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Li M, Xu T, Ruan G, Ou C, Tan B, Zhang S, Li X, You Y, Zhou W, Li J, Li J. Comprehensive insights into pathogenesis, diagnosis, treatment, and prognosis in adult autoimmune enteropathy. Orphanet J Rare Dis 2025; 20:208. [PMID: 40317016 PMCID: PMC12046689 DOI: 10.1186/s13023-025-03731-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Accepted: 04/11/2025] [Indexed: 05/04/2025] Open
Abstract
Autoimmune enteropathy (AIE) constitutes a diverse array of disorders characterized by immune dysregulation and gastrointestinal manifestations, chiefly chronic diarrhea. Due to the small number of reported cohorts, the current knowledge and understanding of adult-onset AIE is rare compared with pediatric or syndromic AIE. Pathogenesis might involve genetic predisposition, aberrant immune homeostasis, comorbidities of autoimmune diseases and environmental trigger. Diagnosis relies on a comprehensive assessment encompassing clinical evaluation, laboratory tests, endoscopic findings and histopathological features, yet distinguishing AIE from other disorders with similar presentations poses diagnostic challenges. Treatment strategies predominantly center on immunosuppressive therapies, exhibiting varied efficacy among individuals. Supportive treatment and prevention and management of complications are also important for prognosis. The prospectives of future researches need to explore the genetic and immunological mechanism, the diagnostic modalities and the treatment strategies to improve patient outcomes.
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Affiliation(s)
- Muhan Li
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Tianming Xu
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Gechong Ruan
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Chengzhu Ou
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Bei Tan
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Shengyu Zhang
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xiaoqing Li
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yan You
- Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
| | - Weixun Zhou
- Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.
| | - Ji Li
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
| | - Jingnan Li
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Hoey P, Kaushik V, Francis L, Adris N. Intestinal failure from thymoma-associated autoimmune enteropathy: a rare case report. Clin J Gastroenterol 2025:10.1007/s12328-025-02119-w. [PMID: 40257552 DOI: 10.1007/s12328-025-02119-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2024] [Accepted: 03/16/2025] [Indexed: 04/22/2025]
Abstract
We describe a case of altered bowel habit, early satiety, anorexia and weight loss caused by autoimmune enteropathy. This diagnosis was confirmed by biopsies obtained from upper gastrointestinal endoscopy and ileocolonoscopy. Further investigations revealed multiple pulmonary nodules which were metastases from a malignant thymoma. The patient was commenced on oral budesonide and Mesalazine, in addition to oral and enteral supplementation driven by the specialist nutrition support team, but she did not achieve histological remission, nor did she demonstrate improvement in her nutritional status. She received 3-weeks of in-patient parenteral nutrition, but then subsequently deteriorated as she declined home parenteral nutrition. The patient died eight months later from complications of her disease. This case highlights the rare manifestation of metastatic thymoma presenting with autoimmune enteropathy that led to intestinal failure and death.
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Affiliation(s)
- Paris Hoey
- Department of Gastroenterology and Hepatology, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia.
- Faulty of Medicine, University of Queensland, Brisbane, QLD, Australia.
| | - Vishal Kaushik
- Department of Gastroenterology and Hepatology, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia
| | - Leo Francis
- Pathology Queensland, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia
| | - Niwansa Adris
- Department of Gastroenterology and Hepatology, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia
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Li MH, Ruan GC, Zhou WX, Li XQ, Zhang SY, Chen Y, Bai XY, Yang H, Zhang YJ, Zhao PY, Li J, Li JN. Clinical manifestations, diagnosis and long-term prognosis of adult autoimmune enteropathy: Experience from Peking Union Medical College Hospital. World J Gastroenterol 2024; 30:2523-2537. [PMID: 38817655 PMCID: PMC11135415 DOI: 10.3748/wjg.v30.i19.2523] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Revised: 02/20/2024] [Accepted: 04/11/2024] [Indexed: 05/20/2024] Open
Abstract
BACKGROUND Autoimmune enteropathy (AIE) is a rare disease whose diagnosis and long-term prognosis remain challenging, especially for adult AIE patients. AIM To improve overall understanding of this disease's diagnosis and prognosis. METHODS We retrospectively analyzed the clinical, endoscopic and histopathological characteristics and prognoses of 16 adult AIE patients in our tertiary medical center between 2011 and 2023, whose diagnosis was based on the 2007 diagnostic criteria. RESULTS Diarrhea in AIE patients was characterized by secretory diarrhea. The common endoscopic manifestations were edema, villous blunting and mucosal hyperemia in the duodenum and ileum. Villous blunting (100%), deep crypt lymphocytic infiltration (67%), apoptotic bodies (50%), and mild intraepithelial lymphocytosis (69%) were observed in the duodenal biopsies. Moreover, there were other remarkable abnormalities, including reduced or absent goblet cells (duodenum 94%, ileum 62%), reduced or absent Paneth cells (duodenum 94%, ileum 69%) and neutrophil infiltration (duodenum 100%, ileum 69%). Our patients also fulfilled the 2018 diagnostic criteria but did not match the 2022 diagnostic criteria due to undetectable anti-enterocyte antibodies. All patients received glucocorticoid therapy as the initial medication, of which 14/16 patients achieved a clinical response in 5 (IQR: 3-20) days. Immunosuppressants were administered to 9 patients with indications of steroid dependence (6/9), steroid refractory status (2/9), or intensified maintenance medication (1/9). During the median of 20.5 months of follow-up, 2 patients died from multiple organ failure, and 1 was diagnosed with non-Hodgkin's lymphoma. The cumulative relapse-free survival rates were 62.5%, 55.6% and 37.0% at 6 months, 12 months and 48 months, respectively. CONCLUSION Certain histopathological findings, including a decrease or disappearance of goblet and Paneth cells in intestinal biopsies, might be potential diagnostic criteria for adult AIE. The long-term prognosis is still unsatisfactory despite corticosteroid and immunosuppressant medications, which highlights the need for early diagnosis and novel medications.
