Ischemic Colitis: A Clinical Case and Concise Review

1
ABSTRACT

A previously healthy 64-year-old lady presented with hematochezia, syncope, and

abdominal discomfort. Colonoscopy revealed findings consistent with segmental ischemic

colitis, which resolved with supportive therapy. Herein we review the case and discuss the

pathophysiology, diagnosis, and management of ischemic colitis.

2
CASE PRESENTATION

A 64-year-old lady with hypothyroidism and celiac disease presented with a one

week history of malaise and abdominal discomfort. On the day of her admission, she had

two syncopal episodes accompanied by hematochezia and melena stools. She denied

nausea, vomiting, hematemesis, diarrhea, or weight loss. She had no recent travel or

antibiotic and NSAID use. She is an ex-smoker and consumes two glasses of wine four times

a week. She had no family history of autoimmune disease, inflammatory bowel disease, or

gastrointestinal malignancy. On examination, she was afebrile. She had an orthostatic drop

and left lower quadrant abdominal tenderness

Laboratory investigations revealed anemia with a hemoglobin of 117 g/L. She had

no previous history of iron-deficiency anemia. Her other blood test results were normal

including complete blood counts, coagulation profile, creatinine and liver enzymes.

Although her CRP was elevated at 117 mg/L (normal <3.1), an autoimmune screen

including anti-neutrophil cytoplasmic antibody (ANCA), anti-nuclear antibody (ANA), and

double-stranded DNA were all negative. Stool cultures and C. difficile toxin were also

negative.

An esophagogastroduodenoscopy performed two days into her admission

demonstrated a small hiatus hernia. Gastric biopsies showed mild chronic gastritis with no

evidence of H. pylori infection. Her colonoscopy, however, revealed a 25 cm segment of

edematous and friable mucosa with loss of vascular margins at the splenic flexure (Figure

1). There was also significant diverticulosis. Colonic biopsy showed pseudomembranous

3
luminal inflammatory exudate, crypt atrophy, and laminal propria fibrosis suspicious for

ischemic colitis with a differential diagnosis of pseudomembranous colitis.

After these procedures, the patient was started on a 7 day course of antibiotic of

ciprofloxacin 500 mg BID and metronidazole 500 mg BID for a diagnosis of acute ischemic

colitis.

Follow up abdominal and pelvic computed tomographic (CT) scan with IV contrast

showed scattered diverticulosis involving the descending and sigmoid colon with no bowel

wall thickening or intestinal pneumatosis. Midline arterial vessels enhanced normally with

no radiological features of bowel ischemia.

4
 DISCUSSION

Epidemiology:

Ischemic colitis is the most common ischemic injury to the lower gastrointestinal

tract (1). Although it is commonly seen in the elderly between ages 70-79 years, it can

occur in almost any age group. Atypical cases have been reported in young healthy

endurance runners who would otherwise have no classical risk factors of hypertension,

cerebrocardiovascular disease, or history of abdominal surgery (2–4). Women are 1.48

times more likely than men to be affected, and the disease is more common in patients with

irritable bowel syndrome (IBS)(5). Although infrequent at baseline (44 cases per 100,000

person-years), the incidence of ischemic colitis is rising. Moreover, most cases of ischemic

colitis likely go undetected because of its short and mild clinical course. Clinical suspicion is

often low for this disease as the clinical presentation of ischemic colitis can be very

heterogeneous (6).

Clinical Presentation:

Like our patient, those with ischemic colitis typically present with sudden left lower

quadrant pain, diarrhea, and bloody stools. Hematochezia and bleeding per rectum are

worrisome complaints in patients with a broad differential diagnosis, and medical trainees

from all levels need to properly assess and identify patients at risk for developing ischemic

colitis. The disease may manifest across a wide spectrum of injury including reversible

colopathy, transient colitis, chronic colitis, stricture, gangrene, and fulminant colitis (1).

5
 Although most cases of ischemic colitis resolve quickly, a few situations warrant

special attention for complications. Isolated right-sided ischemic colitis may reflect super

mesenteric arterial disease with an associated mortality rate as high as 50% (6,7). Early

identification is crucial to prevent complications and to distinguish it from colorectal

carcinoma, which can present similarly (8). Both can also occur concurrently as increased

intracolonic pressure proximal to a colonic lesion can decrease blood flow and cause

ischemia. It is necessary to assess for tissue ischemia because it can affect the integrity of a

surgical anastomosis post resection of an obstructing lesion.

Pathophysiology:

Ischemic colitis can result from modifications in the systemic circulation or

anatomic and functional changes to the local mesenteric vasculature. Elderly patients are at

higher risk because of multiple co-morbidities and more degenerative changes in the

vascular bed. The colon is particularly sensitive to low-flow states because the middle colic

and inferior mesenteric arteries create a watershed area that correspond to the splenic

flexure (Griffith’s point) and recto-sigmoid (Sudeck’s point) segments of the large bowel

(1). The rectum is relatively spared because of its collateral blood supply. Our patient’s

ischemic inflammatory changes were in the left colon in the region of the classic watershed

areas.

