Evidence for a reduced histamine degradation capacity in a subgroup of patients with atopic eczema

doi:10.1016/j.jaci.2005.11.041

Journal of Allergy and Clinical Immunology

Volume 117, Issue 5, May 2006, Pages 1106-1112

https://doi.org/10.1016/j.jaci.2005.11.041 Get rights and content

Background

A diminished histamine degradation based on a reduced diaminoxidase activity is suspected as a reason for non–IgE-mediated food intolerance caused by histamine. Atopic eczema (AE) is often complicated by relapses triggered by IgE-mediated allergy to different kinds of food. However, in a subgroup of patients with AE, allergy testing proves negative, although these patients report a coherence of food intake and worsening of AE and describe symptoms that are very similar to histamine intolerance (HIT).

Objectives

It was the aim of our study to evaluate symptoms of HIT in combination with diaminoxidase levels in a total of 360 individuals consisting of patients with AE (n = 162) in comparison with patients with HIT (n = 124) without AE and healthy control volunteers (n = 85).

Methods

Histamine plasma level was determined with an ELISA and diaminoxidase serum activity with the help of radio extraction assays using [3H]-labeled putrescine-dihydrochloride as a substrate. Detailed clinical evaluations of characteristic features of AE and HIT were performed.

Results

Reduced diaminoxidase serum levels leading to occurrence of HIT symptoms like chronic headache, dysmenorrhea, flushing, gastrointestinal symptoms, and intolerance of histamine-rich food and alcohol were significantly more common in patients with AE than in controls. Reduction of both symptoms of HIT and Severity Scoring of Atopic Dermatitis could be achieved by a histamine-free diet in the subgroup of patients with AE and low diaminoxidase serum levels.

Conclusion

Higher histamine plasma levels combined with a reduced histamine degradation capacity might influence the clinical course of a subgroup of patients with AE.

Clinical implications

As HIT emerges in a subgroup of patients with AE, a detailed anamnestic evaluation of food intolerance and HIT symptoms complemented by an allergological screening for food allergy, a diet diary, and, in confirmed suspicion of HIT, measurement of diaminoxidase activity and a histamine-free diet should be undertaken.

Section snippets

Characterization of patients

A total of 162 adult AE³⁶ patients (age range, 14-86 years; average age, 31.42 ± 12.95 years; 106 female and 56 male) from the Department of Dermatology in Bonn, Germany, were analyzed regarding atopic status, and the severity of the disease was evaluated according to the Diepgen score,³⁷ the criteria of Bos,³⁸ the criteria of Hanifin and Rajka,³⁹ and the Severity Scoring of Atopic Dermatitis (SCORAD) system,⁴⁰ respectively. In parallel, typical clinical symptoms of HIT and a history of food

Symptoms of HIT occur in a subgroup of patients with AE

To analyze the frequency of HIT in patients with AE, we evaluated the occurrence of classical symptoms of HIT in patients with AE selected randomly by a standard questionnaire.

Symptoms of HIT such as chronic headache (P = .003; χ² = 8.556), premenstrual headache and dysmenorrhea (P = .002; χ² = 9.295), flushing (P < .001; χ² = 24.67), gastrointestinal symptoms such as diarrhea, cramps, and meteorism (P < .001; χ² = 38.89) and intolerance of food rich in or releasing histamine (P < .001; χ² =

Discussion

Histamine intolerance is caused by a disproportion of the quantity of histamine and the capacity of histamine degradation. This can be a result of histamine overload and/or diaminoxidase deficiency. Exceeding the individual histamine tolerance gives rise to concentration-dependent histamine-mediated symptoms.43, 44 In sensitive patients, symptoms occur even after oral ingestion of small amounts of histamine that are well tolerated by healthy persons. Symptoms can manifest in multiple organs

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Cited by (69)