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Affiliation(s)
- Mu-Han Li
- Department of Gastroenterology, Chinese Academy of Medical Sciences & Peking Union Medical College Hospital, Beijing 100730, China
| | - Ge-Chong Ruan
- Department of Gastroenterology, Chinese Academy of Medical Sciences & Peking Union Medical College Hospital, Beijing 100730, China
| | - Wei-Xun Zhou
- Department of Pathology, Chinese Academy of Medical Scinences & Peking Union Medical College Hospital, Beijing 100730, China
| | - Xiao-Qing Li
- Department of Gastroenterology, Chinese Academy of Medical Sciences & Peking Union Medical College Hospital, Beijing 100730, China
| | - Sheng-Yu Zhang
- Department of Gastroenterology, Chinese Academy of Medical Sciences & Peking Union Medical College Hospital, Beijing 100730, China
| | - Yang Chen
- Department of Gastroenterology, Chinese Academy of Medical Sciences & Peking Union Medical College Hospital, Beijing 100730, China
| | - Xiao-Yin Bai
- Department of Gastroenterology, Chinese Academy of Medical Sciences & Peking Union Medical College Hospital, Beijing 100730, China
| | - Hong Yang
- Department of Gastroenterology, Chinese Academy of Medical Sciences & Peking Union Medical College Hospital, Beijing 100730, China
| | - Yu-Jie Zhang
- Department of Pathology, Tianjin First Central Hospital, Nankai University, Tianjin 300192, China
| | - Peng-Yu Zhao
- Affairs Office, Chinese Academy of Medical Sciences & Peking Union Medical College Hospital (West campus), Beijing 100032, China
| | - Ji Li
- Department of Gastroenterology, Chinese Academy of Medical Sciences & Peking Union Medical College Hospital, Beijing 100730, China
| | - Jing-Nan Li
- Department of Gastroenterology, Chinese Academy of Medical Sciences & Peking Union Medical College Hospital, Beijing 100730, China
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Norton B, Pelkonen O, Watkins J, Mann S. Localised intestinal Kaposi sarcoma in a patient with non-coeliac seronegative villous atrophy. BMJ Case Rep 2023; 16:e254073. [PMID: 37751975 PMCID: PMC10533734 DOI: 10.1136/bcr-2022-254073] [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: 09/30/2023] Open
Abstract
Seronegative villous atrophy (SNVA) is a diagnostic challenge for gastroenterologists, which is defined by villous atrophy and negative coeliac serology. Non-coeliac forms of SNVA, such as autoimmune enteropathy, can be life-threatening leading to intractable diarrhoea and severe malabsorption that require systemic immunosuppression. When all known causes have been excluded, it is termed idiopathic villous atrophy (IVA). We present a case of non-coeliac SNVA complicated by Kaposi sarcoma (KS). A previously well HIV-negative man in his 30s presented with a 4-month history of watery diarrhoea and 25 kg weight loss. After prolonged investigation, he was diagnosed with non-coeliac SNVA without an identified aetiology that would be consistent with IVA. Clinical recovery was achieved with parenteral nutrition for type II intestinal failure and immunosuppression using high-dose corticosteroids. On subsequent gastroscopy, he was diagnosed with localised intestinal KS prompting cessation of all immunosuppression but remained in clinical remission.
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Affiliation(s)
- Benjamin Norton
- Gastroenterology, Barnet and Chase Farm Hospitals NHS Trust, London, UK
- Gastroenterology, University College London Hospitals NHS Foundation Trust, London, UK
- Centre for Obesity Research, Rayne Institute, Department of Medicine, London, UK
- Department of Gastroenterology, Digestive Diseases & Surgery Institute, Cleveland Clinic London, London, UK
| | - Otso Pelkonen
- Gastroenterology, Barnet and Chase Farm Hospitals NHS Trust, London, UK
| | | | - Steven Mann
- Gastroenterology, Barnet and Chase Farm Hospitals NHS Trust, London, UK
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Aytekin ES, Cagdas D. APECED and the place of AIRE in the puzzle of the immune network associated with autoimmunity. Scand J Immunol 2023; 98:e13299. [PMID: 38441333 DOI: 10.1111/sji.13299] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Revised: 04/27/2023] [Accepted: 05/03/2023] [Indexed: 03/07/2024]
Abstract
In the last 20 years, discoveries about the autoimmune regulator (AIRE) protein and its critical role in immune tolerance have provided fundamental insights into understanding the molecular basis of autoimmunity. This review provides a comprehensive overview of the effect of AIRE on immunological tolerance and the characteristics of autoimmune diseases in Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED), which is caused by biallelic AIRE mutations. A better understanding of the immunological mechanisms of AIRE deficiency may enlighten immune tolerance mechanisms and new diagnostic and treatment strategies for autoimmune diseases. Considering that not all clinical features of APECED are present in a given follow-up period, the diagnosis is not easy in a patient at the first visit. Longer follow-up and a multidisciplinary approach are essential for diagnosis. It is challenging to prevent endocrine and other organ damage compared with other diseases associated with multiple autoimmunities, such as FOXP3, LRBA, and CTLA4 deficiencies. Unfortunately, no curative therapy like haematopoietic stem cell transplantation or specific immunomodulation is present that is successful in the treatment.
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Affiliation(s)
- Elif Soyak Aytekin
- Pediatric Allergy and Immunology, Department of Pediatrics, SBU Dr. Sami Ulus Children Hospital, Ankara, Turkey
| | - Deniz Cagdas
- Division of Pediatric Immunology, Department of Pediatrics, Ihsan Dogramaci Children`s Hospital, Institute of Child Health, Hacettepe University Medical School, Ankara, Turkey
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Thymoma-associated autoimmune enteropathy with colonic stricture: a diagnostic and histological challenge. Clin J Gastroenterol 2021; 15:112-116. [PMID: 34676508 DOI: 10.1007/s12328-021-01531-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Accepted: 10/01/2021] [Indexed: 10/20/2022]
Abstract
Thymoma-associated autoimmune enteropathy is a rare paraneoplastic syndrome that is characterized by severe chronic diarrhea, malabsorption, and specific histological findings. Because of its rarity, it is difficult to diagnose. We describe an adult patient with protracted diarrhea and weight loss that developed recurrent sepsis and progressive colonic stenosis due to thymoma-associated autoimmune enteropathy. Ultimately, the diagnosis thymoma-associated autoimmune enteropathy was established by characteristic intestinal histology, anti-enterocytes antibodies, and thorax imaging. Radical thymectomy was performed without improvement. Therapy with azathioprine and infliximab induced clinical remission with complete recovery of the colonic stenosis.
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van Wanrooij RLJ, Neefjes-Borst EA, Bontkes HJ, Schreurs MWJ, Langerak AW, Mulder CJJ, Bouma G. Adult-Onset Autoimmune Enteropathy in an European Tertiary Referral Center. Clin Transl Gastroenterol 2021; 12:e00387. [PMID: 34333499 PMCID: PMC8323799 DOI: 10.14309/ctg.0000000000000387] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Accepted: 06/28/2021] [Indexed: 11/23/2022] Open
Abstract
INTRODUCTION Adult-onset autoimmune enteropathy (AIE) is a rare cause of severe chronic diarrhea because of small intestinal villous atrophy. We report on patients with adult-onset AIE in an European referral center. METHODS Retrospective study including patients diagnosed with AIE in the Amsterdam UMC, location VUmc, between January 2003 and December 2019. Clinical, serological, and histological features and response to treatment were reported. The specificity of antienterocyte antibodies (AEA) was evaluated by examining the prevalence of AEA in (i) controls (n = 30) and in patients with (ii) AIE (n = 13), (iii) celiac disease (CD, n = 52), (iv) refractory celiac disease type 2 (n = 18), and (v) enteropathy-associated T-cell lymphoma (EATL, n = 10). RESULTS Thirteen AIE patients were included, 8 women (62%), median age of 52 years (range 23-73), and 6 (46%) with an autoimmune disease. AEA were observed in 11 cases (85%), but were also found in CD (7.7%), refractory celiac disease type 2 (16.7%), and EATL (20%). Ten patients (77%) were human leukocyte antigen DQ2.5 heterozygous. Total parenteral nutrition was required in 8 cases (62%). Steroids induced clinical remission in 8 cases (62%). Step-up therapy with rituximab, cyclosporine, infliximab, and cladribine in steroid-refractory patients was only moderately effective. Four patients died (31%), but 4 (31%) others are in long-term drug-free remission after receiving immunosuppressive treatment, including 1 patient who underwent autologous stem cell transplantation. DISCUSSION Adult-onset AIE is a rare but severe enteropathy that occurs in patients susceptible for autoimmune disease. Four patients (31%) died secondary to therapy-refractory malabsorption, while immunosuppressive therapy leads to a long-lasting drug-free remission in one-third of patients.
