A 27-year-old woman has been bothered by bouts of abdominal pain, diarrhea, and constipation for the past 3 years. She has been a graduate student in biology for the past 3 years. On physical examination, vital signs show T 37 C, P 70/min, RR 15/min, and BP 95/65 mm Hg. She is in no distress. Her lungs are clear to auscultation and her heart rate is regular with no murmurs. There is mild abdominal tenderness on deep palpation of the epigastrium, but there are no masses and bowel sounds are present. A stool sample is negative for occult blood. The remainder of the examination is unremarkable. Laboratory studies show Hgb 14.8 g/dL, WBC count 7620/microliter, and platelet count 303,900/microliter. Her random blood glucose is 91 mg/dL, serum creatinine 1.0 mg/dL, and amylase 30 U/L. An abdominal ultrasound shows no abnormal findings.

Questions:

1.1 What should be considered?

There are no acute findings. Acute appendicitis is unlikely, but she should be followed and asked to return if abdominal pain persists and/or worsens. If gallstones are present, they are usually seen with ultrasonography. Acute pancreatitis is unlikely, given the normal amylase value, but she could have chronic pancreatitis. Gastroenteritis from food poisoning is a good possibility, but the history suggests a recurring problem. Peptic ulcer disease is possible.

Further history:

The diarrhea is of low volume and not accompanied by pain. In fact, passing any stool seems to relieve the abdominal pain. However, she has irregular bowel movements, with none some days and up to 5 on others. The pain is usually accompanied by a feeling of bloating. Burping or passing gas seems to relieve the pain. Eating seems to make the pain worse. Her BMI is 23.

Intravenous administration of neostigmine results in episodes of clustered abdominal contractions that recur at 8 minute intervals and that last for 40 minutes.

1.2 What is suggested by these findings?

She has features of irritable bowel syndrome (IBS)

1.3 What is the pathophysiology for this condition?

Persons with IBS do not have more gas or pathologic motility patterns, but instead seem to have exaggerated sensory responses to visceral stimuli.

A small amount of air is swallowed (aerophagia) in the process of eating and drinking, and some of this is burped. The remainder is passed through the small intestine into the colon. Some oxygen is resorbed, but additional gases including hydrogen, hydrogen sulfide, carbon dioxide, and methane are produced from the action of bacteria on residual stool from which water is resorbed. At any time, about 20 mL of gas is present in the GI tract, and about 500 to 1500 mL of flatus is produced each day.

1.4 How is this condition treated?

The patient can be counseled that a serious pathologic condition is not present. Instead, dietary patterns should be sought that help avoid the problem, particularly if certain food or drink triggers episodes. A higher fiber diet often helps.

Anticholinergic drugs may provide temporary relief for acute episodes. Tricyclic antidepressants may help, particularly if the major problem is diarrhea.

Some serotonergic agents have been recently introduced for treatment of IBS. Alosetron (Lotronex ®) is a 5-hydroxytryptamine 3 (5-HT3) receptor antagonist. Plasma concentrations are 30% to 50% lower and less variable in men compared to women given the same oral dose. Alosetron has been approved for use only for women with severe diarrhea-predominant IBS because serious gastrointestinal adverse events, some fatal, have been reported. Tegaserod (Zelnorm ®) is a 5-HT4 receptor partial agonist. It demonstrates high-affinity binding with 5-HT4 receptors without significant binding to 5-HT3 (dopamine) receptors. Activation of 5-HT4 receptors in the gastrointestinal tract stimulates peristalsis and secretion while blocking sensation. Tegaserod is indicated for short-term treatment of women with IBS whose primary bowel symptom is constipation.