What is the difference between Histamine Intolerance, Mast Cell Activation Syndrome (MCAS)and Mastocytosis

Histamine intolerance, mast cell activation syndrome (MCAS) and mastocytosis are related conditions involving mast cell activation and an over-accumulation of histamine in the body. Mast cells are immune cells that play an important role in the body’s response to allergens and other foreign substances or perceived threats, like infections,  by releasing histamine and other inflammatory mediators. However, when these cells accumulate in tissues excessively and are activated inappropriately and too frequently, it can lead to various health problems. In this blog, I will discuss the difference between these conditions.

Histamine Intolerance

Histamine intolerance refers to a condition where the body is unable to degrade histamine fully, leading to excessive accumulation of this compound in the body. Histamine is a chemical compound naturally produced in the body, but it can also be found in many foods.  Histamine is produced by mast cells and basophils in the body, but the mast cells are the main source of histamine. 

Histamine helps the body fight off the threat by dilating blood vessels, increasing blood flow and attracting other immune cells. However, histamine also causes inflammation and irritation in the tissues where it is released. Normally, histamine is quickly metabolised by enzymes such as diamine oxidase (DAO) in the gut upon ingestion and histamine N-methyltransferase (HNMT) systemically before being eliminated from the body. However, some people have low levels of these enzymes or may lack the co-factors needed to activate these enzymes. This ingestion of high histamine-rich foods or alcohol or drugs that release histamine or block the aforementioned enzymes can also lead to a build-up of histamine in the body and triggers symptoms similar to an allergic reaction, such as flushing, itching, hives and anaphylaxis. However, histamine intolerance can lead to a wide range of other symptoms, including headaches and migraines, digestive problems like diarrhoea and abdominal pain, fatigue, anxiety and sleep disturbances.

Mast Cell Activation Syndrome (MCAS)

Mast cell activation syndrome (MCAS) is a recently recognised condition that involves the overactivation of mast cells throughout the body, even in the absence of abnormal mase cells.

 In MCAS,  the mast cells are overly sensitive and release too much histamine and other inflammatory mediators in response to various triggers such as stress, temperature changes, medications, foods, infections and hormonal fluctuations. Unlike histamine intolerance, MCAS is not caused by a lack of enzymes or excess histamine intake but by the overactivation of mast cells leading to excessive production and accumulation of histamine. Some people can have both histamine intolerance, where they lack the ability to metabolise histamine efficiently, and MCAS, where the mast cells are overly sensitive in response to a stimulus/stimuli leading to excessive histamine and other pro-inflammatory mediators.

Mastocytosis

Mastocytosis is a rare condition where there is an abnormal growth and accumulation of mast cells in various organs such as the skin, bone marrow, liver, spleen and lymph nodes. Mastocytosis can be classified into cutaneous mastocytosis (CM), which affects only the skin, and systemic mastocytosis (SM), which affects other organs as well. Mastocytosis can be caused by genetic mutations or unknown factors that lead to the proliferation of mast cells. The excess mast cells can release histamine and other mediators spontaneously or in response to triggers such as physical stimuli, heat, cold, friction, insect bites or stings and certain drugs. The symptoms of mastocytosis depend on the type and location of the mast cells involved but can include skin lesions (such as urticaria pigmentosa), flushing, itching, hives, angioedema (swelling of the face or throat), anaphylaxis (a severe allergic reaction), bone pain, fractures, osteoporosis (bone loss), fatigue, malabsorption (poor absorption of nutrients), weight loss, abdominal pain, diarrhoea, nausea, vomiting, peptic ulcers (sores in the stomach or duodenum), liver enlargement or dysfunction, spleen enlargement or dysfunction, lymph node enlargement or dysfunction and blood disorders (such as anaemia or low platelet count).

Most mastocytosis symptoms are also present in MCAS and the presentation of the two conditions are similar. However, the main difference between MCAS and mastocytosis is that the former involves an overactivation of mast cells, and the latter involves an abnormal accumulation of mast cells.

In essence, while these conditions share the commonality of excessive histamine production, their management and care strategies must be tailored to address the specific underlying mechanisms involved. Recognising the distinct nature of each condition allows for better-targeted approaches and improved health outcomes.

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