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Affiliation(s)
- Roy L J van Wanrooij
- Department of Gastroenterology and Hepatology, Amsterdam UMC, Vrije Universiteit Amsterdam, AGEM Institute, Amsterdam, the Netherlands
| | | | - Hetty J Bontkes
- Laboratory Medical Immunology, Department of Clinical Chemistry, Amsterdam UMC, AGEM Research Institute, AI & I Institute, Amsterdam, the Netherlands
| | - Marco W J Schreurs
- Laboratory Medical Immunology, Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands
| | - Anton W Langerak
- Laboratory Medical Immunology, Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands
| | - Chris J J Mulder
- Department of Gastroenterology and Hepatology, Amsterdam UMC, Vrije Universiteit Amsterdam, AGEM Institute, Amsterdam, the Netherlands
| | - Gerd Bouma
- Department of Gastroenterology and Hepatology, Amsterdam UMC, Vrije Universiteit Amsterdam, AGEM Institute, Amsterdam, the Netherlands
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Iaquinto G, Panico L, Luongo G, Tenneriello V, Iaquinto S, Giardullo N, Rotondi Aufiero V, Mazzarella G, Rispoli R, Lucariello A, Perna A, De Luca A. Adult autoimmune enteropathy in autoimmune hepatitis patient. Case report and literature review. Clin Res Hepatol Gastroenterol 2021; 45:101673. [PMID: 33744411 DOI: 10.1016/j.clinre.2021.101673] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Revised: 01/25/2021] [Accepted: 03/02/2021] [Indexed: 02/04/2023]
Abstract
Autoimmune enteropathy (AIE) is a rare disease characterized by prolonged diarrhea, vomiting and weight loss; although it is mainly a rare pediatric disease, over the years a number of adults have also been found to be affected. In this study, we present a case report of a 73-year-old woman with a history of autoimmune hepatitis, antinuclear (ANA) and positive anti-enterocyte antibodies (AEA), who has suffered two months of intractable diarrhea, nausea, anorexia and severe weight loss. The histological examination of the endoscopic duodenal mucosa biopsies revealed severe shortening and flattening of the villi, resulting in mucosal atrophy. The immunohistochemical study revealed a polymorphic lymphoid population, exhibiting a B cell (CD20+) phenotype in follicles and a T cell phenotype (CD3+) in the diffuse component within the lamina propria. Our patient had a complete recovery after two weeks of taking prednisone and following a gluten-rich diet. To our knowledge this is the first case of autoimmune enteropathy in adults with ANA and AEA 7 years after a diagnosis of autoimmune hepatitis. To date, the patient is still in clinical remission on a low dose of orally administered predinisone without any additional immunosuppression.
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Affiliation(s)
- Gaetano Iaquinto
- Division of Gastroenterology, Department of Internal Medicine, S. Rita Hospital, Atripalda, Avellino, Italy.
| | - Luigi Panico
- Department of Pathology, AORN dei Colli, Monaldi Hospital, Naples, Italy
| | - Gelsomina Luongo
- Department of Pathology, San G. Moscati Hospital, Avellino, Italy
| | | | | | - Nicola Giardullo
- Division of Gastroenterology, San G. Moscati Hospital, Avellino, Italy
| | | | | | - Raffaella Rispoli
- Department of Mental and Physical Health and Preventive Medicine, Section of Human Anatomy, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Angela Lucariello
- Department of Sport Sciences and Wellness, University of Naples "Parthenope", Naples, Italy
| | - Angelica Perna
- Department of Medicine and Health Sciences "Vincenzo Tiberio", University of Molise, Campobasso, Italy
| | - Antonio De Luca
- Department of Mental and Physical Health and Preventive Medicine, Section of Human Anatomy, University of Campania "Luigi Vanvitelli", Naples, Italy
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Chong A, Kashani A, Ansstas M, Jamil L, Guindi M. Seronegative autoimmune enteropathy with duodenal sparing and colonic clues in an adult female. Clin J Gastroenterol 2021; 14:546-550. [PMID: 33630282 DOI: 10.1007/s12328-020-01336-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2019] [Accepted: 12/29/2020] [Indexed: 10/22/2022]
Abstract
Autoimmune enteropathy (AIE) is a rare immune disorder of the gut seldom found in adults and characterized by uncontrollable diarrhea resulting in malabsorption. While AIE is known to be pan-enteric, virtually all cases have presented with altered duodenal histology following known patterns with or without macroscopic change. We describe a unique case of seronegative AIE lacking typical duodenal manifestations in a 43-year-old female. To our knowledge, this is the first report of AIE lacking usual duodenal histologic changes, which resulted in missed diagnosis for years. Ultimately, crypt epithelial apoptosis, mononuclear inflammation of the lamina propria, and goblet cell loss of intestinal mucosa besides the duodenum clinched the diagnosis of AIE. Colonic histologic abnormalities consistent with AIE in the setting of diarrhea with malnutrition despite duodenal sparing should prompt suspicion for AIE given the pan-enteric nature of this disease.
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Affiliation(s)
- Albert Chong
- Keck School of Medicine of the University of Southern California, 1975 Zonal Avenue, Keith Administration 100B, Los Angeles, CA, 90089, USA
| | - Amir Kashani
- Division of Gastroenterology, Hepatology, and Nutrition, University of Utah School of Medicine, 300 North 1900 East SOM 4R118, Salt Lake City, UT, 84132, USA
| | - Michael Ansstas
- Division of Digestive and Liver Disease, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA, 90048, USA
| | - Laith Jamil
- Section of Gastroenterology and Hepatology, Beaumont Hospital-Royal Oak, Administrative Building West, 3711 W 13 Mile Rd, Royal Oak, MI, 48073, USA
| | - Maha Guindi
- Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA, 90048, USA.