Etiology:

Of the cases of ischemic colitis that have a specific identifiable cause, most can be

separated into the categories of thrombophilia and medications (Table 1). Thrombophilia

usually affects younger patients and those with recurrent colonic ischemia. The most

6
common inherited forms are activated protein C (APC) resistance and factor V Leiden

deficiency, while the most common acquired disorder is antiphospholipid antibody.

Medications that cause ischemic colitis work primarily through mechanisms of

vasoconstriction, allergic vasculitis, unmasking underlying thrombophilia, and severe

constipation (1). Cocaine is especially concerning among younger patients because it is

associated with a higher mortality from septic shock (9). Importantly, infectious agents that

include E. coli 0157:H7 and CMV (in immunocompromised patients) can produce a

histologic appearance that resembles ischemic colitis although their etiology remains

infectious inflammation.

Diagnosis:

Abdominal CT scan can support clinical suspicion, identify complications of ischemic

colitis, and help rule out colon cancer in up to 75% of cases (8). However, definitive

diagnosis of ischemic colitis is made by direct visualization of the bowel with biopsies to

confirm pathology. Colonoscopy must be performed carefully so as not to overdistend the

colon because high intraluminal pressures obstruct intestinal blood flow and can worsen

existing ischemic damage (1). Features that suggest ischemic colitis on colonoscopy include

a segmental distribution of disease, rectal sparing, and hemorrhagic nodules, which

represent bleeding into the mucosa and submucosa. The “colon single-stripe sign” is a

single line of erythema with erosions and ulcerations oriented along the longitudinal axis of

the colon (10). This finding corresponds to a 75% histopathologic yield and signifies a

milder course of disease than does a circumferential ulcer (10). Circumferential ulcers are

associated with higher rates of abdominal pain, higher baseline rates of CRP, and longer

7
periods of hospitalization (11). Infarction and ghost cells on pathology are pathognomonic

for ischemic colitis (12).

Histopathologic findings also give clues about the severity of injury. Mucosal and

submucosal hemorrhage and edema with or without partial necrosis and ulceration of the

mucosa indicate mild injury (1). Iron-laden macrophages, submucosal fibrosis, and

pseudomembranes suggest more severe injury and were present in our patient. Although

these findings are also found in C. difficile colitis (13), our patient tested negative for this

disease. Ultimately, she may be at risk of developing a stricture because her colonic lamina

propria showed early signs of fibrotic replacement.

Despite the diagnostic capabilities of colonoscopy, ischemia must be captured at the

right time in order for a definitive diagnosis to be made. It is recommended to perform this

procedure within 48 hours of symptom onset because the mucosal and submucosal surface

can normalize quickly in most cases.

When making a diagnosis of ischemic colitis, it is important to rule out other

possible diagnoses including infectious colitis, inflammatory bowel disease, diverticulitis,

diverticular colitis, and colon carcinoma. The work up should include stool cultures, ova,

and parasites and C. difficile toxin. C. difficile rarely causes bloody stools but it should be

suspected in hospitalized patients with recent antibiotic use, high total white blood cell

counts, and thickening of the colon on CT scan. Increased serum lactate, LDH, elevated

white blood cell counts, and metabolic acidosis indicate advanced tissue damage or

infarction. Endoscopic features of diverticular colitis range from submucosal hemorrhages

8
(peridiverticular red spots referred to as “Fawaz spots”) to chronic active inflammation

resembling inflammatory bowel disease that spares the rectum and terminal ileum.

Treatment:

In the absence of infarction or perforation, the treatment for ischemic colitis is

supportive. Bowel rest and intravenous fluids are standard therapy. Surgery is reserved for

those who have failed medical treatment, have persistent symptoms, or have sustained

complications (i.e. infarction, hemorrhage, strictures, or fulminant colitis). Intraperitoneal

fluid on CT scan, absence of bleeding per rectum suggesting right-sided ischemic colitis,

and renal dysfunction indicate more severe disease and are predictive of surgical

intervention (14,15).

Role of Antibiotics:

Antibiotics are thought to protect against bacterial translocation from the loss of

mucosal integrity. Some experimental studies demonstrate that they reduce the extent and

severity of bowel damage (16,17). However, it is difficult to conduct therapeutic trials

because the prognosis of this disease is good in most cases and large patient sample sizes

are required to show just a modest effect. Some current guidelines recommend empiric

broad-spectrum antibiotics for moderate to severe cases of ischemic colitis. However, a

recent systematic review on this issue found a lack of evidence-based trials to support

antibiotic treatment (18).

9
Prognosis

In over 50% of cases , symptoms of ischemic colitis resolve within 48 hours of onset.

However, the colon can take up to two weeks or more to fully heal. Symptoms that persist

longer than two weeks are associated with a poorer outcome with a higher number of

complications and irreversible disease. These patients are immediate candidates for

surgical bowel resection.

BACK TO THE CASE:

Three days into her admission, the patient’s symptoms were resolving and she had

no evidence of gastrointestinal bleeding. Her hemoglobin returned to baseline (128 g/L)

and she was discharged home uneventfully with outpatient gastroenterology follow up.

