Contents

Search

Crohn's disease; terminal ileitis; regional enteritis; granulomatous enteritis; chronic cicatrizing enteritis

Etiology: 1) unknown 2) tumor necrosis factor alpha may play a role 3) Mycobacterium avium paratuberculosis? 4) exercise lowers risk for Crohn's disease in women [36] 5) exacerbating factors a) cigarette smoking (risk of severe phenotype ~2-fold) [36] b) non-steroidal anti-inflammatory drugs (NSAIDs) c) infectious agents Epidemiology: 1) more common in industrialized nations 2) relative risk higher in smokers 3) 50 cases per 100,000 in USA Pathology: 1) disease can affect any part of the GI tract from mouth to anus 2) disease may be patchy rather than contiguous in distribution (contrast with ulcerative colitis) 3) affects the entire wall of the GI tract (transmural) a) mucuosal granulomas b) fistulas & strictures are frequent complications c) abdominal abscesses & perirectal abscesses are also common 3) frequency of disease distribution: a) ileocolonic (40%) b) colonic (30%) c) small bowel (30%) d) upper GI (esophagus, stomach, duodenum) <5% 4) up-regulation inflammatory molecules: REG4, IL26 5) increased numbers of Enterobacteriaceae & Fusobacteriaceae & diminished numbers of Bacteroidales & Clostridiales found on ileal & rectal biopsy specimens predicts Crohn's disease with relatively high reliability [18] - stool specimens are less reliable Genetics: 1) familial tendency 2) high concordance in twins 3) more common in Jewish & Caucasians 4) allele of caspase recruitment domain protein 15 gene associated with susceptibility 5) susceptbility associated with: a) alleles of IL23R gene b) defects in IRGM, FAM92B, SLC22A4, SLC22A5 c) genetic variations in ATG16L1 (type 10 IBD) [11] Clinical manifestations: 1) indolent onset, variable clinical manifestations 2) characterized by exacerbations & remissions 3) non-bloody diarrhea 4) abdominal pain & tenderness 5) fatigue 6) weight loss 7) rectal pain, hematochezia, purulent discharge from anorectal fistula or abscess 8) fever 9) growth failure in children 10) nausea/vomiting 11) aphthous stomatitis - or other mouth lesions described as tender superficial linear ulcerations along the buccal mucosa [37] 12) abdominal mass - inflammation of the ileum with abscess or phlegmon [37] - ileal dilation due to stricture 13) partial intestinal obstruction a) abdominal distension b) hyperactive bowel sounds 14) extra-intestinal manifestations a) eye: episcleritis, iritis, uveitis b) skin: 1] pyoderma gangrenosum 2] erythema nodosum: frequently a harbinger of active intestinal disease 3] acrodermatitis enteropathica due to zinc deficiency 4] perianal acrochordons (skin tags) c) joints: arthralgias (joint swelling is uncommon) - ankylosing spondylitis, sacroiliitis [3] - see enteropathic arthritis d) hepatic: hepatomegaly, splenomegaly, jaundice e) pulmonary involvement is uncommon [21] - large airways are most commonly affected - parenchymal disease may resemble granulomatosis with polyangiitis [21] - bronchiolitis obliterans with organizing pneumonia - interstitial pneumonitis - necrobiotic pulmonary nodules 15) some patients may have no physical findings Laboratory: 1) complete blood count (CBC) - megaloblastic anemia, leukocytosis, thrombocytosis 2) serum chemistries a) electrolytes b) urea nitrogen c) serum creatinine d) serum bicarbonate e) liver function tests - abnormalities may suggest cholangitis f) nutritional assessment - serum albumin, prealbumin, - serum vitamin B12 may be low (defective ileal absorption) - low serum 25-OH vitamin D common & associated with higher morbidity & disease severity [29] g) monitor serum C-reactive protein as marker of inflammation [30] - monitor patients in remission every 6-12 months [39] 3) stool examination: a) fecal leukocytes b) fecal occult blood c) ova & parasites d) C. difficile toxin if on antibiotics e) cultures for Shigella, Salmonella, Campylobacter, E coli O157:H7 [3] f) fecal calprotectin - helpful to differentiate inflammatory bowel disease from irritable bowel syndrome [33] - monitor patients in remission every 6-12 months [39] 4) blood cultures for suspected sepsis 5) erythrocyte sedimentation rate (ESR) - useful for monitoring response to therapy 6) serum Saccharomyces cerevisiae IgG/IgA 60%; 10% in ulcerative colitis 7) anti-CBir, an antibody against flagellin 8) anti-mannan antibody* anti-laminaribioside antibody* anti-chitobioside antibody* 9) anti-neutrophil cytoplasmic antibodies (ANCA) - p-ANCA 10%, 75% in