Excretion of urinary histamine and N-tele methylhistamine in patients with gastrointestinal food allergy compared to non-allergic controls during an unrestricted diet and a hypoallergenic diet

Martin Raithel, Alexander Hagel, Heinz Albrecht, Yurdaguel Zopf, Andreas Naegel, Hanns-Wolf Baenkler, Fred Buchwald, Hans-Wolfgang Schultis, Juergen Kressel, Eckhart Georg Hahn, Peter Konturek, Martin Raithel, Alexander Hagel, Heinz Albrecht, Yurdaguel Zopf, Andreas Naegel, Hanns-Wolf Baenkler, Fred Buchwald, Hans-Wolfgang Schultis, Juergen Kressel, Eckhart Georg Hahn, Peter Konturek

Abstract

Background: Patients with gastrointestinal food allergy are characterised by increased production of mast cell derived mediators upon allergen contact and present often with unspecific symptoms. The aim of this study was to evaluate urinary histamine and methylhistamine excretion in patients with food allergy and to compare their values with food-tolerant controls.

Methods: In a retrospective case control study the urinary excretion parameters were analysed from 56 patients (40.9, 19 - 58 years) in whom later food challenge tests confirmed food allergy. During their diagnostic work-up urine was collected during a 12-h period under an unrestricted diet with staple foods and a hypoallergenic potato-rice-diet (each 2 days). Healthy controls underwent the same diet types to define normal excretion parameters. Urinary histamine and n-methylhistamine were determined by ELISA or tandem mass spectrometry, respectively, and were expressed as median (25 - 75% range, μg/mmol creatinine x m(2)BSA).

Results: During unrestricted diet urinary histamine was significantly higher in gastrointestinal food allergy than healthy controls (1.42, 0.9 - 2.7 vs 0.87, 0.4 - 1.3; p < 0.0001), while the difference between both groups became marginal during potato-rice diet (1.30, 0.7 - 2.1 vs 1.05, 0.5 - 1.5; p = 0.02). N-methylhistamine was found to be significantly elevated in gastrointestinal food allergy both during unrestricted diet (7.1, 5.0 - 11.2) and potato-rice diet (5.7, 3.7 - 8.7) compared to controls (p < 0.0001). Interestingly, urinary methylhistamine excretion (p < 0.004) and clinical symptom score (p < 0.02) fell significantly when the diet was switched from unrestricted to hypoallergenic food, but was not correlated with symptom scores.

Conclusions: In gastrointestinal food allergy significantly higher levels of urine histamine and methylhistamine excretion were found under unrestricted diet, reflecting an increased secretion of histamine due to offending foods. Measurement of urinary n-methylhistamine levels may help to find out patients with increased histamine production and/or food-allergen induced clinical symptoms, respectively.

Figures

Figure 1
Figure 1
A large number of patients with functional adverse food reactions were identified as carbohydrate malassimilation with/without small intestinal bowel overgrowth (SIBO), while a minority had non-allergic food intolerance or Irritable Bowel Syndrome (IBS). Among the remaining 225 patients an allergic disease could be excluded definitively, while 153 had strong clinical suspicion of gastrointestinally mediated allergy (GMA) and were scheduled for confirmatory food challenge tests. However, only in 56 patients completed diagnostics was obtained and this group with confirmation of allergy is further described as study group GMA.
Figure 2
Figure 2
The control group consisted of 19 healthy volunteers without any food related symptoms and 25 patients with non-allergic food intolerance. As indicated for the 20 patients with carbohydrate malassimilation food allergy was specifically excluded by clinical diagnostics, skin tests, specific serum IgE and in unclear cases (n = 6) even with double-blinded, placebo-controlled food challenges with negative findings.
Figure 3
Figure 3
Urinary histamine excretion (UH) in patients with gastrointestinally mediated allergy (GMA) and controls. Horizontal lines represent the median of the group. Comparison of mediator excretion in both groups during unrestricted diet and a hypoallergenic elimination diet.
Figure 4
Figure 4
Urinary methylhistamine excretion (UMH) in patients with gastrointestinally mediated allergy (GMA) and controls. Horizontal lines represent the median of the group. Comparison of mediator excretion in both groups during unrestricted diet and a hypoallergenic elimination diet.
Figure 5
Figure 5
Distribution of individual urine histamine (UH) values during unrestricted diet in 56 patients with gastrointestinally mediated allergy (GMA) and 44 controls. The grey box represents normal values of UH (mean ± 1 SD of controls).
Figure 6
Figure 6
Distribution of individual urine methylhistamine (UMH) values during unrestricted diet in 56 patients with gastrointestinally mediated allergy (GMA) and 44 controls. The grey box represents normal values for UMH (mean ± 1 SD of controls).

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