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1
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Özer M, Bahadır E, Duran BC, Aytekin C, Özmen S. Drug-induced enterocolitis syndrome in children: report of two cases and a literature review. Turk J Pediatr 2025; 67:101-108. [PMID: 40084725 DOI: 10.24953/turkjpediatr.2025.5461] [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: 10/24/2024] [Accepted: 12/31/2024] [Indexed: 03/16/2025]
Abstract
BACKGROUND Drug-induced enterocolitis syndrome (DIES) is a recently defined clinical entity, first described in 2014. DIES is a hypersensitivity reaction with non-IgE mechanisms involving the gastrointestinal tract, occurring 1 to 4 hours after drug ingestion. Antibiotics are most commonly responsible, particularly amoxicillin or amoxicillin / clavulanic acid (AMX/CL). The main criterion is recurrent, often uncontrollable vomiting occurring 1-4 hours after drug ingestion, without classic IgE-mediated allergic symptoms such as cutaneous or respiratory reactions. To the best of our knowledge, 10 pediatric cases of DIES have been described in the literature. CASE PRESENTATIONS A 4-year-old male and a 14-year-old male presented to our pediatric allergy clinic with a suspected hypersensitivity reaction to AMX/CL, and their specific IgE tests for penicillin G and penicillin V were negative. The younger patient was also tested for specific IgE against amoxicillin and ampicillin, which were also negative. Skin prick tests and intradermal test with AMX/CL were negative in both patients, but oral provocation testing with AMX/CL resulted in abdominal pain, vomiting and lethargy, confirming the diagnosis of DIES. CONCLUSIONS DIES should be considered in patients presenting with vomiting and lethargy following drug ingestion, particularly when IgE-mediated allergies have been ruled out. Early recognition and appropriate management, including drug provocation testing in a controlled setting, are crucial to ensure optimal patient outcomes. By presenting these two rare cases, we aim to raise awareness and deepen the understanding of DIES among healthcare professionals, which could contribute to earlier diagnosis and better patient outcomes.
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Affiliation(s)
- Murat Özer
- Department of Pediatric Immunology and Allergy, Dr. Sami Ulus Maternity Child Health and Diseases Training and Research Hospital, Ankara, Türkiye
| | - Erhan Bahadır
- Department of Pediatric Immunology and Allergy, Dr. Sami Ulus Maternity Child Health and Diseases Training and Research Hospital, Ankara, Türkiye
| | - Bahri Can Duran
- Department of Pediatric Immunology and Allergy, Dr. Sami Ulus Maternity Child Health and Diseases Training and Research Hospital, Ankara, Türkiye
| | - Caner Aytekin
- Department of Pediatric Immunology and Allergy, Dr. Sami Ulus Maternity Child Health and Diseases Training and Research Hospital, Ankara, Türkiye
| | - Serap Özmen
- Department of Pediatric Immunology and Allergy, Dr. Sami Ulus Maternity Child Health and Diseases Training and Research Hospital, Ankara, Türkiye
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2
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Mishra S, Yadav GK, Gupta R, Kumar A. Resin related enterocolitis: An underreported co-occurrence. INDIAN J PATHOL MICR 2024; 67:688-690. [PMID: 38391327 DOI: 10.4103/ijpm.ijpm_627_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Accepted: 11/01/2022] [Indexed: 02/24/2024] Open
Abstract
ABSTRACT Medication resins are often encountered in gastrointestinal biopsy specimens of patients being treated for renal compromise. As important as they are for the electrolyte equilibrium of the patients, they often come with a cost of fatal but reversible damage to the gastrointestinal tract. This often manifests as inflammatory bowel disease in the affected individuals. This misleading manifestation coupled with the lack of patient history further masks resin-related colitis from a pathologist's eyes. Through this report, we convey how meticulous history-taking, representative endoscopic sampling, and recognition under the microscope are vital for timely reporting in conditions like this.
