In mast cells diseases there are a body of medications to help - Highlighted in Pink as you go through.
Beginners -Read this box and boxes in shades of pink ;-) the detail can come later ;-)
Mast cell conditions currently aren't curable but are VERY managable .
You will have looked at the symptoms lists. These are listed by the chemical out of mast cells . The medicines are listed by the chemical and which receptor in the case of histamine they work on. The medications sit in the point on a cell wall were the chemical would sit to cause symptoms -so block that place-called a receptor .
So we understand that the contents of mast cell cause symptoms. these are -
Mast cell stabilisers
Other meds -
and inert ingredients
From humble beginnings as a remedy for seasickness, antihistamines were serendipitously found to have beneficial effects on allergy symptoms. Even now, most of the commercially available products for seasickness are antihistamine drugs. But over the years there have been tremendous strides made in the science of antihistamines.
An antihistamine is not actually the opposite of histamine. Rather, it is a drug (an antagonist) that binds to certain sites (receptors on cells) in the body, in order to prevent histamine from binding. Histamine must bind to these receptors in order to cause a response.
Histamine has 4 recptors ,2 we have medications for . I will refer to these as H1 and H2 . H3 and H4 have drugs in trials.
H1 recptors are found in - Skin, Digestive tract, Brain (inside and lingings ) nerves , eyes, ears, nose , mouth, tounge, throat , upper and lower airways , heart and blood vessel walls .
Medictions which block H1 receptors
There are 2 types of H1 drugs Non drowsy and Drowsy
Non drowsy -Typically once daily dosing . In mast cell these are used a higher doing under medical supervision
Lortetidine (claratin ,clarinex)
Ceterizine ( UK Benadryl , zyrtec )
Fenofexidine (UK telfast )(USA Allegra)
Drowsy h1's cause drowsiness in some mast cell patients. those who expereince this find it passes off in about 2 weeks .
Piriton -Chlorphenamine melate - Note liquid contains alochol for those very sensitive to alcohol
Benadryl-USA = Nytol UK =
Hydroxyzine hydrocholoride -Ucerax UK ,Atarax (USA)
Histamine Receptor 2 -In the disgestive system , heart and blood vessels.
Cimetidine -is a NO - it stops histamine being broken down so makes the probem worse
Most Mast cell patients with systemic conditions-affecting the whole body need two h1 blockers, One H2 blocker and a H1 used for emergency medication .
Prostoglandin production from Mast Cells
Prostoglandins are made from the fat released from the mast cell wall when it is stimulated to release contents . This is turned into aldronic acid - which then becomes prostoglandins -D2 and F2 .
- open up blood vessels to bring more blood to the site of injury/inflammation
- Make smooth muscles contract clearing the body of precieved pathogens
- Airways in lungs , mouth to bottom, bladder , womb
- Cause anxiety
Paractamol / Tylenol
Is a sailiclate which blocks COX 1 preventing production of Postaglandins and prevents -
Vasdodilation- opening of blood vessels
= low Blood pressure, flushing , headaches from blood vessels opening in enclosed spaces like the skull
Blocks crth2-and so-
Stops production of mucous
Stops production of IGE
Stops airway hyperresponsiveness
stops production of interleukin 4, 5 and 13
Allows crth2 cells to die
Nsaids - Aspirin, diclofenac ibruprofen - block cox 1 .
Aspirin and diclofenac contain ascetic acid- vineger which is atrigger for some patients so should not be used in those patients
Has seen sucessful use in producing continious mast cell mediator release to prevent peaks and associated anaphylaxis
any of a group of compounds derived from unsaturated fatty acids, primarily arachidonic acid, - By 5-lipoxygenase - that are extremely potent mediators of immediate hypersensitivity reactions ( allergic reactions from various triggers) and inflammation, producing smooth muscle contraction, especially bronchoconstriction, increased vascular permeability, and migration of leukocytes to areas of inflammation. Certain leukotrienes are collectively known as SRS-A (slow reacting substance of anaphylaxis), the name given to their potent bronchoconstrictor activity 30 years before their structure was elucidated; they also cause leakage of fluid and proteins from the microvasculature.
Miller-Keane Encyclopedia and Dictionary of Medicine, Nursing, and Allied Health, Seventh Edition. © 2003 by Saunders, an imprint of Elsevier, Inc.
Their production accompanies production of hsitamine
Leucotrines are also made from Arachidronic acid from mast cell mebranes
They have individual functions and interact with other mast cell contents .e.g Leucotrine 5 (LE5 ) works on the same cells as prostoglandin D2 . ( see medications ) and image below .
