Mast cell activation syndrome

Additional information

What are mast cells?

Mast cells are special cells in your immune system that help protect your body [1]. They have tiny packets inside them filled with chemicals [1]. These cells can react in different ways depending on the trigger and their location in the body [2].

The most common way mast cells get activated is when allergy antibodies called Immunoglobulin E (IgE) stick to their surface. But they can also be triggered by other signals, like certain receptors that respond to infections or other immune system alerts [3], [4].

When mast cells are activated, they release chemicals that cause many different effects in the body. These chemicals can lead to a variety of symptoms, and their impact on individuals can vary significantly depending on the condition [5], [6].

Symptoms and effects of mast cell activation

When mast cells are activated, they release chemicals that can cause a range of symptoms. These symptoms can be mild, like a bit of itching or redness, or very serious and even life-threatening  [7], [8].

The symptoms can happen suddenly or last for a long time. Sudden symptoms often occur during allergic reactions and might affect just one part of the body, like a skin rash, runny nose, or asthma [8]. However, mast cells can sometimes cause symptoms throughout the entire body, leading to severe reactions such as anaphylaxis [8].

Some people have mast cells that are overly sensitive or have an excessive number of mast cells. This can exacerbate their symptoms or lead to more frequent reactions. For example, in conditions like mastocytosis, the body has too many mast cells, which can lead to severe symptoms [8].

 

What is mast cell activation syndrome (MCAS)?

Mast Cell Activation Syndrome, or MCAS, is a rare condition where mast cells release too many chemicals at once. This causes sudden and severe symptoms that affect different parts of the body [9].

People with MCAS often have episodes that look like severe allergic reactions called anaphylaxis. These episodes can come on quickly and cause symptoms like flushing, swelling, stomach pain, fast heartbeat, low blood pressure, and trouble breathing.

MCAS is part of a group of conditions involving mast cells, including anaphylaxis and mastocytosis (which is when the body has too many mast cells). While these conditions are related, they are not the same [8].

How is mast cell activation syndrome (MCAS) diagnosed?

Doctors diagnose MCAS by looking for three main things [10]:

1. Symptoms: The person has sudden, severe symptoms that affect at least two different parts of the body at the same time. For example, they might experience skin flushing and stomach pain simultaneously, or a rapid heartbeat and difficulty breathing.
2. Lab tests: During these episodes, blood or urine tests show a significant increase in certain chemicals released by mast cells. The most important chemical doctors look for is called tryptase. This chemical usually rises in the blood when mast cells are activated.
3. Response to treatment: The symptoms improve when the person takes medicines that block or calm down mast cells, like antihistamines.

If all three of these things are true, doctors can be confident that the person has MCAS.

 

How is mast cell activation syndrome (MCAS) treated? (including LDN)

Treating MCAS usually involves medicines that help calm down mast cells or block the chemicals they release. Common medicines include:

• Antihistamines: These block histamine, one of the main chemicals that mast cells release. There are two types—H1 and H2 antihistamines—that help with different symptoms [11]. Examples of H1 antihistamines include loratadine, chlorpheniramine and hydroxyzine. Examples of H2 antihistamines include famotidine and cimetidine.
• Leukotriene blockers: These stop other chemicals that can cause inflammation and swelling [12].
• Mast cell stabilisers: These help prevent mast cells from releasing their chemicals  [11]. Examples include sodium cromoglycate and ketotifen.
• Anti-inflammatory drugs: Medicines like aspirin or NSAIDs can help control symptoms  [11].
• Low Dose Naltrexone (LDN): LDN is a medicine used in low doses that may help regulate the immune system and reduce inflammation. Some patients with MCAS find it helpful to manage symptoms, although it’s not yet widely used or fully understood for this purpose. It is usually prescribed by a specialist and used alongside other treatments [13].

Doctors typically begin with the lowest effective dose and adjust it as needed. In some cases, more advanced treatments, such as anti-IgE therapy or targeted drugs that affect mast cells, may be used.

 

Low Dose Naltrexone (LDN) in MCAS treatment

Low-dose naltrexone, or LDN, is a medication that some doctors use in small doses to help calm the immune system and reduce inflammation. While initially developed for other conditions, LDN has gained attention for its potential to help people with Mast Cell Activation Syndrome (MCAS) [13].

LDN works by gently blocking specific receptors in the body for a short time. This “blockade” encourages the body to produce more natural chemicals that help regulate the immune system [14]. By doing this, LDN may help reduce the overactive response of mast cells that causes symptoms in MCAS.

It’s important to know that LDN is not a cure for MCAS, and research on its use for this condition is still limited. However, some patients have found it helpful in managing symptoms when used in conjunction with other treatments, such as antihistamines and mast cell stabilisers.

Because LDN is a prescription medicine, it should only be used under the guidance of a healthcare professional familiar with MCAS. Your doctor can help decide if LDN might be a good option for you and monitor your progress.

 

 

MCAS and Anaphylaxis: What’s the Difference?

Anaphylaxis is a sudden, severe allergic reaction that occurs when mast cells rapidly release a large amount of histamine and other chemicals. This can cause serious problems like swelling of the throat, trouble breathing, a fast or weak heartbeat, and a dangerous drop in blood pressure. Anaphylaxis is a medical emergency that requires immediate treatment [8].

MCAS can cause anaphylaxis, but not all cases of anaphylaxis are due to MCAS. Also, MCAS can cause symptoms that are less severe and don’t always meet the full criteria for anaphylaxis [8].