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Affiliation(s)
- Sonali Mishra
- Department of Pathology and Laboratory Medicine, AIIMS, Rishikesh, Uttarakhand, India
| | - Gajendra K Yadav
- Department of Pathology and Laboratory Medicine, AIIMS, Rishikesh, Uttarakhand, India
| | - Rohit Gupta
- Department of Gastroenterology, AIIMS, Rishikesh, Uttarakhand, India
| | - Arvind Kumar
- Department of Pathology and Laboratory Medicine, AIIMS, Rishikesh, Uttarakhand, India
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3
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Albayrak F, Gür M, Karataş A, Koca SS, Kısacık B. Is the use of secukinumab after anti-TNF therapy greater than expected for the risk of developing inflammatory bowel disease? REUMATOLOGIA CLINICA 2024; 20:123-127. [PMID: 38494303 DOI: 10.1016/j.reumae.2023.11.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Accepted: 11/16/2023] [Indexed: 03/19/2024]
Abstract
OBJECTIVE In this study, our objective was to present real-life data on the incidence of inflammatory bowel disease (IBD) among patients receiving secukinumab treatment. METHODS The study consisted of 209 patients who had prior exposure to anti-tumor necrosis factor (TNF) or were biologically naive. Patients with a pre-existing history of IBD were excluded from the study. RESULTS Of the 209 patients in the study, 176 (84.3%) had ankylosing spondylitis, while 33 (15.7%) had psoriatic arthritis. 112 (53.6%) patients had prior exposure to at least one anti-TNF treatment before initiating secukinumab. IBD developed in 10 (4.8%) of the 209 patients. The incidence of IBD among patients who initiated secukinumab as their first biologic agent was 1%. For patients who had previously received any anti-TNF treatment and subsequently transitioned to secukinumab, the incidence of IBD was 8% (p=0.018, odds ratio (OR): 8.38, 95% CI: 1.04-67.45). A mean of 3.67 months (±4.3) after anti-TNF use, whereas IBD symptoms developed in the biologically naive patient after 15 months. CONCLUSION Our study observed IBD incidence in 4.8% of patients using secukinumab. Patients who initiated secukinumab after previous anti-TNF treatment exhibited a significantly higher rate and risk of developing IBD. The onset of IBD occurred earlier in these patients (mean 3.67 months), whereas a single case of IBD showed a longer duration (15 months). Further studies with larger patient numbers are warranted to provide a more comprehensive understanding of our findings.
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Affiliation(s)
- Fatih Albayrak
- Department of Internal Medicine, Division of Rheumatology, Dr. Ersin Arslan Training and Research Hospital, Şehitkamil, Gaziantep, Turkey.
| | - Mustafa Gür
- Department of Internal Medicine, Division of Rheumatology, Fırat University Faculty of Medicine, Elazığ, Turkey
| | - Ahmet Karataş
- Department of Internal Medicine, Division of Rheumatology, Fırat University Faculty of Medicine, Elazığ, Turkey
| | - Süleyman Serdar Koca
- Department of Internal Medicine, Division of Rheumatology, Fırat University Faculty of Medicine, Elazığ, Turkey
| | - Bünyamin Kısacık
- Department of Rheumatology, Gaziantep Sanko Hospital, Şehitkamil, Gaziantep, Turkey
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4
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Bordin DS, Livzan MA, Gaus OV, Mozgovoi SI, Lanas A. Drug-Associated Gastropathy: Diagnostic Criteria. Diagnostics (Basel) 2023; 13:2220. [PMID: 37443618 DOI: 10.3390/diagnostics13132220] [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: 02/28/2023] [Revised: 05/30/2023] [Accepted: 06/27/2023] [Indexed: 07/15/2023] Open
Abstract
Drugs are widely used to treat different diseases in modern medicine, but they are often associated with adverse events. Those located in the gastrointestinal tract are common and often mild, but they can be serious or life-threatening and determine the continuation of treatment. The stomach is often affected not only by drugs taken orally but also by those administered parenterally. Here, we review the mechanisms of damage, risk factors and specific endoscopic, histopathological and clinical features of those drugs more often involved in gastric damage, namely NSAIDs, aspirin, anticoagulants, glucocorticosteroids, anticancer drugs, oral iron preparations and proton pump inhibitors. NSAID- and aspirin-associated forms of gastric damage are widely studied and have specific features, although they are often hidden by the coexistence of Helicobacter pylori infection. However, the damaging effect of anticoagulants and corticosteroids or oral iron therapy on the gastric mucosa is controversial. At the same time, the increased use of new antineoplastic drugs, such as checkpoint inhibitors, has opened up a new area of gastrointestinal damage that will be seen more frequently in the near future. We conclude that there is a need to expand and understand drug-induced gastrointestinal damage to prevent and recognize drug-associated gastropathy in a timely manner.
