Clinical Case Conference

1. Clinical Case Conference Ravikanth Maddipati 01/26/2010

2. History • CC: Abdominal pain and diarrhea • 38 AA F w/ h/o GERD and depression developed sudden lower abdominal pain with subsequent watery diarrhea the day of admission • Lower abdominal pain was sudden and severe in onset, diffuse, R>L, and w/o distension. Had two episodes of n/v due to pain. • Denies any fevers, chills, hematochezia, melena, hematemsis. Did have a cousin with Crohn’s who was recently admitted for diarrhea 2/2 flare. Otherwise no sick contacts. Ate her usual foods and others who ate the same food did not get sick. • Recent medical and medication history only notable for being placed on amoxicillin for 6 days after having a recent tooth extraction. Otherwise no new meds or recent procedures • On arrival to the ED she was afebrile with normal vital signs. Labs were drawn and CT ab/p was performed. • During the day after admission she developed hematochezia. At this time a GI consult was called.

3. PMH: chronic abdominal pain from GERD and dyspepsia, depression • FH: Cousin with Crohn’s but otherwise no relevant GI history • SH: denies EtOH, + Smoking, no Drugs or IVDU • Allergies: NKDA • Meds: Zoloft, Prevacid, and amoxicillin

4. Physical Exam • Gen: Lying uncomfortably in bed, A&O X 3 • HEENT: Sclera anicteric • Chest: CTAB • Card: RRR, No MRG • Abd: Soft, ND, no HSM. TTP in lower quadrants w/ R>L w/o guarding/rebound, +BS. Otherwise benign abdominal exam. Rectal exam with maroon blood in rectal vault. • Ext: 2+ pulses, No rashes, or edema

5. Admission Labs/Studies • CBC: 10.5/13.1/244 • Metabolic panel, LFT’s, Amylase/Lipase WNL • Tox panel negative • CT Ab/P I+/O+: Diffuse colonic wall thickening, most pronounced in transverse colon, sparing distal sigmoid. Thickness approximately 9mm. Possible pseudo-membranous colitis, Infectious colitis, or IBD.

6. GI Evaluation • Repeat CBC after hematochezia was 7.0/9.5/162. Lactate was 0.6 • Stool studies: negative including C. Diff, E. Coli O:157, and O&P • Colonoscopy was performed • diffuse erythematous mucosa extending from hepatic flexure to proximal sigmoid colon. • areas of granular mucosa but no skip lesions, cobblestoning, or pseudopolyps • Diverticulosis and internal hemorrhoids also seen

7. Pathology : • specimens from hepatic flexure to sigmoid show extensive lamina propria hemorrhage with normal architecture and intact surface epithelium • minimal acute inflammation with unremarkable vasculature. • Acute or chronic colitis is unlikely. Appearance may indicate very early ischemic event.

8. What is your differential diagnosis? • What further studies would you do? • What treatment would your recommend?

9. Intestinal Ischemia • Due to disturbances in the arterial supply or venous drainage of the bowel that can involve the small intestine, the colon, or both. • Bowel can tolerate a 75% reduction of mesenteric blood flow and oxygen consumption for 12 hours • one fifth of the mesenteric capillaries are open at any time, and when oxygen delivery is decreased, the bowel adapts by increasing oxygen extraction • Pattern of injury is usually dictated by vascular supply and areas that lack collaterals

10. Celiac SMA IMA

11. Colonic Ischemia • Usually occurs in older persons and is the most common form of intestinal ischemic injury • Spectrum varies : • Annual incidence in predicated to be 7.2 cases per 100,000 person-years • 3.4 higher incidence in those with IBS than the general population • Risk factors include female gender, age >60, and pre-existing vascular conditions

12. Causes of Colonic Ischemia

13. Back to our patient • She had a CT angio of her abdomen and pelvis which were negative • Further history did not reveal any personal or family history of coagulopathies, vasculitis, prior abdominal surgeries, trauma, or any recent signs or symptoms of hypotension • It was felt her Colonic Ischemia was likely related to amoxicillin use i.e. Antibiotic Associated Hemorrhagic Colitis (AAHC)

