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Article
Diaminoxidase keine diagnostische Hilfe bei Histaminintoleranz
Abstract
Although exact numbers on the prevalence of histamine intolerance are lacking, it seems to be on a rise during the last years. The estimated prevalence in the population is 3%. This is particularly true for middle-aged female patients. A deficiency of 1 of the histamine metabolizing enzymes, diamine oxidase (DAO) has been postulated as the main causal factor. Recently, a commercial radioimmunoassay for determination of DAO activity has been launched. To evaluate the clinical impact of this assay for the diagnosis of histamine intolerance, we performed a prospective, multicentre study in 207 adult patients. In 77 patients, a diagnosis of histamine intolerance was made based on clinical criteria, in 67 a diagnosis "in question", and 61 healthy patients without anamnestic evidence for histamine intolerance served as a control. Interestingly, no correlation between diamine oxidase serum levels and clinical status could be found in any of the 3 groups. We, therefore, recommend further investigations, before determination of DAO serum activity should be used as a screening tool for the diagnosis of histamine intolerance.
... Multiple sets of clinical criteria for HIT diagnosis have been proposed in the literature with the aim of minimizing the confounding effects of other conditions, such as food intolerances [35,41,42], irritable bowel syndrome [43][44][45][46], and non-celiac gluten sensitivity [19,47,48]. In the absence of a universal definition of HIT, a reliable comparison among distinct cohorts remains challenging [49]. In addition, there is also limited knowledge about the possible compensatory mechanisms accounting for the coexistence of low DAO levels and the absence of symptoms among healthy subjects as well as on the potential role of pathogenic mechanisms other than DAO deficiency in patients with HIT and higher DAO levels. ...
... In addition, there is also limited knowledge about the possible compensatory mechanisms accounting for the coexistence of low DAO levels and the absence of symptoms among healthy subjects as well as on the potential role of pathogenic mechanisms other than DAO deficiency in patients with HIT and higher DAO levels. Regarding this aspect, it might be well-accepted that serum DAO levels alone cannot substitute accurate history taking and conventional allergy and gastroenterological workup to rule out alternative diagnoses [49]. Indeed, data from this study further highlight that accurate pre-test stratification of patients might enhance the diagnostic significance of DAO measurement, which might be more fit to identify patients with distinct degrees of symptom severity and treatment susceptibility within the spectrum of HIT rather than surrogating other tools for HIT diagnosis [10,24,26]. ...
Background:
Histamine Intolerance (HIT) is a multifaceted pseudoallergic disorder possibly due to defective histamine metabolism. Diamine oxidase (DAO) contributes to histamine degradation and can be measured in the serum. The role of DAO measurement in the diagnostic work-up of HIT still remains unclear, and conflicting results have been reported in the literature. Therefore, we aimed to evaluate the possible clinical usefulness and consistency of DAO value ranges as provided by the assay manufacturer and verify whether they could predict the response to treatment.
Methods:
We retrospectively analyzed 192 outpatients with HIT symptoms and measured serum DAO values at baseline. Patients were prescribed either with low-histamine diet and/or enzymatic supplementation according to symptom severity and re-evaluated six to eight months later. Patients were stratified into three groups according to DAO levels: <3 U/mL, 3-10 U/mL, and >10 U/mL. HIT severity was assessed on a scale of 1 to 5 before and after treatment.
Results:
A total of 146 patients completed the study. Gastrointestinal and cutaneous symptoms, often associated with headache, were more frequent in subjects with DAO < 10 U/mL. Symptom severity and DAO ranges were correlated. Patients with intermediate DAO levels (3-10 U/mL) showed a more complex clinical phenotype but also a more significant improvement in symptom severity (score reduction 50%, interquartile range (IQR) = 33-60%) when compared to patients with low DAO (40%, IQR = 20-60%; p = 0.045) or high DAO (33%, IQR = 0-50%; p < 0.001). Complex clinical phenotypes were also more frequent in patients with intermediate DAO levels.
