ResourceS

This webpage contains information and handouts to help you manage your condition.

supplements

  • Supplements are provided to patients through Fullscript. Access your account to Dr. Abbott’s dispensary here. 

Mast Cell Activation Syndrome and other Mast Cell Disorders

There are many medications that can act as mast cell activators. Below is a list of medications that either have a known or theoretical risk of activating mast cells and preferred alternatives to those medications. Note that people with mast cell disorders can have variable reactions, and the medications in the "Generally lower risk" list may be a trigger, or one in the "Higher risk" list may be fine for you. This is a general guideline. If you are taking medication you are concerned is causing a reaction, schedule an appointment or talk with your doctor about if and/or how to discontinue that medication.

Important: This document is educational and not a substitute for individualized medical advice. Medication tolerance varies substantially between patients with mast cell disorders.

Medication Class Higher risk / use caution Generally lower risk / often tolerated
Hypnotic/sedative/Anesthetic agents Methohexital, thiopental (causes histamine release), and phenobarbital dexmedetomidine, etomidate, propofol and ketamine.
Inhalant anesthetics Halogenated (isoflurane, sevoflurane, desflurane), and nitrous oxide
Local anesthetic Ester-type more commonly cause reactions: tetracaine, procaine, benzocaine.

Many reactions may occur from preservatives (e.g. methylparaben), sulfites, epinephrine additives

 Amide local anesthetics are generally preferred over ester-type. Amide options in order of preference: bupivacaine, ropivacaine, lidocaine. Opt for preservative free.
Opioids All can trigger mast cell mediator release, avoid if possible. Best options in order of preference (may require adjunct treatment with Zofran/ondansetron due to nausea/vomiting risk):

-Lowest risk: fentanyl (minimal histamine release), sufentanil, alfentanil, remifentanil

-Moderate risk: piritramide, tramadol,  buprenorphine,  Hydromorphone (twice the risk of fentanyl for urticaria), oxycodone, hydrocodone, tapentadol, oxymorphone

-Highest risk: morphine, codeine, Meperidine / pethidine
Nonopioid analgesics NSAIDs (ketorolac, etodolac, nefopam, aspirin, ibuprofen, nabumetone, indomethacin) can increase leukotrienes which is a mast cell mediator.  Note that aspirin can sometimes be used therapeutically in MCAS for elevated prostaglandins.  Celecoxib/Celebrex and/or meloxicam may be better tolerated than other NSAIDS. Acetaminophen, paracetamol, and metamizole
Benzodiazepines Clonazepam. Midazolam and diazepam are likely acceptable, but cause in vitro (test tube) histamine release from mast cells.
Muscle relaxants Nondepolarizing benzylisoquinolines: atracurium and mivacurium cause histamine release.

Nondepolarizing aminosteroids: rocuronium. Rocuronium is one of the more common causes of perioperative anaphylaxis overall, but not necessarily associated with increased incidence in MCAS patients.

 Nondepolarizing Neuromuscular blocking agents: cis-atracurium. This one is generally preferred.

Depolarizing neuromuscular blocking agents: succinylcholine.

Nondepolarizing aminosteroids: pancuronium. Vecuronium is likely acceptable, but causes in vitro (test tube) histamine release from mast cells.
Antibiotics Vancomycin and polymyxin B can cause histamine release, cefuroxime, Gyrase inhibitors, and fluoroquinolones. Fluoroquinolones are also contraindicated in connective tissue disorders as well due to increased risk of tendon rupture and aortic aneurysm/dissection. Roxithromycin, Penicillins, cephalosporins, sulfonamides, and clindamycin
Antidepressants SSRIs (can trigger MCAS, however some patients may tolerate), Bupropion

TCAs with antihistamine properties often beneficial: doxepin, amitriptyline, and clomipramine.

Maprotiline may also be well tolerated.

SNRIs such as duloxetine, and venlafaxine have a variable impact, but may be tolerated in some.
Anticonvulsants Carbamazepine, and topiramate Clonazepam
Peptidergic drugs Icatibant, cetrorelix, sermorelin, octreotide, and leuprolide
X-ray and MRI contrast medium Iodinated contrast medium, and gadolinium chelate (Gd3+). Macrocyclic gadolinium chelate may be a better option such as gadobutrol, gadoterate meglumine, and gadoteridol. Ones that have a higher adverse incidence are linear gadolinium agents such as gadopentate dimeglumine, and gadodiamide. Consider premedication if these are necessary.

*Prior contrast reaction history is more predictive than diagnosis of MCAS alone.

