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Ravikanth Maddipati
01/26/2010
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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.
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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
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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
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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 pseudomembranous colitis, Infectious colitis, or IBD.
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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
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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.
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What is your differential diagnosis?
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What further studies would you do?
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What treatment would your recommend?
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Due to disturbances in the arterial supply or venous
drainage of the bowel that can involve the small
intestine, the colon, or both.
TYPE
FREQUENCY (%)
Colon ischemia
75
Acute mesenteric ischemia
25
Focal segmental ischemia
<5
Chronic mesenteric ischemia
<5
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
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Pattern of injury is usually dictated by vascular
supply and areas that lack collaterals
Celiac
SMA
IMA
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Usually occurs in older persons and is the most
common form of intestinal ischemic injury
Spectrum varies :
TYPE
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FREQUENCY (%)
Reversible colopathy and transient colitis
>50
Transient colitis
10
Chronic ulcerating colitis
20
Stricture
Gangrene
10
15
Fulminant universal colitis
<5
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
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Risk factors include female gender, age >60, and
pre-existing vascular conditions
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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
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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)
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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
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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 rightsided 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.
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“Antibiotic-Associated Hemorrhagic Colitis”. Moulis
H, Vender RJ. J Clin Gastroenterol 1994;18(3):227231
◦ review of 4 cases of AAHC in the setting of Amox/Amp use
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“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
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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.
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“Klebsiella oxytoca as a Causative Organism of Antibiotic-Associated
Hemorrhagic Colitis”. Hogenauer C et. al. N Engl J Med 2006; 355:241826.
◦ 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
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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
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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.
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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