Eosinophilic Gastroenteritis: Using Presenting Findings to Predict Disease Course.

INTRODUCTION: Studies on eosinophilic gastroenteritis have identified broad spectrums of disease. We aimed to characterize subtypes of disease and ascertain outcomes of each group. METHODS: This is a retrospective cohort study from a large tertiary medical center including 35 patients diagnosed with eosinophilic gastroenteritis from 2007 to 2018. We defined 2 groups of patients based on clinical and laboratory findings at presentation. Severe disease was defined as having weight loss at time of presentation, hypoalbuminemia at presentation, serosal disease involvement, or anemia at diagnosis. The remaining patients were labeled as mild disease group. We collected and compared demographic data, clinical features, laboratory findings, an allergy history, and disease course of both cohorts. RESULTS: Among 35 patients with eosinophilic gastroenteritis, 18 patients met the criteria for severe disease and 17 patients for mild disease. Of the patients with severe eosinophilic gastroenteritis, 6 (38%) had remission without chronic symptoms, whereas 10 (63%) had chronic symptoms requiring chronic medical therapy. Of the mild group, 12 patients (80%) had disease remission without chronic medications. An allergy history was more common in the severe disease group (83%) compared with the mild disease group (45%). Prednisone and open capsule budesonide were the most commonly used treatment medications in both groups. DISCUSSION: Patients with eosinophilic gastroenteritis may be characterized into 2 forms. Patients with weight loss at time of presentation, hypoalbuminemia at presentation, serosal disease involvement, or anemia at diagnosis were associated with a chronic disease course requiring chronic medications.

Eosinophilic colitis in adults.

Eosinophilic colitis (EoC) is a pathological entity associated with abnormal infiltration of colonic mucosa by eosinophilic polynuclear cells (Eo). This is a relatively common pathology in infants and children under 2 years old, but is more rare and has been less studied in adults. EoC can be classified as primary or secondary. Primary EoC is, in the majority of cases, related to an allergic reaction, either IgE-mediated and capable of causing an anaphylactic-type food allergy, or not mediated by IgE and capable of giving rise to food enteropathy. The symptoms for adults with EoC are variable and non-specific, diarrhoea and abdominal pain being the most common signs. There is no histological consensus for the diagnosis of EoC. The presence of over 40 Eo per high-power field (×400) in at least two different colonic segments could be suggested as the criterion for the diagnosis. In adults with primary EoC, skin tests are of limited value and the response to a restrictive diet is less effective than in young children, given that IgE or non-IgE-mediated allergic reactions are rarely identified and EoC generally require medical treatment. There is no consensus on the treatment of EoC, but the potential efficacy of corticosteroids and budesonide has been demonstrated in the vast majority of cases studied.

Childhood GPA, EGPA, and MPA.

Antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) is a term used to describe rare primary systemic vasculitides affecting small and medium-sized blood vessels. AAV diseases which include Granulomatosis with Polyangiitis (GPA), Eosinophilic Granulomatosis with Polyangiitis (EGPA), Microscopic Polyangiitis (MPA) and renal limited ANCA vasculitis. These multisystemic disorders involve upper and lower respiratory tract and kidneys associated with organ damage and long term sequelae. Newer understanding of pathogenesis in AAV have paved the way for clinical research with different biologic therapies. In spite of the paucity of clinical trials in pediatric AAV, the long-term survival of patients with AAV has improved dramatically. International collaborations will help to conduct clinical trials in pediatric AAV and help in better understanding of remission rates, relapse rates, and other outcomes. This article aims to provide a comprehensive review of pediatric AAV with a focus on epidemiology, disease pathogenesis, treatment trials, and prognosis.

[Classification of chronic rhinosinusitis with nasal polyps based on eosinophilic inflammation].

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous disorder characterized by chronic sinonasal mucosal inflammation. CRSwNP can be subdivided into two types based on eosinophilic inflammation: eosinophilic CRSwNP (Eos CRSwNP) and non-eosinophilic CRSwNP (Non-Eos CRSwNP). Eos CRSwNP and Non-Eos CRSwNP demonstrate distinct clinical manifestations, treatment outcomes, and cellular and immunopathologic characteristics. However, currently, there is no unified and generally accepted standard to define the Eos CRSwNP. The aim of this review is to compare the advantages and disadvantages of current methods used to classify Eos CRSwNP, in order to lay foundation for further study.

