Mast Cell Activation Syndrome (MCAS)


Mast Cell Activation Syndrome (MCAS) frequently occurs in patients suffering from hypermobile EDS (hEDS). Additionally, it could be accompanied by POTS. This combination of EDS, MCAS and POTS has gathered some attention over the last years and hopefully research will solve the mystery how those three are connected.

MCAS is not the same conditions as Mastocytosis. The latter is a disease in which mast cells start to proliferate in abnormal numbers in different tissue, whereas MCAS is a disorder in which mast cells release specific mediators. However, both disorders lead to similar symptoms. MCAS can affect every system of the body and may manifest with neurological, gastrointestinal, cardial, skin and bronchial symptoms.

Many triggers can cause mast cells to degranulate, which shortly after leads to allergic-like symptoms in different severity.

Symptoms that may occur:

Rash, redness, itching
Fatigue
Flushing
Tachycardia
Low body temperature
Diarrhea, nausea, cramps
Wheezing
Vision problems
Low bone density
Intolerance to food or medication
Urinary urgency
Sometimes even anaphylactic reactions

 

Trigger factors, which can lead to acute episodes:

Heat or cold
Physical activity
Chemicals / medication
Food
Stress
Alcohol

MCAS patients should avoid alcohol!

MCAS patients should avoid alcohol!

 

Diagnosing MCAS is very challenging. If MCAS is suspected, after a thorough medical history has pointed into this direction, the doctor will probably order lab tests to measure the concentration of a few mast cell mediators.

Such as:

Tryptase in blood
Methylhistamine in urine
Heparine in blood

or other markers (like Chromogranine A, Leuktrienes, Prostaglandine D2)

Unfortunately, no worldwide unifying criteria for MCAS exist, and tests can come back negative even though the patient might have MCAS.

 

Suggested criteria by Afrin and Molderings

Both major criteria; or one major and two minor criteria have to be positive.

Major:

  1. Multifocal or disseminated infiltrates of mast cells in bone marrow or other organs (intestines)
  2. Mast cell mediator syndrome

Minor:

  1. Abnormal morphology (spindle-like) in > 25 percent of mast cells in bone marrow or other organs
  2. CD2 and CD25 positive mast cells
  3. Genetic mutation that causes mast cell activation
  4. High concentration of mast cell mediators
  5. Good response to therapy

 

If the patient’s symptoms still resemble mediator release, the physician might try a therapy consisting of a combination of H1 and H2 receptor blocker, and mast cell stabilizers.

Foods with high levels of histamine, for example alcohol, specific medication, and therapies that stimulate the immune system should be avoided.

 

Helpful Smartphone Apps for a histamine-free diet:
http://www.mastzellaktivierung.info/de/therapie_histamin-app.html

 

Emergency information in case of surgery:

In case of a surgery many factors can contribute to the release of mast cell mediators, for example mental stress, bleeding, hypothermia and different medication. Therefore it is important to appropriately plan the patient’s pre-, peri-, and postoperative care.

Prednisolone and H1 and H2 blockers should be administered as mast cell prophylaxis before any surgery or invasive examination.

The patients level of stress should be reduced as far as possible; medication before, during and after surgery (pain meds, anesthesia, antibiotics, muscle relaxants) should be discussed and planned.

A mast cell specific blood analysis for prolonged bleeding time or possible thrombosis is necessary.

During surgery, the patient should be protected from hypothermia and skin irritation, and an atraumatic technique should be used. Anaphylaxis can occur at all times and preventive measures have to be taken (adrenaline, glucocorticoid, H1 antihistamines, volume substitute). Patients who suffer from increased bleeding could benefit from tranexamic acid.

Even after surgery anaphylaxis could occur. Additionally, the patient  has to be monitored for thrombotic events and bleeding.

 

Many drugs have a huge influence on mast cell diseases. Medication that should be avoided, and possible alternative drugs are the following:
(No claim for completeness or correctness)

Antibiotics to be avoided:
Cefotiam, Cefuroxime, Chlortetracycline, Clavulanic acid, D-Cycloserin, Framycetin (Neomycin), Isoniazid, Polymyxin B
Alternative: Roxithromycin

Local anesthesia: In general ester type anesthesia is not well tolerated. Amid type anesthesia might be better.

