Gastrointestinal manifestations of SM: Part 2

In SM, the small intestine is sometimes normal when biopsied.  When comparing data across many studies, it is believed that at least 30% SM patients have small bowel structural abnormalities.
In one study, small nodules in the mucosa could be observed in the small intestine in 73% of patients.  It is thought that the small nodules (1 mm) represent focal edema (localized swelling) in superficial mucosa and intestinal villi, while the larger nodules are focal edema in the lamina propria. These nodules do not represent mast cell aggregates.  On endoscopy, biopsy of these lesions showed no aggregates.   
In 23% of patients, lesions show an indistinct jejunal mucosa pattern, probably from excessive secretions.  13% show a malabsorption pattern with flocculation and segmentation; irritability of the muscularis and circular muscle layer is likely responsible for jejunization of ileum in 18% of patients. 
In one study, 57% of patients had small intestinal mucosal thickening, nodularity and/or polypoid lesions.  In a second study, 29% had small bowel abnormalities, including 14% with jejunal or ileal nodules and 14% malabsorption pattern. 
However, a whole host of abnormalities are sometimes seen: thickened jejunal folds with edema; dilated small bowel; blunted villi; partial villous atrophy or edema; complete villous atrophy; infiltration by eosinophils and/or mast cells; spru like mucousal changes responding to gluten free diet; malabsorption with tetany; osteomalacia; vitamin A deficiency; mesenteric thickening or infiltration; bulls eye lesions.
A key aspect of small intestine disease in SM patients is malabsorption.  Previously thought to be rare, multiple studies have now shown that malabsorption is more common in SM and is due to small intestine defects.  Approximately 5-25% of SM have malabsorption, which is generally mild.  One study of SM patients found that 31% had impaired absorptive function.  This was determined by 72-hour fecal fat studies, D-xylose tolerance testing and Schilling test.  Pancreatic function is normal in all SM patients evaluated in these studies. 
An older study found that 23/34 patients studied had elevated fecal fat excretion.  In most, steatorrhea (excess fat in stool) was mild, but it can be severe.  In one study, four patients with steatorrhea all had abnormal findings on biopsy, including villi changes, increased inflammation in the mucosa, increased plasma cells and eosinophils, and sometimes increased mast cells.
Due to the excess excretion of fat in SM patients, they may have malabsorption of fat soluble vitamins such as D or calcium, causing tetany (involuntary muscle contraction) or osteomalacia (softening of the bones.)  Malabsorption of vitamin A can cause night blindness due to rod cone deficiency in retina.
Rarely, celiac disease is reported with SM.  In order to determine which is present, intestinal mucosa must be examined carefully by microscope.  In SM, patients may have patchy lesions with partial villous atrophy.  Enterocytes are normal, which is not seen in celiac.  Sparseness and destruction of crypts in seen in lamina propria, as well as lesions from mast cell infiltration along with neutrophils and eosinophils.  Villous atrophy secondary to crypt atrophy is sometimes seen.  But in SM, there is no crypt hyperplasia.
There have been a few reports of SM patients with selective deficiency of IgA in duodenal fluid only.
For many years, colon involvement was not considered to be an inherent part of SM. More recently, it has been found that up to 20% of SM patients have colon abnormalities.  Diverticulitis occurs in as many as 19% of patients.  Less distension of rectum is necessary to induce pain or urgency in SM patients.  They are also more likely to have overactive rectal contractility and decreased rectal compliance, making complete defecation more difficult.

13% of patients were found to have nodules in the colon mucosa.  Lesions seen by barium examination are thought to be due to edema and not mast cell infiltration, though mast cell infiltration of the colon has been reported.  Mastocytic enterocolitis has been described.  (I’m doing a separate post on this.)

Abnormalities seen include edema with or without granularity, edema with urticarial lesions, purple pigmented lesions.  Diffuse intestinal telangiectasia is sometimes present.  Biopsies of polypoid lesions show extensive infiltration by histiocyte like cells.  In some patients, colon or rectal mucosa showed mixed infiltrates of mast cells and eosinophils, increased mast cells in perivascular spaces, lamina propria, submucosa or muscularis mucosa. 
Diarrhea is a common complaint of SM patients.  There are several possible causes.  Fat absorption can cause diarrhea, but this is unlikely in SM.  It has been shown in these patients that diarrhea can occur with or without fat malabsorption, indicating that the two processes do not stem from a single origin.  Mast cell patients with diarrhea generally do not have malabsorption.  GI transit time in SM diarrhea patients may be normal or even slow, contributing further to the lack of the clarity.
Specific GI regulatory molecules directly causing diarrhea in SM have not been identified, although mediator release can certainly cause this symptom by various pathways.  PGD2 has been suggested repeatedly as a cause.  PGD2 can be 100X normal in SM patients.  In patients with very high prostaglandin levels, use of aspirin decreased diarrhea. 
The treatment for mast cell diarrhea includes the usual suspects, like H1 and H2 antagonists and cromolyn.  Tixocortol was also found to be helpful in decreasing abdominal pain and stool frequency.  Patients who improved with tixocortol also showed improvement on biopsy, decreased fecal fat excretion and increased absorption.

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.