[CME: Mepolizumab, an Additional Therapeutic Agent for Severe Asthma]. / CME: Mepolizumab, ein weiterer Baustein der individualisierten Therapie des schweren Asthma bronchiale.

CME: Mepolizumab, an Additional Therapeutic Agent for Severe Asthma Abstract. The challenging therapy of severe uncontrollable bronchial asthma aims primarily at sufficient symptom control and the minimization of the exacerbation rate. If, despite extended drug therapy, symptom control is very difficult to achieve, biologics should preferably be used instead of corticosteroid therapy. The aim of this article is to point out these different asthma therapy pathways and to describe diagnostic criteria as well as practical experiences through application in patients.

Eosinophilic gastroenteritis and other eosinophilic gut diseases distal to the oesophagus.

Under normal physiological conditions, eosinophils are present throughout the gastrointestinal tract distal to the squamous oesophagus. Increases in their numbers signify primary and secondary eosinophilic conditions. The rare primary eosinophilic diseases eosinophilic gastroenteritis and eosinophilic colitis affect fewer than ten in 100 000 people, and are characterised by numerous mucosal eosinophils, distributed in sheets and sometimes extending from the mucosa into the submucosa. Pathogenesis of these diseases is poorly understood, but food allergies and intestinal dysbiosis have been implicated. Presentation ranges from vague abdominal symptoms and systemic complaints to, rarely, an acute abdomen with intestinal obstruction. Diagnosis is made from mucosal biopsy samples taken at endoscopy or from surgically resected specimens that demonstrate substantially increased numbers of eosinophils. Eosinophilia secondary to other conditions, such as pathogenic infections, must be excluded. Subtle eosinophilia has also been identified in the duodenum in functional dyspepsia and in the colon in spirochaetosis. Treatment of eosinophilic gastroenteritis and eosinophilic colitis is based on evidence from case reports and small case series, and first-line therapy includes empirical food-elimination diets and single courses of steroids, whereas relapsing or refractory disease might respond to steroid-sparing immunosuppressive agents and biological agents. The progression of disease in eosinophilic gastroenteritis and eosinophilic colitis is variable: a considerable number of patients have just one episode without relapse, whereas others have relapsing-remitting or chronic disease. Primary and secondary eosinophilia in the gastrointestinal tract is increasingly recognised as a clinical conundrum waiting to be solved.

Classification of eosinophilic disorders of the small and large intestine.

Eosinophilic gastrointestinal diseases (EGIDs), including eosinophilic gastroenteritis and eosinophilic colitis, have been increasing in prevalence in Western countries in recent years. Eosinophils are normally scanty in the gastrointestinal tract, and increased numbers of eosinophils can denote pathology. Normal values for tissue eosinophils vary widely between different segments of the colon, thus location of the biopsy is critically important for the interpretation of findings. However, no standard diagnostic criteria have been proposed for the diagnosis of eosinophilic gastroenteritis or eosinophilic colitis. Gut eosinophilia encompasses entitites that are predominantly immunoglobulin E (IgE)-mediated, the primary EGIDs and those that are secondary and not IgE-mediated. A final diagnosis of eosinophilic gastrointestinal diseases requires careful pathological assessment, clinical correlation and exclusion of several differential diagnoses.

Eosinophilic pustular folliculitis: A published work-based comprehensive analysis of therapeutic responsiveness.

