Crohn Disease


Article Author:
Indika Ranasinghe


Article Editor:
Ronald Hsu


Editors In Chief:
Casey Ciresi


Managing Editors:
Avais Raja
Orawan Chaigasame
Khalid Alsayouri
Kyle Blair
Radia Jamil
Erin Hughes
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Navid Mahabadi
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Abbey Smiley
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beenish Sohail
Hajira Basit
Phillip Hynes
Sandeep Sekhon


Updated:
6/18/2019 3:38:15 AM

Introduction

Crohn disease (CD) and ulcerative colitis (UC) are two conditions commonly referred to inflammatory bowel disease (IBD). They are immunologically mediated inflammatory diseases of the gastrointestinal tract. In CD, the inflammation extends through the entire thickness of the bowel wall from the mucosa to the serosa. The disease runs a relapsing and remitting course. With multiple relapses, CD can progress from an initially mild to moderate inflammatory conditions to severe penetrating (fistulization) and/or stricturing disease.[1][2][3][4][5][4]

Etiology

Although the exact etiology of inflammatory bowel disease (IBD) is not known, there is substantial evidence to suggest that the disease is resulting from an inappropriate immune response in the bowel to situations from environmental factors such as drugs, toxins, infections or intestinal microbes in a genetically susceptible host. More than a hundred genes associated with IBD have been identified. In Crohn's disease particularly, there appears to be a genetic association with phenotypes. Specifically, NOD2/CARD15 mutations were found to be associated with a phenotype of Crohn's disease which was associated in those diagnosed at a younger age, with ileal involvement, increased severity of ileal disease requiring surgical intervention/reoperation. In the future, this genotyping could potentially provide prognostic information on the severity of the disease. Furthermore, it could predict which patient's should be considered for surgical management vs. medical management based on a more detailed understanding of genetic analysis.[6]

Epidemiology

Crohn's disease (CD) is most commonly seen in the western developed world in North America, northern Europe, and New Zealand. Its incidence has a bimodal distribution with the onset occurring most frequently between ages 15 to 30 years and 40 to 60 years old. It is more prominent in urban than rural areas. There is a high incidence in Northern Europeans and Jewish descent (incidence 3.2/1000) contrasting to a significant infrequent prevalence in Asians, Africans, and South Americans.[7] However, recent studies have shown a significant increase in incidence in rapidly industrializing areas of Asia, Africa, and Australasia.[8]

Pathophysiology

The pathophysiology is multifactorial and involves genetic predisposition, infectious, immunological, environmental, and dietary. The characteristic transmural inflammation can include the entire GI tract from mouth to the perianal area; although most frequently involve terminal ileum and right colon. The initial lesion starts out as an infiltrate around an intestinal crypt. This goes on to develop an ulceration first in the superficial mucosa and involves to deeper layers. As the inflammation progresses, non-caseating granulomas form involving all layers of the intestinal wall. It can develop into the classic cobblestone mucosal appearances and skip lesions along the length of the intestine sparing areas with normal mucosa. As the flare of Crohn's settles, scarring replaces the inflamed areas of the intestines.[9]

Toxicokinetics

The immune-mediated response in Crohn's disease involves both innate and acquired mechanisms by macrophages, neutrophils, and T-cells in the intestine which promote pro-inflammatory mediators like TNF-alpha. Colonic Crohn's lesions were found to have high levels of cytokines like IFN-gamma, IL-2, IL-12, and IL-18. Crohn's disease is primarily regulated by TH1 and TH17 mediated processes.[10]

History and Physical

Patients with flare-ups of Crohn's disease typically presents with abdominal pain (right lower quadrant), flatulence/bloating, diarrhea (can include mucous and blood), fever, weight loss, anemia.

In severe cases, perianal abscess, perianal Crohn's disease, and cutaneous fistulas can be seen.

