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Is Loperamide Use an Independent Risk Factor for A Fatal outcome of Toxic Megacolon? - A Narrative Clinical Review

by Bente M. van Genderen, Perry JJ van Genderen*

Expertise Centre for Travel-Risk Assessment, Corporate Travel Clinic, Maasboulevard 148, 3011 TX Rotterdam, The Netherlands

*Corresponding author: Perry JJ van Genderen, MD, PhD, MSc, Expertise Centre for Travel-Risk Assessment, Corporate Travel Clinic, Maasboulevard 148, 3011 TX Rotterdam, The Netherlands

Received Date: 27 October 2025

Accepted Date: 03 November 2025

Published Date: 05 November 2025

Citation: van Genderen BM, van Genderen PJJ (2025) Is Loperamide Use an Independent Risk Factor for A Fatal outcome of Toxic Megacolon? - A Narrative Clinical Review - J Surg 10: 11480 https://doi.org/10.29011/2575-9760.011480

Abstract

Background: Loperamide, a phenylpiperidine opioid derivative, is widely used as an empirical and generally safe over-the-counter antidiarrheal agent. Although rare, several reports have linked loperamide use to Toxic Megacolon (TM), a life-threatening condition characterized by severe dilatation of an inflamed colon and systemic toxicity. However, this association remains unclear due to confounding comorbidities and concomitant medications.

Objective: This review aimed to determine whether loperamide use should be considered an independent risk factor for a fatal outcome of TM.

Methods: A systematic literature search was performed in accordance with PRISMA guidelines. A total of 222 articles describing 496 TM cases were identified and analyzed for risk factors associated with fatal outcomes.

Results: Among 496 TM patients, 80 (16.1%) experienced a fatal outcome, and 30 (6.0%) had used loperamide within three months prior to TM onset. Backward logistic regression identified Charlson Comorbidity Index (CCI) score (OR 1.21, 95% CI 1.02–1.43), antidiarrheal regimen without loperamide (OR 2.41, 95% CI 1.17–4.96), and a complicated course of TM (OR 7.53, 95% CI 4.34– 13.09) as significant independent predictors of fatality. Loperamide use was not retained as an independent variable in the final model. Quality assessment rated 85.1% (189/222) of included studies as methodologically low.

Conclusion: Current evidence does not support loperamide as an independent risk factor for fatal toxic megacolon. The findings are limited by incomplete data and low methodological quality across much of the available literature.

Keywords: Complication; Fatal; Imodium; Loperamide; Megacolon; Review; Severe; Toxic

Introduction

Loperamide, commonly known by its brand name Imodium®, is a phenylpiperidine opioid derivative widely used as a safe, over-thecounter antidiarrheal agent for both acute and chronic diarrhea [1]. Its antidiarrheal effect arises from potent μ-opioid receptor agonism within the myenteric plexus of the colon, which reduces propulsive activity, increases non-propulsive contractions, and enhances water and electrolyte absorption [1,2]. Loperamide exhibits limited oral bioavailability due to extensive first-pass hepatic metabolism via CYP3A4 and CYP2C8 and strong plasma protein binding [2]. Moreover, as a P-glycoprotein substrate, loperamide is effectively excluded from the central nervous system, confining its action to the periphery and minimizing morphine-like central effects [1]. At therapeutic doses, common adverse effects include constipation, nausea, and headache, whereas overdose or concurrent inhibition of P-glycoprotein (e.g., by verapamil or ketoconazole) can result in central opioid toxicity and respiratory depression [3]. In recent years, misuse of loperamide at supratherapeutic doses to alleviate opioid withdrawal or induce euphoria has been increasingly reported, sometimes resulting in life-threatening cardiac arrhythmias [3,4]. Toxic megacolon is a severe complication characterized by colonic dilation with systemic toxicity, associated with significant morbidity and mortality [5-12]. Predisposing factors include electrolyte disturbances such as hypokalemia and the use of agents that impair gastrointestinal motility, including opioids, anticholinergics, loperamide, and certain antidepressants [6-11]. Pathophysiologically, deep inflammatory extension into the colonic muscle layers disrupts neuromuscular tone, compounded by the release of relaxant mediators such as nitric oxide, leading to colonic dilatation [5,6]. Although most cases occur secondary to underlying colitis (e.g., ulcerative, infectious, or antibioticassociated) [5-11], a few reports have implicated loperamide use, often in the presence of confounding comorbidities or co-medications [13-18]. Given that loperamide is sometimes prescribed in patients already predisposed to toxic megacolon, its role as an independent or contributory risk factor warrants careful evaluation. This review aims to assess whether available evidence supports loperamide use as an independent risk factor for fatal outcomes in toxic megacolon.

Methods

The review was conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines where applicable [19]. As a result of the design of the underlying studies, mainly consisting of case report and series, a formal PRISMA systematic review and meta-analysis was not deemed possible.

Data Sources and Search Strategies

The search for bibliographic information was conducted in several electronic databases, namely Medline, EMBASE, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, and Google Scholar. This search encompassed articles on toxic megacolon from inception through February 9, 2024. A comprehensive search strategy was employed, utilizing both descriptors and free terms that were relevant to the review question. These search strategies were tailored to each specific bibliographic database with the assistance of a biomedical information specialist from the Erasmus Medical Centre Rotterdam library (Appendix 1). All retrieved results were stored in an Endnote file and subsequently uploaded in Covidence (https://www.covidence. org) for further analysis and supplemented with articles that were identified during manual screening of reference lists. The screening of eligible publications was conducted independently by two evaluators. Initially, the titles and abstracts of all citations were reviewed. Subsequently, the full text of potentially relevant citations was assessed. In the event of discrepancies, consensus was sought between the two reviewers. If consensus could not be reached, a third independent party would be consulted for the final decision.

Inclusion and Exclusion Criteria

English served as a language restriction, signifying that all articles written in languages other than English were omitted from the analysis. In order to be included, articles had to focus on patients diagnosed with toxic megacolon and provide sufficient individual patient data allowing proper risk factor analysis. Selection criteria include case reports or case series studies of toxic megacolon. Reviews, cohort studies, case-control studies and other clinical studies were also considered for inclusion as long as they provided sufficient data on individual cases. Congress abstracts, poster presentations and poster abstracts were excluded. Only studies conducted on human subjects were included; animal and experimental in vitro studies were excluded. Patients diagnosed with acute colonic pseudo-obstruction (Ogilvie syndrome), patients with congenital megacolon (such as Hirschsprung disease), acquired megacolon due to obstruction (such as fecal impaction or volvulus) or chronic megacolon due to American trypanosomiasis (Chagas disease) were excluded from the analysis as well.

Data Extraction and Assessment

Data extraction was conducted by a single reviewer, utilizing a purpose-built data extraction form. Subsequently, a second reviewer crosschecked the extracted data. The collected data encompassed various aspects, including the demographic details of the cases, their clinical presentation (including information on current and previous illnesses), medication usage (including loperamide), potential trigger events in the three months preceding the toxic megacolon event (including endoscopy, barium enema, and loperamide use), results from physical examinations and diagnostic tests (such as imaging), treatment administered, patient outcomes and follow-up information. Follow-up was censored 90 days after the diagnosis of toxic megacolon. Special attention was given to any past or current antidiarrheal treatment or combination of antidiarrheal treatments that the patient had received in the three months before the diagnosis TM was made.

Data Synthesis and Analysis

Extracted data were collected in an EXCEL file after reaching data consensus and subsequently imported into MedCalc for further statistical analysis. For conveniency of analysis, data was summarized as categorical data and grouped according to the principal outcome of toxic megacolon, i.e. a fatal outcome or not. Missing categorical data were grouped with data in which the characteristic was absent.

Definitions

Jalan diagnostic criteria for toxic megacolon: Many authors consider the (adapted) diagnostic criteria of Jalan (see Appendix 2) as the most widely accepted clinical criteria for toxic megacolon [6, 8, 12]. They constitute of the following criteria:

  • Radiographic evidence of colonic distension
  • At least three of the following:
  • Fever >38.6 ⁰C (101.5 ⁰
  • F)
  • Heart rate ≥ 120/min
  • Neutrophilic leucocytosis>10.5x109/L
  • Anemia
  • In addition to the above, at least one of the following:
  • Dehydration
  • Altered consciousness
  • Electrolyte disturbances
  • Hypotension

Cases with toxic megacolon were labeled as typical cases if the patient fulfilled the adapted diagnostic criteria of Jalan for toxic megacolon [6,8]; patients not fulfilling the diagnostic criteria were labeled atypical TM cases.

