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Case of ischemic colitis in a young adolescent associated with triphasic hormonal contraceptive therapy: a case report and review of the literature.

Case Report

An 18-year-old, gravida 0, white female weighing 118 pounds and standing 5'3" tall (body mass index 20.9) was transported by her family to the local emergency department with complaints of significant, unrelenting abdominal pain and five episodes of hematochezia which began 18 hours prior to presentation. There were no other associated or significant physical or biological complaints including fever, chills, sweating, nausea or vomiting. She reported that she had never experienced any similar or related symptoms prior to this presentation.

The patient's past medical history was significant for juvenile chronic polyarthritis diagnosed two years prior to presentation which was being treated with as needed, nightly oral indomethacin 25 mg for pain (last dose two days prior to onset of symptoms); irritable bowel syndrome diagnosed five and one-half years prior to presentation which was not currently being managed with any pharmacotherapy, gastroesophageal reflux disease diagnosed three and one-half years prior to presentation for which she was being treated with oral lansoprazole 30 mg daily; and unipolar depression diagnosed four years prior to presentation which was being pharmacologically managed with oral sertraline 50 mg daily. The only other medication she was taking at the time of presentation was oral ethinyl estradiol/drospirenone (30 mcg/3 mg) which had been taken for four years prior to presentation and was being utilized for the hormonal regulation of her menses. The patient denied any other significant or relevant personal or family past medical history, including thromboembolic disorders. She had no known allergies to foods or medications. Her social history was non-contributory as she denied smoking, the consumption of alcoholic beverages or elicit drugs. She also denied taking any dietary or herbal supplementation or any over-the-counter treatments.

Physical examination upon presentation noted the patient to appear well-nourished, well-developed and in moderate distress. Her abdomen was found to be soft, non-distended with normal bowel sounds but profoundly tender to palpation in the left lower quadrant. No masses or organomegaly were appreciated during the physical examination. Vital signs were within normal limits including a blood pressure of 105/ 74 mmHg, a regular pulse of 73 beats per minutes, a non-labored respiratory rate of 16 breaths per minutes, a peripheral oximetry assessment of 99% while on room air and a temperature of 97.6 degrees Fahrenheit. A complete blood count (CBC) with differential, a serum pregnancy test and a complete serum metabolic panel was obtained along with an abdominal/ pelvic computerized tomography (CT) scan with contrast. Each of the serum laboratory assessments were found to be within normal limits except for a slightly diminished mean corpuscular volume of 79 (normal 81.8-97.9 fL). The CT demonstrated notable sigmoidal wall thickening. The patient was admitted to the hospital and a gastrointestinal (GI) consult was sought. The patient was provided a 1 liter fluid bolus of normal saline followed by a continuous infusion of normal saline administered at a rate of 100 ml/ hr. Her oral indomethacin therapy was not continued in the inpatient setting but her proton pump inhibitor therapy was continued using intravenous pantoprazole 40 mg daily. Her oral ethinyl estradiol/ drospirenone and sertraline therapies were also continued at this point in her inpatient admission. She was also provided intravenous morphine sulfate (2-4 mg) as needed for pain and intravenous ondansetron (4 mg) as needed for nausea.

The GI consult resulted in the performance of a colonoscopy later that evening. The colonoscopy demonstrated, at 30 cm from the anal verge, scattered areas of shallow ulcerations with surrounding erythema separated by normal mucosa (figure 1). These ulcerations extended for approximately 10 cm within the colon (figure 2). Biopsies were taken to further evaluate the ulcerations. Pathology assessments subsequently reported prominent superficial erosive and reactive changes most consistent with colonic ischemia. Due to the lack of any clinically significant indicators of infectious colitis, no bacteriological studies were performed on the biopsy specimens.

Due to the histopathological nature of the ischemic changes, the hormonal contraceptive therapy was discontinued by the GI specialist and the patient was referred to a cardiologist and hematologist on an outpatient basis for further biochemical and hematological evaluation. The patient was ultimately discharged with only minor abdominal complaints of discomfort and receiving therapy with oral hyoscyamine 0.375 mg daily for abdominal cramps in addition to her previous ambulatory oral therapy of as needed indomethacin, lansoprazole and sertraline. Education was provided regarding alternative contraceptive options but no interventional decisions were made at the time of discharge.

