In mast cell activation syndrome (MCAS), part of the immune system reacts too easily and too strongly. The symptoms often come in flare-ups, affect several organs at once and do not fit into any single speciality. This is why many of those affected go without a diagnosis for a long time. This overview explains what lies behind MCAS, which symptoms are typical and how the condition can be tracked down.

What are mast cells?

Mast cells are cells of the immune system. They are found wherever the body comes into contact with the outside world: in the skin and in the mucous membranes of the stomach, gut and airways, but also around blood vessels and nerves. They are, so to speak, the body’s sentries.

Inside them, mast cells store more than 200 messenger substances. The best known is histamine; others include tryptase, prostaglandins, leukotrienes and many inflammatory messengers. When there is danger, they release these substances: blood vessels widen, the skin reddens and itches, mucus is produced and bowel movement increases. This is useful for fighting off pathogens and for wound healing. In an allergy, the same happens in response to a substance that is actually harmless.

What is MCAS?

In MCAS, the mast cells are not increased in number, but they are oversensitive. They release their messenger substances too easily, too often and without adequate reason. Those affected feel the consequences wherever the messengers act, and that can be almost anywhere in the body.

MCAS belongs to a group of mast cell disorders. It should be distinguished from:

Mastocytosis: here the mast cells are abnormally increased in number, usually because of an acquired change in the cells’ genetic material. It is rare and is detected with blood and tissue tests.
Allergy: here the reaction is directed against a specific trigger, such as pollen or nuts, and can be detected with skin or blood tests. In MCAS, by contrast, there are many and changing triggers.
Histamine intolerance: here the gut breaks down histamine from food too slowly. The symptoms are closely linked to eating. In MCAS, the histamine comes from the body’s own mast cells.
Hereditary raised tryptase: some people carry extra copies of the gene for tryptase. Their tryptase level in the blood is permanently somewhat raised, and they are more prone to mast cell symptoms.

The boundaries are fluid, and several of these conditions can occur together.

The complaints

Typical of MCAS is that symptoms occur in several organ systems, often at the same time and in flare-ups. There may be calmer periods between flare-ups. Common symptoms are:

Skin: sudden reddening of the face and upper body (flushing), hot flushes, itching, wheals, swelling of the lips or eyelids.
Stomach and bowel: abdominal pain and cramps, bloating, diarrhoea, nausea, heartburn.
Heart and circulation: racing heart, dizziness, a drop in blood pressure up to fainting, sometimes also temporarily raised blood pressure.
Airways, nose and eyes: blocked or runny nose, throat clearing, a dry, tickly cough, tightness in the chest, burning or itchy eyes.
Nervous system: headaches, light-headedness and difficulty concentrating (often called “brain fog”), abnormal sensations such as tingling, sleep disorders.
General: marked exhaustion, bone and joint pain, a tendency to bruise.

In the most severe case, a mast cell reaction can lead to anaphylaxis, that is, to difficulty breathing and circulatory collapse. This is an emergency. Anyone who has already had such a reaction should carry an emergency kit with adrenaline and discuss with their doctor how to use it.

What sets off the mast cells

In MCAS, everyday stimuli are often enough to trigger a flare-up. The triggers differ from person to person. Frequently mentioned are:

warmth and heat, a hot bath, cold or rapid changes in temperature
pressure, friction or vibration on the skin
physical exertion, stress, lack of sleep and hunger
alcohol and histamine-rich foods such as aged cheese, red wine, cured meats or tuna
fragrances, cleaning products and other chemicals
certain medicines, such as some painkillers, as well as contrast agents and anaesthetics
infections, insect stings and hormonal fluctuations, for example during the menstrual cycle

Knowing your triggers lets you avoid many flare-ups. A symptom diary kept over a few weeks helps to recognise connections.

MCAS and other chronic conditions

MCAS is noticeably often seen together with other conditions that also affect several organ systems: with ME/CFS and Long COVID, with postural tachycardia syndrome (POTS), in which the heart speeds up sharply on standing, and with hypermobile joints as part of Ehlers-Danlos syndrome. How these conditions are connected has not yet been clarified. For the assessment, this means: anyone who has one of them should also consider the others.

How MCAS is diagnosed

MCAS is a clinical diagnosis made after other possible diseases that can also cause such symptoms have been ruled out. There is no single blood test that proves MCAS with certainty. According to the international consensus, three things must come together:

typical symptoms in at least two organ systems that keep recurring
evidence that mast cell messengers rise during a flare-up, ideally tryptase in the blood
an improvement with medicines that specifically target the mast cell messengers

In the laboratory, timing is everything. Tryptase should ideally be measured within one to four hours of the start of a flare-up, and a second time for comparison during a symptom-free period. If it rises during the flare-up by more than 20 per cent plus 2 ng/ml above the resting value, this points to mast cell activation. In addition, breakdown products of histamine, prostaglandin D2 and leukotrienes can be measured in the urine. Because these substances break down quickly, the urine must be collected chilled and tested promptly.

There are several reasons why MCAS is often recognised late: the messengers can only be detected briefly, routine values are usually normal, and the symptoms are spread across many specialities. Each individual test is unremarkable; only the overall picture reveals the connection.

The treatment

Treatment has two aims: to calm the mast cells and to weaken the effect of their messengers. It is built up step by step and adapted to the individual.

Recognising and avoiding triggers: this is the foundation, and sometimes it alone brings a clear improvement.
Diet: a low-histamine diet for a few weeks shows how much food plays a part. It should be supervised so that no nutritional deficiency develops.
Medicines: antihistamines against the two most important histamine receptors (H1 and H2), mast cell stabilisers, which slow the release of the messengers, and leukotriene inhibitors. Treatment usually starts at a low dose, because people with MCAS can also react sensitively to medicines.
Supportive micronutrients: some nutrients, such as vitamin C or the plant substance quercetin, can help to stabilise the mast cells further.

From the point of view of functional medicine, we also ask what keeps the mast cells permanently on alert. To this end, our assessment includes:

dental foci
exposure to mould
diamine oxidase (DAO), the enzyme that breaks down histamine, as well as tryptase and histamine
sensitisation to foods
stool analyses of the gut flora and intestinal lining
the acid-base balance

Where such factors are found and can be treated, the mast cells often settle down.

With us

If you recognise these symptoms in yourself, you can fill in our MCAS questionnaire before the consultation. It classifies your answers according to a checklist and records findings, triggers and previous treatments. The result is not a diagnosis, but it helps us to plan your assessment in a targeted way.

Go to the MCAS questionnaire

Sources

Valent P. et al.: Definitions, criteria and global classification of mast cell disorders with special reference to mast cell activation syndromes: a consensus proposal. International Archives of Allergy and Immunology, 2012.
Valent P. et al.: Diagnosis, Classification and Management of Mast Cell Activation Syndromes (MCAS) in the Era of Personalized Medicine. International Journal of Molecular Sciences, 2020.
Molderings G. J. et al.: Mast cell activation disease: a concise practical guide for diagnostic workup and therapeutic options. Journal of Hematology & Oncology, 2011.
Afrin L. B. et al.: Diagnosis of mast cell activation syndrome: a global “consensus-2”. Diagnosis, 2021.
Lyons J. J. et al.: Elevated basal serum tryptase identifies a multisystem disorder associated with increased TPSAB1 copy number. Nature Genetics, 2016.

Mast cell activation syndrome (MCAS)