Usefulness of the histamine intolerance assessment questionnaire for diagnosis
2021, Revue Francaise d'Allergologie
Citation Excerpt :
Eating histamine-rich food (products with microbial fermentation such as cheese, processed meat, tomato, spinach, blue fish, etc.), alcohol, or drugs that release histamine or block DAO in these patients, can cause symptoms in various organs. Some clinical studies have established a relation between DAO deficiency and specific pathologies, mainly gastrointestinal, respiratory, dermatological diseases and migraine (Fig. 1) [5–16], depending on the expression of histamine receptors (H1–H4) on them. Due to this variability of symptoms, the existence of HIT is frequently underestimated [3,4].
Histamine intolerance results from an imbalance of the ingested histamine and the individual capacity for its degradation. There are numerous tests not validated for the diagnosis of histamine intolerance that are usually found directly by customers, being able to generate a false perception of intolerance when there could be other possible explanations for their symptoms. One of these is the histamine intolerance questionnaire.
To analyse the diagnostic capacity of this questionnaire compared with an objective test of enzymatic activity of the diamine oxidase.
Descriptive and analytical observational study in volunteer adults, who attended for a reason other than suspected histamine intolerance, recruited consecutively from the outpatient departments of a tertiary hospital. Sociodemographic variables, histamine intolerance questionnaire (0–7 points) and DAO activity test were collected. Analysis of ROC curve was performed using the diamine oxidase deficient (< 80 HDU/mL) as a condition and the value of the histamine intolerance questionnaire as a contrast variable to evaluate which could be the most appropriate cut-off point in clinical practice.
A total of 166 Caucasian patients were recruited. ROC curve that contrasts the questionnaire value, quantifying the area under the curve (0.537, P = 0.415) with a 95% CI (0.448–0.625), not finding statistically significant differences for an appropriate cut.
The results of this work do not support the reliability of this questionnaire as a screening method for patients with suspected histamine intolerance. Research should continue in order to clarify, standardize and improve the detection methods of these pathologies.
L’intolérance à l’histamine résulte d’un déséquilibre de l’histamine ingérée et de la capacité individuelle à sa dégradation. Il y a de nombreux tests non validés ciblés pour la détection de l’intolérance à l’histamine et, d’habitude, ce sont ces méthodes d’examen que les patients trouvent plus facilement, en créant ainsi la fausse sensation d’intolérance même quand leurs symptômes pourraient être expliqués par d’autres maladies. L’un de ce test, c’est le « questionnaire d’intolérance à l’histamine ». Le but de cette étude est d’analyser la capacité du questionnaire pour diagnostiquer cette maladie en comparaison avec le test objectif de détermination de l’activité diamine oxydase dans le sérum.
Il s’agit d’une étude analytique et observationnelle réalisée chez des patients adultes consultant pour d’autres symptômes que ceux associés à l’intolérance à l’histamine dans un hôpital de soins tertiaires. Les données suivantes ont été collectées : des variables sociodémographiques, le questionnaire d’intolérance à l’histamine (0–7 points) et le test de détermination de l’activité DAO. Pour l’analyse des courbes ROC, l’on a utilisé le déficit de DAO (< 80 HDU/mL) comme condition et le résultat du questionnaire d’intolérance à l’histamine comme variable de contraste pour évaluer la valeur limite la plus appropriée pour utiliser en pratique clinique.
Un total de 166 patients caucasiens ont été recrutés. En quantifiant l’aire sous la courbe ROC qui fait le contraste de la valeur du questionnaire (0,537, p = 0,415) avec un intervalle de confiance à 95 % (0,448–0,625), l’on n’a pas trouvé de différences significatives pour une valeur limite adéquate.
Les résultats de ce rapport ne supportent pas la fiabilité de ce questionnaire comme méthode de dépistage pour ceux des patients soupçonnés d’avoir de l’intolérance à l’histamine. Il faudra continuer à investiguer pour standardiser ce test ainsi comme pour améliorer les méthodes diagnostiques de ces maladies.
Diamine oxidase (DAO) supplement reduces headache in episodic migraine patients with DAO deficiency: A randomized double-blind trial
2019, Clinical Nutrition
Citation Excerpt :
Headache is one of the symptoms most frequently related to histamine intolerance. Reduced DAO activity has been described by several clinical studies in patients diagnosed with some pathology such as atopic eczema, chronic urticaria, chronic abdominal pain or inflammatory bowel diseases [9,10,12–15]. A recent study also reported a high prevalence (87%) of DAO deficiency in a group of 137 patients diagnosed with migraine [16].
Histamine intolerance is a disorder in the homeostasis of histamine due to a reduced intestinal degradation of this amine, mainly caused by a deficiency in the enzyme diamine oxidase (DAO). Among histamine related symptoms, headache is one of the most recorded. Current clinical strategies for the treatment of the symptomatology related to this disorder are based on the exclusion of foods with histamine or other bioactive amines and/or exogenous DAO supplementation. The aim of this study was to assess the efficacy of a food supplement consisting of DAO enzyme as a preventive treatment of migraine in patients with DAO deficiency through a randomized double-blind trial.
100 patients with confirmed episodic migraine according to current International Headache Society (IHS) criteria and DAO deficiency (levels below 80 HDU/ml) were randomized in two groups. One group received DAO enzyme supplementation and the other received placebo for one month. Clinical outcomes assessed were duration and number of attacks, perception of pain intensity and adverse effects during treatment. The use of triptans was also recorded.
Great variability was found in the duration of migraine attacks reported by placebo and DAO groups. A significant reduction (p = 0.0217) in hours of pain was achieved in patients treated with DAO supplement, with mean durations of 6.14 (±3.06) and 4.76 (±2.68) hours before and after treatment, respectively. A smaller reduction without statistical signification was also observed for this outcome in the placebo group, from 7.53 (±4.24) to 6.68 (±4.42) hours. Only in DAO group, a decrease in the percentage of patients taking triptans was observed. The number of attacks and the scores of pain intensity showed a similar reduction in both groups. No adverse effects were registered in patients treated with DAO enzyme.
Migrainous patients supplemented with DAO enzyme during one month significantly reduced the duration of their migraine attacks by 1.4 h. No statistically significant reduction was found in placebo group before and after treatment. The reduction of pain hours observed in placebo group (0.9 h) could explain the lack of significant differences between both study groups. One month of DAO supplementation has demonstrated a positive trend in the improvement of migraine but more studies with a longer treatment period are needed to better assess the efficacy of DAO supplementation.
ISRCTN10091019; www.isrctn.org.
Measurement of diaminoxidase (DAO) during low-histamine or ordinary diet in patients with and without histamine intolerance
2023, Research Square
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2023, Journal of Clinical Medicine
Is Histamine and Not Acetylcholine the Missing Link between ADHD and Allergies? Speer Allergic Tension Fatigue Syndrome Re-Visited
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The Use of DAO as a Marker for Histamine Intolerance: Measurements and Determinants in a Large Random Population-Based Survey
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Supported by grants from the Deutsche Forschungsgemeinschaft (DFG NO454/1-4 and DFG NO454/2-3) and a BONFOR grant of the University of Bonn. Dr Novak is supported by a Heisenberg-Fellowship, DFG NO454/3-1.

Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest.

View full text

Food allergy, dermatologic diseases, and anaphylaxisEvidence for a reduced histamine degradation capacity in a subgroup of patients with atopic eczema

Background

Objectives

Methods

Results

Conclusion

Clinical implications

Section snippets

Characterization of patients

Symptoms of HIT occur in a subgroup of patients with AE

Discussion

Biochim Biophys Acta

J Biol Chem

J Biol Chem

Biochim Biophys Acta

J Biol Chem

J Allergy Clin Immunol

J Pediatr

FEBS Lett

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Dermatol Sci

Biogenic amines in foods: histamine and food processing

Inflamm Res

Biogenic amines: their importance in foods

Int J Food Microbiol

Human intestinal diamine oxidase: substrate specificity and comparative inhibitor study

Agents Actions

The importance of human intestinal diamine oxidase in the oxidation of histamine and/or putrescine

Arch Immunol Ther Exp (Warsz)

Biochemical, physiological and pathophysiological aspects of intestinal diamine oxidase

Acta Physiol Pol

Human kidney diamine oxidase: heterologous expression, purification, and characterization

J Biol Inorg Chem

Determination of the activity of diamine oxidase in extremely small tissue samples

Inflamm Res

Analysis of tissue and subcellular localization of mammalian diamine oxidase by confocal laser scanning fluorescence microscopy

Inflamm Res

Expression of histamine degrading enzymes in porcine tissues

Inflamm Res

Determination of histamine degradation capacity in extremely small human colon samples

Inflamm Res

Food-induced histaminosis as an epidemiological problem: plasma histamine elevation and haemodynamic alterations after oral histamine administration and blockade of diamine oxidase (DAO)

Agents Actions

Food-induced histaminosis under diamine oxidase (DAO) blockade in pigs: further evidence of the key role of elevated plasma histamine levels as demonstrated by successful prophylaxis with antihistamines

Agents Actions

Intestinal diamine oxidases and enteral-induced histaminosis: studies on three prognostic variables in an epidemiological model

J Neural Transm Suppl

Adverse reactions to food. European Academy of Allergology and Clinical Immunology Subcommittee

Allergy

Histamine-free diet: treatment of choice for histamine-induced food intolerance and supporting treatment for chronic headaches

Clin Exp Allergy

The red wine provocation test: intolerance to histamine as a model for food intolerance

Allergy Proc

Histamine in wine: bronchoconstriction after a double-blind placebo-controlled red wine provocation test

Int Arch Allergy Immunol

Histamin-Intoleranz. Histamin und Seekrankheit

Wine and headache

Int Arch Allergy Immunol

Are adverse effects of sildenafil also caused by inhibition of diamine oxidase?

Urol Int

Plasma histamine and clinical tolerance to infused histamine in normal, atopic and urticarial subjects

Agents Actions

Food allergy, dermatologic diseases, and anaphylaxis
Evidence for a reduced histamine degradation capacity in a subgroup of patients with atopic eczema