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Affiliation(s)
- Dmitry S Bordin
- A.S. Loginov Moscow Clinical Scientific Center, Department of Pancreatic, Biliary and Upper Digestive Tract Disorders, 111123 Moscow, Russia
- Department of Propaedeutic of Internal Diseases and Gastroenterology, A.I. Yevdokimov Moscow State University of Medicine and Dentistry, 127473 Moscow, Russia
- Department of Outpatient Therapy and Family Medicine, Tver State Medical University, 170100 Tver, Russia
| | - Maria A Livzan
- Department of Faculty Therapy and Gastroenterology, Omsk Sate Medical University, 644099 Omsk, Russia
| | - Olga V Gaus
- Department of Faculty Therapy and Gastroenterology, Omsk Sate Medical University, 644099 Omsk, Russia
| | - Sergei I Mozgovoi
- Department of Pathological Anatomy, Omsk Sate Medical University, 644099 Omsk, Russia
| | - Angel Lanas
- Digestive Diseases Service, Aragón Health Research Institute (IIS Aragón), University Clinic Hospital, University of Zaragoza, 50009 Zaragoza, Spain
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5
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Di Filippo P, Venanzi A, Ciarelli F, Panetti B, Di Pillo S, Chiarelli F, Attanasi M. Drug-Induced Enterocolitis Syndrome in Children. Int J Mol Sci 2023; 24:ijms24097880. [PMID: 37175584 PMCID: PMC10178722 DOI: 10.3390/ijms24097880] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Revised: 04/16/2023] [Accepted: 04/24/2023] [Indexed: 05/15/2023] Open
Abstract
Drug-Induced Enterocolitis Syndrome (DIES) is a drug-induced hypersensitivity reaction non-IgE mediated involving the gastrointestinal system that occurs 2 to 4 h after drug administration. Antibiotics, specifically amoxicillin or amoxicillin/clavulanate, represent the most frequent drugs involved. Symptoms include nausea, vomiting, abdominal pain, diarrhea, pallor, lethargy, and dehydration, which can be severe and result in hypovolemic shock. The main laboratory finding is neutrophilic leukocytosis. To the best of our knowledge, 12 cases of DIES (9 children-onset and 3 adult-onset cases) were described in the literature. DIES is a rare clinically well-described allergic disease; however, the pathogenetic mechanism is still unclear. It requires to be recognized early and correctly treated by physicians.
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Affiliation(s)
- Paola Di Filippo
- Department of Pediatrics, University of Chieti, 66100 Chieti, Italy
| | | | | | - Beatrice Panetti
- Department of Pediatrics, University of Chieti, 66100 Chieti, Italy
| | - Sabrina Di Pillo
- Department of Pediatrics, University of Chieti, 66100 Chieti, Italy
| | | | - Marina Attanasi
- Department of Pediatrics, University of Chieti, 66100 Chieti, Italy
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Campora M, Mastracci L, Carlin L, Unti E, Parente P, Fassan M, Ferro J, Errico ME, Donofrio V, Grillo F. Pathologist's approach to paediatric and neonatal eosinophilic gastrointestinal disorders. Pathologica 2022; 114:79-88. [PMID: 35212318 PMCID: PMC9040541 DOI: 10.32074/1591-951x-734] [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: 12/23/2021] [Accepted: 12/23/2021] [Indexed: 11/30/2022] Open
Abstract
Children are not simply miniature adults. The evaluation of their gastrointestinal disorders is therefore different from that in full-grown adults and requires a particular clinical/pathologic approach. Different studies have tried to assess the normal eosinophil distribution in the gastrointestinal tract in adults while very few studies have investigated the paediatric population, consequently complicating the pathologist’s ability in identifying an abnormal number of eosinophils in this setting of patients. When evaluating gastrointestinal tract biopsies with eosinophilia, eosinophilic count must be considered along with other histological features like eosinophil distribution in the gastrointestinal wall, their degranulation, cryptitis and crypt abscesses, other accompanying inflammatory cells, apoptotic bodies, foreign material or microorganisms; these findings, although rarely specific, may be a useful aid for diagnosis. Reports should not include a diagnosis of primary eosinophilic gastrointestinal disorders (EoGID) if clinical data and test results do not rule out other forms of gastrointestinal eosinophilia. A more descriptive definition like “with eosinophilic pattern” should be favoured over a specific diagnosis of “eosinophilic disorder” in order to avoid potential confusion between different entities.