ulcerative colitis 10) see inflammatory bowel disease for therapeutic drug monitoring * 2 of 3 antibodies 99% specific for Crohn's disease Special laboratory: 1) video capsule endoscopy now gold standard for diagnosis & follow-up of small intestinal Crohn's disease (Not according to [37]) - ref [37] cites risk of capsule getting stuck at site of stricture - see MRI enterography in Radiology below 2) colonoscopy a) delineate extent of colonic & terminal ileal disease - patchy superficial ulcerations - rectum is usually unaffected - superficial serpiginous ulcers & cobblestoning in ileum & right colon - nongranulomatous inflammation - microscopic granulomas support diagnosis but are generally absent - more severe disease involves deeper layers of the bowel wall & leads to complications such as strictures and fistulas [3] b) biopsy indicated (required for diagnosis) [3] c) avoid in seriously ill patients - abdominal abscess - small intestine obstruction - toxic megacolon d) advised within 8-10 years of IBD onset; e) high-definition colonoscopy favored over standard definition [23] f) routine performance of chromoendoscopy during IBD surveillance is recommended as an adjunct to high-definition colonoscopy [23]; only in high-risk patients [33] g) narrowband imaging is not a replacement for high-definition, white-light colonoscopy or chromoendoscopy [23] h) no specific recommendation on performance of random biopsies [23] i) after 2 negative scopes, screening intervals of 1-3 years j) 1-2 years after initial endoscopy for more extensive or left-sided colitis k) polypectomy & continued surveillance recommended for adenoma-like dysplasia-associated lesion or mass with no evidence of other flat dysplasia [9] - after complete removal of endoscopically resectable polypoid or nonpolypoid dysplasia, surveillance colonoscopy is recommended rather than colectomy [23] l) for patients with endoscopically invisible dysplasia (confirmed by GI pathologist), referral is suggested to an endoscopist with expertise in IBD surveillance using chromoendoscopy with high-definition colonoscopy [23] m) reduces colorectal cancer risk by 35% [20] 3) sigmoidoscopy is safer than colonoscopy [3] & may be useful to confirm symptoms are due to active Crohn's disease prior to beginning expensive TNF-alpha therapy [3] 4) esophagogastroduodenoscopy (EGD) - biopsy of suspected upper GI Crohn's disease Radiology: 1) upper GI series with small bowel follow-through - suspected upper GI Crohn's disease - small intestine wall thickening - narrowing of the terminal ileum 2) abdominal computed tomography (CT) with oral contrast a) abdominal masses, abscesses b) fistulas c) repeat imaging frequently needed - minimize radiation, - use only when results will affect management - use ultrasound if possible [3] 3) imaging of anus - pelvic MRI is needed in patients with perianal disease - all CT & MRI imaging should include imaging of anus [32] 4) abdominal ultrasound a) hydronephrosis secondary to oxalate stones b) gallstones associated with bile salt deficiency 5) avoid barium enema - may precipitate toxic megacolon in patients with moderate-severe colitis [3] 6) MRI enterography - test of choice for evaluation of extent of disease & assessment of complications in Crohn's disease involving the terminal ileum [37] - preferred over CT to assess treatment response in asymptomatic patients [32] Differential diagnosis: 1) irritable bowel syndrome 2) other forms of colitis a) ulcerative colitis (UC) - involvement of patchy areas vs contiguous involvement for UC - rectal involvement in UC, rare in Crohn's - fistulas, abscesses & strictures rare in UC - perianal disease (rare in UC) - granulomas in 30% of Crohn's, unlikely in UC - rectal bleeding common in UC, less common in Crohn's - tobacco protective for UC, exacerbated in Crohn's b) infectious colitis - bacterial: Shigella, Salmonella, Yersinia, Campylobacter, E. coli O157:H7 - parasites: Entamoeba histolytica, Giardia lamblia c) pseudomembranous colitis d) ischemic colitis e) radiation colitis f) lymphocytic colitis 3) other causes of hematochezia a) colorectal carcinoma b) diverticulosis 4) Meckel's diverticulum: generally painless rectal bleeding 5) other causes of diarrhea 6) infectious ileitis a) Mycobacterium b) Yersinia c) Actinomyces 7) other causes of small bowel obstruction a) intussusception b) adhesions c) lymphoma 8) celiac disease 9) other causes of right lower quadrant pain a) appendicitis b) pelvic inflammatory