Complicated Course Of Toxic Megacolon

A complicated course of toxic megacolon was defined as a course associated with complications like proven sepsis or bacteremia, significant bleeding requiring blood transfusions, hemodynamic shock or a demonstrated perforation of the colon.

Charlson Comorbidity Index (CCI) Score

The Charlson Comorbidity Index is a weighted index consisting of 19 conditions to predict risk of death within 1 year of hospitalization for patients with specific comorbid conditions [20]. A free online calculator (available at www.mdcalc.com) was used to determine a CCI score for each patient.

Antidiarrheal Regimen

An anti-diarrheal regimen was defined as the past or current use of anticholinergic antidiarrheals (like atropine, hyoscamine, dicyclomine, scopolamine, propantheine or clindiniumchlordiazepoxide), narcotic antidiarrheals (like loperamide, diphenoxylate or codein), absorbent antidiarrheals (like kaolin, cholestyramine or colestipol), antisecretory antidiarrheals (like octeotride or racecadotril), non-adsorbable broad spectrum antibiotics like rifaximin and adstringent agents like bismuth salicylate in the three months preceding the TM event. Loperamide (whether or not combined with other antidiarrheals) was reported as a separate (dichotomous) antidiarrheal regimen given the specific interest in loperamide in the context of risk factors for a fatal outcome of toxic megacolon.

Methodological Quality

To assess the methodological quality of case reports and case series, a revised tool for quality appraisal and synthesis was employed [21]. This tool will evaluate four domains: selection, representativeness of cases and ascertainment of outcome and exposure. This resulted in 5 criteria in the form of questions with a binary response (yes/no), whether the item was of high quality or not. These question are listed in Appendix 3. When all 5 criteria were fulfilled the quality of the report was considered good (high methodological quality), moderate when 4 were fulfilled and poor (low methodological quality) when ≤3 were fulfilled. The assessment was carried out by one investigator, with a random sample being crosschecked by another investigator.

Statistical Analysis

Univariate analysis using Mann Whitney test for continuous (not normally distributed) variables and Fisher’s exact test for categorical variables identified risk factors for fatal toxic megacolon. A two-tailed P<0.05 was considered statistically significant. Variables that were significant to P=0.10 and variables that had a priori clinical significance were then analyzed using multivariable logistic regression modeling with fatal toxic megacolon as the dependent (outcome) variable using a backward elimination regression approach. ROC curve analysis was reported as the area under the curve with their respective 95% confidence intervals of the final model. All statistical analyses were performed using MedCalc Statistical Software package version 22.030 (MedCalc Software Ltd, Ostend, Belgium; https://www.medcalc. org; 2024).

Results

Studies Characteristics

A total of 2216 studies were identified through database searching after duplicates had been removed (Figure 1). After screening of titles and abstracts, 447 articles were selected for full-text assessment; 222 articles of them were included in the review (Appendix 4), providing sufficiently detailed case histories of 496 patients with toxic megacolon [13-18, 22-236]. The putative etiologies of TM of these 496 cases are shown in Table 1. Three major etiological clusters could be discerned: one cluster of patients with an inflammatory colitis (n=308 cases), another cluster of patients (n=162) with an infective colitis and a cluster of

miscellaneous causes of colitis constituting the remaining 26 patients, respectively. Eighty of 496 (16.1%) cases with toxic megacolon had a fatal outcome. Thirty of 496 (6.0%) had used loperamide in the three months preceding the TM event. The general characteristics of the 496 included cases are shown in Tables 2,3, grouped according loperamide use or not.

Figure 1: Flowchart for literature search on cases with toxic megacolon.

Inflammatory colitis

Infective colitis

(n=308)

n

%

(n=162)

n

%

Ulcerative colitis

243

78.9

Clostridioides difficile

80

49.4

Crohn’s colitis

49

15.9

Salmonella species

22

13.6

IBD (unspecified)

9

2.9

Campylobacter species

16

9.9

Indeterminate colitis

3

1.0

Entamoeba histolytica

12

7.4

Behҫet’s disease

2

0.6

CMV virus

10

6.2

Collagenous colitis

1

0.3

Shigella species

7

4.3

Adult onset Still’s disease

1

0.3

Cryptosporidium species

2

1.2

Escherichia coli

2

1.2

Miscellaneous colitis

HIV/AIDS

2

1.2

(n=26)

n

%

Drug-induced

8

30.8

Rota virus

2

1.2

Invasive malignancies

6

23.1

Yersinia species

2

1.2

Benign disorders

5

19.2

Unspecified infective colitis

2

1.2

Intoxication

3

11.5

Pseudomonas species

1

0.6

Ischemic

3

11.5

Bacillus licheniformis

1

0.6

Idiopathic

1

3.8

Aspergillosis

1

0.6

Table 1: Putative etiologies of toxic megacolon, divided by etiological subgroup.

Patients with toxic megacolon

Loperamide use

No Loperamide

P-value

(n=30)

(n=466 )

Putative etiology of TM, n (%)

P=0.0015

 Inflammatory colitis (IBD)

10 (33.3%)

298 (63.9%)

 Non-IBD colitis

20 (66.7%)

168 (36.1%)

Age, median (IQR)

41.5

39.0

P=0.22132

(33.0-53.0)

(23.0-56.0)

Sex, n (%)

P=0.8512

 Male

17 (56.7%)

252 (54.1%)

 Female

13 (43.3%)

214 (45.9%)

Charlson Comorbidity Index, median

(IQR)

0

0

P=0.66842

(0-2)

(0-2)

Other antidiarrheal treatment, n (%)

P<0.00011

 Yes

0 (0%)

217 (46.6%)

 No/unknown

30 (100%)

199 (53.4%)

One or more trigger factors for TM, n

(%)

P=1.00001

 Yes

30 (100%)

464 (99.6%)

 No/unknown

0 (0%)

2 (0.4%)

Fulfilling Jalan criteria, n (%)

P=0.58641

 Typical

5 (16.7%)

63 (13.5%)

 Atypical/unknown

25 (83.3%)

403 (86.5%)

Dilatation colon > 6 cm, n (%)

P=0.69211

 Yes

28 (93.3%)

439 (94.2%)

 No/unknown

2 (6.7%)

27 (5.8%)

Management, n (%)

P=0.0289

 Medical

16 (53.3%)

154 (33.0%)

 Medical and surgical

14 (46.7%)

312 (67.0%)

Complicated course, n (%)

P=0.6843

 Yes

10 (33.3%)

139 (29.8%)

 No/unknown

20 (66.7%)

327 (70.2%)

Fatal course, n (%)

P=0.8023 1

 Yes

4 (%)

76 (16.3%)

 No/unknown

26 (%)

390 (83.7%)

1 Fisher’s exact test; 2 Mann-Whitney test

Table 2: General characteristics and outcomes of the patients with Toxic Megacolon (TM), subdivided by loperamide use or not.

FATAL OUTCOME

(80 out of 496 patients)

Independent variables

Coefficient

Std.error

Wald

P-value

Odds ratio

95% CI

Age

0.01505

0.0089942

2.8014

0.0942

Charlson Comorbidity Index

0.18899

0.086439

4.7806

0.0288

1.21

1.02-1.43

Antidiarrheal regimen other than loperamide

0.88093

0.36728

5.7529

0.0165

2.41

1.17-4.96

Complicated course

2.01954

0.28177

51.369

<0.0001

7.53

4.34-13.09

Antibiotic use

-0.69729

0.37558

3.4468

0.0634

Constant

-3.66858

0.42778

73.5442

<0.0001

COMPLICATED COURSE

(149 out of 496 patients)

Independent variables

Coefficient

Standard

Error

Wald

P-value

Odds ratio

95% CI

Medical and surgical management

1.95745

0.28789

46.2311

<0.0001

7.08

4.03-12.45

Inflammatory colitis

-0.69346

0.26999

6.597

0.0102

0.5

0.29-0.85

Antibiotic use

0.41963

0.23237

3.2611

0.0709

Corticosteroid use

-0.42272

0.25605

2.7255

0.0988

Constant

-1.87612

0.30665

37.4309

<0.0001

Table 3: Outcomes of multivariable logistic regression analysis for independent variables for either a fatal outcome or a complicated course of toxic megacolon.

