural Health Settings: A Comprehensive Review.

This comprehensive review delves into the challenges associated with diagnosing and managing unusual cases of eosinophilic enteritis in rural health settings. Eosinophilic enteritis, characterized by an abnormal accumulation of eosinophils in the gastrointestinal (GI) tract, poses distinct difficulties in diagnosis due to its varied presentations. In rural contexts, limited access to specialized diagnostic tools, a shortage of healthcare professionals, and geographical constraints compound these challenges. This abstract encapsulates the critical issues explored in the review, emphasizing the importance of addressing atypical cases and rural healthcare's unique hurdles. The conclusion is a rallying call for collaborative action, advocating for improved education, telemedicine solutions, and enhanced access to specialized care. The implications extend beyond eosinophilic enteritis, with the potential to instigate systemic improvements in rural healthcare globally. This review is a crucial contribution to understanding eosinophilic enteritis in rural settings and advocates for transformative measures to improve diagnosis, management, and overall healthcare outcomes.

Minimally Invasive Approaches to Diagnose and Monitor Eosinophilic GI Diseases.

PURPOSE OF REVIEW: This review seeks to understand novel avenues for eosinophilic GI disease management. Biomarkers offer a unique and non-invasive approach to tracking EoE disease progression. While no biomarkers have definitively met the diagnostic criteria for eosinophilic GI diseases, some biomarkers have been shown to be associated with disease activity. Here, we examine the potential of recently studied biomarkers. RECENT FINDINGS: Current research shows advancements in blood, luminal fluid, and breath testing. Particular areas of interest include mRNA analyses, protein fingerprinting, amplicon sequence variants (ASVs), T cells and IgE receptors, eosinophilic cationic proteins, cytokines, and nitric oxide exhalation. Preliminary results showed that mucosal biomarkers, directly captured from the esophagus, may reflect the best representation of biopsy-based results, in contrast to biomarkers obtained from indirect or peripheral (blood, breath) methods. However, this is based on limited clinical studies without sufficient numbers to evaluate true diagnostic accuracy. Large-scale randomized trials are needed to fully ascertain both the optimal sampling technique and the specific biomarkers that reflect diagnostic status of the disease.

Common and disparate clinical presentations and mechanisms in different eosinophilic gastrointestinal diseases.

Eosinophilic gastrointestinal diseases (EGIDs) are a group of diseases characterized by selective eosinophil infiltration of the gastrointestinal (GI) tract in the absence of other causes of eosinophilia. These diseases are generally driven by type 2 inflammation, often in response to food allergen exposure. Among all EGIDs, the clinical presentation often includes a history of atopic disease with a variety of GI symptoms. EGIDs are traditionally separated into eosinophilic esophagitis (EoE) and non-EoE EGIDs. EoE is relatively better understood and now associated with clinical guidelines and 2 US Food and Drug Administration-approved treatments, whereas non-EoE EGIDs are rarer and less well-understood diseases without US Food and Drug Administration-approved treatments. Non-EoE EGIDs are further subclassified by the area of the GI tract that is involved; they comprise eosinophilic gastritis, eosinophilic enteritis (including eosinophilic duodenitis), and eosinophilic colitis. As with other GI disorders, the disease presentations and mechanisms differ depending on the involved segment of the GI tract; however, the differences between EoE and non-EoE EGIDs extend beyond which GI tract segment is involved. The aim of this article is to summarize the commonalities and differences between the clinical presentations and disease mechanisms for EoE and non-EoE EGIDs.

Eosinophilic Enteritis Causing Recurrent Small Bowel Obstruction: A Case Report.

Eosinophilic enteritis is an inflammatory condition characterized by eosinophilic infiltration of the gastrointestinal tract. This case report highlights a unique presentation of eosinophilic enteritis as a cause of recurrent small bowel obstruction. The diagnosis was elusive despite extensive abdominal imaging. A histopathologic examination of a full-thickness bowel segment showing extensive eosinophilic infiltration in the muscularis propria was vital in establishing the diagnosis. This report underscores the diagnostic complexities associated with eosinophilic enteritis and the need to consider this condition as a potential cause of recurrent abdominal pain and small bowel obstruction.

Eosinophilic enteritis: the great mimic.

