Gastrointestinal manifestations of SM: Part 1

Gastrointestinal symptoms are among the most common in SM, with up to 80% of patients experiencing them regularly.  When averaging figures from many studies, about 51% of SM patients have abdominal pain, 43% have diarrhea, and 28% have nausea and vomiting.  11% of SM patients have GI bleeding, usually in the upper tract.  Other GI problems common in SM include steatorrhea (excess fat in the stool), malabsorption, swollen liver, swollen spleen, free fluid in the abdomen and portal hypertension.  GI distress in SM can be severe and often mimics Irritable Bowel Disease or Zollinger-Ellison Syndrome.
Abdominal pain in SM generally has two types.  The first is epigastric dyspeptic pain, found in the upper abdomen, and is associated with ulcer disease and oversecretion of stomach acid.  Despite early reports that peptic ulcer disease is rare in SM patients, more recent studies have repeatedly disproven this idea.  On average, about 23% of SM patients have peptic ulcer disease.  Ulcers in SM patients with dyspeptic pain are often found on endoscopy.  In one study, 19% had a duodenal ulcer, while 25% had severe duodenitis.
The other type of GI pain is characterized by lower abdominal cramping.  Generally, one type is more prominent in a patient than the other, and they rarely co-occur with equal intensity.
85-100% of SM patients demonstrate increased histamine production.  Histamine is known to stimulate acid secretion, so SM patients are generally expectly to produce too much acid in the stomach.  However, studies have shown a variety of conflicting results.  Some patients produce too much acid, some too little, and some in the normal range.  For those who overproduce acid, the levels can be extremely high, comparable to levels seen in Zollinger-Ellison Syndrome. 
Occasionally, achlorhydria, the absence of gastric acid, has been found in SM patients.  This is thought to be due to atrophic gastritis (chronic inflammation of the stomach mucosa) that leads to impaired signaling from the local cells; however, this is unproven. 
Multiple studies have attempted to link serum histamine levels with normal basal acid secretion.  In one study, all patients had high serum histamine, but 56% had normal basal acid secretion.  This finding can be attributed to several things, including measured histamine not being fully biologically active; circulating histamine level being less important to acid secretion rate than the level of histamine in the local mucosa.  High histamine has been found in the gastric mucosa of several SM patients with dyspeptic pain. 
Furthermore, the authors elaborated that the histamine levels might not have been high enough to stimulate acid production; that the H2 receptors on acid producing (parietal) cells may have become desensitized to such high histamine levels; or that parietal cells were unable to respond to the histamine signaling, for some other reason.  Of these possible explanations, desensitization is supported by previous research, though not in SM patients.
In a study of 21 patients, 30% of them showed abnormalities on upper GI barium studies.  19% had gastric nodules and 11% had gastritis or peptic disease.  Biopsies of gastric mucosa show increased histamine and increased inflammatory cell infiltration with increased mast cells.  GI symptoms did not correlate with mast cell counts.
Common endoscopic findings in SM patients with dyspeptic pain include: acid hypersecretion; peptic ulcer disease; thickened gastric or duodenal folds; nodular mucosal lesions; occasional altered motility; occasional urticarial lesions; and increased infiltration by inflammatory cells with or without increased mast cells.
Studies have shown that approximately 28% of SM patients have esophageal abnormalities.  These include esophagitis, reflux, varices (abnormally enlarged veins that may bleed) or motor uncoordination.  Difficulty swallowing was common in these patients.  When assessed, these patients showed that the lower esophageal sphincter did not close with enough pressure. 
Esophageal motor function was assessed in 16 patients by manometry.  In 15/16 patients, the esophageal body contractions were normal.  In 62% of these patients, the lower esophageal sphincter function was abnormal.  75% of patients had reflux symptoms.  2/16 did not relax the esophageal sphinter during swallowing.
Esophageal varices have been reported in several SM patients.  The current rate of occurrence is listed as 2.5%, but this is likely an underestimation.
References:
Jensen RT. Gastrointestinal abnormalities and involvement in systemic mastocytosis. Hematol Oncol Clin North Am. 2000;14:579–623.
Bedeir A, et al.  Systemic mastocytosis mimicking inflammatory bowel disease: A case report and discussion of gastrointestinal pathology in systemic mastocytosis.  Am J Surg Pathol.  2006 Nov;30(11): 1478-82.
Lee, Jason K, et al.  Gastrointestinal manifestations of systemic mastocytosis.  World J Gastroenterol. 14(45): 7005-7008.