Demographics And Co-Morbidities

As shown in Table 2, patients using loperamide did not significantly differ from those who did not use loperamide with regard to age, sex, CCI score, presence of one or more trigger factors for TM, fulfilling Jalan criteria, dilated colon > 6 cm, complicated course of TM nor did outcome differ. TM patients using loperamide had significantly less frequent a surgical management of TM and significantly more frequently a non-IBD etiology of TM, respectively. More than half of the non-loperamide users had used an antidiarrheal regimen other than loperamide in the three months preceding the TM event.

Potential Trigger Factors In The 3 Months Preceding Toxic Megacolon Event

As shown in Appendix 5, patients with loperamide had undergone endoscopy significantly more frequent and used antibiotics and corticosteroids significantly more frequent than TM patients who did not use loperamide. However, all but 2 patients (who did not use loperamide) had at least one trigger factor for TM.

Management And Prognosis After Diagnosis Of Toxic Megacolon

As shown in Table 2, patients who did not use loperamide had significantly higher rates of a surgical intervention than TM patients who used loperamide. TM patients who used loperamide did not significantly differ from patients who did not use loperamide regarding a complicated course of TM nor the outcome of TM. In Appendix 6 the complication rates of bacteremia/sepsis, shock, perforation and severe bleeding are shown. There were no significant differences in complication rates between TM patients that had used loperamide or not.

Risk Factor Analysis

Backward logistic regression analysis of 496 TM patients identified

Charlson Comorbidity Index (CCI) score (OR 1.21 [95% CI 1.021.43]), any antidiarrheal regimen not containing loperamide (OR

2.41 [95% CI 1.17-4.96]) and a complicated course of TM (OR 7.53 [95% CI 4.34-13.09]) as significant independent variables for a fatal outcome of TM. Loperamide was eliminated as an independent variable from the regression model best explaining the data.

Quality Assessment

Quality assessment of the 222 articles included in the review was rated as of poor methodological quality in the majority (189/222, 85,1%) of the included papers. Methodological quality was rated as high in 6 papers (2.7%) and as moderate in 27 (12.2%) papers (Appendix 3).

Discussion

Diagnostic Criteria For Toxic Megacolon

The current analysis showed that toxic megacolon may be associated with a broad array of underlying medical conditions, including inflammatory bowel disorders and many causes of infective colitis. Even though the adapted Jalan criteria for toxic megacolon have been reported as the most widely accepted ones, in practice they are not consistently used. In this study only in 68 of 496 (13.7%) TM cases the adapted Jalan criteria were fulfilled. This low acceptance rate may relate to the observation that the original Jalan criteria [12] were based on a retrospective analysis of 55 cases of whom the full clinical course was recorded and a known outcome, whereas clinical practice would benefit more from an accurate decision-making tool derived from well-designed prospective studies. In addition, the current analysis further suggests that the adapted Jalan criteria lack sufficient predictive power for a fatal outcome of toxic megacolon. Future prediction models should pay specific attention which parameters best reflect the two major pathophysiological hallmarks of toxic megacolon: severe dilatation of an inflamed colon and clinical signs of systemic toxicity.

Independent Risk Factors For A Fatal Outcome Of Toxic Megacolon

In this narrative clinical review independent variables for a fatal outcome of toxic megacolon were identified by analyzing detailed case histories from a group of 496 published TM cases. In the analysis of all 496 TM cases CCI score, any antidiarrheal regimen other than loperamide and a complicated course of TM were identified as independent risk factors for a fatal outcome.

Use Of Loperamide And Any Antidiarrheal Regimens In Relation To Outcome

Loperamide was eliminated as an independent variable from the regression model best explaining the data. There was not sufficient evidence found to support the hypothesis that loperamide should be considered as an independent risk factor for a fatal outcome of TM. Although speculative, this may suggest that loperamide in itself is not capable of inflicting the typically required deep tissue or even transmural colonic inflammation that is pivotal for the development of toxic megacolon. This assumption, however, is further strengthened by the observation that misuse and intentional overdose of loperamide in patients without any other underlying disorder is primarily associated with potentially fatal cardiac conduction disorders and arrhythmias whereas gastrointestinal manifestations like toxic megacolon have not been reported despite the widespread use of loperamide since its market introduction in the early 1970s [1-3].

Use of Loperamide As Effect Modifier

Based on their of action, loperamide and other antidiarrheal regimens could also be considered as effect modifying drugs in patients with toxic megacolon, worsening outcome by additional inhibition of GI motility in an already compromised colonic motile system. In this respect it is certainly remarkable that loperamide users had similar complication rates in comparison to TM patients not using loperamide, suggesting that from a clinical point of view no clear effect modification became apparent, even though a facilitating role of loperamide in the pathophysiology of toxic megacolon could not be excluded.

Limitations of The Study

The quality of any review is rather dependent on the quality of the articles underlying the review, including their inherent biases like publication and selection biases. A structured quality assessment of all included articles rated the methodological quality of the majority of the included articles as low, which mainly related to insufficient data regarding some parameters. This may probably hamper the generalizability of the current findings to some extent, even though missing data were included in the statistical analyses. On the other hand, the rather high number of case reports - originating from all continents – that were included in the analysis will certainly contribute to the generalizability of the findings but also underlines the global occurrence of toxic megacolon and that there is a continuing need for identification of clinically sound predictive parameters derived from properly designed studies.

Conclusions

Based on the analysis of all patient data Charlson Comorbidity Index score, an antidiarrheal regimen not containing loperamide and a complicated course of TM were identified as independent variables for a fatal outcome of toxic megacolon. There was not sufficient evidence to support the hypothesis that loperamide should be considered as an independent risk factor for a fatal outcome of TM. The study was limited by incomplete data and low methodological quality of many case reports included in this review.

Acknowledgements

The authors wish to express their gratitude to Mr. Lennert Slobbe for inspiring discussions. Mr. Menno Dreischör is thanked for his valuable statistical advices. Mr. Wichor Bramer is thanked for his help in defining the various search strategies to retrieve the literature.

Declarations

Author contributions

Both authors contributed to the study conception and design. Material preparation and data collection were done by both authors. Principal data analysis was done by Perry JJ van Genderen. The first draft of the manuscript was written by Perry JJ van Genderen and both authors had input in the various revisions of the manuscript.

Both authors read and approved the final manuscript.

Conflict of interest

No disclosure or conflicts of interest relevant to this submission. The work presented here was evaluated by the University of South Wales as part of the Master of Science (Expedition and Wilderness Medicine) thesis of Perry JJ van Genderen. It has not published elsewhere nor under consideration for publication at another journal.

Ethical approval

This submitting narrative clinical review is a retrospective systematic review of findings of only published case reports and case series. Ethical clearance was granted by the University of South Wales.