Eosinophilic enteritis (EoN), a subtype of eosinophilic gastrointestinal disease, is a rare and complicated inflammatory condition affecting the small intestine. This case report discusses a 42-year-old patient who presented with acute gastrointestinal symptoms including diarrhea, nausea, and vomiting. Initial laboratory investigations revealed leukocytosis, peripheral eosinophilia, and distinctive imaging findings, prompting further evaluation. Endoscopic evaluation revealed extensive mucosal lesions in the small intestine, with subsequent biopsies confirming eosinophilic infiltration, ultimately leading to the diagnosis of chronic enteritis, probably of an eosinophilic nature. The case highlights the complex differential diagnostic process involved in identifying EoN, which requires a comprehensive understanding of all the clinical and histopathological features of the disease. The efficacy of budesonide therapy is also discussed in the management of EoN and it was evidenced by our patient's positive response to treatment. This case report contributes significant insights into the understanding and management of EoN, providing essential information for the medical community to facilitate accurate diagnosis and tailored therapeutic interventions for individuals experiencing this complex disorder.

Eosinophilic enteritis presenting as intestinal obstruction: case report and review of the literature.

Eosinophilic enteritis (EE) is characterized by intense eosinophilic infiltrate of the gastrointestinal tract. Clinical manifestations depend on the affected segment and intestinal layer. First-line treatment is systemic corticosteroids; surgery is reserved for complications. 84-year-old male patient with a history of right hemicolectomy and two episodes of intestinal obstruction presented to the ED with abdominal pain, distension, nausea, and vomiting. CBC showed leukocytosis and no eosinophilia. Contrast-enhanced CT revealed stenosis with thickening of the distal intestinal wall and partial intestinal obstruction. Colonoscopy found aphthous ulcers. Histopathology reported EE. The patient received budesonide and metronidazole, with resolution within 24 h.

La enteritis eosinofílica (EE) se caracteriza por infiltrado eosinofilico del tracto GI. Las manifestaciones clínicas dependen de la capa intestinal afectada. Se recomiendan esteroides sistémicos como primera línea de tratamiento, reservando la cirugía para complicaciones. Masculino de 84 años con antecedente de hemicolectomía derecha y dos episodios de oclusión intestinal acude al servicio de urgencias con dolor abdominal, distensión, náusea y vómito. Laboratorio reportó leucocitosis, sin eosinofilia. Tomografía con contraste evidenció estenosis, con engrosamiento de la pared del intestino delgado e imagen compatible con oclusión intestinal. La colonoscopía demostró ulceras en íleon terminal la cual reporto EE. Se inició tratamiento con budesonide y metronidazol, con adecuada respuesta y resolución a las 24 h.

The role of biologics in pediatric food allergy and eosinophilic gastrointestinal disorders.

Continuing insight into the molecular mechanisms of atopic disorders has enabled the development of biologics to precisely target these diseases. Food allergy (FA) and eosinophilic gastrointestinal disorders (EGIDs) are driven by similar inflammatory molecular mechanisms and exist along the same atopic disease spectrum. Therefore, many of the same biologics are being investigated to target key drivers of mechanisms shared across the disease states. The enormous potential of biologics for the treatment of FA and EGIDs is highlighted by the significant increases in the number of ongoing clinical trials (more than 30) evaluating their use in these disease states, as well as by the recent US Food and Drug Administration approval of dupilumab for the treatment of eosinophilic esophagitis. Here we discuss past and current research into the use of biologics in FA and EGIDs and their potential role in improving treatment options in the future, with the need to have biologics widely clinically available.

Eosinophilic Gastrointestinal Diseases Beyond the Esophagus: An Evolving Field and Nomenclature.

The eosinophilic gastrointestinal diseases (EGIDs) are a group of chronic, immune-mediated gastrointestinal (GI) diseases characterized by GI symptoms and pathologic eosinophilic infiltration of specific areas within the GI tract in the absence of secondary causes of eosinophilia. The non-eosinophilic esophagitis EGIDs remain understudied and likely underdiagnosed, owing in part to the lack of clarity in the terminology previously used to describe these diseases. The newly established EGID nomenclature framework includes a first-tier description of the specific location of GI tract involvement and a second-tier description with more granular characterizations of disease involvement. EGIDs can involve any segment or layer of the GI tract, so patients can present with a wide array of common, nonspecific GI symptoms. Diagnosing EGIDs requires endoscopic evaluation and biopsies showing increased eosinophilic tissue infiltration in the correct clinical context after ruling out other causes of eosinophilia. Although the pathogenesis is not yet fully understood, EGIDs are likely allergic conditions triggered by food antigen exposure. Most patients are currently treated with corticosteroids, but investigations of other pharmacologic and dietary therapies are ongoing. This article highlights the recently updated EGID nomenclature and summarizes the current understanding of the diagnosis, pathogenesis, and treatment of EGIDs.

