|
1
|
Aggarwal N, Bhatia U, Dwarakanathan V, Singh AD, Singh P, Ahuja V, Makharia GK. Prevalence and etiologies of non-responsive celiac disease: A systematic review and meta-analysis. J Gastroenterol Hepatol 2025; 40:101-107. [PMID: 39557631 DOI: 10.1111/jgh.16808] [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: 07/22/2024] [Accepted: 10/30/2024] [Indexed: 11/20/2024]
Abstract
BACKGROUND AND AIM Non-responsive celiac disease (NRCD) is defined as ongoing symptoms despite 6-12 months of gluten-free diet (GFD), the only known treatment for celiac disease (CeD). There is inconsistency in studies describing the proportion of patients having NRCD and its various causes among patients with CeD. We therefore conducted a systematic review and meta-analysis to determine the prevalence and causes of NRCD. METHODS The PubMed, Embase, Cochrane Library, Scopus, and Web of Science databases were searched for original studies reporting the proportion of patients with persistent symptoms after ≥ 6 months of GFD. Studies reporting the etiologies of NRCD were also identified. The systematic review was conducted as per the Meta-analysis of Observational Studies in Epidemiology guidelines. Statistical analysis was performed in STATA. RESULTS Of 2965 search results, nine studies met the inclusion and exclusion criteria. Five studies (n = 4414) reported data on prevalence, and seven studies (n = 790) reported the causes of NRCD. The pooled prevalence of NRCD was 22% (95% confidence interval, 11-35%). Among patients with NRCD, inadvertent exposure to gluten was the most common cause (33%), followed by functional gastrointestinal disorders including irritable bowel syndrome in 16%. Refractory CeD type II along with its premalignant and malignant sequelae was observed in 7% of patients with NRCD. CONCLUSION One in five patients with CeD may not respond to GFD and would likely be classified as NRCD. Inadvertent gluten exposure was the cause of ongoing symptoms in one-third of patients with NRCD. Improving adherence to GFD along with developing novel therapeutics to mitigate symptoms due to ongoing gluten exposure is critical.
Collapse
Affiliation(s)
- Nishant Aggarwal
- Department of Internal Medicine, William Beaumont University Hospital, Royal Oak, Michigan, USA
| | - Unnati Bhatia
- Department of Internal Medicine, William Beaumont University Hospital, Royal Oak, Michigan, USA
| | - Vignesh Dwarakanathan
- Department of Community Medicine, Employees' State Insurance Corporation Hospital, Chennai, India
| | - Achintya Dinesh Singh
- Department of Gastroenterology and Hepatology, MetroHealth Medical Center, Case Western Reserve University, Cleveland, Ohio, USA
| | - Prashant Singh
- Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan, USA
| | - Vineet Ahuja
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Govind K Makharia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| |
Collapse
|
|
2
|
Meeuwes FO, Brink M, Plattel WJ, Vermaat JSP, Kersten MJ, Wondergem M, Visser O, van der Poel MWM, Oostvogels R, Woei‐A‐Jin FJSH, Böhmer L, Snijders TJF, Huls GA, Nijland M. Enteropathy-associated T-cell lymphoma: A population-based cohort study on incidence, treatment, and outcome in the Netherlands. EJHAEM 2024; 5:1215-1222. [PMID: 39691269 PMCID: PMC11647706 DOI: 10.1002/jha2.1049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Accepted: 10/11/2024] [Indexed: 12/19/2024]
Abstract
Introduction Enteropathy-associated T-cell lymphoma (EATL) is a peripheral T-cell lymphoma (PTCL) with a poor prognosis. Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with or without etoposide consolidated by autologous stem cell transplantation (ASCT) are recommended for fit PTCL patients. The role of etoposide and ASCT in EATL is unclear. Methods This study reports the incidence, treatment, and outcome of EATL patients using the Netherlands Cancer Registry, with nationwide coverage of >95%. Results All patients diagnosed in 1989-2021 (n = 351, 77% treated) were identified (median age 67 years, 56% male, 50% limited stage). Time period analysis assessed trends in primary therapy and overall survival (OS). Treatment included chemotherapy (CT) (34%), surgery (18%), surgery and CT (19%) or CT followed by ASCT (7%). The 5-year OS for treated patients with limited versus advanced stage was 19% and 9% respectively. The 2-year OS improved over time (21%-33%, p = 0.06). Surgery only (hazard ratio [HR] 2.16; 95% confidence interval [CI] 1.55-3.01, p < 0.01) and advanced-stage disease (HR 1.67; 95% CI 1.25-2.23, p = 0.01) were predictors of poor prognosis. ASCT (HR 0.31; 95% CI 0.18-0.56) was associated with improved OS. Conclusion There was no statistical difference in OS between patients treated with or without etoposide. Current first-line treatment is ineffective.
Collapse
Affiliation(s)
- Frederik O. Meeuwes
- Department of HematologyUniversity Medical Center GroningenGroningenthe Netherlands
- Department of HematologyMedisch Spectrum TwenteEnschedethe Netherlands
| | - Mirian Brink
- Department of HematologyUniversity Medical Center GroningenGroningenthe Netherlands
- Department of Research and DevelopmentNetherlands Comprehensive Cancer Organization (IKNL)Utrechtthe Netherlands
| | - Wouter J. Plattel
- Department of HematologyMedisch Spectrum TwenteEnschedethe Netherlands
| | - Joost S. P. Vermaat
- Department of HematologyLeiden University Medical CenterLeidenthe Netherlands
| | - Marie José Kersten
- Department of HematologyAmsterdam University Medical Center, Cancer Center AmsterdamUniversity of AmsterdamAmsterdamthe Netherlands
| | - Mariëlle Wondergem
- Department of HematologyAmsterdam University Medical Center, Cancer Center AmsterdamUniversity of AmsterdamAmsterdamthe Netherlands
| | - Otto Visser
- Department of HematologyIsala HospitalZwollethe Netherlands
| | - Marjolein W. M. van der Poel
- Department of Internal MedicineDivision of HematologyGROW School for Oncology and Developmental Biology, Maastricht University Medical CenterMaastrichtthe Netherlands
| | - Rimke Oostvogels
- Department of HematologyUniversity Medical Center UtrechtUtrechtthe Netherlands
| | | | - Lara Böhmer
- Department of HematologyHaga Teaching Hospitalthe Haguethe Netherlands
| | | | - Gerwin A. Huls
- Department of HematologyUniversity Medical Center GroningenGroningenthe Netherlands
| | - Marcel Nijland
- Department of HematologyUniversity Medical Center GroningenGroningenthe Netherlands
| |
Collapse
|
|
3
|
Verdelho Machado M. Refractory Celiac Disease: What the Gastroenterologist Should Know. Int J Mol Sci 2024; 25:10383. [PMID: 39408713 PMCID: PMC11477276 DOI: 10.3390/ijms251910383] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2024] [Revised: 09/20/2024] [Accepted: 09/25/2024] [Indexed: 10/20/2024] Open
Abstract
Fewer than 1% of patients with celiac disease (CD) will develop refractory CD (RCD). As such, most gastroenterologists might never need to manage patients with RCD. However, all gastroenterologists must be familiarized with the basic concepts of RCD and non-responsive CD (NRCD), since it can present as a severe disease with high mortality, not only due to intestinal failure, but also due to progression to enteropathy-associated T cell lymphoma (EATL) and a higher susceptibility to life-threatening infections. The diagnostic workup and differential diagnosis with other causes of gastrointestinal symptoms and villous atrophy, as well as the differentiation between type I and II RCD, are complex, and may require specialized laboratories and reference hospitals. Immunosuppression is efficient in the milder RCDI; however, the treatment of RCDII falls short, with current options probably only providing transient clinical improvement and delaying EATL development. This review summarizes the current diagnostic and therapeutic approach for patients with RCD that all doctors that manage patients with CD should know.
Collapse
Affiliation(s)
- Mariana Verdelho Machado
- Gastroenterology Department, Hospital de Vila Franca de Xira, 2600-009 Lisbon, Portugal; ; Tel.: +351-912620306
- Gastroenterology Department, Faculdade de Medicina, Lisbon University, 1649-028 Lisboa, Portugal
| |
Collapse
|
|
4
|
Tye‐Din JA. Evolution in coeliac disease diagnosis and management. JGH Open 2024; 8:e13107. [PMID: 38957478 PMCID: PMC11217771 DOI: 10.1002/jgh3.13107] [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] [Received: 03/18/2024] [Revised: 05/04/2024] [Accepted: 05/28/2024] [Indexed: 07/04/2024]
Abstract
The traditional gut-centric view of coeliac disease is evolving as immune and genetic insights underscore the central importance of a systemic, T cell immune response to gluten in disease pathogenesis. As the field increasingly recognize the limitations of small intestinal histology as the diagnostic standard, data supporting the accuracy of an immune (serologic) diagnosis of coeliac disease - well demonstrated in children - are growing for adults. Novel biomarkers such as interleukin-2 that identify the gluten-specific T cell demonstrate high sensitivity and specificity for coeliac disease and offer the potential for a diagnostic approach that avoids the need for gluten challenge. Asymptomatic disease and manifestations outside the gut pose considerable challenges for diagnosis using a case-finding strategy and enthusiasm for population screening is growing. The gluten-free diet remains a highly restrictive treatment and there is a paucity of controlled data to inform a safe gluten intake threshold. Ongoing symptoms and enteropathy are common and require systematic evaluation. Slowly-responsive disease is prevalent in the older patient diagnosed with coeliac disease, and super-sensitivity to gluten is an emerging concept that may explain many cases of nonresponsive disease. While there is great interest in developing novel therapies for coeliac disease, no drug has yet been registered. Efficacy studies are generally assessing drugs in patients with treated coeliac disease who undergo gluten challenge or in patients with nonresponsive disease; however, substantial questions remain around specific endpoints relevant for patients, clinicians and regulatory agencies and optimal trial design. Novel immune tools are providing informative readouts for clinical trials and are now shaping their design.
Collapse
Affiliation(s)
- Jason A Tye‐Din
- Immunology DivisionWalter and Eliza Hall InstituteParkvilleVictoriaAustralia
- Department of Medical BiologyUniversity of MelbourneParkvilleVictoriaAustralia
- Department of GastroenterologyThe Royal Melbourne HospitalParkvilleVictoriaAustralia
- Centre for Food & Allergy ResearchThe Murdoch Children's Research InstituteParkvilleVictoriaAustralia
| |
Collapse
|
|
5
|
Hujoel IA, Hujoel MLA. The Rising Incidence and Poor Outcomes of Enteropathy-Associated T-Cell Lymphoma. Am J Gastroenterol 2024; 119:1412-1416. [PMID: 38235779 DOI: 10.14309/ajg.0000000000002666] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2023] [Accepted: 01/15/2024] [Indexed: 01/19/2024]
Abstract
INTRODUCTION Enteropathy-associated T-cell lymphoma (EATL) is associated with celiac disease. With the rising prevalence of celiac disease, we hypothesized that the prevalence of EATL is also increasing. METHODS We used the Surveillance, Epidemiology, and End Results database, which is a population-based US cancer surveillance program. We used the ICD-0-3 code 9717/3 to identify patients with EATL diagnosed between 2000 and 2020. Incidence rates were calculated using the SEER*Stat software, and annual percent change was calculated using the Joinpoint software. Log-rank tests were used to evaluate for significant difference in survival curves between groups. A Cox proportional hazards regression model was used for continuous variables and quantifying association strength of predictors. RESULTS A total of 463 cases of EATL were identified (273 male, 190 female) with a median age of 65 (range 23-90+) years. Most of the cases were at an advanced stage at diagnosis and were treated with a combination of surgery and chemotherapy. The median survival time was 6 months. The 2000-2020 age-adjusted incidence rate per 100,000 people was 0.014, and the incidence increased between 2000 and 2020, with an annual percent change of 2.58 ( P < 0.05). Increased age at diagnosis and lack of treatment had significant impacts on survival while sex, year of diagnosis, race, and time between diagnosis and treatment had no significant impact on survival. DISCUSSION There was a significant increase in the incidence of EATL in the United States between 2000 and 2020. Survival in this cancer remains poor and unchanged over the past 2 decades.
Collapse
Affiliation(s)
- Isabel A Hujoel
- Division of Gastroenterology, University of Washington, Seattle, Washington, USA
| | - Margaux L A Hujoel
- Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
- Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
| |
Collapse
|
|
6
|
Kurppa K, Mulder CJ, Stordal K, Kaukinen K. Celiac Disease Affects 1% of Global Population: Who Will Manage All These Patients? Gastroenterology 2024; 167:148-158. [PMID: 38290622 DOI: 10.1053/j.gastro.2023.12.026] [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: 11/03/2023] [Revised: 12/19/2023] [Accepted: 12/19/2023] [Indexed: 02/01/2024]
Abstract
Celiac disease is a common gastrointestinal condition with an estimated global prevalence of up to 1%. Adequate long-term surveillance of patients is imperative to ensure strict adherence to treatment with a gluten-free diet and the ensuing clinical and histologic recovery. Traditionally, this has been accomplished by means of regular on-site attendance at specialist health care facilities, accompanied for most patients by follow-up endoscopic and laboratory tests. However, the rapidly increasing prevalence of celiac disease and the limited health care resources challenge the current centralized and nonindividualized follow-up strategies. The improved noninvasive surveillance tools and online health care services are further changing the landscape of celiac disease management. There is a clear need for more personalized and on-demand follow-up based on early treatment response and patient-related factors associated with long-term prognosis. Additional scientific evidence on the optimal implementation of follow-up for pediatric and adulthood celiac disease is nevertheless called for.