Funding

Not applicable

References

  1. Regnard C, Twycross R, Mihalyo M, Wilcock A (2011) Loperamide. J Pain Sympt Manage 42: 319-323.
  2. Malinky CA, Lindsley CW, Han C (2021) DARK Classics in chemical Neuroscience: Loperamide. ACS Chem Neurosci 12: 2964-2973.
  3. Miller HP, Panahi L, Tapia D (2003) Loperamide misuse and abuse. J Am Pharm Assoc 57: S45-S50.
  4. Eggleston W, Palmer R, Dube PA (2019) Loperamide toxicity: recommendations for patient monitoring and management. Clin Toxicol 58: 355-359.
  5. Almottowa HA, Alobaidi AE, Assiri MH (2022) Incidence, prevalence, pathogenesis and manifestations of toxic megacolon. Int J Comm Med Pub Health 9: 947-951.
  6. Sheth SG, LaMont JT (1998) Toxic megacolon. Lancet 351: 509-513.
  7. Frazer C, Hussey L, Bemker M (2018) Gastrointestinal motility problems in critically ill patients. Crit Care Nurs Clin N Am 30: 109-121.
  8. Woodhouse E (2016) Toxic megacolon: a review for emergency department clinicians. J Emerg Nurs 42: 481-486.
  9. Bharucha AE, Philips SF (1999) Megacolon: acute, toxic, and chronic. Curr Treatm Opt Gastroenterol 2: 517-523.
  10. Present DH (1993) Toxic megacolon. Med Clin N Am 77: 1129-1148.
  11. Autenrieth DM, Baumgart DC (2012) Toxic megacolon. Inflamm Bowel Dis 18: 584-591.
  12. Jalan KN, Sircus W, Card WI (1969) An experience of ulcerative colitis. I. Toxic dilation in 55 cases. Gastroenterol 57: 68-82.
  13. Brown JW (1979) Toxic megacolon associated with loperamide therapy. JAMA 241: 501-502.
  14. Walley T, Milson D (1990) Loperamide related toxic megacolon in Clostridium difficile colitis. Postgrad Med J 66: 582.
  15. Schneider A, Rünzi M, Peitgen K (2000) Campylobacter jejuni-induced severe colitis--a rare cause of toxic megacolon. Z Gastroenterol 38: 307-309.
  16. Eronen M, Putkonen H, Hallikainen T, Vartiainen H (2003) Lethal gastroenteritis associated with clozapine and loperamide. Am J Psychiatry 160: 2242-2243.
  17. Kato H, Kato H, Nakamura M, Nakamura A (2007) A case of toxic megacolon secondary to Clostridium difficile-associated diarrhea worsened after administration of an antimotility agent and molecular analysis of recovered isolates. J Gastroenterol 42: 507-508.
  18. McGregor A, Brown M, Thway K, Wright SG (2007) Fulminant amoebic colitis following loperamide use. J Travel Med 14: 61-62.
  19. Page MJ, McKenzie JE, Bossuyt PM (2021) Research Methods& Reporting : The PRISMA 2020 statement : an updated guideline for reporting systematic reviews. BMJ 372: n71.
  20. Charlson ME, Pompei P, Ales KI (1987) A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 40: 373-383.
  21. Bazerbachi F, Haffar S, Szarka LA (2017) Secretory diarrhea and hypokalemia associated with colonic pseudo-obstruction: A case study and systematic analysis of the literature. Neurogastroenterol Motil 29: 11.
  22. Strauss RJ, Flint GW, Platt N (1976) The surgical management of toxic dilatation of the colon: a report of 28 cases and review of the literature. Ann Surg 184: 682-688.
  23. Binder SC, Patterson JF, Glotzer DJ (1974) Toxic megacolon in ulcerative colitis. Gastroenterology 66: 909-915.
  24. Ortiz AN, Salado CT, Ramírez MDDLC (2020) Megacolon in inflammatory bowel disease: response to infliximab. Rev Esp Enferm Dig 112: 90-93.
  25. Shetler K, Nieuwenhuis R, Wren SM, Triadafilopoulos G (2001) Decompressive colonoscopy with intracolonic vancomycin administration for the treatment of severe pseudomembranous colitis. Surg Endosc 15: 653-659.
  26. Whorwell PJ, Isaacson P (1981) Toxic dilatation of colon in Crohn’s disease. Lancet 2: 1334-1337.
  27. Present DH, Wolfson D, Gelernt IM (1988) Medical decompression of toxic megacolon by “rolling”. A new technique of decompression with favorable longterm follow-up. J Clin Gastroenterol 10: 485-490.
  28. Norland CC, Kirsner JB (1969) Toxic dilatation of colon (toxic megacolon): etiology, treatment and prognosis in 42 patients. Medicine (Baltimore) 48: 229-250.
  29. Hartong WA, Arvanitakis C, Skibba RM, Klotz AP (1977) Treatment of toxic megacolon. A comparative review of 29 patients. Am J Dig Dis 22: 195-200.
  30. Linssen A, Tytgat GN (1982) Fulminant onset of Crohn’s disease of the colon (CDC). An observation of six cases. Dig Dis Sci 27: 731-736.
  31. Schofield PF, Mandal BK, Ironside AG (1979) Toxic dilatation of the colon in salmonella colitis and inflammatory bowel disease. Br J Surg 66: 5-8.
  32. Snowden JA, Young MJ, McKendrick MW (1994) Dilatation of the colon complicating acute self-limited colitis. Q J Med 87: 55-62.
  33. Sawada K, Egashira A, Ohnishi K (2005) Leukocytapheresis (LCAP) for management of fulminant ulcerative colitis with toxic megacolon. Dig Dis Sci 50: 767-773.
  34. Keeffe EB, Katon RM, Chan TT (1974) Pseudomembranous enterocolitis. Resurgence related to newer antibiotic therapy. West J Med 121: 462- 472.
  35. Ferrante WA, Egger (1965) Toxic Megacolon Complicating Chronic Ulcerative Colitis. South Med J 58: 969-973.
  36. Benchimol EI, Turner D, Mann EH (2008) Toxic megacolon in children with inflammatory bowel disease: clinical and radiographic characteristics. Am J Gastroenterol 103: 1524-1531.
  37. Grieco MB, Bordan DL, Geiss AC, Beil AR (1980) Toxic megacolon complicating Crohn’s colitis. Ann Surg 191: 75-80.
  38. Actis GC, Ottobrelli A, Pera A (1993) Continuously infused cyclosporine at low dose is sufficient to avoid emergency colectomy in acute attacks of ulcerative colitis without the need for high-dose steroids. J Clin Gastroenterol 17: 10-13.
  39. Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 36-1997. A 58-year-old man with recurrent 41 ulcerative colitis, bloody diarrhea, and abdominal distention. N Engl J Med 1997; 337(21): 1532-1540.
  40. Beaugerie L, Ngô Y, Goujard F (1994) Etiology and management of toxic megacolon in patients with human immunodeficiency virus infection. Gastroenterology 107: 858-863.
  41. Freedman SD, Uppot RN, Mino-Kenudson M (2009) Case records of the Massachusetts General Hospital. Case 26-2009. A 34-year-old man with cystic fibrosis with abdominal pain and distention. N Engl J Med 361: 807-816.
  42. Bundred NJ, Dixon JM, Lumsden AB, Gilmour HM, Davies GC (1985) Free perforation in Crohn’s colitis. A ten-year review. Dis Colon Rectum 28: 35-37.
  43. Maynard III EP, Vickery Jr AL (1977) Colitis with Toxic Megacolon in a 47-YearOld Woman. N Engl J Med 297: 322-330.
  44. Williams CL, Robinson DW (1962) Toxic megacolon syndrome of ulcerative colitis. Ann Surg 155: 233-237.
  45. Rowe RJ (1963) Dilatation of the colon (toxic megacolon) in acute fulminating ulcerative colitis. Dis Colon Rectum 6: 23-36.
  46. Silverberg D, Rogers AG (1964) Toxic Megacolon in Ulcerative Colitis. Can Med Assoc J 90: 357-363.
  47. Atkinson GO, Gay BB, Ball TI, Caplan DB (1983) Yersinia enterocolitica colitis in infants: radiographic changes. Radiology 148: 113-116.
  48. Sánchez-Pérez MA, Muñoz-Juárez M, Luque-de EL (2010) Toxic megacolon secondary to Clostridium difficile colitis. Case report. Rev Gastroenterol Mex 75: 103-106.
  49. Wade JW (2014) Toxic megacolon after abdominoplasty: a case report. Ann Plast Surg 72: 170-171.
  50. Dindyal S, Mistry K, Angamuthu N (2014) MELAS syndrome presenting as an acute surgical abdomen. Ann R Coll Surg Engl 96: 101E-103E.
