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Wu EY, Drage M, Srivastava A, Lisovsky M. Clinicopathological and immunophenotypical characterisation of lymphocytic oesophagitis in adults with Crohn's disease. Histopathology 2025. [PMID: 40223223 DOI: 10.1111/his.15443] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2025] [Revised: 02/16/2025] [Accepted: 02/26/2025] [Indexed: 04/15/2025]
Abstract
AIMS Lymphocytic oesophagitis (LE) is a histological pattern characterised by increased peripapillary lymphocytes and absent or rare granulocytes. Although its association with Crohn's disease (CrD) is established in children, little is known about LE in adult CrD patients. Previous studies have demonstrated immunophenotypical heterogeneity of LE, suggesting its clinical utility in distinguishing CD8 T cell-predominant LE associated with gastroesophageal reflux disease from CD4 T cell-predominant LE associated with other aetiologies. This study aimed to characterise LE and determine its CD4/CD8 immunoprofile in adults with CrD. METHODS AND RESULTS The study included adults with LE and CrD (n = 19) and those without CrD (n = 52). CD4/CD8 lymphocytes were identified by routine immunohistochemistry. The number of lymphocytes was either manually counted or estimated by eye. Compared to patients with LE without Crohn's disease, those with LE and CrD were younger (mean age = 37.9 versus 55.5 years; P < 0.0001), showed oesophageal ulceration (31.6 versus 0%; P = 0.0002) and took fewer medications (median = 4 versus 9; P = 0.0005). LE in CrD was mainly CD4 T cell-predominant (84.2 versus 59.6%; P = non-significant) and with higher CD4/CD8 T cell ratio (median = 2.4 versus 1.1; P < 0.003). When eyeball estimation of CD4/CD8 lymphocyte predominance was compared to actual counting, approximately one-third of total cases showed discordance, with 81% having estimated proportions of CD4/CD8 lymphocytes roughly equal. CONCLUSIONS Patients with LE and CrD are characterised by younger age, oesophageal ulceration and CD4-predominant lymphocytic infiltrate.
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Affiliation(s)
| | - Michael Drage
- Department of Pathology, Mass General Brigham, Harvard Medical School, Boston, MA, USA
| | - Amitabh Srivastava
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Mikhail Lisovsky
- Department of Pathology, Dartmouth-Hitchcock Medical Center, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA
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2
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Wojas O, Krzych-Fałta E, Żybul P, Samoliński B, Przybyłkowski A. Lymphocytic Esophagitis—A Novel Clinicopathologic Variant of Chronic Esophagitis: A Review Paper. GASTROINTESTINAL DISORDERS 2024; 6:885-893. [DOI: 10.3390/gidisord6040062] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2025] Open
Abstract
Background/Objectives: Lymphocytic esophagitis is a rare inflammatory disease of the esophagus, first described in 2006. Since that time, interest in this disease entity has steadily increased, yet specific data on the etiology of the disease are still lacking. Lymphocytic esophagitis co-occurs with esophageal motility disorders, Crohn’s disease, hypersensitivity (allergy, asthma), the use of certain medications, or immune disorders. Risk factors include smoking and alcohol abuse. The disease is more prevalent in women, developing predominantly within the sixth decade of life. The most important symptom is dysphagia, with odynophagia, epigastric, and chest pain or heartburn being less common. No particular endoscopic presentation is pathognomonic for lymphocytic esophagitis, the findings not infrequently resembling those of eosinophilic esophagitis. Conclusions: There is great need for an international consensus defining strict histopathological criteria for the diagnosis of lymphocytic esophagitis as well as relevant diagnostic and therapeutic management. This review paper presents the current state of knowledge on lymphocytic esophagitis.
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Affiliation(s)
- Oksana Wojas
- Department of Prevention of Environmental Hazards, Allergology and Immunology, Medical University of Warsaw, 02-097 Warsaw, Poland
| | - Edyta Krzych-Fałta
- Department of Basic Nursing, Medical University of Warsaw, 01-445 Warsaw, Poland
| | - Paulina Żybul
- Department of Gastroenterology and Internal Medicine, Medical University of Warsaw, 02-097 Warsaw, Poland
| | - Bolesław Samoliński
- Department of Prevention of Environmental Hazards, Allergology and Immunology, Medical University of Warsaw, 02-097 Warsaw, Poland
| | - Adam Przybyłkowski
- Department of Gastroenterology and Internal Medicine, Medical University of Warsaw, 02-097 Warsaw, Poland
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El Halabi M, Saoud C, Nasser SM. Lymphocytic Esophagitis: A Histologic Pattern of Various Underlying Disorders. J Clin Gastroenterol 2024:00004836-990000000-00360. [PMID: 39729980 DOI: 10.1097/mcg.0000000000002067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Accepted: 07/31/2024] [Indexed: 12/29/2024]
Abstract
BACKGROUND Lymphocytic esophagitis (LyE) is a rare condition that has been reported in several case studies, but its diagnostic criteria and clinical significance are inconsistent. There are no established clinical associations, except for Crohn's disease in children. Our study aimed to determine if patients with LyE have distinct demographic or clinical characteristics when compared with patients with increased intraepithelial lymphocytes (IEL) in their esophageal biopsy. METHODS We conducted a retrospective review of all esophageal biopsies between 2008 and 2023 in 2 medical centers. After excluding cases that met criteria for specific disorders, we identified all cases with increased IEL and compared their clinical, demographic, and endoscopic characteristics to those of LyE. RESULTS We identified 381 cases with increased IEL, of which 15 met the criteria for LyE. Patients diagnosed with LyE showed no distinctive demographic, endoscopic, or associated morbidities. The gradual increase in esophageal IEL was not associated with any differences in demographic, endoscopic, or clinicopathologic findings. CONCLUSION Our findings suggest that lymphocytic esophagitis is not a well-defined clinicopathologic entity but rather a rare and nonspecific histologic pattern associated with various esophageal disorders. Further studies should aim to differentiate between the underlying causes of this histologic pattern, rather than defining it as a single clinicopathologic entity.
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Affiliation(s)
| | - Carla Saoud
- School of Medicine, Lebanese American University
| | - Selim M Nasser
- Department of Pathology, School of Medicine, Lebanese American University, Byblos, Lebanon
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Coady LC, Sheahan K, Brown IS, Carneiro F, Gill AJ, Kumarasinghe P, Kushima R, Lauwers GY, Pai RK, Shepherd NA, Slavik T, Srivastava A, Langner C. Esophageal lymphocytosis: exploring the knowns and unknowns of this pattern of esophageal injury. Expert Rev Gastroenterol Hepatol 2024; 18:529-539. [PMID: 39268773 DOI: 10.1080/17474124.2024.2385493] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2024] [Revised: 05/12/2024] [Accepted: 07/23/2024] [Indexed: 09/15/2024]
Abstract
INTRODUCTION Lymphocyte-rich inflammation of the esophageal mucosa has gained increased awareness among pathologists and clinicians recently. Patients usually present with symptoms of esophageal dysfunction, including dysphagia and food bolus impaction. Endoscopy may show changes similar to eosinophilic esophagitis but may also be entirely normal ('microscopic esophagitis'). Three morphological subtypes or variant forms have been described which include lymphocytic, lichenoid and lymphocyte-predominant esophagitis. These need to be discriminated against other distinct causes of esophageal lymphocytosis, such as gastro-esophageal reflux disease and Candida infection. AREAS COVERED This review provides an overview of diagnostic criteria and clinical associations of the disorder and presents an algorithmic approach to diagnosis. A comprehensive literature review was conducted using PubMed, Medline and Google Scholar databases to identify articles related to lymphocyte-rich esophageal inflammation, published up to March 2024. EXPERT OPINION Lymphocyte-rich inflammation needs to be included in the differential diagnosis and clinical work-up of patients with esophageal dysfunction. There is currently considerable morphological overlap among published subtypes or variant forms. Follow-up studies of affected individuals are needed to formalize diagnostic parameters and identify the clinical course of disease in order to optimize treatment modalities.
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Affiliation(s)
- Laoise C Coady
- Department of Histopathology, St. Vincent's University Hospital, Elm Park, Dublin 4, Ireland
| | - Kieran Sheahan
- Department of Histopathology, St. Vincent's University Hospital, Elm Park, Dublin 4, Ireland
- UCD School of Medicine, University College Dublin, Belfield, Dublin 4, Ireland
| | - Ian S Brown
- Envoi Specialist Pathologists, Brisbane, Queensland, Australia
- Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia
- Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia
| | - Fátima Carneiro
- Ipatimup - Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal
- Department of Pathology, Faculty of Medicine of the University of Porto, Alameda Prof. Hernâni Monteiro, Portugal
- Centro Hospitalar Universitário São João, Alameda Prof. Hernani Monteiro, Porto, Portugal
| | - Anthony J Gill
- Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, NSW, Australia
- New South Wales Health Pathology, Department of Anatomical Pathology, Royal North Shore Hospital, St Leonards, NSW, Australia
- Sydney Medical School, University of Sydney, Sydney, NSW, Australia
| | | | - Ryoji Kushima
- Department of Pathology, Shiga University of Medical Science, Otsu, Japan
| | - Gregory Y Lauwers
- Department of Pathology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
- Departments of Pathology and Oncologic Sciences, University of South Florida, Tampa, FL, USA
| | - Rish K Pai
- Department of Laboratory Medicine and Pathology, Mayo Clinic Arizona, Scottsdale, AZ, USA
| | - Neil A Shepherd
- Gloucestershire Cellular Pathology Laboratory, Cheltenham General Hospital, Cheltenham, UK
| | - Tomas Slavik
- Ampath Pathology Laboratories, Pretoria, South Africa
- Department of Anatomical Pathology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa
| | - Amitabh Srivastava
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, USA
| | - Cord Langner
- Diagnostic and Research Institute of Pathology, Diagnostic and Research Center for Molecular BioMedicine, Medical University of Graz, Graz, Austria
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Ryan MA, Ermarth A. Inflammatory Causes of Dysphagia in Children. Otolaryngol Clin North Am 2024; 57:669-684. [PMID: 38637195 DOI: 10.1016/j.otc.2024.03.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/20/2024]
Abstract
Gastroesophageal reflux (GER) and eosinophilic esophagitis (EoE) are the most common inflammatory causes of pediatric dysphagia, but several other less prevalent conditions should be considered. These conditions can affect one or several aspects of the swallowing process. In some inflammatory conditions dysphagia may be an early symptom. Esophagoscopy and instrumental swallow studies are often needed to determine the underlying diagnosis and best treatment plan. In some inflammatory conditions dysphagia can portend a worse outcome and need for more aggressive treatment of the underlying condition. Consultations with speech language pathology, gastroenterology, dietetics, allergy/immunology and/or rheumatology are often needed to optimize management.
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Affiliation(s)
- Marisa A Ryan
- Pediatric Otolaryngology, Peak ENT Associates, 1055 North 300 West, Suite 401, Provo, UT 84604, USA.
| | - Anna Ermarth
- Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology and Nutrition, University of Utah School of Medicine, 81 Mario Capecchi Drive, Salt Lake City, UT 84113, USA
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Olmos JA, Pandolfino JE, Piskorz MM, Zamora N, Díaz MAV, Troche JMR, Guzmán M, Hani A, García LRV, Lukashok HP, Domingues G, Vesco E, Rivas MM, Ovalle LFP, Cisternas D, Vela MF. Latin American consensus on diagnosis of gastroesophageal reflux disease. Neurogastroenterol Motil 2024; 36:e14735. [PMID: 38225792 PMCID: PMC11720354 DOI: 10.1111/nmo.14735] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2022] [Revised: 12/05/2023] [Accepted: 12/18/2023] [Indexed: 01/17/2024]
Abstract
BACKGROUND Diagnosing gastroesophageal reflux disease (GERD) can be challenging given varying symptom presentations, and complex multifactorial pathophysiology. The gold standard for GERD diagnosis is esophageal acid exposure time (AET) measured by pH-metry. A variety of additional diagnostic tools are available. The goal of this consensus was to assess the individual merits of GERD diagnostic tools based on current evidence, and provide consensus recommendations following discussion and voting by experts. METHODS This consensus was developed by 15 experts from nine countries, based on a systematic search of the literature, using GRADE (grading of recommendations, assessment, development and evaluation) methodology to assess the quality and strength of the evidence, and provide recommendations regarding the diagnostic utility of different GERD diagnosis tools, using AET as the reference standard. KEY RESULTS A proton pump inhibitor (PPI) trial is appropriate for patients with heartburn and no alarm symptoms, but nor for patients with regurgitation, chest pain, or extraesophageal presentations. Severe erosive esophagitis and abnormal reflux monitoring off PPI are clearly indicative of GERD. Esophagram, esophageal biopsies, laryngoscopy, and pharyngeal pH monitoring are not recommended to diagnose GERD. Patients with PPI-refractory symptoms and normal endoscopy require reflux monitoring by pH or pH-impedance to confirm or exclude GERD, and identify treatment failure mechanisms. GERD confounders need to be considered in some patients, pH-impedance can identify supragrastric belching, impedance-manometry can diagnose rumination. CONCLUSIONS Erosive esophagitis on endoscopy and abnormal pH or pH-impedance monitoring are the most appropriate methods to establish a diagnosis of GERD. Other tools may add useful complementary information.