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Acute Flare of Adult-Onset Autoimmune Enteropathy Associated With Cyclophosphamide. ACG Case Rep J 2021; 8:e00541. [PMID: 33634202 PMCID: PMC7901791 DOI: 10.14309/crj.0000000000000541] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Accepted: 10/04/2020] [Indexed: 01/01/2023] Open
Abstract
This is a case of adult-onset autoimmune enteropathy (AIE) in a 46-year-old man with multiple autoimmune conditions who presented with worsening disease process after receiving cyclophosphamide. We describe the investigations and management of this patient over a 6-year timeline. The diagnosis and management of AIE is challenging given the heterogeneity in clinicopathologic findings and a small number of adult case reports. We describe the current diagnostic criteria, review the literature on treatment options and outcomes, and discuss the evidence for cyclophosphamide in the treatment of AIE. Adult-onset AIE should be considered in the differential diagnosis of refractory diarrhea and weight loss.
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11
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van Wanrooij RLJ, Bontkes HJ, Neefjes-Borst EA, Mulder CJ, Bouma G. Immune-mediated enteropathies: From bench to bedside. J Autoimmun 2021; 118:102609. [PMID: 33607573 DOI: 10.1016/j.jaut.2021.102609] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2020] [Revised: 01/22/2021] [Accepted: 01/23/2021] [Indexed: 12/13/2022]
Abstract
Immune-mediated enteropathies are caused by excessive reactions of the intestinal immune system towards non-pathogenic molecules. Enteropathy leads to malabsorption-related symptoms and include (severe) chronic diarrhea, weight loss and vitamin deficiencies. Parenteral feeding and immunosuppressive therapy are needed in severe cases. Celiac disease has long been recognized as the most common immune-mediated enteropathy in adults, but the spectrum of immune-mediated enteropathies has been expanding. Histological and clinical features are sometimes shared among these enteropathies, and therefore it may be challenging to differentiate between them. Here, we provide an overview of immune-mediated enteropathies focused on clinical presentation, establishing diagnosis, immunopathogenesis, and treatment options.
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Affiliation(s)
- Roy L J van Wanrooij
- Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Gastroenterology and Hepatology, AGEM Research Institute, Amsterdam, the Netherlands.
| | - Hetty J Bontkes
- Amsterdam UMC, Laboratory Medical Immunology, Department of Clinical Chemistry, AI & I Institute, AGEM Research Institute, Amsterdam, the Netherlands
| | | | - Chris J Mulder
- Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Gastroenterology and Hepatology, AGEM Research Institute, Amsterdam, the Netherlands
| | - Gerd Bouma
- Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Gastroenterology and Hepatology, AGEM Research Institute, Amsterdam, the Netherlands
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12
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Successful Treatment of Refractory Autoimmune Enteropathy With Ustekinumab. ACG Case Rep J 2021; 8:e00520. [PMID: 33457439 PMCID: PMC7808559 DOI: 10.14309/crj.0000000000000520] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Accepted: 09/04/2020] [Indexed: 01/12/2023] Open
Abstract
Autoimmune enteropathy (AIE) is a rare autoimmune disorder that has been described both in pediatric and adult patients and usually causes intractable watery diarrhea. The management of AIE is not standardized because the disease shows variable response to different immunosuppressive regimens including corticosteroids, azathioprine, cyclophosphamide, 6-mercaptopurine, tacrolimus, cyclosporine-A, infliximab, vedolizumab, and abatacept. We present a patient with adult-onset AIE and intractable high-volume diarrhea resulting in numerous hospitalizations and temporary parenteral nutrition, who is now successfully maintained on ustekinumab. Therefore, ustekinumab should be considered for further evaluation as a therapeutic option in cases of refractory AIE.
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13
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Chen CB, Tahboub F, Plesec T, Kay M, Radhakrishnan K. A Review of Autoimmune Enteropathy and Its Associated Syndromes. Dig Dis Sci 2020; 65:3079-3090. [PMID: 32833153 DOI: 10.1007/s10620-020-06540-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Accepted: 08/05/2020] [Indexed: 01/01/2023]
Abstract
Autoimmune enteropathy is an extremely rare condition characterized by an abnormal intestinal immune response which typically manifests within the first 6 months of life as severe, intractable diarrhea that does not respond to dietary modification. Affected individuals frequently present with other signs of autoimmunity. The diagnosis is made based on a characteristic combination of clinical symptoms, laboratory studies, and histological features on small bowel biopsy. Autoimmune enteropathy is associated with a number of other conditions and syndromes, most notably immunodysregulation polyendocrinopathy enteropathy X-linked (IPEX) syndrome and autoimmune polyglandular syndrome type 1 (APS-1). Diagnosis and treatment is challenging, and further research is needed to better understand the pathogenesis, disease progression, and long-term outcomes of these conditions.
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Affiliation(s)
- Charles B Chen
- Department of Pediatric Gastroenterology, Hepatology, and Nutrition, Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH, 44195, USA.
| | - Farah Tahboub
- The University of Jordan School of Medicine, Queen Rania St 212, Amman, Jordan
| | - Thomas Plesec
- Department of Anatomic Pathology, Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH, 44195, USA
| | - Marsha Kay
- Department of Pediatric Gastroenterology, Hepatology, and Nutrition, Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH, 44195, USA
| | - Kadakkal Radhakrishnan
- Department of Pediatric Gastroenterology, Hepatology, and Nutrition, Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH, 44195, USA
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Affiliation(s)
| | - Jayanta Paul
- Department of Gastroenterology Desun Hospital and Heart Institute Kolkata India
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15
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Abstract
PURPOSE OF REVIEW We reviewed the current 'state of the art' on autoimmune enteropathy and small-bowel mucosal atrophy, with the aim of supporting clinicians in a frequently challenging diagnosis through different therapeutic options and prognosis. RECENT FINDINGS The diagnosis of small-bowel diseases has radically changed over the last 10 years. The possibility to 'easily' obtain bioptic samples from the jejunum and ileum by means of the enteroscopic techniques (particularly, device-assisted enteroscopy) and the novel cross-sectional imaging studies have opened the window to new insights on intestinal disorders. Consequentially, the detection of small-bowel mucosal atrophy has become a frequent finding in patients undergoing endoscopic investigation and its differential diagnosis can be challenging at times. Among the 'typical' causes of mucosal atrophy, autoimmune enteropathy has become more frequent than previously thought. However, the final diagnosis of autoimmune enteropathy is a 'puzzle' composed by serological, endoscopic, histological and molecular markers, which should be correctly dealt with in order to reach a certain diagnosis. SUMMARY In conclusion, there is an emerging body of literature about autoimmune enteropathy and small-bowel atrophy. The herein presented practical review on autoimmune enteropathy can be of help to clinicians in their daily practice.