disease (PID) c) ovarian mass d) nephrolithiasis 10) other causes of gastric or duodenal inflammation a) peptic ulcer disease (PUD) b) Zollinger-Ellison (ZE) syndrome c) gastric carcinoma 11) liver involvement suggests primary sclerosing cholangitis [3] Complications: 1) osteoporosis & fractures due to malabsorption (vitamin D & calcium) 2) erythema nodosum (4%), pyoderma gangrenosum (0.8%) [9] 3) resection of the ileum may lead to a) fat (bile acids) & fat-soluble vitamin malabsorption - cholestyramine for chronic non-bloody diarrhea after ileal resection [37,38] - cholestyramine 4 gm BID for bile-salt induced diarrhea - post ileal resection (bile acids resorbed in ileum) [37] b) acrodermatitis enteropathica due to zinc deficiency* (40-50% of Crohn's) [37] c) vitamin B12 deficiency - ileum is site of intrinsic factor - B12 uptake - Crohn's ileitis in the absence of ileal resection is a less common common cause of vitamin B12 deficiency 4) resection of > 200 cm of the small bowel is associated with electrolyte & nutrient malabsorption 5) increased risk of venous thromboembolism [3,14] 6) enteropathic arthritis 7) increased risk of cancer - increased risk of colon cancer - additional risk factors - disease duration - extensive disease - primary sclerosing cholangitis - family history of colorectal cancer [3] - increased risk of cervical cancer & non-melanoma skin cancer [3] - increased risk of oral cancer 8) sepsis may be masked in patients on chronic glucocorticoids - sepsis in patients on chronic glucocorticoids may require stress doses because of adrenal insufficiency 9) nephrolithiasis due to hyperoxaluria & calcium oxalate stones [3] 10) consider enterovesical fistula in patients with cystitis [3] * acrodermatitis enteropathica due to zinc deficiency may occur with small intestinal disease without resection of the ileum [37,38] Management: 1) general a) treat to target - resolution of abdominal pain & diarrhea - resolution of ulceration at ileocolonoscopy - treat to target could overtreat patients with low risk of disease progression - personalized approach [30] b) aggressive early intervention (within 18 months of diagnosis) associated with better outcomes [30 c) assessment & management of stress, depression, & anxiety [33] d) vaccines - pneumococcal vaccine prior to immunosuppressive therapy if possible - seasonal influenza vaccine - avoid live virus vaccines with immunosuppressive therapy - delay live virus vaccination 1-6 months after discontinuation of immunosuppressive therapy - Shingrix vaccine recommended e) monitor symptoms & biomarkers for patients in remission - serum C-reactive protein, fecal calprotectin every 6-12 months [39] 2) pharmacologic agents a) glucocorticoids - prednisone 40-60 mg QD, tapered over 2 months - SoluMedrol 125 mg IV every 6 hours for severe exacerbations - maintenance dose of prednisone may be required - budesonide may be preferred steroid - minimal systemic effects [4] due to high 1st pass hepatic metabolism [3] - right colon disease [3] - controlled-ileal release budesonide (9 mg QD) for mild to moderate disease limited to terminal ileum & right colon [33] - not useful for maintenance of remission > 4 months [3] - avoid glucocorticoids with septic complications, abscesses & fistulas - sepsis may be masked in patients on chronic glucocorticoids - sepsis in patients on chronic glucocorticoids may require stress doses because of adrenal insufficiency b) immunosuppressive agents - indicated as steroid-sparing agents or as primary therapy for fistulous disease - +/- 2-6 months delay before onset of action (not so [3]) - TNF-alpha inhibitor: infliximab, adalimumab, certolizumab - indicated for initial therapy in moderate to severe Crohn's disease [3] - also effective for treatment of enteropathic arthritis - treatment of fistulous disease after surgical drainage of abscesses [3] - use in conjuction with azathioprine or 6-mercaptopurine results in the highest rate of mucosal healing [3] - infliximab: induction with (5 mg/kg at 0, 2, & 6 weeks) [8] - infliximab & adalimumab similar in efficacy & rates of complications [19] - useful for induction of remission [22] - ~ 1/2 of patients discontinue these drugs - adalimumab, infliximab, & infliximab plus azathioprine superior to azathioprine/6-mercaptopurine & certolizumab for both induction & maintenance of remission [22] - adalimumab superior to vedolizumab for maintenance of remission [22] - certolizumab may be TNF-alpha inhibitor of choice during