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Affiliation(s)
- Jorge A. Olmos
- Neurogastroenterology Sector, Hospital de Clinicas Jose de San Martin, Universidad de Buenos Aires, Buenos Aires, Argentina
| | - John E. Pandolfino
- Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - María M. Piskorz
- Neurogastroenterology Sector, Hospital de Clinicas Jose de San Martin, Universidad de Buenos Aires, Buenos Aires, Argentina
| | | | - Miguel A. Valdovinos Díaz
- UNAM, Ciudad de Mexico, Mexico
- Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - José M. Remes Troche
- Institute of Medical Biological Research, Universidad Veracruzana, Veracruz, Mexico
| | - Mauricio Guzmán
- Neurogastroenterology Unit, Gastroenterology Service, Hospital San Martín de La Plata, Buenos Aires, Argentina
| | - Albis Hani
- Hospital San Ignacio-Pontificia Universidad Javeriana, Bogotá, Colombia
| | | | - Hannah Pitanga Lukashok
- Digestive Motility Service, Instituto Ecuatoriano de Enfermedades Digestivas-IECED, Guayaquil, Ecuador
| | | | - Eduardo Vesco
- Neuromotility Unit, Clínica Angloamericana, Lima. Peru
- Universidad Nacional Mayor de San Marcos. Lima, Peru
| | - Mariel Mejia Rivas
- lnternal Medicine, Gastroenterology and Digestive Endoscopy Service, Hospital Vivian Pellas, Managua, Nicaragua
| | - Luis F. Pineda Ovalle
- Neurogastroenterology and Motility Service Motility Instituto Gut Médica, Bogotá, Colombia
| | - Daniel Cisternas
- Clínica Alemana de Santiago, School of Medicine, Universidad del Desarrollo, Clínica Alemana, Vitacura, Chile
| | - Marcelo F. Vela
- Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, Arizona, USA
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Hussein M, Mitchison M, Sweis R. Lymphocytic oesophagitis: diagnosis and management. Clin Med (Lond) 2023; 23:540-544. [PMID: 38065611 PMCID: PMC11298499 DOI: 10.7861/clinmed.2023-0440] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2023]
Abstract
Lymphocytic oesophagitis is a rare inflammatory condition that was first described in 2006. Although it is being increasingly diagnosed, it remains poorly described and characterised. There is limited research on the natural history, diagnosis and management of this condition. The most common presenting symptoms are dysphagia, chest pain and heartburn. Endoscopic features can mimic eosinophilic oesophagitis. International consensus is needed to secure a histological definition, to agree on an endoscopic severity scoring system and to determine an appropriate management algorithm. This review summarises the main evidence for the diagnosis and management of lymphocytic oesophagitis, thus setting the scene for the future directions needed to improve the management of this condition.
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Affiliation(s)
| | | | - Rami Sweis
- University College London Hospital, UK and University College London, UK
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Chauhan A, Das P, Singh A, Mehra L, Rajput MS, Agarwal A, Dutta R, Mehta S, Banyal V, Ahmed A, Mehtab W, Ahuja V, Makharia G. Gastrointestinal tract involvement in patients with potential celiac disease beyond the small intestine: An early proof with IgA anti-tissue transglutaminase-2 antibody deposits. INDIAN J PATHOL MICR 2023; 66:24-30. [PMID: 36656206 DOI: 10.4103/ijpm.ijpm_354_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023] Open
Abstract
BACKGROUND IgA anti-tissue transglutaminase-2 antibody (anti-TG2Ab) deposits in intestinal and extraintestinal organs have been used to link the respective pathological changes in these organs with celiac disease (CeD). AIMS To know if parts of intestine other than the duodenum, such as esophagus, stomach, and colon, have any pathology related to potential CeD or have mucosal IgA anti-TG2 Ab deposits. SETTINGS AND DESIGN A prospective case-control study conducted from April 2018 to December 2019. MATERIALS AND METHODS Nine patients with potential CeD and 27 age- and gender-matched patients with irritable bowel syndrome were recruited as cases and controls, respectively. Mucosal biopsies were collected from esophagus, stomach, duodenum, and rectosigmoid regions, histological changes were evaluated, and IgA anti-TG2 Ab deposits were analyzed in these regions by two-color immunohistochemical staining. STATISTICS Data were analyzed using statistical software Stata 14.0. RESULTS No distinct difference in mucosal lymphocytosis were identified between biopsies of patients with potential CeD and controls at the following sites: esophagus (11.1% vs 0%, P = 0.079), stomach (14.3% vs 7.7%, P = 0.590), and rectum (20% vs 0%, P = 0.067). Co-localized IgA anti-TG2Ab deposits were observed more in potential CeD than in controls at esophagus 22.2% (2/9) vs 0%, P = 0.012; stomach 66.7% (6/9) vs 11.5% (3/26), P < 0.001; and duodenum 66.7% (6/9) vs 0%, P < 0.001 but not at rectum 0% (0/4) vs 0% (0/25). CONCLUSION Although histological changes are not distinct, a subset of subjects with potential CeD has pan-intestinal involvement other than in the duodenum.
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Affiliation(s)
- Ashish Chauhan
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Prasenjit Das
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
| | - Alka Singh
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Lalita Mehra
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
| | - Mahender Singh Rajput
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Ashish Agarwal
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Rimlee Dutta
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Shubham Mehta
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Vikas Banyal
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Anam Ahmed
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Wajiha Mehtab
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Vineet Ahuja
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Govind Makharia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
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Yousef M, Chela H, Ertugrul H, Albarrak A, Basar O, Pasha S, Mousa Y, Al Juboori A, Frazier S, Tahan V, Daglilar E. Lymphocytic Esophagitis: A Case Series of Esophageal Disease with Increasing Frequency. RECENT ADVANCES IN INFLAMMATION & ALLERGY DRUG DISCOVERY 2023; 17:79-84. [PMID: 36718059 DOI: 10.2174/2772270817666230130093341] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Revised: 12/19/2022] [Accepted: 12/30/2022] [Indexed: 02/01/2023]
Abstract
BACKGROUND Lymphocytic esophagitis (LE) is a poorly understood clinical finding that has been increasingly identified in the last decade. Previous studies proposed increased frequency of LE in elderly females, as well as associations with smoking and pediatric Crohn's disease. OBJECTIVE We aimed to determine the patient characteristics and clinical features of our adult LE patients. As inflammation in the esophagus has been linked to cancer, this review also describes this association. However, there are no reported cases of malignant transformation in those with underlying lymphocytic esophagitis. METHODS We retrospectively reviewed records for patients at the University of Missouri Hospital- Columbia (located in the USA) who had a histopathological diagnosis of LE. Cases of LE were identified using the pathology reporting system at the University of Missouri Hospital for esophageal biopsy specimens for the above-mentioned period. RESULTS The data of a total of 20 adult cases with esophageal biopsy specimens consistent with LE were included. CONCLUSION LE seems to be a benign but disturbing clinical problem and should be remembered in elderly females complaining of dysphagia or refractory reflux symptoms. It has similar endoscopic findings of eosinophilic esophagitis with rings and esophagitis. Smoking and hiatal hernia are common risk factors. The majority of LE patients can respond to proton pump inhibitor (PPI) therapy. Endoscopic dilations and steroid therapy should be considered for PPI nonresponder LE patients.
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Affiliation(s)
- Mohamad Yousef
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Missouri, Columbia, Missouri, Mo, USA
| | - Harleen Chela
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Missouri, Columbia, Missouri, Mo, USA
| | - Hamza Ertugrul
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Missouri, Columbia, Missouri, Mo, USA
| | - Abdulmajeed Albarrak
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Missouri, Columbia, Missouri, Mo, USA
| | - Omer Basar
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Missouri, Columbia, Missouri, Mo, USA
| | - Syed Pasha
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Missouri, Columbia, Missouri, Mo, USA
| | - Yousef Mousa
- Department of Pediatrics, Right Way (Germany) Heidekreis-Klinikum GmbH Krankenhaus Walsrode, Walsrode, Germany
| | - Alhareth Al Juboori
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Missouri, Columbia, Missouri, Mo, USA
| | - Shellaine Frazier
- Department of Pathology, University of Missouri, Columbia, Missouri, Mo, USA
| | - Veysel Tahan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Missouri, Columbia, Missouri, Mo, USA
| | - Ebubekir Daglilar
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Missouri, Columbia, Missouri, Mo, USA
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Roach K, Roberts J. A comprehensive summary of disease variants implicated in metal allergy. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH. PART B, CRITICAL REVIEWS 2022; 25:279-341. [PMID: 35975293 PMCID: PMC9968405 DOI: 10.1080/10937404.2022.2104981] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
Allergic disease represents one of the most prominent global public health crises of the 21st century. Although many different substances are known to produce hypersensitivity responses, metals constitute one of the major classes of allergens responsible for a disproportionately large segment of the total burden of disease associated with allergy. Some of the most prevalent forms of metal allergy - including allergic contact dermatitis - are well-recognized; however, to our knowledge, a comprehensive review of the many unique disease variants implicated in human cases of metal allergy is not available within the current scientific literature. Consequently, the main goal in composing this review was to (1) generate an up-to-date reference document containing this information to assist in the efforts of lab researchers, clinicians, regulatory toxicologists, industrial hygienists, and other scientists concerned with metal allergy and (2) identify knowledge gaps related to disease. Accordingly, an extensive review of the scientific literature was performed - from which, hundreds of publications describing cases of metal-specific allergic responses in human patients were identified, collected, and analyzed. The information obtained from these articles was then used to compile an exhaustive list of distinctive dermal/ocular, respiratory, gastrointestinal, and systemic hypersensitivity responses associated with metal allergy. Each of these disease variants is discussed briefly within this review, wherein specific metals implicated in each response type are identified, underlying immunological mechanisms are summarized, and major clinical presentations of each reaction are described.Abbreviations: ACD: allergic contact dermatitis, AHR: airway hyperreactivity, ASIA: autoimmune/ autoinflammatory syndrome induced by adjuvants, BAL: bronchoalveolar lavage, CBD: chronic beryllium disease, CTCL: cutaneous T-cell lymphoma, CTL: cytotoxic T-Lymphocyte, DRESS: drug reaction with eosinophilia and systemic symptoms, GERD: gastro-esophageal reflux disease, GI: gastrointestinal, GIP: giant cell interstitial pneumonia, GM-CSF: granulocyte macrophage-colony stimulating factor, HMLD: hard metal lung disease, HMW: high molecular weight, IBS: irritable bowel syndrome, Ig: immunoglobulin, IL: interleukin, LMW: low molecular weight, PAP: pulmonary alveolar proteinosis, PPE: personal protective equipment, PRR: pathogen recognition receptor, SLE: systemic lupus erythematosus, SNAS: systemic nickel allergy syndrome, Th: helper T-cell, UC: ulcerative colitis, UV: ultraviolet.
