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34-Year-Old Woman With Abdominal Pain and Blood-Streaked Diarrhea

      A 34-year-old woman presented to the emergency department for evaluation of a 12-hour history of sudden severe epigastric pain and bilateral leg weakness during exercise associated with nausea and vomiting. She experienced 2 episodes of diarrhea; 1 of which was blood streaked. The patient reported not eating or drinking much that day. She described a few previous less severe episodes of abdominal pain and diarrhea since childhood associated with certain foods. She denied fever or chills but reported a 5-lb intentional weight loss during the past month. She denied changes in her appetite, myalgia, arthralgia, or vision changes. She had no recent travel, sick contacts, or antibiotic drug use. She denied current pregnancy.
      The patient was previously healthy; her medical history included recurrent urinary tract infections and infertility, with a previous artificial insemination attempt resulting in a missed abortion. Current medication use includes clomiphene and progesterone vaginal suppository.
      At presentation, her vital signs were as follows: temperature, 36.9°C; heart rate, 69 beats/min; respiratory rate, 16 breaths/min; and blood pressure, 98/60 mm Hg. On examination, the patient appeared uncomfortable but was in no acute distress. Her abdomen was soft and nondistended, with positive bowel sounds. She had generalized tenderness in all 4 quadrants, with absence of guarding and rebound tenderness. Her mucous membranes appeared dry. Lower extremity strength was normal. Results of a urine pregnancy test obtained on arrival to the emergency department were negative.
      • 1
        Which one of the following tests would be most appropriate at this time?
        • a
          Fecal occult blood
        • b
          Abdominal radiograph
        • c
          Abdominal ultrasound
        • d
          Abdominal computed tomography (CT)
        • e
          Colonoscopy
      Fecal occult blood testing would not be useful in this patient's situation. The patient would require further evaluation, regardless of the results of the fecal occult blood test. An abdominal radiograph is useful in cases of acute abdominal pain for quickly identifying intraperitoneal free air. In this patient, however, whose examination was nonfocal and lacked peritoneal signs (absence of guarding and rebound tenderness), an abdominal radiograph is not the best test to diagnose the cause of her symptoms.
      Ultrasonography is an accepted method for the evaluation of abdominal pain, especially if the gallbladder or a female pelvic pathologic disorder is suspected based on clinical presentation or examination findings. This patient's presentation (diarrhea and gastrointestinal [GI] bleeding), her negative urine pregnancy test results, and the diffuse nature of her pain on examination do not point toward either of these causes. If her urine pregnancy test result had been positive, an ultrasound would have been an appropriate next step.
      An abdominal CT would be the initial imaging test of choice. Abdominal pain and acute-onset diarrhea raise suspicion for colonic disease in this patient. A CT scan is the preferred initial screening test to rule out a colonic, versus an extracolonic, pathologic disorder. In addition, it provides information on all intra-abdominal and retroperitoneal structures.
      • Theodoropoulou A.
      • Koutroubakis I.E.
      Ischemic colitis: clinical practice in diagnosis and treatment.
      In women of childbearing age, a pregnancy test should be performed before proceeding with CT. Colonoscopy plays an important role in the evaluation of GI bleeding. In patients with ongoing hematochezia, a colonoscopy should be performed as soon as possible. In patients such as this one, in whom there is no sign of active bleeding, a colonoscopy can be performed on a semi-elective basis but would not be the initial diagnostic test.
      An abdominal CT showed wall thickening and inflammation of the distal ileum and splenic flexure. The patient was admitted to the hospital for further evaluation. Overnight, her abdominal pain improved, but did not resolve, with supportive therapy. No additional episodes of emesis, diarrhea, or lower extremity weakness were observed.
      • 2
        Which one of the following tests is the best test to confirm the suspected diagnosis?
        • a
          Serum lactate level
        • b
          Barium enema radiograph
        • c
          Colonoscopy
        • d
          Flexible sigmoidoscopy
        • e
          Mesenteric angiography
      The clinical presentation and CT findings suggest colitis. The differential diagnosis for the cause of colitis includes infectious, inflammatory, and ischemic etiologies. Imaging studies are nonspecific and do not differentiate between these etiologies of colitis.