Successful management of colonic pythiosis in two dogs in Thailand using antifungal therapy.

Gastrointestinal pythiosis is a severe, progressive and often a fatal disease, which is caused by the aquatic pathogen Pythium insidiosum. Treatment is challenging due to the disease's resistance to antifungal drugs. Surgical resection is frequently attempted in cases of pythiosis; however, it can be technically challenging. This report presents two dogs with decreased appetite, abdominal pain, progressive haematochezia, tenesmus and significant weight loss. With the medical histories of both being young canines, living in areas with access to natural water resources and with the main chronic gastrointestinal symptoms having not responded to symptomatic treatment, pythiosis was taken into consideration. Abdominal ultrasound revealed severe, diffuse thickening and loss of normal layering of the colonic wall. These findings led to a differential diagnosis between intestinal neoplasia and fungal disease. Full-thickness biopsies were later performed, and immunohistochemistry staining was suggested for colonic pythiosis. Medical treatment for pythiosis was successful with a combination of oral terbinafine and prednisolone. However, therapy with itraconazole in case 1 did not improve the clinical signs, and in case 2, itraconazole was used after all clinical signs have improved for clinical control. Since then, there has been no recurrence of clinical signs until the time of preparing this report (19 months for case 1, 11 months for case 2 since the cessation of treatment). The treatment was successful based on clinical signs and ultrasonographic data, and the disease remission was not confirmed by advance imaging, monitoring of pythiosis enzyme-linked immunosorbent essay concentration or repeat sampling.

Feline eosinophilic sclerosing fibroplasia - a characteristic inflammatory response in sites beyond the gastrointestinal tract: case report and proposed nomenclature.

Case summary: An adult male neutered Russian Blue cat presented for a right-sided nasal mass with bilateral retropharyngeal and right mandibular lymphadenomegaly. Medial retropharyngeal lymph node excision with nasal mass biopsy revealed eosinophilic sclerosing lymphadenitis and eosinophilic and lymphoplasmacytic rhinitis, respectively. Bacterial culture of the lymph node grew Pseudomonas aeruginosa, and treatment with pradofloxacin was started. Despite initial improvement, clinical signs recurred after 9 months, and fine-needle aspirates of the right mandibular and left medial retropharyngeal lymph nodes showed eosinophilic and mastocytic infiltration. Bacterial culture of the left medial retropharyngeal lymph node grew P aeruginosa, and treatment with anti-inflammatory doses of prednisolone and, later, marbofloxacin was instituted. Relevance and novel information: This report describes a case of feline eosinophilic sclerosing lymphadenitis diagnosed outside of the abdominal cavity and is the first case reported to be associated with P aeruginosa. Feline eosinophilic sclerosing lymphadenitis should be considered as a differential for lymphadenopathy occurring in areas other than the abdominal cavity. Feline eosinophilic sclerosing lymphadenitis may develop in cats due to a species-specific inflammatory response to chronic bacterial and fungal infections.

Psychological Stress Exacerbates Inflammation of the Ileum via the Corticotropin-Releasing Hormone-Mast Cell Axis in a Mouse Model of Eosinophilic Enteritis.

The effects of psychological stress on eosinophilic gastrointestinal disorders have not been elucidated. This study investigated the effects of psychological stress in a mouse model of eosinophilic enteritis (EoN). BALB/c mice were treated with ovalbumin (OVA) to create an EoN model and subjected to either water avoidance stress (WAS) or sham stress (SS). Microscopic inflammation, eosinophil and mast cell counts, mRNA expression, and protein levels of type 2 helper T cell (Th2) cytokines in the ileum were compared between groups. We evaluated ex vivo intestinal permeability using an Ussing chamber. A corticotropin-releasing hormone type 1 receptor (CRH-R1) antagonist was administered before WAS, and its effects were analyzed. WAS significantly increased diarrhea occurrence and, eosinophil and mast cell counts, and decreased the villus/crypt ratio compared to those in the SS group. The mRNA expression of CRH, interleukin IL-4, IL-5, IL-13, eotaxin-1, and mast cell tryptase ß2 significantly increased, and the protein levels of IL-5, IL-13, and OVA-specific immunoglobulin E (IgE) also significantly increased in the WAS group. Moreover, WAS significantly increased the intestinal permeability. The CRH-R1 antagonist significantly inhibited all changes induced by WAS. Psychological stress exacerbated ileal inflammation via the CRH-mast cell axis in an EoN mouse model.