Eosinophilic pustular folliculitis (EPF) is a non-infectious inflammatory dermatosis of unknown etiology that principally affects the hair follicles. There are three variants of EPF: (i) classic EPF; (ii) immunosuppression-associated EPF, which is subdivided into HIV-associated (IS/HIV) and non-HIV-associated (IS/non-HIV); and (iii) infancy-associated EPF. Oral indomethacin is efficacious, especially for classic EPF. No comprehensive information on the efficacies of other medical management regimens is currently available. In this study, we surveyed regimens for EPF that were described in articles published between 1965 and 2013. In total, there were 1171 regimens; 874, 137, 45 and 115 of which were applied to classic, IS/HIV, IS/non-HIV and infancy-associated EPF, respectively. Classic EPF was preferentially treated with oral indomethacin with efficacy of 84% whereas topical steroids were preferred for IS/HIV, IS/non-HIV and infancy-associated EPF with efficacy of 47%, 73% and 82%, respectively. Other regimens such as oral Sairei-to (a Chinese-Japanese herbal medicine), diaminodiphenyl sulfone, cyclosporin and topical tacrolimus were effective for indomethacin-resistant cases. Although the preclusion of direct comparison among cases was one limitation, this study provides a dataset that is applicable to the construction of therapeutic algorithms for EPF.

A pilot study of symptom profiles from a polyp vs an eosinophilic-based classification of chronic rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis (CRS) is likely a biologically heterogeneous disease process. Current guidelines propose subclassification using polyp status while others propose using mucosal eosinophilia. We hypothesized that appropriate CRS subclassification would increase homogeneity of baseline symptoms, and identify characteristic symptoms of each subtype. METHODS: A total of 57 CRS patients undergoing surgery prospectively completed a preoperative battery of 73 questions relating to symptoms including the 22-item Sino-Nasal Outcome Test (SNOT-22) and 29-item Patient-Reported Outcomes Measurement Information System (PROMIS-29) general quality of life (QOL) measures. Eosinophilic cationic protein (ECP) levels were determined from ethmoid, uncinate, and polyp tissue homogenates using enzyme-linked immunosorbent assay (ELISA) and normalized to total protein. Patients were classified as eosinophilic (eCRS) or non-eosinophilic (neCRS) using a 95th percentile threshold established from control tissue from 82 patients without CRS. Separate pairwise comparisons were performed on patient-reported symptoms using polyp and eosinophilic status. RESULTS: Of the 57 patients, 28 had CRS with nasal polyps (CRSwNP); 27 of 57 patients had eCRS (CRSwNP, n = 21; CRS without nasal polyps [CRSsNP], n = 6). CRSwNP patients had increased need to blow nose, frequency of nasal congestion, more severe difficulty breathing through nose, more severe nasal discharge, but less cough (p < 0.05). eCRS patients had more bothersome loss of taste/smell, ear pain, sneezing, severe difficulty breathing through nose, and severe nasal congestion compared to neCRS patients (p < 0.05). CONCLUSION: Subclassifying CRS with symptoms alone is difficult with neither polyp status nor eosinophilia giving a distinctive clinical symptom profile. However, certain symptoms may help otolaryngologists identify CRS subtypes, which may help guide future treatments. Further validation and evaluation of prognosis following treatment is required to evaluate appropriate means of subclassifying CRS.

World Health Organization-defined eosinophilic disorders: 2015 update on diagnosis, risk stratification, and management.

DISEASE OVERVIEW: The eosinophilias encompass a broad range of non-hematologic (secondary or reactive) and hematologic (primary, clonal) disorders with potential for end-organ damage. DIAGNOSIS: Hypereosinophilia has generally been defined as a peripheral blood eosinophil count greater than 1,500/mm(3) and may be associated with tissue damage. After exclusion of secondary causes of eosinophilia, diagnostic evaluation of primary eosinophilias relies on a combination of morphologic review of the blood and marrow, standard cytogenetics, fluorescent in situ-hybridization, flow immunocytometry, and T-cell clonality assessment to detect histopathologic or clonal evidence for an acute or chronic myeloid or lymphoproliferative disorder. RISK STRATIFICATION: Disease prognosis relies on identifying the subtype of eosinophilia. After evaluation of secondary causes of eosinophilia, the 2008 World Health Organization establishes a semi-molecular classification scheme of disease subtypes including 'myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB, or FGFR1', chronic eosinophilic leukemia, not otherwise specified, (CEL, NOS), lymphocyte-variant hypereosinophilia, and idiopathic hypereosinophilic syndrome (HES), which is a diagnosis of exclusion. RISK-ADAPTED THERAPY: The goal of the therapy is to mitigate eosinophil-mediated organ damage. For patients with milder forms of eosinophilia (e.g. < 1,500/mm(3) ) without symptoms or signs of organ involvement, a watch and wait approach with close-follow-up may be undertaken. Identification of rearranged PDGFRA or PDGFRB is critical because of the exquisite responsiveness of these diseases to imatinib. Corticosteroids are first-line therapy for patients with lymphocyte-variant hypereosinophilia and HES. Hydroxyurea and interferon-alpha have demonstrated efficacy as initial treatment and steroid-refractory cases of HES. In addition to hydroxyurea, second line cytotoxic chemotherapy agents and hematopoietic cell transplant have been used for aggressive forms of HES and CEL with outcomes reported for limited numbers of patients. Although clinical trials have been performed with anti IL-5 (mepolizumab) and anti-CD52 (alemtuzumab) antibodies, their therapeutic role in primary eosinophilic diseases and HES has yet to be established.