[FIGURE 1 OMITTED]

[FIGURE 2 OMITTED]

An outpatient echocardiogram was obtained to rule out a thrombus or other cardiac-related abnormalities. No cardiac or valvular abnormalities or thrombi were noted. A hematology consultation was subsequently obtained to rule out a hypercoagulable state. A series of serum laboratory assessments were obtained including; a CBC with peripheral smear, cryoglobulins, cryofibrinogens, C-reactive protein (CRP), protein S activity and antigen, anti-neutrophil cytoplasmic antibodies, lupus anticoagulant, activated protein C (APC) resistance assay, prothrombin gene mutation assay, factor V Leiden assay, factor VIII activity level and a D-dimer assay. All assessments were reported to be within normal physiological limits except for the APC resistance assay, which was reported low at 0.7 (normal 2.0-4.0 L). An additional series of serum laboratory assessments were subsequently ordered and included; serum protein electrophoresis, anti-cardiolipin antibody assay for IgG, IgA and IgM, anti-[beta]2 glycoprotein-I antibody for IgG and IgM, and a repeat of the APC resistance assay. Each of these additional serum laboratory assessments were found to be within normal physiological limits, including the repeat APC resistance assay which was found to have normalized to a value of 2.5 L. No additional pharmacotherapy was initiated by either of the consulted specialists. Since discharge from the hospital and the discontinuation of the combination hormonal contraceptive therapy (time frame=20 months at time of manuscript submission), the patient continues to deny having any subsequent hematochezia or abdominal pain.

Discussion

Ischemic colitis is more commonly found in elderly patients with cardiovascular or other diseases. In young women, ischemic colitis is more commonly associated with medications, infections or hypovolemia/hypoperfusion. In addition to the clinical presentation, the diagnosis of ischemic colitis is customarily determined from a combination of assessments including radiological, pathological, histological, immunological and bacteriological evaluations; in conjunction with a detailed medication history. (17) Common locations for colonic ischemia are found in the regions of splenic flexure which is supplied by a narrow terminal branch of the superior mesenteric artery, and the rectosigmoid junction which is supplied by a narrow terminal branch of the inferior mesenteric artery. These areas are commonly referred to as the watershed areas (18). Oral contraceptives increase the risk of thrombus formation by decreasing coagulation inhibitors anti-thrombin III, Protein C and Protein S and at the same time there is modest increases the levels of factor VII, factor VIII, factor X, prothrombin, and fibrinogen. (19)

It is believed that the first reported case of gastrointestinal ischemia associated with the use of hormonal contraceptive agents was published in 1963 by Reed and Coon. (20) Their report described a 37-year-old female who had been treated with a hormonal contraceptive agent for two months when she presented with acute abdominal pain. During laparotomy it was determined that she had a gangrenous small bowel in conjunction with thrombotic occlusion of her superior mesenteric vein. The patient did not survive the event, which clearly represents the potential outcome of this type of complication associated with these agents. Several of the case reports found in the literature had a similar outcome (death), although approximately one-third of the reported cases resulted in what might be described by most as spontaneous, reversible events following symptomatic treatment and discontinuation of the hormonal contraceptive. (21) The table on the opposite page is site-specific summaries of the published literature on case reports of GI-based ischemic and/or thrombotic events associated with the use of hormonal contraceptive agents.

Our patient was found to ischemic finding in the rectosigmoid area. There was a discussion as to possibility of indomethacin being a possible cause of the ischemia in addition to the oral contraceptive. The Naranjo score was applied to the oral contraceptive and found to be 7 making this adverse reaction propable. (16) In addition the patient has continued to use indomethacin on as needed bases for her juvenile rheumatoid arthritis and has not reported similar symptoms.