      • Elder K.
      • Lashner B.A.
      • Al Solaiman F.
      Clinical approach to colonic ischemia.
      A serum lactate level could refer to either a serum l-lactate or a serum d-lactate level. An elevated serum l-lactate level would indicate either tissue hypoxia (type A lactic acidosis) or decreased clearance of lactic acid, which occurs most commonly with liver disease (type B lactic acidosis). d-Lactate is produced by bacteria in the gut and is metabolized slowly by humans. Patients with short-bowel syndrome can develop lactic acidosis from elevated serum levels of d-lactate.
      • Luft F.C.
      Lactic acidosis update for critical care clinicians.
      An elevated serum lactate level would not confirm the diagnosis of colitis or clarify the underlying etiology.
      In the evaluation of suspected colitis, CT has largely replaced barium enema. A barium enema would not provide further diagnostic information beyond what is already known from CT, and residual contrast may hinder further diagnostic evaluations, such as endoscopy.
      • Theodoropoulou A.
      • Koutroubakis I.E.
      Ischemic colitis: clinical practice in diagnosis and treatment.
      • Stamatakos M.
      • Douzinas E.
      • Stefanaki C.
      • et al.
      Ischemic colitis: surging waves of update.
      Endoscopy is the preferred method for confirming the diagnosis and cause of colitis.
      • Theodoropoulou A.
      • Koutroubakis I.E.
      Ischemic colitis: clinical practice in diagnosis and treatment.
      • Elder K.
      • Lashner B.A.
      • Al Solaiman F.
      Clinical approach to colonic ischemia.
      • Stamatakos M.
      • Douzinas E.
      • Stefanaki C.
      • et al.
      Ischemic colitis: surging waves of update.
      In this patient, flexible sigmoidoscopy would not allow visualization of the affected areas of bowel; therefore, colonoscopy is the best test to confirm the diagnosis.
      Mesenteric angiography would not be the next step in the evaluation of colitis. It may play a role in the evaluation of ischemic colitis if there is isolated right-sided colonic involvement (possible superior mesenteric artery occlusion) or if there is a question as to whether a patient has mesenteric ischemia or colonic ischemia.
      • Theodoropoulou A.
      • Koutroubakis I.E.
      Ischemic colitis: clinical practice in diagnosis and treatment.
      • Stamatakos M.
      • Douzinas E.
      • Stefanaki C.
      • et al.
      Ischemic colitis: surging waves of update.
      A colonoscopy was performed next and showed areas of irregular erosion and ulceration starting at the splenic flexure and involving the distal colon. The mucosa in the distal ileum, as well as the cecum; ascending, transverse, and sigmoid colon; and rectum, appeared normal. A biopsy of the area of segmental colitis showed edema and hemorrhage in the lamina propria and superficial epithelial necrosis.
      In patients with findings of colitis on CT, stool antimicrobial assessment (including Clostridium difficile toxin testing) to assess for infectious colitis is often completed before proceeding with colonoscopy. In this case, stool antimicrobial assessment was initiated but not completed before colonoscopy. The patient's ongoing abdominal pain and the distribution of colonic lesions on CT, which raised concern for skip lesions of Crohn disease, led to the pursuit of early colonoscopy. Stool assessment ultimately revealed few fecal leukocytes and a negative polymerase chain reaction result for Shiga toxin. The stool cultures for enteric pathogens were negative for Salmonella, Shigella, Campylobacter, Yersinia, and Aeromonas.
      • 3
        Which one of the following diagnoses is most likely in this patient?
        • a
          Ulcerative colitis
        • b
          Crohn disease
        • c
          Transient ischemic colitis
        • d
          Gangrenous ischemic colitis
        • e
          Infectious colitis
      In ulcerative colitis, one would expect to see mucosal disease (erythema, edema, hemorrhage, or ulceration) starting at the rectum and extending proximally. Biopsy findings would include diffuse crypt architectural irregularity and reduced crypt numbers.
      • Fauci A.S.
      Harrison's Principles of Internal Medicine.
      • Bentley E.