Eosinophilic pustular folliculitis: the transition in sex differences and interracial characteristics between 1965 and 2013.

Eosinophilic pustular folliculitis (EPF) is characterized by a non-infectious infiltration of eosinophils in the hair follicles. It has three variants: (i) classic EPF; (ii) immunosuppression-associated EPF, which herein is subdivided into HIV-associated (IS/HIV) and non-HIV-associated (IS/non-HIV); and (iii) infancy-associated EPF (I-EPF). The rarity of EPF has hindered our understanding of this entity. To examine the characteristics of EPF, with respect to age, sex, race, and chronology, published in case reports to date, we queried PubMed using the following terms: ("eosinophilic pustular folliculitis" [All Fields] OR "eosinophilic folliculitis" [All Fields]) AND ("1965/1/1" [PDAT]: "2013/12/31" [PDAT]). Additional Japanese cases were collected from Igaku Chuo Zasshi through Ichushi-Web, JDream III, and secondhand quotations from domestic periodicals published in Japan. Proceedings were excluded. The PubMed search produced 275 citations containing 358 cases of EPF (224 men, 132 women, and two of unspecified sex); these cases involved classic EPF (101 Japanese and 81 non-Japanese), IS/HIV (4 Japanese and 85 non-Japanese), IS/non-HIV (4 Japanese and 20 non-Japanese), and I-EPF (4 Japanese and 59 non-Japanese). Ichushi generated an additional 148 citations containing 207 cases of Japanese (148 men and 59 women), which included cases of classic EPF (181 cases), IS/HIV (14 cases), IS/non-HIV (9 cases), and I-EPF (3 cases). There was no sex difference in the classic EPF cases reported between 2003 and 2013, whereas IS/HIV, IS/non-HIV, and I-EPF were predominated by men. There is room for reconsideration of sex differences, particularly with regard to classic EPF. The rarity and specificity of I-EPF in Japan may reflect a state of uncertainty about this entity.

Proton pump inhibitor responsive esophageal eosinophilia, a distinct disease entity?

Recent studies have suggested the existence of a patient population with esophageal eosinophilia that responds to proton pump inhibitor therapy. These patients are being referred to as having proton pump inhibitor responsive esophageal eosinophilia (PPI-REE), which is currently classified as a distinct and separate disease entity from both gastroesophageal reflux disease (GERD) and eosinophilic esophagitis (EoE). The therapeutic effect of proton pump inhibitor (PPI) on PPI-REE is thought to act directly at the level of the esophageal mucosa with an anti-inflammatory capacity, and completely independent of gastric acid suppression. The purpose of this manuscript is to review the mechanistic data of the proposed immune modulation/anti-inflammatory role of the PPI at the esophageal mucosa, and the existence of PPI-REE as a distinct disease entity from GERD and EoE.

World Health Organization-defined eosinophilic disorders: 2014 update on diagnosis, risk stratification, and management.