Stool studies should have been performed to rule out infectious cause of the ischemic changes. The gastroenterologist did not feel that these were warranted. He was confident that the ischemia was related to a low blood flow state with the most likely cause from the third generation oral contraceptive. According to Cecil Medicine 23rd edition, patients on a third generation oral contraceptive are at two times greater risk of deep venous clot formation when compared to second generation oral contraceptives. (83) While our patient's ischemia was likely arterial in nature, it does increase the probability that the cause of the ischemia is related to the oral contraceptive.

Conclusion

Although relatively rare, gastrointestinal ischemia can be a serious and costly complication resulting in profound morbidity and even death in women taking hormonal contraceptive products. This case exemplifies the clinical necessity to include acute gastrointestinal vascular thrombosis and ischemia within the medical differential diagnosis in patients presenting with acute abdominal pain, with or without hematochezia, especially in young women treated with combination hormonal contraceptives.

Note

This case report was previously presented at the American College of Osteopathic Emergency Physician spring 2011 conference April 26-30, 2011. It was presented as a poster and oral presentation.

References

(1.) Kiley J, Hammond C. Combined oral contraceptives: a comprehensive review. Clin Obstet Gyn 2007;50:868-77.

(2.) Fraser IS. Forty years of combined oral contraception: the evolution of a revolution. Med J Aust 2000;173:541-4.

(3.) Vessey MP, Doll R. Investigation of relation between use of oral contraceptives and thromboembolic disease. Br Med J 1968;2:199-205.

(4.) Sartwell PE, Masi AT, Arthes FG, et al. Thromboembolism and oral contraceptives: an epidemiologic case-control study. Am J Epidemiol 1969;90:365-80.

(5.) Stadel BV. Oral contraceptives and cardiovascular disease. N Engl J Med 1981;305:612-8.

(6.) Croft P, Hannaford PC. Risk factors for acute myocardial infarction in women: evidence from the Royal College of General Practitioners' oral contraception study. Br Med J 1989;298:165-8.

(7.) La Vecchia C, Franceschi S, Decarli A, et al. Risk factors for myocardial infarction in young women. Am J Epidemiol 1987;125:832-43.

(8.) Stolley PD, Strom BL, Sartwell PE. Oral contraceptives and vascular disease. Epidemiol Rev 1989;11:241-3.

(9.) Carter CJ. Oral contraceptives and thrombosis. Curr Opin Pulm Med 2000;6:296-300.

Please contact the authors for a complete list of references.

D. Kade Rasmussen, DO

Emergency Medicine Resident at the Ohio Valley Medical Center in Wheeling

Larry W. Segars, PharmD, DrPH, FCCP, BCPS

Associate Professor of Pharmacology and Preventive Medicine, Chair, Department of Pharmacology/ Microbiology, Kansas City University of Medicine & Biosciences
Table 1 Previously reported colonic ischemia
secondary to the oral contraceptives

                                            Average length
Location                   Number    Age     of treatment

Sigmoid colon (22-32)        12     20-49      6m-10yr

Descending/transverse        34     16-50       1m-7yr
colon (24, 32-44)

Super Mesenteric             23                3wk-5yr
Artery (45-58)

Celiac artery (59-64)        6                 2m-5yrs

Superior Mesenteric Vein     24     16-48      2m-10yr
(15,20,46-47,65-80)

Location                   Complicating Factors

Sigmoid colon (22-32)      naratriptan use (25),
                           sumatriptan (28)-9

Descending/transverse      2 pt restarted OCG and developed
colon (24, 32-44)          a second ischemic colitis (40)

Super Mesenteric           all used combination therapy
                           but two that used progesterin
Artery (45-58)             only therapy (47,56)

Celiac artery (59-64)      one patient had occlusion of
                           celiac and SMA (62), one pt
                           had prothrombin gene 20210 (61)

Superior Mesenteric Vein   23 patient required surgical
(15,20,46-47,65-80)        resection
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Title Annotation:Scientific Article
Author:Rasmussen, D. Kade; Segars, Larry W.
Publication:West Virginia Medical Journal
Article Type:Case study
Date:Sep 1, 2011
Words:1954
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