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Mast Cell Activation Syndrome Treatment

Question# 928

I recently had a patient with MCAS (Mast Cell Activation Syndrome) who had self treated with Epi pen and an antihistamine prior to our arrival. Though they did not require treatment from paramedics, it did get me wondering how we should be managing MCAS when it presents as anaphylaxis.

The directive states clearly “exposure to probable allergen” as an indication for treating a patient under the allergic reaction directive. My understanding is that MCAS has no specific exogenous trigger or allergen like typical anaphylaxis, but will present with the same life threatening symptoms and has the same first line treatment as anaphylaxis caused by an allergen.

Are we authorized to treat known MCAS patients presenting with symptoms of anaphylaxis under our current directive? Are there any special considerations in treating these patients that would differ from anaphylaxis caused by allergen?

Answer:

Mast cells are the key allergy cells responsible for immediate allergic reactions. When activated, they release chemical products called mediators, either rapidly from storage granules (like histamine and tryptase) or more slowly when newly synthesized (like prostaglandins and leukotrienes).

In typical allergic reactions, activation occurs when IgE antibodies on mast cell surfaces bind to specific allergens. This is called secondary activation, since it is triggered by an external stimulus (e.g., food, insect venom, medications).

In some conditions, however, mast cells become defective and release mediators because of internal or clonal defects.

An example being the clinical condition you outlined: Idiopathic Mast Cell Activation Syndrome (MCAS), where episodes of mast cell mediator release cause anaphylaxis-like symptoms without a clear allergen trigger. The trigger is endogenous or idiopathic rather than a clear external allergen.

Clinically, MCAS decompensation can look identical to anaphylaxis: airway edema, hypotension, bronchospasm, wheezing, stridor, urticaria, cardiovascular collapse, and GI symptoms.

The first-line and cornerstone treatment is thus epinephrine, if indicated by symptom severity. In MCAS, antihistamines like diphenhydramine (a first-generation H1 blocker) may also play a role, though they are supportive and not life-saving. They come with side effects (e.g., sedation, anticholinergic effects), so their use should follow epinephrine, not replace it.

While epinephrine remains the first-line, life-saving treatment for both typical anaphylaxis and MCAS-related episodes, the decision to administer it under the current ALS PCS can be complicated. This is because the directive specifies “exposure to a probable allergen”.

Given the complexity of the patient in front of you, we’d encourage a patch to a base hospital physician who can help you create a treatment plan for this patient, but if treating within the medical directive, please ensure detailed documentation to ensure we understand your mental model.

Interesting, the World Allergy Organization (WAO) states that anaphylaxis is highly likely when one of the following two criteria exist:

1 – acute onset of an illness (minutes to several hours) with involvement of the skin, mucosal tissue, or both (e.g. generalized hives, pruritis or flushing, swollen lips-tongue-uvula) AND at least one of the following:

  1. Airway/breathing compromise (e.g. dyspnea, wheeze/bronchospasm/stridor, hypoxemia
  2. Circulation (hypotension, syncope, incontinence)
  3. Severe GI symptoms (e.g. severe crampy abdominal pain, repetitive vomiting)

 2 – acute onset of age-related hypotension or bronchospasm or laryngeal involvement after exposure to a known or highly probably allergen for that patient, even in the absence of typical skin involvement.

For brevity, the WAO states that even in the absences of a known exposure, patients can still meet the definition of anaphylaxis. Thus, if the patient presents as anaphylactic and has no history of MCAS, then manage as anaphylaxis even if they are not aware of exposure to an allergen.

While not specifically related to MCAS, if you’re interested in additional educational content surrounding anaphylaxis, please feel free to listen to the Critical Levels podcast about anaphylaxis, available in MedicLEARN (2023 Elective CME)

References

American Academy of Allergy Asthma & Immunology - Mast Cell Activation Syndrome: https://www.aaaai.org/conditions-treatments/related-conditions/mcas

World Allergy Organization Anaphylaxis Guidance 2020: https://www.worldallergyorganizationjournal.org/article/S1939-4551(20)30375-6/fulltext

UpToDate: Mast cell disorder: An Overview

Published

06 October 2025

ALSPCS Version

5.4

Views

15

Please reference the MOST RECENT ALS PCS for updates and changes to these directives.