Deception in Crohn ’ s Disease : A Case of Cryptogenic Multifocal Ulcerous Stenosing Enteritis

C l i n M e d International Library Citation: Shen H, Cave DR, Katz S (2016) Deception in Crohn’s Disease: A Case of Cryptogenic Multifocal Ulcerous Stenosing Enteritis. J Clin Gastroenterol Treat 2:021 Received: January 11, 2016: Accepted: April 18, 2016: Published: April 21, 2016 Copyright: © 2016 Shen H, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Shen et al. J Clin Gastroenterol Treat 2016, 2:021


Introduction
Cryptogenic multifocal ulcerous stenosing enteritis (CMUSE) is a rare idiopathic disease characterized by multiple small intestinal fibrous strictures with superficial ulcerations with a chronic or relapsing clinical course responding favorably to glucocorticosteroids.It has been mainly reported from Asia and Europe.We report a patient with chronic anemia with melena and intermittent abdominal pain who was diagnosed with CMUSE by small bowel resection.

Case Report
A 30-year-old man of Indian origin presented to the gastroenterology clinic in April 2013, with a history of anemia bloating.At follow-up, iron was 25 but his ferritin was normal.Pathology revealed multifocal ulcerous stenosing enteritis as reviewed by 3 pathologists.Post-operative infliximab was started as an attempt to preclude recurrent inflammation.However, due to the poor response, it was switched to adalimumab.He was also treated with rifaximin for small intestinal bacterial overgrowth.He has improved remarkably with lessened iron infusion requirement and is now having 1-2 bowel movements a day.

Discussion
CMUSE was first described by Debray et al. in 1964 [1].There have been about sixty cases of CMUSE published [2].Matsumoto et al. [3] reported 15 cases from Japan between 1964 and 2006, in which the illness was named chronic nonspecific multiple ulcers of the small intestine (CNSU).All of them presented with anemia and 10/15 patients underwent multiple small bowel resections due to recurrent strictures.Oral 5-aminosalicylic acid, prednisolone, or azathioprine failed to induce mucosal healing or prevent the recurrence of small intestinal ulcers.A French study [4] published 12 cases of CMUSE between 1965 and 1993.Despite surgery, symptoms recurred in seven of ten patients with strictures in four.Glucocorticosteroid therapy was effective but led to dependency.Kohoutová et al. [5] reported 3 cases diagnosed between 1994 and 2009 in Czech Republic, with colicky abdominal pain, recurrent ileus and weight loss, responding to glucocorticosteroid therapy.Double balloon enteroscopy were used to dilate the tandem tight jejunal stenosis.Two cases diagnosed by means of double balloon enteroscopy in Korea in 2007 were presented with chronic recurrent abdominal pain and melena [6].One patient underwent surgery because of retention of a capsule endoscope at the stenotic site.
The etiology and pathogenesis of CMUSE remains poorly understood.One hypothesis claims overstimulated production of fibrous tissue due to disturbance of proinflammatory cytokines, growth factors or collagen degradation [2,5].Perlemuter et al. [4,7] reported a case of CMUSE associated with heterozygous type I C2 deficiency and 5 cases related to either arterial stenosis or aneurysm, proposing that CMUSE may be an atypical type of vasculitis or a disease mimicking vasculitis.However, these findings were not confirmed [3,6].A recent study identified homozygous deletion mutations in PLA2G4A as a cause of CMUSE in two affected siblings [8].This could be a potential diagnostic and/or therapeutic target in the future.
The clinicopathological features of CMUSE have been summarized as follows: (1) chronic iron-deficiency anemia due to small intestinal occult blood loss, (2) rarely diarrhea, malabsorption, hematochezia or fever, (3) unexplained small intestinal strictures found in adolescent and middle-aged subjects, often requiring multiple resections of the small bowel, (4) multiple superficial ulceration of the mucosa and submucosa, predominantly in the ileum (the terminal ileum is usually spared) with infiltration of plasma cells, lymphocytes, and eosinophils, (5) a chronic or relapsing clinical course, even after surgery, (6) no biological signs of systemic inflammatory reaction, C-reactive protein (CRP) and other acute inflammatory reactants remain within normal limits or slightly increased, and (7) beneficial effect of systemic glucocorticosteroids [3,4,7].Our patient was presented with chronic anemia with melena and recurrent abdominal pain.No diarrhea, malabsorption, hematochezia or fever was documented.His small bowel resection for the strictures with intraoperative enteroscopy revealed six tight ulcerated stenoses.The capsule endoscopy was found to be retained at the second stricture.
The other entities causing multifocal small bowel ulcerations mainly include Crohn's disease (CD), chronic ulcerative jejunoileitis (CUJI), nonsteroidal anti-inflammatory drug (NSAID) or potassium tablets induced enteropathy, lymphoma, Behçet's disease, infections (e.g.tuberculosis), trauma and ischemia.A comparison of different clinicopathological features among CD, CUJI and CMUSE is listed in table 1 [9][10][11][12].Our patients did not have CUJI or celiac disease in the   absence of villous atrophy and malabsorption.The absence of small intestinal transmural and granulomatous inflammatory process ruled out CD.
The treatment of CMUSE is usually symptomatic with iron replacement either oral or by infusion.Systemic glucocorticosteroid therapy is still the mainstay of treatment, but results in steroid dependence [2][3][4][5].A case of steroid-refractory CMUSE was reported by Kim et al. [13].Oral 5-aminosalicylic acid or azathioprine were reported to be ineffective to induce mucosal healing or to prevent small intestinal strictures [3].Recently, de Schepper et al. [14] reported an anti-tumor necrosis factor (TNF)-alpha therapy (infliximab) induced remission for 6 months in a 29-year-old male patient with CMUSE.However, a recent meta-analysis cannot exclude that anti-TNF-alpha therapy may increase the long term risk of lymphoma in patients with inflammatory bowel disease [15].Anti-TNF-alpha therapy should be used with caution in patients with CMUSE.The intestinal strictures can be treated by either surgical resection or double balloon enteroscopy [5,16].
The prognosis of CMUSE remains unclear.Due to the relapsing clinical course (even after surgery) of CMUSE, our patient was started on infliximab post-operatively and then switched to adalimumab.Although he failed to respond to infliximab initially, he has improved remarkably while on adalimumab and treatment of bacterial overgrowth.To date, the optimal treatment strategy for CMUSE is still open to discussion, anti-TNF may be considered in some cases.

Figure 1 :
Figure 1: Intra-operative enteroscopy findings.It showed a tight ulcerated stenosis of the mid-jejunum.

Figure 2 :
Figure 2: The gross finding of the resected specimen.It showed multiple fibrous stenoses and ulcers.