      • Jenkins D.
      • Campbell F.
      • Warren B.
      How could pathologists improve the initial diagnosis of colitis? evidence from an international workshop.
      The rectal mucosa was not involved in this case, making ulcerative colitis unlikely. Crohn disease could account for the colonic and distal ileal involvement seen on CT; however, on a colonoscopy one would expect to see a cobblestone pattern of ulcerations enclosing islands of normal mucosa.
      • Fauci A.S.
      Harrison's Principles of Internal Medicine.
      Biopsy findings would include granulomas and focal or patchy inflammation.
      • Bentley E.
      • Jenkins D.
      • Campbell F.
      • Warren B.
      How could pathologists improve the initial diagnosis of colitis? evidence from an international workshop.
      Transient ischemic colitis is the most likely diagnosis in this case. The scattered erosions and ulcerations seen on the colonoscopy, combined with the biopsy findings of superficial mucosal edema, hemorrhage, and epithelial necrosis, are classic.
      • Scharff J.R.
      • Longo W.E.
      • Vartanian S.M.
      • Jacobs D.L.
      • Bahadursingh A.N.
      • Kaminski D.L.
      Ischemic colitis: spectrum of disease and outcome.
      Other findings on the colonoscopy in ischemic colitis include edematous and fragile mucosa, scattered erythema, purple hemorrhagic nodules, and sharp demarcation of the area of involved bowel. In severe forms of ischemic colitis, the mucosa appears cyanotic, and pseudomembranes, pseudopolyps, and pseudotumors may be seen. In gangrenous ischemic colitis, bluish-black mucosal nodules may be present.
      • Zou X.
      • Cao J.
      • Yao Y.
      • Liu W.
      • Chen L.
      Endoscopic findings and clinicopathologic characteristics of ischemic colitis: a report of 85 cases.
      The clinical suspicion for infectious colitis was low in this case because the patient had no recent travel or dietary history to suggest exposure to enteric pathogens. Furthermore, results of stool studies were negative. The patient was treated supportively for a diagnosis of transient ischemic colitis based on her colonoscopy and clinical presentation. Her abdominal pain resolved, and she continued to remain free of recurrence of diarrhea or GI bleeding. She did not experience any recurrent lower extremity weakness with ambulation.
      • 4
        Which one of the following statements is true regarding this patient's disease?
        • a
          It most commonly involves the right colon.
        • b
          Abdominal pain, GI bleeding, and diarrhea are the most common presenting symptoms.
        • c
          Young, healthy persons are at highest risk for this disease.
        • d
          Male sex is a risk factor for this disease.
        • e
          Cardiac thromboembolism is the most common cause of this disease.
      The right colon is infrequently involved in ischemic colitis. It most commonly involves watershed areas of the bowel, such as the splenic flexure and rectosigmoid junction.
      • Zou X.
      • Cao J.
      • Yao Y.
      • Liu W.
      • Chen L.
      Endoscopic findings and clinicopathologic characteristics of ischemic colitis: a report of 85 cases.
      In one series, the splenic flexure was involved in 57% of patients, and the sigmoid and rectum were involved in 9%.
      • Huguier M.
      • Barrier A.
      • Boelle P.Y.
      • Houry S.
      • Lacaine F.
      Ischemic colitis.
      Involvement of the left colon (80%) is much more common than that of the right colon (4.7%).
      • Zou X.
      • Cao J.
      • Yao Y.
      • Liu W.
      • Chen L.
      Endoscopic findings and clinicopathologic characteristics of ischemic colitis: a report of 85 cases.
      The most common presenting symptoms of ischemic colitis include abdominal pain (49%-78%), GI bleeding (62%-77%), and diarrhea (33%-38%).
      • Zou X.
      • Cao J.
      • Yao Y.
      • Liu W.
      • Chen L.
      Endoscopic findings and clinicopathologic characteristics of ischemic colitis: a report of 85 cases.
      • Huguier M.
      • Barrier A.
      • Boelle P.Y.
      • Houry S.
      • Lacaine F.
      Ischemic colitis.