Crohn's disease is associated with extraintestinal manifestations including episcleritis, uveitis, stomatitis, aphthous ulcers, liver steatosis, gallstones, cholangitis, primary sclerosing cholangitis, nephrolithiasis, hydronephrosis, urinary tract infections, arthritis (spine - sacral, knee, ankles, hips, wrist, elbows), ankylosing spondylitis, erythema nodosum, and pyoderma gangrenosum.[11]

Evaluation

Stool tests to rule out infections include culture and sensitivities, ovum and parasites, Clostridium difficile toxins, leukocyte count.  Stool for calprotectin can detect active CD and also used for monitoring disease.[12][13][14][15]

Blood tests including baseline CBC and a metabolic panel can highlight the presence of anemia (B12  or iron deficiency) or liver disease. Special serology such as normal anti-neutrophil cytoplasmic antibodies (ANCA) and raised anti-saccharomyces cerevisiae antibodies (ASCA) can distinguish Crohn's disease from ulcerative colitis. C-reactive protein (CRP) or sedimentary rate (ESR) can reflect the severity of the inflammation.

CT scan/MRE of the abdomen and pelvis can detect abscesses and fistulization. The choice between CT or MR enterography is largely directed at minimizing radiation exposure in younger populations. Both give a higher definition of the diseased intestine. However, MRI can provide more detail when investigating the fistulizing disease. The use of video capsule endoscopy (VCE) can visualize the small bowel for CD when regular endoscopy or colonoscopy cannot reach to visualize these areas.

Before initiation of any treatment, vaccination history (tetanus, diphtheria, pertussis, HPV, influenza, pneumococcal, hepatitis A, hepatitis B, MMR, VZV) should be known, if no prior history titers of MMR, VZV, and hepatitis A/B should be checked. Baseline PPD with CXR should also be checked before any treatment. Baseline thiopurine methyltransferase (TPMT) levels should be checked before deciding on treatment options. Low levels of TMPT may result in increased risk of side effects, whereas very high levels may decrease the effectiveness of prescribed treatment.

Treatment / Management

The medical treatment is broadly grouped into two classes:

  • Mild to moderate disease can be treated by oral mesalamine, immunomodulators such as thiopurines (mercaptopurines, azathioprine), methotrexate, and steroids.
  • Moderate to severe disease (including fistulizing disease) will be best treated using a combination of immunomodulators and biologics (infliximab, adalimumab, golimumab, vedolizumab) or biologics alone.[10]

Biologics are immunoglobulins engineered to direct against specific cytokines or receptors involving in the inflammation process. Each biologic agent works against one specific site at a molecular level. Anti-tumor necrosis factor (TNF) alpha is a monoclonal antibody that can block the TNF in the circulation from their inflammatory actions. Anti-integrin agents are adhesion molecule inhibitors that bind the subunits of the MAdCAM receptors of the endothelial cells at the inflammatory sites. They halt the trafficking of lymphocytes from the circulation into the wall of the intestine, thereby stopping the inflammatory response targeted at the bowel.  Examples of anti-TNF agents are infliximab, adalimumab, golimumab. Examples of adhesion molecule inhibitors are natalizumab, vedolizumab. Vedolizumab is gut-specific and has less systemic side effects. Many newer therapeutic agents for inflammatory bowel disease are in the pipeline.

Surgical treatments are used for complications such as bowel obstructions, abscess, fistulas, or perforated bowel.

Dietician input and nutritional supplementation are highly recommended before and during treatment of Crohn's disease.[16][17][18][19]

Enhancing Healthcare Team Outcomes

The diagnosis and management of Crohn disease is an interprofessional that includes a nurse practitioner, internists, hematologist, gastroenterologist, general surgeon, dietitian, stoma nurse and a pharmacist. The disorder affects many organs in the body and hence the appropriate specialist should be consulted early on in the disease course. The disorder is usually managed with medications but complications require surgery. Most patients have relapses and remissions and need life long follow up. The prognosis for most patients with crohn disease is guarded and the quality of life is poor. [20](Level V)

 

 


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Crohn Disease - Questions

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What is best treatment for a patient requiring elective surgery for Crohn disease with obstructive symptoms?



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What is not a microscopic feature of Crohn disease?



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Which is true about surgery for Crohn disease?



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Which medication is used to treat Crohn disease?



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A 17-year-old female presents with a 4-month history of vague abdominal pain and low-grade fever. She says she has extreme pain when she defecates. She has general malaise and arthralgia. Her abdominal radiographs are unremarkable and rectal exam is very painful. Colonoscopy revealed significant inflammation in the ileocecal area with skip lesions. Biopsy revealed transmural lesions with a neutrophilic infiltrate. What is the most likely diagnosis?



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Which gene is clearly identified in patients with inflammatory bowel disease?



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Which monoclonal antibody is used in the treatment of Crohn disease?



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What organism is most commonly implicated in Crohn disease?



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Which of the following is NOT a feature of Crohn disease?



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Which of the following disorders has a propensity to affect the terminal ileum more than other parts of the intestine?



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Crohn disease is most common in which segment of bowel?



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Which of the following is a false statement about Crohn Disease?



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A female with recurrent abdominal pain, weight loss, and intermittent tenesmus undergoes a colonoscopy. Biopsy of the mucosa reveals discontinuous transmural inflammation associated with deep mucosal ulcers and granulomas. What is the most likely diagnosis?



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An elemental diet is best suited for patients with which condition?



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Which of the following is not true of Crohn disease (CD)?



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Which of the following is NOT a feature of Crohn disease?



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A patient is taken to the operating room for surgery for appendicitis. In the operating room, he has a normal appendix but is found to have ileitis. What is the most appropriate management for this patient?



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Fistulae are most common in which gastrointestinal disease?



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A 29-year-old female with vague abdominal pain undergoes a barium study. The radiologist reports that there is a "cobblestone" appearance of the terminal ileum. Which is the most likely diagnosis?



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Which is the false statement about Crohn's disease?



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What is the etiology of Crohn disease?



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Which of the following is used for initial treatment of Crohn disease?



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Which is implicated in the etiology of Crohn disease?



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Which is best for the treatment of Crohn disease (CD)?



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What is the most commonly involved area in Crohn disease?



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Select the condition not commonly seen as an extraintestinal complication of Crohn disease (CD).



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Which of the following drugs is NOT used to treat Crohn disease?



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Which of the following does NOT characterize Crohn disease?



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Which of the following is the best initial management of mild Crohn disease (CD) of the distal rectum?



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A person with long-standing Crohn disease presents with megaloblastic anemia. What is the likely etiology?



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Which of the following diseases specifically affects the terminal ileum?



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Granulomas are seen in which of the following diseases?



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Which disease process can cause transmural inflammation?



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What condition has anti-saccharomyces cerevisiae antibodies?



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Which of the following diseases is most likely to present with an abdominal mass?



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Which of the following is the most common eye complication in patient's with Crohn disease?



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Which one of the following statements is not true regarding arthritis associated with Crohn disease (CD)?



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All of the following are principal components of a treatment program for children with Crohn disease (CD), except:



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What does a "string sign" seen on an upper gastrointestinal series examination indicate?



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Crohn disease can affect:



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A 56-year-old obese male with diabetes and Crohn disease presents with severe abdominal pain, nausea, and vomiting. He says the pain started a few hours ago after a meal. He is not able to lie down. Examination reveals a tender rigid abdomen with rebound and guarding. What is the next step?



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In an obese diabetic patient with Crohn disease undergoing abdominal surgery, what is the major concern post operatively?



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Which of the following tests should be ordered in a patient suspected of having Crohn disease?



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Which medication is often used initially for a patient with newly diagnosed Crohn disease?



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In a 23-year-old patient with Crohn disease (CD) wants to know about pregnancy, what is the correct statement?



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Which of the following statements is true of Crohn disease?



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Which patients can benefit from low-residue diets?



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A 15 year old female has a 6 month history of weight loss, intermittent fevers, pain with defecation, periumbilical abdominal pain, and diarrhea. She has seen blood per rectum on several occasions. Select the most likely diagnosis.



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28 year old female with Crohn disease who is on Infliximab for maintenance treatment just found out she is 6 weeks pregnant. She would like to know if it is safe for her to continue or change her current medication during the course of her pregnancy. Which of the following would be the safest medication for her to be on and not adversely affect her pregnancy?



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A 35-year-old patient with Crohn disease and multiple episodes of flare-ups presents with rectal pain on defecation and new yellowish discharge from his perianal area. What is the best modality of investigating this complication?



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A 24-year-old female presents to her primary care provider with complaints of “weird bowel movements,” and specks of blood in her stools. She reports that she has always had irregular bowel movements, but now the stool seems to float in the toilet. When asked about any additional symptoms, she notes that she has lost about 10 pounds over the last few months without a change in her appetite. Which of the following is associated with her likely diagnosis?



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A patient presents with chronic crampy abdominal pain and diarrhea. She reports no bloody stools but has experienced weight loss the past few months without any associated changes to her habits. The patient also reports new lesions on her mouth. Which of the following gene defects is associated with the most likely disease present in this patient?



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A client has been admitted with Crohn disease and a flare-up. Which of the following nursing interventions and medications are appropriate in the care of this client? Select all that apply.



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A 28-year-old male was admitted with a 5-week history of abdominal pain and bloody diarrhea. He had lost 4 kg in weight. He smoked 20 cigarettes a day. On examination, his mucous membrane was mild pale and moist, and a temperature of 37.7 C The physical examination was unremarkable except for a mild tenderness over the right iliac fossa. Laboratory investigations showed a low hemoglobin of 11.2 mg/l with a normal white-blood-cell count. Urea and electrolytes were normal. Investigation on his anemic state showed normal folate, serum vitamin B12, ferritin, and iron. His total serum protein was lower than the normal range. Fecal examination and culture were normal. No autoimmune antibody was detected to a broad range of autoantigens including DNA, and neutrophil cytoplasmic antigens (ANCA). Sigmoidoscopy revealed bleeding and mucopurulent secretion in a red, granular mucosa and a small area of ulceration in the epithelium and the presence of many crypt abscesses. Few granulomas (non-caseating) were also revealed. Colonoscopy showed inflammatory strictures in the ascending and transverse colons. His therapy consisted of corticosteroids that achieved his improvement. What is the most likely diagnosis?



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Two patients, patient A and patient B, both have Crohn disease involving the terminal ileum and were managed surgically by resection of the terminal ileum and undergoing end-to-end anastomosis using a linear stapler. However, in patient A, more than 100 cm of the ileum was resected, while in patient B, only 60 cm of the terminal ileum was resected. Which of the following complications is expected to happen in patient A but less likely to occur in patient B?



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Crohn Disease - References

References

Lightner AL,McKenna NP,Alsughayer A,Loftus EV Jr,Raffals LE,Faubion WA,Moir C, Anti-TNF biologic therapy does not increase postoperative morbidity in pediatric Crohn's patients. Journal of pediatric surgery. 2019 Jan 18;     [PubMed]
Marazuela García P,López-Frías López-Jurado A,Vicente Bártulos A, Acute abdominal pain in patients with Crohn's disease: what urgent imaging tests should be done? Radiologia. 2019 Feb 13;     [PubMed]
Aksan A,Farrag K,Stein J, An update on the evaluation and management of iron deficiency anemia in inflammatory bowel disease. Expert review of gastroenterology     [PubMed]
Hwang JH,Yu CS, Depression and resilience in ulcerative colitis and Crohn's disease patients with ostomy. International wound journal. 2019 Mar;     [PubMed]
Fadeeva NA,Korneeva IA,Knyazev OV,Parfenov AI, Biomarkers of inflammatory bowel disease activity. Terapevticheskii arkhiv. 2018 Dec 30;     [PubMed]
Parfenov AI,Knyazev OV,Kagramanova AV,Fadeeva NA, Personalized medicine in the treatment of inflammatory bowel diseases. Terapevticheskii arkhiv. 2018 Feb 15;     [PubMed]
Kedia S,Das P,Madhusudhan KS,Dattagupta S,Sharma R,Sahni P,Makharia G,Ahuja V, Differentiating Crohn's disease from intestinal tuberculosis. World journal of gastroenterology. 2019 Jan 28;     [PubMed]
Moon JS, Clinical Aspects and Treatments for Pediatric Inflammatory Bowel Diseases. Pediatric gastroenterology, hepatology     [PubMed]
Brown SR,Fearnhead NS,Faiz OD,Abercrombie JF,Acheson AG,Arnott RG,Clark SK,Clifford S,Davies RJ,Davies MM,Douie WJP,Dunlop MG,Epstein JC,Evans MD,George BD,Guy RJ,Hargest R,Hawthorne AB,Hill J,Hughes GW,Limdi JK,Maxwell-Armstrong CA,O'Connell PR,Pinkney TD,Pipe J,Sagar PM,Singh B,Soop M,Terry H,Torkington J,Verjee A,Walsh CJ,Warusavitarne JH,Williams AB,Williams GL,Wilson RG, The Association of Coloproctology of Great Britain and Ireland consensus guidelines in surgery for inflammatory bowel disease. Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland. 2018 Dec;     [PubMed]
de Kloet LC,Schagen SEE,van den Berg A,Clement-de Boers A,Houdijk MECAM,van der Kaay DCM, [Growth failure as a symptom of inflammatory bowel disease]. Nederlands tijdschrift voor geneeskunde. 2018 Nov 19;     [PubMed]
Rodríguez-Lago I,Ferreiro-Iglesias R,Nos P,Gisbert JP, Management of acute severe ulcerative colitis in Spain: A nationwide clinical practice survey. Gastroenterologia y hepatologia. 2019 Feb;     [PubMed]
Ambruzs JM,Larsen CP, Renal Manifestations of Inflammatory Bowel Disease. Rheumatic diseases clinics of North America. 2018 Nov;     [PubMed]
Inokuchi T,Takahashi S,Hiraoka S,Toyokawa T,Takagi S,Takemoto K,Miyaike J,Fujimoto T,Higashi R,Morito Y,Nawa T,Suzuki S,Nishimura M,Inoue M,Kato J,Okada H, Long-term outcomes of patients with Crohn's disease who received infliximab or adalimumab as the first-line biologics. Journal of gastroenterology and hepatology. 2019 Feb 6;     [PubMed]
Khan S,Rupniewska E,Neighbors M,Singer D,Chiarappa J,Obando C, Real-world evidence on adherence, persistence, switching and dose escalation with biologics in adult inflammatory bowel disease in the United States: A systematic review. Journal of clinical pharmacy and therapeutics. 2019 Mar 14;     [PubMed]
Zaidi D,Wine E, Regulation of Nuclear Factor Kappa-Light-Chain-Enhancer of Activated B Cells (NF-κβ) in Inflammatory Bowel Diseases. Frontiers in pediatrics. 2018;     [PubMed]
Coward S,Clement F,Benchimol EI,Bernstein CN,Avina-Zubieta JA,Bitton A,Carroll MW,Hazlewood G,Jacobson K,Jelinski S,Deardon R,Jones JL,Kuenzig ME,Leddin D,McBrien KA,Murthy SK,Nguyen GC,Otley AR,Panaccione R,Rezaie A,Rosenfeld G,Peña-Sánchez JN,Singh H,Targownik LE,Kaplan GG, Past and Future Burden of Inflammatory Bowel Diseases Based on Modeling of Population-Based Data. Gastroenterology. 2019 Jan 10;     [PubMed]
Ghersin I,Khteeb N,Katz LH,Daher S,Shamir R,Assa A, Trends in the epidemiology of inflammatory bowel disease among Jewish Israeli adolescents: a population-based study. Alimentary pharmacology     [PubMed]
Greuter T,Piller A,Fournier N,Safroneeva E,Straumann A,Biedermann L,Godat S,Nydegger A,Scharl M,Rogler G,Vavricka SR,Schoepfer AM, Upper Gastrointestinal Tract Involvement in Crohn's Disease: Frequency, Risk Factors, and Disease Course. Journal of Crohn's     [PubMed]
Fumery M,Pariente B,Sarter H,Savoye G,Spyckerelle C,Djeddi D,Mouterde O,Bouguen G,Ley D,Peneau A,Dupas JL,Turck D,Gower-Rousseau C, Long-term outcome of pediatric-onset Crohn's disease: A population-based cohort study. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. 2018 Dec 23;     [PubMed]
Targan SR, Biology of inflammation in Crohn's disease: mechanisms of action of anti-TNF-a therapy. Canadian journal of gastroenterology = Journal canadien de gastroenterologie. 2000 Sep;     [PubMed]

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