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Affiliation(s)
- Ka Roach
- Allergy and Clinical Immunology Branch (ACIB), National Institute of Occupational Safety and Health (NIOSH), Morgantown, WV, USA
| | - Jr Roberts
- Allergy and Clinical Immunology Branch (ACIB), National Institute of Occupational Safety and Health (NIOSH), Morgantown, WV, USA
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11
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Chauhan A, Das P, Singh A, Dutta R, Rajeshwari M, Rajput MS, Agarwal A, Banyal V, Upadhay A, Ahuja V, Makharia G. Pan-Gastrointestinal Tract Mucosal Pathologies in Patients with Celiac Disease with the Demonstration of IgA Anti-Transglutaminase Mucosal Deposits: A Case-Control Study. Dig Dis Sci 2022; 67:3649-3661. [PMID: 34499270 DOI: 10.1007/s10620-021-07246-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2021] [Accepted: 08/23/2021] [Indexed: 01/12/2023]
Abstract
BACKGROUND While celiac disease (CeD) is considered to affect primarily the small intestine, pathological changes in other parts of the gastrointestinal tract (GIT) are also known to occur. IgA anti-tissue transglutaminase-2 antibody (anti-TG2 Ab) deposits at the site of involvement is one of the methods to establish CeD-related tissue pathology. AIMS To explore the utility of IgA anti-TG2 Ab deposits in pan-gastrointestinal mucosal biopsies as evidence of CeD-related pathologies. METHODS Forty-two treatment-naive patients with CeD and 45 patients with irritable bowel syndrome were included as cases and controls, respectively. Mucosal biopsies were collected from the esophagus, stomach, duodenum, and rectosigmoid regions at baseline from cases and controls, and additionally after 6-months of gluten-free diet in cases. All biopsies were evaluated for histological changes and subjected to dual-color immunohistochemical staining for identifying IgA anti-TG2 Ab deposits. RESULTS Significantly higher number of patients with CeD had lymphocytic esophagitis (9.7% vs. 0%, P = 0.05), lymphocytic gastritis (35% vs. 8.8%, P < 0.01) and lymphocytic colitis (17.4% vs. 0%, P < 0.05) than that in controls. IgA anti-TG2 Ab deposits were observed in significantly more numbers in esophagus (30.9% vs. 6%, P < 0.001), stomach (62.2% vs. 9.3%, P < 0.01), duodenum (88.5% vs. 0%, P < 0.001) and rectum (17.4% vs. 0%, P < 0.05) than that in controls. There was a decline, but not statistically significant, in severity of lymphocytosis and intensity of IgA anti-TG2 Ab deposits in follow-up biopsies. CONCLUSION Significantly higher number of patients with CeD had evidence of lymphocytic infiltration and IgA anti-TG2 deposits along GIT suggesting that CeD affects other parts of GIT.
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Affiliation(s)
- Ashish Chauhan
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Prasenjit Das
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
| | - Alka Singh
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Rimlee Dutta
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
| | - Madhu Rajeshwari
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
| | - Mahendra Singh Rajput
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Ashish Agarwal
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Vikas Banyal
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Ashish Upadhay
- Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, India
| | - Vineet Ahuja
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Govind Makharia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India.
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12
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Abstract
This review summarizes our current understanding of lymphocytic esophagitis (LE), a novel form of chronic esophagitis that incorporates distinctive histologic, clinical, and endoscopic features. First described as a histologic entity, a diagnosis of LE requires intraepithelial lymphocytosis without significant granulocytic inflammation and some evidence of epithelial damage; the rationale for and studies supportive of these histologic criteria are discussed within. Clinically, the majority of patients who present with histologically confirmed LE are older women or patients with underlying immunologic abnormalities, such as Crohn disease, rheumatologic disorders, or common variable immunodeficiency. The most common presenting symptom of LE is dysphagia, and the endoscopic findings can vary from normal mucosa to mucosal changes that resemble eosinophilic esophagitis: edema, rings, furrows, and plaques. The incidence of luminal strictures and the persistent dysphagia and/or lymphocytosis present in some patients provide evidence that LE is a chronic inflammatory disorder, at least within a subset of individuals. Several histologic mimics of LE are examined, as are disagreements surrounding the LE diagnosis.
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13
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Kővári B, Pai RK. Upper Gastrointestinal Tract Involvement in Inflammatory Bowel Diseases: Histologic Clues and Pitfalls. Adv Anat Pathol 2022; 29:2-14. [PMID: 34310370 PMCID: PMC8663524 DOI: 10.1097/pap.0000000000000311] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
The upper gastrointestinal (UGI) manifestations of inflammatory bowel diseases (IBDs) are frequently obscured by classic ileal and colonic symptoms and are reported to involve only 0.5% to 4% of adult patients. However, because of the improvement of endoscopic techniques and the growing use of esophagogastroduodenososcopy with biopsy, both asymptomatic and clinically significant esophageal, gastric, and duodenal manifestations are increasingly recognized. The UGI involvement in IBD was historically synonymous with Crohn's disease (CD), but the doctrine of ulcerative colitis (UC) being limited to the colon has been challenged, and UC-related gastroduodenal lesions have been reported. The diagnosis of UGI IBD should ideally rely on a combination of the clinical history, endoscopic picture, and histologic features. Although endoscopic changes such as aphthoid or longitudinal ulcers and bamboo-joint-like pattern are suggestive of CD, histologic evaluation increases the sensitivity of the IBD diagnosis since histologic alterations may be present in endoscopically unremarkable mucosa. Conversely, in many cases, the histologic findings are nonspecific, and the knowledge of clinical history is vital for reaching an accurate diagnosis. The presence of epithelioid granuloma is highly suggestive of CD but is present in a minority of CD cases; thus, pathologists should be aware of how to diagnose UGI IBD in the absence of granulomata. This article reviews the most important clinical, endoscopic, and histologic features of IBD-associated esophagitis, gastritis, and duodenitis, as well as the IBD-related manifestations in the biliary tract and the postcolectomy setting.
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Affiliation(s)
- Bence Kővári
- Department of Pathology, Henry Lee Moffitt Cancer Center and Research Institute, Tampa, FL
- Department of Pathology, University of Szeged and Albert Szent-Györgyi Health Center, Szeged, Hungary
| | - Rish K. Pai
- Department of Laboratory Medicine and Pathology, Mayo Clinic Arizona, Scottsdale, AZ
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14
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Zaver HB, Ghoz H, Malviya BJ, Brahmbhatt B, Palmer WC, Lacy BE, DeVault KR, Krishna M, Bi Y. Lymphocytic Esophagitis: Assessing Risk Factors and Clinical Outcomes. Dig Dis Sci 2021; 66:3976-3984. [PMID: 33216240 DOI: 10.1007/s10620-020-06706-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2020] [Accepted: 11/02/2020] [Indexed: 12/26/2022]
Abstract
BACKGROUND Lymphocytic esophagitis is a rare esophageal condition. Our knowledge of potential risk factors and treatment outcomes of lymphocytic esophagitis is limited. AIM To investigate potential risk factors associated with the development of lymphocytic esophagitis and compare clinical characteristics and treatment outcomes of patients diagnosed with lymphocytic esophagitis to patients diagnosed with eosinophilic esophagitis. METHODS This is a multicenter retrospective study. Lymphocytic esophagitis patients were identified based on pathology results between 1997 and 2019. Control groups consisted of patients with normal esophageal biopsies and patients diagnosed with eosinophilic esophagitis. Thirteen potential risk factors for lymphocytic esophagitis were analyzed using univariate and multivariate models including IBD, achalasia, hyperlipidemia, hypothyroidism, celiac sprue, CVID, H. pylori, thymoma, aspirin, opioids, ACE-I, metformin, and statin use. Comparative statistics were performed. RESULTS Ninety-four adult patients with lymphocytic esophagitis, 344 with eosinophilic esophagitis, and 5202 control patients with normal esophageal biopsies were analyzed. Age older than 60 [adjusted odd ratio (AOR) 1.03, 95% CI 1.02-1.05, p = 0.001], aspirin use (2.7, 95% CI 1.4-4.9, p = 0.001), statin use (2.2, 95% CI 1.2-4.2, p = 0.01), or a diagnosis of achalasia (2.4, 95% 1.08-5.67, p = 0.03) were associated with lymphocytic esophagitis. Compared to eosinophilic esophagitis, lymphocytic esophagitis patients were more likely to respond to medical treatment (95% CI 2.54-12.8, p = 0.0001). CONCLUSIONS Our data suggests that lymphocytic esophagitis is more likely to be found in older female patients and is significantly associated with achalasia, statin, and aspirin use. Compared to eosinophilic esophagitis, lymphocytic esophagitis is more likely to respond to treatment with medical therapy.
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Affiliation(s)
- Himesh B Zaver
- Department of Internal Medicine, Mayo Clinic, Jacksonville, FL, USA
| | - Hassan Ghoz
- Division of Gastroenterology and Hepatology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA
| | - Balkishan J Malviya
- Division of Gastroenterology and Hepatology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA
| | - Bhaumik Brahmbhatt
- Division of Gastroenterology and Hepatology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA
| | - William C Palmer
- Division of Gastroenterology and Hepatology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA
| | - Brian E Lacy
- Division of Gastroenterology and Hepatology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA
| | - Kenneth R DeVault
- Division of Gastroenterology and Hepatology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA
| | - Murli Krishna
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Jacksonville, FL, USA
| | - Yan Bi
- Division of Gastroenterology and Hepatology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA.
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15
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Salimian KJ, Birkness-Gartman J, Waters KM. The path(ology) from reflux oesophagitis to Barrett oesophagus to oesophageal adenocarcinoma. Pathology 2021; 54:147-156. [PMID: 34711413 DOI: 10.1016/j.pathol.2021.08.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Revised: 08/23/2021] [Accepted: 08/23/2021] [Indexed: 02/07/2023]
Abstract
This review seeks to summarise the steps in the path from reflux oesophagitis to Barrett oesophagus to oesophageal adenocarcinoma. The epidemiology, clinical presentation, definitions, pathological features, diagnostic pitfalls, and emerging concepts are reviewed for each entity. The histological features of reflux oesophagitis can be variable and are not specific. Cases of reflux oesophagitis with numerous eosinophils are difficult to distinguish from eosinophilic oesophagitis and other oesophagitides with eosinophils (Crohn's disease, medication effect, and connective tissue disorders). In reflux oesophagitis, the findings are often most pronounced in the distal oesophagus, the eosinophils are randomly distributed throughout the epithelium, and eosinophilic abscesses and degranulated eosinophils are rare. For reflux oesophagitis with prominent lymphocytes, clinical history and ancillary clinical studies are paramount to distinguish reflux oesophagitis from other causes of lymphocytic oesophagitis pattern. For Barrett oesophagus, the definition remains a hotly debated topic for which the requirement for intestinal metaplasia to make the diagnosis is not applied unanimously across the globe. Assessing for dysplasia is a challenging aspect of the histological interpretation that guides clinical management. We describe the histological features that we find useful in making this evaluation. Oesophageal adenocarcinoma has been steadily increasing in incidence and has a poor prognosis. The extent of invasion can be overdiagnosed due to a duplicated muscularis mucosae. We also describe the technical factors that can lead to challenges in distinguishing the mucosal and deep margins of endoscopic resections. Lastly, we give an overview of targeted therapies with emerging importance and the ancillary tests that can identify the cases best suited for each therapy.
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Affiliation(s)
- Kevan J Salimian
- Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | | | - Kevin M Waters
- Department of Pathology and Laboratory Medicine, Cedars Sinai Medical Center, Los Angeles, CA, USA.
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16
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Muller K, Xiao J, Putra J, Rothstein R, McCourt C, Konnikova L, Lisovsky M. Lymphocytic Esophagitis With Predominance of CD4 T Cells and Expansion of Th1 Cells Is Associated With Achalasia. Am J Clin Pathol 2021; 156:278-287. [PMID: 33609026 PMCID: PMC12096299 DOI: 10.1093/ajcp/aqaa239] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
OBJECTIVES Although histologic features in biopsies suggesting a possibility of achalasia would be helpful diagnostically, such features remain unknown. The goal of this study was to explore the prevalence, histologic features, and immunophenotype of lymphocytic esophagitis (LyE) in achalasia biopsies. METHODS The study group consisted of 57 patients with achalasia. Controls comprised 52 patients with severe gastroesophageal reflux disease (GERD) and normal esophageal motility. CD4/CD8 immunophenotype of lymphocytes was analyzed by immunohistochemistry. RESULTS LyE was identified in 30% (17/57) of patients with achalasia and 6% (3/52) of patients with GERD, indicating a strong association with achalasia (odds ratio, 6.94; 95% confidence interval, 1.90-25.38). LyE was focal in 59% (10/17) of the cases and diffuse in 41% (7/17). CD4 T-cell predominance over CD8 T cells was observed in 88% of patients with achalasia and LyE. T helper 1 (Th1) cells, but not T helper 2 cells, were expanded in CD4 T cells; in the absence of evident infection, this was compatible with the role of Th1 cells in organ-specific autoimmunity. CONCLUSIONS Achalasia should be considered in the differential diagnosis of clinical entities associated with CD4-predominant LyE. Additional studies to explore the significance of Th1 cells in achalasia-associated LyE are warranted.