Collapse
Affiliation(s)
- Kalle Kurppa
- Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; Tampere Center for Child, Adolescent, and Maternal Health Research, Tampere University, Tampere, Finland; Department of Pediatrics, Tampere University Hospital, Tampere, Finland; University Consortium of Seinäjoki, Seinäjoki, Finland.
| | - Chris J Mulder
- Department of Gastroenterology, Amsterdam University Medical Center, Amsterdam, The Netherlands; Location Vrije Universiteit, Amsterdam, The Netherlands
| | - Ketil Stordal
- Division of Pediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway; Department of Pediatric Research, Faculty of Medicine, University of Oslo, Oslo, Norway
| | - Katri Kaukinen
- Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; Department of Internal Medicine, Tampere University Hospital, Tampere, Finland
| |
Collapse
|
|
7
|
Schiepatti A, Maimaris S, Scarcella C, Pignatti P, Betti E, Shoval Y, Arpa G, Ciccocioppo R, Biagi F. Flow cytometry for the assessment and monitoring of aberrant intraepithelial lymphocytes in non-responsive celiac disease and non-celiac enteropathies. Dig Liver Dis 2024; 56:795-801. [PMID: 37968145 DOI: 10.1016/j.dld.2023.10.025] [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: 07/22/2023] [Revised: 10/19/2023] [Accepted: 10/27/2023] [Indexed: 11/17/2023]
Abstract
BACKGROUND Few data are available on flow cytometry (FC) for monitoring intraepithelial lymphocytes (IELs) in refractory celiac disease (RCD), non-responsive celiac disease (NRCD), and non-celiac enteropathies (NCEs). AIMS 1) To investigate the significance of monitoring IELs immunophenotype with FC in patients with NRCD, RCD and NCEs; 2) to evaluate FC concordance with immunohistochemistry (IHC) and γ-TCR clonality analysis. METHODS Patients investigated between January-2012 and February-2023 were divided into two groups: 1)confirmed RCD or NRCD being investigated for persistent symptoms and suspected complications of celiac disease (CD); 2)NCEs lacking clinical/histological response. Clinical/molecular features and outcomes were retrospectively collected and analysed according to presence/absence of aberrant IELs on FC (cut-off≥20 % CD103+sCD3-CD8-iCD3+ IELs). RESULTS 52 patients (18 RCD,21 NRCD,13 NCEs; 38F, 55±13 years; median follow-up 30 months, IQR 2-58) underwent 100 FC IELs determinations. 22/52 had ≥2 FC determinations and IEL phenotype remained unchanged over time in all them (κ=1.00). Aberrant IEL phenotype in CD was associated with increased mortality (HR 4.2, 95 % CI 1.5-11.9, p < 0.01). No patients with NCEs had an aberrant IEL phenotype at FC, although 3/13 developed lymphoma and 4/13 died. Concordance of FC was fair with both IHC (κ=0.40) and γ-TCR clonality analysis (κ=0.22). CONCLUSION FC is accurate for assessing and monitoring IEL phenotype and providing important prognostic information in celiac patients. Further study is needed on its role in NCEs.
Collapse
Affiliation(s)
- Annalisa Schiepatti
- Department of Internal Medicine and Therapeutics, University of Pavia, Italy; Istituti Clinici Scientifici Maugeri IRCCS, Gastroenterology Unit of Pavia Institute, Italy.
| | - Stiliano Maimaris
- Department of Internal Medicine and Therapeutics, University of Pavia, Italy; Istituti Clinici Scientifici Maugeri IRCCS, Gastroenterology Unit of Pavia Institute, Italy
| | - Chiara Scarcella
- Department of Internal Medicine and Therapeutics, University of Pavia, Italy
| | - Patrizia Pignatti
- Allergy and Immunology Unit Istituti Clinici Scientifici Maugeri, IRCCS, Pavia, Italy
| | - Elena Betti
- Department of Internal Medicine, San Matteo Hospital Foundation, University of Pavia, Pavia, Italy
| | - Yiftach Shoval
- Department of Internal Medicine and Therapeutics, University of Pavia, Italy
| | - Giovanni Arpa
- Department of Molecular Medicine, Unit of Anatomic Pathology, University of Pavia, Italy; Unit of Anatomic Pathology, ICS Maugeri-IRCCS SpA SB, 27100 Pavia, Italy
| | - Rachele Ciccocioppo
- Gastroenterology Unit, Department of Medicine, Azienda Ospedaliera Universitaria Integrata Policlinico G.B. Rossi and University of Verona, Verona, Italy
| | - Federico Biagi
- Department of Internal Medicine and Therapeutics, University of Pavia, Italy; Istituti Clinici Scientifici Maugeri IRCCS, Gastroenterology Unit of Pavia Institute, Italy
| |
Collapse
|
|
8
|
Lenti MV, Broglio G, Lucioni M, Corazza GR. Refractory celiac disease and lymphomagenesis. PEDIATRIC AND ADULT CELIAC DISEASE 2024:207-227. [DOI: 10.1016/b978-0-443-13359-6.00007-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
|
|
9
|
Stuver R, Epstein-Peterson ZD, Horwitz SM. Few and far between: clinical management of rare extranodal subtypes of mature T-cell and NK-cell lymphomas. Haematologica 2023; 108:3244-3260. [PMID: 38037801 PMCID: PMC10690914 DOI: 10.3324/haematol.2023.282717] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2023] [Accepted: 07/03/2023] [Indexed: 12/02/2023] Open
Abstract
While all peripheral T-cell lymphomas are uncommon, certain subtypes are truly rare, with less than a few hundred cases per year in the USA. There are often no dedicated clinical trials in these rare subtypes, and data are generally limited to case reports and retrospective case series. Therefore, clinical management is often based on this limited literature and extrapolation of data from the more common, nodal T-cell lymphomas in conjunction with personal experience. Nevertheless, thanks to tremendous pre-clinical efforts to understand these rare diseases, an increasing appreciation of the biological changes that underlie these entities is forming. In this review, we attempt to summarize the relevant literature regarding the initial management of certain rare subtypes, specifically subcutaneous panniculitis-like T-cell lymphoma, hepatosplenic T-cell lymphoma, intestinal T-cell lymphomas, and extranodal NK/T-cell lymphoma. While unequivocally established approaches in these diseases do not exist, we make cautious efforts to provide our approaches to clinical management when possible.
Collapse
Affiliation(s)
- Robert Stuver
- Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center.
| | - Zachary D Epstein-Peterson
- Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center; Department of Medicine, Weill Cornell Medical College
| | - Steven M Horwitz
- Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center; Department of Medicine, Weill Cornell Medical College; Cellular Therapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
| |
Collapse
|
|
10
|
Scarmozzino F, Pizzi M, Pelizzaro F, Angerilli V, Dei Tos AP, Piazza F, Savarino EV, Zingone F, Fassan M. Refractory celiac disease and its mimickers: a review on pathogenesis, clinical-pathological features and therapeutic challenges. Front Oncol 2023; 13:1273305. [PMID: 38023263 PMCID: PMC10662059 DOI: 10.3389/fonc.2023.1273305] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2023] [Accepted: 10/20/2023] [Indexed: 12/01/2023] Open
Abstract
Refractory celiac disease (RCD) and enteropathy-associated T-cell lymphoma (EATL) are rare, yet severe complications of celiac disease (CD). Over the last decades, several studies have addressed the biology and clinical-pathological features of such conditions, highlighting unique disease patterns and recurrent genetic events. Current classification proposals identify two forms of RCD, namely: (i) type 1 RCD (RCD-I), characterized by phenotypically normal intra-epithelial lymphocytes (IELs); and (ii) type 2 RCD (RCD-II), featuring phenotypically aberrant IELs. While RCD-I likely represents a gluten-independent dysimmune reaction against small bowel epithelial cells, RCD-II is better considered an in situ aggressive T-cell lymphoma, with high rates of progression to overt EATL. The diagnosis of RCD and EATL is often challenging, due to misleading clinical-pathological features and to significant overlap with several CD-unrelated gastro-intestinal disorders. Similarly, the treatment of RCD and EATL is an unmet clinical need for both gastroenterologists and hematologists. Moving from such premises, this review aims to provide a comprehensive view of RCD and EATL, specifically considering their pathogenesis and the many still open issues concerning their diagnosis and clinical management.
Collapse
Affiliation(s)
- Federico Scarmozzino
- Surgical Pathology and Cytopathology Unit, Department of Medicine-DIMED, University of Padua School of Medicine, Padua, Italy
| | - Marco Pizzi
- Surgical Pathology and Cytopathology Unit, Department of Medicine-DIMED, University of Padua School of Medicine, Padua, Italy
| | - Filippo Pelizzaro
- Gastroenterology Unit, Department of Surgical, Gastroenterological and Oncological Sciences -DISCOG, University of Padua School of Medicine, Padua, Italy
| | - Valentina Angerilli
- Surgical Pathology and Cytopathology Unit, Department of Medicine-DIMED, University of Padua School of Medicine, Padua, Italy
| | - Angelo Paolo Dei Tos
- Surgical Pathology and Cytopathology Unit, Department of Medicine-DIMED, University of Padua School of Medicine, Padua, Italy
| | - Francesco Piazza
- Hematology & Clinical Immunology Unit, Department of Medicine-DIMED, University of Padua School of Medicine, Padua, Italy
| | - Edoardo Vincenzo Savarino
- Gastroenterology Unit, Department of Surgical, Gastroenterological and Oncological Sciences -DISCOG, University of Padua School of Medicine, Padua, Italy
| | - Fabiana Zingone
- Gastroenterology Unit, Department of Surgical, Gastroenterological and Oncological Sciences -DISCOG, University of Padua School of Medicine, Padua, Italy
| | - Matteo Fassan
- Surgical Pathology and Cytopathology Unit, Department of Medicine-DIMED, University of Padua School of Medicine, Padua, Italy
- Veneto Institute of Oncology, IOV-IRCCS, Padua, Italy
| |
Collapse
|
|
11
|
Vauquelin B, Rivière P. [Celiac disease]. Rev Med Interne 2023; 44:539-545. [PMID: 37558601 DOI: 10.1016/j.revmed.2023.07.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Revised: 06/12/2023] [Accepted: 07/25/2023] [Indexed: 08/11/2023]
Abstract
Celiac disease is a frequent auto-immune disease characterized by villous atrophy related to gluten intake in patients with genetic susceptiblity. Patients do not present symptoms in the majority of cases. Presence of the disease must be investigated in case of digestive symptoms or presence of auto-immune disease. Diagnosis is based on anti-transglutaminase antibody and dudodenal biospies. The only available treatment is gluten-free diet. Associated auto-immune diseases must be investigated, especially thyroiditis. Complications related to nutritional deficiency must be accounted for also.
Collapse
Affiliation(s)
- B Vauquelin
- Service d'hépato-gastroentérologie et oncologie digestive, centre médico-chirurgical Magellan, CHU de Bordeaux, Bordeaux, France
| | - P Rivière
- Service d'hépato-gastroentérologie et oncologie digestive, centre médico-chirurgical Magellan, CHU de Bordeaux, Bordeaux, France.
| |
Collapse
|
|
12
|
Bhansali RS, Barta SK. SOHO State of the Art Updates and Next Questions | Challenging Cases in Rare T-Cell Lymphomas. CLINICAL LYMPHOMA, MYELOMA & LEUKEMIA 2023; 23:642-650. [PMID: 37302955 PMCID: PMC10524462 DOI: 10.1016/j.clml.2023.05.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/18/2023] [Accepted: 05/19/2023] [Indexed: 06/13/2023]
Abstract
Mature T- and NK-cell neoplasms (MTNKN) collectively represent a rare disorder, representing less than 15% of all non-Hodgkin lymphoma (NHL) cases and qualifying for orphan disease designation by the U.S. Food and Drug Administration (FDA). These consist of 9 families in the fifth revised WHO classification of lymphoid neoplasms, which are made up of over 30 disease subtypes, underscoring the heterogeneity of clinical features, molecular biology, and genetics across this disease group. Moreover, the 5 most common subtypes (peripheral T-cell lymphoma, not otherwise specified; nodal TFH cell lymphoma, angioimmunoblastic type; extranodal NK-cell/T-cell lymphoma; adult T-cell leukemia/lymphoma; and ALK-positive or -negative anaplastic large cell lymphoma) comprise over 75% of MTNKN cases, so other subtypes are exceedingly rare in the context of all NHL diagnoses and consequently often lack consensus on best practices in diagnosis and management. In this review, we discuss the following entities-enteropathy-associated T-cell lymphoma (EATL), monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), hepatosplenic T-cell lymphoma (HSTCL), subcutaneous panniculitis-like T-cell lymphoma (SPTCL), and primary cutaneous ɣδ T-cell lymphoma (PCGD-TCL) - with an emphasis on clinical and diagnostic features and options for management.
Collapse
Affiliation(s)
- Rahul S Bhansali
- Department of Medicine, Division of Hematology and Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA
| | - Stefan K Barta
- Department of Medicine, Division of Hematology and Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA.
| |
Collapse
|
|
13
|
Valvano M, Fabiani S, Monaco S, Calabrò M, Mancusi A, Frassino S, Rolandi C, Mosca M, Faenza S, Sgamma E, Cesaro N, Latella G. Old and New Adjunctive Therapies in Celiac Disease and Refractory Celiac Disease: A Review. Int J Mol Sci 2023; 24:12800. [PMID: 37628981 PMCID: PMC10454405 DOI: 10.3390/ijms241612800] [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] [Received: 05/26/2023] [Revised: 07/13/2023] [Accepted: 08/12/2023] [Indexed: 08/27/2023] Open
Abstract
Celiac disease (CD) is a chronic enteropathy caused by the ingestion of gluten in a genetically susceptible individual. Currently, a gluten-free diet (GFD) is the only recommended treatment. However, unintentional gluten ingestion or a persistent villous atrophy with malabsorption (regardless of a strict GFD) as in the case of Refractory Celiac Disease (RCD) represents a major issue. In this review, we have analysed and discussed data from both randomized controlled trials and observational studies concerning adjunctive therapies as well as novel therapies for the treatment of CD and RCD. The literature search was carried out through Medline and Scopus. In total, 2268 articles have been identified and 49 were included in this review (36 studies resulting from the search strategy and 13 from other sources). Today, GFD remains the only effective treatment, although steroids, mesalamine, and more recently biological therapies have found space in the complex management of RCD. Currently, studies evaluating the effectiveness of novel therapies are still limited and preliminary results have been controversial.