A4-Is involved in the production of B4
for full detail see mast cells .
- Spasm of airway muscles -smooth muscle contraction .
- Spasm of oter muscles -bladder, mouth -bottom
- Swelling and fluid loss from blood
- Low blood pressure
They are relased in higher volumes at night , causing night time waking and day time low energy
TNF alpha- Tumor necrosis factor alpha - Comes from mast cells and is also produced from Leucotrine B4 ( LTB4)
Has affects all over the body
In the hypothalamus:
Stimulation of the hypothalamic-pituitary-adrenal axis by stimulating the release of corticotropin releasing hormone (CRH)
On the liver: stimulating the acute phase response, leading to an increase in C-reactive protein and a number of other mediators. It also induces insulin resistance by promoting serine-phosphorylation of insulin receptor substrate-1 (IRS-1), which impairs insulin signaling
Increases gut permability ,leading to more protiens getting into the blood . These are then treated as non self and antibodies made/immune response activated .
TNF alpha blockers - reduce the actions and release of TNF alpha .
Enbrel- Enteracept is the longest used
Because these drug reduce the abilities of the immune system to act. Those taking it are at high risk from any infections .
Reported Dec 2012 to have cred angiodeama in a patient with crones
Leucotrine blockers are avilable . Zyflo blocks before leucotrines are made and the production of TNF aplha and IL beta .
Montelukast blocks leucotrines from working on cyst1 receptors .
Leukotriene inhibitors (or modifiers), such as montelukast (trade names Singulair and Montelo-10), zafirlukast, Pranlukast and zileuton,
Improvements in -
Airway symptoms -wheeziness , swelling
Over all swelling level
Caution -Montelukast has been reported to cuase depression so if you are depressed then this should be bourne in mind.
Mast cel stabilisers - make mast cells release less hitamine and prostoglandins and heparin .But does not block the relase of cytokines /interlukins .
Cytokines /interleukins are important in many functions .
Resreach continuing as to wether other mast cell chemicals are reduced in volumes released e.g -Others made on activation - leuoctines , platlet activating factor ,tnf alpha at 12 hours
and those stored in granules - serotonin ,tnfalpha -immediate relase - chymase , tryptase , renin
BUT - It cant block all mast cell action as it is needed within the immune system .
This explains why some patients get little benfit from gastrocrom were as others get a huge amount .
Sodium Cromlyn - "gastrocrom "or "Nalcrom"
Is a mast cell stabiliser . It is poorly absorbed into the wider circulation . 57mg remains out of 800mg daily oral dose . This is because the majority is removed from the circulation by the liver .
At this dose it reduces bone pain, flushing and brain fog. It takes 6 weeks to begin working and needs 6 months to see full benefit
Recant research has proven quercitin is more effect than gastrpcrom alone is reducing histamine and prostoglandin release ( (Theoharidies 2012) research into which combination should work best of gastrocrom , quercitin and ketitofen is now underway
Sodium cromlyn -can be used on an individual system or at higher doses to get some systemic benfits -
Gastrocrom is expensive - a generic now exists but some paients who have swapped have found it less effective . It takes 6 weeks to bein being effective and is at its max after 6 months .those who find it works replort less overall histamine , prostoglandin and heparin symptoms and less bone pain and brain fog at 6 months .
Inhaled sodium cromlyn is availble in a
Intal - nebulaiser . It is also availble in
Rynacrom - nasal
eye preperations .
Ketitofen is also a well used mast cell stabiliser- which is also a histamine recptor 1 blocker . USA -it cna now be ordered and imported on a physicans prescription - follow link .
Ketotifen - lowers tnfalpha after 10 weeks .
Doxepin is an antidepressant but it has mast cell stabilising and blocks histamine receptor 1 and histamine recptor 2 . Some patients find that they dont tolerate doxepin because it raises serotonin and some mast cell pts have high serotonin from mast cells and plateltts degranulating .
Patients report - using gastrocrom and ketitofen togther works better than any one drug alone .
Cyclizine is ahistamine receptor 1 blocking antisickness . Which can be given orally , under the skin (subcuatniously )or into avein ( intravenous )
Like many H1 blockers it can cause drowsyness
Absolute NO's - Metroclopamide ( maxalon )
Ondnasatron and family of drugs can be effective with serotonin and histamine nausea
Most patients with mast cell conditions will have some pain from the histamine actions on nerves directly , from bone pain, pain from swelling and spasms .
