Clinical diagnosis
Case 281
【Progress】
Colon endoscopy showed longitudinal ulcer, pseudo-polyposis and skip lesions of rectosigmoid colon and terminal ileum, implying diagnosis of Crohn’s disease. She was prescribed to take prednisolone (PSL) 20mg/day at first, being scheduled to gradual reduce of PSL.
【Discussion】
Cytokine is a substance composed of peptide or protein that connects or interacts between cell and cell like a cellular phone in human and human. Cytokines are largely categorized into two types; one is for initiation, preservation and aggravation of counterattack for pathogens that is called inflammation cytokine; another is for end of counterattack against pathogens that is called anti-inflammation cytokine (1, 2). The two representative inflammatory cytokines are interleukin (IL) 6 and tumor necrosis factor (TNF). Both contribute to produce antibody production. Of these, TNF is known to be involved in emerging inflammatory bowel diseases. TNFα is secreted by macrophages and TNFβ is done by lymphocytes (3). Meanwhile, one of the representative anti-inflammation cytokines is transforming growth factor (TGF β). TGFα is secreted by epithelial cells for its regeneration while TGFβ is done by lymphocytes, indicating pure cytokine (4-6).
Inflammatory bowel diseases of ulcerative colitis (UC) and Crohn disease (CD) are caused by inflammatory cytokines. Although its mechanism is not well clarified, it is thought that antibody is, first produced against unknown antigen such as virus, bacteria or allergic component of food material whose antigen is similar as a substance of intestinal mural component. Then, when the responsible antigen is exposed continuously, the produced antibody by B cells stimulated by IL6 and TNF attack not only extra body antigen but also auto-intestine itself, inducing inflammatory bowel disease. As a result, TNF stimulation contributes to emerge inflammatory bowel disease more than IL6 since anti TNF is more effective on inflammatory bowel disease than anti IL6 (3).
One of the differences between UC and Crohn’s disease is presence of absence of proliferation of mural fibrosis. Skipped thickness of bowel mural is characteristic of CD, leading often surgical bowel resection. Unabsorbed fibrosis is found in cases of skin keloid, liver cirrhosis and CD that are created by myofibroblasts. Fibrosis created by fibroblasts can be absorbed inducing almost disappearing, while fibrosis created by myofibroblasts can be permanent. Myofibroblasts emerged by transforming intestinal (stellate cells) fibroblasts, epithelial fibroblasts and bone marrow derived stem cells via TGFβ secreted by lymphocytes, inducing permanent fibrosis (4-6). Then, CD disease itself is the disorder of unknown continuous inflammation and its restoration after inflammation. Anti TGFβ has been tried but not effective on CD at present, but anti TNF is effective for achieving remission (4-6).
MRI contributes to identify CD lesions. MRI protocols are: balanced FFE, Fat sat T2WI and T1WI & Gd-enhanced T1WI under mannitol in water solution of 2 % (7). Viewing the images taken by MRI, checking the following findings are required to be crucial; mural thickness (3. 5. 10mm), lesion length (5cm. 10cm, 15cm), mural enhancement: fat sat T2WI gray, light and high light, Gd enhanced T1WI (homogeneous, mucosal, layered) comb sign and creeping fat sign (fibrofatty proliferation). The staging of none, mild, moderate and severe by scoring the above findings should be documented in case of image interpretation (7-9) .
【Summary】
We presented a thirty three-year-old female presented in our hospital for repeated abdominal pain and diarrhea sometimes associated with fever. CT depicted layered mural of ileum end and severe stenosis of recto-sigmoid colon. Colon endoscopy showed longitudinal ulcer and pseudo-polyposis implying diagnosis of Crohn’s disease (CD). It is borne in mind that cytokine is largely categorized into inflammation cytokine (IL1, IL6 and TNF) and anti-inflammation cytokine (TGFβ). It is considered that CD emerges in case of disorder of cytokine secretion of TNF and TGFβ, leading to longitudinal ulcer by continuous inflammation via TNF and permanent thick fibrosis by myo-fibroblastic cell via TGFβ. Anti TNF induces remission of inflammation but anti TGFβ is not effective to inhibit formation of thick fibrosis at present. MRI with balanced FFE, fat sat T2WI and T1WI & Gd-enhanced T1WI under mannitol in water solution of 2 % is effective to visualize mural thickness, fibrofatty proliferation, stricture, mural enhancement and com sign.
【References】
1.Xavier RJ, et al. Unravelling the pathogenesis of inflammatory bowel disease. Nature. 2007;448:427–434.
2.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
3.Baumgart DC, et al. Inflammatory bowel disease: clinical aspects and established and evolving therapies. Lancet. 2007;369:1641–1657.
4.Meng, Xiao-ming et al. "TGF-β: the master regulator of fibrosis". Nature Reviews Nephrology. 2016; 12 (6): 325–338.
5.Salajegheh, Ali. “Transforming Growth Factor α and β (TGF-α and TGF-β).” SpringerLink, Springer, Cham, 1 Jan. 1970
6.Kurahara, LH, et al. Intestinal Myofibroblast TRPC6 Channel May Contribute to Stenotic Fibrosis in Crohn's Disease. Inflammatory Bowel Diseases. 2015; 21: 496–506,
7.Puylaert, C, et al. Crohn's disease - role of MRI. Radiology Assistant. https://radiologyassistant.nl/abdomen/bowel/crohn-s-disease. Dated August 16, 2022
8.Punwani S. et al. Mural inflammation in Crohn's disease: location-matched histologic validation of MR imaging features. Radiology 2009;252:712-720
9.Rimola J. et al. Characterization of inflammation and fibrosis in Crohn's disease lesions by magnetic resonance imaging. Am J Gastroenterol. 2015; 110:432-440
2022.10.28