Collapse
Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | - Giovanni Latella
- Gastroenterology Unit, Division of Gastroenterology, Hepatology and Nutrition, Department of Life, Health and Environmental Sciences, University of L’Aquila, Piazzale Salvatore Tommasi 1, 67100 L’Aquila, Italy; (M.V.); (S.F.); (S.M.); (M.C.); (A.M.); (S.F.); (C.R.); (M.M.); (S.F.); (E.S.); (N.C.)
| |
Collapse
|
|
14
|
Rouvroye MD, Bontkes HJ, Bol JGJM, Lissenberg-Witte B, Byrnes V, Bennani F, Jordanova ES, Wilhelmus MMM, Mulder CJ, van der Valk P, Rozemuller AJM, Bouma G, Van Dam AM. Cerebellar presence of immune cells in patients with neuro-coeliac disease. Acta Neuropathol Commun 2023; 11:51. [PMID: 36966322 PMCID: PMC10040112 DOI: 10.1186/s40478-023-01538-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Accepted: 03/01/2023] [Indexed: 03/27/2023] Open
Abstract
Although various neurodegenerative disorders have been associated with coeliac disease (CD), the underlying neuropathological link between these brain and gut diseases remains unclear. We postulated that the neuronal damage sporadically observed in CD patients is immune-mediated. Our aim was to determine if the loss of neurons, especially Purkinje cells, coincides with microglia activation and T- and B-cell infiltration in the cerebellum of patients with CD and a concomitant idiopathic neurological disease affecting the cerebellum (NeuroCD). Post-mortem cerebellar tissue was collected of validated NeuroCD cases. Gender- and age-matched genetic spinocerebellar ataxia (SCA) controls and non-neurological controls (NNC) were selected based on clinical reports and pathological findings. Cerebellar tissue of seventeen patients was included (6 NeuroCD, 5 SCA, 6 NNC). In SCA cases we found that the Purkinje cell layer was 58.6% reduced in comparison with NNC. In NeuroCD cases this reduction was even more prominent with a median reduction of 81.3% compared to NNC. Marked increased numbers of both CD3+ and CD8+ cells were observed in the NeuroCD but not in SCA patients. This coincided with significantly more microglial reactivity in NeuroCD patients. These findings demonstrate that the massive loss of Purkinje cells in the cerebellum of neuro CD patients is accompanied by local innate and T-cell mediated immune responses.
Collapse
Affiliation(s)
- Maxine D Rouvroye
- Department of Gastroenterology and Hepatology, AGEM Research Institute, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
- Department of Anatomy and Neurosciences, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, De Boelelaan 1108, 1081 HZ, Amsterdam, The Netherlands
- Department of Gastroenterology and Hepatology, Spaarne Gasthuis, Boerhavelaan 22, 2035 RC, Haarlem, The Netherlands
| | - Hetty J Bontkes
- Medical Immunology Laboratory, Department of Clinical Chemistry, Amsterdam Infection and Immunity Institute, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - John G J M Bol
- Department of Anatomy and Neurosciences, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, De Boelelaan 1108, 1081 HZ, Amsterdam, The Netherlands
| | - Birgit Lissenberg-Witte
- Department of Epidemiology and Data Science, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Valerie Byrnes
- Department of Gastroenterology and Hepatology, Galway University Hospitals, Galway, Ireland
| | - Fadel Bennani
- Department of Pathology, Mayo University Hospital, National University of Ireland Galway Affiliated Hospital, Galway, Ireland
| | - Ekaterina S Jordanova
- Department of Gynecology and Obstetrics, Center for Gynecologic Oncology Amsterdam, Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands
| | - Micha M M Wilhelmus
- Department of Anatomy and Neurosciences, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, De Boelelaan 1108, 1081 HZ, Amsterdam, The Netherlands
| | - Chris J Mulder
- Department of Gastroenterology and Hepatology, AGEM Research Institute, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Paul van der Valk
- Department of Pathology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Annemieke J M Rozemuller
- Department of Pathology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Gerd Bouma
- Department of Gastroenterology and Hepatology, AGEM Research Institute, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Anne-Marie Van Dam
- Department of Anatomy and Neurosciences, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, De Boelelaan 1108, 1081 HZ, Amsterdam, The Netherlands.
| |
Collapse
|
|
15
|
Elli L, Soru P, Roncoroni L, Rossi FG, Ferla V, Baldini L, Nandi N, Scaramella L, Scricciolo A, Rimondi A, Fusco N, Croci GA, Gianelli U, Cro L, Barbieri M, Lombardo V, Costantino A, Vaira V, Ferrero S, Tontini GE, Barigelletti G, Fabiano S, Doneda L, Vecchi M. Clinical features of type 1 and 2 refractory celiac disease: Results from a large cohort over a decade. Dig Liver Dis 2023; 55:235-242. [PMID: 36096991 DOI: 10.1016/j.dld.2022.08.022] [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: 04/19/2022] [Revised: 08/09/2022] [Accepted: 08/11/2022] [Indexed: 02/01/2023]
Abstract
OBJECTIVES Refractory celiac disease (RCeD) is a rare complication of celiac disease (CeD) with a severe prognosis. We describe a cohort of patients with RCeD, their clinical and histological features at diagnosis, after therapy and at lymphoma onset, and the rate and causes of death over a 17-year follow-up. METHODS We retrospectively enrolled RCeD-I and RCeD-II patients attending our center between January 2002 and October 2019. Medical data were collected at diagnosis and during monitoring. Response to therapy, changes in RCeD molecular markers, number of hospitalizations, discharge diagnosis, and cause and date of death were evaluated. The control cohort consisted of 1015 responsive CeD patients. RESULTS Compared with RCeD-I, RCeD-II more frequently exhibits diarrhea (83 vs 64%), anemia (61 vs 50%), hypoalbuminemia (70 vs 21%), parenteral nutrition need (48 vs 7%), ulcerative jejuno-ileitis (7 vs 39%), and extended small intestinal atrophy (62 vs 21%). One RCeD-I and six RCeD-II patients developed lymphoma. Ten RCeD-II patients died, four from lymphoma progression. Among RCeD-II patients, atrophy extension was the only parameter correlated with hypoalbuminemia and mortality. CONCLUSIONS Clinical severity, response to therapy, and mortality differ between RCeD-I and RCeD-II. Atrophy extension, evaluated at capsule endoscopy, was associated with disease severity and mortality.
Collapse
Affiliation(s)
- Luca Elli
- Department of Pathophysiology and Transplantation, University of Milan, Milan 20122, Italy; Center for Prevention and Diagnosis of Celiac Disease and Division of Gastroenterology and Endoscopy, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via F. Sforza 35, Milan 20122, Italy.
| | - Pietro Soru
- Department of Pathophysiology and Transplantation, University of Milan, Milan 20122, Italy; Center for Prevention and Diagnosis of Celiac Disease and Division of Gastroenterology and Endoscopy, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via F. Sforza 35, Milan 20122, Italy
| | - Leda Roncoroni
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan 20133, Italy
| | - Francesca Gaia Rossi
- Division of Hematology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via F. Sforza 35, Milan 20122, Italy
| | - Valeria Ferla
- Division of Hematology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via F. Sforza 35, Milan 20122, Italy
| | - Luca Baldini
- Division of Hematology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via F. Sforza 35, Milan 20122, Italy; Department of Oncology and Hemato-Oncology, University of Milan, Milan 20122, Italy
| | - Nicoletta Nandi
- Department of Pathophysiology and Transplantation, University of Milan, Milan 20122, Italy; Center for Prevention and Diagnosis of Celiac Disease and Division of Gastroenterology and Endoscopy, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via F. Sforza 35, Milan 20122, Italy
| | - Lucia Scaramella
- Center for Prevention and Diagnosis of Celiac Disease and Division of Gastroenterology and Endoscopy, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via F. Sforza 35, Milan 20122, Italy
| | - Alice Scricciolo
- Center for Prevention and Diagnosis of Celiac Disease and Division of Gastroenterology and Endoscopy, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via F. Sforza 35, Milan 20122, Italy
| | - Alessandro Rimondi
- Department of Pathophysiology and Transplantation, University of Milan, Milan 20122, Italy; Center for Prevention and Diagnosis of Celiac Disease and Division of Gastroenterology and Endoscopy, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via F. Sforza 35, Milan 20122, Italy
| | - Nicola Fusco
- Biobank for Translational Medicine Unit (B4MED), Division of Pathology, IEO European Institute of Oncology, University of Milan, Via Ripamonti 435, 20132 Milan, Italy
| | - Giorgio Alberto Croci
- Department of Pathophysiology and Transplantation, University of Milan, Milan 20122, Italy; Division of Pathology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via F. Sforza 35, Milan 20122, Italy
| | - Umberto Gianelli
- Department of Pathophysiology and Transplantation, University of Milan, Milan 20122, Italy; Division of Pathology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via F. Sforza 35, Milan 20122, Italy
| | - Lilla Cro
- Servizio di Citofluorimetria, Laboratorio Centrale, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Marzia Barbieri
- Servizio di Citofluorimetria, Laboratorio Centrale, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Vincenza Lombardo
- Center for Prevention and Diagnosis of Celiac Disease and Division of Gastroenterology and Endoscopy, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via F. Sforza 35, Milan 20122, Italy
| | - Andrea Costantino
- Department of Pathophysiology and Transplantation, University of Milan, Milan 20122, Italy; Center for Prevention and Diagnosis of Celiac Disease and Division of Gastroenterology and Endoscopy, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via F. Sforza 35, Milan 20122, Italy
| | - Valentina Vaira
- Department of Pathophysiology and Transplantation, University of Milan, Milan 20122, Italy; Division of Pathology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via F. Sforza 35, Milan 20122, Italy
| | - Stefano Ferrero
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan 20133, Italy; Division of Pathology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via F. Sforza 35, Milan 20122, Italy
| | - Gian Eugenio Tontini
- Department of Pathophysiology and Transplantation, University of Milan, Milan 20122, Italy; Center for Prevention and Diagnosis of Celiac Disease and Division of Gastroenterology and Endoscopy, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via F. Sforza 35, Milan 20122, Italy
| | - Giulio Barigelletti
- Cancer Registry Unit, Fondazione IRCCS Istituto Nazionale dei Tumori Milano, Milan Italy
| | - Sabrina Fabiano
- Cancer Registry Unit, Fondazione IRCCS Istituto Nazionale dei Tumori Milano, Milan Italy
| | - Luisa Doneda
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan 20133, Italy
| | - Maurizio Vecchi
- Department of Pathophysiology and Transplantation, University of Milan, Milan 20122, Italy; Center for Prevention and Diagnosis of Celiac Disease and Division of Gastroenterology and Endoscopy, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via F. Sforza 35, Milan 20122, Italy
| |
Collapse
|
|
16
|
Donnelly SC. Extensive Mucosal Disease: Coeliac Disease and Eosinophilic Enteritis. INTESTINAL FAILURE 2023:161-175. [DOI: 10.1007/978-3-031-22265-8_12] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
|
|
17
|
Packova B, Kohout P, Dastych M, Prokesova J, Grolich T, Kroupa R. Malignant complications of celiac disease: a case series and review of the literature. J Med Case Rep 2022; 16:460. [PMID: 36503568 PMCID: PMC9743581 DOI: 10.1186/s13256-022-03682-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Accepted: 11/18/2022] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Celiac disease is an immune-mediated enteropathy triggered by gluten in genetically susceptible individuals. Diagnosis is based on evaluating specific autoantibodies and histopathologic findings of duodenal biopsy specimens. The only therapy for celiac disease is a gluten-free diet. Celiac disease can be complicated by malnutrition, other autoimmune diseases, refractoriness to treatment, and gastrointestinal tumors. This article presents seven cases of malignancies in patients with celiac disease. Its objective is to raise awareness of the malignant complications of celiac disease, leading to earlier diagnosis and improved outcomes. CASE PRESENTATION Seven cases of malignant complications of celiac disease occurred among 190 patients followed at the Department of Internal Medicine and Gastroenterology, University Hospital Brno from 2014 to 2021. We describe these cases and the presentation, diagnostic process, course, management, and outcomes for each, along with proposed potential risk factors of malignant complications. There was one Caucasian man who was 70 years old and six Caucasian women who were 36, 46, 48, 55, 73, and 82 years old in our cohort. Of the seven cases of malignancies in our cohort, four patients were diagnosed with small bowel adenocarcinoma, one with diffuse large B-cell lymphoma, one with carcinoma of the tongue, and one with colorectal carcinoma. CONCLUSIONS Malignancies occurred in 3.7% of patients followed up for celiac disease. Awareness of the malignant complications of celiac disease, risk factors, presentation, and disease course could lead to earlier diagnosis and improved outcomes.
Collapse
Affiliation(s)
- Barbora Packova
- Department of Internal Medicine and Gastroenterology, University Hospital Brno, Faculty of Medicine, Masaryk University, Jihlavska 20, 62500 Brno, Czech Republic
| | - Pavel Kohout
- grid.4491.80000 0004 1937 116XDepartment of Internal Medicine, Third Faculty of Medicine, Charles University Prague and Teaching Thomayer Hospital, 14059 Prague, Czech Republic
| | - Milan Dastych
- Department of Internal Medicine and Gastroenterology, University Hospital Brno, Faculty of Medicine, Masaryk University, Jihlavska 20, 62500 Brno, Czech Republic
| | - Jitka Prokesova
- Department of Internal Medicine and Gastroenterology, University Hospital Brno, Faculty of Medicine, Masaryk University, Jihlavska 20, 62500 Brno, Czech Republic
| | - Tomas Grolich
- Department of Surgery, University Hospital Brno, Faculty of Medicine, Masaryk University, 62500 Brno, Czech Republic
| | - Radek Kroupa
- Department of Internal Medicine and Gastroenterology, University Hospital Brno, Faculty of Medicine, Masaryk University, Jihlavska 20, 62500 Brno, Czech Republic
| |
Collapse
|
|
18
|
High Prevalence of Functional Gastrointestinal Disorders in Celiac Patients with Persistent Symptoms on a Gluten-Free Diet: A 20-Year Follow-Up Study. Dig Dis Sci 2022:10.1007/s10620-022-07727-x. [PMID: 36401140 PMCID: PMC10352160 DOI: 10.1007/s10620-022-07727-x] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Accepted: 07/20/2022] [Indexed: 11/19/2022]
Abstract
BACKGROUND Ongoing symptoms in treated celiac disease (CD) are frequent and are commonly thought of as being due to infractions to a gluten-free diet (GFD) or complications. AIMS To study the etiology and natural history of clinically relevant events (CREs) throughout follow-up and identify predictors thereof to guide follow-up. METHODS CREs (symptoms/signs requiring diagnostic/therapeutic interventions) occurring in celiac patients between January-2000 and May-2021 were retrospectively collected between June and September 2021 and analysed. RESULTS One-hundred-and-eighty-nine adult patients (133 F, age at diagnosis 36 ± 13 years, median follow-up 103 months, IQR 54-156) were enrolled. CREs were very common (88/189, 47%), but hardly due to poor GFD adherence (4%) or complications (2%). Interestingly, leading etiologies were functional gastrointestinal disorders (30%), reflux disease (18%) and micronutrient deficiencies (10%). Age at diagnosis ≥ 45 years (HR 1.68, 95%CI 1.05-2.69, p = 0.03) and classical pattern of CD (HR 1.63, 95%CI 1.04-2.54, p = 0.03) were predictors of CREs on a multivariable Cox model. At 5 years, 46% of classical patients ≥ 45 years old at diagnosis were event-free, while this was 62% for non-classical/silent ≥ 45 years, 60% for classical < 45 years, and 80% for non-classical/silent < 45 years. CONCLUSIONS CREs occurred in almost half of CD patients during follow-up, with functional disorders being very common. New follow-up strategies for adult CD may be developed based on age and clinical pattern at diagnosis.