Conclusions:
HIT is characterized by typical symptoms and low levels of DAO activity. Symptom severity was associated with the degree of DAO deficiency. Patients with DAO values between 3 and 10 U/mL show the best response to treatment (low-histamine diet and/or DAO supplementation). DAO value could arguably be considered as a predictor of clinical response to treatment. Prospective studies are needed to confirm these data.
... Other limitations would be the cross-sectional design without a control group, the lack of other determinations (IgE, histamine, allergens), the lack of follow-up, or the lack of repeated DAO activity levels in the same patient [37,38]. The strengths are the measurement of the NPIF and to relate it for the first time with DAO activity and histamine intolerance in AR, but even the analysis of DAO activity has been called into question as a diagnostic method for histamine intolerance [10,25,29,30,39]. This study opens up a range of possibilities, but the degree of the relationship found might not be enough to define the real link between DAO activity and AR severity. ...
... However, DAO activity could be considered in the future as a biomarker to differentiate between severity groups. On the other hand, there is some controversy about which measure is the best to assess DAO, whether its levels or its activity [19,25,29,39,40,41,42]. This work demonstrates that the same conclusions are not applicable for both parameters. ...
Introducción: La rinitis es una inflamación del revestimiento mucoso de la nariz que
se define por su presentación clínica, caracterizada por cinco síntomas cardinales:
rinorrea, estornudos, prurito nasal y congestión. La fisiopatología del prurito sigue sin
conocerse con exactitud. Muchos mediadores han sido puestos en relación, siendo la
histamina uno de los persistentes candidatos y el más estudiado a lo largo de décadas.
La diamino oxidasa es la enzima más importante en el metabolismo de la histamina
ingerida. La intolerancia a la histamina pertenece al grupo de reacciones de hipersensibilidad no IgE-mediadas que resulta de un desequilibrio de la histamina acumulada y la capacidad para su degradación causado por un fallo en la función enzimática de la DAO. Este hecho podría ser el causante de un agravamiento de la rinitis. El objetivo
de este estudio es identificar la prevalencia de déficit en la actividad de la enzima
diamino oxidasa en pacientes con rinitis.
Material y métodos: Fase de reclutamiento del estudio “Tratamiento con diamino-oxidasa
en pacientes con rinitis: un ensayo clínico aleatorizado, controlado y doble ciego
para comprobar la eficacia y seguridad (Estudio DAO-RIN)”. Se reclutaron pacientes
diagnosticados de rinitis alérgica y no alérgica con pruebas cutáneas realizadas y se
realizó estimación de actividad de la diamino oxidasa.
Resultados: 45 pacientes fueron reclutados, 24 con rinitis no alérgica y 21 con rinitis
alérgica.El peak fl ow nasal inspiratorio en rinitis no alérgica obtuvo una media de
92,08 L/min y de 96,19 L/min para rinitis alérgica. Los valores de diamino oxidasa
fueron 107,63 HDU/L frente 82,95 HDU/L.
Discusión: Parece existir una menor actividad de la enzima diamino oxidasa en pacientes
con rinitis alérgica, coincidiendo esto a su con un menor valor de peak flow nasal inspiratorio.
... Es gibt kein zuverlässiges, etabliertes Para meter für die Diagnose eines Histamininto leranzsyndroms. Die diagnostische Bedeutung einer DAO Bestimmung in Blut wird kontrovers disku tiert [11, 12]. Einige Laboratorien geben sol che Angaben bei der DAOBestimmung ab: – DAO < 3 U/ml: sehr geringe Enzymak tivität, – DAO 3 – 10 U/ml: mittlere Enzymakti vität, – DAO > 10 U/ml: normale Enzymaktivi tät. ...
