Combined Case Presentation
Gratian Salaru, M.D.1 and Eric Shen, M.D.2
From the Departments of Pathology1 and Gastroenterology2, UMDNJ/RWJMS
The patient is a 31 y/o female who presented to the ER complaining of abdominal pain. The pain initially started 1-week prior in the epigastric region. The pain was crampy in nature and felt like she was "kicked". The pain was intermittent, lasted a few minutes at a time, and did not radiate. It was associated with meals and had no alleviating factors. The pain persisted throughout the week. However, 2 days prior to admission, the pain became more severe with the cramping occurring more often. The morning of admission, she awoke with worsening of the pain. The pain localized in the RLQ. It was 10/10 in severity, constant, non-radiating, and made worse with movement. She also felt nauseous at the time but did not vomit. Only lying on her right side relieved the pain. There was no relief with Tums or Zantac. She had 1 episode of watery, non-bloody stool in the morning. She denied any recent antibiotic use, recent travel, or unusual food intake. She ate a buffet dinner the night before. Her LMP was 2 weeks ago and was normal.
She was seen at her PMD’s office in the morning and sent to the ER from there.
βhCG (-) Calcium 9.4
What would you do next?
She was admitted to the regular floor and was started on IV fluids (D5 1/2NS at 100cc/hr). Stool studies were sent for culture, ova¶sites and Clostridium difficile. She was started on Levaquin 500mg po QD. It was decided that she would undergo an esophago-gastro-duodenoscopy and colonoscopy in the AM. The next morning she reported decreased abdominal pain but noted several watery bowel movements with scant amounts of blood since being admitted.
The colonoscopy revealed minimal patchy inflammation in the distal sigmoid and mild internal hemorrhoids. Then, the colonoscope was passed 10 cm into the terminal ileum, which appeared normal. Biopsies were taken of the terminal ileum and the inflamed colon.
Because of the possibility of ischemic colitis, a hypercoagulable workup was ordered including factor V Leiden, prothrombin gene mutation, lupus anticoagulant, protein C & S activity, antithrombin III levels and homocysteine level. The GI specialist had recommended her stop her oral contraceptive pills but she did not want to do that until she spoke to her gynecologist. Her diet was advanced as tolerated. She was started on Pepcid 40mg po qd for her gastritis. Her pain eventually subsided and she was discharged to home on day #3 on Levaquin 500mg po qd x a total of 5 days. She was told to follow up with hematology for the hypercoagulable labs and with gastroenterology for the biopsy results.
Are you thinking of any possible diagnoses?
Chronic acute colitis with focal acute cryptitis (center). Admixed neutrophilic and lymphocytic infiltrates.
Chronic inflammatory infiltrates in the vicinity of a prominent lymphoid aggregate
Higher magnification of the previous section; inflammatory cells are present diffusely in the superficial mucosa.
Submucosal congestion, marked, with dilated blood vessels and focal edema. Consistent with ischemic changes.
Mixed eosinophilic and neutrophilic infiltrates, in the background of ischemic colitis. There is a degree of architectural distorsion in the mucosa, with focal crypt drop-outs.
Moderate edema of the lamina propria. This change can be seen in ischemic colitis. To a lesser extent, it can be seen as an artifact of tissue collection and processing.
Dilated capillaries, regenerative changes, edema and mild inflammation. Consistent with ischemic changes.
Are you changing your diagnosis?
AntiThrombin III Deficiency
Antithrombin III is a plasma protease inhibitor that neutralizes thrombin by irreversibly forming a 1:1 complex. ATIII deficiency is found in ~1% of outpatients under 70 years old with a first venous thrombosis. The odds ratio for thrombosis with ATIII deficiency is 10-20. The most common symptom is venous thrombosis of the lower extremity, which occurs at an early age and peaks in the second decade of life. Arterial thrombosis occurs infrequently (~1% of affected patients). Modest reductions in plasma ATIII concentration are found in users of oral contraceptives.
Ischemic Colitis in Young Adults
Spontaneous ischemic colitis is an established clinical entity first described in 1963. Ischemic colitis has been generally considered a disease of elderly patients with the incidence increasing with advancing age. However, it also occurs in healthy adults under the age of 60. It typically affects young adults in the context of an overt, precipitating disorder such as hypovolemic shock, vasculitis, or drug use.
Several case reports of young patients taking oral contraceptives developing ischemic colitis appeared in the literature beginning in the 1970’s. One study showed a greater than six fold relative risk for the occurrence of ischemic colitis among oral contraceptive users. A retrospective study in 1995 showed that out of 18 patients under the age of 40 years with ischemic colitis, 10(59%) were using exogenous hormonal therapy.
All types of oral contraceptives have been associated with ischemic colitis:
The presentation is very similar to that in the elderly. Characteristically, patients present with acute, severe abdominal pain, usually in the left lower quadrant, followed by the development of bloody diarrhea.
The findings on physical exam are relatively benign. Laboratory testing may show a modest leukocytosis.
OCP-induced ischemic colitis can be caused by arterial occlusion or venous occlusion. The proposed mechanism of estrogen-induced colitis is induction of a hypercoagulable state, but hyperplasia of arterial endothelium may also be a factor. The distribution of the injury is usually segmental but may involve the entire colon. The watershed areas of mesenteric vascular supply, specifically the splenic flexure and rectosigmoid, are most commonly affected. Colonoscopy usually shows segmental, confluent, or patchy areas of mucosal friability and hyperemia. The number of reported cases of OCP-induced colitis has been decreasing over time, and their clinical characteristics have been changing. Current cases have followed a generally more benign course, not requiring the bowel resections of earlier reports.
Ischemic colitis: gross mucosal necrosis
This may be due to the decrease in estrogen dose used in OCPs in the last decade. Differential diagnosis would include acute infectious enteritis, pseudomembranous colitis, and inflammatory bowel disease. Other less likely possibilities include diverticulitis, bowel strangulation, arteriovascular malformations, and acute mesenteric ischemia. Management requires supportive treatment and frequent monitoring. Symptoms are usually self-limited and of brief duration, usually resolving in 2-4 days. In those patients receiving estrogen therapy, continued use of estrogen is problematic. Two studies suggest that ongoing use of estrogen results in an increased risk of recurrent ischemia, however, since the illness is generally benign and self-limited, this increased risk may be acceptable in some patients.