pregnancy - certolizumab is pegylated thus should have minimal placental transfer [3] - routine monitoring of TNF-alpha inhibitor levels with ELISA not currently recommended [NGC,NICE] - discontinuation of TNF-alpha inhibitor associated with relapse more often than not [30] - TNF-alpha inhibitor may be more effective when use in combination with an immunomodulator such as azathioprine [3] - natalizumab [5], vedolizumab [33] for disease refractory to TNF inhibitor - ustekinumab for patients with prior treatment failure or without prior exposure to TNF inhibitors [33] - risankizumab (Skyrizi) for moderate to severe Crohn's disease - azathioprine (Imuran) 100-150 mg QD - azathioprine + methotrexate no better than placebo for induction of remission [22] - effective for reduction of remission in combination with adalimumab or infliximab [22] - useful for maintenance of remssion [22] - check thiopurine methyltransferase in erythrocytes prior to administration [3] - 6-mercaptopurine (Purinethol) 50 mg QD - 6-mercaptopurine + methotrexate no better than placebo for induction of remission [22] - useful for maintenance of remssion [22] - methotrexate for severe, unresponsive disease - cyclosporine for severe, unresponsive disease - thalidomide induces remission in children with refractory Crohn's disease (46% vs 8% for placebo) [17] c) 5-aminosalicylates have minimal efficacy in Crohn's disease [3] - sulfasalazine (Azulfidine) for mild-moderate Crohn's colitis [3,33] - olsalazine (Dipentum) - mesalamine (Asacol, Pentasa) - may be useful for small bowel disease - not as effective as in ulcerative colitis because of the transmural pathology in Crohn's disease d) NSAIDS may exacerbate disease activity [33] e) metronidazole (Flagyl) - 250 mg QID or 10-20 mg/kg/day - indications - colonic, fistulous disease (fistulas) - perirectal abscess - do not use as primary therapy [33] f) ciprofloxacin may be useful in selected patients [3] g) antidiarrheal agents - loperamide 1-2 tabs BID-QID - cholestyramine 4 gm BID for bile-salt induced diarrhea - post ileal resection (bile acids resorbed in ileum) [37] h) vitamin B12 monthly injections for extensive ileal disease or prior ileal resection 3) extraintestinal manifestations of Crohn's disease typically resolve with treatment of the underlying inflammatory bowel disease [3] - pharmaceuticals that treat both inflammatory bowel disease & enteropathic arthritis include: - sulfasalazine, azathioprine, methotrexate, TNF-alpha inhibitors, glucocorticoids [3,38] - case of oral presentation of Crohn's disease [24] - mesalamine & prednisone initiated & slowly tapered - maintenance of remission with mercaptopurine - oral lesions slowly resolved over 12 months 4) surgery a) NOT cured by surgical resection (in contrast with ulcerative colitis) b) indications: - obstruction - pyogenic abscess - fistulas refractory to medical therapy - intestinal perforation - toxic megacolon - refractory disease - severe hemorrhage c) colectomy is advised for patients with non-adenoma-like dysplasia-associated lesion or mass [9] d) also see complications e) post-surgical management [31] - early pharmacologic prophylaxis - exception: low-risk patients who refuse therapy - cholestyramine for chronic non-bloody diarrhea after ileal resection [37,38] - cholestyramine 4 gm BID for bile-salt induced diarrhea - post ileal resection (bile acids resorbed in ileum) [37] - vitamin B12 monthly injections for prior ileal resection - use TNF-alpha inhibitor or thiopurine - exception: 3-12 months of metronidazole for low-risk patients - do not use mesalamine (or other 5-aminosalicylates), budesonide, or probiotics after surgical remission - postoperative endoscopic monitoring at 6-12 months after surgical resection - start or escalate TNF-alpha inhibitor, thiopurine, or both for asymptomatic endoscopic recurrence [31] 5) diet a) high fiber diet may reduce risk of flares [27] b) low-residue diet when obstructive symptoms present c) total parenteral nutrition (TPN) for severe, unresponsive disease d) fish oil may be of some benefit e) increase fruits & vegetables - exception; symptomatic or significant fibrostricturing Crphn's disease, restrict insoluble fiber intake [35] f) reduce consumption of saturated fats [35] 6) smoking exacerbates Crohn's disease [33] 7) cancer surveillance by colonoscopy after 10 years of disease a) hemoccult cards are not useful b) flexible sigmoidoscopy is not useful c) ref [3] suggests colonoscopy every 1-2 years