Pain is also a trigger of Mast Cells .
Paracetamol and Tramadol are recognised as the 2 safe ana;gesics in mast cell conditions
Opiates are known to cause mast cell degranulation and are not tolerated by most patients .
NSAIDS - are tolerated by some but not others . Aspiirin and ibruprofen aren't tolerated by pts with vinigars as a trigger
Medications with muscle relaxant properties-
- Buscopan- hyocine butylbromide
Can interact with antihistamines causing enhanced drowsyness . In me this =sleeping like a baby ( BNF interactions 2012 )
If pain is an issue , this should be discussed witha mast cell speclaist .
Tricyclics should not be used for neuropathic pain due to them interactiong with EPIPENs (BNF interactions 2012 )
Gabapentin is used by many patients for the neuropathic pain . pregablin has not been trialed in patients with mast cell conditions
SSRI's/SSNI's - are poorly tolerated , so not used for neuropathic pain in mast cell . Esp in patients who have high serotonin . With the risk of serotonin syndrome
Anxiety is both a symptom and trigger of mast cell activity
The symptom part comes from histamine affecting the mood centres in mixed organic brain syndrome aka brain fog . This mainfests in patients as annoyance, irritability or rages .
Also from prostoglandin release .
Alongside h1 and prostoglandin treatments . Benzodiazepines are favoured for use in anxiety in mast cell .
Happens in mast cell . Some patients have clincially low serotonin but many have high .
Treating it is challenging . Tetracyclics are the best tolerated .
Tricyclics interact with epinpeherine ( EPIPEN ) causing high blood pressure and arrythmias (BNfinteractions 2012)
SSRI/SSNI - have the risk of increasing serotonin and causing serotonin syndrome
MOAI's are tolerated but not popular with patients as they have dietery restriction and most patients already have highly restricted diets
See Big change
Heparin comes out of mast cells also through acting on histamine recptor 3 more is relased from cells. This circulates in high levels . This leads to clacium been drawn out of the bones continiously . This leads to - low other risk- osteoprosis in any/ all mast cell patients . Poor gut absorbtion of clacium and vitamin d compounds the problem .
ALL MAST CELL paients should have a BONE DENSITY SCAN ON DIAGNOSIS
- This should be replaced with vitamin d and claium supplement -with consideration to risk of formation of kidney stones
- Biphosphonates can be used -but there is ableeding risk and increased bone pain associated with this
- Mast cell stabilisers reduce the overall level of heparin circulating and can halt bone loss
The high calcium circulating can lead to renal stones .
Any pain on either side of the abdomen by the bottom of the ribs at the back may be kidney stones and needs investigating . This is done with a ultrasound scan which is painless and extrenal to the body .
The high heparin can lead to bleeding - from nose, bottom , womb - between cycles or post menopausal . ANY new bleeding must be investiaged and if no cause is found , then it could be attributed to mast cell .
Inert Ingrdeients as Triggers In Mast cell and Idioapthic Angiodeama
In mast cell we are aware of our triggers . In the early stages, which you may be in , you may not know your triggers and find the idea of introducing new medications rather worrying .
Each patient with mast cell is individual in their triggers . Many have no problems with the inert ingredients but some of us do .
This is a list of things which I know bother various people . With hints as to wether this is likley to be a problem for you ;-)
Corn starch , maize starch , modified maize starch
- If you find you react to custards and gravies .
Alcohol - Ethnol
-Alcoholic beverages are obvious . 50% of mast cell patients have problem with alochol as a trigger . You are likley to have worked this out elsewere ;-)
- In capsules also pre geltinised corn flour
- If jelly (o) is a problem for you
Vinegar -Ascetic acid
- If you have found meals give you instant stomach acid pain.
- in many products inc breakfast cereals
- availble as a sugar subsitute "splenda" .used in some hospitals
Asulphamine K (potassium)
- if you are avoiding diet drinks
To show ho we need to follow our bodies -
i don't tolerate - sodium leureth sulphate
=itching all over , so I have aspartamine . But a freind of mine , also a mast cell patient can't
tolerate aspartamine at all she has sodium leuereth sulpate instead !!!!!
What is most important is to listen to your body ;-)
Mast cell is good at complaining ;-)
Acute episodes of hereditary angioedema do not respond to adrenaline, antihistamine and corticosteroids.
Fortunately most acute episodes of Type I and II hereditary angioedema are non life-threatening.
The mainstay of emergency medical treatment is intravenous C1 inhibitor concentrate (a blood product).
