Could an excess of histamine cause anaphylaxis?

Dr Janice Joneja was asked whether and excess of histamine in someone who was histamine intolerant?


My 34 year old daughter has severe anaphylaxis to milk protein, and also Type 1 diabetes, celiac disease, and asthma.  Normally her anaphylaxis is triggered immediately as she eats a food contaminated with milk protein. 

Over the last year, she has had three anaphylaxis episodes after eating in restaurants.  The first one happened three hours after eating lunch in a restaurant.  She is quite sure she did not ingest dairy. The second one happened after brunch in a restaurant, but again hours after eating the food. That time she had eggs, potatoes and fruit, as well as two alcoholic drinks.  She woke up from a nap with anaphylaxis. 

The third severe anaphylaxis happened during sleep, after eating shrimp seviche and having two drinks about 7 or 8 hours earlier in a restaurant.  She had to be taken by ambulance to the hospital.  She was covered head to toe in hives, had a severe gut issue, very low blood pressure, heartburn, heart racing, etc.  She has eaten at this restaurant many times but had never had the seviche which is raw shrimp cured in lime juice. 

She went back to the restaurant and the manager assured her there was no dairy, but her reaction was like a delayed dairy reaction. Could this be a histamine reaction and if so how should she treat it?

Dr Joneja's answer:

There are two points to consider in this case:

  1.  Your daughter’s diagnosed allergy to milk proteins, which has resulted in anaphylaxis in the past
  2. The delayed reaction to a meal extremely high in histamine

An allergic reaction involves release of inflammatory mediators from primed mast cells.  The first powerful mediator released is histamine, followed by a number of others, each of which has its own effect in the body. The symptoms typically occur within minutes, even seconds, of the allergenic food entering the body.  In an anaphylactic reaction the symptoms are severe and in rare cases can lead to anaphylactic shock and death.

It is known that an allergic reaction can escalate to life-threatening anaphylaxis in people who also have histamine intolerance. Histamine intolerance is usually due to a deficiency in diamine oxidase (DAO), the enzyme that rids the body of excess histamine. When the enzyme is inadequate in breaking down the excess histamine fast enough to maintain a level below a person’s “limit of tolerance” (the level above which symptoms appear) symptoms of histamine sensitivity develop, which initially are indistinguishable from allergy. So, a person with a severe allergy who consumes a diet rich in histamine-containing and releasing foods is at risk for both an enhanced allergic reaction (anaphylaxis) and/or an exaggerated response to histamine. 

In your daughter’s case, each of the restaurant meals you mention are very high in histamine.  Specifically, ceviche is an appetizer made from raw fish marinated in lime or lemon juice with olive oil and spices.  All of those ingredients are high in histamine and are not allowed on a histamine-restricted diet.  Furthermore, the addition of alcoholic drinks will increase the level of histamine enormously.

This meal likely overwhelmed her DAO’s ability to rid her body of excess histamine and resulted in a reaction that resulted in all the symptoms of anaphylaxis, but which were delayed, rather than immediate. This reaction was likely due to histamine rather than an anaphylactic reaction, but nevertheless it would be wise for your daughter to undergo further investigations to identify other foods in addition to milk to which she may be allergic, before concluding that the reactions were indeed due to histamine intolerance rather than allergy.

Unfortunately, we do not have any accurate tests that would provide a diagnosis of histamine intolerance.  Some labs do offer tests for determining a person’s DAO in blood, but we are not at the stage in which we could predict the clinical significance of those levels in practice.  Histamine levels could also be measured, but because of fluctuations in these levels throughout the day, and our lack of equating histamine and clinical outcomes, such testing has no real value in diagnosis and management at this time.

My advice to your daughter would be to follow a histamine-restricted diet (see the second half of this article  for more on the diet) and to take a DAO supplement such as DAOSin, Histame or HistamAid immediately before a meal likely to be high in histamine – such as in a restaurant – to reduce her risk of such severe reactions in the future.
(She can buy DAO supplements under the trade names DAOSiN and Histame in the UK and Swanson's DAOSiN in the US.

June 2016

If you found this article interesting, you will find many more articles on anaphylaxis here, and reports of research into anaphylaxis here.
You can also find articles on peanut and tree-nut allergy here, cow's milk allergies here, egg allergy here, histamine intolerance hereand articles on a wide range of other allergic and intolerance reactions to a wide range of other foods here.


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