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Ahmed Z, Imdad A, Connelly JA, Acra S. Autoimmune Enteropathy: An Updated Review with Special Focus on Stem Cell Transplant Therapy. Dig Dis Sci 2019; 64:643-654. [PMID: 30415406 PMCID: PMC8260026 DOI: 10.1007/s10620-018-5364-1] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2018] [Accepted: 11/01/2018] [Indexed: 12/12/2022]
Abstract
Autoimmune enteropathy (AIE) is a complex disease affecting both children and adults. Although associated with significant morbidity and mortality, the pathophysiology of the disease and its treatment have not been well characterized. This study aims to review the medical literature available on this rare but clinically significant ailment, to help establish a better understanding of its pathophysiology and enumerate the available diagnostic and treatment modalities. A literature search was conducted on PubMed using key terms related to autoimmune enteropathy and intractable diarrhea, with no restrictions on the date of publication or language. We found a total of 98 reports of AIE published in the form of case reports and case series. The evidence reviewed suggests that AIE is a multifaceted disorder that requires a high index of suspicion in the appropriate clinical setting to be able to make an early diagnosis. Current evidence supports the use of supportive care to correct nutritional and metabolic deficiencies, and immunosuppressives and immunomodulators as directed therapies. Hematopoietic stem cell transplant is an aggressive, but successful curative modality for patients with AIE as part of immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome. Cumulative clinical experience with management of AIE has allowed improved outcomes in transplanted and non-transplanted AIE patients even though morbidity and mortality with are still high in patients with this condition. More research is needed to further define the role of new therapies for AIE, and a central registry with participation of multiple institutions might help share and standardize care of patients with this rare but serious condition.
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Affiliation(s)
- Zunirah Ahmed
- School of Medicine, University of Alabama, Montgomery Campus, 2055 E South Blvd Ste 202, Montgomery, AL, 36116, USA
| | - Aamer Imdad
- Division of Pediatric Gastroenterology, SUNY Upstate Medical University, 725 Irving Street, Suite 501, Syracuse, NY, 13210, USA
| | - James A Connelly
- Division of Pediatric Hematology-Oncology, Vanderbilt University Medical Center, 2100 Children's Way, Nashville, TN, 37212, USA
| | - Sari Acra
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Vanderbilt University Medical Center, 2100 Children's Way, Nashville, TN, 37212, USA.
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17
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Sharma A, Choung RS, Wang XJ, Russo PA, Wu TT, Nehra V, Murray JA. Features of Adult Autoimmune Enteropathy Compared With Refractory Celiac Disease. Clin Gastroenterol Hepatol 2018; 16:877-883.e1. [PMID: 29307846 DOI: 10.1016/j.cgh.2017.12.044] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2017] [Revised: 12/13/2017] [Accepted: 12/26/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Little is known about the features of immune-mediated non-celiac villous atrophies, such as autoimmune enteropathy (AIE). We investigated the demographic, clinical, and histologic features of adults with AIE compared to adults with refractory celiac disease type 1. We also report outcomes of treatment with open-label budesonide. METHODS We performed a retrospective case-control of patients with AIE (n = 30) seen at the Mayo Clinic (in Rochester, Minnesota) from 2000 through 2015. Patients with refractory celiac disease type 1 who were treated with open-label budesonide served as controls (n = 42). Biopsy specimens were reviewed for all patients. We collected demographic, clinical, biochemical and histologic data from patients. We also collected data on responses to open-capsule budesonide from patients with AIE (available from 22 patients) and controls (available from 42 patients); the median duration of follow up was 28 months (range, 0-1421 months). RESULTS Patients with AIE had a higher proportion of men (60%) and were younger (mean, 44 ± 18 years) than patients with refractory celiac disease type 1 (29% men; P = .002 and mean age, 57 ± 16 years; P = .007). A higher proportion of patients with AIE presented with chronic diarrhea (100%) and weight loss (90%) than patients with refractory celiac disease type 1 (71%; P < .001 and 71%; P = .05, respectively). Based on histologic analysis, there was no significant difference in degree of villous atrophy in intestinal tissues from patients with AIE vs controls (P = .68). However, a greater proportion of patients with RCD had increased intraepithelial lymphocytes (>40 per 100 epithelial cells in 100%) compared with patients with AIE (in 50%) (P = .003). Conventional therapy (systemic steroids) had failed in most patients with AIE (a complete clinical response was reported in only 7 patients) before treatment with open-capsule budesonide was initiated. A clinical response to open-capsule budesonide was reported for 85% of patients with AIE (50% complete response, 35% partial response) compared to 92% of controls (68% complete response, 24% partial response). CONCLUSIONS In a retrospective study of 30 patients with AIE, followed for a median 28 months, we found this disease to have has distinct demographic, clinical, and histologic characteristics compared to refractory celiac disease type 1. Most patients with AIE (85%) have a clinical response to budesonide, all of whom were unsuccessfully treated with conventional therapies.
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Affiliation(s)
- Ayush Sharma
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Rok Seon Choung
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Xiao Jing Wang
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Pierre A Russo
- Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
| | - Tsung-Teh Wu
- Division of Anatomic Pathology, Mayo Clinic, Rochester, Minnesota
| | - Vandana Nehra
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Joseph A Murray
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
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18
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Umetsu SE, Brown I, Langner C, Lauwers GY. Autoimmune enteropathies. Virchows Arch 2017; 472:55-66. [PMID: 29022145 DOI: 10.1007/s00428-017-2243-7] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2017] [Revised: 09/25/2017] [Accepted: 09/29/2017] [Indexed: 12/14/2022]
Abstract
Autoimmune enteropathy (AIE) is a rare condition characterized by intractable diarrhea and immune-mediated injury of the intestinal mucosa. As the clinical and histopathologic manifestations of this disease are highly variable, its diagnosis is challenging for both clinicians and pathologists. In fact, the term autoimmune enteropathies is likely more appropriate since the clinicopathologic manifestations are observed in association with a heterogeneous group of disorders. The pathophysiology of AIE has not been fully elucidated. It appears to result from dysregulation of intestinal immunity and particularly in children, often presents in association with immunodeficiency. The overarching histopathologic changes seen in AIE include mucosal inflammation and epithelial injury, although this can manifest in the form of different patterns. Recognition of the clinical settings and of the various histologic patterns can aid the pathologist in establishing the correct diagnosis.