Interactions

disease interactions

Related

distinguishing features of ulcerative colitis vs Crohn's disease enteropathic arthritis; inflammatory bowel-associated arthritis inflammatory bowel disease in pregnancy ulcerative colitis (UC)

Specific

Crohn's ileitis

General

inflammatory bowel disease

Database Correlations

OMIM correlations

References

  1. Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 341-43
  2. Manual of Medical Therapeutics, 28th ed, Ewald & McKenzie (eds), Little, Brown & Co, Boston, 1995, pg 358
  3. Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2006, 2009, 2012, 2015, 2018, 2021. - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  4. Prescriber's Letter 8(11):64 2001
  5. Journal Watch 23(4):34, 2003 Ghoush S et al Natalizumab for active Crohn's disease. N Engl J Med 348:24, 2003 PMID: 12510039 - von Andrian UH & Engelhardt B Alpha4 integrins as therapeutic targets in autoimmune disease. N Engl J Med 348:68, 2003 PMID: 12510047
  6. Prescriber's Letter 12(9): 2005 Drug Therapy for Ulcerative colitis Detail-Document#: 211112 (subscription needed) http://www.prescribersletter.com
  7. Dotan I, Fishman S, Dgani Y, Schwartz M, Karban A, Lerner A, Weishauss O, Spector L, Shtevi A, Altstock RT, Dotan N, Halpern Z. Antibodies against laminaribioside and chitobioside are novel serologic markers in Crohn's disease. Gastroenterology. 2006 Aug;131(2):366-78. PMID: 16890590
  8. D'Haens G, Baert F, van Assche G, Caenepeel P, et al, Inflammatory Bowel Disease Research Group; North-Holland Gut Club. Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn's disease: an open randomised trial. Lancet. 2008 Feb 23;371(9613):660-7. PMID: 18295023
  9. Farhi D et al. Significance of erythema nodosum and pyoderma gangrenosum in inflammatory bowel diseases: A cohort study of 2402 patients. Medicine (Baltimore) 2008 Sep; 87:281. PMID: 18794711
  10. Farraye FA et al AGA Medical Position Statement on the Diagnosis and Management of Colorectal Neoplasia in Inflammatory Bowel Disease. Gastroenterology 2010, 138(2):738-745 PMID: 20141809 http://www.gastrojournal.org/article/S0016-5085(09)02202-1/fulltext corresponding NGC guideline withdrawn Dec 2015
  11. OMIM :accession 611081
  12. Colombel JF, Sandborn WJ, Reinisch W Infliximab, azathioprine, or combination therapy for Crohn's disease. N Engl J Med. 2010 Apr 15;362(15):1383-95 PMID: 20393175
  13. Regueiro M, Mardini H. Treatment of perianal fistulizing Crohn's disease with infliximab alone or as an adjunct to exam under anesthesia with seton placement. Inflamm Bowel Dis. 2003 Mar;9(2):98-103. PMID: 12769443
  14. Grainge MJ et al. Venous thromboembolism during active disease and remission in inflammatory bowel disease: A cohort study. Lancet 2010 Feb 20; 375:657. PMID: 20149425 - Nguyen GC and Yeo EL. Prophylaxis of venous thromboembolism in IBD. Lancet 2010 Feb 20; 375:616. PMID: 20149426