If this is unavailable, fresh frozen plasma can be infused, but this occasionally exacerbates the angioedema.
New medications inhibit bradykinin, e.g. icatibant, or kallikrein, e.g. ecallantide. Ecallantide has been reported to cause anaphylaxis in some cases.
The chance of an attack can be reduced with the following medications
C1 inhibitor concentrate infused an hour before a surgical procedure
Anabolic steroids (stanazolol, oxandrolone and danazol) to increase circulating levels of normal functional C1 inhibitor. These have 'male-like' hormonal activity, so may cause weight gain, menstrual irregularities and virilism ( masclinistaion -hair ) .
Tranexamic acid has been used in pre-pubertal children and may be effective in Type III herediary angioedema.
As a Guide -Most mast cell patients need 2 Histamine recptor 1 blockers 1 histamine recptor 2 blocker , a prostoglandin blocker , a leucotrine blocker =/- a mast cell stabiliser . If symptoms arent controlled on this then immune modulation is used .
This is begun with h1 and h2 blockers, then Leucotrine blockers added ,then other meds.
We also use a H1 blocker as an emergency medication. the drowsy ones work for this -Piriton or Nytol(UK) which is benadryl US .
All Drugs have 2 names (at least ) the trade name -Given by the developing drug company and the generic Name -which is the same the world over . In this I use the gneric names with brand names in brackets . The generic is written on all boxes in smaller writing .
Drugs are made by companies and sold by the soley for 7 years . There is much debate wether generics are as good as the brand drugs for patients .
In mast cell patients find they have problems with certain inert ingredients ( see bottom of page ) so this should guide drug preperation choice .
For example the author does better mostly on branded drugs except ceterizine which I tolerate the generics better
Tips on finding hiding absolute NO's and patient triggers
-Alochol wipes for skin, surfaces , in cleaning products and personal care products , creams and ointments , moisturisers
-Dextran /dextrin -in eye drops , many sweetened products inc breakfast cereals .
-Gelatin - medical exmaination gels , ECG tabs, Defib pads (possibly) Ultrasound gel (also alcohol )
Premedication as per protocol ( at bottom of page ) should be used for any invasive procedures or surgery . Guidlines on safest anesthetic also at the bottom of the page
WHAT YOU SHOULD KNOW ABOUT ANESTHESIA – IT COULD SAVE YOUR LIFE
Nancy Gould and Regis (Gigi) Park
Surgery is a stressful experience. For a patient with mast cell disease, that stress is compounded by the possibility of complications including anaphylaxis, cardiovascular collapse, increased bleeding and even death. Therefore, general anesthesia is considered a high-risk procedure in patients with mast cell disease. It is critical that all members of the patient’s operating team take proper precautions before, during, and after surgery to protect against
potentially life-threatening mast cell activation
PLANNING FOR SURGERY SHOULD BEGIN AS SOON AS THE NEED FOR SURGERY ARISES
It is imperative that good communication is established between the patient, referring physician, surgeon, anesthesiologist, nurses, and all others involved in the patient’s care before, during, and after surgery. The surgeon must be aware of the patient’s mast cell disease and inform themselves of the measures necessary to keep the patient as free of symptoms as possible. Additionally, the patient should contact the anesthesiologist assigned to their care as soon as possible after surgery has been scheduled. Both regional and general anesthetics can cause lifethreatening complications. An experienced anesthesiologist is aware of medications known to cause mast cell
degranulation and medications that stabilize mast cells. If the patient is satisfied that their anesthesiologist fully understands the importance of planning around the mast cell disease, it will go a long way toward calming the patient, which in turn may reduce mast cell mediator release.
Symptoms should be as well-controlled as possible in the days prior to surgery. The patient should carefully avoid known triggers of mast cell activity and should take their medications as prescribed. Those medications include H1 and H2 histamine receptor blockers such as Allegra (H1) and Zantac (H2). A mast cell stabilizer such as disodium cromoglycate or ketotifen, and medications targeting other mast cell mediators should be taken regularly if they are
part of the patient’s normal drug regimen.
