Combination therapy using fexofenadine, disodium cromoglycate, and a hypoallergenic amino acid-based formula induced remission in a patient with steroid-dependent, chronically active ulcerative colitis.

Corticosteroids and 5-aminosalicylic acid are the primary standard therapy for inflammatory bowel disease. Recent immunologic data implicate an involvement of mast cell activation followed by increased histamine secretion and elevated tissue concentrations of histamine in the pathogenesis of ulcerative colitis. In the present case, the clinical course of a 35-year-old man with steroid-dependent chronic active ulcerative colitis, who did not respond to high-dose steroids, antibiotics, or azathioprine during 3 years, is reported. Clinical disease activity and established serological markers were recorded during 6 weeks of unsuccessful therapy and during the next 6 weeks, as a new nonsedative antihistaminergic drug, a mast cell stabilizer, and an hypoallergenic diet were implemented in addition to conventional therapy. Induction of remission was achieved within 2 weeks after treatment with fexofenadine, disodium cromoglycate, and an amino acid-based formula. Clinical disease activity, stool frequency, leukocytes, c-reactive protein, and orosomucoid levels in serum decreased rapidly. Daily steroid administration could be gradually reduced along with 6 weeks of this treatment. This report suggests that histamine and mast cell activity may be important pathophysiological factors responsible for persistent clinical and mucosal inflammatory activity in ulcerative colitis despite the use of steroids. In ulcerative colitis, patients unresponsive to conventional treatment, therapeutic considerations should also include an antiallergic approach when further signs of atopy or intestinal hypersensitivity are present.

Urinary excretion of N-methylhistamine as a marker of disease activity in inflammatory bowel disease.

OBJECTIVE: Mast cells are thought to participate in the pathogenesis of inflammatory bowel disease (IBD). In this study, urinary excretion of N-methylhistamine (UMH), a stable metabolite of the mast cell mediator histamine, was evaluated as an indicator of disease activity in patients with IBD. METHODS: Urinary excretion of UMH (microg/mmol creatinine x m2 body surface area) was measured by radioimmunoassay in 55 controls, 56 patients with Crohn's disease, and in 36 patients with ulcerative colitis. Excretion rates were correlated with clinical, serological, and endoscopic disease activity, disease extent, and location. RESULTS: Urinary excretion of UMH was found to be significantly elevated in IBD. Patients with active Crohn's disease (7.1 +/- 4.2, p = 0.002 vs controls) and active ulcerative colitis (8.1 +/- 4.8, p = 0.02 vs controls) had higher rates of UMH excretion than patients in remission (6.3 +/- 3.8 and 5.2 +/- 2.3, respectively) or controls (4.6 +/- 1.9). In Crohn's disease and ulcerative colitis, a significant correlation of UMH excretion with clinical disease activity was obtained (Crohn's Disease Activity Index r2 = 0.58, Clinical Activity Index r2 = 0.57, p < 0.0001). Serologically, orosomucoid showed the best positive correlation with disease activity (Crohn's Disease Activity Index r2 0.80, Clinical Activity Index r2 = 0.86, p < 0.0001), but UMH excretion was found to reflect disease activity more accurately than C-reactive protein (Crohn's Disease Activity Index r2 = 0.46, Clinical Activity Index r2 = 0.42, p < 0.0001). No association between UMH excretion and disease type or localization could be found in Crohn's disease. However, UMH excretion correlated strongly with endoscopic severity of inflammation in Crohn's disease (Crohn's Disease Endoscopic Index of Severity r2 = 0.70, p < 0.0001) or disease extent in ulcerative colitis. CONCLUSIONS: Urinary excretion of the histamine metabolite UMH is enhanced in IBD. It appears to represent an integrative parameter to monitor clinical and endoscopic disease activity in IBD, which appears to be influenced most likely by mediators released from histamine-containing cells, such as intestinal mast cell subtypes.

Release of mast cell tryptase from human colorectal mucosa in inflammatory bowel disease.