  15. Lichtenstein GR, Hanauer SB, Sandborn WJ et al Management of Crohn's disease in adults. Am J Gastroenterol. 2009 Feb;104(2):465-83 PMID: 19174807
  16. Khalili H et al Physical activity and risk of inflammatory bowel disease: prospective study from the Nurses's Health Study cohorts. BMJ 2013;347:f6633 PMID: 24231178 http://www.bmj.com/content/347/bmj.f6633
  17. Lazzerini M et al Effect of Thalidomide on Clinical Remission in Children and Adolescents With Refractory Crohn Disease. A Randomized Clinical Trial. JAMA. 2013;310(20):2164-2173 PMID: 24281461 http://jama.jamanetwork.com/article.aspx?articleid=1785463
  18. Gevers D et al. The treatment-naive microbiome in new-onset Crohn's disease. Cell Host Microbe 2014 Mar 12; 15:382 PMID: 24629344
  19. Osterman MT et al. Comparative effectiveness of infliximab and adalimumab for Crohn's disease. PMID: 23811254
  20. Ananthakrishnan AN et al. Colonoscopy is associated with a reduced risk for colon cancer and mortality in patients with inflammatory bowel diseases. Clin Gastroenterol Hepatol 2014 Jul 17 PMID: 25041865 http://www.cghjournal.org/article/S1542-3565%2814%2901047-7/abstract
  21. Nelson BA, Kaplan JL, El Saleeby CM, Lu MT, Mark EJ Case 39-2014 - A 9-Year-Old Girl with Crohn's Disease and Pulmonary Nodules. N Engl J Med 2014; 371:2418-2427 PMID: 25517709 http://www.nejm.org/doi/full/10.1056/NEJMcpc1410938
  22. Hazlewood GS et al. Comparative effectiveness of immunosuppressants and biologics for inducing and maintaining remission in Crohn's disease: A network meta-analysis. Gastroenterology 2015 Feb; 148:344 PMID: 25448924
  23. Laine L et al. SCENIC international consensus statement on surveillance and management of dysplasia in inflammatory bowel disease. Gastrointest Endosc 2015 Mar; 81:489 PMID: 25708752 http://www.giejournal.org/article/S0016-5107%2814%2902578-4/abstract
  24. Aguirre A, Nugent CA Images in Clinical Medicine: Oral Manifestation of Crohn's Disease. N Engl J Med 2015; 373:1250. September 24, 2015 PMID: 26398073 http://www.nejm.org/doi/full/10.1056/NEJMicm1413715
  25. Terdiman JP, Gruss CB, Heidelbaugh JJ et al American Gastroenterological Association Institute guideline on the use of thiopurines, methotrexate, and anti-TNF-alpha biologic drugs for the induction and maintenance of remission in inflammatory Crohn's disease. Gastroenterology. 2013 Dec;145(6):1459-63 PMID: 24267474
  26. Baumgart DC, Sandborn WJ Crohn's disease. Lancet. 2012 Nov 3;380(9853):1590-605. PMID: 22914295
  27. Brotherton CS et al. Avoidance of fiber is associated with greater risk of Crohn's disease flare in a 6-month period. Clin Gastroenterol Hepatol 2015 Dec 31 PMID: 26748217
  28. Oikonomou KA, Kapsoritakis AN, Stefanidis I, Potamianos SP. Drug-induced nephrotoxicity in inflammatory bowel disease. Nephron Clin Pract. 2011;119(2):c89-94; Review. PMID: 21677443 Free Article
  29. Kabbani TA, Koutroubakis IE, Schoen RE et al Association of Vitamin D Level With Clinical Status in Inflammatory Bowel Disease: A 5-Year Longitudinal Study. Am J Gastroenterol. 2016 May;111(5):712-9. PMID: 26952579