... Wie zwei Studien, basierend auf der Anamnese mit allergieähnlichen Symptomen nach Auf nahme von histaminreichen Nahrungsmitteln gezeigt haben, bietet die Bestimmung der DAOAktivität im Serum in der alltäglichen klinischen Praxis wegen großen Überlap pungen keine Hilfestellung für die Diagnose einer Histaminintoleranz. Bei den drei Grup pen von gesunden Probanden, Patienten mit möglicher Histaminintoleranz und Patien ten mit anamnestisch sehr wahrscheinlicher Histaminintoleranz kamen sowohl tiefe wie normale als auch erhöhte Werte vor [11, 12]. Seit November 2011 steht gemäß Anga ben der Schweizerischen Interessengemein schaft HistaminIntoleranz (SIGHI) (www. ...
... Other limitations would be the cross-sectional design without a control group, the lack of other determinations (IgE, histamine, allergens), the lack of follow-up, or the lack of repeated DAO activity levels in the same patient [37,38]. The strengths are the measurement of the NPIF and to relate it for the first time with DAO activity and histamine intolerance in AR, but even the analysis of DAO activity has been called into question as a diagnostic method for histamine intolerance [10,25,29,30,39]. This study opens up a range of possibilities, but the degree of the relationship found might not be enough to define the real link between DAO activity and AR severity. ...
... However, DAO activity could be considered in the future as a biomarker to differentiate between severity groups. On the other hand, there is some controversy about which measure is the best to assess DAO, whether its levels or its activity [19,25,29,39,40,41,42]. This work demonstrates that the same conclusions are not applicable for both parameters. ...
Aim:
To analyze the diamine oxidase (DAO), the main catabolic enzyme of histamine, degradation activity and its relation with symptoms of persistent allergic rhinitis.
Methods:
In this descriptive and analytical observational study, we collected DAO activity levels and the nasal peak inspiratory flow.
Results:
Enzymatic activity deficit in 108 patients was 46.3% (95% CI, 0.44 - 0.63), 33.33% in mild and 47.92% in moderate/severe rhinitis (p = 0.376). The nasal peak inspiratory flow in patients with a deficit in DAO activity was 76.30 ± 28.40 L/min compared to 93.62 ± 37.50 L/min in patients with normal enzymatic activity (p = 0.010).
Conclusions:
It seems that the lower the catabolic activity of DAO, the lower the nasal peak inspiratory flow observed. Although DAO activity levels could be a severity biomarker in allergic rhinitis, a cause-effect association cannot be concluded. The enzyme could be another actor in the pathophysiology of allergic rhinitis.
... Other limitations would be the cross-sectional design without a control group, the lack of other determinations (IgE, histamine, allergens), the lack of follow-up, or the lack of repeated DAO activity levels in the same patient [37,38]. The strengths are the measurement of the NPIF and to relate it for the first time with DAO activity and histamine intolerance in AR, but even the analysis of DAO activity has been called into question as a diagnostic method for histamine intolerance [10,25,29,30,39]. This study opens up a range of possibilities, but the degree of the relationship found might not be enough to define the real link between DAO activity and AR severity. ...
... However, DAO activity could be considered in the future as a biomarker to differentiate between severity groups. On the other hand, there is some controversy about which measure is the best to assess DAO, whether its levels or its activity [19,25,29,39,40,41,42]. This work demonstrates that the same conclusions are not applicable for both parameters. ...
Introducción: La rinitis es una inflamación del revestimiento mucoso de la nariz que se caracteriza por rinorrea, estornudos, prurito nasal y congestión. La fisiopatología del prurito sigue sin conocerse con exactitud. Muchos mediadores han sido puestos en relación, siendo la histamina uno de los persistentes candidatos y el más estudiado a lo largo de décadas. La diamino oxidasa es la enzima más importante en el metabolismo de la histamina ingerida. La intolerancia a la histamina resulta de un desequilibrio de la histamina acumulada y la capacidad para su degradación causado por un fallo en la función enzimática de la diamino oxidasa. Este hecho podría ser el causante de un agravamiento de la rinitis. El objetivo de este estudio es identificar la prevalencia de déficit en la actividad de la enzima diamino oxidasa en pacientes con rinitis alérgica.
Material y métodos: Estudio observacional de tipo transversal en el que a pacientes diagnosticados de rinitis alérgica se les realizó una extracción sanguínea para estimar la actividad de la enzima diamino oxidasa, así como medir el peak flow nasal inspiratorio y la calidad de vida mediante el test SPRINT-15.
