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Mast cell activation syndrome (MCAS): from flare-ups to freedom

Mast cell activation syndrome (MCAS) is a condition where part of your immune system behaves like a faulty alarm. Instead of only reacting to genuine threats, mast cells can release powerful chemicals at the wrong time, or in the wrong amount. The result? Flushing, gut symptoms, dizziness, rashes, breathing problems – sometimes all at once.

For many people, the journey to an MCAS diagnosis is long and frustrating. Symptoms are real, but tests can be normal. You may be told it is “just anxiety” or “just allergies”, even when your body is clearly saying otherwise.

This guide walks you through what MCAS is, how it is diagnosed, and which treatments may help – including medicines available from medicalmojo.co.uk after completing an online consultation, such as sodium cromoglycate, ketotifen and Low Dose Naltrexone (LDN).

Please note that you can arrange follow-up consultations with our prescriber FREE of charge. Please contact us for further details.

What are mast cells?

Mast cells are immune cells that sit in tissues all over the body – especially where your body meets the outside world: skin, airways, gut, blood vessels and nerves [1], [2]. You can think of them as sentinel cells. Their job is to notice danger and respond quickly.

What’s inside a mast cell?

Inside each mast cell are tiny packets (granules) filled with chemicals such as:

• Histamine
• Tryptase
• Prostaglandins
• Leukotrienes
• Many different cytokines and growth factors [3], [5]

When mast cells are activated, they release these chemicals into the surrounding tissue and bloodstream. This can be helpful – for example, fighting parasites or reacting to a bee sting – but it can also cause symptoms such as itching, swelling, wheezing, diarrhoea or a drop in blood pressure [5], [6].

How do mast cells get activated?

The “classic” way is through IgE-mediated allergy. Allergy antibodies called IgE sit on the surface of mast cells. When they recognise an allergen (for example, peanut protein or pollen), they trigger the cell to degranulate and release its chemicals [3].

However, mast cells can also be activated by many non-IgE pathways, including:

• Complement proteins
• Certain infections
• Physical triggers (heat, cold, vibration)
• Drugs and contrast media
• Neuro immune signals through receptors such as MRGPRX2 [3], [4]

This is one reason MCAS can be so confusing: not all reactions show up on standard allergy tests.

What is mast cell activation syndrome (MCAS)?

Mast cell activation syndrome is a condition in which mast cells release excessive mediators, too often, in response to triggers that would not usually elicit such a strong reaction [7], [8].

People with MCAS typically experience recurrent episodes of symptoms that look allergic – flushing, hives, gut pain, breathlessness, palpitations – but:

• Allergy testing may be negative, and
• There may be no single obvious trigger.

MCAS sits within a wider group of mast cell disorders that also includes:

• Anaphylaxis – a severe, sudden reaction where mast cells release a massive amount of mediators in a short time.
• Mastocytosis – a condition where the body has too many mast cells, often due to a genetic mutation such as KIT D816V [8], [5].

In MCAS, the problem is usually how mast cells behave, not how many there are. You can have a normal mast cell count, but those cells are overreactive.

Types of MCAS

Experts now describe three main categories of MCAS [8], [10]:

Primary (clonal) MCAS

• Mast cells carry a genetic change (often KIT D816V) that makes them more active.
• Frequently overlaps with mastocytosis.
• May need more specialised monitoring and, in some cases, targeted treatments.

Secondary MCAS

Mast cells are over activated because of an external driver, such as:

• IgE-mediated allergy
• Autoimmune disease
• Chronic infection or inflammation [8]

Treating the underlying trigger is key.

Idiopathic MCAS

• Symptoms and lab results fit MCAS, but no apparent trigger or mutation is found.
• This is often the label when everything else has been ruled out.

Some people sit in more than one category – for example, a clonal mast cell disorder plus strong allergic triggers – which can make symptoms more complex [10].

Common symptoms of MCAS

Because mast cells are distributed throughout the body, MCAS can affect multiple organ systems simultaneously. Symptoms often come in episodes – “flares” – that may last minutes, hours or days [8], [9], [11].