The patient’s complete medication list should be reviewed by the surgical team prior to surgery and any necessary medication changes should be thoroughly discussed with the patient. For example, if the patient regularly takes a
medication in the family known as beta blockers for blood pressure or heart rate abnormality, a change to another drug should be considered well before surgery is scheduled. Beta blockers are generally avoided in people with mast cell disease undergoing surgery because they interfere with an important natural control of mast cell activation. These drugs may also interfere with the use of epinephrine, which may be required if the patient has a major release of mast cell mediators resulting in low blood pressure during surgery. Other drugs that may interfere with control of blood pressure during surgery must be carefully reviewed by the patient’s physician before the
surgery. It may be necessary to perform a “graded challenge” procedure in the hospital under the supervision of an allergist and an anesthesiologist for certain medications if there is no history of exposure to that medication. This procedure usually starts with scratching the skin with a small amount of medication followed by injection of increasing amounts with careful monitoring after each injection. Resuscitation equipment and drugs including epinephrine must be readily available during the procedure.
PRECAUTIONS TAKEN IN THE HOURS PRIOR TO SURGERY WILL HELP THE PATIENT GO
INTO SURGERY IN THE BEST POSSIBLE CONDITION
For pre-operative control of anxiety and the reduction of mast cell activity, drugs in the valium family (diazepam, midazolam, lorazepam) are usually effective. Some procedures require the patient not to take anything by mouth including medications after midnight of the night before the surgery. In this case, H1 and H2 blockers should be administered intravenously prior to the surgery. The use of corticosteroids, such as prednisone, has also been suggested although there is no evidence that the short-term use of steroids reduces the ability of mast cells to
release the chemicals contained in their granules. However, corticosteroids may reduce the extent of other inflammatory reactions that result from mast cell activation. A tube may be inserted into an artery and attached to a device allowing the anesthesiologist to vigilantly monitor
blood pressure without having to periodically inflate a blood pressure cuff. In addition, a tube is inserted into a vein and securely taped in place, with intravenous (IV) fluids running to keep the patient well-hydrated in all surgeries involving general anesthesia or conscious sedation. This tube will also make it possible to immediately administer any emergency medications that may be needed. In the operating room, the patient should not be allowed to become either too cold or over-heated. Warm blankets should be used, and all IV fluids should be warmed before they are given. In addition, there should be a minimum of noise and bustle around the patient prior to the administration of the anesthetic in order to reduce the possibility of anxiety-triggered mast cell mediator release.
An emergency situation may arise in which a person with mast cell disease requires immediate surgery. Wearing a MedicAlert bracelet could be a life-saver if this happens. Inscriptions vary depending upon the patient’s specific needs, but generally include the patient’s diagnosis and drug sensitivities. Emergency response team members can
access more detailed information 24 hours a day, 7 days a week from the MedicAlert organization by dialling the toll-free number on the bracelet. MedicAlert is a non-profit organization serving patients world-wide. There are nominal membership and annual fees with financial assistance available for those in need. For more information,
please visit www.medicalert.org or dial 888-633-4298 within the U.S. or 209-668-3333 from outside the U.S.
Alternatively, there are several companies that manufacture and inscribe medical identification jewellery. These products are available on the internet and are also carried by some jewellery stores and pharmacies. It may be wise to select jewellery which provides space for a miniature version of the patient’s medical history (often supplied by
the manufacturer as part of the cost) in addition to the inscription. Although these companies do not have a 24 hour information center, they do not require membership or annual fees and may be preferable for some patients. It may also be helpful for mast cell patients to carry with them at all times emergency information, written on their physician’s letterhead, which contains a list of current medications and other instructions for treatment in the event of severe symptoms.
Constant attention from the anesthesiologist is required for the safety of a patient with mast cell disease during surgery, as some of the early symptoms of mast cell mediator release such as flushing, hives, and early signs of obstructed breathing can be masked by the surgical drapes covering much of the patient’s skin and by the use of an airway tube during anesthesia.
Should anaphylaxis occur during surgery, the drug thought to be responsible should be discontinued immediately and epinephrine should be administered. Airway support with 100% oxygen, IV replacement fluids to compensate for dilated blood vessels, H1 and H2 antihistamines, bronchodilators, and corticosteroids may also be given.
Continuous IV epinephrine and other “vasopressor drugs” may be necessary to keep blood pressure from falling.
However, it is important to keep in mind that not all hypotensive episodes during surgery are due to mast cell degranulation and anaphylaxis. A serum tryptase level obtained during the hypotensive episode and its comparison with pre-surgery or “baseline” level may be helpful to determine whether the episode is due to mast cell degranulation.
Records from prior surgeries should be examined and drugs tolerated in those procedures should be preferred if possible. Prior to the administration of any drugs associated with surgery, it is important that an IV is running, that
epinephrine is available for immediate intramuscular (IM) or IV administration, and that emergency equipment is
easily accessible in case of an adverse reaction.
