Crohn’s disease (CD), a subentity of inflammatory bowel disease (IBD), is a chronic relapsing/remitting disorder characterized by segmental and transmural intestinal inflammation affecting the entirety of the gastrointestinal (GI) tract from mouth to anus. Patients most typically present with abdominal pain, bloody diarrhea, fatigue, anemia, weight loss, and/or extra-intestinal manifestations. However, gastroduodenal CD may present with symptoms of epigastric pain, dyspepsia, early satiety, anorexia, nausea, vomiting, and weight loss.
The first report of duodenal involvement of CD was described by Gottlieb and Alpert in 1937,1 and later Ross2 reported gastric CD in 1949. Recent reports suggest that upper GI tract (esophageal, gastric, and/or duodenal) involvement occurs in 0.5–4.0% of symptomatic adults with CD, with the majority having concomitant terminal ileal and colonic disease.3 This incidence may be underestimated because upper endoscopy is not routinely performed in the initial evaluation of adult CD as in the pediatric population.4
Isolated gastric CD accounts for less than 0.07% of adult CD patients and is even rarer in the pediatric population.5 Isolated duodenal CD is limited to a few cases in the adult literature.6,7 A recent pediatric study also identified 2 incident cases of stricturing duodenal CD which partially responded to intensive medical therapy and ultimately required laparoscopic gastroduodenostomy.8 Duodenal CD typically manifests as single, short segment duodenal strictures surrounded by nodular and ulcerated mucosa, rather than a fistulizing or perforating phenotype.9 Patients are usually asymptomatic and diagnosed incidentally following cross-sectional imaging and/or esophagogastroduodenoscopy. Symptomatic cases, clinically manifesting as small bowel obstruction, are associated with a worse prognosis and more severe disease course.9,10 We present a case of pediatric CD with rare isolated duodenal involvement resulting in severe stricturing.
A 12-year-old African American female with iron deficiency anemia presented with 2 months of weight loss, decreased appetite, abdominal pain, and bilious emesis. Physical examination revealed generalized abdominal tenderness and epigastric fullness. Laboratory evaluation was notable for thrombocytosis and elevated serum inflammatory markers. Initially, an upper GI series showed severe gastric distension and gastric outlet obstruction (Fig. 1A). Subsequent magnetic resonance enterography demonstrated marked distension of the stomach, first and second portions of the duodenum, with a decompressed third portion (Fig. 1B and C). The remainder of the visualized small and large bowel was normal. At first, only upper endoscopy was performed, given the presenting symptom of emesis without diarrhea or hematochezia, and revealed complete obstruction at the second portion of the duodenum (Fig. 2A). Biopsies showed chronic gastritis and mildly active duodenitis with chronicity proximal to the stricture. There was no evidence of granulomas, viral inclusions, or malignancy.
She subsequently underwent laparotomy guided by endoscopy to resect a long-segment stricture of the third and fourth portions of the duodenum with duodenojejunostomy. Gross nodularity was noted on the serosal aspect at the level of the ligament of Treitz. Pathology of the resected bowel demonstrated chronic lymphocytic inflammation and multiple granulomas were seen on a seromuscular biopsy of the proximal jejunum (Fig. 2B and C). Testing for both chronic granulomatous disease and tuberculosis was negative. Postoperatively, she received total parenteral nutrition and required nasogastric tube decompression for high-volume output.
Additional investigation was aimed to identify the etiology of her severe duodenal inflammation and stricturing. Fecal calprotectin was normal at 40.7 mg/kg. Repeat endoscopy after surgery showed duodenitis with increased eosinophils (40 per high-power field) and several nonbleeding duodenal ulcers (Fig. 3A). The anastomotic site had chronic active duodenitis with full-thickness ulceration (Fig. 3B). The colon and terminal ileum were endoscopically and histologically normal (Fig. 3C and D). Helicobacter pylori, viral, and fungal stains were negative. Further evaluation including anti-nuclear antibody, myeloperoxidase antibody, cytoplasmic and perinuclear anti-cytoplasmic antibodies, and radioallergosorbent testing were also negative. An IBD diagnostic panel was positive for anti-Saccharomyces cerevisiae IgA and IgG antibodies, consistent with CD. She also had elevated tissue transglutaminase (TTG) IgA antibody (41 U/mL), deamidated gliadin IgA antibody (134 U/mL), and antiendomysial IgA antibody titer (1:5) in the setting of a normal total IgA level.