BACKGROUND: Histologic detection of mast cells cannot adequately reflect their function and state of activation, since degranulated mast cells may escape from histologic assessment. To better define the role of mast cells in inflammatory bowel disease, the spontaneous secretion of mast cell tryptase, a highly mast cell specific protease, was measured from colorectal samples. METHODS: After detection of the initial basal tryptase release, gut mucosal samples were incubated in a modified Hanks/RPM1 medium using a mucosa oxygenation system. Spontaneous tryptase secretion from 153 viable samples of 22 controls, 30 patients with Crohn disease (CD) and 19 with ulcerative colitis (UC) was followed over 4 h. Tryptase was measured by radioimmunoassay. RESULTS: The rates of the initial basal tryptase release revealed that mast cell activation occurs during active inflammation in CD and UC. While the time course of tryptase release was similar in all three groups, spontaneous tryptase secretion (over 4 h) was found to be significantly enhanced and prolonged only in UC (P < 0.01 compared to controls), but not in CD. CONCLUSIONS: This study provides clear evidence from viable endoscopic colorectal samples that mast cell mediators were secreted during active inflammation in CD and UC. However, the extent of mast cell involvement and activation differs considerably between CD and UC. Significantly increased rates of tryptase secretion were found both in non-inflamed and inflamed tissue of UC, indicating that mast cell involvement is a typical feature of UC.

Immunoglobulin E and eosinophilic cationic protein in segmental lavage fluid of the small and large bowel identify patients with food allergy.

OBJECTIVE: Members of the general population often assume that they suffer from food allergy, but the true prevalence is low. Testing for the diagnosis of food-related hypersensitivity entails laborious procedures, including GI endoscopy. Our objective was to develop an endoscopic screening approach for food allergy. METHODS: Endoscopically guided segmental lavage was performed in 11 patients with GI allergy and in 20 controls during lower GI endoscopy of the terminal ileum, the coecum, and the rectosigmoid. Eosinophilic cationic protein (ECP) and protein were measured in native lavage fluid, and immunoglobulin E (IgE) was also measured after a 10-fold lavage concentration. RESULTS: IgE/protein in lavage fluid from the coecum (0.055 +/- 0.068 U/mg vs 0.003 +/- 0.012 U/mg; p = 0.001) and the rectosigmoid (0.134 +/- 0.170 U/mg vs 0.019 +/- 0.042 U/mg; p < 0.05) was significantly elevated in patients with GI allergy. ECP/protein was significantly elevated at the terminal ileum (22.95 +/- 37.67 microg/mg vs 7.09 +/- 7.68 microg/mg; p < 0.05) and the rectosigmoid (23.66 +/- 19.43 microg/mg vs 11.97 +/- 16.39 microg/mg; p < 0.05). The combined use of GI lavage IgE and ECP as a diagnostic test for food allergy resulted in a sensitivity of 91% and a specificity of 80%. CONCLUSIONS: In endoscopically guided segmental lavage fluid, IgE and ECP/protein are increased in patients with food allergy. These measurements seem to offer an attractive diagnostic tool and may serve as a screening method.

Secretion and tissue content of eosinophil cationic protein in Crohn's disease.

To define further the role of eosinophils in the pathogenesis of Crohn's disease, the secretion rate and tissue content of eosinophilic cationic protein (ECP) were measured in colorectal samples. Mucosal biopsies were obtained from 22 controls and 20 patients with Crohn's disease during colonoscopy. After measurement of the initial basal ECP, release samples were incubated using a mucosa oxygenation system. Spontaneous and antiimmunoglobulin E (anti-IgE)-induced secretions of ECP were measured at different time points. For detection of the remaining tissue, ECP amount samples were mechanically homogenized after the incubation period. ECP measurement was performed by radioimmunoassay. Spontaneous ECP secretion rates during the incubation period were similar in all patient groups, whereas the initial basal ECP secretion was significantly increased in tissue affected by Crohn's disease. After stimulation with anti-IgE, ECP secretion was increased two-fold in controls and three-fold in patients with Crohn's disease. In tissue affected by Crohn's disease, ECP levels were found to be significantly increased in most segments of the lower gastrointestinal tract with the highest ECP concentrations in affected mucosa. This functional study demonstrates an enhanced immunologically mediated ECP secretion and an accumulation of ECP in the intestinal mucosa of Crohn's disease, indicating a local upregulation of eosinophils.