  51. Kwon H, Lee HH, Paik CR (2016) Toxic megacolon and interstitial pneumonia caused by cytomegalovirus infection in a pediatric patient with acute lymphoblastic leukemia receiving chemotherapy. Blood Res 51: 281-285.
  52. Kobayashi R, Matsumoto S, Yoshida Y (2016) Tacrolimus Therapy for Three Patients with Elderly-Onset Ulcerative Colitis: Report of Three Cases. Case Rep Gastroenterol 10: 392-398.
  53. Kwok M, Maurice A, Lisec C, Brown J (2016) Campylobacter colitis: Rare cause of toxic megacolon. Int J Surg Case Rep 27: 141-143.
  54. Quddus A, Martin-Perez B, Schoonyoung H (2015) Toxic megacolon during pregnancy in ulcerative colitis: A case report. Int J Surg Case Rep 11: 83-86.
  55. Inoue K, Wakabayashi N, Fukumoto K (2012) Toxic megacolon associated with cytomegalovirus infection in a patient with steroidnaïve ulcerative colitis. Intern Med 51: 2739-2743.
  56. Hokama A, Ohira T, Kishimoto K (2012) Impending megacolon: small bowel distension as a predictor of toxic megacolon in ulcerative colitis. Intern Emerg Med 7: 487-488.
  57. Sidebotham EL, Sepkowitz K, Price AP (2010) Eradication of cryptosporidium from a defunctionalized colon limb by refeeding stoma effluent. J Pediatr Surg 45: 33-36.
  58. Zamani F, Amiri A, Mohit M (2009) CMV infection in a pregnant woman complicated by toxic megacolon and mesenteric vein thrombosis. Turk J Gastroenterol 20: 234-235.
  59. Candiotto A, Pascoli I, Gritti A (2010) Toxic megacolon complicating a Clostridium difficile infection in a pregnant woman. J Med Microbiol 59: 124-126.
  60. Malkan AD, Pimiento JM, Maloney SP (2010) Unusual manifestations of Clostridium difficile infection. Surg Infect (Larchmt) 11: 333-337.
  61. Earhart MM (2008) The identification and treatment of toxic megacolon secondary to pseudomembranous colitis. Dimens Crit Care Nurs 27: 249-254.
  62. Fitzgerald SC, Conlon S, Leen E, Walsh TN (2009) Collagenous colitis as a possible cause of toxic megacolon. Ir J Med Sci 178: 115-117.
  63. Geenen EV, Sachar DB (2012) Infliximab in Crohn’s diseaseassociated toxic megacolon. J Clin Gastroenterol 46: 321-323.
  64. Mann AP, McCague A, Lalezarzadeh F (2011) Surgical outcome of communityacquired Clostridium difficile colitis presenting as toxic megacolon: case report. Surg Infect (Larchmt) 12: 317-320.
  65. Mai CM, Yeh CC (2011) Toxic megacolon with abdominal compartment syndrome. J Trauma 71: E44.
  66. Bains S, Lloyd GM, Sutton CD (2009) A case of toxic megacolon in a patient with collagenous colitis. Tech Coloproctol 13: 165-166.
  67. Hung CW, Wu WF, Wu CL (2009) Rotavirus gastroenteritis complicated with toxic megacolon. Acta Paediatr 98: 1850-1852.
  68. Nayar DM, Vetrivel S, McElroy J (2006) Toxic megacolon complicating Escherichia coli O157 infection. J Infect 52: 103-106.
  69. Hisada T, Miyamae Y, Mizuide M (2006) Acute thrombocytopenia associated with preexisting ulcerative colitis successfully treated with colectomy. Intern Med 45: 87-91.
  70. Sato H, Suzuki Y, Fukasawa M (2006) De novo multiple endocrine neoplasia type 2B with noncardiogenic pulmonary edema as the presenting symptom. Endocr J 53: 523-529.
  71. White M, Shah N, Lindley K (2006) Pain management in fulminating ulcerative colitis. Paediatr Anaesth 16: 1148-1152.
  72. Tsuchiya T, Watanabe T, Konishi T, Nagawa H (2006) Toxic megacolon associated with Crohn’s disease. Gastrointest Endosc 64: 1012-1013.
  73. Mohite U, Kell J, Haj MA (2007) Invasive aspergillosis localised to the colon presenting as toxic megacolon. Eur J Haematol 78: 270-273.
  74. Stelzmueller I, Goegele H, Biebl M (2007) Clostridium difficile colitis in solid organ transplantation--a single-center experience. Dig Dis Sci 52: 3231-3236.
  75. Ng SC, Kamm MA (2007) Fulminant Crohn’s colitis: when only an antibody will do. Inflamm Bowel Dis 13: 971-974.
  76. Kötter I, Wacker A, Koch S (2007) Anakinra in patients with treatment resistant adult-onset Still’s disease: four case reports with serial cytokine measurements and a review of the literature. Semin Arthritis Rheum 37: 189-197.
  77. Helleman JN, Hendriks J, Deblier I (2007) Mycotic aneurysm of the descending thoracic aorta. Review and case report. Acta Chir Belg 107: 544-547.
  78. Blossom DB, Lewis F, McDonald LC (2008) The changing spectrum of clostridium difficile associated disease: implications for dentistry. J Am Dent Assoc 139: 42-47.
  79. Berman L, Carling T, Fitzgerald TN (2008) Defining surgical therapy for pseudomembranous colitis with toxic megacolon. J Clin Gastroenterol 42: 476-480.
  80. Sinagra E, Orlando A, Renna S (2013) Is really megacolon a contraindication to infliximab in Crohn’s disease? Acta Gastroenterol Belg 76: 442-444.
  81. Deleanu B, Prejbeanu R, Vermesan D (2014) Acute abdominal complications following hip surgery. Chirurgia (Bucur) 109: 218-222.
  82. Toro A, Cappello G, Mannino M, Di Carlo I (2014) Could the complications of megacolon be avoided by monitoring the risk patients? Chirurgia (Bucur) 109: 550-554.
  83. Narabayashi K, Inoue T, Sakanaka T (2014) Oral tacrolimus for megacolon in patients with severe ulcerative colitis. Intern Med 53: 1755-1758.
  84. Jambet S, Guiu B, Olive-Abergel P (2012) Psychiatric drug-induced fatal abdominal compartment syndrome. Am J Emerg Med 30: 513. e5-7.
  85. Castillo A, López J, Panadero E (2012) Conservative surgical treatment for toxic megacolon due to Clostridium difficile infection in a transplanted pediatric patient. Transpl Infect Dis 14: 34-37.
  86. Laurent S, Reenaers C, Detroz B (2005) A patient who survived total colonic ulcerative colitis surinfected by cytomegalovirus complicated by toxic megacolon and disseminated intravascular coagulation. Acta Gastroenterol Belg 68: 276-279.
  87. Yada S, Matsumoto T, Kudo T (2005) Colonic obstruction due to giant inflammatory polyposis in a patient with ulcerative colitis. J Gastroenterol 40: 536-539.
  88. Stelzmueller I, Dunst KM, Hengster P (2005) A cluster of rotavirus enteritis in adult transplant recipients. Transpl Int 18: 470-474.
  89. Haraguchi M, Komuta K, Furui J, Kanematsu T (2004) Colostomy with vancomycin administration as an effective treatment for toxic megacolon associated with fulminant pseudomembranous colitis: a case report. Asian J Surg 27: 236-237.
  90. Carbone JV (1976) Editorial: Toxic megacolon. West J Med 124: 136137.
  91. Mendonca HL, Vieta JO, Korelitz BI (1977) Perforation of the colon in unsuspected amebic colitis: report of two cases. Dis Colon Rectum 20: 149-153.
  92. Tochen ML, Campbell JR (1977) Colitis in children with the hemolyticuremic syndrome. J Pediatr Surg 12: 213-219.
  93. Leventhal A, Gimmon Z (1978) Toxic idiopathic megacolon: fatal outcome in a mentally retarded adolescent. Dis Colon Rectum 21: 383-386.
  94. Rimmer D, Lander M, Shepherd R (1980) Antibiotic-associated pseudomembranous colitis with toxic megacolon: two case reports in children. Aust Paediatr J 16: 287-289.
  95. Richardson JH, Buisseret PD (1981) Acquired megacolon associated with acute lead poisoning. Br Med J (Clin Res Ed) 283: 104-105.
  96. Wig JD, Talwar BL, Bushnurmath SR (1981) Toxic dilatation complicating fulminant amoebic colitis. Br J Surg 68: 135-136.
  97. Bolton RP, Read AE (1982) Clostridium difficile in toxic megacolon complicating acute inflammatory bowel disease. Br Med J (Clin Res Ed) 285: 475- 476.
  98. Cone JB, Wetzel W (1982) Toxic megacolon secondary to pseudomembranous colitis. Dis Colon Rectum 25: 478-482.