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Affiliation(s)
- Kristen Muller
- Department of Pathology, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA
| | - Jenny Xiao
- Department of Pediatrics, UPMC Children’s Hospital of Pittsburgh, Pittsburgh, PA, USA
| | - Juan Putra
- Department of Pathology, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA
| | - Richard Rothstein
- Section of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA
| | - Collin McCourt
- Department of Pediatrics, UPMC Children’s Hospital of Pittsburgh, Pittsburgh, PA, USA
| | - Liza Konnikova
- Department of Pediatrics, UPMC Children’s Hospital of Pittsburgh, Pittsburgh, PA, USA
- Department of Immunology, University of Pittsburgh, Pittsburgh, PA, USA
| | - Mikhail Lisovsky
- Department of Pathology, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA
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17
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Neutrophils, eosinophils, and intraepithelial lymphocytes in the squamous esophagus in subjects with and without gastroesophageal reflux symptoms. Hum Pathol 2021; 115:112-122. [PMID: 34181982 DOI: 10.1016/j.humpath.2021.06.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Revised: 06/17/2021] [Accepted: 06/18/2021] [Indexed: 02/07/2023]
Abstract
Whilst intraepithelial lymphocytes (IELs) are considered normal within the distal esophageal mucosa, they have an increasingly recognised role in the pathogenesis of reflux esophagitis, and IEL quantification establishes the diagnosis of lymphocytic esophagitis. Knowledge regarding the upper limit of a normal IEL count in health is lacking. We studied 117 non-healthcare seeking adult volunteers from a random community sample (the Kalixanda study) with esophageal biopsies 2 cm above the gastroesophageal junction. Subjects were divided into four groups based on the presence or absence of gastro-esophageal reflux symptoms and/or esophagitis on endoscopy. Asymptomatic subjects with no endoscopic esophagitis were selected as controls, and the cell counts in this group were used to define the upper limit of normal of IELs, eosinophils and neutrophils. The entire sample was used to identify independent predictors of increased cellular counts by logistic regression analysis. None of the healthy controls had an IEL count of more than three per five high power fields (HPF), and therefore this was considered as the upper limit of normal; no controls had eosinophils or neutrophils in esophageal biopsies. Independent predictors of an elevated IEL count were spongiosis on histology (OR 11.17, 95% CI 3.32-37.58, P < 0.01) and current smoking (OR 4.84, 95% CI 1.13-2.71, P = 0.03). A receiver operating characteristics analysis concluded that a threshold of 3 IELs/5HPFs performs best in predicting reflux symptoms when a normal esophageal mucosa is visualized on endoscopy (sensitivity = 100.0%, specificity = 35.2%). The healthy esophageal mucosa does not contain more than three IELs per five HPF in the distal esophagus.
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18
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Biedermann L, Straumann A, Greuter T, Schreiner P. Eosinophilic esophagitis-established facts and new horizons. Semin Immunopathol 2021; 43:319-335. [PMID: 34097125 PMCID: PMC8241662 DOI: 10.1007/s00281-021-00855-y] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2020] [Accepted: 03/23/2021] [Indexed: 12/13/2022]
Abstract
Despite dramatic advances in our understanding of the pathogenesis and course of disease in the relatively short timeframe since the discovery and first description of eosinophilic esophagitis (EoE) less than three decades ago, many open questions remain to be elucidated. For instance, we will need to better characterize atypical clinical presentations of EoE and other forms of esophageal inflammatory conditions with often similar clinical presentations, nut fulfilling current diagnostic criteria for EoE and to determine their significance and interrelationship with genuine EoE. In addition, the interrelationship of EoE with other immune-mediated diseases remains to be clarified. Hopefully, a closer look at the role of environmental factors and their interaction with genetic susceptibility often in context of atopic predisposition may enable identifying the candidate substances/agents/allergens and potentially earlier (childhood) events to trigger the condition. It appears plausible to assume that in the end—comparable to current concepts in other immune-mediated chronic diseases, such as for instance inflammatory bowel disease or asthma bronchiale—we will not be rewarded with the identification of a “one-and-only” underlying pathogenetic trigger factor, with causal responsibility for the disease in each and every EoE patient. Rather, the relative contribution and importance of intrinsic susceptibility, i.e., patient-driven factors (genetics, aberrant immune response) and external trigger factors, such as food (or aero-) allergens as well as early childhood events (e.g., infection and exposure to antibiotics and other drugs) may substantially differ among given individuals with EoE. Accordingly, selection and treatment duration of medical therapy, success rates and extent of required restriction in dietary treatment, and the need for mechanical treatment to address strictures and stenosis require an individualized approach, tailored to each patient. With the advances of emerging treatment options, the importance of such an individualized and patient-centered assessment will increase even further.
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Affiliation(s)
- Luc Biedermann
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.
| | - Alex Straumann
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Thomas Greuter
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.,Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne, Switzerland
| | - Philipp Schreiner
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
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19
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Wojas O, Żalikowska-Gardocka M, Krzych-Fałta E, Szczepankiewicz B, Samel-Kowalik P, Samoliński B, Przybyłkowski A. A case of lymphocytic esophagitis in a woman with multiple allergies. Allergy Asthma Clin Immunol 2021; 17:56. [PMID: 34099042 PMCID: PMC8186211 DOI: 10.1186/s13223-021-00558-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2020] [Accepted: 05/18/2021] [Indexed: 02/08/2023] Open
Abstract
Background Lymphocytic esophagitis is a newly recognized entity of unknown origin. Dysphagia is defined as difficulty swallowing and represents a common symptom in the general population with a prevalence of approximately 20%. Chronic inflammation of the esophageal wall may manifest itself clinically and endoscopically, mimicking inflammation of another origin. However, little is known about the pathogenesis of the disease, as patients are seldom suspected and rarely diagnosed with lymphocytic esophagitis. Case presentation Here, we present a rare case of lymphocytic esophagitis in a patient with multiple allergies and suspected eosinophilic esophagitis. A 28-year-old woman with polyvalent sensitization to food and inhalant allergens presented with intermittent dysphagia, a sensation of a foreign body in the throat, itchiness of the oral cavity after ingesting certain foods, heartburn, and prolonged chewing time. A skin prick test showed positive results for birch-tree, alder, hazel, and rye pollen, as well as house dust mites. Apart from obesity (BMI 30 kg/m2), multiple pustules and excoriations on the skin, her physical examination was insignificant. Esophagogastroduodenoscopy (EGD) was performed revealing full-length but discrete trachealization of the esophagus. A barium swallow test showed slowing of esophageal peristalsis in the recumbent position. No esophageal pathology was observed. A histopathological analysis of mucosal samples revealed slight hyperplasia of the basal layer of the esophagus, and the stomach showed changes typical of chronic gastritis. Conclusions In summary, this clinical case illustrates that lymphocytic esophagitis, as a newly recognized entity, should be considered in the differential diagnosis of chronic dysphagia. Additionally, when treating allergic patients, clinicians should be aware that lymphocytic esophagitis, distinct from eosinophilic esophagitis, should be considered in the diagnosis of patients with atopy and upper gastrointestinal symptoms.
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Affiliation(s)
- O Wojas
- Department of Prevention of Environmental Hazard and Allergology, Medical University of Warsaw, Warsaw, Poland
| | - M Żalikowska-Gardocka
- Department of Gastroenterology and Internal Medicine, Medical University of Warsaw, Warsaw, Poland.
| | - E Krzych-Fałta
- Department of Prevention of Environmental Hazard and Allergology, Medical University of Warsaw, Warsaw, Poland
| | - B Szczepankiewicz
- Department of Pathomorphology, Medical University of Warsaw, Warsaw, Poland
| | - P Samel-Kowalik
- Department of Prevention of Environmental Hazard and Allergology, Medical University of Warsaw, Warsaw, Poland
| | - B Samoliński
- Department of Prevention of Environmental Hazard and Allergology, Medical University of Warsaw, Warsaw, Poland
| | - A Przybyłkowski
- Department of Gastroenterology and Internal Medicine, Medical University of Warsaw, Warsaw, Poland
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20
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Malone V, Sheahan K. Novel and rare forms of oesophagitis. Histopathology 2020; 78:4-17. [PMID: 33382498 DOI: 10.1111/his.14284] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Revised: 10/09/2020] [Accepted: 10/20/2020] [Indexed: 12/11/2022]
Abstract
Our understanding of inflammatory diseases of the gastrointestinal tract, including those of the oesophagus, has expanded in recent years. Once attributed almost exclusively to gastro-oesophageal reflux disease or infection, it is now recognised that oesophagitis may occur due to a variety of distinct disease entities. Many of these conditions cause debilitating and persistent symptoms, impacting upon quality of life and necessitating ongoing surveillance and treatment. This review will consider the clinical, endoscopic and histopathological features of these novel and rare forms of oesophagitis.
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Affiliation(s)
- Victoria Malone
- Department of Histopathology, St Vincent's University Hospital, School of Medicine and Medical Science, University College Dublin, Dublin, Ireland
| | - Kieran Sheahan
- Department of Histopathology, St Vincent's University Hospital, School of Medicine and Medical Science, University College Dublin, Dublin, Ireland
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21
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Moiseff R, Olson N, Suriawinata AA, Rothstein RI, Lisovsky M. CD8 T-Cell-Predominant Lymphocytic Esophagitis is One of the Major Patterns of Lymphocytic Inflammation in Gastroesophageal Reflux Disease. Arch Pathol Lab Med 2020; 145:1138-1143. [PMID: 33373450 DOI: 10.5858/arpa.2020-0430-oa] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/30/2020] [Indexed: 11/06/2022]
Abstract
CONTEXT.— Published reports have suggested an association of lymphocytic esophagitis (LyE) with gastroesophageal reflux disease (GERD) and primary motility disorders and have also shown that GERD and motility disorders frequently overlap. These findings make it difficult to determine the true relationship between LyE and GERD, which may be confounded by the presence of motility disorders with LyE. OBJECTIVE.— To characterize patterns of lymphocytic inflammation in patients with GERD that have no motility abnormalities. DESIGN.— We identified 161 patients seen at our institution from 1998 to 2014, who were diagnosed with GERD, had normal esophageal motility, and available esophageal biopsies. LyE was defined as peripapillary lymphocytosis with rare or absent granulocytes. CD4 and CD8 immunophenotype of lymphocytes was evaluated using immunohistochemistry. RESULTS.— We found increased intraepithelial lymphocytes in 13.7% of patients with GERD. Two major patterns and 1 minor pattern of lymphocytic inflammation were observed as follows: (1) LyE (in 6.8% [11 of 161] of patients and typically focal), (2) dispersed lymphocytes in an area of reflux esophagitis (in 5.6% [9 of 161] and typically diffuse), and (3) peripapillary lymphocytes in an area of reflux esophagitis (in 1.2% [2 of 161]). CD8 T cells significantly outnumbered CD4 T cells in 91% of patients with lymphocytic esophagitis and 100% of patients with dispersed lymphocytes (9 of 9) or peripapillary lymphocytes (2 of 2) in the area of reflux esophagitis. CONCLUSIONS.— These findings suggest that LyE is one of the major patterns of lymphocytic inflammation in GERD. CD8 T-cell-predominant immunophenotype may be useful as a marker of GERD in the differential diagnosis of LyE.
