Clinical diagnosis
Case 277
【Progress】
Colon endoscopy showed multiple ulcers and biopsy revealed remodeling of abnormal crypt architecture and basal plasma cell cytosis, compatible with ulcerative colitis. High fever was still consistent despite steroid of 80 mg/day administration. Several days after, he was transported to university hospital that serves not just internal medical treatment but also preparation of surgical management. He was finally treated with whole colectomy because of sudden worsening of toxic megacolon, being afraid of endotoxin septic shock.
【Discussion】
Ulcerative colitis (UC) is categorized on location of appearance: proctitis, rectal sigmoiditis, pancolitis (1-3). Further, it is clinically categorized; mild, moderate and severe. Mild indicates hematemesis three or less/per day and laboratory test reveals normal; moderate 4 to 6 stools with no sign of symptoms; severe; more than 6 bloody stools daily with fever above 37.5°C: fulminant, more than 10 bloody stools, fever above 37.5°C, colon dilatation (1-3). Toxic megacolon indicates severe UC with colon dilatation of above 5.5 cm in size (1).
Villi own crypt structure that composes of stem cells at its bottom, colonocytes which function absorption of water and electrolytes, Goblet cells which secret mucin, resultant in lubricating the lumen not just for the content smoothly moving but also for pathogen not adhering to colon membrane, and enteroendocrine cells that secrete vasoactive intestinal peptide hormone that inhibit gastrin release and stimulate water and electrolyte secretion. Histologic findings of UC revealed architectural distortion of the crypt that indicates its shortening, decreased branching and basal plasmacytosis (4, 5).
Plasmacytes are differentiated from B cells and function to produce antibody. Their differentiation comes from stimulation via cytokines mainly from helper T cells via macrophages. Tumor necrosis factor (TNF) is one of the cytokines to promote B cell differentiation: TNFα is secreted mainly from macrophages and TNFβ mainly from T cell (6-8). TNF stimulates to form germ center and follicles of lymph nodes against bacterial and virus infection. There are two kinds of tumor necrosis factor receptor (TNFR) in each : TNFR1 is present on each body cell and TNFR2, on each immune cell (6-8). The cells owned TNFR1 are incorporated the route of necrosis and apoptosis. Namely, in a healthy condition, TNF works to fight off pathogens when bacteria and virus infection invade and thereafter pathogens are defeated and works to tranquilize inflammation by apoptosis of excessive cells in charge of inflammation. For some reason, probably immune-predominant dysregulation, inflammation does not cease but continues chronically, inducing swollen, flame, fever leading injury of healthy cells. In case of intestine, it induces edema, ulcer, hemorrhage from ulcer and fever emerge, namely inflammatory bowel disease.
TNF high values are found in rheumatoid arthritis, psoriatic arthritis, UC and Crohn disease. Further, TNF is reported to play a central role to cause depression, Alzheimer, multiple sclerosis, systemic lupus erythematosus, hepatitis C and endotoxin septic shock (8-10). Once endotoxin was prevailed to be used, the essential substance of endotoxin is TNF.
TNF is also one member of chemokines which cause neutrophils move to infected target lesions and high values in blood test. Neutrophils infiltrate target lesion with bringing about to induce permeability of blood vessels, namely, edema and inflame.
However, it is not yet to be clarified why chronic inflammation by TNF emerge. There are hypotheses; while immune response usually work against pathogen in feces, various antibodies for pathogen antigen are created; some antigen is common with a component of epithelial cell; produced antibodies to common antigen attacks intestinal epithelial cells: antibodies are continued to produce although antibody production should be ceased by apoptosis or necrosis of epithelial cells with common antigen of immune cells (6-8). Further, it is unknown why disease of UC initiate from rectum and continuously flamed toward sigmoid colon, ascending colon, transverse colon, ascending colon and cecum, finally over the entire colon.
【Summary】
We presented a twenty-year-old male for high fever, bloody diarrhea for approximately one month. Whole colon dilatation was found on abdominal CT. High fever rising to 40℃ of body temperature emerged. He received whole colectomy for being afraid of toxic megacolon, endotoxin septic shock. It is borne in mind that TNF plays a central role of causing UC. TNFα is secreted mainly from macrophages and TNFβ mainly from T cell.
It functions not only to fight off pathogens of bacillus and virus, producing to form follicle and germ center of lymph node, namely producing antibodies and to soothe inflammation by apoptosis and necrosis of inflammatory cells whose duties ended. UC emerges when mechanism of soothing inflammation is dysregulated and/or when some common antigen with pathogen component and intestinal epithelium component expose continuously to immune system.
【References】
1.Strong SA. Management of Acute Colitis and Toxic Megacolon. Clin Colon Rectal Surg. 2010 Dec; 23(4): 274–284.
2.Silverberg MS, et al. Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: Report of a Working Party of the 2005 Montreal World Congress of Gastroenterology. Can J Gastroenterol. 2005;19(Suppl A):5–36.
3.Baumgart DC, et al. Inflammatory bowel disease: clinical aspects and established and evolving therapies. Lancet. 2007;369:1641–1657.
4.Baumgart DC, et al. Inflammatory bowel disease: cause and immunobiology. Lancet. 2007;369:1627–1640.
5.Xavier RJ, et al. Unravelling the pathogenesis of inflammatory bowel disease. Nature. 2007;448:427–434.
6.Stange EF, et al. European evidence based consensus on the diagnosis and management of Crohn’s disease: definitions and diagnosis. Gut. 2006;55(Suppl 1):i1–i15
7.Silverberg MS, et al. Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: Report of a Working Party of the 2005 Montreal World Congress of Gastroenterology. Can J Gastroenterol. 2005;19(Suppl A):5–36.
8.Danese S, et al. Ulcerative colitis. N Engl J Med. 2011 Nov 3;365(18):1713-25. doi: 10.1056/NEJMra1102942. Review.
9.Di Sabatino A, et al. Recent advances in understanding ulcerative colitis. Intern Emerg Med. 2012 Apr;7(2):103-11. doi: 10.1007/s11739-011-0719-z. Epub 2011 Nov 9. Review.
10.McGuckin MA, et al. Intestinal barrier dysfunction in inflammatory bowel diseases. Inflamm Bowel Dis. 2009 Jan;15(1):100-13.
2022.9.12