Mast cell activation syndrome: A common yet underdiagnosed condition

Mast cell activation syndrome (MCAS) is a relatively new but increasingly recognised condition caused by the excessive release of chemicals from mast cells. These immune cells play a role in allergic reactions and inflammation, but in MCAS, they become overactive, leading to a wide range of symptoms across different body systems. The condition is more common than previously thought and remains underdiagnosed due to its varied presentation.

What conditions are linked to MCAS?

MCAS is often found alongside other chronic conditions, including:

• Joint hypermobility syndrome (including Ehlers-Danlos syndrome - hEDS)
• Postural orthostatic tachycardia syndrome (POTS)
• Long Covid
• Chronic fatigue conditions
• Irritable bowel syndrome (IBS) and other gut disorders

These associations suggest that MCAS may play a broader role in immune system dysfunction and chronic illness.

What symptoms can MCAS cause?

Because mast cells are found throughout the body, symptoms can affect multiple organs, making MCAS difficult to diagnose. Common symptoms include:

• Skin: Flushing, itching, hives, swelling
• Gastrointestinal system: Abdominal pain, nausea, diarrhoea, food intolerances
• Cardiovascular system: Dizziness, palpitations, low blood pressure
• Respiratory system: Wheezing, nasal congestion, throat swelling
• Neurological system: Brain fog, headaches, anxiety, fatigue

Symptoms can fluctuate in severity and may be triggered by stress, certain foods, temperature changes or hormonal fluctuations.

How is MCAS diagnosed?

A diagnosis of MCAS is based on three main criteria:

1. Symptoms consistent with mast cell activation in at least two organ systems.
2. Positive test results: Laboratory markers such as elevated tryptase, histamine or prostaglandins.
3. Positive response to treatment, such as antihistamines or mast cell stabilisers.

Since test results can fluctuate, clinical assessment is key in confirming the diagnosis.

What treatments are available?

Treatment is highly individualised, as patients may respond differently to various therapies. Management often includes:

• Antihistamines (H1 and H2 blockers) to reduce allergic-type symptoms.
• Mast cell stabilisers such as cromolyn sodium or ketotifen.
• Leukotriene inhibitors to target inflammatory pathways.
• Low-histamine diets to minimise dietary triggers.
• Medications for symptom control, including beta-blockers for heart rate issues and corticosteroids for severe reactions.

Most patients require a combination of treatments to manage their symptoms effectively.

How do gut health and hormones affect MCAS?

• Poor gut health can worsen MCAS symptoms by increasing inflammation and allowing more triggers to enter the bloodstream. Managing gut health with probiotics, digestive enzymes, and dietary changes may improve treatment response.
• Hormonal imbalances, particularly fluctuations in oestrogen and cortisol, can affect mast cell activity, leading to symptom flares. Some women notice changes in symptoms during menstrual cycles or menopause.

MCAS is a common but underdiagnosed condition with a broad range of symptoms affecting multiple organ systems. It’s closely linked to conditions like POTS, joint hypermobility syndrome, and long Covid. Diagnosis requires a combination of symptom assessment, lab tests, and treatment response, while management often involves multiple treatments tailored to the individual. Factors like gut health and hormones can influence symptom severity and treatment success, making a holistic approach essential for long-term management.