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Affiliation(s)
- Robin Moiseff
- From the Department of Pathology (Moiseff, Olson, Suriawinata, Lisovsky)
| | - Nicholas Olson
- From the Department of Pathology (Moiseff, Olson, Suriawinata, Lisovsky).,Olson is currently located at Physicians Laboratory in Sioux Falls, South Dakota
| | | | - Richard I Rothstein
- and Section of Gastroenterology and Hepatology (Rothstein), at Dartmouth-Hitchcock Medical Center and Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire
| | - Mikhail Lisovsky
- From the Department of Pathology (Moiseff, Olson, Suriawinata, Lisovsky)
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22
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Lisovsky M. Inflammatory conditions of the esophagus: an update. Ann N Y Acad Sci 2020; 1481:5-10. [PMID: 32783223 DOI: 10.1111/nyas.14450] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Revised: 07/06/2020] [Accepted: 07/08/2020] [Indexed: 12/24/2022]
Abstract
A variety of inflammatory disorders involve the esophagus. This commentary discusses the pathology of some forms of esophagitis, with an emphasis on recent developments. The initial section focuses on some common forms of nonreflux esophagitis, including lymphocytic esophagitis and eosinophilic esophagitis. Recent studies suggest that lymphocytic esophagitis may be associated with esophageal motility disorders and gastroesophageal reflux disease. Immunophenotypic features of intraepithelial lymphocytes may be helpful in distinguishing these conditions. Updates on the criteria and the limitations of histologic approach to the diagnosis of eosinophilic esophagitis are presented and new diagnostic adjuncts are discussed. In the remaining section, novel entities, such as IgG4-related esophagitis, are discussed. IgG4-related esophagitis has been recognized as a cause of esophageal lymphoplasmacytic inflammation. Increased understanding of esophageal inflammation remains an important goal that likely will lead to new approaches in the therapy of inflammatory esophageal diseases.
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Affiliation(s)
- Mikhail Lisovsky
- Department of Pathology, Dartmouth-Hitchcock Medical Center and Geisel Medical School at Dartmouth, Lebanon, New Hampshire
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Islam S, Lee A, Lampe G. Lymphocytic esophagitis: An Australian (Queensland) case series of a newly recognized mimic of eosinophilic esophagitis. JGH OPEN 2019; 3:400-404. [PMID: 31633045 PMCID: PMC6788373 DOI: 10.1002/jgh3.12175] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/08/2018] [Revised: 02/11/2019] [Accepted: 02/24/2019] [Indexed: 11/06/2022]
Abstract
Background and Aim Lymphocytic esophagitis (LoE) is a recently described upper gastrointestinal tract "disorder" diagnosis of which hinges on histology and is characterized by the excessive infiltration of lymphocytes in the peripapillary fields of the esophageal epithelium, with clinical manifestations similar to those of eosinophilic esophagitis (EoE). In this article, we aim to describe for the first time the clinico-pathological characteristics of a large cohort of Australian (Queensland) cases of LoE. Methods Histological data that fulfilled the criteria (predominant lymphocytic infiltration in the peripapillary fields, none or minimal neutrophils or eosinophils, and no infection) were collected between January 2014 and May 2016 from a number of major Queensland Public Hospital anatomical pathology laboratories. Patient presentations were subsequently examined to compile clinical and endoscopic correlates. Results A total of 62 cases of LoE were identified. The median age was 55 years, with 59.6% of subjects being male. Major clinical manifestations included dysphagia (32), epigastric or abdominal pain (8), gastro-esophageal reflux (8), association with Crohn's disease (8), and vomiting or diarrhea (6). Endoscopy was normal in 47% of cases; 47% had appearances similar to those of EoE. There were three cases with associated mild monilial esophagitis (6%). Conclusion LoE is a relatively recently recognized condition of the esophagus with variable clinical and endoscopic findings. Diagnosis is based on characteristic histological features. Further investigation is needed to ascertain the etiopathology and natural history of the condition and to establish a safe and effective treatment regimen.
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Affiliation(s)
- Shamsul Islam
- Department of Gastroenterology, QE-II Jubilee Hospital, Senior Lecturer of Medicine The University of Queensland Brisbane Queensland Australia
| | - Antonio Lee
- Department of Gastroenterology, QE-II Jubilee Hospital, Senior Lecturer of Medicine The University of Queensland Brisbane Queensland Australia
| | - Guy Lampe
- Department of Anatomical Pathology Princess Alexandra Hospital Brisbane Queensland Australia
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Esophagitis in patients without gastroesophageal reflux disease or eosinophilic esophagitis: diagnostic considerations. Curr Opin Gastroenterol 2019; 35:379-386. [PMID: 33216485 DOI: 10.1097/mog.0000000000000539] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
PURPOSE OF REVIEW A multitude of inflammatory diseases other than gastroesophageal reflux disease (GERD) and eosinophilic esophagitis can affect the esophagus. Despite the deceptively simple organization of squamous mucosa and its limited number of inflammatory responses, a wide array of histologic patterns can be seen in inflammatory disorders involving the esophagus. Each such histologic pattern is associated with a limited number of underlying conditions, and the clinician can use this information to narrow the differential diagnosis. The purpose of this review is to review and discuss the pathologic diagnosis of esophagitis caused by conditions other than GERD or eosinophilic esophagitis, with an emphasis on recent developments in the field. RECENT FINDINGS Recent studies suggest that lymphocytic esophagitis may be a histologic manifestation of esophageal motility disorders. Immunophenotypic features of infiltrating lymphocytes may be helpful in this scenario. immunoglobulin G4-related disease has been implicated as a cause of esophageal inflammation with ulceration, strictures, and mass-forming fibrosis, whereas epidermoid metaplasia has been linked molecularly to the squamous cell neoplasia pathway. SUMMARY Improved knowledge and appreciation of the pathology of esophageal inflammation are needed to better understand the pathogenesis of various types of esophagitis, and to inform new approaches to the therapy and management of inflammatory esophageal diseases.
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Kim GH, Jung KW. [Emerging Issues in Esophageal Motility Diseases]. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2019; 73:322-326. [PMID: 31234622 DOI: 10.4166/kjg.2019.73.6.322] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/23/2019] [Revised: 05/23/2019] [Accepted: 05/23/2019] [Indexed: 01/07/2023]
Abstract
With the advances in technology and medical knowledge, new diseases are being identified and investigated. Esophageal motility disorders have been re-defined using high-resolution manometry and their pathogenesis are being better understood. The use of opioid analgesics is increasing worldwide, particularly in the United States, but their chronic use can cause opioid-induced esophageal dysfunction, which mimics spastic motor disorders, including achalasia type 3 or 2 and esophagogastric junction outflow obstruction. Eosinophilic esophagitis is identified by eosinophilic infiltration confirmed on a pathological examination. The condition is often associated with esophageal motility abnormalities. On the other hand, recent studies have suggested that muscle-predominant eosinophilic infiltration, eosinophilic esophageal myositis, might manifest as spastic motor disorders, including achalasia or jackhammer esophagus. Lymphocytic esophagitis is an unusual esophageal condition, which is confirmed by the increased number of lymphocytes in the esophageal epithelium. Although several reports have supported the existence of lymphocytic esophagitis, it is still unclear whether lymphocytic esophagitis is a distinct disease entity or another spectrum of other esophageal diseases, such as gastroesophageal reflux disease or eosinophilic esophagitis. This review presents evidence and reports on the emerging issues in esophageal motility disorders, including opioid-induced esophageal dysfunction, eosinophilic esophagitis with eosinophilic esophageal myositis, and lymphocytic esophagitis.
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Affiliation(s)
- Ga Hee Kim
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Kee Wook Jung
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Habbal M, Scaffidi MA, Rumman A, Khan R, Ramaj M, Al-Mazroui A, Abunassar MJ, Jeyalingam T, Shetty A, Kandel GP, Streutker CJ, Grover SC. Clinical, endoscopic, and histologic characteristics of lymphocytic esophagitis: a systematic review. Esophagus 2019; 16:123-132. [PMID: 30370453 DOI: 10.1007/s10388-018-0649-1] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2018] [Accepted: 10/10/2018] [Indexed: 02/03/2023]
Abstract
OBJECTIVE Lymphocytic esophagitis (LyE) is a novel, yet poorly described, clinicopathologic entity. The aim of this systematic review was to characterize the demographic, clinical, endoscopic, and histologic features of LyE in observational studies of adult and pediatric patients. DESIGN We searched the Embase, MEDLINE, and SCOPUS databases for relevant studies in 2018. Two authors reviewed and extracted data from studies that met the inclusion and exclusion criteria. RESULTS We identified 20 studies for analysis of demographic, clinical, and endoscopic features of LyE. The mean age ranged from 9 to 67 years. When pooled, there were 231 (52.7%) patients with LyE that were female. The most common presenting symptom was dysphagia reported in 191 (48.8%) patients. On endoscopy, most patients with LyE tended to have abnormal findings (69.0%), which included erosive esophagitis, multiple esophageal rings, linear furrows, and narrow-caliber esophagus. In the 31 studies used to assess the histologic definition, the cut-off number of intraepithelial lymphocytes (IELs) was reported in 16 (51.6%) studies, peripapillary IEL specification in 18 (58.1%) studies, and presence of spongiosis in 6 (19.4%) studies. CONCLUSION We identified a spectrum of demographic, clinical, and endoscopic findings characteristic of patients with LyE. A consensus on the diagnostic criteria of LyE is required.
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Affiliation(s)
- Mohamad Habbal
- Division of Gastroenterology, St. Michael's Hospital, Department of Medicine, University of Toronto, St. Michael's Hospital, 30 Bond Street, 16-036 Cardinal Carter Wing, Toronto, ON, M5B 1W8, Canada
| | - Michael A Scaffidi
- Division of Gastroenterology, St. Michael's Hospital, Department of Medicine, University of Toronto, St. Michael's Hospital, 30 Bond Street, 16-036 Cardinal Carter Wing, Toronto, ON, M5B 1W8, Canada
| | - Amir Rumman
- Division of Gastroenterology, St. Michael's Hospital, Department of Medicine, University of Toronto, St. Michael's Hospital, 30 Bond Street, 16-036 Cardinal Carter Wing, Toronto, ON, M5B 1W8, Canada
| | - Rishad Khan
- Division of Gastroenterology, St. Michael's Hospital, Department of Medicine, University of Toronto, St. Michael's Hospital, 30 Bond Street, 16-036 Cardinal Carter Wing, Toronto, ON, M5B 1W8, Canada
| | - Mirusha Ramaj
- Division of Gastroenterology, St. Michael's Hospital, Department of Medicine, University of Toronto, St. Michael's Hospital, 30 Bond Street, 16-036 Cardinal Carter Wing, Toronto, ON, M5B 1W8, Canada
| | - Ahmed Al-Mazroui
- Division of Gastroenterology, St. Michael's Hospital, Department of Medicine, University of Toronto, St. Michael's Hospital, 30 Bond Street, 16-036 Cardinal Carter Wing, Toronto, ON, M5B 1W8, Canada
| | - Michael J Abunassar
- Division of Gastroenterology, St. Michael's Hospital, Department of Medicine, University of Toronto, St. Michael's Hospital, 30 Bond Street, 16-036 Cardinal Carter Wing, Toronto, ON, M5B 1W8, Canada
| | - Thurarshen Jeyalingam
- Division of Gastroenterology, St. Michael's Hospital, Department of Medicine, University of Toronto, St. Michael's Hospital, 30 Bond Street, 16-036 Cardinal Carter Wing, Toronto, ON, M5B 1W8, Canada
| | - Akshay Shetty
- Division of Gastroenterology, St. Michael's Hospital, Department of Medicine, University of Toronto, St. Michael's Hospital, 30 Bond Street, 16-036 Cardinal Carter Wing, Toronto, ON, M5B 1W8, Canada
| | - Gabor P Kandel
- Division of Gastroenterology, St. Michael's Hospital, Department of Medicine, University of Toronto, St. Michael's Hospital, 30 Bond Street, 16-036 Cardinal Carter Wing, Toronto, ON, M5B 1W8, Canada
| | - Catherine J Streutker
- Department of Laboratory Medicine, St. Michael's Hospital, University of Toronto, Toronto, Canada
| | - Samir C Grover
- Division of Gastroenterology, St. Michael's Hospital, Department of Medicine, University of Toronto, St. Michael's Hospital, 30 Bond Street, 16-036 Cardinal Carter Wing, Toronto, ON, M5B 1W8, Canada.
