This paper describes a distinct group of GI patients with chronic abdominal pain and symptoms of GI dysmotility, features that mimic the features of entities such as IBS, FD, or IGP, but who actually suffer from gastrointestinal mast cell excess and/or instability. These patients frequently exhibit features of mast cell excess, including positive history of food and/or environmental allergies, signs and symptoms such as flushing, pruritus, tachycardia, asthma, headache, or dermatographism, and suggestive lab data such as elevated serum IgE levels or whole-blood histamine levels greater than 300
]. The corresponding plasma histamine level would be 3
In the current literature, there are two loosely defined entities associated with increased numbers on mast cells on gastrointestinal biopsies. The first of these is mastocytic enterocolitis. Mastocytic enterocolitis is defined as more than 20 mast cells per high-power field by tryptase stain in individuals with chronic diarrhea of unknown etiology [20
]. Mast cell activation syndrome occurs in individuals who have symptoms associated with mast cell instability including dermatographism, flushing, mental fog, or poor concentration, abdominal pain, diarrhea, anaphylaxis, and asthma who have a dramatic improvement in their symptoms in response to antihistamines and H2 blockers. Intriguingly, in this group, the numbers of mast cells on gastrointestinal biopsies by CD117 or tryptase were between 17 and 23 cells per high-power field [24
]. These distinguishing features between our cohort and the two other published GI mast cell disorders are summarized in .
Table 6 Comparison between different GI mast cell diseases [20, 24].
As mentioned in the introduction to this paper, IBS has been associated with elevated mast cell numbers [6
] and food allergy [16
]. The cohort we describe herein has several features that distinguish it from mastocytic enterocolitis and mast cell activation syndrome. They are (1) documented GI dysmotility, (2) nocturnal awakening, (3) elevated histamine levels, (4) history of food or environmental allergy, (5) significantly higher numbers of mast cells per high-power field, that is, approximately 40 per high-power field on average. As such, we propose that our cohort of patients represents a possible third entity wherein elevated numbers of mast cells are noted on gastrointestinal biopsies in patients who have previously been classified as having IBS, functional dyspepsia, or idiopathic gastroparesis. We suggest that this disorder could potentially be referred to as allergic mastocytic gastroenteritis and colitis as these patients have documented allergies, elevated histamine levels, and nocturnal awakening. Nocturnal awakening has been associated with uncontrolled asthma [31
] and in our cohort differentiates our patients from those with true IBS as defined by ROME III criteria. We believe that as in asthma, nocturnal awakening in our cohort was due to a spike in leukotrienes.
As other authors have suggested, treatment of gastrointestinal mast cell disease should be focused on blockade of H1 and H2 and mast cell stabilization. These therapeutic approaches include H1 receptor antagonists such as diphenhydramine (Benadryl), cetirizine (Zyrtec), loratadine (Claritin) [13
], H2 receptor antagonists such as ranitidine (Zantac) and famotidine (Pepcid), and mast cell membrane stabilizers such as oral cromolyn sodium (Gastrocrom) [32
]. Because of the nocturnal awakening observed in our patients, we would also suggest adding an antileukotriene such as montelukast (Singulair) or a 5-liopoxygenase inhibitor such as zileuton extended-release tablets (Zyflo CR). In patients with more severe symptoms that significantly disrupt their activities of daily living and/or sleep, we suggest the addition of budesonide (Entocort) or a short course of prednisone.
In conclusion, herein we report a cohort of patients with gastrointestinal mast cell disease separate and distinct from systemic mastocytosis and the aforementioned GI mast cell disorders. Further characterization of this possible disorder is needed in order to clearly distinguish these patients from those with IBS or systemic mastocytosis.