  99. Brawner SD, Tishler JM, Rubin E, Luna RF (1983) Computerized tomographic demonstration of toxic megacolon: report of a case. Comput Radiol 7: 279-281.
  100. Templeton JL (1983) Toxic megacolon complicating pseudomembranous colitis. Br J Surg 70: 48.
  101. Reddy KR, Thomas E (1983) Toxic megacolon after proctosigmoidoscopy in ulcerative colitis. South Med J 76: 1072-1073.
  102. Cooksey G, Gunn A, Wotherspoon WC (1985) Surgery for acute ulcerative colitis and toxic megacolon during pregnancy. Br J Surg 72: 547.
  103. González A, Vargas V, Guarner L (1985) Toxic megacolon in typhoid fever. Arch Intern Med 145: 2120.
  104. Anderson JB, Tanner AH, Brodribb AJ (1986) Toxic megacolon due to Campylobacter colitis. Int J Colorectal Dis 1: 58-59.
  105. Stuart RC, Leahy AL, Cafferkey MT, Stephens RB (1986) Yersinia enterocolitica infection and toxic megacolon. Br J Surg 73: 590.
  106. Pockros PJ, Weiss JB, Strum WB (1986) Toxic megacolon complicating Campylobacter enterocolitis. J Clin Gastroenterol 8: 318-319.
  107. Connolly GM, Gazzard BG (1987) Toxic megacolon in cryptosporidiosis. Postgrad Med J 63: 1103-1104.
  108. Biggs BA, Crowe SM, Lucas CR (1987) AIDS related Kaposi’s sarcoma presenting as ulcerative colitis and complicated by toxic megacolon. Gut 28: 1302-1306.
  109. Wilson SE, Robinson G, Williams RA (1989) Acquired immune deficiency syndrome (AIDS). Indications for abdominal surgery, pathology, and outcome. Ann Surg 210: 428-434.
  110. Upadhyay AK, Neely JA (1989) Toxic megacolon and perforation caused by Shigella. Br J Surg 76: 1217.
  111. Riedler L, Wohlgenannt D, Stoss F (1989) Endoscopic decompression in “toxic megacolon”. Surg Endosc 3: 51-53.
  112. Gill KP, Feeley TM, Keane FB (1989) Toxic megacolon and perforation caused by Salmonella. Br J Surg 76: 796.
  113. Merrin P, Lancaster Smith MJ (1989) Leukaemoid reaction and ulcerative colitis. Gut 30: 1154-1155.
  114. Wilson AP, Ridgway GL, Sarner M (1990) Toxic dilatation of the colon in shigellosis. BMJ 301: 1325-1326.
  115. Prats E, Banzo J, Nerin J (1991) Toxic megacolon detected by Tc-99m HMPAO mixed leukocyte scan. Clin Nucl Med 16: 365-366.
  116. Velanovich V, LaPorta AJ, Garrett WL (1992) Pseudomembranous colitis leading to toxic megacolon associated with antineoplastic chemotherapy. Report of a case and review of the literature. Dis Colon Rectum 35: 369-372.
  117. Panos MZ, Wood MJ, Asquith P (1993) Toxic megacolon: the kneeelbow position relieves bowel distension. Gut 34: 1726-1727.
  118. Vyas SK, Law NN, Hill S, Loehry CA (1993) Toxic megacolon with late perforation in Campylobacter colitis--a cautionary tale. Postgrad Med J 69: 322-324.
  119. Wodziński MA, Snowden JA, Reilly JT (1994) Toxic megacolon complicating chemotherapy for acute myeloid leukaemia. Postgrad Med J 70: 921-923.
  120. Kotanagi H, Fukuoka T, Shibata Y (1994) A case of toxic megacolon in ulcerative colitis associated with cytomegalovirus infection. J Gastroenterol 29: 501-505.
  121. Sankaran SK, Veitch PC (1995) Crohn’s disease presenting as toxic megacolon in an elderly man. Aust N Z J Med 25: 539-540.
  122. Soin B, Thyveetil MD, Desai A (1998) Sub-total colectomy for perforated toxic megacolon in pregnancy. J Obstet Gynaecol 18: 601.
  123. Igarashi C, Hori T, Yoshida M (1997) Acute fulminant ulcerative colitis with toxic megacolon. Acta Paediatr Jpn 39: 237-240.
  124. Horie Y, Chiba M, Miura K (1997) Crohn’s disease associated with renal amyloidosis successfully treated with an elemental diet. J Gastroenterol 32: 663-667.
  125. Edwards DP, Saleemi MA, Grundy C, Chisholm EM (1997) Clostridium difficile toxic megacolon following splenectomy. J R Army Med Corps 143: 167-168.
  126. Kuroki K, Masuda A, Uehara H, Kuroki A (1998) A new treatment for toxic megacolon. Lancet 352: 782.
  127. Kanaji S, Okuma K, Tokumitsu Y (1998) Hemophagocytic syndrome associated with fulminant ulcerative colitis and presumed acute pancreatitis. Am J Gastroenterol 93: 1956-1959.
  128. Jennings LJ, Hanumadass M (1998) Silver sulfadiazine induced Clostridium difficile toxic megacolon in a burn patient: case report. Burns 24: 676- 679.
  129. Klauber E, Briski LE, Khatib R (1998) Cytomegalovirus colitis in the immunocompetent host: an overview. Scand J Infect Dis 30: 559-564.
  130. Jackson TL, Young RL, Thompson JS, McCashland TM (1999) Toxic megacolon associated with Campylobacter jejuni colitis. Am J Gastroenterol 94: 280-282.
  131. Arai H, Hanai H, Furuta T (1999) A patient who survived total colonic type ulcerative colitis complicated by toxic megacolon, disseminated intravascular 52 coagulation, methicillin-resistant Staphylococcus aureus infection and bilateral femoral phlebothrombosis. J Gastroenterol 34: 395-399.
  132. Ciftci AO, Karnak I, Senocak ME (1999) Spectrum of complicated intestinal amebiasis through resected specimens: incidence and outcome. J Pediatr Surg 34: 1369-1373.
  133. Sanz AM, Codina JG, Rodriguez MP (2000) Toxic megacolon: a rare presentation of primary lymphoma of the colon. Eur J Gastroenterol Hepatol 12: 583-586.
  134. García-Osogobio S, Takahashi T, Gamboa-Domínguez A (2000) Toxic pseudomembranous colitis in a patient with ulcerative colitis. Inflamm Bowel Dis 6: 188-190.
  135. Irefin SA, Farid IS, Senagore AJ (2000) Urgent colectomy in a patient with membranous tracheal disruption after severe vomiting. Anesth Analg 91: 1300-1302.
  136. Sharma RA, Steward WP, West KP (2001) Hemingway D. Toxic megacolon: remember cytomegalovirus. Hosp Med 62: 178-179.
  137. Backer AID, Overbeke LNV, Mortelé KJ (2001) Inflammatory pseudopolyposis in a patient with toxic megacolon due to pseudomembranous colitis. JBR-BTR 84: 201.
  138. Chaudhuri A, Bekdash BA (2002) Toxic megacolon due to Salmonella: a case report and review of the literature. Int J Colorectal Dis 17: 275279.
  139. Greenstein AJ, Greenstein RJ, Sachar DB (1980) Toxic dilatation in amebic colitis: successful treatment without colectomy. Am J Surg 139: 456-458.
  140. Bhangale N, Doctor S, Desai D, Abraham P (2022) Clostridioides difficile infection presenting as ileus. Australasian Med J 15: 361-364.
  141. Pennington CR, Bickerstaff KI, Lyall MH (1980) Salmonella infection with colitis. J Infect 2: 181-183.
  142. Samanci NS, Cebeci E, Ergen A (2016) A Case of Ulcerative Colitis Accompanied by Hemolytic Uremic Syndrome. Turkish Nephrology Dialysis Transplantation 25: 83-85.
  143. Schwörer H, Bohn M, Waezsada SY (2001) Successful treatment of megacolon associated with colitis with a nitric oxide synthase inhibitor. Am J Gastroenterol 96: 2273-2274.
  144. Siado S, Jiménez HC, Montalvo CMM (2018) Megacolon toxic of idiophatic origin: Case report. Revista colombiana de Gastroenterología 33: 166-171.
  145. Hayes-Lattin BM, Curtin PT, Fleming WH (2002) Toxic megacolon: a lifethreatening complication of high-dose therapy and autologous stem cell transplantation among patients with AL amyloidosis. Bone Marrow Transplant 30: 279-285.
  146. Ooi BS, Remzi FH, Fazio VW (2003) Turnbull-Blowhole colostomy for toxic ulcerative colitis in pregnancy: report of two cases. Dis Colon Rectum 46: 111-115.
  147. Dobson G, Hickey C, Trinder J (2003) Clostridium difficile colitis causing toxic megacolon, severe sepsis and multiple organ dysfunction syndrome. Intensive Care Med 29: 1030.
  148. Bello CS, Al-Barki AA, El-Awad ME, Patel RV (2003) Shigella flexneri bacteremia in a child. Saudi Med J 24: 403-405.