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Döhla M, Leichauer K, Gockel I, Niebisch S, Thieme R, Lundell L, Schumacher J, Becker J, Rieker RJ, Hartmann A, Vieth M, Veits L. Characterization of esophageal inflammation in patients with achalasia. A retrospective immunohistochemical study. Hum Pathol 2019; 85:228-234. [DOI: 10.1016/j.humpath.2018.11.006] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2018] [Accepted: 11/01/2018] [Indexed: 01/15/2023]
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Mounajjed T. Drug-induced Injury, Infections, and Congenital and Miscellaneous Disorders. SURGICAL PATHOLOGY OF NON-NEOPLASTIC GASTROINTESTINAL DISEASES 2019:81-118. [DOI: 10.1007/978-3-030-15573-5_5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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30
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Zeng C, Vanoni S, Wu D, Caldwell JM, Wheeler JC, Arora K, Noah TK, Waggoner L, Besse JA, Yamani AN, Uddin J, Rochman M, Wen T, Chehade M, Collins MH, Mukkada VA, Putnam PE, Naren AP, Rothenberg ME, Hogan SP. Solute carrier family 9, subfamily A, member 3 (SLC9A3)/sodium-hydrogen exchanger member 3 (NHE3) dysregulation and dilated intercellular spaces in patients with eosinophilic esophagitis. J Allergy Clin Immunol 2018; 142:1843-1855. [PMID: 29729938 PMCID: PMC6448407 DOI: 10.1016/j.jaci.2018.03.017] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2017] [Revised: 03/15/2018] [Accepted: 03/26/2018] [Indexed: 12/17/2022]
Abstract
BACKGROUND Eosinophilic esophagitis (EoE) is characterized by histopathologic modifications of esophageal tissue, including eosinophil-rich inflammation, basal zone hyperplasia, and dilated intercellular spaces (DIS). The underlying molecular processes that drive the histopathologic features of EoE remain largely unexplored. OBJECTIVE We sought to investigate the involvement of solute carrier family 9, subfamily A, member 3 (SLC9A3) in esophageal epithelial intracellular pH (pHi) and DIS formation and the histopathologic features of EoE. METHODS We examined expression of esophageal epithelial gene networks associated with regulation of pHi in the EoE transcriptome of primary esophageal epithelial cells and an in vitro esophageal epithelial 3-dimensional model system (EPC2-ALI). Molecular and cellular analyses and ion transport assays were used to evaluate the expression and function of SLC9A3. RESULTS We identified altered expression of gene networks associated with regulation of pHi and acid-protective mechanisms in esophageal biopsy specimens from pediatric patients with EoE (healthy subjects, n = 6; patients with EoE, n = 10). The most dysregulated gene central to regulating pHi was SLC9A3. SLC9A3 expression was increased within the basal layer of esophageal biopsy specimens from patients with EoE, and expression positively correlated with disease severity (eosinophils/high-power field) and DIS (healthy subjects, n = 10; patients with EoE, n = 10). Analyses of esophageal epithelial cells revealed IL-13-induced, signal transducer and activator of transcription 6-dependent SLC9A3 expression and Na+-dependent proton secretion and that SLC9A3 activity correlated positively with DIS formation. Finally, we showed that IL-13-mediated, Na+-dependent proton secretion was the primary intracellular acid-protective mechanism within the esophageal epithelium and that blockade of SLC9A3 transport abrogated IL-13-induced DIS formation. CONCLUSIONS SLC9A3 plays a functional role in DIS formation, and pharmacologic interventions targeting SLC9A3 function may suppress the histopathologic manifestations in patients with EoE.
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Affiliation(s)
- Chang Zeng
- Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Simone Vanoni
- Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Institute of Pharmacology and Toxicology, Paracelsus Medical University, Salzburg, Austria
| | - David Wu
- Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Julie M Caldwell
- Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Justin C Wheeler
- Division of Pathology and Laboratory Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Kavisha Arora
- Division of Pulmonary Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Taeko K Noah
- Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Lisa Waggoner
- Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - John A Besse
- Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Amnah N Yamani
- Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Jazib Uddin
- Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Mark Rochman
- Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Ting Wen
- Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Mirna Chehade
- Mount Sinai Center for Eosinophilic Disorders, Jaffe Food Allergy Institute, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Margaret H Collins
- Division of Pathology and Laboratory Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Vincent A Mukkada
- Division of Gastroenterology, Nutrition and Hepatology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Philip E Putnam
- Division of Gastroenterology, Nutrition and Hepatology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Anjaparavanda P Naren
- Division of Pulmonary Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Marc E Rothenberg
- Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Simon P Hogan
- Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Department of Pathology, Mary H Weiser Food Allergy Center, Michigan Medicine, University of Michigan, Ann Arbor, Mich.
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Patil DT, Hammer S, Langer R, Yantiss RK. Lymphocytic esophagitis: an update on histologic diagnosis, endoscopic findings, and natural history. Ann N Y Acad Sci 2018; 1434:185-191. [PMID: 29797752 DOI: 10.1111/nyas.13710] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2017] [Revised: 03/11/2018] [Accepted: 03/14/2018] [Indexed: 12/14/2022]
Abstract
Lymphocytic esophagitis is a histologic pattern of injury characterized by increased intraepithelial lymphocytes (>20/high-power field) with rare, or absent granulocytes. Lymphocytes tend to be more numerous in the peripapillary epithelium, and are often associated with evidence of mucosal injury, edema, and scattered dyskeratotic cells. More than a decade following its original description, lymphocytic esophagitis remains an enigmatic entity with variable clinical presentations, associated disorders, etiologies, treatment, and natural history. Most of the confusion regarding the clinical significance of this disorder stems from its diagnostic criteria: lymphocytic esophagitis is currently defined based entirely on histologic criteria, despite the common occurrence of lymphocytosis in a variety of unrelated inflammatory conditions of the esophagus. The goal of this review is to summarize the literature regarding lymphocytic esophagitis and focus on key clinicopathologic features that distinguish it from other esophageal disorders that can show increased numbers of intraepithelial lymphocytes.
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Affiliation(s)
- Deepa T Patil
- Department of Pathology, Cleveland Clinic, Lerner College of Medicine, Cleveland, Ohio
| | - Suntrea Hammer
- Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Rupert Langer
- Institute of Pathology, University of Bern, Bern, Switzerland
| | - Rhonda K Yantiss
- Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, New York
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Tripathi M, Streutker CJ, Marginean EC. Relevance of histology in the diagnosis of reflux esophagitis. Ann N Y Acad Sci 2018; 1434:94-101. [PMID: 29766511 DOI: 10.1111/nyas.13742] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2017] [Revised: 03/20/2018] [Accepted: 03/27/2018] [Indexed: 12/16/2022]
Abstract
Reflux esophagitis is an important clinical diagnosis; however, the histologic findings can be nonspecific and overlap with other entities. Various benign changes can produce diagnostic difficulties for pathologists. In this review, the typical histologic findings of gastroesophageal reflux disease (GERD) of the esophagus are discussed, along with the issues relating to clinical correlation and technical aspects of endoscopic biopsies and specimen processing. The literature has been reviewed to discuss histologic definitions of GERD as well as current and developing controversies in the area of GERD. Histologic features are not entirely sensitive or specific for GERD. Awareness of these problems is essential; clinical and endoscopic information can be very useful in distinguishing GERD from other inflammatory lesions.
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Affiliation(s)
- Monika Tripathi
- Department of Histopathology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Catherine J Streutker
- Department of Laboratory Medicine, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada
| | - E Celia Marginean
- Department of Laboratory Medicine, Ottawa Hospital, Ottawa, Ontario, Canada
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33
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Saunsbury E, Yanagisawa Y, Colleypriest B. Lymphocytic oesophagitis: an emerging cause of dysphagia. Br J Hosp Med (Lond) 2018; 79:290-291. [PMID: 29727223 DOI: 10.12968/hmed.2018.79.5.290] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Affiliation(s)
- Emma Saunsbury
- CT1, Department of Acute Medicine, Royal United Hospital Bath NHS Trust, Bath BA1 3NG
| | | | - Benjamin Colleypriest
- Consultant Gastroenterologist, Department of Gastroenterology, Royal United Hospital Bath NHS Trust, Bath
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Abstract
PURPOSE OF REVIEW Lymphocytic esophagitis (LE) is an unusual esophageal condition defined by an increased number of lymphocytes in the esophageal epithelium. With few published studies of LE available, it is unclear whether LE is a truly distinct clinical entity or a histological manifestation of other known gastrointestinal disorders. This review summarizes recent studies of lymphocytic esophagitis. RECENT FINDINGS Studies have suggested that LE may be related to eosinophilic esophagitis (EoE) or a manifestation of gastroesophageal reflux disease (GERD). There is an association between LE and Crohn's disease in children, but not in adults. Patients with LE frequently report symptoms of dysphagia and GERD. Treatment options for LE are limited and involve symptom management similar to treatment of EoE or GERD, including proton pump inhibitors (PPI), swallowed topical steroids, and endoscopic dilation. With no formal definition and a variety of clinical presentations and endoscopic findings, diagnosis and management of symptomatic LE patients is challenging for clinicians.
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Affiliation(s)
- Anh D Nguyen
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Texas Southwestern Medical Center, Dallas, TX, 75231, USA
| | - Kerry B Dunbar
- Esophageal Diseases Center, Division of Gastroenterology and Hepatology, Department of Medicine, Dallas VA Medical Center and the University of Texas Southwestern Medical Center, GI Lab-CA 111-B1, Dallas VAMC, 4500 South Lancaster Road, Dallas, TX, 75231, USA.
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Panarelli NC. Other Forms of Esophagitis: It Is Not Gastroesophageal Reflux Disease, So Now What Do I Do? Surg Pathol Clin 2017; 10:765-779. [PMID: 29103532 DOI: 10.1016/j.path.2017.07.001] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/07/2023]
Abstract
Esophagitis results from diverse causes, including gastroesophageal reflux, immune-mediated or allergic reactions, therapeutic complications, and infections. The appropriate clinical management differs in each of these situations and is often guided by pathologic interpretation of endoscopic mucosal biopsy specimens. This review summarizes the diagnostic features of unusual forms of esophagitis, including eosinophilic esophagitis, lymphocytic esophagitis, esophagitis dissecans superficialis, drug-induced esophageal injury, and bullous disorders. Differential diagnoses and distinguishing features are emphasized.
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Affiliation(s)
- Nicole C Panarelli
- Department of Pathology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10467, USA.
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Johncilla ME, Srivastava A. Esophagitis unrelated to reflux disease: current status and emerging diagnostic challenges. Virchows Arch 2017; 472:29-41. [DOI: 10.1007/s00428-017-2238-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2017] [Revised: 09/18/2017] [Accepted: 09/20/2017] [Indexed: 02/07/2023]
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Pleet JL, Taboada S, Rishi A, Milman PJ, Trindade AJ. Rings in the esophagus are not always eosinophilic esophagitis: Case series of ring forming lymphocytic esophagitis and review of the literature. Endosc Int Open 2017; 5:E484-E488. [PMID: 28573181 PMCID: PMC5451283 DOI: 10.1055/s-0043-106579] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2016] [Accepted: 02/15/2017] [Indexed: 01/31/2023] Open
Abstract
Background and study aims Lymphocytic esophagitis (LyE) is a form of chronic esophagitis characterized by edema and lymphocytic infiltration of the epithelial peripapillary fields, without eosinophils. Its significance is unclear, as it was previously thought to have little clinical impact. More recent literature, however, describes a paradigm shift suggesting a distinct entity. We report on 3 patients with dysphagia who were found to have esophageal rings on endoscopy. Histology was consistent with LyE. Additional features reported in this cohort included an esophageal web, esophageal pseudodiverticula and esophageal erythema. We also report a current literature review of the topic. The literature review reported here includes another 37 patients with LyE and rings, for a total of 40 patients. Patients with LyE may present with esophageal rings and other findings. LyE should be considered in the differential diagnosis of esophageal rings.
