Medication Summary

Medications that may aid in controlling or treating toxic megacolon include corticosteroids, immunosuppressants, and/or immunomodulators. Antibiotics may be administered to prevent or treat infection.

Note that certain agents may exacerbate toxic megacolon, such as opioids, antidepressants, nonsteroidal anti-inflammatories, antidiarrheals, and anticholinergics.

Class Summary

Corticosteroids have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids also modify the body's immune response to diverse stimuli.

Hydrocortisone (Solu-Cortef, Cortef)

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Hydrocortisone decreases inflammation by suppressing the migration of polymorphonuclear leukocytes and reversing increased capillary permeability.

Methylprednisolone (A-Methapred, Depo-Medrol, Medrol, Solu-Medrol)

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Methylprednisolone decreases inflammation by suppressing the migration of polymorphonuclear leukocytes and reversing increased capillary permeability.

Class Summary

Immunosuppressant agents inhibit immune reactions resulting from diverse stimuli.

Cyclosporine (Neoral, Gengraf, Sandimmune)

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Cyclosporine is used in acute, severe ulcerative colitis that is refractory to IV corticosteroids. An 11-amino acid cyclic peptide and a natural product of fungi, it acts on T-cell replication and activity.

Cyclosporine is a specific modulator of T-cell function and an agent that depresses cell-mediated immune responses by inhibiting helper T-cell function. Preferential and reversible inhibition of T lymphocytes in the G0 or G1 phase of the cell cycle is suggested.

Cyclosporine binds to cyclophilin, an intracellular protein, which, in turn, prevents formation of interleukin-2 and the subsequent recruitment of activated T cells.

Cyclosporine has about 30% bioavailability, but there is marked interindividual variability. This agent specifically inhibits T-lymphocyte function, with minimal activity against B cells. Maximum suppression of T-lymphocyte proliferation requires that the drug be present during the first 24 hours of antigenic exposure.

Cyclosporine suppresses some humoral immunity and, to a greater extent, cell-mediated immune reactions (eg, delayed hypersensitivity, allograft rejection, experimental allergic encephalomyelitis, graft-vs-host disease) for a variety of organs.

Class Summary

Immunomodulatory agents regulate immune reactions that are responsible for inflammation.

Infliximab (Remicade)

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Infliximab neutralizes the cytokine TNF-alpha and inhibits its binding to the TNF-alpha receptor. Mix in 250 mL normal saline for infusion over 2 hours. It must be used with a low-protein-binding filter (1.2 µm or less).

Questions

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Media Gallery

Toxic Megacolon. A 22-year-old man presented with abdominal pain, passage of blood and mucus per rectum, abdominal distention, fever, and disorientation. Findings from sigmoidoscopy confirmed ulcerative colitis. Abdominal radiographs obtained 2 days apart show mucosal edema and worsening of the distention in the transverse colon. The patient's clinical condition deteriorated over the next 36 hours despite steroid and antibiotic therapy, and the patient had to undergo a total colectomy and ileostomy.
Toxic Megacolon. A 72-year-old woman presented with vomiting and abdominal distention. The supine (right) and erect (left) plain abdominal radiographs show gross dilatation of the colon with multiple air-fluid levels. On further questioning, the patient revealed that she was taking diuretics for hypertension. Blood biochemical tests revealed markedly lowered potassium levels. After potassium replacement therapy, the patient's pseudo-obstruction completely resolved.
Toxic Megacolon. Gross pathology specimen from a case of pseudomembranous colitis demonstrating characteristic yellowish plaques.
Toxic Megacolon. Computed tomography scan from a patient with pseudomembranous colitis demonstrating the classic accordion sign.
Toxic Megacolon. Plain abdominal radiograph from a patient with known ulcerative colitis who presented with an acute exacerbation of his symptoms. This image shows thumbprinting in the region of the splenic flexure of the colon.
Toxic Megacolon. Increased postrectal space is a known feature of ulcerative colitis.
Toxic Megacolon. A 45-year-old woman presented with acute pain and colitis of uncertain etiology. The radiograph shows an increase in gaseous distention of the distal transverse colon, now measuring up to 80 mm in diameter (it was 60 mm 2 days previous). The transverse colon and sigmoid colon are both featureless, consistent with severe colitis. There is fecal loading in the right side of colon. No evidence of free gas or pneumatosis intestinalis is noted. The appearance is concerning for toxic megacolon. Courtesy of Craig Hacking, MBBS, Associate Professor, Royal Brisbane and Women’s Hospital (Radiopaedia.org, rID: 79194).