GLOBAL COMMENTS:

I think this is an interesting and important clinical case as it’s occurrence is usually

underestimated. I believe also that many clinicians not familiar with the entity of “ischemic

colitis” confuse this with “gut infarction”. I think it would add significant clinical utility to

the paper to make this distinction and include the differences in clinical features, as well as

histological and radiological findings. I don’t think you have made this distinction as clearly

as it needs to be. This could be done with the addition of a paragraph clearly separating the

2 entities.

10
I would also direct you to a paper Newman and Cooper Canadian Journal of

Gastroenterology 16(9): 597-600, 2002 “Lower Gastrointestinal Bleeding and Ischemic

Colitis that describes a moderate-sized cohort in a Toronto hospital and contributes to the

distinction between infarction and ischemia.

11
REFERENCES

1. Feuerstadt P, Brandt LJ. Colon ischemia: recent insights and advances. Curr
Gastroenterol Rep. 2010 Oct;12(5):383–90.

2. Grames C, Berry-Cabaá n CS. Ischemic colitis in an endurance runner. Case Rep

3. Cubiella Fernaá ndez J, Nuá nñ ez Calvo L, Gonzaá lez Vaá zquez E, Garcíáa Garcíáa MJ, Alves
Peá rez MT, Martíánez Silva I, et al. Risk factors associated with the development of ischemic
colitis. World J. Gastroenterol. 2010 Sep 28;16(36):4564–9.

4. Moses FM. Exercise-associated intestinal ischemia. Curr Sports Med Rep. 2005
Apr;4(2):91–5.

5. Higgins PDR, Davis KJ, Laine L. Systematic review: the epidemiology of ischaemic
colitis. Aliment. Pharmacol. Ther. 2004 Apr 1;19(7):729–38.

6. Montoro MA, Brandt LJ, Santolaria S, Gomollon F, Saá nchez Pueá rtolas B, Vera J, et al.
Clinical patterns and outcomes of ischaemic colitis: results of the Working Group for the
Study of Ischaemic Colitis in Spain (CIE study). Scand. J. Gastroenterol. 2011
Feb;46(2):236–46.

7. Guttormson NL, Bubrick MP. Mortality from ischemic colitis. Dis. Colon Rectum.
1989 Jun;32(6):469–72.

8. Deepak P, Devi R. Ischemic colitis masquerading as colonic tumor: case report with
review of literature. World J. Gastroenterol. 2011 Dec 28;17(48):5324–6.

9. Elramah M, Einstein M, Mori N, Vakil N. High mortality of cocaine-related ischemic

10. Zuckerman GR, Prakash C, Merriman RB, Sawhney MS, DeSchryver-Kecskemeti K,

11. Beppu K, Osada T, Nagahara A, Matsumoto K, Shibuya T, Sakamoto N, et al.

12. Mitsudo S, Brandt LJ. Pathology of intestinal ischemia. Surg. Clin. North Am. 1992
Feb;72(1):43–63.

13. Dignan CR, Greenson JK. Can ischemic colitis be differentiated from C difficile colitis
in biopsy specimens? Am. J. Surg. Pathol. 1997 Jun;21(6):706–10.

14. O’Neill S, Yalamarthi S. Systematic review of the management of ischaemic colitis.

12
15. Paterno F, McGillicuddy EA, Schuster KM, Longo WE. Ischemic colitis: risk factors for
eventual surgery. Am. J. Surg. 2010 Nov;200(5):646–50.

16. Redan JA, Rush BF Jr, Lysz TW, Smith S, Machiedo GW. Organ distribution of gut-
derived bacteria caused by bowel manipulation or ischemia. Am. J. Surg. 1990
Jan;159(1):85–89; discussion 89–90.

17. Plonka AJ, Schentag JJ, Messinger S, Adelman MH, Francis KL, Williams JS. Effects of
enteral and intravenous antimicrobial treatment on survival following intestinal ischemia
in rats. J. Surg. Res. 1989 Mar;46(3):216–20.

18. Díáaz Nieto R, Varcada M, Ogunbiyi OA, Winslet MC. Systematic review on the
treatment of ischaemic colitis. Colorectal Dis. 2011 Jul;13(7):744–7.

13
Figure 1:

Figure 1A: normal vascular pattern of

mucosa (unaffected section)

Figure 1B: pale, edematous colonic

mucosa with absent vascular pattern and

overlying white exudate in a

segmental distribution.

Figure 1C: complete loss of vascular

pattern, friable mucosa as indicated by

erythema, edema and granularity

14
Table 1: Causes of Ischemic Colitis

Causes of Ischemic Colitis

Thrombophilia  Inherited: APC resistance, Factor V Leiden deficiency

 Acquired: antiphospholipid antibody

Medications  Cocaine

 Digoxin

 Pseudoephedrine

 Amphetamines

 Sumatriptan

 Alosetron

Mechanical Obstruction  Colon cancer

 Fecal impaction

Small Vessel Disease  Diabetes, hypertension, hypercholesterolemia

 Vasculitis

Other  Long-distance running, extreme physical exertion

15