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Affiliation(s)
| | - Luca Mastracci
- Anatomic Pathology, Ospedale Policlinico San Martino IRCCS, Genova, Italy.,Anatomic Pathology, Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genova, Genova, Italy
| | - Luca Carlin
- Anatomic Pathology, Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genova, Genova, Italy
| | - Elettra Unti
- Unit of Pathology, Civico-Di Cristina-Benfratelli Hospitals, Palermo, Italy
| | - Paola Parente
- Unit of Pathology, Fondazione IRCCS Casa Sollievo della Sofferenza, Viale Cappuccini 1, 71013 San Giovanni Rotondo, FG, Italy
| | - Matteo Fassan
- Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, Padua, Italy.,Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
| | - Jacopo Ferro
- Anatomic Pathology, Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genova, Genova, Italy
| | - Maria Elena Errico
- Anatomia Patologica, Unit of Pathology, AORN Santobono Pausilipon, Ospedale Pausilipon, Naples, Italy
| | - Vittoria Donofrio
- Anatomia Patologica, Unit of Pathology, AORN Santobono Pausilipon, Ospedale Pausilipon, Naples, Italy
| | - Federica Grillo
- Anatomic Pathology, Ospedale Policlinico San Martino IRCCS, Genova, Italy.,Anatomic Pathology, Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genova, Genova, Italy
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Mori F, Liccioli G, Fuchs O, Barni S, Giovannini M, Sarti L, Novembre E, Caubet JC. Drug-induced enterocolitis syndrome: Similarities and differences compared with food protein-induced enterocolitis syndrome. Pediatr Allergy Immunol 2021; 32:1165-1172. [PMID: 33651420 DOI: 10.1111/pai.13491] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2020] [Revised: 02/20/2021] [Accepted: 02/22/2021] [Indexed: 11/29/2022]
Abstract
In 2014, drug-induced enterocolitis syndrome (DIES) was described for the first time. It is still a poorly known disease with symptoms that typically resemble those of food protein-induced enterocolitis syndrome (FPIES). To date, six more cases of DIES have been described and new clinical diagnostic criteria have been proposed based on those in the international guidelines for FPIES. In this paper, the authors describe three more cases of DIES. In addition, similarities and differences with FPIES have been deeply analyzed. To date, several unanswered questions need to be addressed, but clinicians must be instructed how to identify DIES, in order to make an allergy workup and give definite therapeutic indications to patients, especially in children where DIES seems to be more frequent.
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Affiliation(s)
- Francesca Mori
- Department of Paediatric Medicine, Allergy Unit, Meyer Children's Hospital, Florence, Italy
| | - Giulia Liccioli
- Department of Paediatric Medicine, Allergy Unit, Meyer Children's Hospital, Florence, Italy
| | - Oliver Fuchs
- Division of Pediatric Allergology and Pulmonology, University Children's Hospital, Inselspital, University of Bern, Bern, Switzerland
| | - Simona Barni
- Department of Paediatric Medicine, Allergy Unit, Meyer Children's Hospital, Florence, Italy
| | - Mattia Giovannini
- Department of Paediatric Medicine, Allergy Unit, Meyer Children's Hospital, Florence, Italy
| | - Lucrezia Sarti
- Department of Paediatric Medicine, Allergy Unit, Meyer Children's Hospital, Florence, Italy
| | - Elio Novembre
- Department of Paediatric Medicine, Allergy Unit, Meyer Children's Hospital, Florence, Italy
| | - Jean-Christoph Caubet
- Department of the Child and Adolescent, Pediatric Allergy Units, Geneva University Hospitals, Geneva, Switzerland
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Functional metabolomics reveal the role of AHR/GPR35 mediated kynurenic acid gradient sensing in chemotherapy-induced intestinal damage. Acta Pharm Sin B 2021; 11:763-780. [PMID: 33777681 PMCID: PMC7982426 DOI: 10.1016/j.apsb.2020.07.017] [Citation(s) in RCA: 50] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2020] [Revised: 07/14/2020] [Accepted: 07/15/2020] [Indexed: 12/26/2022] Open
Abstract
Intestinal toxicity induced by chemotherapeutics has become an important reason for the interruption of therapy and withdrawal of approved agents. In this study, we demonstrated that chemotherapeutics-induced intestinal damage were commonly characterized by the sharp upregulation of tryptophan (Trp)−kynurenine (KYN)−kynurenic acid (KA) axis metabolism. Mechanistically, chemotherapy-induced intestinal damage triggered the formation of an interleukin-6 (IL-6)−indoleamine 2,3-dioxygenase 1 (IDO1)−aryl hydrocarbon receptor (AHR) positive feedback loop, which accelerated kynurenine pathway metabolism in gut. Besides, AHR and G protein-coupled receptor 35 (GPR35) negative feedback regulates intestinal damage and inflammation to maintain intestinal integrity and homeostasis through gradually sensing kynurenic acid level in gut and macrophage, respectively. Moreover, based on virtual screening and biological verification, vardenafil and linagliptin as GPR35 and AHR agonists respectively were discovered from 2388 approved drugs. Importantly, the results that vardenafil and linagliptin significantly alleviated chemotherapy-induced intestinal toxicity in vivo suggests that chemotherapeutics combined with the two could be a promising therapeutic strategy for cancer patients in clinic. This work highlights GPR35 and AHR as the guardian of kynurenine pathway metabolism and core component of defense responses against intestinal damage.
