Michael Weidenhiller

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 (μg/mmol creatinine × m2 body surface area) was measured by radioimmunoassay in 55 controls, 56 patients with Crohns 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 Crohns 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 Crohns disease and ulcerative colitis, a significant correlation of UMH excretion with clinical disease activity was obtained (Crohns 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 (Crohns 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 (Crohns 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 Crohns disease. However, UMH excretion correlated strongly with endoscopic severity of inflammation in Crohns disease (Crohns 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.

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 μg/mg vs 7.09 ± 7.68 μg/mg; p < 0.05) and the rectosigmoid (23.66 ± 19.43 μg/mg vs 11.97 ± 16.39 μg/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.

The Malabsorption of Commonly Occurring Mono and Disaccharides: Levels of Investigation and Differential Diagnoses

BACKGROUND Adverse food reactions (AFR) have has recently attracted increased attention from the media and are now more commonly reported by patients. Its classification, diagnostic evaluation, and treatment are complex and present a considerable challenge in clinical practice. Non-immune-mediated types of food intolerance have a cumulative prevalence of 30% to 40%, while true (immune-mediated) food allergies affect only 2% to 5% of the German population. METHOD We selectively searched the literature for pertinent publications on carbohydrate malabsorption, with special attention to published guidelines and position papers. RESULTS Carbohydrate intolerance can be the result of a rare, systemic metabolic defect (e.g., fructose intolerance, with a prevalence of 1 in 25,000 persons) or of gastrointestinal carbohydrate malabsorption. The malabsorption of simple carbohydrates is the most common type of non-immune-mediated food intolerance, affecting 20% to 30% of the European population. This condition is caused either by deficient digestion of lactose or by malabsorption of fructose and/or sorbitol. Half of all cases of gastrointestinal carbohydrate intolerance have nonspecific manifestations, with a differential diagnosis including irritable bowel syndrome, intolerance reactions, chronic infections, bacterial overgrowth, drug side effects, and other diseases. The diagnostic evaluation includes a nutritional history, an H2 breath test, ultrasonography, endoscopy, and stool culture. CONCLUSION The goals of treatment for carbohydrate malabsorption are to eliminate the intake of the responsible carbohydrate substance or reduce it to a tolerable amount and to assure the physiological nutritional composition of the patients diet. In parallel with these goals, the patient should receive extensive information about the condition, and any underlying disease should be adequately treated.

Microscopic (collagenous and lymphocytic) colitis triggered by food allergy

Collagenous and lymphocytic colitis1,2 are rare3 diseases of unknown aetiology but several issues,1–3,5 in particular the good response to budesonide,7 are suggestive of immunopathology. Patients have watery diarrhoea without abnormal findings on colonoscopy1–5 but with increased numbers of intraepithelial lymphocytes, mast cells, and eosinophils5 on histological examination. We report six patients seen between 1993 and 1999 who were first diagnosed as having collagenous/lymphocytic colitis. Signs of allergy entailed a work up for food allergy. (table 1) View this table: Table 1  Patient characteristics All patients were investigated with skin prick testing, total and allergen specific …

Standardised evaluation of urinary excretion of N-tele-methylhistamine in different periods of age in a healthy population.

Allergy frequency is still increasing in industrial countries, but monitoring of allergic and inflammatory conditions may be difficult. The incidence of allergy and elevated IgE serum levels has been reported to decrease with age. The measurement of urinary excretion of N-tele-methylhistamine is a valuable diagnostic tool to monitor disease activity in allergic or inflammatory conditions (e.g. food allergy, inflammatory bowel diseases, microscopic colitis), but there are only rare data on histamine production and excretion in different periods of age in a healthy adult population [1].

Long-Term Partial Remission of AutoImmune Thrombocytopenia in a Patient Treated with the Anti-Tumor Necrosis Factor-Alpha Antibody Infliximab for Refractory Fistulizing Crohn’s Disease

Background: Up to the present date, the treatment of recurrent chronic fistulas occurring with Crohn’s disease represents a challenging task for both internists and surgeons alike. Methods: Conservative methods of treatment using steroids, dietotherapy, antibiotics or immunosuppressive agents are not particularly effective in treating fistulas. Treatment with anti-tumor necrosis factor-α (TNFα) antibodies results in more remissions of fistulas. However, its use requires appropriate medical experience and causes substantial costs. Surgical procedures such as fistula sanitation or protective ileostomy are often obfuscated by the recurrence of the condition. The efficiency of anti-TNFα antibodies for the treatment of active Crohn’s disease has been evidenced through several multicenter, double-blind, placebo-controlled studies. Results: Here we report the successful anti-TNFα treatment of a patient suffering from chronic, fistulizing, therapy-resistant Crohn‘s disease and a concomitant chronic autoimmune thrombocytopenia. The chimeric anti-TNFα antibody infliximab markedly reduced the disease activity of Crohn’s disease, and, in addition, substantially increased the platelet counts. After infliximab application, no other treatment of autoimmune thrombocytopenia was required. After infliximab therapy, autoantibodies to dsDNS could be observed. However, there were no signs of a lupus-like disease. Conclusion: This report indicates a favorable therapeutic response of autoimmune thrombocytopenia associated to Crohn’s disease.