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Affiliation(s)
- Julia L. Pleet
- Department of Medicine, Division of Gastroenterology, Hofstra Northwell School of Medicine, Long Island Jewish Medical Center, New Hyde Park, New York, United States
| | - Sofia Taboada
- Department of Pathology, Hofstra Northwell School of Medicine, Long Island Jewish Medical Center, New Hyde Park, New York, United States
| | - Arvind Rishi
- Department of Pathology, Hofstra Northwell School of Medicine, Long Island Jewish Medical Center, New Hyde Park, New York, United States
| | - Perry J. Milman
- Lake Success Gastroenterology, Lake Success, New York, United States
| | - Arvind J. Trindade
- Department of Medicine, Division of Gastroenterology, Hofstra Northwell School of Medicine, Long Island Jewish Medical Center, New Hyde Park, New York, United States,Corresponding author Arvind J. Trindade, MD Division of GastroenterologyLong Island Jewish Medical CenterHofstra Northwell School of MedicineNorthwell Health System
270-05 76
th
Avenue
New Hyde Park, NY 11040+1-718-470-5509
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Gonzalez-Cordero PL, Rubio-Fernández A, Fernandez-Gonzalez N, Dueñas-Sadornil C, Molina-Infante J. Lymphocytic esophagitis: A rare finding in adult patients with dysphagia and food impaction. GASTROENTEROLOGIA Y HEPATOLOGIA 2017; 41:31-32. [PMID: 28089355 DOI: 10.1016/j.gastrohep.2016.11.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/06/2016] [Accepted: 11/23/2016] [Indexed: 11/29/2022]
Affiliation(s)
| | | | | | - Carmen Dueñas-Sadornil
- Department of Gastroenterology, Hospital Universitario San Pedro de Alcantara, Caceres, Spain
| | - Javier Molina-Infante
- Department of Gastroenterology, Hospital Universitario San Pedro de Alcantara, Caceres, Spain
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Jideh B, Keegan A, Weltman M. Lymphocytic esophagitis: Report of three cases and review of the literature. World J Clin Cases 2016; 4:413-418. [PMID: 28035315 PMCID: PMC5156879 DOI: 10.12998/wjcc.v4.i12.413] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2016] [Revised: 07/20/2016] [Accepted: 09/22/2016] [Indexed: 02/05/2023] Open
Abstract
Lymphocytic esophagitis (LyE) is a rare condition characterised histologically by high numbers of esophageal intraepithelial lymphocytes without significant granulocytes infiltration, in addition to intercellular edema (“spongiosis”). The clinical significance and natural history of LyE is poorly defined although dysphagia is reportedly the most common symptom. Endoscopic features range from normal appearing esophageal mucosa to features similar to those seen in eosinophilic esophagitis, including esophageal rings, linear furrows, whitish exudates, and esophageal strictures/stenosis. Symptomatic gastroesophageal reflux disease is an inconsistent association. LyE has been associated in paediatric Crohn’s disease, and recently in primary esophageal dysmotility disorder in adults. There are no studies assessing effective treatment strategies for LyE; empirical therapies have included use of proton pump inhibitor and corticosteroids. Esophageal dilatation have been used to manage esophageal strictures. LyE has been reported to run a benign course; however there has been a case of esophageal perforation associated with LyE. Here, we describe the clinical, endoscopic and histopathological features of three patients with lymphocytic esophagitis along with a review of the current literature.
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Putra J, Muller KE, Hussain ZH, Parker S, Gabbard S, Brickley EB, Lacy BE, Rothstein R, Lisovsky M. Lymphocytic Esophagitis in Nonachalasia Primary Esophageal Motility Disorders: Improved Criteria, Prevalence, Strength of Association, and Natural History. Am J Surg Pathol 2016; 40:1679-1685. [PMID: 27526295 PMCID: PMC5613759 DOI: 10.1097/pas.0000000000000712] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Lymphocytic esophagitis (LE) is a histologic pattern with no established clinical correlates in the majority of patients. The goal of this study was to evaluate the association between nonachalasia primary esophageal motility disorders (PEMD) and LE. Sixty-nine patients with PEMD and esophageal biopsies, including 22 with nutcracker esophagus, 33 with ineffective motility, and 14 with diffuse spasm, constituted the study group. The control group consisted of 70 patients with severe dysmotility-negative gastroesophageal reflux disease requiring referral for Nissen fundoplication. To improve the criteria for LE, a lymphocyte reference range at different esophageal levels was first established in 17 healthy volunteers. The cutoffs for normal intraepithelial lymphocytes, defined as lymphocyte levels not exceeding mean level±2 SDs, were set at 62, 46, and 41 lymphocytes per high-power field at 0 to 2, 5, and 10 cm above the gastroesophageal junction, respectively. Predominantly focal peripapillary LE was observed in approximately 40% of patients with nutcracker esophagus or diffuse spasm and in 20% of patients with ineffective motility, in comparison with 4% of patients with dysmotility-negative gastroesophageal reflux disease (P<0.035 vs. any subtype of PEMD). Overall, LE was strongly associated with PEMD in multivariate analysis (adjusted odds ratio, 7.93; 95% confidence interval, 2.26-27.9; P=0.001). LE had a chronic course in 56% of the patients with follow-up biopsies. In conclusion, LE has a strong association with PEMD, suggesting the utility of LE in raising the possibility of PEMD.
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Affiliation(s)
- Juan Putra
- Department of Pathology, Dartmouth-Hitchcock Medical Center, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA
| | - Kristen E. Muller
- Department of Pathology, Dartmouth-Hitchcock Medical Center, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA
| | - Zilla H. Hussain
- Section of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA
| | - Siddhartha Parker
- Section of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA
| | - Scott Gabbard
- Section of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA
| | - Elizabeth B. Brickley
- Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA
| | - Brian E. Lacy
- Section of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA
| | - Richard Rothstein
- Section of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA
| | - Mikhail Lisovsky
- Department of Pathology, Dartmouth-Hitchcock Medical Center, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA
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Another New Esophagitis: The Lymphocyte Gets Its Turn. Dig Dis Sci 2016; 61:2765-2766. [PMID: 27480085 DOI: 10.1007/s10620-016-4267-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
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Lisovsky M, Westerhoff M, Zhang X. Lymphocytic esophagitis: a histologic pattern with emerging clinical ramifications. Ann N Y Acad Sci 2016; 1381:133-138. [PMID: 27635640 DOI: 10.1111/nyas.13260] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2016] [Revised: 08/22/2016] [Accepted: 08/23/2016] [Indexed: 02/05/2023]
Abstract
The clinical significance of lymphocytic esophagitis (LyE), which is characterized by the prominence of peripapillary intraepithelial lymphocytes (IELs) without significant granulocytosis, remains poorly understood. During the last few years, plausible clinical correlates and novel approaches for stratification of LyE have started to emerge. Association with Crohn's disease has been established in children, but is not observed in adults. In adults, the form of LyE showing CD4+ -predominant IELs has been recently found to be associated with non-achalasia primary motility abnormalities. GERD is another possible association. The most common clinical manifestations of adult LyE are dysphagia and normal endoscopic appearance of the esophagus. LyE should be reported by pathologists in order to distinguish it from its mimics, such as eosinophilic esophagitis, and to assist in directing the next steps in evaluation for known associated diseases, such as Crohn's disease or motility disorders.
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Affiliation(s)
- Mikhail Lisovsky
- Department of Pathology, Dartmouth-Hitchcock Medical Center and Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire
| | - Maria Westerhoff
- Department of Anatomic Pathology, University of Washington School of Medicine, Seattle, Washington
| | - Xuchen Zhang
- Department of Pathology, Yale University School of Medicine, New Haven, Connecticut.
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Pasricha S, Gupta A, Reed CC, Speck O, Woosley JT, Dellon ES. Lymphocytic Esophagitis: An Emerging Clinicopathologic Disease Associated with Dysphagia. Dig Dis Sci 2016; 61:2935-2941. [PMID: 27343035 PMCID: PMC5021567 DOI: 10.1007/s10620-016-4230-2] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2016] [Accepted: 06/09/2016] [Indexed: 12/12/2022]
Abstract
BACKGROUND Lymphocytic esophagitis (LyE) is a recently described clinicopathological condition, but little is known about its features and clinical associations. AIM The aim of this study was to characterize patients with LyE, compare them to non-LyE controls, and identify risk factors. METHODS We conducted a retrospective study of all patients ≥18 years old who underwent upper endoscopy with esophageal biopsy between January 1, 2000, and June 1, 2012. Archived pathology slides were re-reviewed, and LyE was diagnosed if there was lymphocyte-predominant esophageal inflammation with no eosinophils or granulocytes. Three non-LyE controls groups were also defined: reflux, eosinophilic esophagitis (EoE), and normal. Clinical data were extracted from electronic medical records, and LyE cases were compared to non-LyE controls. RESULTS Twenty-seven adults were diagnosed with LyE, and the majority were female (63 %). The most common symptom was dysphagia (70 %). Fifty-two percentage had a prior or current diagnosis of reflux. Endoscopic findings included strictures (37 %), erosive esophagitis (33 %), rings (26 %), and hiatal hernia (26 %); 33 % of patients required dilation. After histology re-review, 78 % of LyE patients were found to have more than 20 lymphs/hpf. In comparison with the normal, reflux and EoE controls, patients with LyE tended to be nonwhite (p < 0.01), were more commonly tobacco users (p = 0.02) and less likely to have seasonal allergies (p = 0.02). CONCLUSION LyE commonly presents with dysphagia due to esophageal strictures which require dilation. Smoking was associated with LyE, whereas atopy was not. LyE should be considered as a diagnostic possibility in patients with these characteristics undergoing upper endoscopy.
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Affiliation(s)
- Sarina Pasricha
- Division of Gastroenterology and Hepatology, Center for Esophageal Diseases and Swallowing, University of North Carolina at Chapel Hill (UNC-CH), CB#7080, Bioinformatics Building, 130 Mason Farm Rd., Chapel Hill, NC, 27599-7080, USA
| | - Amit Gupta
- Department of Medicine, University of Michigan, Ann Arbor, MI, USA
| | - Craig C Reed
- Division of Gastroenterology and Hepatology, Center for Esophageal Diseases and Swallowing, University of North Carolina at Chapel Hill (UNC-CH), CB#7080, Bioinformatics Building, 130 Mason Farm Rd., Chapel Hill, NC, 27599-7080, USA
| | - Olga Speck
- Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - John T Woosley
- Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Evan S Dellon
- Division of Gastroenterology and Hepatology, Center for Esophageal Diseases and Swallowing, University of North Carolina at Chapel Hill (UNC-CH), CB#7080, Bioinformatics Building, 130 Mason Farm Rd., Chapel Hill, NC, 27599-7080, USA.
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Rubio CA, Ichiya T, Schmidt PT. Lymphocytic oesophagitis, eosinophilic oesophagitis and compound lymphocytic-eosinophilic oesophagitis I: histological and immunohistochemical findings. J Clin Pathol 2016; 70:208-216. [PMID: 27471274 DOI: 10.1136/jclinpath-2016-203782] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2016] [Revised: 06/21/2016] [Accepted: 07/02/2016] [Indexed: 01/18/2023]
Abstract
AIMS To report four histological-immunohistochemical oesophagitis phenotypes. METHODS Oesophageal biopsies from 311 patients were stained with H&E and with CD3, a T cell marker. Additional immunohistochemical stains (n=413) were performed in 77 cases. RESULTS Four histological-immunohistochemical oesophagitis phenotypes were recorded: lymphocytic oesophagitis (LyE, ≥40 CD3+ lymphocytes/HPF in CD3 immunostain), eosinophilic oesophagitis (EoE, ≥15 eosinophils/HPF in H&E stain), lymphocytic infiltration (≤39 CD3+/HPF) and compound lymphocytic oesophagitis-eosinophilic oesophagitis (Co LyE-EoE). At index biopsy, 28.3% (n=88) had LyE, 21.2% (n=66) EoE, 10.6% (n=33) Co LyE-EoE and 39.9% (n=124) lymphocytic infiltration. A persistent oesophagitis phenotype was found in 42.5% (37/87) in the first follow-up biopsy, in 34.4% (21/61) in the second follow-up biopsy and in 48.1% (26/54) in the third follow-up biopsy. Using βF1 immunostain, two different surface T cell receptors were detected in LyE and Co Lye-EoE: one having ≥40 βF1+/HPF (βF1+ high) and the other having <39 βF1+/HPF (βF1+ low). CONCLUSIONS Based on the literature regarding the significance of intraepithelial lymphocytes (IELs) in the initiation of EoE, we submit that the IEL phenotypes in LyE might differ from those found in EoE as they were unable to elicit the same eosinophilic response. Recent studies disclosed that group 2 innate lymphocytes (ILC2s), enriched in EoE, remain undetected in CD3 immunostain as they lack surface markers for T, B, natural killer (NK) or NK T cells. If ILC2s also participate in the lymphocytic infiltration of EoE, then the frequency of cases with Co LyE-EoE here reported might have been much higher. The four oesophagitis phenotypes described are easy to recognise, provided that the dual staining procedure (H&E-CD3) is implemented.