Three months later, she returned with bilious emesis and malnutrition requiring total parenteral nutrition. She was given intravenous steroids, started infliximab (10 mg/kg at weeks 0, 2, and 6), and discharged on a soft mechanical diet. Prior to her first maintenance infliximab dose, she had recurrent bilious emesis (drug level of 18 μg/mL and no detectable antibodies). Repeat magnetic resonance enterography showed a dilated proximal duodenum and stomach with an anastomotic site stricture, requiring multiple endoscopic balloon dilations without improvement. A 15-mm lumen-apposing metal stent (LAMS) was deployed over a guidewire across the 10-mm stricture to help alleviate the obstruction and dilate it over 2 months.
During that time, she significantly improved and advanced to a regular diet. She continued to receive a proton-pump inhibitor, low-dose oral steroids, and infliximab (10 mg/kg every 4 weeks and later every 8 weeks) as maintenance therapy. Repeat endoscopy 18 months after initiation of infliximab showed complete visual improvement of the duodenal inflammation with biopsies revealing only a mild increase in intraepithelial lymphocytes in the duodenum and jejunum without villous atrophy. The colon was once again visually and histologically normal.
This case presented with a wide differential diagnosis that included H. pylori, celiac disease, eosinophilic GI disease, autoimmune disease, and GI tumors. Detection of noncaseating granulomas, only found with deeper seromuscular biopsy, ultimately helped diagnose CD. Interestingly, the patient’s celiac markers were elevated. The prevalence of serologic celiac disease in patients with IBD has previously been described and is thought to relate to mucosal barrier defects.11 Increased intestinal tight junction permeability may lead to increased antigen presentation and, therefore, generation of autoantibodies.12 TTG can also be overexpressed in apoptotic tissue, such as mucosal lesions due to chronic bowel inflammation.13 Other studies have also described false-positive anti-TTG antibodies as a phenomenon of autoimmunity.14 Celiac markers, repeated after initiation of IBD therapy, had normalized without gluten restriction. Moreover, the classical features of celiac disease were never present on duodenal biopsies.
The treatment of this patient’s stricturing CD involved a multifaceted approach including early surgical intervention, total parenteral nutrition, prolonged steroids, anti-tumor necrosis factor (TNF) therapy, and endoscopic dilations. The effectiveness of infliximab in isolated gastroduodenal CD is limited to a few adult case reports with unknown long-term outcomes.15,16 In a prospective study, 19 of 119 adults with CD had upper GI tract involvement, and of those 11 were treated with anti-TNF therapy (10 with infliximab and 1 with adalimumab). After 12 weeks, 8 of the 11 patients had significant macroscopic improvement and 7 had significant histologic improvement of their upper GI disease.17 Here we discuss a pediatric case where infliximab was used to maintain long-term disease remission.
Management of stricturing disease typically also involves a combination of surgical resection and endoscopic balloon dilation to relieve obstruction while maximizing bowel conservation. Indications for surgery include failure of medical management with intractable pain, bleeding, perforation, and fistulous disease.18 Endoscopic dilation has been noted to have 87% short-term clinical efficacy with major complications arising in 2.9% of procedures. With a 2-year follow-up period, 70.5% of patients had recurrence of symptoms, 59.6% required redilation, and 30.8% required surgical intervention. Patients with small bowel disease had a higher risk for symptom recurrence and repetitive dilations.19
In this case, a LAMS was used when the patient’s anastomotic duodenal stricture did not respond to dilation alone. LAMS was initially developed to drain peripancreatic fluid collections by creating a cyst-gastrostomy, but they have also been used to stent short luminal strictures.20 The distal flange was deployed downstream to the stricture under fluoroscopic guidance, and the stent’s proximal end was then deployed under both fluoroscopic and endoscopic guidance. The stents are fully covered to prevent tissue ingrowth and therefore have decreased stent migration risk and are endoscopically removable with a snare or forceps. LAMS has been used to stent esophageal and duodenal strictures in adults21; however, their use in pediatrics is rare.
In conclusion, it is atypical to have isolated duodenal CD present as early gastric outlet obstruction. This case emphasizes that a high index of suspicion is necessary to diagnose isolated duodenal CD. It also highlights the many therapeutic challenges we faced, requiring a multidisciplinary approach involving anti-TNF, surgical, and advanced endoscopic treatments. We discuss the novel use of LAMS as an adjunct therapy to alleviate obstructive symptoms.