Resultados: 38 pacientes fueron reclutados. El 55,26% presentaban déficit de actividad enzimática. El peak flow nasal inspiratorio obtuvo una media de 95,92 L/min, siendo de 86,42 L/min para los pacientes con déficit frente a 107,64 L/min para los que tenían una actividad enzimática normal (p =0,02).
Discusión: El déficit de actividad diamino oxidasa se asocia a una menor capacidad nasal inspiratoria.
... Die Diagnosestellung anhand der Messung der DAO-Enzymaktivität im Blut ist nicht aussagekräftig. Untersuchungen bei Betroffenen im Vergleich zu gesunden Kontrollen legen nahe, dass die Werte zwischen Betroffenen und Gesunden vergleichbar sind [29,30]. Mittels DAO-spezifischer monoklonaler Antikörper ließ sich die DAO auch nicht im Serum -zumindest nicht in relevanter Menge -sondern nur in den bekannten Geweben wie Niere, Darm und Plazenta sowie in Spermienflüssigkeit nachweisen [23]. ...
Nahrungsmittelunverträglichkeiten sind objektiv nachweisbar deutlich seltener als subjektiv empfunden. Insbesondere zum wissenschaftlichen Kenntnisstand nicht allergischer Überempfindlichkeitsreaktionen bestehen große Defizite. Ein Beispiel ist die Histaminunverträglichkeit, die aufgrund der starken Thematisierung in den Medien und im Internet von Betroffenen oftmals als Auslöser ihrer Gesundheitsbeschwerden vermutet wird. Die wissenschaftliche Evidenz für die postulierten Zusammenhänge ist begrenzt, eine verlässliche Laborbestimmung zur definitiven Diagnose nicht vorhanden. Die vorliegende Stellungnahme der Arbeitsgruppe Nahrungsmittelallergie der Deutschen Gesellschaft für Allergologie und klinische Immunologie (DGAKI) in Zusammenarbeit mit dem Ärzteverband Deutscher Allergologen (AeDA), der Pädiatrischen Allergologie und Umweltmedizin (GPA) sowie der Schweizerischen Gesellschaft für Allergologie und Immunologie (SGAI) beleuchtet die Datenlage für das Krankheitsbild der Unverträglichkeit gegenüber oral aufgenommenem Histamin, fasst wichtige Aspekte und deren Konsequenzen zusammen und schlägt ein praktikables diagnostisches und therapeutisches Vorgehen vor.
... Some studies have proposed that determining blood DAO activity may be helpful in identifying subjects with symptoms associated with histamine intolerance [63,83,84]. In contrast, three studies did not find a significant relationship between the clinical history of patients with typical symptoms of histamine intolerance and blood DAO activity values, concluding that this technique cannot be recommended as a diagnostic tool in routine clinical practice until studies have validated its effectiveness [98][99][100]. Moreover, the work performed by Schnoor et al. also reported a high interassay variation in DAO activity values that made the proper classification of histamine-intolerant subjects impossible [100]. ...
Histamine intolerance, also referred to as enteral histaminosis or sensitivity to dietary histamine, is a disorder associated with an impaired ability to metabolize ingested histamine that was described at the beginning of the 21st century. Although interest in histamine intolerance has considerably grown in recent years, more scientific evidence is still required to help define, diagnose and clinically manage this condition. This article will provide an updated review on histamine intolerance, mainly focusing on its etiology and the existing diagnostic and treatment strategies. In this work, a glance on histamine intoxication will also be provided, as well as the analysis of some uncertainties historically associated to histamine intoxication outbreaks that may be better explained by the existence of interindividual susceptibility to ingested histamine.