Typical symptom clusters include:

Skin

• Flushing (sudden redness or heat)
• Itching or burning sensations
• Hives (urticaria)
• Swelling of lips, eyelids, hands or feet (angio?oedema)

Gut and digestion

• Nausea and vomiting
• Cramping abdominal pain
• Bloating
• Diarrhoea or, less often, constipation
• Symptoms that worsen after certain foods, alcohol or temperature changes

Heart and circulation

• Fast heartbeat (palpitations)
• Low blood pressure, dizziness or near fainting
• “Adrenaline rush” feelings without a clear cause

Breathing

• Nasal congestion, sneezing
• Wheezing, chest tightness
• Shortness of breath

Other symptoms

• Headaches or migraines
• Muscle and joint pain
• Fatigue and “crash” days after flares
• Anxiety, sense of doom, or feeling “wired but tired”

To raise suspicion for MCAS, doctors usually look for episodes that affect at least two systems at the same time – for example, flushing + gut pain, or hives + wheeze + dizziness [10], [11].

Triggers that can set off MCAS symptoms

Everyone’s trigger pattern is slightly different, but common ones include [8], [9], [11]:

Foods and drinks

• • High histamine foods (aged cheese, cured meats, wine, fermented foods)
  • Alcohol
  • Food additives in some people

Temperature and physical factors

• • Heat, cold, sudden temperature changes
  • Exercise or exertion
  • Pressure or vibration on the skin

Medications and chemicals

• • Some painkillers (e.g. NSAIDs)
  • Opiates
  • Certain antibiotics
  • Contrast dyes used in scans
  • Strong smells, perfumes or cleaning products

Infections and inflammation

• • Viral or bacterial infections
  • Chronic inflammatory conditions

Hormones and stress

• • Menstrual cycle changes
  • Psychological stress or lack of sleep

Not everyone reacts to all of these. Some people have a very narrow set of triggers, while others feel as if “everything sets me off”.

How MCAS differs from anaphylaxis

Anaphylaxis is a medical emergency where mast cells release a huge amount of mediators very quickly. It typically causes:

• Swelling of the throat or tongue
• Severe breathing difficulty
• A fast or weak pulse
• A sudden drop in blood pressure
• Collapse or loss of consciousness [8]

MCAS can cause anaphylaxis, but many people with MCAS have repeated, less severe episodes that do not meet full anaphylaxis criteria. In simple terms:

• Anaphylaxis = a single, severe event that can happen once or rarely.
• MCAS = an underlying condition where mast cells are easily triggered, causing recurrent flares that may range from mild to life-threatening [8], [11].

Why is the diagnosis of MCAS so challenging?

Diagnosing MCAS is difficult for several reasons [8], [11].

• Symptoms are non-specific and overlap with many other conditions (IBS, anxiety, POTS, asthma, chronic urticaria, food allergy, endocrine problems, and more).
• Key lab markers such as tryptase can return to normal quickly, so timing of tests is critical.
• Some people have clear clinical MCAS but normal tryptase, so doctors must rely on other mediators and the overall picture  [8], [11].
• There is a risk of over diagnosis if MCAS is labelled without proper testing and exclusion of other causes.

Because of this, most expert groups recommend that MCAS be diagnosed only when all three pillars are met:

1. Typical multi-system symptoms in episodes
2. Objective rise in mast cell mediators during symptoms
3. Clear improvement with mast cell–directed treatment  [8], [10],   [11].

How is mast cell activation syndrome (MCAS) diagnosed?

Most expert groups now agree that MCAS should be diagnosed only when three key criteria are met  [8], [10], [11].

Typical symptoms in episodes

• Recurrent attacks affecting at least two organ systems at the same time
• For example: flushing + gut pain, or hives + wheeze + dizziness

Objective evidence of mast cell activation

• A rise in mast cell mediators (usually in blood or urine) during a flare, compared with the person’s usual baseline

Response to mast cell–directed treatment

• Symptoms improve with medicines that block or calm mast cells (e.g. antihistamines, mast cell stabilisers)

If one of these pillars is missing, doctors are encouraged to continue seeking other explanations rather than jumping straight to an MCAS label [8], [11].

Laboratory tests used in diagnosing MCAS

Serum tryptase – the key blood marker

Tryptase is an enzyme stored in mast cell granules. When mast cells degranulate, tryptase is released into the bloodstream. It is currently the most widely used laboratory marker for mast cell activation [8], [11], [14].

There are two important ways it is used:

Baseline tryptase

• Measured when you are well, outside of a flare.
• A persistently raised baseline (often > 20 ng/mL) can suggest systemic mastocytosis or increased mast cell burden [14].
• Mildly raised baseline tryptase can also be seen in hereditary alpha tryptasemia (H?T), a genetic trait that may increase mast cell-related symptoms in some people [14].