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Key Words
- 1-MT, 1-methyl-tryptophan
- AG, AG490
- AHR
- AHR, aryl hydrocarbon receptor
- ARNT, aryl hydrocarbon receptor nuclear translocator
- BCA, bicinchoninic acid
- BSA, bovine serum albumin
- CH, CH223191
- CPT-11, irinotecan
- CYP1A1, cytochrome P450 1A1
- DAI, disease activity index
- DMSO, dimethyl sulfoxide
- DPP-4, dipeptidyl peptidase-4
- DRE, dioxin response elements
- DSS, dextran sulphate sodium
- Dens-Cl, N-diethyl-amino naphthalene-1-sulfonyl chloride
- Dns-Cl, N-dimethyl-amino naphthalene-1-sulfonyl chloride
- ECL, enhanced chemiluminescence
- ELISA, enzyme-linked immunosorbent assay
- ERK1/2, extracellular regulated protein kinases 1/2
- ESI, electrospray ionization
- FBS, fetal bovine serum
- GE, gastric emptying
- GFP, green fluorescence protein
- GI, gastrointestinal transit
- GPR35
- GPR35, G protein-coupled receptor 35
- Gradually sensing
- HE, hematoxylin and eosin
- HRP, horseradish peroxi-dase
- IBD, inflammatory bowel disease
- IDO1, indoleamine 2,3-dioxygenase 1
- IL-6, interleukin-6
- IS, internal standard
- Intestinal toxicity
- JAK2, janus kinase 2
- KA, kynurenic acid
- KAT, kynurenine aminotransferase
- KYN, kynurenine
- Kynurenine pathway
- LC–MS, liquid chromatography–mass spectrometry
- LPS, lipopolysaccharides
- Linag, linagliptin
- MOE, molecular operating environment
- MOI, multiplicity of infection
- MRM, multiple-reaction monitoring
- MTT, thiazolyl blue tetrazolium bromide
- PBS, phosphate buffer saline
- PDB, protein data bank
- PDE5, phosphodiesterase type-5
- PF, PF-04859989
- PMA, phorbol 12-myristate 13-acetate
- PMSF, phenylmethylsulfonyl fluoride
- RIPA, radioimmunoprecipitation
- RPKM, reads per kilobase per million mapped reads
- RPMI 1640, Roswell Park Memorial Institute 1640
- RT-PCR, real-time polymerase chain reaction
- STAT3, signal transducer and activator of transcription 3
- Trp, tryptophan
- VCR, vincristine
- Vard, vardenafil
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Petitpain N, D'Amico F, Yelehe-Okouma M, Jouzeau JY, Netter P, Peyrin-Biroulet L, Gillet P. IL-17 Inhibitors and Inflammatory Bowel Diseases: A Postmarketing Study in Vigibase. Clin Pharmacol Ther 2021; 110:159-168. [PMID: 33411953 DOI: 10.1002/cpt.2155] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2020] [Accepted: 12/09/2020] [Indexed: 12/16/2022]
Abstract
Several gastrointestinal symptoms and chronic inflammatory bowel diseases (IBDs) have been reported after therapy with IL-17 inhibitors. To date, however, no study has shown a clear association between these drugs and IBD onset. We searched on Vigibase, the worldwide pharmacovigilance database, to investigate reporting prevalence, characteristics, and prognosis of all gastroenterological adverse events in patients treated with IL-17 inhibitors. In total, 1,129 gastrointestinal Individual Case Safety Reports (ICSRs) were identified, including 850 IBD (42.5% Crohn's disease, 31.9% ulcerative colitis, and 25.6% undifferentiated IBD) and 279 colitis (mainly undifferentiated colitis (79.2%), and microscopic colitis (10.4%)). ICSRs were associated with secukinumab (SEC, 83.6%) or ixekizumab (IXE, 16.3%), whereas only one colitis occurred with brodalumab (0.1%). Most IBD and colitis cases were detected within 6 months from therapy start in both the SEC (68.8% and 73.5%) and IXE groups (100% and 66.7%). Patients' outcomes were reported in 428 ICSRs (37.9%). Complete or ongoing recovery from symptoms was detected in about two-thirds of patients experiencing IBD (59.5%) or colitis (64.2%), whereas in the other cases, there was no recovery (33.9% and 29.5%) or there were sequelae (5.4% and 4.2%). Fatal events occurred in four patients (1.2%) in the IBD group (3 after SEC and on1e with IXE) and two SEC-treated subjects in the colitis group (2.1%). Treatment with IL-17 inhibitors is associated with a relevant number of exacerbations and new onset of IBD and colitis. Careful evaluation of gastrointestinal symptoms and the monitoring of intestinal inflammatory biomarkers should be recommended before prescribing these drugs.
