A 2 year old patient has been given the diagnosis of "Histamine Intolerance" and the list of foods to avoid is extensive. Specifically avoiding foods that require "Diamine oxidase" to break down any histamine in food. I can find very little information about this condition. Can you send me in a direction to find out more on this intolerance?


Thank you for your recent inquiry.

Unfortunately this is a very poorly defined area so I can understand why you have had difficulty finding information in the medical literature (although lay websites and chatter boxes can be easily found on an internet search).Nonetheless there is a body of medical literature incriminating histamine intolerance in the production of certain symptoms, mainly in the area of urticaria and atopic dermatitis. But there is still some controversy over the existence of this phenomenon. The abstracts copied below are a representative sample of studies dealing with this issue and further references are contained within these sources.

Thank you again for your inquiry and we hope this response is helpful to you.

Allergy. 2010 Jan;65(1):78-83. Epub 2009 Oct 1.
Effects of a pseudoallergen-free diet on chronic spontaneous urticaria: a prospective trial.
Magerl M, Pisarevskaja D, Scheufele R, Zuberbier T, Maurer M.
Allergie-Centrum-Charité, Department of Dermatology and Allergy, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Background: Chronic spontaneous urticaria is a skin disorder that is difficult to manage and can last for years. 'Pseudoallergens' are substances that induce hypersensitive/intolerance reactions that are similar to true allergic reactions. They include food additives, vasoactive substances such as histamine, and some natural substances in fruits, vegetables and spices. Eliminating pseudoallergens from the diet can reduce symptom severity and improve patient quality of life.
Aim: To assess the effects of a pseudoallergen-free diet on disease activity and quality of life in patient's chronic spontaneous urticaria.
Methods: Study subjects had moderate or severe chronic spontaneous urticaria that had not responded adequately to treatment in primary care. For 3 weeks, subjects followed a pseudoallergen-free diet. They kept a clinical diary, which recorded their wheal and pruritus severity each day, to yield a clinical rating of chronic spontaneous urticaria severity (the UAS4 score). The subjects also completed the DLQI, a validated quality-of-life instrument. Use of antihistamines and glucocorticoids was minimized, recorded, and analysed. Subjects were classified into nine response categories, according to the changes in symptom severity (UAS4), quality of life (DLQI) and medication usage.
Results: From the 140 subjects, there were 20 (14%) strong responders and 19 (14%) partial responders. Additionally, there were nine (6%) subjects who made a substantial reduction in their medication without experiencing worse symptoms or quality of life.
Conclusions: Altogether the pseudoallergen-free diet is beneficial for one in three patients. The pseudoallergen-free diet is a safe, healthy and cost-free measure to identify patients with chronic spontaneous urticaria that will benefit from avoiding pseudoallergens

Acta Derm Venereol. 2009;89(1):52-6.
Exogenous histamine aggravates eczema in a subgroup of patients with atopic dermatitis.
Worm M, Fiedler EM, Dölle S, Schink T, Hemmer W, Jarisch R, Zuberbier T.
Department of Dermatology and Allergology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Food and beverages may contain high amounts of histamine and thus may cause symptoms after ingestion. The aim of this study was to investigate the role of ingested histamine in atopic dermatitis. Patients with atopic dermatitis had to maintain a histamine-free diet for one week. Consecutively, double-blind, placebo-controlled provocations were performed with histamine-hydrochloride and placebo. The clinical outcome was assessed by determination of the SCORAD. Before and 30 min after each provocation blood was collected for measurement of plasma histamine levels and diamine oxidase activity. Thirty-six patients with atopic dermatitis completed the diet. Twelve of 36 showed a significant improvement of the SCORAD after one week of the diet. After provocation tests 11 of 36 showed aggravation of eczema. Plasma histamine was significantly higher in patients with atopic dermatitis compared with controls (p><0.001), whereas diamine oxidase activity was similar in both groups. Our data indicate that ingestion of moderate or high amounts of histamine-hydrochloride may aggravate eczema in a subgroup of patients with atopic dermatitis. Plasma histamine and diamine oxidase activity were not associated with the clinical response to histamine

J Allergy Clin Immunol. 2006 May;117(5):1106-12. Epub 2006 Feb 8.
Evidence for a reduced histamine degradation capacity in a subgroup of patients with atopic eczema.
Maintz L, Benfadal S, Allam JP, Hagemann T, Fimmers R, Novak N.
Department of Dermatology, University of Bonn, Germany.
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.