      Age is a risk factor for ischemic colitis, with elderly patients being at a higher risk than young, healthy patients. In addition, females are at higher risk for ischemic colitis than are males. Other risk factors include cardiovascular disease, hypertension, chronic obstructive pulmonary disease, constipation, and the use of predisposing medications (nonsteroidal anti-inflammatory drugs, diuretics, antihypertensives, laxatives, oral contraceptives, and anticonvulsants).
      • Theodoropoulou A.
      • Koutroubakis I.E.
      Ischemic colitis: clinical practice in diagnosis and treatment.
      • Elder K.
      • Lashner B.A.
      • Al Solaiman F.
      Clinical approach to colonic ischemia.
      • Zou X.
      • Cao J.
      • Yao Y.
      • Liu W.
      • Chen L.
      Endoscopic findings and clinicopathologic characteristics of ischemic colitis: a report of 85 cases.
      • Huguier M.
      • Barrier A.
      • Boelle P.Y.
      • Houry S.
      • Lacaine F.
      Ischemic colitis.
      • Higgins P.D.
      • Davis K.J.
      • Laine L.
      Systematic review: the epidemiology of ischaemic colitis.
      Hypotension and hypovolemia, not cardiac thromboembolism, are the most common mechanisms by which ischemic colitis occurs.
      • Elder K.
      • Lashner B.A.
      • Al Solaiman F.
      Clinical approach to colonic ischemia.
      This patient's clinical presentation with abdominal pain, GI bleeding, and diarrhea is consistent with a typical case of ischemic colitis. Her young age, lack of comorbid disease, and absence of predisposing medication use, however, make her case atypical. She was at risk for hypovolemia secondary to poor oral intake and exercise when her symptoms developed, and she was hypotensive at presentation. Her hypotension and hypovolemia were treated by intravenous fluid resuscitation with normal saline on hospital admission. The hypotension responded to fluid rehydration, with no further recurrence during hospitalization.
      • 5
        What should this patient be told about her prognosis?
        • a
          Most cases improve quickly with supportive treatment and fully resolve within a few weeks.
        • b
          Isolated right colon involvement is associated with better outcomes.
        • c
          Chronic ischemic colitis develops in approximately 50% of patients.
        • d
          Surgical intervention does not have a role in the treatment of chronic ischemic colitis.
        • e
          Long-term anticoagulation is indicated in the presence of abnormal coagulation studies.
      Most cases of ischemic colitis are of a mild form (transient ischemic colitis) that resolves with supportive measures, including intravenous hydration, hemodynamic stabilization, discontinuation of offending medications, bowel rest, and antibiotic drug therapy.
      • Elder K.
      • Lashner B.A.
      • Al Solaiman F.
      Clinical approach to colonic ischemia.
      • Stamatakos M.
      • Douzinas E.
      • Stefanaki C.
      • et al.
      Ischemic colitis: surging waves of update.
      It can be difficult on initial presentation to distinguish mild forms of ischemic colitis from severe forms that may require surgical intervention. One risk factor for more severe disease associated with worse outcomes is right-sided colonic involvement.
      • Montoro M.A.
      • Brandt L.J.
      • Santolaria S.
      • et al.
      Clinical patterns and outcomes of ischaemic colitis: results of the Working Group for the Study of Ischaemic Colitis in Spain (CIE study).
      Eighteen percent of patients develop chronic ischemic colitis.
      • Montoro M.A.
      • Brandt L.J.
      • Santolaria S.
      • et al.
      Clinical patterns and outcomes of ischaemic colitis: results of the Working Group for the Study of Ischaemic Colitis in Spain (CIE study).
      They may experience diarrhea, protein-losing enteropathy, or GI bleeding, and their disease may progress to stricture formation or gangrene.
      • Stamatakos M.
      • Douzinas E.
      • Stefanaki C.
      • et al.
      Ischemic colitis: surging waves of update.
      Malnutrition from protein-losing enteropathy and symptomatic stricture are indications for surgical intervention in patients with chronic ischemic colitis.
      • Elder K.
      • Lashner B.A.
      • Al Solaiman F.
      Clinical approach to colonic ischemia.
