Case Control Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 28, 2019; 25(8): 967-979
Published online Feb 28, 2019. doi: 10.3748/wjg.v25.i8.967
Triggers of histologically suspected drug-induced colitis
Thorsten Brechmann, Katharina Günther, Matthias Neid, Wolff Schmiegel, Andrea Tannapfel
Thorsten Brechmann, Katharina Günther, Wolff Schmiegel, Department of Gastroenterology and Hepatology, Ruhr-University Bochum, Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil gGmbH, Bochum 44789, Germany
Matthias Neid, Andrea Tannapfel, Institute of Pathology, Ruhr-University Bochum, Bochum 44789, Germany
Wolff Schmiegel, Department of Internal Medicine, University Hospital Knappschaftskrankenhaus, Ruhr-University Bochum, Bochum 44892, Germany
Author contributions: Schmiegel W, Brechmann T, and Tannapfel A developed the idea and designed the study. Brechmann T and Günther K collected and analysed the data. Neid M and Günther K performed the histopathological reassessment. Brechmann T drafted the manuscript. Günther K, Neid M, Schmiegel S, and Tannapfel A revised the manuscript.
Institutional review board statement: The study protocol was approved by the institutional review board of the Ruhr-university Bochum [registration number 16-5963] on the basis of the ethical guidelines of the Declaration of Helsinki and its later revisions.
Informed consent statement: Written, informed consents were obtained from all patients before specific examinations and procedures such as colonoscopy and biopsy. For this retrospective study informed consent was neither practicable nor necessary.
Conflict-of-interest statement: The authors declare no conflict of interest.
Data sharing statement: All authors had unlimited access to the data.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Thorsten Brechmann, MD, Doctor, Senior Researcher, Department of Gastroenterology and Hepatology, Ruhr-University Bochum, Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil gGmbH, Bürkle-de-la-Camp-Platz 1, Bochum 44789, Germany. thorsten.brechmann@rub.de
Telephone: +49-234-3023411 Fax: +49-234-3026707
Received: November 27, 2018
Peer-review started: November 27, 2018
First decision: December 20, 2018
Revised: January 22, 2019
Accepted: January 26, 2019
Article in press: January 26, 2019
Published online: February 28, 2019
Processing time: 92 Days and 20.5 Hours
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.

Keywords: Drug toxicity; Drug-induced colitis; Ischaemic colitis; Drug-associated gastrointestinal disease; Atherosclerosis; Colonic ischaemia; Nonsteroidal anti-inflammatory drugs; Fibrates

Core tip: Several drugs have been attributed to drug-induced colitis (DiC). In this systematical age- and gender-matched retrospective cohort study based on histopathological findings DiC was associated with drugs predominantly indicated for the treatment of cardiovascular and related diseases, nonsteroidal anti-inflammatory drugs, with atherosclerosis, particularly coronary heart disease, and hyperlipoproteinaemia. Histopathology was reassessed in three groups (DiC with atherosclerosis, DiC without atherosclerosis and ischaemic colitis each); both DiC groups presented milder inflammation than ischaemic colitis; DiC patients with atherosclerosis exhibited histological features from both other groups. In conclusion, atherosclerosis and microcirculatory disturbances seem to play an important pathogenetic role.