Event (acute) tryptase

• Measured during or shortly after a reaction – ideally within 1–4 hours of the onset of severe symptoms.
• Doctors compare this to your baseline using the increase in the event-related tryptase>120%+2 ng/mL to confirm the involvement of the mast cell (MC) lineage and serves as a diagnostic criterion of MCAS.

If this threshold is met, it is strong evidence of systemic mast cell activation, such as in anaphylaxis or a major MCAS flare [14].

A normal tryptase does not rule out MCAS, especially in milder or more localised forms, but a clear rise that meets the 20% + 2 rule helps confirm mast cell involvement.

Other mast cell mediators

Because tryptase is not always elevated, especially in non-anaphylactic flares, specialists may also look at other mediators  [8], [11]:

• Urinary N-methylhistamine (a breakdown product of histamine)
• Urinary prostaglandin D2 (PGD2) or its stable metabolite 11 beta PGF2 alpha
• Urinary leukotriene E4 (LTE4)

These are usually measured in a 24-hour urine collection during a period with frequent symptoms. Raised levels can support the diagnosis of MCAS, but they are:

• Less standardised than tryptase
• Sometimes harder to access outside specialist centres
• Influenced by other conditions (e.g. allergy, inflammation)  [8], [11].

Histamine, DAO and histamine degradation

Some private laboratories also measure:

• Plasma or serum histamine
• Diamine oxidase (DAO) – the main enzyme that breaks down histamine in the gut
• Histamine degradation capacity – a functional test of how well your serum clears histamine

These tests can show that your body has reduced capacity to break down histamine, which may explain why you react strongly to high histamine foods or bacterial overgrowth in the gut. However, they do not prove or disprove MCAS on their own. They are best viewed as supporting information alongside the core criteria [15].

Challenges in diagnosing MCAS

Diagnosing MCAS is rarely straightforward. Key challenges include [8], [11].

Overlap with other conditions

• • Flushing, gut pain, headaches, dizziness and fatigue can occur in many disorders (thyroid disease, POTS, IBS, anxiety, chronic urticaria, coeliac disease, infections, endocrine problems and more).

Timing of tests

• • Mediators like tryptase and histamine can return to normal within hours.
  • If blood or urine is collected too late, results may look normal even after a significant flare.

Risk of over diagnosis

• • Because MCAS is now better known, some people are given the label without proper exclusion of other causes. This can delay the right treatment.

For these reasons, most guidelines stress that MCAS should be diagnosed by clinicians who are experienced in mast cell disorders, and only after careful evaluation of other possibilities [8],[10],[11].

Types of MCAS and when bone marrow tests are needed

As noted earlier, MCAS can be:

• Primary (clonal) – due to a genetic change in mast cells, often associated with mastocytosis [10]
• Secondary – driven by another condition such as allergy, autoimmune disease or chronic infection [8]
• Idiopathic – no apparent cause found [8]

When is a bone marrow biopsy considered?

In adults, a bone marrow biopsy is usually considered when there is concern about systemic mastocytosis or another clonal mast cell disorder. This might be the case if [8]:

• Baseline tryptase is persistently elevated (often > 20 ng/mL)
• There are skin lesions suggestive of cutaneous mastocytosis
• A KIT D816V mutation is detected in blood
• There are unexplained abnormalities in blood counts or organ function

The biopsy allows pathologists to look directly at mast cells in the bone marrow and apply the World Health Organisation (WHO) criteria for systemic mastocytosis [16].

For many people with suspected non clonal MCAS, a bone marrow biopsy is not needed, especially if baseline tryptase is normal and there are no worrying blood or organ findings.

Conditions that can mimic MCAS

A careful work-up is essential because many conditions can mimic MCAS but require different treatment [8], [11]. Examples include:

Cardiovascular problems

• • Arrhythmias, heart failure, postural tachycardia syndrome (POTS)

Endocrine and metabolic disorders

• • Thyroid disease
  • Adrenal disorders (e.g. adrenal insufficiency, phaeochromocytoma)
  • Carcinoid syndrome

Skin conditions

• • Chronic spontaneous urticaria
  • Eczema, rosacea

Neurological and autonomic disorders

• • Epilepsy
  • Autonomic dysfunction
  • Migraine disorders

Gastrointestinal conditions

• • Coeliac disease
  • Inflammatory bowel disease
  • Irritable bowel syndrome
  • Infections or SIBO

Mental health conditions

• • Panic disorder
  • Generalised anxiety or health anxiety

Ruling these out (or treating them where present) is an essential part of good MCAS care.