Collapse
|
|
19
|
Green PHR, Paski S, Ko CW, Rubio-Tapia A. AGA Clinical Practice Update on Management of Refractory Celiac Disease: Expert Review. Gastroenterology 2022; 163:1461-1469. [PMID: 36137844 DOI: 10.1053/j.gastro.2022.07.086] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Revised: 07/21/2022] [Accepted: 07/23/2022] [Indexed: 12/02/2022]
Abstract
DESCRIPTION The purpose of this expert review is to summarize the diagnosis and management of refractory celiac disease. It will review evaluation of patients with celiac disease who have persistent or recurrent symptoms, differential diagnosis, nutritional support, potential therapeutic options, and surveillance for complications of this condition. METHODS This expert review was commissioned and approved by the American Gastroenterological Association (AGA) Institute Clinical Practice Updates Committee (CPUC) and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership and underwent internal peer review by the CPUC and external peer review through standard procedures of Gastroenterology. These Best Practice Advice (BPA) statements were drawn from a review of the published literature and from expert opinion. Since systematic reviews were not performed, these BPA statements do not carry formal ratings of the quality of evidence or strength of the presented considerations. Best Practice Advice Statements BEST PRACTICE ADVICE 1: In patients believed to have celiac disease who have persistent or recurrent symptoms or signs, the initial diagnosis of celiac disease should be confirmed by review of prior diagnostic testing, including serologies, endoscopies, and histologic findings. BEST PRACTICE ADVICE 2: In patients with confirmed celiac disease with persistent or recurrent symptoms or signs (nonresponsive celiac disease), ongoing gluten ingestion should be excluded as a cause of these symptoms with serologic testing, dietitian review, and detection of immunogenic peptides in stool or urine. Esophagogastroduodenoscopy with small bowel biopsies should be performed to look for villous atrophy. If villous atrophy persists or the initial diagnosis of celiac disease was not confirmed, consider other causes of villous atrophy, including common variable immunodeficiency, autoimmune enteropathy, tropical sprue, and medication-induced enteropathy. BEST PRACTICE ADVICE 3: For patients with nonresponsive celiac disease, after exclusion of gluten ingestion, perform a systematic evaluation for other potential causes of symptoms, including functional bowel disorders, microscopic colitis, pancreatic insufficiency, inflammatory bowel disease, lactose or fructose intolerance, and small intestinal bacterial overgrowth. BEST PRACTICE ADVICE 4: Use flow cytometry, immunohistochemistry, and T-cell receptor rearrangement studies to distinguish between subtypes of refractory celiac disease and to exclude enteropathy-associated T-cell lymphoma. Type 1 refractory celiac disease is characterized by a normal intraepithelial lymphocyte population and type 2 is defined by the presence of an aberrant, clonal intraepithelial lymphocyte population. Consultation with an expert hematopathologist is necessary to interpret these studies. BEST PRACTICE ADVICE 5: Perform small bowel imaging with capsule endoscopy and computed tomography or magnetic resonance enterography to exclude enteropathy-associated T-cell lymphoma and ulcerative jejunoileitis at initial diagnosis of type 2 refractory celiac disease. BEST PRACTICE ADVICE 6: Complete a detailed nutritional assessment with investigation of micronutrient and macronutrient deficiencies in patients diagnosed with refractory celiac disease. Check albumin as an independent prognostic factor. BEST PRACTICE ADVICE 7: Correct deficiencies in macro- and micronutrients using oral supplements and/or enteral support. Consider parenteral nutrition for patients with severe malnutrition due to malabsorption. BEST PRACTICE ADVICE 8: Corticosteroids, most commonly open-capsule budesonide or, if unavailable, prednisone, are the medication of choice and should be used as first-line therapy in either type 1 or type 2 refractory celiac disease. BEST PRACTICE ADVICE 9: Patients with refractory celiac disease require regular follow-up by a multidisciplinary team, including gastroenterologists and dietitians, to assess clinical and histologic response to therapy. Identify local experts with expertise in celiac disease to assist with management. BEST PRACTICE ADVICE 10: Patients with refractory celiac disease without response to steroids may benefit from referral to a center with expertise for management or evaluation for inclusion in clinical trials.
Collapse
Affiliation(s)
| | - Shirley Paski
- Cedars-Sinai Medical Center, Los Angeles, California
| | - Cynthia W Ko
- Department of Medicine, University of Washington, Seattle, Washington.
| | - Alberto Rubio-Tapia
- Celiac Disease Program, Division of Gastroenterology, Hepatology, and Nutrition, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, Ohio
| |
Collapse
|
|
20
|
Nandi N, Croci GA, Rossi FG, Cro L, Vecchi M, Elli L. Normalization of duodenal mucosa after treatment with Janus kinase (JAK) inhibitor in refractory celiac disease type 2. Clin Res Hepatol Gastroenterol 2022; 46:101960. [PMID: 35623554 DOI: 10.1016/j.clinre.2022.101960] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2022] [Revised: 05/12/2022] [Accepted: 05/16/2022] [Indexed: 02/04/2023]
Affiliation(s)
- Nicoletta Nandi
- Department of Pathophysiology and Transplantation, University of Milan, Milan 20122, Italy; Center for Prevention and Diagnosis of Celiac Disease and Division of Gastroenterology and Endoscopy, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via F. Sforza 35, Milan 20122, Italy
| | - Giorgio Alberto Croci
- Department of Pathophysiology and Transplantation, University of Milan, Milan 20122, Italy; Division of Pathology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via F. Sforza 35, Milan 20122, Italy
| | - Francesca Gaia Rossi
- Division of Hemaotology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via F. Sforza 35, Milan 20122, Italy
| | - Lilla Cro
- Servizio di Citofluorimetria, Laboratorio Centrale, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Maurizio Vecchi
- Department of Pathophysiology and Transplantation, University of Milan, Milan 20122, Italy; Center for Prevention and Diagnosis of Celiac Disease and Division of Gastroenterology and Endoscopy, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via F. Sforza 35, Milan 20122, Italy
| | - Luca Elli
- Department of Pathophysiology and Transplantation, University of Milan, Milan 20122, Italy; Center for Prevention and Diagnosis of Celiac Disease and Division of Gastroenterology and Endoscopy, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via F. Sforza 35, Milan 20122, Italy.
| |
Collapse
|
|
21
|
Penny HA, Rej A, Baggus EMR, Coleman SH, Ward R, Wild G, Bouma G, Trott N, Snowden JA, Wright J, Cross SS, Hadjivassiliou M, Sanders DS. Non-Responsive and Refractory Coeliac Disease: Experience from the NHS England National Centre. Nutrients 2022; 14:nu14132776. [PMID: 35807956 PMCID: PMC9268848 DOI: 10.3390/nu14132776] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2022] [Revised: 06/21/2022] [Accepted: 06/27/2022] [Indexed: 02/04/2023] Open
Abstract
We characterised the aetiology of non-responsive coeliac disease (NRCD) and provided contemporary mortality data in refractory coeliac disease (RCD) from our centre. We also measured urine gluten immunogenic peptides (GIPs) in patients with established RCD1 to evaluate gluten exposure in these individuals. Methods: This was a longitudinal cohort study conducted in Sheffield, UK. Between 1998 and 2019, we evaluated 285 adult (≥16 years) patients with NRCD or RCD. Patients with established RCD1 and persisting mucosal inflammation and/or ongoing symptoms provided three urine samples for GIP analysis. Results: The most common cause of NRCD across the cohort was gluten exposure (72/285; 25.3%). RCD accounted for 65/285 patients (22.8%), 54/65 patients (83.1%) had RCD1 and 11/65 patients (16.9%) had RCD2. The estimated 5-year survival was 90% for RCD1 and 58% for RCD2 (p = 0.016). A total of 36/54 (66.7%) patients with RCD1 underwent urinary GIP testing and 17/36 (47.2%) had at least one positive urinary GIP test. Conclusion: The contemporary mortality data in RCD2 remains poor; patients with suspected RCD2 should be referred to a recognised national centre for consideration of novel therapies. The high frequency of urinary GIP positivity suggests that gluten exposure may be common in RCD1; further studies with matched controls are warranted to assess this further.
Collapse
Affiliation(s)
- Hugo A. Penny
- Academic Unit of Gastroenterology, Royal Hallamshire Hospital, Sheffield S10 2JF, UK; (A.R.); (E.M.R.B.); (S.H.C.); (R.W.); (G.W.); (N.T.); (S.S.C.)
- Correspondence: (H.A.P.); (D.S.S.); Tel.: +44-0114-271-1900 (H.A.P. & D.S.S.)
| | - Anupam Rej
- Academic Unit of Gastroenterology, Royal Hallamshire Hospital, Sheffield S10 2JF, UK; (A.R.); (E.M.R.B.); (S.H.C.); (R.W.); (G.W.); (N.T.); (S.S.C.)
| | - Elisabeth M. R. Baggus
- Academic Unit of Gastroenterology, Royal Hallamshire Hospital, Sheffield S10 2JF, UK; (A.R.); (E.M.R.B.); (S.H.C.); (R.W.); (G.W.); (N.T.); (S.S.C.)
| | - Sarah. H. Coleman
- Academic Unit of Gastroenterology, Royal Hallamshire Hospital, Sheffield S10 2JF, UK; (A.R.); (E.M.R.B.); (S.H.C.); (R.W.); (G.W.); (N.T.); (S.S.C.)
| | - Rosalie Ward
- Academic Unit of Gastroenterology, Royal Hallamshire Hospital, Sheffield S10 2JF, UK; (A.R.); (E.M.R.B.); (S.H.C.); (R.W.); (G.W.); (N.T.); (S.S.C.)
| | - Graeme Wild
- Academic Unit of Gastroenterology, Royal Hallamshire Hospital, Sheffield S10 2JF, UK; (A.R.); (E.M.R.B.); (S.H.C.); (R.W.); (G.W.); (N.T.); (S.S.C.)
| | - Gerd Bouma
- Department of Gastroenterology, Vrije Universiteit Medical Center, 1117 Amsterdam, The Netherlands;
| | - Nick Trott
- Academic Unit of Gastroenterology, Royal Hallamshire Hospital, Sheffield S10 2JF, UK; (A.R.); (E.M.R.B.); (S.H.C.); (R.W.); (G.W.); (N.T.); (S.S.C.)
| | - John A. Snowden
- Department of Haematology, Royal Hallamshire Hospital, Sheffield Teaching Hospital NHS Foundation Trust, Sheffield S10 2JF, UK; (J.A.S.); (J.W.)
| | - Josh Wright
- Department of Haematology, Royal Hallamshire Hospital, Sheffield Teaching Hospital NHS Foundation Trust, Sheffield S10 2JF, UK; (J.A.S.); (J.W.)
| | - Simon S. Cross
- Academic Unit of Gastroenterology, Royal Hallamshire Hospital, Sheffield S10 2JF, UK; (A.R.); (E.M.R.B.); (S.H.C.); (R.W.); (G.W.); (N.T.); (S.S.C.)
| | - Marios Hadjivassiliou
- Department of Neurology, Royal Hallamshire Hospital, Sheffield Teaching Hospital NHS Foundation Trust, Sheffield S10 2JF, UK;
| | - David S. Sanders
- Academic Unit of Gastroenterology, Royal Hallamshire Hospital, Sheffield S10 2JF, UK; (A.R.); (E.M.R.B.); (S.H.C.); (R.W.); (G.W.); (N.T.); (S.S.C.)
- Correspondence: (H.A.P.); (D.S.S.); Tel.: +44-0114-271-1900 (H.A.P. & D.S.S.)
| |
Collapse
|
|
22
|
Tye‐Din JA. Review article: Follow-up of coeliac disease. Aliment Pharmacol Ther 2022; 56 Suppl 1:S49-S63. [PMID: 35815829 PMCID: PMC9542881 DOI: 10.1111/apt.16847] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Revised: 02/12/2022] [Accepted: 02/13/2022] [Indexed: 12/09/2022]
Abstract
Coeliac disease is a lifelong immune-mediated enteropathy with systemic features associated with increased morbidity and modestly increased mortality. Treatment with a strict gluten-free diet improves symptoms and mucosal damage but is not curative and low-level gluten intake is common despite strict attempts at adherence. Regular follow-up after diagnosis is considered best-practice however this is executed poorly in the community with the problem compounded by the paucity of data informing optimal approaches. The aim of dietary treatment is to resolve symptoms, reduce complication risk and improve quality of life. It follows that the goals of monitoring are to assess dietary adherence, monitor disease activity, assess symptoms and screen for complications. Mucosal disease remission is regarded a key measure of treatment success as healing is associated with positive health outcomes. However, persistent villous atrophy is common, even after many years of a gluten-free diet. As the clinical significance of asymptomatic enteropathy is uncertain the role for routine follow-up biopsies remains contentious. Symptomatic non-responsive coeliac disease is common and with systematic follow-up a cause is usually found. Effective models of care involving the gastroenterologist, dietitian and primary care doctor will improve the consistency of long-term management and likely translate into better patient outcomes. Identifying suitable treatment targets linked to long-term health is an important goal.