  30. Colombel JF, Narula N, Peyrin-Biroulet L. Management Strategies to Improve Outcomes of Patients with Inflammatory Bowel Diseases. Gastroenterology. 2016 Oct 5. PMID: 27720840
  31. Nguyen GC et al. American Gastroenterological Institute guideline on the management of Crohn's disease after surgical resection. Gastroenterology 2016 Nov 10; PMID: 27840074 - Regueiro M et al. American Gastroenterological Association technical review on the management of Crohn's disease after surgical resection. Gastroenterology 2016 Nov 10 PMID: 27840073
  32. Crohn Disease Expert Panel, including the Society of Abdominal Radiology Crohn's Disease-Focused Panel, the Society of Pediatric Radiology, and the American Gastroenterological Association. In: Anello J, Feinberg B, Heinegg J et al New Clinical Practice Guidelines, February 2018. Medscape. February 07, 2018 https://reference.medscape.com/viewarticle/892328 - Bruining DH, Zimmermann EM, Loftus EV Jr, et al. Consensus Recommendations for Evaluation, Interpretation, and Utilization of Computed Tomography and Magnetic Resonance Enterography in Patients With Small Bowel Crohn's Disease. Gastroenterology. 2017 Dec 30. PMID: 29329905 http://www.gastrojournal.org/article/S0016-5085(17)36658-1/fulltext
  33. Lichtenstein GR, Loftus EV, Isaacs KL et al. ACG clinical guideline: Management of Crohn's disease in adults. Am J Gastroenterol 2018 Apr; 113:481-517 PMID: 29610508 http://gi.org/wp-content/uploads/2018/04/ajg201827.pdf
  34. Feld L, Glick LR, Cifu AS. Diagnosis and Management of Crohn Disease. JAMA. Published online April 10, 2019 PMID: 3096932 https://jamanetwork.com/journals/jama/fullarticle/2730734
  35. Levine A, Rhodes JM, Lindsay JO et al. Dietary guidance for patients with inflammatory bowel disease from the international organization for the study of inflammatory bowel disease. Clin Gastroenterol Hepatol 2020 Feb 14 PMID: 32068150 https://www.cghjournal.org/article/S1542-3565(20)30185-3/pdf
  36. Walsh N Smoking Worsens Crohn's Disease - Smokers were more likely to have stricturing or penetrating disease, Canadian study showed. MedPage Today December 10, 2020 https://www.medpagetoday.com/meetingcoverage/aibd/90134 - Chattha R, et al Smoking status increases the likelihood of advanced disease phenotype in Crohn's disease. Advances in Inflammatory Bowel Disease (AIBD) 2020; Poster 016.
  37. NEJM Knowledge+ Gastroenterology
  38. NEJM Knowledge+ Complex Medical Care
  39. Ananthakrishnan AN, Adler J, Chachu KA et al AGA Clinical Practice Guideline on the Role of Biomarkers for the Management of Crohn's Disease. PMID: 37981354 Gastroenterology. 2023 Dec;165(6):1367-1399 https://www.gastrojournal.org/article/S0016-5085(23)05064-3/fulltext
  40. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Crohn's Disease https://www.niddk.nih.gov/health-information/digestive-diseases/crohns-disease