How is mast cell activation syndrome treated?

Treatment focuses on two main goals:

1. Calm the mast cells – so they are less likely to fire.
2. Block the mediators – so when they do fire, symptoms are reduced.

Most people need a combination of medicines and lifestyle changes tailored to their triggers and symptom pattern [11].

1. Antihistamines

Histamine is one of the best-known mast cell mediators. Antihistamines block their effects at the receptor level.

H1 antihistamines – mainly help with skin and upper airway symptoms:

• • Examples: loratadine, chlorpheniramine, hydroxyzine [11]. Often used in higher or divided doses in MCAS (under medical supervision).

H2 antihistamines – work on histamine receptors in the stomach and blood vessels:

• • Examples: famotidine, cimetidine [11].
  • May help with reflux, abdominal pain and flushing.

At medicalmojo.co.uk, famotidine 20 mg tablets are available after online consultation when clinically appropriate.

2. Mast cell stabilisers

These medicines help reduce mast cells’ tendency to degranulate.

Sodium cromoglycate (cromolyn sodium)

• • Can be used orally for gut-dominant symptoms and sometimes systemically [11].
  • Nalcrom® 100 mg capsules are an example of an oral sodium cromoglycate product available from medicalmojo.co.uk (subject to clinical suitability).

Ketotifen

• • Has both antihistamine and mast cell–stabilising properties [11].
  • Available as tablets and liquids; Zaditen® Elixir (ketotifen 1 mg/5 ml) is one option stocked by medicalmojo.co.uk.

These medicines often need to be introduced slowly and taken regularly rather than just “as needed”.

3. Leukotriene blockers

Leukotrienes are inflammatory mediators released by mast cells and other immune cells.

• Medicines such as montelukast block leukotriene receptors and can help with wheeze, chest tightness and some gut symptoms in selected patients [12].

4. Anti-inflammatory medicines

In some cases, carefully selected NSAIDs or low-dose aspirin can help control symptoms related to prostaglandins, but they can also worsen symptoms in others [11]. A specialist should guide any use.

5. Low Dose Naltrexone (LDN)

Low Dose Naltrexone (LDN) is an off-label treatment that has gained interest in MCAS and other chronic inflammatory conditions.

• At low doses, naltrexone briefly blocks opioid receptors, which appears to trigger a rebound increase in the body’s own endorphins and regulatory immune signals [17].
• This may help modulate immune activity, including mast cell behaviour, in some people [18].
• Evidence is still emerging, but case reports and small studies suggest that LDN can improve symptoms such as pain, fatigue and inflammation in selected patients [18], [19], [20].

At medicalmojo.co.uk, LDN is available as a compounded medicine after an online consultation with a prescriber familiar with its use in MCAS and related conditions.

LDN is not a cure and is usually used alongside antihistamines, mast cell stabilisers and lifestyle measures.

6. Other and advanced treatments

In more complex or severe cases, specialists may also consider:

• Anti-IgE therapy (e.g. omalizumab) – particularly when IgE-mediated allergy is a strong driver [11].
• Targeted therapies for clonal mast cell disease (e.g. tyrosine kinase inhibitors in systemic mastocytosis) [11].
• Epinephrine auto-injectors and now the nasal sprays for patients at risk of anaphylaxis.

These are usually initiated and monitored in secondary or tertiary care.

Lifestyle and self-management strategies

Medicines are only part of the picture. Many people with MCAS find that symptoms improve when they:

Identify and avoid key triggers

Keeping a symptom and trigger diary can be very helpful.

Consider a low-histamine diet trial.

Under dietetic or medical guidance, especially if weight loss or food restriction is a concern.

Support gut health

Treating SIBO or dysbiosis where present, and avoiding foods that clearly worsen symptoms [6].

Optimise sleep and stress management.

Poor sleep and chronic stress can both prime mast cells.

Have an emergency plan

For those at risk of severe reactions, this may include carrying antihistamines and an adrenaline auto injector, and knowing when to seek urgent care.

MCAS and anaphylaxis: what’s the difference?