... Bei Verdacht auf Unverträglichkeit gegenüber oral aufgenommenem Histamin stehen keine objektiven Laborparameter zur Dia gnose zur Verfügung [1]. Auch die Messung des Diaminoxidase-Spiegels im Serum und die Histamin-Bestimmung im Plasma haben sich nicht als aussagekräftig erwiesen [7,8,9,10]. Tatsächlich ist es fraglich, ob das Serum zur Messung der Diaminoxidase überhaupt geeignet ist [11]. ...
The so-called histamine intolerance is a popular disorder which is most often selfdiagnosed. As the diagnosis mainly depends on self-reporting of clinical symptoms it is mandatory to make sure that reproducibility, a prerequisite for an adverse reaction, is present. A dietetic approach is only reasonable if ingested histamine does indeed elicit objective and provocable reactions. If histamine intolerance is confirmed, an individual therapeutic strategy is required.
Histamine plays a major role in inflammation associated with many different diseases, including allergies, autoimmune diseases and cancer, but it also has important physiological effects. Although mast cells and basophils are the main sources of histamine it can be differentially produced and released by enterochromaffin-like cells, certain nerve cells, and even neutrophils in certain pathological settings. This chapter highlights the recent developments regarding the major contributions of histamine to inflammation by acting not only through H1-receptors (H1R) but also H2R and H4R. These receptors determine both the severity of inflammation and also have immunomodulatory effects in various lymphocytes. Recent evidence also suggests a dual role for histamine in various autoimmune inflammatory disease and certain cancers, where differential receptor expressions for the amine determine the severity of these diseases but also play a role in tumour surveillance.
Histamine is a biogenic amine involved in important physiological activities in the organism, but its ingestion through food is associated with the onset of health disorders. Histamine intoxication, previously known as scombroid fish poisoning, is caused by the intake of foods with high levels of histamine. According to official European Union reports, more than 90% of the outbreaks registered in the last years were caused by the consumption of fish and seafood products. Histamine intolerance, on the other hand, arises when histamine degradation is impaired, mainly by a lower diamine oxidase (DAO) activity. Some of the uncertainties classically associated with histamine intoxication may be explained by this enzymatic deficit in a sensitive population. This chapter reviews the adverse effects of histamine from food within a risk analysis framework, focusing specifically on the components of risk assessment and management.
Adverse food reactions are far more often perceived than objectively verified. In our scientific knowledge on non-allergic adverse reactions including the so called histamine intolerance, there are large deficits. Due to the fact that this disorder is increasingly discussed in the media and the internet, more and more people suspect it to be the trigger of their symptoms. The scientific evidence to support the postulated link between ingestion of histamine and adverse reactions is limited, and a reliable laboratory test for objective diagnosis is lacking. This position paper by the “Food Allergy” Working Group of the German Society for Allergology and Clinical Immunology (DGAKI) in collaboration with the German Association of Allergologists (AeDA), the Society for Pediatric Allergology and Environmental Medicine (GPA), and the Swiss Society for Allergology and Immunology (SGAI) reviews the data on the clinical picture of adverse reactions to ingested histamine, summarizes important aspects and their consequences, and proposes a practical diagnostic and therapeutic approach.
Immunologically mediated hypersensitivity to foods is defined as food allergy, mainly due to immunglobulins of class E (IgE) triggering immediate reactions (type I hypersensitivity) with possible involvement of mucosa, skin, airways, intestinal tract, and the vascular system. Primary food allergy is based on (early) IgE sensitization against animal (e. g., cow’s milk, hen’s eggs) or plant proteins (e. g. peanut, hazelnut or wheat). In the case of secondary food allergies, IgE against pollen proteins (e. g., birch) reacts to structurally related food proteins (with cross-reactions to stone and pit fruits). Non-immunological food intolerance reactions are mostly based on carbohydrate malassimilation (e. g., lactose intolerance, fructose malabsorption) and are rarely due to pseudo-allergies (e. g., flavors, dyes, preservatives) primarily in patients with chronic urticaria. Common intestinal symptoms are mainly due to functional disorders (e. g., irritable bowel disease), rarely because of inflammatory intestinal diseases (e. g., celiac disease). Histamine intolerance, gluten hypersensitivity, and so-called food type III hypersensitivities are controversial diagnoses. The aforementioned disease entities/models are of variable importance for the affected individuals, the public health system, and society in general.