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Affiliation(s)
- C A Rubio
- Department of Pathology, Karolinska Institute and University Hospital, Stockholm, Sweden
| | - T Ichiya
- Department of Medicine, Center for Digestive Diseases, Karolinska Institute and University Hospital, Stockholm, Sweden
| | - P T Schmidt
- Department of Medicine, Center for Digestive Diseases, Karolinska Institute and University Hospital, Stockholm, Sweden
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Straumann A, Blanchard C, Radonjic-Hoesli S, Bussmann C, Hruz P, Safroneeva E, Simon D, Schoepfer AM, Simon HU. A new eosinophilic esophagitis (EoE)-like disease without tissue eosinophilia found in EoE families. Allergy 2016; 71:889-900. [PMID: 26970242 DOI: 10.1111/all.12879] [Citation(s) in RCA: 49] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/06/2016] [Indexed: 12/30/2022]
Abstract
BACKGROUND Eosinophilic esophagitis (EoE) is a rapidly emerging, chronic inflammatory, genetically impacted disease of the esophagus, defined clinically by symptoms of esophageal dysfunction and, pathologically, by an eosinophil-predominant tissue infiltration. However, in four EoE families, we have identified patients presenting with EoE-typical and corticosteroid-responsive symptoms, but without tissue eosinophilia. The aim of this study was to clinically and immunologically characterize these patients with EoE-like disease. METHODS Five patients suffering from an EoE-like disease were evaluated with endoscopic, histologic, functional, and quantitative immunohistological examinations, and mRNA expression determination. RESULTS The frequency of first-generation offspring of patients affected by EoE or EoE-like disease was 40%. Immunofluorescence analysis confirmed an almost complete absence of eosinophils in the esophageal tissues of patients with EoE-like disease, but revealed a considerable T-cell infiltration, comparable to EoE. In contrast to EoE, eotaxin-3 mRNA and protein were markedly reduced in EoE-like disease (P < 0.05). The mRNA expression levels of three selected EoE genes (eotaxin-3, MUC4, and CDH26) allowed to discriminate between EoE-like disease, EoE, and normal epithelium. CONCLUSIONS Patients suffering from 'EoE without eosinophilia' do not fulfill formally the diagnostic criteria for EoE. However, their clinical manifestation, immunohistology, and gene expression pattern, plus the fact that they bequeath EoE to their offspring, suggest a uniform underlying pathogenesis. Conventional EoE, with its prominent eosinophilia, therefore appears to be only one phenotype of a broader 'inflammatory dysphagia syndrome' spectrum. In this light, the role of the eosinophils, the definition of EoE, and its diagnostic criteria must likely be reconsidered.
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Affiliation(s)
- A. Straumann
- Swiss EoE Clinic and EoE Research Network; Olten Switzerland
| | | | | | - Ch. Bussmann
- Division of Pathology; Histopathology Viollier; Basel Switzerland
| | - P. Hruz
- Department of Gastroenterology; University Hospital; Basel Switzerland
| | - E. Safroneeva
- Institute of Social and Preventive Medicine; University of Bern; Bern Switzerland
| | - D. Simon
- Department of Dermatology; Inselspital; University Hospital Bern; Bern Switzerland
| | - A. M. Schoepfer
- Division of Gastroenterology; Centre Hospitalier Universitaire Vaudois (CHUV); Lausanne Switzerland
| | - H.-U. Simon
- Institute of Pharmacology; University of Bern; Bern Switzerland
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Post-ablation lymphocytic esophagitis in Barrett esophagus with high grade dysplasia or intramucosal carcinoma. Mod Pathol 2016; 29:599-606. [PMID: 26965580 DOI: 10.1038/modpathol.2016.50] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2015] [Revised: 02/05/2016] [Accepted: 02/08/2016] [Indexed: 12/13/2022]
Abstract
In patients who have undergone ablation therapy for treatment of Barrett's esophagus with dysplasia, histologic features of eosinophilic esophagitis, but not lymphocytic esophagitis, have been described. We evaluated for histologic evidence of eosinophilic esophagitis and lymphocytic esophagitis and correlated with endoscopic findings in this population. A single-institution Barrett's esophagus registry was searched for patients who had received radiofrequency ablation, cryotherapy, or both for treatment of Barrett's esophagus with dysplasia. Clinical and endoscopic data were collected and biopsies were reviewed for inflammation and reactive changes at three time points: pre-intervention, first surveillance after ablation therapy, and most recent surveillance. Of the 173 patients initially identified, 102 met the inclusion criteria. Intraepithelial eosinophils were increased at first surveillance (60%, P=0.096) and last surveillance (69%, P=0.048) compared with pre-intervention (50%), although histologic evidence of post-ablation eosinophilic esophagitis was not significant. Prevalence of lymphocytic esophagitis was significantly higher at first surveillance (17%, P=0.02) and at last surveillance (43%, P<0.001), compared with pre-intervention (7%). Smoking, hyperlipidemia, and cryotherapy were identified as independent risk factors for developing histologic lymphocytic esophagitis. This is the first report that histologic evidence of lymphocytic esophagitis increased over time in patients undergoing ablation for Barrett's esophagus with dysplasia. Though the pathophysiology of lymphocytic esophagitis remains unknown, patients in our study with a history of smoking, hyperlipidemia, or cryotherapy were more likely to develop post-ablation lymphocytic esophagitis.
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Maejima R, Uno K, Iijima K, Fujishima F, Noguchi T, Ara N, Asano N, Koike T, Imatani A, Shimosegawa T. A Japanese case of lymphocytic esophagitis. Dig Endosc 2016; 28:476-480. [PMID: 26589889 DOI: 10.1111/den.12578] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2015] [Revised: 11/12/2015] [Accepted: 11/16/2015] [Indexed: 12/25/2022]
Abstract
We report the case of a 68-year-old Japanese man diagnosed with lymphocytic esophagitis (LE), a rare disease associated with refractory dysphagia. He has had severe dysphagia and heartburn since 2007. Findings of esophagogastroduodenoscopy (EGD) carried out by a local physician in 2010 showed pale mucosa with white exudate and lateral furrows in the esophagus. He was referred to Tohoku University Hospital in 2012, because the symptoms did not improve, despite regular use of a proton pump inhibitor (PPI). At that time, EGD revealed the coexistence of a slight stricture in the upper esophagus, the histopathological findings of which included a predominantly peri-papillary distribution of abundant, infiltrating CD3+ /CD4+ /CD8+ /CD20- lymphocytes without any granulocytes (CD4+ : CD8+ = 3.3:1). These were consistent with a diagnostic criteria of LE. Thereafter, severe dysphagia with food impaction occurred twice a month, despite the long-term use of a PPI, and EGD showed worsened strictures, where endoscopic ultrasonography findings showed marked circumferential thickness of the mucosal and submucosal layers. Then, one session of endoscopic balloon dilatation dramatically improved the dysphagia. Accordingly, LE should be considered an important differential diagnosis of refractory dysphagia based on the characteristic features of endoscopic and pathological findings.
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Affiliation(s)
- Ryuhei Maejima
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Kaname Uno
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Katsunori Iijima
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | | | - Tetsuya Noguchi
- Department of Gastroenterology, Miyagi Cancer Center, Natori, Japan
| | - Nobuyuki Ara
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Naoki Asano
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Tomoyuki Koike
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Akira Imatani
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Tooru Shimosegawa
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
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Lymphocytic Esophagitis With CD4 T-cell-predominant Intraepithelial Lymphocytes and Primary Esophageal Motility Abnormalities: A Potential Novel Clinicopathologic Entity. Am J Surg Pathol 2016; 39:1558-67. [PMID: 26379147 DOI: 10.1097/pas.0000000000000493] [Citation(s) in RCA: 66] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Lymphocytic esophagitis (LE) is an uncommon poorly defined histologic pattern. Its significance is largely unknown. The goal of our study was to characterize LE clinically, histologically, and immunophenotypically. Biopsies of 45 patients with LE and no intraepithelial granulocytes were selected throughout a 36-month period during routine diagnostic work. After reevaluation, complete absence of intraepithelial granulocytes was confirmed in 21 patients (LE-NG group), and few granulocytes were found in 24 patients (LE-FG). The control group consisted of 28 patients with active esophagitis consistent with reflux and overtly increased intraepithelial lymphocytes (REIL). The ratio of CD4:CD8 intraepithelial lymphocytes (IEL)>1 indicated predominance of CD4 IEL; the ratio ≤1 indicated predominance of CD8 IEL. Dysphagia was the primary complaint in 71%, 54%, and 39% of the patients with LE-NG, LE-FG, and REIL, respectively (P=0.04, LE-NG vs. REIL). Importantly, primary esophageal motility abnormalities were found in 10/11 (91%) tested LE-NG patients, 6/10 (60%) LE-FG patients, and 6/11 (54%) REIL patients. CD4 IELs were predominant in 81%, 50%, and 39% of LE-NG, LE-FG, and REIL cases, respectively (P=0.004, LE-NG vs. REIL), and in 90%, 83%, and 88% of the cases with primary motility abnormalities from the same groups. The prevalence of primary motility abnormalities was significantly higher in patients with CD4-predominant esophagitis than in patients with CD8-predominant esophagitis from all groups (21/24 [83%] vs. 2/8 [25%], P=0.005). A distinctive type of LE with predominance of CD4 IEL is associated with primary motility abnormalities suggesting a diagnostic utility of evaluating CD4 and CD8 subpopulations of T cells in LE.
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49
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Allen JI, Katzka D, Robert M, Leontiadis GI. American Gastroenterological Association Institute Technical Review on the Role of Upper Gastrointestinal Biopsy to Evaluate Dyspepsia in the Adult Patient in the Absence of Visible Mucosal Lesions. Gastroenterology 2015; 149:1088-118. [PMID: 26278504 DOI: 10.1053/j.gastro.2015.07.040] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Affiliation(s)
- John I Allen
- Section of Digestive Diseases, Yale University School of Medicine, New Haven, Connecticut
| | - David Katzka
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Marie Robert
- Department of Pathology, Yale School of Medicine, New Haven, Connecticut
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Abstract
OBJECTIVES To describe four cases of an uncommon type of acalculous cholecystitis/cholangitis characterized by increased intraepithelial lymphocytes within the biliary epithelium. METHODS Cases were prospectively compiled during regular surgical pathology sign-out. Clinical information was obtained from the electronic medical record and the gross appearance from the surgical pathology reports. Microscopic examination was performed with emphasis on the type, location, and distribution of the inflammatory pattern; presence of intraepithelial lymphocytes (>30 per 100 biliary cells); and presence of metaplasia and epithelial hyperplasia. Immunohistochemical stains for CD3, CD8, and IgG4 were performed in some cases. RESULTS All patients were adults who had either biliary pain or obstructive symptoms. All gallbladders had a relatively normal gross appearance and did not contain gallstones or biliary sludge. Microscopic examination showed numerous intraepithelial lymphocytes in the biliary epithelium. The mucosa was frequently expanded by dense inflammatory cell infiltrates. The inflammatory process was more severe in the infundibulum and bile ducts than in the body of the gallbladder. The intraepithelial lymphocytes were CD3+, CD8+. IgG4+ plasma cells were absent. CONCLUSIONS The term lymphocytic cholecystitis/cholangitis is proposed. The potential clinical implications and pathogenesis of this inflammatory pattern and the differential diagnosis with other forms of acalculous cholecystitis are discussed.
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Affiliation(s)
- Jose Jessurun
- Department of Pathology and Laboratory Medicine, New York-Presbyterian Hospital, Weill Cornell Medical College, New York, NY
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