Histamine Intolerance and Chronic Urticaria

What Is Histamine Intolerance?

Histamine intolerance or histamine sensitivity is a disorder in which someone has an impaired ability to metabolize ingested histamine. Histamine is one of the molecules involved in allergic reactions, and is normally released by mast cells, but it can also be present in food. People who have difficulty metabolizing histamine will therefore be more sensitive to foods that contain it in large quantities than most people. Symptoms include:

- Sneezing / Congestion / Dyspnea

- Gastrointestinal disturbance (bloating, flatulence, diarrhea, pain, constipation, nausea, vomiting)

- Headache / dizziness

- Tachycardia / low blood pressure / syncope

- Itching / flush / hives / eczema / swelling

Why does it happen?

Histamine poisoning can happen to anyone in the presence of very high concentrations in foods. Cases of histamine intoxication have been reported following consumption of spoiled fish, for example. Some people however, will react to much lower concentrations of histamine in food.

There are two main pathways for histamine metabolism. The first pathway starts with an enzyme called Histamine-N-Methytransferase (HNMT) and the second starts with the enzyme Diamine Oxidase (DAO). DAO is restricted to specific tissues while HNMT is more widely expressed. DAO however is the primary metabolic pathway for histamine in the gut, which makes it more important for metabolizing histamine from food.

There are known mutations in the genes that code for DAO that affect its functionality or expression. Some studies have found, for instance, that individuals with symptoms of histamine intolerance have lower plasma concentration of DAO. DAO deficiency can also be an acquired condition caused by a pathology or a drug. Inflammatory bowel diseases for instance are known to impair DAO activity by damaging the intestinal mucosa. Some drugs as well as alcohol, vitamin C and vitamin B1 are also known known to inhibit DAO, which might cause temporary histamine sensitivity.

How is it diagnosed?

A patient with at least 2 symptoms of histamine intolerance, no known food allergy, mast cell disease or gastrointestinal disease is put on a low-histamine diet. If symptoms improve, tests can be done to assess DAO activity in plasma or intestinal biopsy, possible genetic mutations and markers of histamine metabolism in urine.

How is it treated?

The only currently available treatment for histamine sensitivity is the low-histamine diet. Since the low-histamine diet is quite restrictive, DAO supplementation using pig or plant DAO is currently being studied as an adjunct treatment to allow for a bit more diversity in the diet.

How Is Histamine Sensitivity Related to Chronic Urticaria?

In some rare cases, chronic spontaneous urticaria is due to histamine sensitivity and can resolve by adopting a low-histamine diet. In a study from 2016 for instance, while some patients reported improvement on a low-histamine diet, only 2 of 157 CSU patients could be diagnosed with histamine sensitivity. It is unlikely that CSU is associated with histamine sensitivity in the absence of gastrointestinal symptoms, because that is the main area of exposure to dietary histamine.