DISEASE OVERVIEW: The eosinophilias encompass a broad range of nonhematologic (secondary or reactive) and hematologic (primary, clonal) disorders with potential for end-organ damage. DIAGNOSIS: Hypereosinophilia (HE) has generally been defined as a peripheral blood eosinophil count greater than 1,500/mm(3) and may be associated with tissue damage. After exclusion of secondary causes of eosinophilia, diagnostic evaluation of primary eosinophilias relies on a combination of morphologic review of the blood and marrow, standard cytogenetics, fluorescent in situ hybridization, flow immunocytometry, and T-cell clonality assessment to detect histopathologic or clonal evidence for an acute or chronic myeloid or lymphoproliferative disorder. RISK STRATIFICATION: Disease prognosis relies on identifying the subtype of eosinophilia. After evaluation of secondary causes of eosinophilia, the 2008 World Health Organization establishes a semimolecular classification scheme of disease subtypes including "myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB, or FGFR1', chronic eosinophilic leukemia, not otherwise specified" (CEL, NOS), lymphocyte-variant HE, and idiopathic hypereosinophilic syndrome (HES), which is a diagnosis of exclusion. RISK-ADAPTED THERAPY: The goal of therapy is to mitigate eosinophil-mediated organ damage. For patients with milder forms of eosinophilia (e.g., <1,500/mm(3)) without symptoms or signs of organ involvement, a watch and wait approach with close-follow-up may be undertaken. Identification of rearranged PDGFRA or PDGFRB is critical because of the exquisite responsiveness of these diseases to imatinib. Corticosteroids are first-line therapy for patients with lymphocyte-variant HE and HES. Hydroxyurea and interferon-alpha have demonstrated efficacy as initial treatment and steroid-refractory cases of HES. In addition to hydroxyurea, second-line cytotoxic chemotherapy agents and hematopoietic cell transplant have been used for aggressive forms of HES and CEL with outcomes reported for limited number of patients. Although clinical trials have been performed with anti-IL-5 (mepolizumab) and anti-CD52 (alemtuzumab) antibodies, their therapeutic role in primary eosinophilic diseases and HES has yet to be established.

Advances in the diagnosis and treatment of eosinophilia.

PURPOSE OF REVIEW: Eosinophils play an important role in the pathogenesis of allergic, infectious and malignant diseases. Over the last decade, new diagnostic tools and treatment modalities have led to the re-evaluation of the existing definition of eosinophilic disorders. This review discusses a recent proposal for new terminology and classification of hypereosinophilia. The results of targeted therapy for hypereosinophilia-related disorders are also summarized. RECENT FINDINGS: A panel of multidisciplinary experts agreed on unifying definitions and criteria of eosinophilia-associated disorders and created a new classification of hypereosinophilia-related conditions based on clinical, haematological and laboratory findings as well as the underlying cause of hypereosinophilia. Recent results of the treatment of idiopathic hypereosinophilic syndrome (HES) with the anti-interleukin 5 monoclonal antibody mepolizumab showed its efficacy and manageable safety profile. The treatment of platelet-derived growth factor alpha (PDGFRA)-positive HES with imatinib demonstrated long-lasting efficacy and low likelihood of drug resistance. SUMMARY: The unifying terminology and definitions should aid physicians caring for patients with hypereosinophilia. Despite much progress, serum biomarkers correlate with disease severity and predict responses to treatment that are needed. There is also a great need for understanding and specific therapy for PDGFRA-negative HES.

Update on the classification and treatment of localized scleroderma.

Morphea or localized scleroderma is a distinctive inflammatory disease that leads to sclerosis of the skin and subcutaneous tissues. It comprises a number of subtypes differentiated according to their clinical presentation and the structure of the skin and underlying tissues involved in the fibrotic process. However, classification is difficult because the boundaries between the different types of morphea are blurred and different entities frequently overlap. The main subtypes are plaque morphea, linear scleroderma, generalized morphea, and pansclerotic morphea. With certain exceptions, the disorder does not have serious systemic repercussions, but it can cause considerable morbidity. In the case of lesions affecting the head, neurological and ocular complications may occur. There is no really effective and universal treatment so it is important to make a correct assessment of the extent and severity of the disease before deciding on a treatment approach.

Mucosal-type eosinophilic gastroenteritis in Thailand: 12-year retrospective study.