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Affiliation(s)
- Nadine Petitpain
- Regional Centre of Pharmacovigilance, University Hospital of Nancy, Vandoeuvre-lès-Nancy, France
| | - Ferdinando D'Amico
- Department of Biomedical Sciences, Humanitas University, Milan, Italy.,Department of Gastroenterology and Inserm NGERE U1256, University Hospital of Nancy, University of Lorraine, Vandoeuvre-lès-Nancy, France
| | - Melissa Yelehe-Okouma
- Regional Centre of Pharmacovigilance, University Hospital of Nancy, Vandoeuvre-lès-Nancy, France
| | - Jean-Yves Jouzeau
- Department of Clinical Pharmacology and Toxicology, University Hospital of Nancy, Vandoeuvre-lès-Nancy, France.,Ingénierie Moléculaire et Ingénierie Articulaire (IMoPA), UMR-7365 CNRS, Faculté de Médecine, University of Lorraine and University Hospital of Nancy, Vandoeuvre-lès-Nancy, France
| | - Patrick Netter
- Ingénierie Moléculaire et Ingénierie Articulaire (IMoPA), UMR-7365 CNRS, Faculté de Médecine, University of Lorraine and University Hospital of Nancy, Vandoeuvre-lès-Nancy, France
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology and Inserm NGERE U1256, University Hospital of Nancy, University of Lorraine, Vandoeuvre-lès-Nancy, France
| | - Pierre Gillet
- Regional Centre of Pharmacovigilance, University Hospital of Nancy, Vandoeuvre-lès-Nancy, France.,Ingénierie Moléculaire et Ingénierie Articulaire (IMoPA), UMR-7365 CNRS, Faculté de Médecine, University of Lorraine and University Hospital of Nancy, Vandoeuvre-lès-Nancy, France
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10
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Hewlings S, Kalman D. A Review of Zinc-L-Carnosine and Its Positive Effects on Oral Mucositis, Taste Disorders, and Gastrointestinal Disorders. Nutrients 2020; 12:nu12030665. [PMID: 32121367 PMCID: PMC7146259 DOI: 10.3390/nu12030665] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2020] [Revised: 02/17/2020] [Accepted: 02/27/2020] [Indexed: 12/14/2022] Open
Abstract
Zinc-L-carnosine (ZnC), also called polaprezinc known as PepZin GI™, is a chelated compound that contains L-carnosine and zinc. It is a relatively new molecule and has been associated with multiple health benefits. There are several studies that support ZnC’s benefits in restoring the gastric lining, healing other parts of the gastrointestinal (GI) tract, improving taste disorders, improving GI disorders, and enhancing skin and liver. Oral mucositis is a common complication of cytotoxic radiotherapy and/or chemotherapy. It occurs in almost every person with head and neck cancer who receive radiotherapy. It is often overlooked because it is not considered life threatening. However, mucositis often leads to a decreased quality of life and cessation of treatment, ultimately decreasing positive outcomes. Therefore, solutions to address it should be considered. The primary mechanisms of action are thought to be localized and related to ZnC’s anti-inflammatory and antioxidant functions. Therefore, the purpose of this review is to discuss the research related to ZnC and to explore its benefits, especially in the management of conditions related to damaged epithelial cells, such as oral mucositis. Evidence supports the safety and efficacy of ZnC for the maintenance, prevention, and treatment of the mucosal lining and other epithelial tissues. The research supports its use for gastric ulcers (approved in Japan) and conditions of the upper GI and suggests other applications, particularly for oral mucositis.