Searching the internet for an explaination of recurring symptoms, many people come across the so-called histamine intolerance disorder. Also many practitioners like to diagnose this disorder without making sure that reproducibility, a prerequisite for an adverse reaction, is present. Consequently, presumably affected persons are often advised to follow a low-histamine diet. Depending on the source of information, these diets often avoid a huge variety of foods containing more or less histamine, which has a considerable impact on patient quality of life. While most persons benefit from such a diet in the beginning – this might be due to the change in dietary habits or the expectation of symptom improvement by dieting – in the long run the expected loss of symptoms will not happen. Underlying a diminished capacity for histamine degradation, the lack of partial or complete symptom improvement might be due to the fact that endogenous histamine release is responsible for reactions. The role of ingested histamine is discussed controversially. However, it is more than obvious that the histamine content of a certain food alone is not enough to predict its tolerance.
If histamine intolerance is suspected, an individual diagnostic and therapeutic procedure is mandatory in order to minimize avoidance and to preserve a high quality of life. Ideally this is done in a close cooperation between allergologists and nutritionists/dieticians.
EC number 1.4.3.22 Systematic name histamine:oxygen oxidoreductase (deaminating) Recommended name diamine oxidase Synonyms AGAO [42,61] Amine oxidase [61,65] BSAO [51] Copper amine oxidase [64] DAO [40,44,47,49,52,53,55,56,60,62,66] Diamine oxidase [40,43,44,60,62,63] ELAO [46,51] GPAO [46] LCAO [37,54] LSAO [46,48,51] PKAO [51] PPLO [42] PSAO [42,43,51,54,64] hDAO [63] histaminase [59] histamine oxidase [39] pea seedling amine oxidase [64] rhDAO [42] Additional information ( the enzyme is a member of the coppercontaining amine oxidase, CAO, family of enzymes [66]) [66]
Low-histamine diets are very popular and often self-imposed among people suspecting histamine intolerance. Most of these diets avoid a huge variety of foods containing more or less histamine, which has a considerable impact on their quality of life, but in most cases no long-term benefit. Underlying a diminished capacity for histamine degradation, the lack of partial or complete symptom improvement might be due to the fact that endogenous histamine release could also be responsible for symptoms. The role of ingested histamine-below the level for intoxication-is discussed controversially. However, it is obvious that the histamine content of a certain food alone is not enough to predict its tolerance. If histamine intolerance is suspected, an individual diagnostic and therapeutic procedure is mandatory in order to minimize avoidance and to preserve a high quality of life. Ideally this is done in a close cooperation between allergists and nutritionists.
Background. Histamine intolerance results from an imbalance between histamine intake and degradation. In healthy persons, dietary histamine can be sufficiently metabolized by amine oxidases, whereas persons with low amine oxidase activity are at risk of histamine toxicity. Diamine oxidase (DAO) is the key enzyme in degradation. Histamine elicits a wide range of effects. Histamine intolerance displays symptoms, such as rhinitis, headache, gastrointestinal symptoms, palpitations, urticaria and pruritus.
Objective. Diagnosis of histamine intolerance until now is based on case history; neither a validated questionnaire nor a routine test is available.
It was the aim of this trial to evaluate the usefullness of a prick-test for the diagnosis of histamine intolerance.
Methods. Prick-testing with 1% histamine solution and wheal size-measurement to assess the relation between the wheal in prick-test, read after 20 to 50 minutes, as sign of slowed histamine degradation as well as history and symptoms of histamine intolerance.
Results. Besides a pretest with 17 patients with HIT we investigated 156 persons (81 with HIT, 75 controls): 64 out of 81 with histamine intolerance(HIT), but only 14 out of 75 persons from the control-group presented with a histamine wheal ≥3 mm after 50 minutes (P < .0001).
Conclusion and Clinical Relevance. Histamine-50 skin-prickt-test offers a simple tool with relevance.
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