Collapse
Affiliation(s)
- J. A. Tye‐Din
- Immunology DivisionThe Walter and Eliza Hall InstituteParkvilleVictoriaAustralia,Department of Medical BiologyUniversity of MelbourneParkvilleVictoriaAustralia,Department of GastroenterologyThe Royal Melbourne HospitalParkvilleVictoriaAustralia,Centre for Food & Allergy ResearchMurdoch Children’s Research InstituteParkvilleVictoriaAustralia
| |
Collapse
|
|
23
|
Makharia GK, Chauhan A, Singh P, Ahuja V. Review article: Epidemiology of coeliac disease. Aliment Pharmacol Ther 2022; 56 Suppl 1:S3-S17. [PMID: 35815830 DOI: 10.1111/apt.16787] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2021] [Revised: 01/05/2022] [Accepted: 01/11/2022] [Indexed: 12/12/2022]
Abstract
Coeliac disease is an immune-mediated disease caused by ingestion of gluten in genetically susceptible individuals. Coeliac disease has been thought to affect mainly people of European origin but subsequently many studies revealed that it affects people living in North America, Oceania, South America, Asia as well as Africa. The global pooled seroprevalence and prevalence of biopsy-confirmed coeliac disease are 1.4% and 0.7% respectively. The pooled incidence rates in women and men are 17.4 (95% CI: 13.7-21.1) and 7.8 (95% CI: 6.3-9.2) per 100 000 person-years respectively. The systematic reviews, based on many population-based data, suggest that both the prevalence and the incidence of coeliac disease has increased over past three decades, which may be attributable not only to an increase in the detection rate (improvement in diagnostic tests, simplification of diagnostic criteria and increase in awareness about the disease) but also because of modernisation and globalisation related changes in the dietary practices including increase in the use of convenience food and dietary gluten. In addition to genetic factors, while there are many environmental risk factors, including age at the first introduction of gluten, breastfeeding, caesarean section, exposure to antibiotics and gut microbiome; the amount of gluten ingestion during early part of life, however, has been shown to increase the risk of coeliac disease, and this is relevant from the point of view of primary prevention. In this review, we have reviewed and summarised the literature, up till year 2021, related to the global and continent-wise epidemiology and risk factors associated with coeliac disease.
Collapse
Affiliation(s)
- Govind K Makharia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Ashish Chauhan
- Department of Gastroenterology, Indira Gandhi Medical College and Hospital, Shimla, India
| | - Prashant Singh
- Department of Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Vineet Ahuja
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| |
Collapse
|
|
24
|
Hue SSS, Ng SB, Wang S, Tan SY. Cellular Origins and Pathogenesis of Gastrointestinal NK- and T-Cell Lymphoproliferative Disorders. Cancers (Basel) 2022; 14:2483. [PMID: 35626087 PMCID: PMC9139583 DOI: 10.3390/cancers14102483] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Revised: 05/08/2022] [Accepted: 05/13/2022] [Indexed: 11/25/2022] Open
Abstract
The intestinal immune system, which must ensure appropriate immune responses to both pathogens and commensal microflora, comprises innate lymphoid cells and various T-cell subsets, including intra-epithelial lymphocytes (IELs). An example of innate lymphoid cells is natural killer cells, which may be classified into tissue-resident, CD56bright NK-cells that serve a regulatory function and more mature, circulating CD56dim NK-cells with effector cytolytic properties. CD56bright NK-cells in the gastrointestinal tract give rise to indolent NK-cell enteropathy and lymphomatoid gastropathy, as well as the aggressive extranodal NK/T cell lymphoma, the latter following activation by EBV infection and neoplastic transformation. Conventional CD4+ TCRαβ+ and CD8αβ+ TCRαβ+ T-cells are located in the lamina propria and the intraepithelial compartment of intestinal mucosa as type 'a' IELs. They are the putative cells of origin for CD4+ and CD8+ indolent T-cell lymphoproliferative disorders of the gastrointestinal tract and intestinal T-cell lymphoma, NOS. In addition to such conventional T-cells, there are non-conventional T-cells in the intra-epithelial compartment that express CD8αα and innate lymphoid cells that lack TCRs. The central feature of type 'b' IELs is the expression of CD8αα homodimers, seen in monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), which primarily arises from both CD8αα+ TCRαβ+ and CD8αα+ TCRγδ+ IELs. EATL is the other epitheliotropic T-cell lymphoma in the GI tract, a subset of which arises from the expansion and reprograming of intracytoplasmic CD3+ innate lymphoid cells, driven by IL15 and mutations of the JAK-STAT pathway.
Collapse
Affiliation(s)
- Susan Swee-Shan Hue
- Department of Pathology, National University Hospital, Singapore 119074, Singapore; (S.S.-S.H.); (S.W.)
| | - Siok-Bian Ng
- Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119074, Singapore;
- Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore
| | - Shi Wang
- Department of Pathology, National University Hospital, Singapore 119074, Singapore; (S.S.-S.H.); (S.W.)
| | - Soo-Yong Tan
- Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119074, Singapore;
| |
Collapse
|
|
25
|
Felber J, Bläker H, Fischbach W, Koletzko S, Laaß M, Lachmann N, Lorenz P, Lynen P, Reese I, Scherf K, Schuppan D, Schumann M, Aust D, Baas S, Beisel S, de Laffolie J, Duba E, Holtmeier W, Lange L, Loddenkemper C, Moog G, Rath T, Roeb E, Rubin D, Stein J, Török H, Zopf Y. Aktualisierte S2k-Leitlinie Zöliakie der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS). ZEITSCHRIFT FUR GASTROENTEROLOGIE 2022; 60:790-856. [PMID: 35545109 DOI: 10.1055/a-1741-5946] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Affiliation(s)
- Jörg Felber
- Medizinische Klinik II - Gastroenterologie, Hepatologie, Endokrinologie, Hämatologie und Onkologie, RoMed Klinikum Rosenheim, Rosenheim, Deutschland
| | - Hendrik Bläker
- Institut für Pathologie, Universitätsklinikum Leipzig AöR, Leipzig, Deutschland
| | | | - Sibylle Koletzko
- Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital, LMU-Klinikum München, München, Deutschland.,Department of Pediatrics, Gastroenterology and Nutrition, School of Medicine Collegium Medicum University of Warmia and Mazury, 10-719 Olsztyn, Polen
| | - Martin Laaß
- Klinik und Poliklinik für Kinder- und Jugendmedizin, Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden, Dresden, Deutschland
| | - Nils Lachmann
- Institut für Transfusionsmedizin, Charité - Universitätsmedizin Berlin, Berlin, Deutschland
| | - Pia Lorenz
- Deutsche Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS), Berlin, Deutschland
| | - Petra Lynen
- Deutsche Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS), Berlin, Deutschland
| | - Imke Reese
- Ernährungsberatung und -therapie Allergologie, München, Deutschland
| | - Katharina Scherf
- Institute of Applied Biosciences Department of Bioactive and Functional Food Chemistry, Karlsruhe Institute of Technology (KIT), Karlsruhe, Deutschland
| | - Detlef Schuppan
- Institut für Translationale Immunologie, Johannes Gutenberg-Universität Mainz, Mainz, Deutschland.,Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Michael Schumann
- Medizinische Klinik I für Gastroenterologie, Infektiologie und Rheumatologie, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Deutschland
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
26
|
Grewal JK, Kassardjian A, Weiss GA. Successful novel use of tofacitinib for type II refractory coeliac disease. BMJ Case Rep 2022; 15:e244692. [PMID: 35418371 PMCID: PMC9013952 DOI: 10.1136/bcr-2021-244692] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/25/2022] [Indexed: 01/03/2023] Open
Abstract
Refractory coeliac disease (RCD) occurs when patients with confirmed CD have continuous or recurrent malabsorption and enteropathy after at least 12 months on a gluten-free diet. Differentiating between type I and type II RCD is key as the latter is associated with T-cell aberrancy and considered prelymphoma, with high mortality rates. Current treatment regimens for type II RCD include corticosteroids, biologics and chemotherapy, but there are no proven therapies for this serious condition. Our patient is a middle-aged woman who developed postpartum type II RCD. When she failed multiple drug classes, we did a trial of tofacitinib. Our clinical experience with use of a janus kinase inhibitor was successful, with no associated adverse events. This is the first report in the literature of RCD remission in response to tofacitinib. The use of this novel agent shows promise in reversing this potentially fatal condition.
Collapse
Affiliation(s)
- Jasleen Kaur Grewal
- Division of Gastroenterology, Deparment of Medicine, Southern California Kaiser Permanente, San Diego, California, USA
| | | | - Guy A Weiss
- Celiac Disease Program, University of California Los Angeles David Geffen School of Medicine, Los Angeles, California, USA
| |
Collapse
|
|
27
|
Ferretti F, Branchi F, Orlando S, Roncoroni L, Barigelletti G, Fabiano S, Vecchi M, Penagini R, Doneda L, Elli L. Effectiveness of Capsule Endoscopy and Double-Balloon Enteroscopy in Suspected Complicated Celiac Disease. Clin Gastroenterol Hepatol 2022; 20:941-949.e3. [PMID: 33189853 DOI: 10.1016/j.cgh.2020.11.010] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Revised: 10/31/2020] [Accepted: 11/06/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Complicated celiac disease (CCD) is a rare but severe condition with a poor prognosis. Guidelines recommend use of capsule endoscopy (CE) to explore the small bowel (SB), followed by a double-balloon enteroscopy (DBE) in selected cases with suspected CCD. Our study aimed to evaluate the diagnostic yield (DY) of CE and DBE in identifying and monitoring CCD. METHODS Consecutive suspected CCD patients were enrolled prospectively to undergo CE and/or DBE in the presence of: persistent symptoms despite a correct gluten-free diet (GFD), increased anti-transglutaminase antibodies titer, lack of adherence to the GFD, and CCD monitoring. The DY of CE and DBE were calculated. The incidence of neoplastic complications and mortality were assessed. RESULTS In total, 130 patients (97 women; age, 49 ± 16 y) underwent 151 CEs and 23 DBEs. The DY of CE was 46%. Patients older than age 50 years (at CE examination or at CD diagnosis) with a CD duration shorter than 5 years were at higher risk of positive CE (relative risk, 1.6 and 1.7 in case of enrollement or CD diagnosis after 50 years of age, and 1.5 in case of short CD duration; P < .05) than their counterparts. Up to 40% of SB lesions were unreachable by upper endoscopy. At the end of the diagnostic work-up, 25 patients with premalignant/malignant lesions were identified: 12 type 1 refractory CD (RCD-1), 7 type 2 RCD (RCD-2), and 6 enteropathy-associated T-cell lymphoma (EATL). Six patients died: 2 patients with RCD-2 and 4 patients with EATL. CONCLUSIONS In case of suspected CCD, CE should be the first-line approach to detect complications and to identify patients deserving DBE. Older and symptomatic patients with suspected CCD deserve a careful evaluation of the SB, especially during the first years after diagnosis.
Collapse
Affiliation(s)
- Francesca Ferretti
- Center for the Prevention and Diagnosis of Celiac Disease, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Gastroenterology and Endoscopy Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
| | - Federica Branchi
- Center for the Prevention and Diagnosis of Celiac Disease, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Gastroenterology and Endoscopy Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
| | - Stefania Orlando
- Center for the Prevention and Diagnosis of Celiac Disease, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Gastroenterology and Endoscopy Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Leda Roncoroni
- Center for the Prevention and Diagnosis of Celiac Disease, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Department of Biomedical, Surgical and Dental Sciences, Milan, Italy
| | - Giulio Barigelletti
- Cancer Registry Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Nazionale dei Tumori Milano, Milan Italy
| | - Sabrina Fabiano
- Cancer Registry Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Nazionale dei Tumori Milano, Milan Italy
| | - Maurizio Vecchi
- Center for the Prevention and Diagnosis of Celiac Disease, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Gastroenterology and Endoscopy Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
| | - Roberto Penagini
- Gastroenterology and Endoscopy Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
| | - Luisa Doneda
- Department of Biomedical, Surgical and Dental Sciences, Milan, Italy
| | - Luca Elli
- Center for the Prevention and Diagnosis of Celiac Disease, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Gastroenterology and Endoscopy Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy.
| |
Collapse
|
|
28
|
Demiroren K. Possible relationship between refractory celiac disease and malignancies. World J Clin Oncol 2022; 13:200-208. [PMID: 35433292 PMCID: PMC8966511 DOI: 10.5306/wjco.v13.i3.200] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Revised: 08/16/2021] [Accepted: 03/07/2022] [Indexed: 02/06/2023] Open
Abstract
Celiac disease (CeD) is a chronic autoimmune disorder that is triggered by gluten in genetically susceptible individuals, and that is characterized by CeD-specific antibodies, HLA-DQ2 and/or HLA-DQ8 haplotypes, enteropathy and different clinical pictures related to many organs. Intestinal lymphoma may develop as a result of refractory CeD. If a patient diagnosed with CeD is symptomatic despite a strict gluten-free diet for at least 12 months, and does not improve with severe villous atrophy, refractory CeD can be considered present. The second of the two types of refractory CeD has abnormal monoclonal intraepithelial lymphocytes and can be considered as pre-lymphoma, and the next picture that will emerge is enteropathy-associated T-cell lymphoma. This manuscript addresses "CeD and malignancies" through a review of current literature and guidelines.
Collapse
Affiliation(s)
- Kaan Demiroren
- Department of Pediatric Gastroenterology, University of Health Sciences, Yuksek Ihtisas Teaching Hospital, Bursa 16000, Turkey
| |
Collapse
|
|
29
|
Single-Cell Analysis of Refractory Celiac Disease Demonstrates Inter- and Intra-Patient Aberrant Cell Heterogeneity. Cell Mol Gastroenterol Hepatol 2022; 14:173-192. [PMID: 35338007 PMCID: PMC9123272 DOI: 10.1016/j.jcmgh.2022.03.005] [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] [Received: 11/25/2021] [Revised: 03/14/2022] [Accepted: 03/15/2022] [Indexed: 12/10/2022]
Abstract
BACKGROUND & AIMS Refractory celiac disease type II (RCDII) is a rare indolent lymphoma in the small intestine characterized by a clonally expanded intraepithelial intracellular CD3+surfaceCD3-CD7+CD56- aberrant cell population. However, RCDII pathogenesis is ill-defined. Here, we aimed at single-cell characterization of the innate and adaptive immune system in RCDII. METHODS Paired small intestinal and blood samples from 12 RCDII patients and 6 healthy controls were assessed by single-cell mass cytometry with a 39-cell surface marker antibody panel, designed to capture heterogeneity of the innate and adaptive immune system. A second single-cell mass cytometry panel that included transcription factors and immune checkpoints was used for analysis of paired samples from 5 RCDII patients. Single-cell RNA sequencing analysis was performed on duodenal samples from 2 RCDII patients. Finally, we developed a 40-marker imaging mass cytometry antibody panel to evaluate cell-cell interactions in duodenal biopsy specimens of RCDII patients. RESULTS We provide evidence for intertumoral and intratumoral cell heterogeneity within the duodenal and peripheral aberrant cell population present in RCDII. Phenotypic discrepancy was observed between peripheral and duodenal aberrant cells. In addition, we observed that part of the aberrant cell population proliferated and observed co-localization of aberrant cells with CD163+ antigen-presenting cells (APCs) in situ. In addition, we observed phenotypic discrepancy between peripheral and duodenal aberrant cells. CONCLUSIONS Novel high-dimensional single-cell technologies show substantial intertumoral and intratumoral heterogeneity in the aberrant cell population in RCDII. This may underlie variability in refractory disease status between patients and responsiveness to therapy, pointing to the need for personalized therapy in RCDII based on patient-specific immune profiles.