      The role of hypercoagulable states in the pathogenesis of ischemic colitis is unclear. There is no evidence that diagnosing and treating a hypercoagulable state in a patient with an initial episode of colonic ischemia is beneficial.
      This young woman was treated conservatively with intravenous fluids and morphine. She was counseled regarding the importance of maintaining adequate hydration before, during, and after exercise. She was discharged from the hospital and did not report recurrence of abdominal pain or bloody diarrhea during 1-year follow-up.

      Discussion

      Ischemic colitis is a relatively uncommon condition, occurring at an incidence of 4 to 44 cases per 100,000 person-years in the general population, with a higher incidence in patients older than 65 years.
      • Higgins P.D.
      • Davis K.J.
      • Laine L.
      Systematic review: the epidemiology of ischaemic colitis.
      In the young woman described in this case, ischemic colitis was not considered the most likely diagnosis on initial evaluation. The early CT findings of colitis involving the distal ileum and colon suggested an inflammatory etiology, namely, Crohn disease. Colonoscopy proved invaluable in making the diagnosis, as the pathologic findings in inflammatory and ischemic colitis are distinct. With the correct diagnosis, we were able to provide appropriate treatment for this patient.
      Most cases of ischemic colitis are mild in severity and resolve with conservative therapy. Of patients whose disease initially resolves, 13% experience a recurrence of ischemia.
      • Paterno F.
      • McGillicuddy E.A.
      • Schuster K.M.
      • Longo W.E.
      Ischemic colitis: risk factors for eventual surgery.
      Approximately 20% of patients with ischemic colitis have severe disease and, ultimately, require surgical intervention.
      • Stamatakos M.
      • Douzinas E.
      • Stefanaki C.
      • et al.
      Ischemic colitis: surging waves of update.
      • Paterno F.
      • McGillicuddy E.A.
      • Schuster K.M.
      • Longo W.E.
      Ischemic colitis: risk factors for eventual surgery.
      Risk factors for severe disease include right-sided colonic involvement, peripheral vascular disease, atrial fibrillation, tachycardia, absence of GI bleeding, intensive care unit admission, requirement for vasopressor therapy, mechanical ventilation, intraperitoneal fluid on CT, and an increased serum l-lactate level at presentation.
      • Paterno F.
      • McGillicuddy E.A.
      • Schuster K.M.
      • Longo W.E.
      Ischemic colitis: risk factors for eventual surgery.
      Clear indications for immediate surgical intervention include peritonitis and pneumoperitoneum.
      • Paterno F.
      • McGillicuddy E.A.
      • Schuster K.M.
      • Longo W.E.
      Ischemic colitis: risk factors for eventual surgery.
      Fortunately, this patient remained hemodynamically stable in the hospital, and her symptoms resolved with conservative therapy.
      This case raised a question as to the role of hypercoagulable states in ischemic colitis. Although there is no evidence that diagnosing and treating hypercoagulable states in patients with colonic ischemia is beneficial, expert consensus still favors oral anticoagulation in patients with severe or recurrent ischemic colitis in whom thromboembolism, secondary to a hypercoagulable state, is the most likely cause.
      • Elder K.
      • Lashner B.A.
      • Al Solaiman F.
      Clinical approach to colonic ischemia.
      Hypercoagulable states may play a larger role in younger individuals, such as this patient without other risk factors for colonic ischemia. Further study in this area is needed. We hypothesized that our patient's transient ischemia was secondary to hypotension and hypovolemia, occurring with exercise and inadequate hydration and did not screen for hypercoagulable states. If she were to develop recurrent ischemia, it would be reasonable to screen for hypercoagulable states at that time and treat with anticoagulation if present.

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        Ischemic colitis: clinical practice in diagnosis and treatment.
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        Clinical approach to colonic ischemia.
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        Ischemic colitis: surging waves of update.
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        How could pathologists improve the initial diagnosis of colitis? evidence from an international workshop.
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        Ischemic colitis: spectrum of disease and outcome.
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        Endoscopic findings and clinicopathologic characteristics of ischemic colitis: a report of 85 cases.
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        Systematic review: the epidemiology of ischaemic colitis.
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