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Author

Fadi Alali, MD Fellow, Department of Gastroenterology, Ascension Providence Hospital

Disclosure: Nothing to disclose.

Coauthor(s)

Michael H Piper, MD Clinical Assistant Professor, Department of Internal Medicine, Division of Gastroenterology, Wayne State University School of Medicine; Consulting Staff, Digestive Health Associates, PLC

Michael H Piper, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Gastroenterology, American College of Physicians, Michigan State Medical Society

Disclosure: Nothing to disclose.

Chief Editor

Burt Cagir, MD, FACS Associate Regional Dean and Professor of Surgery, Geisinger Commonwealth School of Medicine; Director, General Surgery Residency Program, Executive Director, Donald Guthrie Foundation for Research and Education, Guthrie Robert Packer Hospital; Medical Director, Guthrie/RPH Skills and Simulation Lab; Associate in Surgery, Guthrie Robert Packer Hospital and Corning Hospital

Burt Cagir, MD, FACS is a member of the following medical societies: American College of Surgeons, Association of Program Directors in Surgery, Society for Surgery of the Alimentary Tract

Disclosure: Nothing to disclose.

Additional Contributors

Clifford Y Ko, MD, MS Professor, Department of Surgery, University of California, Los Angeles, David Geffen School of Medicine

Clifford Y Ko, MD, MS is a member of the following medical societies: American College of Surgeons, American Medical Association, American Society of Colon and Rectal Surgeons, Association for Academic Surgery, California Medical Association, New York Academy of Sciences

Disclosure: Nothing to disclose.

George Y Wu, MD, PhD Professor, Department of Medicine, Director, Hepatology Section, Herman Lopata Chair in Hepatitis Research, University of Connecticut School of Medicine

George Y Wu, MD, PhD is a member of the following medical societies: American Association for the Study of Liver Diseases, American Gastroenterological Association, American Medical Association, American Society for Clinical Investigation, Association of American Physicians

Disclosure: Nothing to disclose.

Lisa M Rossi, MD Fellow, Department of Gastroenterology-Hepatology, University of Connecticut School of Medicine

Disclosure: Nothing to disclose.

Deepika Devuni, MD Assistant Professor of Gastroenterology, University of Massachusetts Medical School

Deepika Devuni, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American Association of Physicians of Indian Origin, American College of Gastroenterology, American Gastroenterological Association, American Society of Transplantation

Disclosure: SIte PI for: Sequana Medical .

Brian Lin New York College of Osteopathic Medicine

Brian Lin is a member of the following medical societies: American College of Osteopathic Family Physicians, American College of Osteopathic Internists, American College of Physicians, American Medical Student Association/Foundation, Asian Pacific American Medical Student Association, Student Osteopathic Medical Association

Disclosure: Nothing to disclose.

Acknowledgements

Douglas M Heuman, MD, FACP, FACG, AGAF Chief of GI, Hepatology, and Nutrition at North Shore University Hospital/Long Island Jewish Medical Center; Professor, Department of Medicine, Hofstra North Shore-LIJ School of Medicine

Douglas M Heuman, MD, FACP, FACG, AGAF is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Physicians, and American Gastroenterological Association

Disclosure: Novartis Grant/research funds Other; Bayer Grant/research funds Other; Otsuka Grant/research funds None; Bristol Myers Squibb Grant/research funds Other; Scynexis None None; Salix Grant/research funds Other; MannKind Other

Terence David Lewis, MBBS, FRACP, FRCPC, FACP Program Director, Internal Medicine Residency, & Assistant Chairman, Associate Professor, Department of Internal Medicine, Division of Gastroenterology, Loma Linda University Medical Center

Terence David Lewis, MBBS, FRACP, FRCPC, FACP is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Medical Association, California Medical Association, Royal College of Physicians and Surgeons of Canada, and Sigma Xi

Disclosure: Nothing to disclose.

Jerome H Liu, MD Staff Physician, Department of Surgery, University of California at Los Angeles Medical Center

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment