CHAPTER 98 Small-Intestinal Ulcerations

1 JWST654-c98 JWST654-TalleyPrinter: Yet to ComeJuly 4, 2016 13:59 279mm 216mmCHAPTER 98 Small-Intestinal UlcerationsReza Y. Akhtar and Blair S. LewisHenry D. Janowitz Division of Gastroenterology, Mount Sinai School of Medicine, New York, NY, USAS ummaryThe differential diagnoses of ulcers of the small bowel arewell known. They include Crohn s disease, non-steroidal anti-inflammatory drugs (NSAIDs), radiation, vasculitis, medicationeffects, some infections, and certain neoplasms (Table ).Nonetheless, when faced with the finding of ulceration in the smallbowel, it can be difficult to come up with a final diagnosis. Crohn sdisease is most common, but NSAID use is also frequently , then, does a physician make the diagnosis of Crohn s diseasebased on the presence of ulcers seen only on endoscopy, capsule orotherwise?In the past, we were confident in making the diagnosis in the clin-ical setting of pain and diarrhea in a young person in whom a smallbowel series showed ileitis.

2 We clearly should be able to do the samewith endoscopic findings; that is, to combine the clinical scenariowith the endoscopic, rather than the radiographic, findings. Therecan be other evidence to support a diagnosis of Crohn s, includinga family history of inflammatory bowel disease (IBD) and abnor-mal serologies of antineutrophil cytoplasmic antibodies (ANCA)and anti-Saccharomyces cerevisiaeantibodies (ASCA), though thisis not the intended use of these blood tests. Endoscopic biopsy typ-ically cannot differentiate a Crohn s ulcer from an NSAID testing, such as computed tomographic (CT) scanning, gen-erally provides no additional information beyond what is suppliedby endoscopy. Grading the severity of inflammatory findings oncapsule endoscopy can provide more certainty in making a 45-year-old female presents with a history of obscuregastrointestinal (GI) bleeding. Her first episode was at 20 years ofage.

3 Since then, multiple episodes have occurred, occasionallyrequiring transfusion of packed red blood cells (RBCs). Evaluations,including colonoscopy, upper endoscopy, and bleeding scan, areunrevealing. Additionally, CT scan, Meckel s scan, and small bowelseries are normal. Her history is otherwise remarkable, except for rareNSAID use and hypertension, for which she takes endoscopy is performed and discloses diffuse mucosaledema and erythema associated with scattered ulceration andluminal narrowing at the mid-ileum (Figure ). These findingscorrelate to an activity score of 1232. Serologies of ASCA andp-ANCA are negative. Other laboratory values are the capsule exam, a double-balloon enteroscopy (DBE)from the transrectal approach is performed. Endoscopically, the areaand affected regions of the small bowel are identical to the capsulestudy. Biopsies reveal active inflammation. The clinical history,endoscopic appearance, and biopsies are consistent with Crohn are we to make the diagnosis of Crohn s disease in our casestudy?

4 There is no history of radiation therapy and no history ofmedication use, except the limited NSAID use described. diarrhea, simply bleeding. This is known to occur in Crohn s,but it is an unusual presentation. We can look for other evidenceto support our diagnosis, including a family history of IBD (there isnone) and serologies such as ANCA and ASCA (they are negative).These serologies help differentiate ulcerative colitis from Crohn s,but are now being used by physicians to confirm a diagnosis of sus-pected Crohn s disease. Unfortunately, using these serologies for thispurpose is not supported by the literature [1]. ASCA is detectedin 39 70% of patients with Crohn s disease and in only 0 5% ofhealthy subjects [1, 2]. The sensitivity of ASCA in correctly identi-fying Crohn s disease is 55%. ANCA is positive in 2 28% of Crohn spatients and in 20 85% of ulcerative colitis patients. It also has a lowsensitivity for diagnosing ulcerative colitis, at 56%.

5 Another way to diagnose Crohn s disease is to make a tissue diag-nosis. DBE is used to deeply intubate the small bowel from either theperoral or the transrectal approach [3]. Unfortunately, the hallmarkfinding of non-caseating granulomas is seen in a minority of cases[4]. Endoscopic biopsy cannot differentiate a Crohn s ulcer from anNSAID ulcer, though it can exclude neoplastic change, if testing, such as CT scanning, generally provides no informa-tion beyond what is found with capsule endoscopy [5]. Enlargedlymph nodes can be seen in chronic inflammatory changes, but thisfinding may only fuel the thought that there is a EndoscopyCapsule endoscopy has provided us with the ability to detectmucosal inflammatory change of the small intestine often missedby other techniques. In a pooled data analysis, comparing capsuleCHAPTER 98 Practical Gastroenterology and Hepatology Board Review Toolkit, , , , Keith D.

6 Lindor. 2016 John Wiley & Sons, Ltd. Published 2016 by John Wiley & Sons, Ltd. Companion website: : Yet to ComeJuly 4, 2016 13:59 279mm 216mm2 Small-Intestinal UlcerationsTable in the small s diseaseUlcerative jejuno-ilietisZollinger Ellison syndrome (ZES)Infections: mycobacterium, syphilis, typhoid and histoplasmosisMedications: potassium, non-steroidal anti-inflammatory drugs (NSAIDs)Vasculitis: polyarteritis nodosa, Churg Strauss disease, rheumatoid arthritis,systemic lupus erythematosis (SLE), Behc et s disease, Wegener s granulomatosis,cryoglobulinemia, Henoch Schonlein purpuraRadiation enteritisMeckel s diverticulumDuplication cystGraft-versus-host disease (GVHD)Neoplasms: adenocarcinoma, carcinoid, lymphomaendoscopy with ileocolonoscopy, push enteroscopy, and smallbowel series, capsule endoscopy had a miss rate for ulcers of [6]. A meta-analysis of studies comparing capsule endoscopyto other imaging modalities of the small bowel for IBD establishedthat capsule endoscopy has an incremental diagnostic yield of 25 40% over other modalities, including CT enterography, small bowelseries, and ileocolonoscopy [7].

7 One report described finding smallbowel ulcers in 22 patients in whom no ulcers could be identifiedby any other means [8]. These included Crohn s in 9, ulceratedneoplasms in 3, and Behc et s in 2. Yet, turning the ability to detectulcerations into a diagnosis has been difficult. The most commonclinical scenario is the opposite of that in the case study: it typicallyinvolves applying capsule endoscopy in patients with symptoms ofCrohn s disease in an effort to find Ulcerations . Suspicion of Crohn sdisease was previously defined at the discretion of the treatingphysician, and was usually considered when a patient had eitherabdominal pain or persistent diarrhea. Yields of capsule endoscopyare low when performed in patients with abdominal pain alone [9]or in patients with abdominal pain and diarrhea alone [10]. Theaddition of a sign or symptom of inflammation increases the yieldof capsule endoscopy. In the CEDAP-Plus study of 50 patients withsuspected Crohn s disease, signs of inflammation included elevatederthrocyte sedimentation rate, elevated C-reactive protein (CRP),thrombocytosis, and leukocytosis.

8 The finding of one of these mark-ers in addition to symptoms of pain and diarrhea increased the yieldof capsule endoscopy with an odds ratio of [11]. A landmarkpaper by Fireman enrolled patients with abdominal pain, diarrhea,anemia, and weight loss [12]. These patients had had symptomsfor an average of years and all had normal colonoscopies, upperendoscopies, and small bowel series. Crohn s disease was diagnosedin 12 of the 17 by capsule endoscopy. In a consensus paper, the Inter-national Conference of Capsule Endoscopy defined which patientsshould be suspected of having Crohn s disease [13]. The algorithmpresented includes individuals with symptoms plus either extrain-testinal manifestations, inflammatory markers, or abnormal imag-ing studies (Figure ). Unfortunately, none of this helps us withthe patient described in the case study, who has bleeding as the presence of inflammatory changes in the small bowel can notonly be seen in a variety of disease states, but can also be notedin normal individuals.

9 Goldstein conducted a trial comparing theeffects of naproxen, celecoxib, and placebo in the small bowel [14].Before randomization, all volunteers were forbidden NSAIDs for aperiod of 2 weeks. Goldstein reported that of the healthy vol-unteers had mucosal breaks after this run-in period. The study didnot measure these ulcers, and since these cases were excluded, we doFigure edema, luminal narrowing, and ulceration at capsule Abdominal painChronic DiarrheaWeight LossGrowth FailureColumn AGI SxFeverArthritis/ArthalgiasPyoderma / PerianalPSC/CholangitisColumn BExtraintestinal SxIron deficiencyESR/CRPL eukocytosisSerologiesColumn CInflammatory MarkersSB seriesCT scanColumn DAbnl ImagingSuspected Crohn's1 from A, 1 from othersFigure for suspected Crohn s disease. Source: Mergener 2007 [13]. Reproduced with permmission of Georg 98 JWST654-c98 JWST654-TalleyPrinter: Yet to ComeJuly 4, 2016 13:59 279mm 216mmSmall- intestinal Ulcerations3 Figure view of an activity score.

10 Source: Courtesy of Given Imaging, know their number or severity. Thus, ulcers in the small bowelmay be normal. How does one make a diagnosis?These differing clinical scenarios show the complexity of tryingto make a diagnosis based on an endoscopic image alone. Are theulcers seen on the capsule study in the case example a normal find-ing, secondary to the patient s occasional NSAID use, or do theyrepresent Crohn s disease? Though a few small ulcers may be nor-mal or may be secondary to NSAID use, most experts would agreethat numerous large ulcers can only mean Crohn s disease. This ismuch like our feelings toward ileitis seen on a small bowel changes are quite pronounced and could never been felt tobe normal or secondary to NSAID use. The necessity of grading theseverity of inflammatory change noted on capsule exams raises theneed for a scoring index. An index has been created and validated,and is presently part of standard capsule software (Figure ) [15].