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Affiliation(s)
- Sarah E Umetsu
- Department of Pathology, University of California, San Francisco, 505 Parnassus Avenue, Room M551A, Box 0102, San Francisco, CA, 94143-0102, USA.
| | - Ian Brown
- Envoi Pathology, Kelvin Grove, Qld, Australia
| | - Cord Langner
- Institute of Pathology, Medical University of Graz, Graz, Austria
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Diffuse Autoimmune Enteropathy and Colopathy in an Adult Patient Successfully Treated With Adalimumab and a Review of the Literature. Am J Ther 2017; 23:e963-8. [PMID: 25379737 DOI: 10.1097/mjt.0000000000000119] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Autoimmune enteropathy (AIE) is a rare disease that causes intractable diarrhea not responsive to a gluten free diet and must be distinguished from refractory sprue. It is associated with circulating autoantibodies against goblet cells and enterocytes. AIE mainly involves the small intestines, with very few cases reported in adults. Because of the paucity of cases, the epidemiology of the disease remains unclear, and treatment is based on the cases found in the literature. Of the 35 adult cases reported, only 4 involved the colon. Because of the low number of cases, there have been no clear recommendations on treatment modalities with most reports heavily emphasizing steroids as the mainstay of treatment. We present the case of adult female patient who developed postpartum AIE and colopathy with profuse diarrhea successfully treated with adalimumab and a review of the literature. To the best of our knowledge, this case is only the fourth case of a tumor necrosis factor alpha antagonist being used in the treatment of AIE and the first case of adalimumab being used.
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Abstract
Autoimmune enteropathy (AIE) is rare but damaging. The lack of consistent objective findings makes diagnosis a challenge. A 45-year-old male developed noninfectious diarrhea with significant weight loss and electrolyte abnormalities. Computed tomography delineated enteritis. Colonoscopy and esophagogastroduodenoscopy showed villous atrophy, chronic inflammation, and ulceration of the terminal ileum and cecum. Pathology showed cryptitis with apoptosis and abscesses throughout the small and large bowel and absent goblet cells. Steroids rapidly improved symptoms. Anti-enterocyte antibody serologies were negative. Management can be challenging, and, in this case, the patient initially improved with budesonide and infliximab but required alternative anti-tumor necrosis factor therapy after relapsing. This is an unusual presentation of seronegative AIE, which should be considered in cases of persistent severe diarrhea.
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21
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New insights into immune mechanisms underlying autoimmune diseases of the gastrointestinal tract. Autoimmun Rev 2015; 14:1161-9. [PMID: 26275585 DOI: 10.1016/j.autrev.2015.08.004] [Citation(s) in RCA: 88] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2015] [Accepted: 08/05/2015] [Indexed: 02/07/2023]
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Abstract
Tropical sprue (TS) is a malabsorption syndrome of presumed infectious aetiology that affects residents of (or visitors to) the tropics. The histological changes of TS are similar to those of coeliac disease, with increased intraepithelial lymphocytes being central to both. Unlike in coeliac disease, however, a completely flat small bowel biopsy is uncommon in TS. TS typically involves the terminal ileum, whereas coeliac disease does not. Small intestinal bacterial overgrowth (SIBO) has been defined as an increase in number and/or a change in the type of bacteria in the upper gut. Conditions that predispose to SIBO are largely those that decrease or interfere with small bowel motility. The mucosal histology is variable, and may include modest villous blunting accompanied by increased lamina propria and epithelial inflammation. Autoimmune enteropathy (AE) is a family of rare diseases that share common themes such as immunodeficiency states and autoantibodies. AE cases typically have marked villous atrophy similar to that in fully developed coeliac disease, but they lack the intense surface epithelial lymphocytosis. Apoptosis and lymphocyte infiltration at the base of the crypts, crypt abscesses and cryptitis are also seen. Patients with anti-goblet cell antibodies can have a lack of goblet cells, endocrine cells, and Paneth cells.
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23
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Mirtavoos-Mahyari H, Khosravi A, Esfahani-Monfared Z, Shadmehr MB. Two thymus-related autoimmune disorders: a case report and review of the literature. Onco Targets Ther 2014; 7:633-6. [PMID: 24872711 PMCID: PMC4025932 DOI: 10.2147/ott.s58194] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Thymoma is the most common tumor in the anterior mediastinum. A 56-year-old man presented unremitting and periodic chronic diarrhea of 9 weeks duration, and clinical examination revealed a huge nonhomogeneous mass lesion in the right lung and leukocytosis. He was treated with CHOP regimen (cyclophosphamide 1,200 mg/m2, doxorubicin 50 mg/m2, vincristine 1.5 mg/m2, and prednisolone 75 mg/m2 × 5 days) based on lung mass computed tomography-guided biopsy, but he was reevaluated because neither symptom improved. Surprisingly, celiac disease was documented with increased titer of immunoglobulin antibodies to gliadin and tissue transglutaminase. Lung mass rebiopsy and thymectomy demonstrated thymoma. After surgery, the patient showed aplastic anemia that responded well to cyclosporine. At 2-year follow-up, the patient’s hematologic status and diarrhea were completely recovered and no symptom and/or sign of thymoma recurrence was seen.
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Affiliation(s)
- Hanifeh Mirtavoos-Mahyari
- Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Adnan Khosravi
- Tobacco Prevention and Control Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Zahra Esfahani-Monfared
- Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Behgam Shadmehr
- Tracheal Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
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24
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Xu RY, Wan YP, Zhou YQ, Lu LP, Chen ZQ, Wu YJ, Cai W. Glutamine-supplemented parenteral nutrition and probiotics in four adult autoimmune enteropathy patients. Gut Liver 2014; 8:324-8. [PMID: 24827631 PMCID: PMC4026652 DOI: 10.5009/gnl.2014.8.3.324] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
To evaluate the effects of glutamine-supplemented parenteral nutrition (PN) and probiotics in adult autoimmune enteropathy (AIE) patients. Four adult AIE patients were identified from April 2006 to January 2012. Clinical and nutritional data were obtained from the patients' medical records. Glutamine-supplemented PN started immediately when the AIE diagnosis was confirmed. The total PN duration was 351 days. According to the PN prescription, the average caloric intake ranged from 20 to 25 kcal/kg/day, and the protein intake ranged from 1.2 to 1.5 g/kg/day. Alanyl-glutamine (20 g/day) was administered to AIE patients for 4 weeks followed by a 2-week break, and this treatment schedule was repeated when PN lasted for more than 6 weeks. Body weight gain and an increased serum albumin level were achieved after PN, and defecation frequency and quality also improved. Each patient received oral supplements, 250 mL of Ensure and two probiotics capsules (each capsule containing 0.5×108 colonies) three times a day when enteral nutrition started. Three AIE patients were successfully weaned off PN, and one patient died of pneumonia. Glutamine-supplemented PN and probiotics show promise in managing patients with AIE and related malnutrition.