Clin Exp Allergy. 1993 Dec;23(12):982-5.
Histamine-free diet: treatment of choice for histamine-induced food intolerance and supporting treatment for chronic headaches.
Wantke F, Götz M, Jarisch R.
Dermatologic and Pediatric Allergy Clinic Vienna, Austria.
Histamine-induced food intolerance is not IgE-mediated. Skin-prick testing and specific IgE to food allergens are typically negative. Food rich in histamine or red wine may cause allergy-like symptoms such as sneezing, flush, skin itching, diarrhoea and even shortness of breath. The suspected reason is a diminished histamine degradation based on a deficiency of diamine oxidase. As diamine oxidase cannot be supplemented, a histamine-free diet was implemented to reduce histamine intake. Forty-five patients with a history of suffering from intolerance to food or wine (n = 17) and chronic headache (n = 28) were put on the diet over months to years. Fish, cheese, hard cured sausages, pickled cabbage and alcoholic beverages had to be avoided. Complaint intensity and drug-use per week prior to and 4 weeks after a histamine-free diet were compared. After 4 weeks on the diet 33/45 patients improved considerably (P < 0.01), eight of them had total remission. In 12/45 patients, however, no changes in symptoms were observed. Symptoms of food or wine intolerance significantly decreased (P < 0.02; treatment of choice), headaches decreased in frequency (P < 0.001), duration and intensity. After eating histamine-rich food symptoms were reproducible and could be eliminated by anti-histamines in most patients. These data indicate the role of histamine in food and wine intolerance and that histamine-rich food causes a worsening of symptoms in patients suffering from chronic headaches. Results obtained support the hypothesis of a deficiency of diamine oxidase in patients with intolerance to food or wine.

Am J Clin Nutr. 2007 May;85(5):1185-96.
Histamine and histamine intolerance.
Maintz L, Novak N.
Department of Dermatology, University of Bonn, Bonn, Germany.
Histamine intolerance results from a disequilibrium of accumulated histamine and the capacity for histamine degradation. Histamine is a biogenic amine that occurs to various degrees in many foods. In healthy persons, dietary histamine can be rapidly detoxified by amine oxidases, whereas persons with low amine oxidase activity are at risk of histamine toxicity. Diamine oxidase (DAO) is the main enzyme for the metabolism of ingested histamine. It has been proposed that DAO, when functioning as a secretory protein, may be responsible for scavenging extracellular histamine after mediator release. Conversely, histamine N-methyltransferase, the other important enzyme inactivating histamine, is a cytosolic protein that can convert histamine only in the intracellular space of cells. An impaired histamine degradation based on reduced DAO activity and the resulting histamine excess may cause numerous symptoms mimicking an allergic reaction. The ingestion of histamine-rich food or of alcohol or drugs that release histamine or block DAO may provoke diarrhea, headache, rhinoconjunctival symptoms, asthma, hypotension, arrhythmia, urticaria, pruritus, flushing, and other conditions in patients with histamine intolerance. Symptoms can be reduced by a histamine-free diet or be eliminated by antihistamines. However, because of the multifaceted nature of the symptoms, the existence of histamine intolerance has been underestimated, and further studies based on double-blind, placebo-controlled provocations are needed. In patients in whom the abovementioned symptoms are triggered by the corresponding substances and who have a negative diagnosis of allergy or internal disorders, histamine intolerance should be considered as an underlying pathomechanism.

Phil Lieberman, M.D.

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