To recap:

• Anaphylaxis is a sudden, severe reaction where mast cells release a large amount of mediators in a short time. It is a medical emergency requiring immediate treatment with adrenaline and emergency care [8].
• MCAS is a chronic condition where mast cells are easily triggered, causing repeated episodes of symptoms that may range from mild to severe. Some of these episodes may meet criteria for anaphylaxis; others may not  [8], [11].

In practice, some people with MCAS will have both:

• Frequent “everyday” flares (flushing, gut pain, brain fog), and
• Occasional full-blown anaphylactic reactions.

These patients usually need close specialist follow-up and a clear emergency plan.

Concluding remarks

Mast cell activation syndrome is a complex but increasingly recognised condition. It sits at the crossroads of allergy, immunology and chronic inflammatory disease. Diagnosis relies on:

• Recognising typical multi system symptom patterns
• Demonstrating objective mast cell mediator release (especially tryptase)
• Showing a clear response to mast cell–directed treatment

For people who meet these criteria, a combination of antihistamines, mast cell stabilisers, leukotriene blockers, lifestyle changes and, in some cases, Low Dose Naltrexone (LDN) can make a meaningful difference to quality of life.

Because MCAS overlaps with many other conditions, working with clinicians experienced in mast cell disorders is essential. This helps avoid misdiagnosis, ensures that serious conditions such as systemic mastocytosis are not missed, and allows treatment to be tailored to the individual.

At medicalmojo.co.uk, our online MCAS service aims to support this journey by offering evidence-based treatment options, including licensed medicines such as sodium cromoglycate and famotidine, as well as compounded options such as LDN and ketotifen liquids, following a structured online consultation.

This information is for general guidance only and is not a substitute for medical advice. Always discuss diagnosis and treatment options with your doctor or specialist.

This information is for general guidance only. For medical advice, please consult your doctor or healthcare provider.

References

What are mast cells?

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[2] Da Silva, E.Z.M., Jamur, M.C. & Oliver, C. (2014). Mast cell function: a new vision of an old cell. Journal of Histochemistry & Cytochemistry, 62(10), 698–738.

What’s inside a mast cell?

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What is mast cell activation syndrome (MCAS)?

[7] Akin, C., Valent, P. & Metcalfe, D.D. (2010). Mast cell activation syndrome: proposed diagnostic criteria. Journal of Allergy and Clinical Immunology, 126(6), 1099–1104.
[8] Gülen, T. (2024). Using the proper criteria for MCAS. Current Allergy and Asthma Reports, 24, 39–51.

Types of MCAS

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Common symptoms of MCAS

[11] Weiler, C.R., Austen, K.F., Akin, C., Barkoff, M.S., Bernstein, J.A., Bonadonna, P., et al. (2019). AAAAI Mast Cell Disorders Committee Work Group Report: mast cell activation syndrome (MCAS) diagnosis and management. Journal of Allergy and Clinical Immunologynology, 144(4), 883–896.

Laboratory tests are used in diagnosing MCAS.

[12] Tolar, J., Tope, W.D., & Neglia, J.P. (2004). Leukotriene?receptor inhibition for the treatment of systemic mastocytosis. New England Journal of Medicine, 350(7), 735–736.
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[14] Valent, P., Akin, C. and Arock, M., 2024. Reversible elevation of tryptase over the individual’s baseline: why is it the best biomarker for severe systemic mast cell activation and MCAS?. Current Allergy and Asthma Reports, 24(3), pp.133-141.

Histamine, DAO and histamine degradation

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Types of MCAS and when bone marrow tests are needed

[16] Pardanani, A., 2016. Systemic mastocytosis in adults: 2017 update on diagnosis, risk stratification and management. American journal of haematology, 91(11), pp.1146-1159.

Low Dose Naltrexone (LDN)

[17] Courier Pharmacy. (2025). How does LDN work? [online] Available at: https://courierpharmacy.co.uk/how-does-ldn-work/ [Accessed 10 Nov. 2025].

[18] Courier Pharmacy. (2025). LDN and MCAS. [online] Available at: https://courierpharmacy.co.uk/ldn-and-mcas/ [Accessed 10 Nov. 2025].

[19] Medical Mojo. (2025). Fibromyalgia and LDN. [online] Available at: https://medicalmojo.co.uk/fibromyalgia-and-ldn/ [Accessed 10 Nov. 2025].

[20] Medical Mojo. (2025). Long COVID and LDN. [online] Available at: https://medicalmojo.co.uk/long-covid-and-ldn/ [Accessed 10 Nov. 2025].