Anesthesia to be avoided: Curare, Methohexital, Phenobarbital, Propanidid
Alternative: Propfol, Ketamine

Muscle relaxants to be avoided: Alcuronium, Atracurium, Doxacurium, Gallamine, Metocurine, Mivacurium, Pancuronium, Succinylcholine (Suxamethonium), Tubocurarine
Alternative: Cisetracurium, Vecuronium, Rocuronium

Heart and blood pressure medication to be avoided: Alpha and Betablocker (for example Alprenolol), Chinidin, Dihydrazaline, Furosemide, Propafenone, Reserpine, Verapamil

Cough and asthma medication to be avoided: Acetylcysteine, Ambroxol, Aminophylline, Codeine, Theophylline

Anti-cramping medication to be avoided: Metoclopramid, Papaverin, Pilocarpine, Scopolamin

Opiate/Opoids to be avoided: Morphium, Codeine, Pethidine
Alternative: Remifentanil, Alfentanil, Fentanyl, Oxycodone, Piritramide, Tramadol

Other pain meds to be avoided: Acemitacin, Acetylsalicyl acid, Diclofenac, Flurbiprofen, Indometacin, Ketoprofen, Meclofenamic acid, Mefenamic acid, Naproxen, Noscapine, Pyrazolone, Sufentanil, Toradol (Ketorolac)
Alternative: Ibuprofen, Fenbufen, Levamisol, Paracetamol, Cannabinoids

Antipsychotics to be avoided: Bupropion, Carbamazepine, Diazepam, Diphenhydramine, Flunitrazepam, Thiopental
Alternative: Chlorpromazine, Haloperidol, Amitryptiline, Doxepin, Clomipramine, Maprotiline, Clonazepam, Triazolam, Oxazepam
Basically, all antipsychotic medication releases mast cell mediators if administered in therapeutic concentration.

Contrast to be avoided: Contrast dye with iodine (ionic), Gadoliniumchelate
Alternative: Non-ionic contrast dye or mast cell prophylaxis with prednisolone, H1 und H2 Blocker

Other things to be avoided: Latex gloves, ethanol (caution with ethanol in medication)

Albumin solution, NaCl and Ringers solution could be used as plasma substitute.

 

MCAS patients, who went into anaphylactic shock in the past, should always carry an emergency kit with them, containing the following for example:

Ceterizine or Fenistil liquid, Celestamine N liquid, and in case of breathing and circulatory issues an additional epinephrine pen, like Fastject Autoinjektor (learn how to use the pen!).

For patients with asthmatic issues an inhaler containing Salbutamol helps.

 

Emergency medication for MCAS patients

Emergency medication for MCAS patients

 

Sources:

SIGHI
www.histaminintoleranz.ch

 

Sido B, Dumoulin FL, Homann J, Hertfelder HJ, Bollmann M, Molderings GJ. Chirurgische Eingriffe an Patienten mit Mastzellüberaktivitätserkrankung. Der Chirurg. 2014 Apr 1;85(4):327-33.

Pöhlau D, Raithel M, Haenisch B, Harzer S, Molderings G. Neurologische und psychiatrische Symptome der systemischen MCAD. NeuroTransmitter. 2015 Ausgabe 9.

The Mastocytosis Society
http://www.tmsforacure.org/documents/ER_Protocol.pdf

 

Brockow K, Metcalfe DD. Mastocytosis. Current opinion in allergy and clinical immunology. 2001 Oct 1;1(5):449-54.

Afrin LB, Pöhlau D, Raithel M, Haenisch B, Dumoulin FL, Homann J, Mauer UM, Harzer S, Molderings GJ. Mast cell activation disease: an underappreciated cause of neurologic and psychiatric symptoms and diseases. Brain, behavior, and immunity. 2015 Nov 30;50:314-21.

EDNF presentation of Prof. Anne Maitland
http://ehlers-danlos.com/2014-annual-conference-files/Anne%20Maitland.pdf

http://www.mastcellmaster.com

http://ecnm.net

 

http://ehlers-danlos.com/2012-annual-conference-files/Smith_Mast_Cell_Disorders_r2-1.pdf

http://mastcellresearch.com

 

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