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Affiliation(s)
- Susan Hewlings
- Central Michigan University, Department of Nutrition and Dietetics Mount Pleasant, MI 48859, USA
- Correspondence:
| | - Douglas Kalman
- College of Healthcare Sciences, Nova Southeastern University, Fort Lauderdale 33314, USA;
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11
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Gastrointestinal adverse effects of nintedanib and the associated risk factors in patients with idiopathic pulmonary fibrosis. Sci Rep 2019; 9:12062. [PMID: 31427707 PMCID: PMC6700168 DOI: 10.1038/s41598-019-48593-4] [Citation(s) in RCA: 50] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2018] [Accepted: 08/08/2019] [Indexed: 02/07/2023] Open
Abstract
Nausea and diarrhea are the most common adverse effects of nintedanib in patients with idiopathic pulmonary fibrosis (IPF). However, the clinical risk factors for these side effects remain unknown. In the present study, we investigated the characteristics of patients who developed gastrointestinal side effects during nintedanib treatment for IPF and determined the risk factors for these side effects. We enrolled 77 patients with IPF who received nintedanib between October 2015 and March 2018. Performance status (PS) as a patient’s general condition, body mass index (BMI), modified Medical Research Council Dyspnea Scale score, severity of IPF at nintedanib initiation, and gastrointestinal toxicity of nintedanib were evaluated. In total, 25 and 27 patients exhibited nausea and diarrhea, respectively, during the follow-up period. A poor PS, low BMI, and full dosage of nintedanib at treatment initiation were risk factors for nausea. A low BMI was a significant risk factor for diarrhea, which could be prevented by combination treatment with nintedanib and prednisolone. In addition, the mean annual rate of decline in forced vital capacity was significantly greater in patients with nausea than in patients without nausea. In conclusion, our findings suggest that patients with a low BMI and/or poor PS and those who receive the full nintedanib dosage at treatment initiation are more susceptible to gastrointestinal adverse effects during nintedanib treatment. Addition of prednisolone to the treatment regimen may prevent the development of diarrhea during treatment.
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Brechmann T, Günther K, Neid M, Tannapfel A, Schmiegel W. Phenotype of histologically suspected drug-induced colitis; results of a comparative, retrospective cohort study. Scand J Gastroenterol 2019; 54:855-862. [PMID: 31215277 DOI: 10.1080/00365521.2019.1630674] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Background/aims: Drug-induced colitis (DiC) is a rarely reported form of colonopathy and data about the clinical and endoscopic characteristics are scarce. The aim was to investigate the phenotype of DiC. Methods: Patients in a retrospective case control study were assigned to either DiC or one of two age- and gender-matched control groups (non-inflammatory controls and inflammatory colitis from other causes) based on histopathological findings. Patients' basic characteristics, symptoms, biochemical results and endoscopic appearance were collected. Statistical analysis included ANOVA, the chi-squared test and two-tailed t-test. Results: A total of 211 patients with DiC were included (97 males, age 62.1 ± 16.1 years, BMI 25.9 ± 6.1 kg m-2). In comparison to both control groups, DiC patients presented higher ASA and ECOG-scores and more particularly atherosclerotic comorbidities. The most abundant symptoms were abdominal pain (51.8%), diarrhoea (50.7%) and haematochezia (24.3%). The red blood cell count demarcated anaemia (12.7 ± 2.3 mg/dl) and C-reactive protein was slightly elevated (2.7 ± 5.2 mg/dl). The endoscopic features included erythema (46.9%), oedema (29.9%), erosions (29.9%) and ulcers (14.7%). The inflammation affected the rectum rarely (2.4%) but affected the rest of the colon without predilection in a segmental manner (p<.05). The severity of DiC was mostly mild (85.7%). Conclusions: The phenotype of DiC differs slightly from that of colitis from other causes. Taking the clinical features into account might help to confirm drug-induced aetiology once the pathologist has raised the suspicion.