OBJECTIVE: To evaluate the clinical features and natural course of disease among patients with mucosal-type eosinophilic gastroenteritis in Thailand. MATERIAL AND METHOD: The present study was conducted by retrospectively searching for the ICD-10 code for eosinophilic gastroenteritis (EGE) among medical records for the period 2001-2012. Clinical and pathological specimens were reviewed using the same diagnostic criteria. Appropriate tests were conducted to exclude other secondary causes of EGE. All patients had to have either received empirical treatment for parasitic infections or were tested for parasites in the stool. After the diagnosis had been established, each patient received 30-40 mg/day of oral prednisoloneforfour weeks, which was tapered down as clinical status improved. All patients were followed up by monitoring clinical symptoms and relevant laboratory findings. Patients who did not maintain follow-up appointments were contacted by telephone and asked about their clinical symptoms. RESULTS: Seventeen patients with a diagnosis of mucosal-type E (6 male, 11 female, M:F ratio 1:1.83) were found. Mean age at the time of presentation was 52.5 +/- 13.04 years. Four patients (23.5%) had either allergic or atopic conditions. Chronic diarrhea and weight loss were the most common initial presentation in 16 patients (94.1%). Microscopically and macroscopically, bloody diarrhea was observed in 13 cases (76.5%). Four patients were found to have protein-losing enteropathy. Peripheral eosinophilia was found in 10 patients (58.8%) with absolute eosinophil counts between 744 and 23,550 cells/mm3. Eight of these had an absolute eosinophil count in the hypereosinophilic range (> 1,500 cells/mm3). All patients treated with prednisolone treatment showed symptomatic improvement within four weeks. One patient's symptom resolved spontaneously, without treatment. Thirteen patients relapsed during the tapering-off of prednisolone. Seven patients showed complete remission. Three patients subsequently developed cancer (lung, breast, and bladder) after EGE was diagnosed. CONCLUSION: EGE, although uncommon, is present in Thailand, where parasitic infections continue to be a significant public-health problem.

Diagnostic complexities of eosinophilia.

CONTEXT: The advent of molecular tools capable of subclassifying eosinophilia has changed the diagnostic and clinical approach to what was classically called hypereosinophilic syndrome. OBJECTIVES: To review the etiologies of eosinophilia and to describe the current diagnostic approach to this abnormality. DATA SOURCES: Literature review. CONCLUSION: Eosinophilia is a common, hematologic abnormality with diverse etiologies. The underlying causes can be broadly divided into reactive, clonal, and idiopathic. Classically, many cases of eosinophilia were grouped together into the umbrella category of hypereosinophilic syndrome, a clinical diagnosis of exclusion. In recent years, an improved mechanistic understanding of many eosinophilias has revolutionized the way these disorders are understood, diagnosed, and treated. As a result, specific diagnoses can now be assigned in many cases that were previously defined as hypereosinophilic syndrome. Most notably, chromosomal rearrangements, such as FIP1L1-PDGFRA fusions caused by internal deletions in chromosome 4, are now known to be associated with many chronic eosinophilic leukemias. When present, these specific molecular abnormalities predict response to directed therapies. Although an improved molecular understanding is revolutionizing the treatment of patients with rare causes of eosinophilia, it has also complicated the approach to evaluating and treating eosinophilia. Here, we review causes of eosinophilia and present a framework by which the practicing pathologist may approach this diagnostic dilemma. Finally, we consider recent cases as clinical examples of eosinophilia from a single institution, demonstrating the diversity of etiologies that must be considered.

Persistent hypereosinophilia with Wells syndrome.

Since Wells and Smith first described cases of eosinophilic cellulitis (Wells syndrome; WS) in 1979, it has been noted that some but not all patients with WS present with eosinophilia. In the face of idiopathic persistent eosinophilia patients will also then fall within the hypereosinophilic syndrome (HES), which represents a multifarious spectrum of disorders of varying severity, causes and outcomes. In this article we propose that patients who present within the HES spectrum with cutaneous findings of WS and with no extracutaneous disease be classified as having 'persistent hypereosinophilia with Wells syndrome' (PHEWS).