 Non-ionic contrast media preferred: iohexol, iopamidol, iopromide, ioxilan, ioversol, iotrolan, and iodixanol
Plasma substitutes Hydroxyethyl starch, and Gelatine-based plasma substitutes Albumin solution, 0.9% NaCl solution, and Ringer's solution
Cardiovascular drugs β-Adrenoceptor antagonists,  Adenosine and protamine can cause histamine release ARBs (sartans), calcium channel antagonists, ivabradine, and much else. Beta-blockers should be used cautiously in patients at high risk for anaphylaxis because they may reduce responsiveness to epinephrine (propranolol has higher risk than metoprolol). Likewise ACE inhibitors may worsen anaphylaxis and increase risk of angioedema through bradykinin accumulation.
Reversal of neuromuscular blockade  Neostigmine, and Sugammadex
Antiseptics Chlorhexidine can be a cause of perioperative anaphylaxis in the general population. Alcohol, and povidone-iodine
Intravenous fluids Hydroxyethyl starch, and Gelatine-based plasma substitutes Generally preferred: crystalloids such as normal saline, Lactated Ringer’s, Plasma-Lyte and D5W. Albumin is generally tolerated but reactions can occur.
Common labor and delivery drugs Oxytocin (possible trigger in some, consider premedication with antihistamines), prostaglandins (generally tolerated, but may be a trigger in some), methylergonovine, tocolytic agent (terbutaline)- Acceptable, though role of prostaglandins in causing or worsening reactions is unclear
Wound care Avoid plasters or adhesives if have significant skin reactions (such as in cutaneous mastocytosis). If they must be used, use an adhesive removal and slow removal of plaster/adhesive. Consider protecting the skin with Mepitac or Mepilex.
Misc. Alcohol containing medications and drinks and blood transfusion (may cause reactions in some) atropine, glycopyrrolate, ondansetron, aprotinin (fibrin glue), dyes, and latex (if no allergy)

Excipients

  • Excipients are inactive ingredients added to medications and are often the culprit in reactions to medications. These can be avoided by compounding the medication at a compounding pharmacy. Here is a tool that you can use to check for inactive ingredients in medications (search the specific drug name, scroll down to ingredients and appearance): https://dailymed.nlm.nih.gov/dailymed/
  • Common excipients that can cause reactions in some individuals include: polyethylene glycol (PEG), polysorbate 80, dyes, titanium dioxide, lactose and corn starch. Past reaction or tolerance is the biggest clue to future reactions.

General Medication/Supplement advice

  • Start one medication or supplement at a time to evaluate tolerance.
  • If you are highly sensitive and starting a higher-risk medication or a new medication/supplement, consider introducing it at the lowest possible dose along with H1 and H2 antihistamines to help reduce the risk of reactions.

Other Perioperative Considerations:

  • Develop a preoperative plan with your doctor: It can be helpful to increase mast cell stabilizing medications prior to operations, and to take them until the day of surgery (if they need to be discontinued) and there may be premedication recommendations your doctor can recommend to discuss with the surgeon such as IV antihistamine use or steroids. It is common to use IV Benadryl or other antihistamines prior to other IV medications or contrast to reduce reaction risk.
  • Avoid abrupt discontinuation of chronic antihistamines or mast cell stabilizers before surgery unless specifically instructed
  • If you have had a reaction to a previous anesthetic, find out what it was and request a different anesthetic agent
  • Inform staff of adhesive/fragrance sensitivities
  • Discuss preferred medications with anesthesiologist and surgeon before surgery
  • Request slow medication administration when possible
  • Other triggers to consider: psychological stress and anxiety, pain, environmental factors (too cold/hot of operating room, or changes in temperature), pressure (tourniquet, BP cuff), friction (tape) or other mechanical irritation, trauma, dry skin, histamine rich foods and odors (perfumes). It helps to minimize operative time, have optimal positioning, a quiet environment, reduce stress, control pain, maintain moderate/normal room temperature (can use heat maintenance devices, warm intravenous and irrigation fluids), moisturize skin, avoid puncturing blisters, avoid pressure and friction during procedures, request fragrance-free and a single occupancy room. Avoid rapid IV medication administration, and opioids given as bolus.
  • Depending on the severity of the Mast Cell Disorder, it may be helpful to get markers before the surgery such as tryptase levels (can be a helpful reference point).
  • Patients with systemic mastocytosis generally carry higher perioperative anaphylaxis risk than typical MCAS patients.
  • Epinephrine is first-line treatment for anaphylaxis and should not be withheld.

 

Resources:

  • Molderings GJ, Haenisch B, Brettner S, et al. Pharmacological treatment options for mast cell activation disease. Naunyn Schmiedebergs Arch Pharmacol. 2016;389(7):671-694. doi:10.1007/s00210-016-1247-1
  • Kumaraswami S, Farkas G. Management of a Parturient with Mast Cell Activation Syndrome: An Anesthesiologist's Experience. Case Rep Anesthesiol. 2018;2018:8920921. Published 2018 May 22. doi:10.1155/2018/8920921
  • Hepner, David. Perioperative Management of Patient with MCD. TMS training August 5, 2024
  • Pascale Dewachter, Mariana C. Castells, David L. Hepner, Claudie Mouton-Faivre; Perioperative Management of Patients with Mastocytosis. Anesthesiology 2014; 120:753–759 doi: https://doi.org/10.1097/ALN.0000000000000031

Postural Othrostatic Tachycardia Syndrome (POTS)

  • I perform an in office NASA lean test that is a screening test for POTS. If the results indicate that dysautonomia is likely, further evaluation of a tilt table and QSART testing is done.
  • Additional resources for POTS is coming soon

Hypermobility Spectrum Disorders

Dietary Resources

Patient Handouts