Mast Cell Activation Syndrome

Mast Cell Activation Syndrome – An Overview

Mast Cell Activation Syndrome (MCAS – also known as Mast Cell Activation Disorder) is a relatively unknown condition that may affect some people with Postural Tachycardia Syndrome (PoTS) and is caused by abnormal mast cells or abnormal release of chemicals contained within them. 

PoTS and MCAS are not very well understood and the overlap between the two conditions is complicated. At this moment in time there may seem to be more questions than answers. One of the biggest challenges is that patients’ clinical presentation can vary substantially, not only from person to person, but even within a patient from one point in time to another.

Normal Mast Cell Function

Mast cells are a normal part of our bodies’ immune system and help to fight infection. They constantly interact with the environment, and these are the cells that may be involved in allergic and inflammatory reactions. Mast cells are found in most organs of the body, and especially in locations that are in close contact with the external environment, such as skin, airways, and intestines. When they are activated, they release many chemicals, such as histamine, that create the symptoms that we commonly associate with allergies.

Mast Cell Disorders

When mast cell function or numbers are abnormal, this can result in a number of different medical conditions: 

1. Mastocytosis occurs when there are too many mast cells in the body. This condition does not occur in PoTS.  

2. MCAS is a condition affecting several body systems where there is a normal number of mast cells, but they don’t function properly. It is likely that the signs and symptoms of MCAS are caused by the chemicals being released inappropriately when mast cells are stimulated. It was first recognised in 1991 and the diagnostic criteria were proposed in 2010. An additional diagnostic consensus has more recently been proposed by Dr L Afrin. An infection such as COVID-19 can cause an increase in symptoms.

The most common signs and symptoms of mast cell activation syndrome (in over 50% of patients) include:  

• Fatigue
• Skin writing (Dermographism)
• Pain all over the body (Fibromyalgia) 
• Near fainting and fainting 
• Headache
• Itching/nettle rash (urticaria)
• Tingling
• Nausea/vomiting
• Chills
• Skin swelling, which moves around the body
• Eye irritation  
• Breathlessness

Others signs and symptoms reported include:

• Variable blood pressure 
• Excessively fast heart rate 
• Blocked nose 
• Wheezing 
• Flushing 
• Diarrhoea, abdominal cramps, nausea 

On rare occasions, some people with MCAS may have a severe life-threatening allergic reaction (anaphylaxis), which includes rapid swelling under the skin, and tissues of the mouth and airways (angioedema), which requires immediate medical treatment.   

It is important to remember that many of these symptoms can occur in other conditions and if patients have these symptoms, it does not necessarily mean that they have MCAS. They must have additional features as seen in the diagnostic criteria below.  

Diagnosis

Diagnosis of MCAS is usually made when similar conditions, such as mastocytosis or pheochromocytoma (a growth on the adrenal glands), have been ruled out and the following three criteria are met.

1. Typical clinical signs and symptoms – as in the list above.
2. High levels of chemicals released by the mast cells during an episode are found in the blood or urine. The tests should be done during or shortly after an episode.  Possible tests include- Tryptase (serum or plasma), Urine Methyl Histamine, Urine Prostaglandin F2 alpha, Urine Prostaglandin D2, Urine Prostaglandin DM.
3. Appropriate response to typical treatments for MCAS.

As it can be challenging to diagnose MCAS, rather than attempting testing (as testing facilities may not be available), some clinicians will initiate a trial of medication used to treat MCAS, and observe if the patient improves.

Triggers

Most MCAS patients have identifiable triggers which cause the mast cells to release their chemicals. However, these triggers can be very variable and sometimes it can be difficult to identify them. Known triggers should obviously be avoided if possible.  

This is a list of some of the common triggers: 

• alcohol
• heat
• medication
  • antibiotics
  • non-steroidal anti-inflammatory drugs (e.g. ibuprofen and aspirin)
  • morphine
  • certain drugs used to relax muscles during surgery
  • substances used to improve visibility of organs during certain x-rays
• medical procedures (e.g. general anaesthesia, biopsy, endoscopy)
• wasp/bee stings and other insect bites
• fever or infection including COVID-19
• exercise
• physical stimulation (e.g. pressure, friction)
• emotions/stress

These are some other triggers reported by MCAS patients:

• certain foods
• environmental toxins (e.g. pesticides/perfumes)
• bacteria/fungi/mould
• artificial colours/flavourings
• menstrual cycle

There are potentially many more symptoms and triggers not on these lists, but because many patients present differently, it is impossible to list them all.

Treatment

There is no permanent cure available for MCAS and management is based on the avoidance of triggers, and medication to help to control symptoms. A low histamine diet may help some patients.

The following are medications used to help control symptoms of MCAS: 

1. Medication that blocks histamine. There are four types of histamine receptor within the body – H1, H2, H3 and H4. Medication is often divided into H1 antihistamines such as cetirizine, fexofenadine, loratadine and H2 antihistamines such as cimetidine and famotidine. These medications help dampen down the effect of histamine released by the mast cells. 
2. Medication that stabilises the mast cells to stop them releasing their chemicals. Examples include sodium chromoglycate, ketotifen and montelukast.

MCAS in PoTS and Hypermobility

MCAS is thought to be common in the general population, and therefore is likely to also occur in patients with hypermobile Ehlers-Danlos Syndrome (hEDS) and hypermobility spectrum disorder (HSD). Researchers have noted a possible link between hEDS and MCAS.    

The treatment for mast cell disorders in patients with hypermobility disorders is the same as in those without.

The triad of PoTS, MCAS and EDS hypermobility are being increasingly identified in patients.