Ravikanth Maddipati01/26/2010

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.

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

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

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.

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

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.

What is your differential diagnosis?

What further studies would you do?

What treatment would your recommend?

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

TYPE FREQUENCY (%)Colon ischemia 75

Acute mesenteric ischemia 25

Focal segmental ischemia <5

Chronic mesenteric ischemia <5

Celiac

SMA

IMA

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

TYPE FREQUENCY (%)Reversible colopathy and transient colitis >50Transient colitis 10Chronic ulcerating colitis 20Stricture 10Gangrene 15Fulminant universal colitis <5

Allergy Amyloidosis Heart failure or cardiac arrhythmias Hematologic disorders and coagulopathies

o APC resistance, AT def, PNH, PV, SCD Infection

o O157:H7,o Parasites(angiostrongylus)o Viruses(HBV, HCV, CMV)

Inferior Mesenteric artery Thrombosis Long-distance running Medications and Toxins: Alosetron, Cocaine, OCP, Antibiotics, Ergots,

Amphetamines, Laxatives, NSAIDs Pheochromocytoma Ruptured Ectopic pregnancy Shock Surgery Thromboembolism Trauma Vasculitis: Buerger’s, FMD, Kawasaki, PAN, SLE, Takayasu, Rheumatoid

vasculitis. Volvulus or strangulated hernia

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)

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.

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

“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.

“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.

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