The Economic Burden of Eosinophilic Gastritis and Eosinophilic Enteritis in the United States.

INTRODUCTION: Eosinophilic gastritis and eosinophilic enteritis (EoG/EoN) are associated with a substantial clinical burden. However, limited information is available regarding the economic burden of EoG/EoN. This study was conducted to compare healthcare resource use (HRU) and costs among patients with EoG/EoN versus without EoG/EoN in the USA. METHODS: Administrative claims data from the IBM MarketScan® Commercial Claims and Encounters (CCAE) and Medicare Supplemental and Coordination of Benefits Databases (2009-2019) was used to identify two cohorts of patients. Patients without EoG/EoN were matched 3:1 to patients with EoG/EoN on sex, year of birth, and healthcare plan type. Study measures included demographic characteristics, select comorbidities, all-cause HRU, and costs. Comparisons were made over a 1-year period following EoG/EoN diagnosis for patients with EoG/EoN and an eligible date for patients without EoG/EoN. RESULTS: A total of 2219 patients with EoG/EoN and 6657 patients without EoG/EoN were analyzed. Significantly higher proportions of patients with EoG/EoN versus without EoG/EoN had comorbid conditions. Rates of all-cause HRU were significantly higher among patients with EoG/EoN versus patients without EoG/EoN (adjusted rate ratio [95% confidence interval]: inpatient visits, 6.26 [5.26, 7.46]; outpatient visits, 1.17 [1.16, 1.19]; emergency department visits, 2.11 [1.98, 2.25]; all p < 0.001). Patients with EoG/EoN incurred significantly higher costs versus patients without EoG/EoN (adjusted mean cost difference $31,180; p < 0.001). Cost differences were largely due to outpatient (adjusted mean cost difference $14,018; p < 0.001) and inpatient (adjusted mean cost difference $11,224; p < 0.001) costs. CONCLUSION: The economic burden associated with EoG/EoN is substantial, with patients with EoG/EoN having a higher rate of HRU and incurring $31,180 more than patients without EoG/EoN on average. Most of the cost difference was attributable to outpatient and inpatient costs. Cost-saving strategies to lower the burden of illness in this patient population are needed.

Benralizumab Completely Depletes Gastrointestinal Tissue Eosinophils and Improves Symptoms in Eosinophilic Gastrointestinal Disease.

BACKGROUND: Previous studies of targeted eosinophil biologics in eosinophilic esophagitis have yielded mixed results. Possible explanations include incomplete eosinophil depletion with anticytokine (anti-IL-5) treatments and/or irreversible fibrotic tissue changes contributing to symptomatology. OBJECTIVE: To characterize the therapeutic effect of eosinophil depletion in patients with hypereosinophilic syndrome with varied eosinophilic gastrointestinal (GI) disorders. METHODS: Hematologic, histologic, endoscopic, and clinical symptoms for a subset (n = 7) of hypereosinophilic syndrome patients with GI tissue eosinophilia enrolled in a phase 2 clinical trial of benralizumab (anti-IL-5RA) were assessed before and after treatment (NCT02130882). RESULTS: Blood and GI tissue eosinophils were completely depleted in all segments of the GI tract, and all patients reported improved GI symptoms, in some cases as early as after the first monthly dose. Some patients had recurrent symptomatic flares without recurrent peripheral or tissue eosinophilia, in most cases after prolonged symptomatic remission and in the setting of liberalization of dietary restrictions and/or tapering of background therapy. Although eosinophil-associated histologic changes improved in all segments, epithelial changes persisted in the esophagus and stomach in patients with recurrent disease flares even after 1 year of treatment. Serum tryptase and GI mast cells were generally unchanged with treatment, and increases were not associated with disease flares. Serum levels of IL-4 and IL-5 increased with benralizumab treatment (both P < .05). CONCLUSIONS: Benralizumab treatment completely depleted blood and GI tissue eosinophilia in patients with eosinophilic GI disorders, but clinical response, while encouraging, was heterogeneous. Residual symptoms in some patients may reflect persistent epithelial changes in the upper GI tract.