Collapse
|
|
30
|
Muramoto K, Kaida S, Miyake T, Nishimura R, Kito K, Shiohara M, Kushima R, Shimizu T, Tani M. Rare monomorphic epithelial intestinal T-cell lymphoma of the stomach with a giant gastric perforation rescued by liver-covering sutures followed by a total gastrectomy and lateral hepatectomy: a case report. Surg Case Rep 2022; 8:27. [PMID: 35129729 PMCID: PMC8821748 DOI: 10.1186/s40792-022-01381-1] [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] [Received: 09/14/2020] [Accepted: 01/28/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), a type of peripheral T-cell lymphoma, rarely involves the stomach as the primary organ. Advanced MEITL, for which there is currently no established treatment, causes gastrointestinal perforations and is characterized by a poor response to chemotherapy. CASE PRESENTATION A 69-year-old man had undergone chemotherapy for MEITL of the whole stomach. He subsequently developed acute abdominal pain, and computed tomography revealed a giant perforation in the anterior gastric wall adjacent to the lateral segment of the liver. The perforation was rescued through closure with liver-covering sutures. Thereafter, a total gastrectomy and a left hepatectomy were performed and he recovered enough to tolerate oral intake. However, despite ongoing chemotherapy, the patient died 83 days after the gastric perforation (10 months after being diagnosed with the lymphoma) owing to rapid progression of the MEITL. CONCLUSION In the rare case of a giant gastric perforation after chemotherapy for gastric MEITL, rescue is possible through liver-covering sutures followed by a total gastrectomy and lateral hepatectomy.
Collapse
Affiliation(s)
- Keiji Muramoto
- Department of Surgery, Shiga University of Medical Science, Seta, Tsukinowa-cho, Otsu, Shiga, 520-2192, Japan
| | - Sachiko Kaida
- Department of Surgery, Shiga University of Medical Science, Seta, Tsukinowa-cho, Otsu, Shiga, 520-2192, Japan.
| | - Toru Miyake
- Department of Surgery, Shiga University of Medical Science, Seta, Tsukinowa-cho, Otsu, Shiga, 520-2192, Japan
| | - Rie Nishimura
- Department of Gastroenterology and Hematology, Shiga University of Medical Science, Seta, Tsukinowa-cho, Otsu, Shiga, 520-2192, Japan
| | - Katsuyuki Kito
- Department of Gastroenterology and Hematology, Shiga University of Medical Science, Seta, Tsukinowa-cho, Otsu, Shiga, 520-2192, Japan
| | - Masanori Shiohara
- Department of Clinical Laboratory Medicine and Diagnostic Pathology, Shiga University of Medical Science, Seta, Tsukinowa-cho, Otsu, Shiga, 520-2192, Japan
| | - Ryoji Kushima
- Department of Clinical Laboratory Medicine and Diagnostic Pathology, Shiga University of Medical Science, Seta, Tsukinowa-cho, Otsu, Shiga, 520-2192, Japan
| | - Tomoharu Shimizu
- Medical Safety Section, Shiga University of Medical Science Hospital, Seta, Tsukinowa-cho, Otsu, Shiga, 520-2192, Japan
| | - Masaji Tani
- Department of Surgery, Shiga University of Medical Science, Seta, Tsukinowa-cho, Otsu, Shiga, 520-2192, Japan
| |
Collapse
|
|
31
|
Raiteri A, Granito A, Giamperoli A, Catenaro T, Negrini G, Tovoli F. Current guidelines for the management of celiac disease: A systematic review with comparative analysis. World J Gastroenterol 2022; 28:154-175. [PMID: 35125825 PMCID: PMC8793016 DOI: 10.3748/wjg.v28.i1.154] [Citation(s) in RCA: 64] [Impact Index Per Article: 21.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Revised: 08/08/2021] [Accepted: 12/25/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Wheat and other gluten-containing grains are widely consumed, providing approximately 50% of the caloric intake in both industrialised and developing countries. The widespread diffusion of gluten-containing diets has rapidly led to a sharp increase in celiac disease prevalence. This condition was thought to be very rare outside Europe and relatively ignored by health professionals and the global media. However, in recent years, the discovery of important diagnostic and pathogenic milestones has led to the emergence of celiac disease (CD) from obscurity to global prominence. These modifications have prompted experts worldwide to identify effective strategies for the diagnosis and follow-up of CD. Different scientific societies, mainly from Europe and America, have proposed guidelines based on CD's most recent evidence.
AIM To identify the most recent scientific guidelines on CD, aiming to find and critically analyse the main differences.
METHODS We performed a database search on PubMed selecting papers published between January 2010 and January 2021 in the English language. PubMed was lastly accessed on 1 March 2021.
RESULTS We distinguished guidelines from 7 different scientific societies whose reputation is worldwide recognized and representative of the clinical practice in different geographical regions. Differences were noted in the possibility of a no-biopsy diagnosis, HLA testing, follow-up protocols, and procedures.
CONCLUSION We found a relatively high concordance between the guidelines for CD. Important modifications have occurred in the last years, especially about the possibility of a no-biopsy diagnosis in children. Other modifications are expected in the next future and will probably involve the extension of the non-invasive diagnosis to the adult population and the follow-up modalities.
Collapse
Affiliation(s)
- Alberto Raiteri
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna 40138, Italy
| | - Alessandro Granito
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna 40138, Italy
| | - Alice Giamperoli
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna 40138, Italy
| | - Teresa Catenaro
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna 40138, Italy
| | - Giulia Negrini
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna 40138, Italy
| | - Francesco Tovoli
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna 40138, Italy
| |
Collapse
|
|
32
|
Abstract
Celiac disease is a chronic, immune-mediated enteropathy driven by dietary gluten found in genetically susceptible hosts. It has a worldwide distribution, is one of the most common autoimmune disorders globally, and is the only autoimmune condition for which the trigger is known. Despite advances in characterizing mechanisms of disease, gaps in understanding of celiac disease pathogenesis remain. A "frontier" concept is considering what moves an HLA-DQ2 or DQ8-positive individual from asymptomatic gluten tolerance to celiac disease manifestation. In this arena, environmental triggers, including age at the time of initial gluten exposure, the occurrence of usual childhood viral infections, and microbiome alterations have emerged as key events in triggering the symptomatic disease. Pathologists play a major role in frontier aspects of celiac disease. This includes the discovery that duodenal mucosal histology in follow-up biopsies does not correlate with ongoing patient symptoms, antitissue transglutaminase antibody titers and diet adherence in celiac disease patients. Further, in light of recent evidence that the detection of monoclonal T-cell populations in formalin-fixed biopsies is not specific for type II refractory celiac disease, pathologists should resist performing such analyses until common causes of "apparent" refractoriness are excluded. The promise of therapies in celiac disease has led to clinical trials targeting many steps in the inflammatory cascade, which depend upon a pathologist's confirmation of the initial diagnosis and evaluation of responses to therapies. As pathologists continue to be active participants in celiac disease research, partnering with other stakeholders, we will continue to impact this important autoimmune disease.
Collapse
Affiliation(s)
- Natalie Patel
- El Camino Pathology Medical Group, Mountain View, CA
| | - Marie E Robert
- Department of Pathology and Medicine, Yale University School of Medicine, New Haven, CT
| |
Collapse
|
|
33
|
Das P, Makharia G, Datta Gupta S. Pathology of Malabsorption Syndrome. SURGICAL PATHOLOGY OF THE GASTROINTESTINAL SYSTEM 2022:279-338. [DOI: 10.1007/978-981-16-6395-6_9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
|
|
34
|
Leyden D, Melby N. Enteropathy-associated T-cell lymphoma manifesting as non-specific abdominal pain: A case report highlighting the dangers of relying on Google Translate for clinical history taking. Clin Case Rep 2021; 9:e05139. [PMID: 34934495 PMCID: PMC8650750 DOI: 10.1002/ccr3.5139] [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] [Received: 08/17/2021] [Revised: 11/14/2021] [Accepted: 11/15/2021] [Indexed: 11/09/2022] Open
Abstract
We present the case of a 60-year-old man with non-specific abdominal pain. We explore how communication between doctor and patient was challenged by a language barrier. We also consider how the ability to take an accurate clinical history differed between Google Translate and an accredited medical phone translation service.
Collapse
Affiliation(s)
- Deirbhile Leyden
- Ulster HospitalSouth Eastern Health and Social Care TrustDundonaldNorthern Ireland
| | - Niamh Melby
- Ulster HospitalSouth Eastern Health and Social Care TrustDundonaldNorthern Ireland
| |
Collapse
|
|
35
|
Primary Gastrointestinal T-Cell Lymphoma and Indolent Lymphoproliferative Disorders: Practical Diagnostic and Treatment Approaches. Cancers (Basel) 2021; 13:cancers13225774. [PMID: 34830926 PMCID: PMC8616126 DOI: 10.3390/cancers13225774] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2021] [Revised: 11/15/2021] [Accepted: 11/16/2021] [Indexed: 12/12/2022] Open
Abstract
Simple Summary It is challenging for pathologists to diagnose primary gastrointestinal T-cell neoplasms. Besides the rarity of the diseases, the small biopsy material makes it more difficult to differentiate between non-neoplastic inflammation and secondary involvement of extra gastrointestinal lymphoma. Since this group of diseases ranges from aggressive ones with a very poor prognosis to indolent ones that require caution to avoid overtreatment, the impact of the diagnosis on the patient is enormous. Although early treatment of aggressive lymphoma is essential, the treatment strategy is not well established, which is a problem for clinicians. This review provides a cross-sectional comparison of histological findings. Unlike previous reviews, we summarized up-to-date clinically relevant information including the treatment strategies as well as practical differential diagnosis based on thorough literature review. Abstract Primary gastrointestinal (GI) T-cell neoplasms are extremely rare heterogeneous disease entities with distinct clinicopathologic features. Given the different prognoses of various disease subtypes, clinicians and pathologists must be aware of the key characteristics of these neoplasms, despite their rarity. The two most common aggressive primary GI T-cell lymphomas are enteropathy-associated T-cell lymphoma and monomorphic epitheliotropic intestinal T-cell lymphoma. In addition, extranodal natural killer (NK)/T-cell lymphoma of the nasal type and anaplastic large cell lymphoma may also occur in the GI tract or involve it secondarily. In the revised 4th World Health Organization classification, indolent T-cell lymphoproliferative disorder of the GI tract has been incorporated as a provisional entity. In this review, we summarize up-to-date clinicopathological features of these disease entities, including the molecular characteristics of primary GI T-cell lymphomas and indolent lymphoproliferative disorders. We focus on the latest treatment approaches, which have not been summarized in existing reviews. Further, we provide a comprehensive review of available literature to address the following questions: How can pathologists discriminate subtypes with different clinical prognoses? How can primary GI neoplasms be distinguished from secondary involvement? How can these neoplasms be distinguished from non-specific inflammatory changes at an early stage?
Collapse
|
|
36
|
Alvarez-Lesmes J, Chapman JR, Poveda JC. Pitfalls in gastrointestinal tract haematopoietic lesions. Pathology 2021; 54:177-183. [PMID: 34801278 DOI: 10.1016/j.pathol.2021.08.010] [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: 08/15/2021] [Accepted: 08/23/2021] [Indexed: 02/07/2023]
Abstract
Specimens from the gastrointestinal (GI) tract are among the most commonly encountered in routine pathology practice worldwide. It is well known that the luminal GI tract is home to various areas rich in mucosa-associated lymphoid tissue (MALT), whether native or acquired. The latter may be particularly problematic due to its well-known predisposing factors such as Helicobacter pylori infection and autoimmune conditions. Nevertheless, native GI structures are often the subject of query, particularly in conditions that may mimic lymphoproliferative conditions, including infectious and inflammatory diseases. Herein, we describe and share common clinicopathological findings in our daily practice that are challenging to distinguish from subtle low-grade neoplastic lymphoproliferative disorders.
Collapse
Affiliation(s)
- Jessica Alvarez-Lesmes
- Department of Pathology, Division of Hematopathology, Division of Gastrointestinal Pathology, University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center, and Jackson Memorial Hospital, Miami, FL, USA
| | - Jennifer R Chapman
- Department of Pathology, Division of Hematopathology, Division of Gastrointestinal Pathology, University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center, and Jackson Memorial Hospital, Miami, FL, USA
| | - Julio C Poveda
- Department of Pathology, Division of Hematopathology, Division of Gastrointestinal Pathology, University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center, and Jackson Memorial Hospital, Miami, FL, USA.
| |
Collapse
|
|
37
|
Rouvroye MD, Slottje P, van Gils T, Mulder CJ, Muris JW, Walstock D, Reinders M, Bouma G. Insight in the diagnosis and treatment of coeliac disease in general practice: A survey and case vignette study among 106 general practitioners. Eur J Gen Pract 2021; 27:313-319. [PMID: 34743668 PMCID: PMC8583831 DOI: 10.1080/13814788.2021.1985455] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Background Coeliac disease (CD) is a highly prevalent (∼1%) disease that allegedly remains undiagnosed in over 80% of the cases because of atypical symptoms or silent disease. Currently, it is unknown how GPs deal with (suspected) CD. Objectives This study aimed to better understand the diagnostic approach and the clinical reasoning process of GPs concerning CD and concurrently address diagnostic pitfalls. Methods A questionnaire with case vignettes to assess the knowledge, diagnostic reasoning pattern and practice for CD by GPs was developed. It was sent through academic GP research networks (encompassing over 1500 GPs) in two large cities and to smaller practices in rural areas. The questionnaire was composed of seven background questions, 13 questions related to four case vignettes and six additional CD-related questions Results Responses were received from 106 GPs. Knowledge on risk factors for CD and appropriate testing of at-risk populations was limited. Twenty-two percent would diagnose CD in adults exclusively based on serology, without histopathological confirmation. In total, 99% would refer a newly diagnosed patient to a dietitian to initiate a gluten-free diet (GFD). In the absence of symptoms, only 33% would initiate a GFD. Conclusion The results of this study have given us insight into the diagnostic process of GPs encountering patient with gluten-related complaints. Multiple serology test is available and used, while a positive serology test is not always followed up by a gastroduodenal biopsy to confirm the diagnosis. Most GPs would refer a symptomatic CD patient to a dietician for a GFD.