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Affiliation(s)
- Ren Ying Xu
- Department of Clinical Nutrition, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China
| | - Yan Ping Wan
- Department of Clinical Nutrition, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China
| | - Yi Quan Zhou
- Department of Clinical Nutrition, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Li Ping Lu
- Department of Clinical Nutrition, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhi Qi Chen
- Department of Clinical Nutrition, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ying Jie Wu
- Department of Clinical Nutrition, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Wei Cai
- Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Clinical Nutrition Center, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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25
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Valitutti F, Barbato M, Aloi M, Marcheggiano A, Di Nardo G, Leoni S, Iorfida D, Corazza GR, Cucchiara S. Autoimmune enteropathy in a 13-year-old celiac girl successfully treated with infliximab. J Clin Gastroenterol 2014; 48:264-266. [PMID: 24504079 DOI: 10.1097/mcg.0b013e31829e460e] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
Autoimmune enteropathy (AIE) is a rare cause of small bowel villous atrophy, characterized by malabsorption, unresponsiveness to dietary restriction, circulating autoantibodies to enterocytes, and an overall predisposition to autoimmunity. Albeit mainly regarded as a disease of early childhood, several adult-onset AIE cases have been identified. This report describes for the first time the life-threatening clinical presentation and the management of overlapping AIE in a compliant-to-diet young celiac girl. A 13-year-old celiac girl was admitted because of vomiting, weight loss, diarrhea, hypoproteinemia, and neurological disturbances such as head tremors, vertical nystagmus, and lower limb hyperesthesia. Before this, she had always been compliant on a strict gluten-free diet and her medical history was unremarkable. The diagnosis of AIE was established on histologic findings and on the presence of antienterocyte antibodies. She was initially treated with high-dose Methylprednisolone and Azathioprine. However, only Infliximab proved itself as a highly effective tool for achieving clinical remission and restoring small bowel villous architecture.
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Affiliation(s)
- Francesco Valitutti
- *Pediatric Gastroenterology and Liver Unit, Department of Pediatrics, University Hospital Umberto I †Department of Clinical Science, Sapienza University of Rome, Rome ‡First Department of Medicine, Fondazione Policlinico S. Matteo, University of Pavia, Pavia, Italy
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26
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Yee EU, Goldsmith JD. Diarrheal Illness in the Pediatric Population: A Review of Neonatal Enteropathies and Childhood Idiopathic Inflammatory Bowel Disease. Surg Pathol Clin 2013; 6:523-543. [PMID: 26839099 DOI: 10.1016/j.path.2013.05.006] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/05/2023]
Abstract
In the clinical context of pediatric diarrheal illness, the interpretation of endoscopic mucosal biopsies varies significantly from that in adults. This review outlines these differences by first describing a host of diarrheal illnesses that are nearly exclusive to the pediatric age group. The final portion of this article describes salient pathologic differences between adult and pediatric idiopathic inflammatory bowel disease. The goal of this review is to provide a brief description of each disease process and focus on practical aspects of diagnosis that are applicable for pathologists working in general practice settings.
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Affiliation(s)
- Eric U Yee
- Department of Pathology, Harvard Medical School, Beth Israel Deaconess Medical Center, Children's Hospital Boston, 330 Brookline Avenue, Boston, MA 02215, USA
| | - Jeffrey D Goldsmith
- Department of Pathology, Harvard Medical School, Beth Israel Deaconess Medical Center, Children's Hospital Boston, 330 Brookline Avenue, Boston, MA 02215, USA.
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27
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Gentile NM, Murray JA, Pardi DS. Autoimmune enteropathy: a review and update of clinical management. Curr Gastroenterol Rep 2013. [PMID: 22810979 DOI: 10.1007/sl1894-012-0276-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
Autoimmune enteropathy (AIE) is a rare condition characterized by intractable diarrhea, histologic changes on small intestinal biopsy, and failed response to dietary manipulation that also may present with extraintestinal manifestations. In many patients, immunosuppressive therapies are necessary. Although AIE is more common in infants, adult involvement has also been documented. Much of what is known about AIE has been gathered from case reports and small case series; therefore, more research in this evolving field is needed. IPEX (immunodysregulation polyendocrinopathy enteropathy X-linked syndrome) and APECED (autoimmune phenomena, polyendocrinopathy, candidiasis, and ectodermal dystrophy) are systemic forms of AIE.
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Affiliation(s)
- Nicole M Gentile
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
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28
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Gentile NM, Murray JA, Pardi DS. Autoimmune enteropathy: a review and update of clinical management. Curr Gastroenterol Rep 2012; 14:380-5. [PMID: 22810979 PMCID: PMC3912565 DOI: 10.1007/s11894-012-0276-2] [Citation(s) in RCA: 75] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Autoimmune enteropathy (AIE) is a rare condition characterized by intractable diarrhea, histologic changes on small intestinal biopsy, and failed response to dietary manipulation that also may present with extraintestinal manifestations. In many patients, immunosuppressive therapies are necessary. Although AIE is more common in infants, adult involvement has also been documented. Much of what is known about AIE has been gathered from case reports and small case series; therefore, more research in this evolving field is needed. IPEX (immunodysregulation polyendocrinopathy enteropathy X-linked syndrome) and APECED (autoimmune phenomena, polyendocrinopathy, candidiasis, and ectodermal dystrophy) are systemic forms of AIE.
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Affiliation(s)
- Nicole M Gentile
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
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29
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Murray JA, Rubio-Tapia A. Diarrhoea due to small bowel diseases. Best Pract Res Clin Gastroenterol 2012; 26:581-600. [PMID: 23384804 PMCID: PMC3621726 DOI: 10.1016/j.bpg.2012.11.013] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2012] [Accepted: 11/14/2012] [Indexed: 01/31/2023]
Abstract
Small intestinal diseases are a common, though often overlooked cause of diarrhoeal illness. Fully 1% of the Caucasian population are affected by coeliac disease and a substantial portion of children living in poverty in the developing world are affected by environmental enteropathy. These are but two examples of the many diseases that cause mucosal injury to the primary digestive and absorptive organ in our body. While diarrhoea may be a common, though not universally seen symptom of small bowel mucosal disease, the consequent malabsorption can lead to substantial malnutrition and nutrient deficiencies. The small intestine, unlike the colon, has been relatively inaccessible, and systematic evaluation is often necessary to identify and treat small intestinal mucosal diseases that lead to diarrhoea. Immunodeficiency states, including HIV enteropathy, adult autoimmune enteropathy, drug-associated enteropathy, and tropical sprue continue to occur and require specific therapy. All patients with severe diarrhoea or diarrhoea associated with features suggestive of malabsorption may have a disease of the small intestinal mucosa that requires careful evaluation and targeted management.
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Affiliation(s)
- Joseph A. Murray
- Corresponding author. Tel.: +1 507 255 5713; fax: +1 507 255 6318.