IV preparations without preservative should be used.
Drugs to avoid include ethanol, dextran, and non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen
and toradol (unless the patient is already successfully taking a drug in this family), polymyxin B, amphoteracin B,
quinine, dextromethorphan, α-adrenergic blockers, β-adrenergic blockers, and anticholinergic drugs as well as
drugs mentioned in specific categories below.
Local anesthetics – True allergic reactions to local anesthetics resulting from mast cell degranulation are thought
to be rare. Skin testing and graded challenge protocols have been published and may be administered by an allergist
prior to the surgery if questions arise regarding the safe use of a local anesthetic in a patient. If possible,
preservative-free local anesthetic should be used in these tests, as the preservative often present in local anesthetics
can cause a mast cell reaction. In general, local anesthetics in the “ester” group should be avoided. This group
includes procaine, chloroprocaine, tetracaine, and benzocaine. Anaphylactic reactions to local anesthetics in the
“amide” group are rare. This group includes lidocaine, mepivacaine, prilocaine, bupivacaine, levobupivacaine, and
Muscle relaxants - Muscle relaxants are the most likely group of the anesthetic drugs to cause anaphylaxis.
Succinylcholine, D-tubocurarine, metocurine, doxacurium, atracurium, and mivacurium are more likely to cause a
severe reaction than rocuronium or the so-called nondepolarizing muscle relaxants such as pancuronium or
vercuronium. Some studies have reported increased numbers of anaphylactic reactions to rocuronium, however, so
it may not be appropriate as the first choice for patients with mast cell disease.
Induction drugs - These are medications given to initiate anesthesia. It is rare for mast cell activation to occur in
response to the use of propofol, ketamine, or the benzodiazepine drugs such as midazolam.
Inhaled anesthetics - Sevoflurane is an inhibitor of mast cell activation and is less likely to cause liver damage
than other inhaled anesthetics in this family.
Opiates and opioids - Oral opioid drugs for pain relief may be tolerated by some mast cell disease patients, but
their use should be approached with caution, beginning with very small doses. All drugs in this category are
capable of causing mast cell mediator release.
Surgery for a person with mast cell disease involves exposure to drugs and conditions that may trigger extensive
mast cell degranulation. It should be emphasized that it is often impossible to predict or avoid the risk of adverse
events which may occur in surgery due to the administration of drugs and the procedure itself. The risk can be
reduced, though, if the mast cell disease is brought to the attention of everyone involved in the patient’s care and
measures are taken to reduce the possibility of mast cell mediator release. Careful planning is important, beginning
from the time a need for surgery has been defined and continuing through the immediate pre-operative period,
anesthesia, surgery, and recovery. The choice of drugs is of major importance, and the anesthesiologist, the
surgeon, the nursing staff, the patient’s physician, and the patient should form a working team to ensure that
surgery presents the fewest possible dangers for the patient.
Neither The Mastocytosis Society nor the authors intend that this information replace medical advice
given by the patient’s doctor. Patients are encouraged to consult with their doctor regarding medications
and procedures related to surgery.
Hazards in operative management of patients with systemic mastocytosis; HW Scott Jr, WCV Parris, PC Sandidge,
JA Oates, LJ Roberts II; Annals of Surgery, May 1983;197(5):507-514
Anesthetic management of systemic mastocytosis: experience with 42 cases; WCV Parris, HW Scott, and
BE Smith; Anesthesia and Analgesia (1986)65:S117 (Abstract)
Urticaria Pigmentosa: An anesthetic challenge; Eric P Greenblatt, Linda Chen; Journal of Clinical Anesthesia,
Mastocytosis: Perioperative considerations; VA Goins; AORN Journal December 1991;54(6):1229-1238
Anesthesia in a patient with malignant systemic mastocytosis using a total intravenous anesthetic technique;
A Borgeat and YA Ruetsch; Anesthesia and Analgesia (1998);86:442-444
Treatment of systemic mast cell disorders; AS Worobec; Hematology/Oncology Clinics of North America (June
Treatment of mastocytosis: pharmacologic basis and current concepts; G Marone, G Spadaro, F Granata,
M Triggiani; Leukemia Research, July 2001;25:583-594
Mastocytose: Anesthésie générale par rémifentanil et sévoflurane; L Auvray, B Letourneau, M Freysz; Ann Fr
Anesth Réanim 2001;20:635-638 (article in French)
Mastocytosis: Current concepts in diagnosis and treatment; L Escribano, C Akin, M Castells, A Orfao,
DD Metcalfe; Annuals of Hematology (2002);81:677-690
Anaphylaxis during the perioperative period; DL Hepner and MC Castells; Anesthesia and Analgesia
The authors wish to thank Cem Akin MD, PhD, for his review of this article.
