Meta Analysis Of Cryptogenic Multifocal Ulcerous Stenosing Enteritis And Expression Of TNF-α In Intestinal Tissue

Cryptogenic multifocal ulcerous stenosing enteritis (CMUSE) is a rareidiopathic disease, of which the cause is as yet unknown. It characterized bychronic and relapsing bouts of intestinal obstruction accompanied withabdominal pain, occult intestinal bleeding, iron deficiency anemia,hypoalbuminemia, edema, growth retardation and so on. Pathologic featuresinclude unexplained strictures in small bowel with superficial ulcerationinvolved the mucosa and submucosa without extension deeper into underlyingtissues, sometimes consisting of neutrophils and few eosinophils.Inflammatory bowel disease (Chron’s disease), intestinal tuberculosis andintestinal ulcers secondary to non-steroidal anti-inflammatory drugs are themain differential diagnosis. Treatment is symptomatic, with no particularmedical therapy except for systemic glucocorticosteroids, however, mostpatients develop corticosteroid dependence or corticosteroid refractory.Without causal treatment so far, most patients usually respond to surgicalresection to solve recurrent obstructive events. The clinical features, diagnosispoints, treatment are significantly different from other intestinal diseases. Inthis study we try to analyze retrospectively the clinical features of CMUSEpatients who was treated in our hospital, summarize the clinical characters ofreported cases around the world, and try to find the pathogenesis of thecondition.Part1Cryptogenic Multifocal Ulcerous Stenosing Enteritis in1CaseReportObjective：Diagnose and analyze the CMUSE cases in our hospital, research the espression of TNF-α in the lesions of intestinal tissue, to explorethe pathogenesis of the disease.Methods：Collect the information and pathological section of the patientwho was addicted at22March,2012in our hospital. Retrospectively analyzedthe clinical features and pathological characteristics. Observe the TNF-αexpression in intestinal tissue through immunohistochemical stainingtechnique. To diagnose and analyze the CMUSE characteristics and findpossible pathogenesis.Results：The patient in our hospital was a middle-aged femal, wascharacterized clinically by relapsing bouts of iron deficiency anemia,obstruction, black stool hypoalbuminemia and intestine luminal stenosis onabdominal CT. Capsule enteroscopy detected segmental edema andlongitudinal ulcers covered with yellow moss involvement of the smallintestine. Laparotomy showed ileum segmental stenosis with capsuleendoscopy stranded, carried out small intestinal resection, postoperativepathological showed ulcers with partial mucosa effusion, necrosis andgranulation,13pieces of mesenteric lymph nodes reactive hyperplasia.Masson staining and Sirius red staining showed fibrous tissue expressionincreased, immunohistochemical staining showed mucosa and submucosainfiltrated of TNF-α positive cells.Conclusions: This CMUSE corresponds to present CMUSE diagnosticmain point around the world. Fibroblasts produce more collagen fibers that isstimulated by inflammatory cytokine TNF-α may be a key factor to thepathogenesis of CMUSE.Part2Meta-analysis of Cryptogenic multifocal ulcerous stenosingenteritisObjective: Summarize the clinical features of reported domestic andoverseas CMUSE cases and the clinical reatures compared with Asia andEurope cases. Methods: The literatures which reported cases meet the criteria ofCMUSE are selected by searching the Chinese databases including CNKI, VIP,Wanfang Data and PubMed. Then the clinical and histological features aresummarized and anylized.Results: From1996to2013,18CMUSE cases meet the diagnosticcriterion. The female patients are more than males. The mean age onset is36years old. The age at the time of the onset ranged from23months to37years.The main symptoms are abdominal pain, iron deficiency anemia and melena.There are no specific laboratory tests for diagnose of CMUSE. The faeces arepositive for occult blood. Peripheral blood test reveals decrease of hemoglobinand serum albumin. C-reactive protein, erythrocyte sedimentation rate andother acute inflammatory reactants are usually within their normal ranges orslightly increase. The level of platelet sometimes elevate. Abdominalcomputed tomography (CT) and X-ray often fail to show intestinalinflammation or sequelae of inflammation such as strictures, the digestivetract imaging more sensitive. Gastroscopy and colonoscopy rarely foundlesions, except the lesion was located in duodenum and the terminal ileum.Double-balloon enteroscopy and Capsule endoscopy are useful in diagnosingCMUSE disease and other inflammatory diseases in the small intestine. Thedisorder seems to be mostly localized in the ileum, partially in jejunum andduodenum, the ulcers are not transmural and typically remain shallow, onlyinvolve the mucosa and submucosa. Nonspecific inflammatory changes arepresent with neutrophils, mononuclear cells, eosinophils and plasma cells,without giant cells or other typical features of granulomatous inflammation. Infurther differential diagnosis of CMUSE, other small intestine diseases mustbe excluded, especially Crohn’s disease, NSAIDs-induced enteropathy andtuberculosis. Therapy with systemic corticosteroids is the treatment of choice.7cases get mucosal healing or to prevent small intestinal strictures through,but3cases develop corticosteroid dependence and3cases change intocorticosteroid refractory. Treatment with oral olsalazine and sulfasalazine areineffective.1patient has Raynaud’s phenomenon, a sicca syndrome, asthma, pain in left elbow, and wrist joint with intra-articular swelling. Another patienthas carcinoma in digestive system.Conclusions: The Chinese cases, generally observed in young women,are characterized clinically by abdominal pain, iron deficiency anemia andmelena. Low levels of hemoglobin and serum albumin. The faeces are positivefor occult blood. The histological feature shows the ulcers are not transmuraland typically remain shallow, only involve the mucosa and submucosa. Thefibrosis and inflammatory infiltration can reach deep tissue, this may lead tothe thickening of the submucosa, with mild-moderate inflammatory changesmainly, there is no changes such as granuloma, villous atrophy,lymphoproliferative, or giant cell granuloma. The clinical characteristicsbetween European and Asian are similar.