  149. Pascu M, Müller AR, Wiedenmann B, Dignass AU (2003) Rescue therapy with tacrolimus in a patient with toxic megacolon. Int J Colorectal Dis 18: 271-275.
  150. Adorian C, Khoury G, Tawil A, Sharara A (2003) Behçet’s disease complicated by toxic megacolon. Dig Dis Sci 48: 2366-2368.
  151. Maconi G, Sampietro GM, Ardizzone S (2004) Ultrasonographic detection of toxic megacolon in inflammatory bowel diseases. Dig Dis Sci 49: 138-142.
  152. Williams EV, Drew PJ, Gaffney C (2001) Pancolitis associated with docetaxel: a rare cause of megacolon. Breast 10: 346-347.
  153. Garate ADV, Rocha TB, Almeida LR (2021) Treatment of acute severe ulcerative colitis using accelerated infliximab regimen based on infliximab trough level: A case report. World J Clin Cases 9: 32193226.
  154. Khan AB, Al Mussallam B, Alshakweer W, Al Badri R (2010) Cytomegalovirus associated toxic megacolon in an immunocompetent host. A case report. Eur Surg Acta Chir Austriaca 42: 53-57.
  155. Suciu N, Benedek Z, Sorlea S, Coroş MF (2019) Toxic Megacolon – the Complication of an Infection with Clostridium difficile after an Odontogenic Abscess. Case Presentation. J Interdisc Med 4: 150-154.
  156. Arsan C, Gonzalez OY, Gillespie TL (2016) A Fatal Case of Clostridium difficile Enterocolitis following Diverting Loop Ileostomy Reversal. Surg Infect Case Rep 1: 16-18.
  157. Kressner MS, Williams SE, Biempica L, Das KM (1982) Salmonellosis complicating ulcerative colitis. Treatment with trimethoprimsulfamethoxazole. JAMA 248: 584-585.
  158. Blackwell V, Travis S (2011) Toxic dilatation of the colon. Medicine (GBR) 39: 105-107.
  159. Hassan S, Alam SN, Syed NU, Ismail M (2022) Campylobacter jejuni pancolitis complicated by toxic megacolon in an immunocompetent host. BMJ Case Rep 15: e249801.
  160. Biebl M, Stelzmüller I, Nachbaur D (2006) Fatal Clostridium difficileassociated toxic megacolon following unrelated stem-cell transplantation. Eur Surg Acta Chir Austriaca 38: 217-221.
  161. Glotzer DJ, Yuan RH, Patterson JF (1964) Ulcerative Colitis Complicated by Toxic Megacolon, Polyserositis and Hemorrhagic Leukoencephalitis with Recovery. Ann Surg 159: 445-450.
  162. Belin RP, Walder AI, Griffen WO (1966) Chronic ulcerative colitis complicated by toxic megacolon. Arch Surg 93: 631-633.
  163. Holzbach RT (1969) Toxic megacolon in pregnancy. Am J Dig Dis 14: 908-910.
  164. Mir-Madjlessi SH, Farmer RG (1972) Behçet’s syndrome, Crohn’s disease and toxic megacolon. Cleve Clin Q 39: 49-55.
  165. Axelrod M, Allon O, Felton M, Goldfinger M (1975) Clindamycinassociated colitis with toxic megacolon. JAMA 233: 419-420.
  166. Shin JL, Gardiner GW, Deitel W, Kandel G (2004) Does whipworm increase the pathogenicity of Campylobacter jejuni? A clinical correlate of an experimental observation. Can J Gastroenterol 18: 175-177.
  167. Moulin V, Dellon P, Laurent O (2011) Toxic megacolon in patients with severe acute colitis: computed tomographic features. Clin Imaging 35: 431-436.
  168. Sayedy L, Kothari D, Richards RJ (2010) Toxic megacolon associated Clostridium difficile colitis. World J Gastrointest Endosc 2: 293-297.
  169. Arumilli B, Koneru P, Fayyaz I (2010) Toxic megacolon from hypervirulent Clostridium difficile infection (ribotype 027) following elective total knee 57 replacement: an emerging challenge in modern health care. BMJ Case Rep 2010: bcr06.2009.2017.
  170. Patel A, Gossett JJ, Benton T (2012) Fulminant Clostridium difficile toxic megacolon in a pediatric heart transplant recipient. Pediatr Transplant 16: E30-34.
  171. Umehara Y, Kudo M, Kawasaki M (2010) Endoscopic findings of intestinal Behçet’s disease complicated with toxic megacolon. Endoscopy 2: E173-173.
  172. McGuire E, Tiberi S, Ciesielczuk H, Melzer M (2018) Shigellosis and toxic megacolon secondary to Shigella flexneri serotype 3a: The challenges of laboratory diagnosis. Int J Infect Dis 70: 104-106.
  173. Wilke K, Helbig S, de With K (2018) Serum vancomycin concentrations after oral and intracolonic vancomycin administration in a patient with colonic discontinuity and severe Clostridium difficile infection. Am J Health Syst Pharm 75: e189-e193.
  174. Curraize CD, Rousseau C, Corvec S (2018) Variable spectrum of disease and risk factors of peripartum Clostridium difficile infection: report of 14 cases from French hospitals and literature review. Eur J Clin Microbiol Infect Dis 37: 2293-2299.
  175. Ong S, Mohaidin N (2018) Imaging features of toxic megacolon. BMJ Case Rep 2018: bcr2018227121.
  176. Oguri N, Sakuraba A, Morikubo H (2019) Community-acquired fulminant colitis caused by binary toxin-producing Clostridium difficile in Japan. Clin J Gastroenterol 12: 325-329.
  177. Yu S, Abdelkarim A, Nawras A (2016) Fecal Transplant for Treatment of Toxic Megacolon Associated With Clostridium Difficile Colitis in a Patient With Duchenne Muscular Dystrophy. Am J Ther 23: 609-613.
  178. Gurrado A, Isernia RM, Luca AD (2018) Congenital diaphragmatic disease: An unusual presentation in adulthood. Case report. Int J Surg Case Rep 48: 34-37.
  179. Luthe SK, Sato R (2017) Cecal Perforation Associated with Clostridium difficile Infection: A Case Report. J Emerg Med 52: 554-556.
  180. Mostafazadeh B, Farzaneh E, Paeezi M, Nikkhah F (2017) Toxic megacolon as a rare complication following atropine therapy due to organophosphate poisoning: A case report. Med Leg J 85: 221-223.
  181. Peters S, Wise M, Buckley B (2017) An unexpected complication following uterine artery embolisation. BMJ Case Rep 2017: bcr2016217238.
  182. Zwischenberger BA, Vargas HD (2014) Toxic colitis with megacolon in a patient with malrotation. Am Surg 80: E356-368.
  183. Vaiphei K, Trehan A, Sachdeva M, Malhotra P (2015) A young leukemic patient with unusual catastrophic intestinal complication. Indian J Pathol Microbiol 58: 48-54.
  184. Fernandes LG, Ferreira NR, Cardiga R, Póvoa P (2015) Severe hypercalcaemia and colon ischaemia: dehydration as an unusual cause? BMJ Case Rep 2015: bcr2014208809.
  185. Costello SP, Chung A, Andrews JM, Fraser RJ (2015) Fecal Microbiota Transplant for Clostridium difficile Colitis-Induced Toxic Megacolon. Am J Gastroenterol 110: 775-777.
  186. Orabona R, Valcamonico A, Salemme M, Manenti S, Tiberio G, et al. (2015) Fulminant ulcerative colitis in a healthy pregnant woman. World J Gastroenterol 21: 6060-6064.
  187. Tariq S, Farooq A, Ali I, Wijesinghe H (2015) Toxic colonoscopy-how investigating active inflammatory bowel disease can lead to the serious complication of toxic megacolon. BMJ Case Rep 2015: bcr2015209769.
  188. Popa D, Laszlo M, Ciobanu L (2015) Self-Administered Home Series Fecal “Minitransplants” for Recurrent Clostridium difficile Infection on a Rectal Remnant. J Gastrointestin Liver Dis 24: 531-533.
  189. Koizumi Y, Kachi A, Tsuboi K (2019) Clostridioides difficile-related toxic megacolon after Cryptococcus neoformans cellulitis: A complex of two rare infections in an immunocompromised host. J Infect Chemother 25: 379-384.
  190. Brunelli R, Perrone S, Perrone G (2019) New-onset ulcerative colitis in pregnancy associated to toxic megacolon and sudden fetal decompensation: Case report and literature review. J Obstet Gynaecol Res 45: 1215-1221.