Collapse
Affiliation(s)
- Maxine D Rouvroye
- Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology & Metabolism, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
| | - Pauline Slottje
- Department of General Practice and Elderly Care Medicine, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.,Department of General Practice and Elderly Care Medicine, Amsterdam UMC, Vrije Universiteit Amsterdam, Academic Network of General Practice, Amsterdam, the Netherlands
| | - Tom van Gils
- Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology & Metabolism, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
| | - Chris J Mulder
- Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology & Metabolism, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
| | - Jean W Muris
- Department of Family Medicine, Care and Public Health Research Institute CAPHRI, Maastricht University, Maastricht, the Netherlands
| | - Dick Walstock
- Department of General Practice and Elderly Care Medicine, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.,Department of General Practice and Elderly Care Medicine, Amsterdam UMC, Vrije Universiteit Amsterdam, Academic Network of General Practice, Amsterdam, the Netherlands
| | - Marcel Reinders
- Department of General Practice and Elderly Care Medicine, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
| | - Gerd Bouma
- Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology & Metabolism, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
| |
Collapse
|
|
38
|
Pelizzaro F, Marsilio I, Fassan M, Piazza F, Barberio B, D’Odorico A, Savarino EV, Farinati F, Zingone F. The Risk of Malignancies in Celiac Disease-A Literature Review. Cancers (Basel) 2021; 13:cancers13215288. [PMID: 34771450 PMCID: PMC8582432 DOI: 10.3390/cancers13215288] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2021] [Revised: 10/15/2021] [Accepted: 10/19/2021] [Indexed: 12/14/2022] Open
Abstract
Celiac disease (CeD) is an immune-mediated enteropathy precipitated by ingestion of gluten in genetically predisposed individuals. Considering that CeD affects approximately 1% of the Western population, it may be considered a global health problem. In the large majority of cases, CeD has a benign course, characterized by the complete resolution of symptoms and a normal life expectancy after the beginning of a gluten-free-diet (GFD); however, an increased risk of developing malignancies, such as lymphomas and small bowel carcinoma (SBC), has been reported. In particular, enteropathy-associated T-cell lymphoma (EATL), a peculiar type of T-cell lymphoma, is characteristically associated with CeD. Moreover, the possible association between CeD and several other malignancies has been also investigated in a considerable number of studies. In this paper, we aim to provide a comprehensive review of the current knowledge about the associations between CeD and cancer, focusing in particular on EATL and SBC, two rare but aggressive malignancies.
Collapse
Affiliation(s)
- Filippo Pelizzaro
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padova, 35128 Padova, Italy; (F.P.); (I.M.); (B.B.); (A.D.); (E.V.S.); (F.F.)
| | - Ilaria Marsilio
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padova, 35128 Padova, Italy; (F.P.); (I.M.); (B.B.); (A.D.); (E.V.S.); (F.F.)
| | - Matteo Fassan
- Surgical Pathology and Cytopathology Unit, Department of Medicine (DIMED), University Hospital of Padova, 35128 Padova, Italy;
- Veneto Oncology Institute, IOV-IRCCS, 35128 Padova, Italy
| | - Francesco Piazza
- Department of Medicine, Hematology, University Hospital of Padova, 35128 Padova, Italy;
| | - Brigida Barberio
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padova, 35128 Padova, Italy; (F.P.); (I.M.); (B.B.); (A.D.); (E.V.S.); (F.F.)
| | - Anna D’Odorico
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padova, 35128 Padova, Italy; (F.P.); (I.M.); (B.B.); (A.D.); (E.V.S.); (F.F.)
| | - Edoardo V. Savarino
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padova, 35128 Padova, Italy; (F.P.); (I.M.); (B.B.); (A.D.); (E.V.S.); (F.F.)
| | - Fabio Farinati
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padova, 35128 Padova, Italy; (F.P.); (I.M.); (B.B.); (A.D.); (E.V.S.); (F.F.)
| | - Fabiana Zingone
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padova, 35128 Padova, Italy; (F.P.); (I.M.); (B.B.); (A.D.); (E.V.S.); (F.F.)
- Correspondence:
| |
Collapse
|
|
39
|
Wang M, Yu M, Kong WJ, Cui M, Gao F. Association between intestinal neoplasms and celiac disease: A review. World J Gastrointest Oncol 2021; 13:1017-1028. [PMID: 34616509 PMCID: PMC8465454 DOI: 10.4251/wjgo.v13.i9.1017] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Revised: 06/02/2021] [Accepted: 07/30/2021] [Indexed: 02/06/2023] Open
Abstract
Celiac disease (CD) is a chronic immune-mediated intestinal disease with genetic susceptibility. It is characterized by inflammatory damage to the small intestine after ingestion of cereals and products containing gluten protein. In recent years, the global prevalence rate of CD has been approximately 1%, and is gradually increasing. CD patients adhere to a gluten-free diet (GFD) throughout their entire life. However, it is difficult to adhere strictly to a GFD. Untreated CD may be accompanied by gastrointestinal symptoms, such as diarrhea, abdominal pain, and extraintestinal symptoms caused by secondary malnutrition. Many studies have suggested that CD is associated with intestinal tumors such as enteropathy-associated T-cell lymphoma (EATL), small bowel cancer (SBC), and colorectal cancer. In this study, we reviewed related studies published in the literature to provide a reference for the prevention and treatment of intestinal tumors in patients with CD. Compared with the general population, CD patients had a high total risk of SBC and EATL, but not colorectal cancer. The protective effect of GFD on CD-related malignancies is controversial. Further studies are needed to confirm whether GFD treatment can reduce the risk of intestinal neoplasms in CD.
Collapse
Affiliation(s)
- Man Wang
- Department of Gastroenterology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, Xinjiang Uygur Autonomous Region, China
| | - Ming Yu
- Department of General Practice, Xiangyang Central Hospital, The Affiliated Hospital of Hubei University of Arts and Science, Xiangyang 441021 Hubei Province, China
| | - Wen-Jie Kong
- Department of Gastroenterology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, Xinjiang Uygur Autonomous Region, China
| | - Mei Cui
- Department of Pathology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, Xinjiang Uygur Autonomous Region, China
| | - Feng Gao
- Department of Gastroenterology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, Xinjiang Uygur Autonomous Region, China
| |
Collapse
|
|
40
|
Villanacci V, Vanoli A, Leoncini G, Arpa G, Salviato T, Bonetti LR, Baronchelli C, Saragoni L, Parente P. Celiac disease: histology-differential diagnosis-complications. A practical approach. Pathologica 2021; 112:186-196. [PMID: 33179621 PMCID: PMC7931573 DOI: 10.32074/1591-951x-157] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Accepted: 06/24/2020] [Indexed: 02/08/2023] Open
Abstract
Celiac disease is a multi-factorial chronic inflammatory intestinal disease, characterized by malabsorption resulting from mucosal injury after ingestion of wheat gluten or related rye and barley proteins. Inappropriate T-cell-mediated immune response against ingested gluten in genetically predisposed people, leads to characteristic histological lesions, as villous atrophy and intraepithelial lymphocytosis. Nevertheless, celiac disease is a comprehensive diagnosis with clinical, serological and genetic characteristics integrated with histological features. Biopsy of duodenal mucosa remains the gold standard in the diagnosis of celiac disease with the recognition of the spectrum of histological changes and classification of mucosa damage based on updated Corazza-Villanacci system. Appropriate differential diagnosis evaluation and clinical context also for the diagnosis of complications is, moreover, needed for correct histological features interpretation and clinical management.
Collapse
Affiliation(s)
| | - Alessandro Vanoli
- Anatomic Pathology Unit, Department of Molecular Medicine, University of Pavia, Italy.,Anatomic Pathology Unit, IRCCS San Matteo Hospital of Pavia, Italy
| | | | - Giovanni Arpa
- Anatomic Pathology Unit, Department of Molecular Medicine, University of Pavia, Italy.,Anatomic Pathology Unit, IRCCS San Matteo Hospital of Pavia, Italy
| | - Tiziana Salviato
- Department of Diagnostic, Clinic and Public Health Medicine, University of Modena and Reggio Emilia, Modena, Italy
| | - Luca Reggiani Bonetti
- Department of Diagnostic, Clinic and Public Health Medicine, University of Modena and Reggio Emilia, Modena, Italy
| | | | - Luca Saragoni
- Department of Pathological Anatomy, AUSL Romagna, Morgagni-Pierantoni Hospital, Forlì, Italy
| | - Paola Parente
- Pathology Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, FG, Italy
| |
Collapse
|
|
41
|
Bassi M, Mohapatra S, Sharma P, Korman A, Pitchumoni CS, Broder A. Hematemesis as an Initial Presentation of Enteropathy-Associated T-Cell Lymphoma. Cureus 2021; 13:e16992. [PMID: 34377617 PMCID: PMC8349507 DOI: 10.7759/cureus.16992] [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] [Accepted: 08/08/2021] [Indexed: 11/05/2022] Open
Abstract
Enteropathy-associated T-cell lymphoma (EATL) is a tumor of intraepithelial T-lymphocytes arising in the small intestine. Based on the genetic profile, immunohistochemistry, and histology, EATL is divided into two subtypes. EATL type I occurs in individuals with celiac disease (CD) while EATL type II is a sporadic form that occurs in individuals without CD. Intensive chemotherapy and surgery are the mainstay treatment. However, despite the currently available treatment options, the five-year survival rate is only 9%. EATL presents as abdominal pain, nausea, or slow gastrointestinal bleeding. Severe bleeding leading to hemodynamic instability is rarely known in EATL. Therefore, we present a unique case of EATL who presented with acute and severe gastrointestinal bleeding with no prior history of CD.
Collapse
Affiliation(s)
- Mehak Bassi
- Division of Internal Medicine, Saint Peter's University Hospital/Rutgers Robert Wood Johnson School of Medicine, New Brunswick, USA
| | - Sonmoon Mohapatra
- Division of Gastroenterology and Hepatology, Saint Peter's University Hospital/Rutgers Robert Wood Johnson School of Medicine, New Brunswick, USA
| | - Parth Sharma
- Department of Internal Medicine, All India Institute of Medical Sciences, New Delhi, New Delhi, IND
| | - Andrew Korman
- Division of Gastroenterology and Hepatology, Saint Peter's University Hospital/Rutgers Robert Wood Johnson School of Medicine, New Brunswick, USA
| | - C S Pitchumoni
- Division of Gastroenterology and Hepatology, Saint Peter's University Hospital/Rutgers Robert Wood Johnson School of Medicine, New Brunswick, USA
| | - Arkady Broder
- Division of Gastroenterology and Hepatology, Saint Peter's University Hospital/Rutgers Robert Wood Johnson School of Medicine, New Brunswick, USA
| |
Collapse
|
|
42
|
Al Somali Z, Hamadani M, Kharfan-Dabaja M, Sureda A, El Fakih R, Aljurf M. Enteropathy-Associated T cell Lymphoma. Curr Hematol Malig Rep 2021; 16:140-147. [PMID: 34009525 DOI: 10.1007/s11899-021-00634-4] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/12/2021] [Indexed: 01/13/2023]
Abstract
PURPOSE OF REVIEW Enteropathy-associated T cell lymphoma (EATL) is a rare subtype of mature T cell lymphoma. The available literature about this rare type T cell lymphoma is relatively limited. This article provides a summary and review of the available literature addressing this entity in terms of risk factors, pathogenesis, diagnostic, and therapeutic options. RECENT FINDINGS EATL has two distinct subtypes. Type I EATL, now known as EATL, is closely, but not exclusively linked to celiac disease (CD), and it is primarily a disease of Northern European origin. It accounts for < 5% of peripheral T cell lymphoma (PTCL). Risk factors for EATL include advanced age, male sex, and most importantly, genetic susceptibility in the form of HLA-DQ2 homozygosity. The pathogenesis of EATL is closely related to celiac disease as it shares common pathogenic features with refractory celiac disease. The gold standard of diagnosis is histological diagnosis. EATL carries an aggressive course and a poor prognosis. Treatment of EATL includes surgery, induction chemotherapy, and consolidation in first complete remission and autologous stem cell transplant. The role of targeted and biologic therapies in newly diagnosed EATL patients along with relapsed, refractory cases is evolving and discussed in this review. EATL is an aggressive peripheral T cell lymphoma with poor overall treatment outcome using currently available therapy options. Clinical trials are considered the best approach for treatment of EATL. Early diagnosis and early referral to specialized centers would be the best way to deal with such patients. Development of new prognostic models and early surgical intervention are warranted. Prevention is where all the efforts should be spent, by counseling patients with CD regarding the importance of adherence to gluten-free diet and development of periodic surveillance programs in celiac disease patients for early detection of pre-lymphoma lesions.
