What is mast cell activation syndrome (MCAS)?

What are mastocytes? 

Mast cells are cells of the immune system. They come from stem cells located in the bone marrow, then pass into the bloodstream in the form of "progenitors" and finish their maturation in the connective tissue, particularly in the skin, but also in the digestive, respiratory, ENT and urogenital mucous membranes.

Mast cells contain numerous granules rich in histamine and heparin.

Mast cells are there to protect us from possible aggression. They perform a variety of functions:

• Immune defence,
  
• Defence against tumour proliferation,
  
• Wound healing,
  
• Fibrosis process (transformation of a tissue in our body into a fibrous tissue that has lost the properties of the initial tissue),
  
• Angiogenesis (the process of growing new blood vessels from already existing ones).
  

When stimulated, mast cells release substances that they synthesise locally into the bloodstream. They are then said to "degranulate", releasing microscopic granules from their cytoplasm. These granules contain histamine, heparin, prostaglandins, leukotrienes, cytokines and many other substances.

In mast cell activation syndrome (MCAS), mast cells are easily overstimulated, reacting and degranulating abnormally in reaction to certain stimuli.

What is mast cell activation syndrome (MCAS)? 

Mast cell activation syndrome (MCAS) is one of a group of diseases known as mastocytoses. These diseases are characterised by the abnormal proliferation of mast cells under the effect of an acquired activating mutation of the CKIT gene, and their mutation in various organs such as the skin, bone marrow, liver, spleen, digestive tract and bones. Mastocytosis is also characterised by autonomous and unregulated activation of mutated mast cells which leads to excessive degranulation.

In MCAS, mast cells activate abnormally. The release of mast cells leads to acute and/or chronic symptoms.

Acute symptoms include:

• Flushing: intense redness with tingling and/or burning sensations,
  
• Itching - day and night,
  
• Profuse sweating, not caused by exertion,
  
• Hives,
  
• Digestive problems such as abdominal pain, diarrhoea, nausea, gastro-oesophageal reflux, etc.
  
• Urinary problems with bladder damage such as interstitial cystitis,
  
• Headaches,
  
• Malaise, which can lead to anaphylactic shock (a serious and potentially life-threatening allergic reaction).
  

Chronic symptoms include:

• Severe asthma,
  
• Osteoporosis, sometimes leading to bone fractures,
  
• Inflammation in the organs where mast cells regularly degranulate, which results in tendonitis, neuroinflammation, memory and concentration problems, etc.
  

In addition, significant fatigue and chronic daytime and nocturnal pain generally set in for the long term, greatly disrupting patients' daily lives. 

How is mast cell activation syndrome (MCAS) diagnosed? 

Symptoms can vary from patient to patient. Generally, if mast cell activation syndrome (MCAS) is diagnosed, it is because the symptoms are severe.

The diagnosis is difficult to establish because the symptoms can be multiple and can vary depending on the patient, and are not specific of MCAS.

It is their repetition and accumulation that allows the diagnosis of mast cell activation syndrome.

Medical treatment often begins after a long period of misdiagnosis, during which the patient is seen by different specialists, depending on the organs affected. Then, in view of the diversity of the symptoms, a consultation in internal medicine is often suggested in order to rule out systemic diseases. The patient is then referred to a specialised centre or clinic. At this stage, the diagnosis can finally be established or confirmed.

What is the treatment plan for mast cell activation syndrome (MCAS)? 

There is no cure for mastocytosis. The aim of the treatment is to improve patients' quality of life.

The main treatment for mast cell activation syndrome (MCAS) is based on:

• Therapeutic education of the patient,
  
• Strict avoidance of known triggers (food, medication, insect bites, excessive physical activity, extreme temperatures, etc.),
  
• Antihistamines and anti-leukotrienes, in particularly high doses. These are two substances released by mast cells,
  
• A mast cell stabiliser (sodium cromoglicate),
  
• Numerous symptomatic medications aimed directly at the organs affected, 
  
• In some cases, background treatment may be considered. This is generally an anti-IgE biotherapy such as omalizumab.
  

Treatments are generally taken on a long-term basis to ensure a better quality of life for patients. As a result, some patients can lead an almost normal life.

In other cases, patients are too severely affected by the various symptoms. In such cases, they can get additional support from social workers and mental health specialists. 

Finally, joining a patient support group or an online patient community can be beneficial for people affected by MCAS.