  191. Luciano E, Macek S, Pacheco F, Solh W (2023) Synchronous colon cancer presenting as toxic megacolon in a patient with ulcerative colitis: A case report. Int J Surg Case Rep 112: 108984.
  192. Rajack F, Medford S, Naab T (2023) Clostridioides difficile infection leading to fulminant colitis with toxic megacolon. Autops Case Rep 13: e2023457.
  193. Santucci W, Noori J, Yang L (2024) Secukinumab induced colitis resulting in toxic megacolon. ANZ J Surg 94: 472-473.
  194. Alaoui OM, Douqchi B, Bella I (2024) Severe Sepsis Secondary to Toxic Megacolon Revealing an Inflammatory Bowel Disease. Cureus 16: e51459.
  195. Rehman R, Camhi S, Shapiro J (2024) An Adolescent with Undiagnosed Ulcerative Colitis Presenting with Toxic Megacolon and Cavitary Pulmonary Nodules. R I Med J (2013) 107: 21-22.
  196. Kwok WC, Tam T, Lam D (2018) First reported case of afatinibassociated toxic megacolon. Respirol Case Rep 6: e00360.
  197. Yusof S, Zhao Y, Quah J (2020) Amoebic toxic megacolon with polyhelminthic coinfection: Case presentation and review of intestinal polyparasitic infections. Int J Surg Case Rep 71: 151-154.
  198. Cho JH, Choi JH (2020) Cytomegalovirus ileo-pancolitis presenting as toxic megacolon in an immunocompetent patient: A case report. World J Clin Cases 8: 552-559.
  199. Bandaru SK (2022) Toxic Megacolon Due to Fulminant Clostridioides difficile Infection. N Engl J Med 387: 1309.
  200. Jang E, Chung JH (2021) Communicating multiple tubular enteric duplication with toxic megacolon in an infant: A case report. Medicine (Baltimore) 100: e25772.
  201. Irabien M, Arreba P, Zárate JOD (2021) Ustekinumab treatment for toxic megacolon in severe colonic Crohn’s disease. Rev Esp Enferm Dig 113: 189-192.
  202. Apostolov R, Nicolaides S, Vasudevan A (2020) Megacolon Complicating Ulcerative Colitis and Clostridiodes Infection. Am J Med Sci 360: e1-e2.
  203. Belvedere S, Foster JD, Soucisse ML (2020) Toxic megacolon due to Salmonella acute infectious colitis requiring total colectomy following loop ileostomy closure. ANZ J Surg 90: E200-E201.
  204. French B, Mandell K, Martinez R (2018) Diagnosis and Treatment of Invasive Aspergillus fumigatus Wound Infection Following Subtotal Colectomy for Perforated Toxic Megacolon in an Immunosuppressed Patient. Wounds 30: E102-E104.
  205. Clark C, Murray EV (2020) Campylobacter colitis leads to toxic megacolon and multiple organ failure. BMJ Case Rep 13: e233373.
  206. Chang SH, Sun HY, Shun CT, Wei SC (2020) A case with cytomegalovirus colitis and toxic megacolon initially diagnosed as Crohn’s disease. J Formos Med Assoc 119: 1442-1444.
  207. Aksakal G, Ng S, An V (2019) An unusual case of caecal perforation following ileostomy reversal. BMJ Case Rep 12: e229961.
  208. Ali MSM (2023) Toxic Megacolon: A Conundrum. PriMera Sci Surg Res Pract 2: 12-14.
  209. Kramer P, Wittenberg J (1981) Colonic gas distribution in toxic megacolon. Gastroenterology 80: 433-437.
  210. Burke GW, Wilson ME, Mehrez IO (1988) Absence of diarrhea in toxic megacolon complicating Clostridium difficile pseudomembranous colitis. Am J Gastroenterol 83: 304-307.
  211. Chartrand-Lefebvre C, Heppell J, Potvin C (1990) Outcome of Toxic Megacolon During Pregnancy. Can J Gastroenterol 90: 230-234.
  212. Edwards DP, Saleemi MA, Grundy C, Chisholm EM (1997) Clostridium difficile toxic megacolon following splenectomy. J R Army Med Corps 143: 167-168.
  213. Carmeliet T, Zachée P, Dits H (2019) Acute primary abdominal compartment syndrome due to Clostridium difficile induced toxic megacolon: a case report and review of the literature. Anaesthesiol Intensive Ther 51: 273-282.
  214. Bhargava A, Mahakalkar C, Kshirsagar S, Yachmaneni A (2024) Toxic Megacolon: A Sequelae of Clostridioides difficile Infection in a Case of Necrotizing Fasciitis. Cureus 16: e53034.
  215. Berkowitz D (1967) Asymptomatic megacolon persisting six years after toxic dilatation of the colon. Report of a case. Am J Dig Dis 12: 1062-1066.
  216. Babu TA, Ananthakrishnan S, Jayakumar P, Kullu P (2014) Unusual complication of toxic megacolon in typhoid colitis. Indian J Pediatr 81: 504-506.
  217. Atherton LD, Leib ES, Kaye MD (1984) Toxic megacolon associated with methotrexate therapy. Gastroenterol 86: 1583-1588.
  218. Antonopoulos P, Almyroudi M, Kolonia V (2013) Toxic Megacolon and Acute Ischemia of the Colon due to Sigmoid Stenosis Related to Diverticulitis. Case Rep Gastroenterol 7: 409-413.
  219. Draganescu M, Baroiu L, Iancu A (2017) Clostridium Difficile Infection Complicated By Toxic Megacolon In Immunocompetent Patient. ARS Medica Tomitana 1: 39-46.
  220. Dumitru IM, Dumitru E, Rugina S, Tuta LA (2017) Toxic Megacolon - A Three Case Presentation. J Crit Care Med (Targu Mures) 3: 39-44.
  221. Tan CB, Rajan D, Shah M (2012) Toxic megacolon from fulminant Clostridium difficile infection induced by topical silver sulphadiazine. BMJ Case Rep 2012: bcr2012006460.
  222. Wruble LD, Duckworth JK, Duke DD, Rothschild JA (1966) Toxic dilatation of the colon in a case of amebiasis. N Engl J Med 275: 926928.
  223. Weledji EP, Takere MM, Fon P (2022) A case of a toxic megacolon and acute appendicitis in HIV/ AIDS. Austin J Clin Case Rep 9: 1256.
  224. Verma S, Chandran VA, Gulati A (2021) Toxic Megacolon as a Complication of Crohns Disease: A Case Report. J Med Sci Clin Res 09: 10-15.
  225. Sugiyama M, Kusumoto E, Ota M (2016) Induction of potentially lethal hypermagnesemia, ischemic colitis, and toxic megacolon by a preoperative mechanical bowel preparation: report of a case. Surg Case Rep 2: 18.
  226. Spinale RC, Meeker JF (1986) Toxic megacolon with perforation in fulminant Crohn’s disease: report of a case and review of the literature. J Am Osteopath Assoc 86: 298-300.
  227. Sánchez DS, Calixto EA, Navarrete J (2023) Toxic Megacolon in a Patient with Clostridium Difficile Infection with Diverticulitis. Case Report. Int J Med Sci Clin Res Studies 03: 145-146.
  228. Alvarado L, Bahmad H, Mejia O (2021) Rectal endometriosis presenting as toxic megacolon. Autops Case Rep 11: e2021319.
  229. Sachs AN (2017) Toxic Megacolon. In: Dangleben DA, Madbak FG, editors. Acute Care General Surgery: Springer International Publishing AG; 2017. p147-152.
  230. Nozari N (2017) Perforated Toxic Megacolon: Fatal Presentation of Ulcerative Colitis. Int J Innovative Studies Med Sci 1: 1.
  231. Mogan GR, Sachar DB, Bauer J, Salky B, Janowitz HD (1980) Toxic megacolon in ulcerative colitis complicated by pneumomediastinum: report of two cases. Gastroenterology 79: 559-562.
  232. Maksić MM, Đokić AZ, Zdravković ND (2022) Toxic megacolon after irrational antibiotic treatment of pregnat patient with Covid 19: Case report. Hosp Pharmacol - Int Multidiscipl J 9: 1189-1195.
  233. Kerstens J, Diebels I, Gheldere CD, Vanclooster P (2016) Blowhole Colostomy for Clostridium difficile-Associated Toxic Megacolon. Case Rep Surg 2016: 5909248.
  234. Hefaiedh R, Cheikh M, Ennaifer R (2013) Toxic megacolon complicating a first course of Crohn’s disease: about two cases. Clin Pract 3: e24.
  235. Hayashi H, Tajima JY, Yokoi R (2023) Patient with suspected severe acute respiratory syndrome coronavirus 2 infection with successful emergency surgery for ulcerative colitis-associated toxic megacolon. Surg Case Rep 9: 32.
  236. Fukui S, Hojo A, Sawada U, Kura Y (2023) Toxic megacolon in Clostridium difficile colitis. ID Cases 33: e01858.

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