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Clinical diagnosis

Case 169

4. Pseudo-membrane colitis


【Progress】
 Colon endoscope was inserted to the descending colon and was unable to insert to the more oral side due to the existence of stool. It showed multiple white-colored bulges indicative of pseudo-membrane. Biopsy was conducted to the one of the bulges. Histological findings revealed ulceration composed of mononuclear leukocytes, pooling of mucin substance and granulation tissue, implying pseudomembranous colitis.

【Discussion】
 Megacolon is categorized into two types: acute and chronic. Acute megacolon is called toxic megacolon and caused by ulcerative colitis, Crohn’s disease, infectious colitis and pseudo-membrane colitis (1, 2). Bowel wall is composed of mucosal layer, mucosal muscle, propriate mucosal layer, muscle layer and serosa layer. When the lesion is limited to the mucosa to propriate mucosal layers, acute toxic megacolon (ATM) does not happen. ATM is brought by paralysis of smooth muscle layer which is caused by nitrogen oxide production from inflammatory cells (3, 4). Further, ATM is worsened by cytokines from leukocytes (1). In short, ATM occurs now that the lesion activates to invade from mucosal layer to smooth muscle layer. ATM is not related to imbalance of electrolytes or disorder of nerves. Meanwhile, chronic megacolon such as Hirschsprung disease and chronic pseudo-intestinal obstruction appear due to disorder of Auerbach nerve plexus and/or Cajal cells.
 ATM was present in 5-6% of patients with ulcerative colitis patients, 2.3 % of those with Crohn’s disease and 3% of pseudomembranous colitis. ATM is defined as ;the dilatation of 6.5 cm or greater on transverse colon diameter; any 3 of the following fever > 38.5 centigrade, Leukocytosis > 10500/mm3, tachycardia 120/min, anemia; any 1 of the following dehydration, altered mental status, electrolytes abnormality, hypotention (1-3).In our case, he had slight fever, WBC 10200/mm3 , dehydration and more than 10 cm of transverse colon, indicating yet to ATM, probably prior to ATM. Endoscopic colonoscope and biopsy revealed pseudomembranous colitis.
 The risk factors of pseudomembranous colitis is as follows (5); taking antibiotics or anticancer drugs; over age 65 years; having a weakened immune system; having a colon disease such as inflammatory disease or colon cancer. Our case was an eighty year-old male, having SLE and rheumatic fever, taking steroid indicative of weak immune system. Pseudomembranous colitis is mainly caused by toxins produced by Clostridium difficile(CD), a gram-positive anaerobic bacillus. Toxin A (enterotoxin) and toxin B (cytotoxin) and ribotype 027 (a marker of virulent CD strain) are useful for diagnosis of pseudomembranous colitis (5-7). The toxins attack the mucosal layers, resulting in cytoplasmic contraction of mucosal cells, hemorrhage, inflammation, cellular necrosis and protein loss. Further, they increase capillary permeability and peristalsis, inciting diarrhea and bleeding. Psudomembrane is pathologically formed by necrotic mucoepithelial cells, muscus, fibrin and neutrophils. The main predisposing area is mucoepithelial sub-layer of the mucosal layer. Basically, the layers of mucosal muscularis, submucosa and smooth muscularis are not involved.
 Although not so often, pseudomembrane colitis is reported to be caused by the other etiology rather than Clostridium difficile such as infectious colitis of Campylobacter, cytomegalovirus, Escherichia coli O157, Salmonella, and ischemic colitis by occlusive mesenteric arteries (9-12).
 As treatment, when intravenous vancomycin is not effective, administration of intracolonic vancomycin and intravenous tigecycline are promising managements.


【Summary】
 We present an eighty year-old male suffering from persistent diarrhea for approximately 20 days. Abdomen radiograph and CT showed marked dilatation of transverse colon of more than 10 cm or larger dilatation, suspicious of megacolon. Colon endoscope and histologic examination of biopsy specimen showed pseudomembranous colitis. It is borne in mind that when a transverse colon is dilated more than 6.5 cm or larger, ulcerative colitis, Crohn’ disease, pseudomembranous colitis and infectious colitis are listed. The symptoms are crucial for differential diagnosis: bloody stool, diarrhea whether acute or chronic. Megacolon is categorized into chronic or acute. As chronic megacolon, Hirschsprung disease and chronic pseudo-intestinal obstruction are listed. Pseudomembranous colitis is mainly caused by toxins produced by Clostridium difficile; Toxin A (enterotoxin) and toxin B (cytotoxin) and ribotype 027. Intravenous vancomycin, administration of intracolonic vancomycin and intravenous tigecycline are promising managements.


【References】
1.Dumitru, IM, et al. Toxic Megacolon – A Three Case Presentation. J Crit Care Med (Targu Mures). 2017 Feb; 3(1): 39–44.
2.Sheth SG, et al. Toxic megacolon. Lancet. 1998 Feb 14. 351(9101):509-13..
3.Mourelle M, et al. Induction of nitric oxide synthase in colonic smooth muscle from patients with toxic megacolon. Gastroenterology. 1995 Nov. 109(5):1497-502.
4.Guslandi M. Nitric oxide and inflammatory bowel diseases. Eur J Clin Invest. 1998 Nov. 28(11):904-7.
5.Sartelli M, et al. WSES guidelines for management of Clostridium difficile infection in surgical patients. World J Emerg Surg. 2015;10:38.
6.Shivashankar R, et al. Clinical factors associated with development of severe-complicated Clostridium difficile infection. Clin Gastroenterol Hepatol. 2013;11(11):1466–71.
7.Stallmach A. Clostridium difficile infection: What is currently available for treatment? Internist (Berl). 2016;57(12):1182–1190.
8.Khanafer N, et al. Factors predictive of severe Clostridium difficile infection depend on the definition used. Anaerobe. 2016;37:43–8.
9.C. R. Dignan, et al. Can ischemic colitis be differentiated from C difficile colitis in biopsy specimens? The American Journal of Surgical Pathology, vol. 21, no. 6, pp. 706–710, 1997.
10.Villanacci, S, et al., “Pseudomembranous collagenous colitis with superimposed drug damage,” Pathology—Research and Practice, vol. 209, no. 11, pp. 735–739, 2013.
11.A. Uc, F, et al. Pseudomembranous colitis with Escherichia coli O157:H7. Journal of Pediatric Gastroenterology and Nutrition, vol. 24, no. 5, pp. 590–593, 1997.
12.Surawicz CM, et al. Pseudomembranous colitis: causes and cures. Digestion; 60, 91–100, 1999.

2019.11.13



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