Copyright 2010. The Mastocytosis Society, Inc. All Rights Reserved.
Valerie M. Slee, Chair, Board of Directors
23 Camelot Dr. Shrewsbury, MA 01545 • Phone: 508-842-3080 • Fax: 508-842-2051 •
E-mail:firstname.lastname@example.org • Web: www.tmsforacure.org
The Mastocytosis Society • P.O. Box 731 • Brenham, TX 77834
Medical Emergency Response Plan
for Systemic Mastocytosis, Mast Cell Activation, and Anaphylaxis
If the patient presents with flushing, rash, hives, swelling, abdominal pain, nausea, vomiting,
shortness of breath, wheezing or hypotension, respond with the following:
• Epinephrine 0.3 cc of 1/1000 and repeat 3x at 5-minute intervals if BP < 90 systolic (0.1 cc
for children under 12)
- Piriton -Chlorpherimine mealate -10mg IV (UK)
• Benadryl (Generic: diphenhydramine)(NOT CETERIZINE ) 25-50 mg (12.5-25 for children under 12) orally,
intramuscular or intravenously every 2—4 hours or (USA)
Atarax (Generic: hydroxizine) 25mg
(12.5 mg for children under 12) orally every 2—4 hours
- Solucorcef ( generic hydrocortisone ) 200mg IV/IM (UK)
• Solu-Medrol (Generic: methylprednisolone) 120 mg (40 mg for children under 12) IV/IM
• Oxygen by mask 100% (15L) or nasal canula maximum 5l
• Albuterol nebulization
-IVI -NOT DEXTRAN
Call 999 / 911 and take the patient to the closest Emergency Room.
Add IV ranitidine if availble
Pre-medication for major and minor procedures and for radiology procedures
with and without dyes:
• Prednisone 50 mg orally (20 mg for children under 12) 24 hours and 1—2 hours prior to
• Benadry1 (Generic: diphenhydramine) 25-50 mg orally (12.5 mg for children under 12) or
Atarax (Generic: hydroxizine) 25 mg orally, 1 hour prior to surgery
• Zantac (Generic: ranitidine) 150 mg orally (20 mg for children under 12) 1 hour prior to
• Singulair (Generic: montelukast
10 mg orally (5 mg for children under 12) 1 hour prior to
Drugs to be avoided:
• Aspirin and non-steroidal anti-inflammatory medications
• Morphine, codeine derivatives
The Mastocytosis Society thanks Dr. Mariana Castells for this emergency protocol.
Adapted with UK anaphylaxis guidelines and drug names
Supplements - as with all conditions many supplent options can pop up.Supplenets are regualted by food not drug guidelines and as such are not drugs .
Severalsupplenets are known to be useful in Mast cell .These are the result of medical research .
Vitamin C -Up to 750mga day -mast cell sabiliser
Vitamin c is
Quercitin and bromlyn - In sachet form or tablets -mast cell tabiliser
leutolin from olive oil
All medicatons have side effects . How you deal with this is very individual .I operate.If I know its safe fr me from a mast cell point of view and is ok preperation wise - see lower .Then I commence it and don't look at the side effect list .If I get a new symptom - absolutely new as its easy to blame existing symptoms on meds . esp if you don't like taking meds ;-) Then I check to see if its a side effect .
Medication weight - with a mast cell diseases we will typically be on 4-10 medications several times a day .This can be very hard to level in your mind .Part of it is the age old - maybe ive got better and dont need them anymore ;-0) yes, ive been there, even with my medical background . From chatting to many masties .We all seem to go through this and not wanting meds or messing with them can be a large part of denial .(see big change )
If you understand that your mast cells are splitting putting chemicals into your system . Then protecting yourself from the effects from them seems sensible .
Will the meds harm me - All the meds we use have long term good safety records . There are patients who have been on meds for over 30yrs and have not had any negative effects from the drugs .
I see it like a chemical barrier protecting me from reactions .A freind sees it as a cage , to control her gremlin .
Drug Interactions -
There is a wealth of knowldge on how drugs work together .Pharmacists are speclaist in interactions . There are safe reliable publications which are not drug company information (promotional material based .
When beginning any new medication ,supplemnet or hebal / homeopahathy preperation you should check with a parmacist that it wont mix badly with any current meds .