1. Gottlieb C, Alpert S. Regional jejunitis. Am J Roentgenol. 1937; 38:881–883
2. Ross J. Cicatrizing enteritis, colitis and gastritis: a case report. Gastroenterology. 1949; 13:344–350
3. Talabur Horje CS, Meijer J, Rovers L, van Lochem EG, Groenen MJ, Wahab PJ. Prevalence of upper gastrointestinal lesions at primary diagnosis in adults with inflammatory bowel disease. Inflamm Bowel Dis. 2016; 22:E33–E34
4. Turner D, Griffiths AM. Esophageal, gastric, and duodenal manifestations of IBD and the role of upper endoscopy in IBD diagnosis. Curr Gastroenterol Rep. 2009; 11:234–237
5. Ingle SB, Adgaonkar BD, Jamadar NP, Siddiqui S, Hinge CR. Crohn’s disease with gastroduodenal involvement: diagnostic approach. World J Clin Cases. 2015; 3:479–483
6. Song DJ, Whang IS, Choi HW, Jeong CY, Jung SH. Crohn’s disease confined to the duodenum: a case report. World J Clin Cases. 2016; 4:146–150
7. Karateke F, Menekşe E, Das K, Ozyazici S, Demirtürk P. Isolated duodenal Crohn’s disease: a case report and a review of the surgical management. Case Rep Surg. 2013; 2013:421961
8. Burgess CJ, Gillett P, Mitchell D, Hammond P, Henderson P, Wilson DC. Incidence of paediatric stricturing duodenal Crohn disease: a 19-year population-based cohort study. J Pediatr Gastroenterol Nutr. 2019; 69:539–543
9. Magro F, Rodrigues-Pinto E, Coelho R, et al. Is it possible to change phenotype progression in Crohn’s disease in the era of immunomodulators? Predictive factors of phenotype progression. Am J Gastroenterol. 2014; 109:1026–1036
10. Lazarev M, Huang C, Bitton A, et al. Relationship between proximal Crohn’s disease location and disease behavior and surgery: a cross-sectional study of the IBD Genetics Consortium. Am J Gastroenterol. 2013; 108:106–112
11. Jandaghi E, Hojatnia M, Vahedi H, Shahbaz-Khani B, Kolahdoozan S, Ansari R. Is the prevalence of celiac disease higher than the general population in inflammatory bowel disease? Middle East J Dig Dis. 2015; 7:82–87
12. Schumann M, Siegmund B, Schulzke JD, Fromm M. Celiac disease: role of the epithelial barrier. Cell Mol Gastroenterol Hepatol. 2017; 3:150–162
13. Tavakkoli H, Haghdani S, Adilipour H, et al. Serologic celiac disease in patients with inflammatory bowel disease. J Res Med Sci. 2012; 17:154–158
14. Clemente MG, Musu MP, Frau F, Lucia C, De Virgiliis S. Antitissue transglutaminase antibodies outside celiac disease. J Pediatr Gastroenterol Nutr. 2002; 34:31–34
15. Kim YL, Park YS, Park EK, et al. Refractory duodenal Crohn’s disease successfully treated with infliximab. Intest Res. 2014; 12:66–69
16. Inayat F, Ullah W, Hussain Q, Shafique K. Crohn’s disease presenting as gastric outlet obstruction: a therapeutic challenge? BMJ Case Rep. 2017; 2017
17. Annunziata ML, Caviglia R, Papparella LG, Cicala M. Upper gastrointestinal involvement of Crohn’s disease: a prospective study on the role of upper endoscopy in the diagnostic work-up. Dig Dis Sci. 2012; 57:1618–1623
18. Shapiro M, Greenstein AJ, Byrn J, et al. Surgical management and outcomes of patients with duodenal Crohn’s disease. J Am Coll Surg. 2008; 207:36–42
19. Bettenworth D, Mücke MM, Lopez R, et al. Efficacy of endoscopic dilation of gastroduodenal Crohn’s disease strictures: a systematic review and meta-analysis of individual patient data. Clin Gastroenterol Hepatol. 2019; 17:2514–2522.e8
20. Yang D, Nieto JM, Siddiqui A, et al. Lumen-apposing covered self-expandable metal stents for short benign gastrointestinal strictures: a multicenter study. Endoscopy. 2017; 49:327–333
21. Westerveld D, Schlachterman A, Draganov PV, Yang D. The use of a lumen-apposing metal stent for a short malignant duodenal stricture in a patient with a coexisting metal biliary stent. VideoGIE. 2017; 2:305–306