In simple terms, anaphylaxis is a severe reaction that can occur once or rarely. In contrast, MCAS is a condition in which mast cells are more easily triggered, causing repeated episodes of symptoms that may or may not be as severe as anaphylaxis.

Common symptoms of mast cell activation syndrome (MCAS)

MCAS can cause a wide variety of symptoms because mast cells affect many parts of the body. Symptoms often come and go suddenly and can vary from person to person. Some of the most common symptoms include [8]:

• Skin: Flushing (redness), itching, hives, swelling
• Stomach and digestion: Nausea, vomiting, stomach cramps, diarrhoea
• Heart and blood vessels: Fast heartbeat, low blood pressure, dizziness, fainting
• Breathing: Nasal congestion, sneezing, wheezing, shortness of breath
• Other symptoms: Headaches, muscle pain, fatigue, anxiety

Symptoms can affect two or more parts of the body simultaneously during an episode. Because these symptoms are common in many conditions, it can sometimes be hard to diagnose MCAS without detailed testing.

Laboratory tests used in diagnosing mast cell activation syndrome (MCAS)

To confirm MCAS, doctors need to see evidence that mast cells are releasing their chemicals during symptoms. This is done through blood and urine tests.

The most important test looks for a chemical called tryptase in the blood. Tryptase levels usually rise when mast cells are activated. Doctors compare the tryptase level during an episode with the person’s usual baseline level. If the tryptase during symptoms is significantly higher, it supports the diagnosis of MCAS [8], [11].

Other chemicals can be measured in urine, like histamine breakdown products and prostaglandin D2. These can also indicate mast cell activation, but they are less specific and more challenging to test for [8].

It’s important to collect blood or urine samples as soon as possible after symptoms start, because these chemicals can return to normal quickly.

 

 

Challenges in diagnosing mast cell activation syndrome (MCAS)

Diagnosing MCAS can be difficult because its symptoms are similar to those of many other health problems. People with MCAS might have symptoms like flushing, headaches, stomach pain, or a fast heartbeat, but these can also happen in other conditions.

Doctors need to carefully rule out other causes before diagnosing MCAS. Sometimes, patients are mistakenly told they have MCAS when their symptoms come from something else.

Another challenge is that key lab tests, such as tryptase levels, need to be performed quickly after symptoms begin. If the test is performed too late, the chemical levels may have returned to normal, making it more difficult to confirm the diagnosis.

Because of these difficulties, diagnosing MCAS often takes time and multiple tests and requires doctors who are experienced in recognising this condition.

Types of mast cell activation syndrome (MCAS)

There are different types of MCAS, depending on what causes the mast cells to become overactive:

• Primary (or clonal) MCAS: This happens when the mast cells themselves have a genetic change or mutation that makes them more active than usual. This type is often linked to conditions like mastocytosis, where there are too many mast cells in the body [10].
• Secondary MCAS: This type occurs when something outside the mast cells, like an allergy or infection, triggers them to release chemicals too often  [8].
• Idiopathic MCAS: In this type, doctors don’t find a clear cause for the mast cells’ overactivity. It’s diagnosed when symptoms fit the criteria for MCAS, but no genetic changes or triggers are found [8].

Sometimes, people can have a mix of these types, which can make symptoms more severe or more complicated to treat.

 

When is a bone marrow test needed for MCAS?

If an adult exhibits skin symptoms that suggest mastocytosis—a condition in which specific immune cells called mast cells accumulate in the skin—doctors may conduct a blood test to screen for a particular genetic mutation, known as the KIT D816V mutation. This mutation is often linked to mastocytosis.

If this mutation is found in the blood, doctors usually recommend a bone marrow biopsy. This means taking a small sample from inside the bone marrow (the soft tissue inside your bones) to look more closely at the mast cells.

The biopsy helps doctors confirm whether the mastocytosis is systemic, meaning it affects not just the skin but also other parts of the body, like the bone marrow and organs. This is important because systemic mastocytosis may require different treatments and monitoring [8].

This approach follows the official guidelines set by the World Health Organisation to make sure the diagnosis is accurate and complete [15].

 

Conditions that can mimic mast cell activation syndrome (MCAS)

Some health problems can cause symptoms that look like MCAS but are actually different conditions. This can make diagnosing MCAS tricky [8].

For example, symptoms like flushing, headaches, stomach pain, or a fast heartbeat can happen with:

• Heart problems like heart attacks or irregular heartbeats
• Hormone issues like thyroid problems or adrenal gland disorders
• Skin conditions like eczema or rosacea
• Nervous system problems like seizures or fainting
• Mental health issues like anxiety or panic attacks
• Digestive problems like irritable bowel syndrome or infections

Because these conditions can look similar to MCAS, doctors need to carefully check and rule them out before confirming an MCAS diagnosis. This helps avoid misdiagnosis and ensures the proper treatment.

 

Concluding remarks

Mast Cell Activation Syndrome (MCAS) is a condition where mast cells release too many chemicals, causing sudden and severe symptoms. While it can be serious, diagnosing MCAS is often challenging because its symptoms are similar to those of many other health problems.

Doctors use specific tests and criteria to help confirm the diagnosis, but sometimes it takes time and careful investigation to do so. Treatment focuses on calming the mast cells and managing symptoms, often with medicines like antihistamines and mast cell stabilisers. Some newer treatments, such as Low-Dose Naltrexone (LDN), may also be beneficial.

Patients need to work closely with their healthcare team to develop a treatment plan tailored to their specific needs. Further research is required to improve diagnosis and develop new treatments for MCAS.

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

References:

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