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30
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Bishu S, Arsenescu V, Lee EY, Vargas HD, de Villiers WJS, Arsenescu R. Autoimmune enteropathy with a CD8+ CD7- T-cell small bowel intraepithelial lymphocytosis: case report and literature review. BMC Gastroenterol 2011; 11:131. [PMID: 22126605 PMCID: PMC3287162 DOI: 10.1186/1471-230x-11-131] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2011] [Accepted: 11/29/2011] [Indexed: 01/26/2023] Open
Abstract
Background Adult onset autoimmune enteropathy (AIE) is a rare condition characterized by diarrhea refractory to dietary therapy diagnosed in patients with evidence of autoimmune conditions. Auto-antibodies to gut epithelial cells and other tissues are commonly demonstrated. Despite increasing awareness, the pathogenesis, histologic, immunologic and clinical features of AIE remain uncertain. There remains controversy regarding the diagnostic criteria, the frequency and types of auto-antibodies and associated autoimmune conditions, and the extent and types of histologic and immunologic abnormalities. CD4+ T-cells are thought to at least responsible for this condition; whether other cell types, including B- and other T-cell subsets are involved, are uncertain. We present a unique case of AIE associated with a CD8+CD7- lymphocytosis and review the literature to characterize the histologic and immunologic abnormalities, and the autoantibodies and autoimmune conditions associated with AIE. Case Presentation We present a case of immune mediated enteropathy distinguished by the CD8+CD7- intra-epithelial and lamina propria lymphocytosis. Twenty-nine cases of AIE have been reported. The majority of patients had auto-antibodies (typically anti-enterocyte), preferential small bowel involvement, and predominately CD3+ CD4+ infiltrates. Common therapies included steroids or immuno-suppressive agents and clinical response with associated with histologic improvement. Conclusions AIE is most often characterized (1) IgG subclass anti-epithelial cell antibodies, (2) preferential small bowel involvement, and (3) CD3+ alphabeta TCR+ infiltrates; there is insufficient evidence to conclude CD4+ T-cells are solely responsible in all cases of AIE.
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Affiliation(s)
- Shrinivas Bishu
- Department of Internal Medicine, University of Kentucky Medical Center, 800 Rose Street, Lexington, Kentucky 40536, USA.
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31
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Montalto M, D'Onofrio F, Santoro L, Gallo A, Gasbarrini A, Gasbarrini G. Autoimmune enteropathy in children and adults. Scand J Gastroenterol 2010; 44:1029-36. [PMID: 19255930 DOI: 10.1080/00365520902783691] [Citation(s) in RCA: 72] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Autoimmune enteropathy is a rare disorder characterized by severe and protracted diarrhea, weight loss from malabsorption and immune-mediated damage to the intestinal mucosa, generally occurring in infants and young children, although some cases of adult onset have been reported in the literature. Pathogenetic mechanisms involve immunological disorders, in which the presence of antienterocyte autoantibodies, although detected since first description, seems now to be secondary. As occurs frequently in autoimmunity, subjects with autoimmune enteropathy may be affected by other autoimmune disorders, sometimes leading to particular forms, i.e. the IPEX syndrome and the APECED syndrome. The prognosis of autoimmune enteropathy patients depends on the severity of digestive symptoms (including fecal output), on the severity and extension of histological lesions along the gastrointestinal apparatus, and on the presence of extra-intestinal involvement. Management of autoimmune enteropathy patients is based on nutritional support and adequate hydration to ensure optimal growth and development, together with immunosuppressive therapy. Recently, biological agents have been introduced, with apparent beneficial effects.
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Affiliation(s)
- Massimo Montalto
- Institute of Internal Medicine, Catholic University, Rome, Italy.
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Gishen FS, Tookman AJ. An unusual case of malignant thymoma associated graft-versus-host disease. BMJ Case Rep 2009; 2009:bcr05.2009.1866. [PMID: 21853007 DOI: 10.1136/bcr.05.2009.1866] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
A woman in her early 50s presented with recurrent severe chest infections. Investigations revealed a low white cell count and a diagnosis of autoimmune neutropenia was made. Subsequently, an infiltrating thymic tumour (mitoses only) in the absence of myasthenia gravis was found. She underwent radical surgery. When neutropenic, she complained of painful, swollen joints and soft tissues. She was started on steroids and immunosuppressants and her pain settled. The following year, she had local malignant recurrence confirmed on imaging. She declined chemotherapy or targeted somatostatin and opted for alternative therapies. She developed a microcytic anaemia and commenced erythropoietin. This coincided with the development of a painful expanded rib lesion, hypercalcaemia, and ascites. She remained unwell with periodical flares in disease affecting many different organs and continued to mount a significant immunological response to her thymic tumour, manifesting as biopsy proven graft-versus-host disease involving joints, skin and lungs. This has been a complex clinical case involving multiple specialities, including haematology, oncology, immunology, endocrinology and palliative medicine.
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Affiliation(s)
- Faye Sara Gishen
- Marie Curie Cancer Care, Edenhall Hospice, Hampstead, 11 Lyndhurst Gardens, London NW3 5NS, UK
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Akram S, Murray JA, Pardi DS, Alexander GL, Schaffner JA, Russo PA, Abraham SC. Adult autoimmune enteropathy: Mayo Clinic Rochester experience. Clin Gastroenterol Hepatol 2007; 5:1282-90; quiz 1245. [PMID: 17683994 PMCID: PMC2128725 DOI: 10.1016/j.cgh.2007.05.013] [Citation(s) in RCA: 162] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Autoimmune enteropathy is a rare cause of intractable diarrhea associated with circulating gut autoantibodies and a predisposition to autoimmunity. It is rarely observed in adults, with only 11 cases reported to date. METHODS Fifteen adults with autoimmune enteropathy were identified at the Mayo Clinic, Rochester, from May 2001-June 2006. The demographic, clinical, and treatment data were abstracted from their records. RESULTS The study population was 87% white, 47% female, with median age of 55 years (interquartile range, 42-67 years). All patients had protracted diarrhea, weight loss, and malnutrition. Celiac disease was excluded by lack of response to gluten-free diet or absence of the celiac disease susceptibility HLA genotypes. Fourteen patients were tested for gut epithelial cell antibodies, and 93% were positive for anti-enterocyte and/or anti-goblet cell antibodies. Predisposition to autoimmune diseases was noted in 80%, as indicated by a variety of circulating autoantibodies. Small intestinal histopathologic findings included subtotal villous atrophy and lymphoplasmacytic infiltration in the lamina propria with relatively few surface intraepithelial lymphocytes. T-cell receptor gene rearrangement studies were negative in all cases. Immunosuppressive therapy was required in 93% of cases. Clinical improvement was noted in 60% after 1-8 weeks of steroid therapy. CONCLUSIONS Autoimmune enteropathy is a heterogeneous disease and should be considered in the differential diagnosis of malabsorption and small bowel villous atrophy. The presence of gut epithelial cell antibodies can help confirm the diagnosis. No single agent is unequivocally effective in inducing remission, and immunosuppressive therapy is required in most cases.
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Affiliation(s)
- Salma Akram
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, MN
| | - Joseph A. Murray
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, MN
| | - Darrell S. Pardi
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, MN
| | - Glenn L. Alexander
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, MN
| | - John A. Schaffner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, MN
| | - Pierre A. Russo
- Department of Pathology and Laboratory Medicine, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania
| | - Susan C. Abraham
- Division of Anatomic Pathology, Department of Pathology, Mayo Clinic College of Medicine, Rochester, Minnesota
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