Collapse
Affiliation(s)
- Zakiah Al Somali
- Adult Hematology/HSCT, Oncology Center, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia
| | - Mehdi Hamadani
- Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Mohamed Kharfan-Dabaja
- Division of Hematology-Oncology and Blood and Marrow Transplantation and Cellular Therapies Program, Mayo Clinic, Jacksonville, FL, USA
| | - Ana Sureda
- Hematology Department, Catalan Institute of Oncology, Barcelona, Spain
| | - Riad El Fakih
- Adult Hematology/HSCT, Oncology Center, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia
| | - Mahmoud Aljurf
- Adult Hematology/HSCT, Oncology Center, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia.
| |
Collapse
|
|
43
|
Montoro-Huguet MA, Belloc B, Domínguez-Cajal M. Small and Large Intestine (I): Malabsorption of Nutrients. Nutrients 2021; 13:1254. [PMID: 33920345 PMCID: PMC8070135 DOI: 10.3390/nu13041254] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2021] [Revised: 04/06/2021] [Accepted: 04/07/2021] [Indexed: 02/06/2023] Open
Abstract
Numerous disorders can alter the physiological mechanisms that guarantee proper digestion and absorption of nutrients (macro- and micronutrients), leading to a wide variety of symptoms and nutritional consequences. Malabsorption can be caused by many diseases of the small intestine, as well as by diseases of the pancreas, liver, biliary tract, and stomach. This article provides an overview of pathophysiologic mechanisms that lead to symptoms or complications of maldigestion (defined as the defective intraluminal hydrolysis of nutrients) or malabsorption (defined as defective mucosal absorption), as well as its clinical consequences, including both gastrointestinal symptoms and extraintestinal manifestations and/or laboratory abnormalities. The normal uptake of nutrients, vitamins, and minerals by the gastrointestinal tract (GI) requires several steps, each of which can be compromised in disease. This article will first describe the mechanisms that lead to poor assimilation of nutrients, and secondly discuss the symptoms and nutritional consequences of each specific disorder. The clinician must be aware that many malabsorptive disorders are manifested by subtle disorders, even without gastrointestinal symptoms (for example, anemia, osteoporosis, or infertility in celiac disease), so the index of suspicion must be high to recognize the underlying diseases in time.
Collapse
Affiliation(s)
- Miguel A. Montoro-Huguet
- Departamento de Medicina, Psiquiatría y Dermatología, Facultad de Ciencias de la Salud y del Deporte, University of Zaragoza, 50009 Zaragoza, Spain
- Unidad de Gastroenterología, Hepatología y Nutrición, Hospital Universitario San Jorge de Huesca, 22004 Huesca, Spain; (B.B.); (M.D.-C.)
- Aragonese Institute of Health Sciences (IACS), 50009 Zaragoza, Spain
| | - Blanca Belloc
- Unidad de Gastroenterología, Hepatología y Nutrición, Hospital Universitario San Jorge de Huesca, 22004 Huesca, Spain; (B.B.); (M.D.-C.)
- Aragonese Institute of Health Sciences (IACS), 50009 Zaragoza, Spain
| | - Manuel Domínguez-Cajal
- Unidad de Gastroenterología, Hepatología y Nutrición, Hospital Universitario San Jorge de Huesca, 22004 Huesca, Spain; (B.B.); (M.D.-C.)
- Aragonese Institute of Health Sciences (IACS), 50009 Zaragoza, Spain
| |
Collapse
|
|
44
|
Susan SSH, Ng SB, Wang S, Tan SY. Diagnostic approach to T- and NK-cell lymphoproliferative disorders in the gastrointestinal tract. Semin Diagn Pathol 2021; 38:21-30. [PMID: 34016481 DOI: 10.1053/j.semdp.2021.03.004] [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: 01/21/2021] [Revised: 03/11/2021] [Accepted: 03/22/2021] [Indexed: 12/13/2022]
Abstract
Most gastrointestinal NK and T cell lymphomas are aggressive in behavior, although in recent years a subset of indolent lymphoproliferative disorders have been described, which must be distinguished from their more malignant mimics. Intestinal T-cell lymphomas may arise from intra-epithelial lymphocytes and display epitheliotropism, such as enteropathy-associated T-cell lymphoma and monomorphic epitheliotropic intestinal T-cell lymphoma. They are both aggressive in behavior but differ in their clinic-pathological features. On the other hand, intra-epithelial lymphocytes are not prominent in intestinal T-cell lymphoma, NOS, which is a diagnosis of exclusion and probably represents a heterogeneous group of entities. Indolent lymphoproliferative disorders of NK- and T-cells of both CD8 and CD4 subsets share a chronic, recurring clinical course but display differences from each other. CD8+ T-cell lymphoproliferative disorder of GI tract has a low proliferative fraction and does not progress nor undergo large cell transformation. Whilst NK-cell enteropathy runs an indolent clinical course, it may display a high proliferation fraction. On the other hand, CD4+ indolent T-cell lymphoproliferative disorder displays variable proliferation rates and may progress or transform after a number of years. In Asia and South America, it is not uncommon to see involvement of the gastrointestinal tract by EBV-associated extranodal NK/T cell lymphoma, nasal type, which must be distinguished from NK cell enteropathy and EBV-associated mucocutaneous ulcers.
Collapse
Affiliation(s)
- Swee-Shan Hue Susan
- Department of Pathology, National University Hospital Health Service, Singapore, Singapore; Department of Pathology, National University of Singapore Yong Loo Lin School of Medicine, Singapore, Singapore
| | - Siok-Bian Ng
- Department of Pathology, National University of Singapore Yong Loo Lin School of Medicine, Singapore, Singapore
| | - Shi Wang
- Department of Pathology, National University Hospital Health Service, Singapore, Singapore
| | - Soo-Yong Tan
- Department of Pathology, National University of Singapore Yong Loo Lin School of Medicine, Singapore, Singapore.
| |
Collapse
|
|
45
|
Zammit SC, Elli L, Scaramella L, Sanders DS, Tontini GE, Sidhu R. Small bowel capsule endoscopy in refractory celiac disease: a luxury or a necessity? Ann Gastroenterol 2021; 34:188-195. [PMID: 33654358 PMCID: PMC7903573 DOI: 10.20524/aog.2021.0586] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2020] [Accepted: 10/27/2020] [Indexed: 12/11/2022] Open
Abstract
Background Small bowel capsule endoscopy (SBCE) has an established role in the management of refractory celiac disease (RCD) for the detection of complications. The aim of this study was to define the role of SBCE in the management of patients with RCD. Method Patients with histologically confirmed RCD who underwent successive SBCEs were recruited retrospectively from 2 tertiary centers. Results Sixty patients with RCD were included. The percentage extent of the affected small bowel (SB) mucosa improved on repeating a second SBCE in 26 patients (49.1%) (median 27.6% vs. 18.1%, P=0.007). Patients with RCD type II had more extensive disease than those with RCD type I on first (41.4% vs. 19.2%, P=0.004) and second (29.8% vs. 12.0%, P=0.016) SBCE. Patients with RCD type I tended to show a greater improvement in percentage of abnormal SB involved on repeat SBCE compared to those with RCD type II (P=0.049). Nine patients (15%) had RCD-related complications. Five patients developed ulcerative jejunoileitis, 3 patients developed enteropathy-associated T-cell lymphoma, and 1 patient developed cutaneous T-cell lymphoma. Conclusions SBCE can be a useful tool for monitoring the effects of treatment, primarily following its initiation. Patients with RCD type II have more extensive SB disease, equating to a more aggressive disease pattern.
Collapse
Affiliation(s)
- Stefania Chetcuti Zammit
- Gastroenterology Department, Sheffield Teaching Hospitals, United Kingdom (Stefania Chetcuti Zammit, David S. Sanders, Reena Sidhu)
| | - Luca Elli
- Centre for Prevention and Diagnosis of Coeliac Disease, Gastroenterology and Endoscopy Unit, Department of Pathophysiology and Transplantation, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Italy (Luca Elli, Lucia Scaramella, Gian Eugenio Tontini)
| | - Lucia Scaramella
- Centre for Prevention and Diagnosis of Coeliac Disease, Gastroenterology and Endoscopy Unit, Department of Pathophysiology and Transplantation, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Italy (Luca Elli, Lucia Scaramella, Gian Eugenio Tontini)
| | - David S Sanders
- Gastroenterology Department, Sheffield Teaching Hospitals, United Kingdom (Stefania Chetcuti Zammit, David S. Sanders, Reena Sidhu)
| | - Gian Eugenio Tontini
- Centre for Prevention and Diagnosis of Coeliac Disease, Gastroenterology and Endoscopy Unit, Department of Pathophysiology and Transplantation, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Italy (Luca Elli, Lucia Scaramella, Gian Eugenio Tontini)
| | - Reena Sidhu
- Gastroenterology Department, Sheffield Teaching Hospitals, United Kingdom (Stefania Chetcuti Zammit, David S. Sanders, Reena Sidhu)
| |
Collapse
|
|
46
|
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.
Collapse
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
| |
Collapse
|
|
47
|
Cellular and molecular bases of refractory celiac disease. INTERNATIONAL REVIEW OF CELL AND MOLECULAR BIOLOGY 2021; 358:207-240. [PMID: 33707055 DOI: 10.1016/bs.ircmb.2020.12.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Refractory celiac disease (RCD) encompasses biologically heterogeneous disorders that develop in a small proportion (0.3%) of individuals with celiac disease that are associated with high morbidity. Two broad categories are currently recognized, type I (RCD I) and type II (RCD II), based on immunophenotypic and molecular features of the intraepithelial lymphocytes (IELs). RCD I is characterized by a polyclonal expansion of IELs displaying a normal immunophenotype, while RCD II represents a clonal proliferation of immunophenotypically "aberrant" IELs, and is considered a low-grade lymphoproliferative disorder. The pathogenesis of RCD I has not been clarified, but limited studies suggest multifactorial etiology. On the other hand, recent immunologic, molecular and immunophenotypic analyses have proposed lineage-negative innate IELs to be the cell of origin of a proportion of RCD II cases. Furthermore, sequencing studies have identified frequent, recurrent, activating mutations in members of the JAK-STAT pathway in RCD II. This finding, in conjunction with prior in vitro experimental observations, suggests roles of deregulated cytokine signaling in disease pathogenesis. In this review, we describe current understanding of environmental, immune and genetic factors associated with the development of RCD and briefly discuss diagnostic and therapeutic considerations.
Collapse
|
|
48
|
Chibbar R, Nostedt J, Mihalicz D, Deschenes J, McLean R, Dieleman LA. Refractory Celiac Disease Type II: A Case Report and Literature Review. Front Med (Lausanne) 2020; 7:564875. [PMID: 33344468 PMCID: PMC7746862 DOI: 10.3389/fmed.2020.564875] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2020] [Accepted: 11/03/2020] [Indexed: 12/11/2022] Open
Abstract
We present an unusual case of 68-year-old male, who presented with acute abdomen, ulcerative jejunitis with perforation, and 2 months later with perforation of the sigmoid colon. We will also discuss difficulties in the delay in diagnosis of refractory celiac disease (RCD), specifically the atypical presentation, multiple surgeries, the consecutive failure of distinct therapeutic options, and multiple complications that occurred within the 3 months since first presentation.
Collapse
Affiliation(s)
- Richa Chibbar
- Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, AB, Canada.,Division of Gastro, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, United States
| | - Jordan Nostedt
- Division of General Surgery, Department of Surgery, University of Alberta, Edmonton, AB, Canada
| | - Dana Mihalicz
- Division of General Surgery, Department of Surgery, University of Alberta, Edmonton, AB, Canada
| | - Jean Deschenes
- Department of Laboratory Medicine and Pathology, Cross Cancer Institute, University of Alberta, Edmonton, AB, Canada
| | - Ross McLean
- Department of Laboratory Medicine, Royal Alexandra Hospital, University of Alberta, Edmonton, AB, Canada
| | - Levinus A Dieleman
- Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, AB, Canada
| |
Collapse
|
|
49
|
Rej A, Aziz I, Sanders DS. Coeliac disease and noncoeliac wheat or gluten sensitivity. J Intern Med 2020; 288:537-549. [PMID: 32573000 DOI: 10.1111/joim.13120] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2020] [Revised: 04/15/2020] [Accepted: 04/21/2020] [Indexed: 12/15/2022]
Abstract
Coeliac disease (CD) and noncoeliac wheat or gluten sensitivity (NCWS/NCGS) are common gluten-related disorders. Both conditions can present with gastrointestinal and extraintestinal manifestations, which can be a challenge for physicians to discern between. Whilst coeliac serology and histological assessment are required for the diagnosis of CD, there are no clear biomarkers for the diagnosis of NCGS. The management of both conditions is with a gluten-free diet (GFD), although the duration, as well as strictness of adherence to a GFD in NCGS, is unclear. Adherence to a GFD in CD can also be challenging, with recent developments of noninvasive assessments, although histological assessment via duodenal biopsies remains the gold standard. The management of refractory coeliac disease remains particularly challenging, often requiring specialist input. Whilst wheat is noted to be a trigger for symptom generation in NCGS, it is unclear which components of wheat are responsible for symptom generation in this group, with further research required to elucidate the pathophysiology.
Collapse
Affiliation(s)
- A Rej
- From the, Academic Unit of Gastroenterology, Royal Hallamshire Hospital, Sheffield Teaching Hospital NHS Foundation Trust, Sheffield, UK
| | - I Aziz
- From the, Academic Unit of Gastroenterology, Royal Hallamshire Hospital, Sheffield Teaching Hospital NHS Foundation Trust, Sheffield, UK.,Department of Infection, Immunity and Cardiovascular Disease, Academic Unit of Gastroenterology, University of Sheffield, Sheffield, UK
| | - D S Sanders
- From the, Academic Unit of Gastroenterology, Royal Hallamshire Hospital, Sheffield Teaching Hospital NHS Foundation Trust, Sheffield, UK.,Department of Infection, Immunity and Cardiovascular Disease, Academic Unit of Gastroenterology, University of Sheffield, Sheffield, UK
| |
Collapse
|
|
50
|
Abstract
PURPOSE OF REVIEW The aim of this review is to provide insight into the diagnosis and management of patients with refractory coeliac disease (RCD) and highlight recent advances in this field. RECENT FINDINGS The diagnosis of RCD can be more accurately confirmed with flow cytometry in addition to immunohistochemistry. Dietary input and excretion of gluten immunogenic peptides can help rule out gluten contamination, and therefore, substantiate a diagnosis of RCD type I. Small bowel capsule endoscopy (SBCE) is important at diagnosis and follow-up in addition to duodenal histology. Apart from ruling out complications, it can give information on extent of disease in the small bowel, and therefore, help assess response to therapy. Those patients with a poor response can have earlier intensification of therapy, which may result in an improved outcome. RCD also occurs in patients with serology negative coeliac disease but with an increased mortality compared with patients with serology-positive coeliac disease. SUMMARY Patients with RCD can present with persistent symptoms of malnutrition but can also be completely asymptomatic. Serology is not a reliable marker to detect refractory disease. Immunostaining and flow cytometry are necessary for a diagnosis of RCD. Small bowel endoscopy enables disease extent to be assessed and allows for small bowel biopsies to be taken in case of suspicious lesions. Small bowel radiology can be complementary to small bowel endoscopy.
Collapse
|