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Affiliation(s)
- Thorsten Brechmann
- Department of Gastroenterology and Hepatology, Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil gGmbH , Bochum , Germany
| | - Katharina Günther
- Department of Gastroenterology and Hepatology, Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil gGmbH , Bochum , Germany
| | - Matthias Neid
- Institute of Pathology, Ruhr-University , Bochum , Germany
| | | | - Wolff Schmiegel
- Department of Gastroenterology and Hepatology, Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil gGmbH , Bochum , Germany
- Department of Internal Medicine, University Hospital Knappschaftskrankenhaus , Bochum , Germany
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Brechmann T, Günther K, Neid M, Schmiegel W, Tannapfel A. Triggers of histologically suspected drug-induced colitis. World J Gastroenterol 2019; 25:967-979. [PMID: 30833802 PMCID: PMC6397729 DOI: 10.3748/wjg.v25.i8.967] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2018] [Revised: 01/22/2019] [Accepted: 01/26/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Drug toxicity is a common and even serious problem in the gastrointestinal tract that is thought to be caused by a broad spectrum of agents. Although withdrawal of the causative agent would cure the disease knowledge is scarce and mostly derives from case reports and series.
AIM To investigate potential triggers of drug-induced colitis (DiC).
METHODS We conducted a retrospective, observational case control study. Patients were assigned to DiC or one of two age- and gender-matched control groups (non-inflammatory controls and inflammatory colitis of another cause) based on histopathological findings. Histopathology was reassessed in a subset of patients (28 DiC with atherosclerosis, DiC without atherosclerosis and ischaemic colitis each) for validation purposes. Medical history was collected from the electronic database and patient records. Statistical analysis included chi-squared test, t-test, logistic and multivariate regression models.
RESULTS Drug-induced colitis was detected in 211 endoscopically sampled biopsy specimens of the colon mucosa (7% of all screened colonoscopic biopsy samples); a total of 633 patients were included equally matched throughout the three groups (291 males, mean age: 62.1 ± 16.1 years). In the univariate analysis, DiC was associated with diuretics, dihydropyridines, glycosides, ASS, platelet aggregation inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs), statins and fibrates, and with atherosclerosis, particularly coronary heart disease, and hyperlipoproteinaemia. Echocardiographic parameters did not show substantial differences. In the multivariate analysis only fibrates [odds ratio (OR) = 9.1], NSAIDs (OR = 6.7) and atherosclerosis (OR = 2.1) proved to be associated with DiC. Both DiC reassessment groups presented milder inflammation than ischaemic colitis. The DiC patients with atherosclerosis exhibited histological features from both DiC without atherosclerosis and ischaemic colitis.
CONCLUSION Several drugs indicated for the treatment of cardiovascular and related diseases are associated with DiC. Atherosclerosis and microcirculatory disturbances seem to play an important pathogenetic role.
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Affiliation(s)
- Thorsten Brechmann
- Department of Gastroenterology and Hepatology, Ruhr-University Bochum, Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil gGmbH, Bochum 44789, Germany
| | - Katharina Günther
- Department of Gastroenterology and Hepatology, Ruhr-University Bochum, Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil gGmbH, Bochum 44789, Germany
| | - Matthias Neid
- Institute of Pathology, Ruhr-University Bochum, Bochum 44789, Germany
| | - Wolff Schmiegel
- Department of Gastroenterology and Hepatology, Ruhr-University Bochum, Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil gGmbH, Bochum 44789, Germany
- Department of Internal Medicine, University Hospital Knappschaftskrankenhaus, Ruhr-University Bochum, Bochum 44892, Germany
| | - Andrea Tannapfel
- Institute of Pathology, Ruhr-University Bochum, Bochum 44789, Germany
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Abstract
PURPOSE OF REVIEW Not all injuries of the terminal ileum are Crohn's disease. It is the purpose of this review to consider the differential diagnosis of other acute and chronic ileal lesions. RECENT FINDINGS The recognition of a granulomatous disease of the terminal ileum, distinct from tuberculosis, dates back over 85 years and perhaps much farther, but over the past decades, many other clinical pathologic entities have been described that are neither tuberculosis nor Crohn's eponymous regional enteritis. In recent years, the catalog of lesions mimicking Crohn's disease of the small bowel and proposals for differential diagnosis and treatment have expanded to include newly reported appendiceal pathology, primary cancers and lymphomas of the intestine, unexpected metastases from distant organs, unusual infections, vasculitides and other ischemic conditions, Behçet's disease, endometriosis, and drug reactions. A diagnosis of Crohn's disease should not be a reflex action in the face of small bowel structural or inflammatory lesions without consideration of pathology in adjacent organs, primary and metastatic lesions of the small intestine, infections, vascular diseases, infiltrative diseases, drug injury, or other "idiopathic" conditions.
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