Immunoglobulin E production in chronic pancreatitis.

Objectives Serum immunoglobulin E (IgE) was investigated in patients with chronic pancreatitis in order to elucidate possible disease mechanisms linking pancreatitis, adverse reaction to foods and allergy. Design and methods Serum IgE was analysed in 86 nonatopic patients with advanced chronic pancreatitis and 54 non‐atopic controls. IgE detection was performed by enzyme‐linked immunofluorescence. Results Mean IgE levels (± standard error of mean) in chronic pancreatitis patients (286.1 ± 49 kU/l) were found to be significantly elevated compared to controls (67.7 ± 11 kU/l; P < 0.0001). Normal IgE levels (< 100 kU/l) were present in 40/54 control patients (74.1%), but only 39/86 pancreatitis patients (45.3%). Of the patients with chronic pancreatitis, 47/86 (54.6%) had clearly elevated IgE levels of > 100 kU/l and their IgE values did not show a Gaussian distribution. However, nine‐fold higher IgE levels were found in chronic pancreatitis patients with alcohol consumption of > 25 g/day and exocrine insufficiency (915.5 ± 240 kU/l) than in pancreatitis patients with normal exocrine function and no alcohol consumption (103.4 ± 43 kU/l; P < 0.001). Moreover, acute episodes of chronic pancreatitis were found to increase serum IgE levels. Conclusions In patients with chronic pancreatitis, serum IgE production is markedly enhanced, especially during acute inflammatory episodes or when alcohol is consumed. Since abstinence from alcohol and pancreatic enzyme substitution are associated with clearly lower IgE levels, it may be concluded that pancreatic insufficiency with reduced nutrient digestion and alcohol consumption stimulate IgE production. This finding gives rise to the speculation that, apart from pancreatic inflammation, cross‐linking of IgE with alimentary or other antigens might be involved in the pathophysiology of a subpopulation of patients with chronic pancreatitis and manifest pancreatic insufficiency.

Diagnostic use of mucosa oxygenation and histamine release experiments in patients with gastrointestinally mediated allergy (GMA)

Gastrointestinal complaints after ingestion of certain foodstuffs often pose diagnostic problems in various clinical situations like food hypersensitivity, irritable bowel syndrome, inflammatory bowel disease etc [1]. A functional histamine release from intact human biopsies of the small intestine has been described in 1989 [2]. This study investigated histamine release from gut mucosal samples in gastrointestinally mediated allergy (GMA) in response to antigens that had been proven by blinded, placebo-controlled oral challenge (BPCFC) as causative allergens or tolerated foodstuffs.

Evaluation of spontaneous histamine release from colorectal mucosa in patients with colorectal adenoma, patients with gastrointestinally mediated allergy and in a healthy control group

Histamine enhances gut epithelial cell proliferation [1, 2]. Thus, elevated histamine concentrations in colonic tissue might contribute to colorectal carcinogenesis. The aim of this investigation was to assess the rate of spontaneous histamine release (SHR) from colorectal mucosa in patients with colorectal adenoma, patients with confirmed gastrointestinally mediated allergy and a healthy control group with normal colorectal findings.

Enhanced mstamine production in collagenous colitis (CC) during unrestricted and elimination (potato-rice) diet

Background: The cause of CC is unknown, but the activation of inflammatory cells like eosinophils or mast cells has been described, suggesting an allergic pathomechanism. Additionally, the therapeutic efficacy of fecal stream diversion shows that luminal factors play an important role in the pathogenesis of CC. Taken together, this is suggestive for a role of food allergy in CC. Methods: In 13 patients with CC, 12-h-urine (for histamine (UH) and methyl-histamine (UMH)) was collected during a non-restricted diet (NO) and a elimination diet (ED) consisting of potato and rice. The values obtained were compared with those of patients with food allergy (FA)(n=42) and healthy controls (n=27). Measurement was performed using a RIA (Methyl-Histamine: Pharmacia, Freiburg, Germany; Histamine: Coulter-Immunotech, Hamburg, Germany). Results: When tested during NO, 27 urine samples or patients with CC were available (for ED: 20). UMH was significantly elevated when compared with controls (p=0.02), but not UH. UMH was unchanged, when the patients were switched on a elimination diet in contrast to values obtained in patients with food allergy, who showed similar elevation of UH and UMH, but a significant reduction under ED (p=0.02 for both). Conclusion: In patients with CC, the extensive activation of mast cells appears not to be influenced by an elimination diet. This finding suggests an induction of histamine secretion by rice and potato. Since allergic reactions to potato or rice are rare, this could be realized by salicylates, which are present abundantly in potatoes. This could further add to the evidence of an association of NSAID-consumption and presence of Cc.