14. Antibiotic Associated Hemorrhagic Colitis • Incidence of AAHC is unknown but appears to be more common in Japan • Most common antibiotics associated with AAHC are penicillin derivatives like amoxicillin and ampicillin. • Has been seen with macrolides, cephalosporin's, quinolones, and tetracycline's • Most commonly via oral route but paraenteral route can also lead to AAHC • Onset of symptoms generally within 2-7 days of taking antibiotic. • Sudden onset lower abdominal pain with associated loose stool • Hematochezia usually follows 4-6hrs later • Laboratory, radiologic, and colonoscopic findings similar to CI from other causes but AAHC is associated with a predominance of right-sided lesions • Symptoms resolve 1-3 days after discontinuation of offending agent followed by mucosal healing in 4-12 days • Path shows ischemic changes with increased sub-epithelial erythrocytes, with little-to-no mucosal inflammation • Mechanism is unknown but theories include hypersensitivity/allergic reaction, unidentified respiratory pathogen interacting with PCN derivatives, direct toxic effects of PCN, K. oxytoca overgrowth.

15. Case Series of AAHC • “Antibiotic-Associated Hemorrhagic Colitis”. Moulis H, Vender RJ. J ClinGastroenterol 1994;18(3):227-231 • review of 4 cases of AAHC in the setting of Amox/Amp use

16. Endoscopic Classification of AAHC • “An endoscopic study of antibiotic-associated hemorrhagic colitis”. Kishida T et. al. J. Nippon Med. Sch., Vol. 59, No. 6, 1992 • A study of 48 patients admitted to a Japanese hospital between 1978 and 1991 who underwent colonoscopy within 72hrs from onset of AAHC • Patient population consisted of equal number of women and men between ages 15-81 who were mainly treated with Ampicillin or amoxicillin for URI type symptoms but 2 cases of prophylactic use for dental extraction also included. • Endoscopic findings were categorized as major and minor findings • Major findings: Diffuse mucosal hemorrhage, Spotty mucosal hemorrhage, linear mucosal hemorrhage • Minor findings: Irregular ulcers, Aphthoid ulcers, linear erosions • Histological data was available for 24 patients and showed hemorrhage and mild to moderate inflammatory cell infiltration in the lamina propria mucosae.

17. Klebsiellaoxytoca and AAHC • “Klebsiella oxytoca as a Causative Organism of Antibiotic-Associated Hemorrhagic Colitis”. Hogenauer C et. al. N Engl J Med 2006; 355:2418-26. • Study of 22 consecutive patients with suspected AAHC with 6 out 22 as confirmed case via endoscopic and histopathologic criteria. • Stool samples from 6 AAHC cases cultured for K. oxytoca and its cytotoxicity was assayed • One of the isolated K. oxytoca strains was inoculated into rats treated with amoxicillin-cavulanate and assessed for development of AAHC • 5/6 patients with AAHC had K. oxytoca isolated and all those strains shown to be cytotoxic • Those on NSAID had more severe AAHC then those not. • K. oxytoca also found in 1.6% of control subjects, none of which had any diarrhea • All rats treated with amoxicillin-clavulanate and inoculated with K. oxytoca developed AAHC (histopathologic diagnosis) similar to that found in human subjects while none of the rats treated with antibiotics but not inoculated with K. oxytoca developed AAHC. • Conclusion: K. oxytoca exists temporarily in colon of some people on antibiotic therapy. This leads to overgrowth of K. oxytoca resulting in high cytotoxin concentration and mucosal damage.

18. Other Medication induced cause of Colonic Ischemia

19. Follow-up • Diagnosed patient with Amoxicillin induced AAHC • Hematochezia stopped 2-3 days after antibiotics were stopped • Was scheduled to see me in clinic but did not show multiple times