By doing this you will prevent any problems .There is a full list of NO drugs in Mast cell - to be avoided at the bottom of this page .
Antihistamines can cause drowsiness . Many mast cells patients dont get this as a side effect .But if you do it normally passes off after 2 weeks .
Antihistamines can be drying so you may find your alittle dry up your nose ;-)
Antihistamines -in non mast cells pts cause high pulse .
BUT in mast cell patients the antihisatmines stop that histamine thats in your system -
- Making your heart go fast - so you feel better
- Making your blood vessels porous so you swell up
- Stops you felling dizzy because you havent lost fluid so your blood pressure is perfect
Is traditionally treted with oral nysyatin-this contains sulphites .Or with creams and pesseries .These contain corn flour and alochol .
Oral fluconazole is useful alterntive availble in liquid form if capsules are aproblem .
There are several drugs in Trials .
Masitinib, a selective oral tyrosine kinase inhibitor, effectively inhibits the survival, migration and activity of mast cells. This is being trailed for MS and with patients with systemic mastocytosi in Poland - Phase 3 .
Mastinib has been used sucessfully in dogs with mast cell disease . These trails are looking into how this drug works in specific conditions .
Histamine receptor 3 blockers
Histamine receptor 4 blockers
Histamine receptor 3 was discovered in 2003 . Since then drug companies have indenfied agents which block it and these are in clinical trials. There are several phases to clinical trials . The stage of FDA approval apply to all government approval worldwide . Different countries approve different drugs.
Histamine receptor 3 blockers are in phase
Ciclosporin reduces the activity of the immune system by interfering with the activity and growth of T cells.
As we know (from about mast cells page ) t cells have a central role in producing antibodies and for killing bad cells as the come into the body ( tkiller cells ). Alongside directly actiavting mast cells .they produce interferons and cytokines which cause mast cell activation and have many functions within the immune system .
So reducing these activities is usefull in autoimmune mast cell activation .
It can cause liver problems and dosing has to be done carefully with regualr levels being taken on commencement weekly and longterm at set intervals -normally monthly. When the levels of cliclosporin are checked liver function is checked at the same time .
Used in organ trasnsplant to avoid rejection , psriosis and many other t cell autoimmune conditions
It acts by inhibiting the metabolism of folic acid.
It is used in treatment of cancer, autoimmune diseases, ectopic pregnancy, and for the induction of medical abortions.
It is used as a treatment for some autoimmune diseases, including rheumatoid arthritis, psoriasis, psoriatic arthritis, lupus and Crohn's disease, to name a few.
Although methotrexate was originally designed as a chemotherapy drug (in high doses), in low doses methotrexate is a generally safe and well tolerated drug in the treatment of certain autoimmune diseases. Because of its effectiveness, low-dose methotrexate is now first-line therapy for the treatment of rheumatoid arthritis. Though methotrexate for autoimmune diseases is taken in lower doses than it is for cancer, side effects such as hair loss, nausea, headaches, and skin pigmentation are still common.
It is a potent chemoattractant - creates asignal which attracts - neutrophils, and promotes the expression of adhesion molecules on endothelial cells ( mast cells ) , helping neutrophils migrate.
On macrophages: stimulates phagocytosis, and production of IL-1 oxidants and the inflammatory lipid prostaglandin E2 PGE2
On other tissues: increasing insulin resistance.
A local increase in concentration of TNF will cause the cardinal signs of Inflammation to occur: heat, swelling, redness, pain and loss of function.
Whereas high concentrations of TNF induce shock-like symptoms, the prolonged exposure to low concentrations of TNF can result in cachexia, a wasting syndrome.
A H1 and H2 blocker
10mg up to 3x a day
150mg twice aday (up to 300mg twice a day )
Download on medical staff page
Medications of interest include -
tranilast -TNFalpha blocker
IUPAC Name [(3R)-4-(4-chloro-benzyl)-7-fluro-5-(methylsulfunyl)-1,2,3,4-
A prostoglandin D1 recpetor blocker of flushing ;-) At expereimental stage
conatains vinigar so same issue with other meds apply (aspirin ) but is actually ablocker not a stop it being made - drug
also contains sulphur
UNDER THE RADAR - Many of us find that beginning with standard doses brings side effects .It has been noticed and it works -that by beginning with a small increnet of the full dose . begin low and increase it each day over aperiod of time .How long it will take to get to full dose depends on many factors - please understand this does NOT apply if it cuases any allergic /anaphylatic sysmptoms -Then it should go on the naughty list