Mast Cell Activation Syndrome
Mast cells are a type of white blood cell that are present all over the body and can either suppress or increase inflammation depending on the circumstances they find themselves in. The mast cells have receptors for allergens, pathogens, neurotransmitters, neuropeptide and hormones. Stored inside the mast cells are a number of different “mediators” which are released when these cells are “triggered.” These mediators are contained in small sacks inside the cell called vesicles and when the mediators are released from these vesicles, the process is called degranulation.
Mast cell activation syndrome is an immunological condition in which there is a normal amount of mast cells in the body, but they are highly sensitive. When triggered inappropriately, they cause degranulation and release of mediators such as histamine from the mast cell into the blood.
MCAS is a common disorder that is characterised by this uncontrolled mast cell activation resulting in allergies and systemic inflammation. It is though that up to 17% of the population in Germany is affected by MCAS ( Molderings, G.J., Haenisch, B et al 2013). A mutation in the genes that controls the mast cells is thought to be responsible for the development of MCAS. Evidence suggests that this mutation is not inherited (germline) but rather are acquired or somatic. It is thought that in most patients with MCAS, mutations occur in one or more of the regulatory genes in their mast cells. These mutations are switched on by epigenetic changes. Epigenetics looks at changes in the way that genes are expressed without any structural changes occurring to the DNA molecule. Epigenetic changes can be influenced by factors like, disease state, age and lifestyle.
Thus, although MCAS is technically thought of as an immune disorder it has been found that a lot of mast cells end up being deposited in the gut which then produces both symptoms in the gut and systemically. The most common symptoms reported by patients suffering from MCAS are:
· Itching-chronic urticaria
· Near syncope (fainting)
· Postural orthostatic tachycardia syndrome (POTS)
When it comes to MCAS virtually all body systems can be affected (Afrin, L.B. and Molderings, G.J., 2014).
In many instances since there are associated gut symptoms many doctors mistake MCAS for IBS and other such conditions (Barbara, G., Stanghellini, V et al 2004).
Diagnosis of MCAS
There is currently no universal algorithm that clinicians can use to arrive at a diagnosis of MACS, however the following is used to help arrive at such a diagnosis:
· Patient history
· Differential diagnosis consideration-is something else causing the symptoms
· Physical examination
· Baseline laboratory tests
· Specific chemical mediator testing of the blood and urine, e.g., tryptase levels
· Tissue or bone marrow biopsy
Treatment of MCAS
The first step is to try and identify the root causes and eliminate the triggers. Once this is done then sufferers of MCAS may be prescribed a combination of the following types of medications (Molderings, G.J., Haenisch, B 2016).
· Emergency medicine such as EpiPen
· Preventative medicines such as anti-histamine that block the actions of the mediators
· Preventative medications that inhibit the release of mast cell mediators (ketotifen)
· Preventative medications that inhibit the production of mast cell mediators (NSAIDs, steroids, vitamin C)
· Other drugs prescribed by specialists such as hydroxyurea
Antihistamine as their name suggests they block the action of histamine, so they block the action of a released mediator while mast cell stabilisers such as ketotifen block the release of the mediators. Ketotifen is not currently available from UK pharmacies and has to be compounded specially by compounding pharmacies, such as Courier Pharmacy.
Afrin, L.B. and Molderings, G.J., 2014. A concise, practical guide to diagnostic assessment for mast cell activation disease. World Journal of Hematology, 3(1), pp.1-17.
Barbara, G., Stanghellini, V., De Giorgio, R., Cremon, C., Cottrell, G.S., Santini, D., Pasquinelli, G., Morselli-Labate, A.M., Grady, E.F., Bunnett, N.W. and Collins, S.M., 2004. Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome. Gastroenterology, 126(3), pp.693-702.
Molderings, G.J., Haenisch, B., Bogdanow, M., Fimmers, R. and Nöthen, M.M., 2013. Familial occurrence of systemic mast cell activation disease. PloS one, 8(9), p.e76241.
Molderings, G.J., Haenisch, B., Brettner, S., Homann, J., Menzen, M., Dumoulin, F.L., Panse, J., Butterfield, J. and Afrin, L.B., 2016. Pharmacological treatment options for mast cell activation disease. Naunyn-Schmiedeberg's Archives of Pharmacology, 389(7), pp.671-694.