How is mast cell activation managed?

Management of Mast Cell Activation

Management of mast cell activation depends on symptom severity and should include H1 and H2 antihistamines as first-line therapy, with cromolyn sodium for gastrointestinal symptoms, corticosteroids and benzodiazepines for severe episodes, and immediate intramuscular epinephrine for anaphylaxis. 1

Acute Management of Severe Mast Cell Activation

For hypotensive episodes or anaphylaxis, patients must assume the supine position immediately and receive intramuscular epinephrine. 1

• Laryngeal angioedema requires intramuscular epinephrine 1
• Bronchospasm can be treated with intramuscular epinephrine or inhaled albuterol 1
• All patients at risk for severe reactions should carry an epinephrine autoinjector 1, 2
• After epinephrine administration, transport to the emergency department by ambulance while maintaining supine position 1
• Additional acute interventions include fluid resuscitation, intravenous epinephrine, and discontinuation of suspected triggering drugs or anesthetic agents 1

Preventive Pharmacologic Management

First-Line Therapy: Antihistamines

H1 antihistamines (cetirizine, diphenhydramine, or hydroxyzine) are the cornerstone of preventive therapy. 1, 2

• Nonsedating H1 antihistamines are generally preferred 1
• Doses can be increased to 2-4 times the standard FDA-approved dose for adequate symptom control 1, 2
• High doses require careful monitoring for cardiotoxicity 2
• Sedating H1 antihistamines may cause drowsiness, impair driving ability, and lead to cognitive decline, particularly in elderly patients 1

H2 antihistamines should be added for gastrointestinal symptoms or to augment cardiovascular symptom control. 1, 2

• Ranitidine or famotidine are effective options 2
• Combined H1 and H2 therapy is particularly effective for severe pruritus and wheal formation when monotherapy fails 2

Second-Line Therapy: Mast Cell Stabilizers

Oral cromolyn sodium is effective for gastrointestinal symptoms including abdominal bloating, diarrhea, and cramps. 1

• Benefits may extend to neuropsychiatric manifestations 1
• Cromolyn works by inhibiting sensitized mast cell degranulation and preventing mediator release 3
• Approximately 8% of the dose is absorbed and rapidly excreted unchanged 3
• Divided dosing with weekly upward titration to the target dose improves tolerance and adherence 1
• For asthma-related mast cell activation, the usual starting dosage is one vial by nebulization four times daily at regular intervals 3
• It may take up to two weeks (or one month) of regular treatment to bring symptoms under control 3
• Must be taken regularly even when asymptomatic, as it prevents rather than treats acute symptoms 3

Additional Preventive Options

Doxepin, a potent H1 and H2 antihistamine with tricyclic antidepressant activity, may reduce central nervous system manifestations. 1

• However, it may cause drowsiness and cognitive decline, particularly in the elderly 1
• May increase suicidal tendencies in children and young adults with depression 1

Corticosteroids are helpful in reducing the frequency and severity of mast cell activation symptoms. 1

• Particularly useful for prolonged episodes 4
• In patients chronically receiving corticosteroids, dosage should be maintained when introducing cromolyn sodium 3
• If improvement occurs, attempt gradual tapering of corticosteroid dosage 3

Benzodiazepines may help reduce the frequency and severity of symptoms. 1

Trigger Identification and Avoidance

The first step in prevention is identifying and avoiding specific triggers. 1, 2

Common triggers to avoid include:

• Insect venoms (patients with systemic mastocytosis sensitive to insect venom should undergo lifelong venom immunotherapy) 1
• Temperature extremes (hot temperatures more than cold) 2
• Mechanical irritation 1
• Alcohol 1
• Certain medications (aspirin, radiocontrast agents, specific anesthetic agents) 1
• Anxiety and stress 2
• Pain itself (which creates a challenging cycle where inadequate pain control worsens symptoms) 5, 2

Special Considerations for Pain Management

Opioids like morphine and codeine should be used with caution due to their potential to trigger mast cell activation, though they should not be withheld if needed since pain itself can trigger mast cell degranulation. 1, 5

• Fentanyl and remifentanil are considered safer opioid options 5, 2
• IV administration of opioids is generally preferred over oral administration to ensure reliable drug delivery and minimize gastrointestinal exposure 5
• Consider pre-treatment with antihistamines (H1 and H2 blockers) and mast cell stabilizers before administering opioids 5
• Have emergency medications (epinephrine, corticosteroids, additional antihistamines) readily available when administering opioids 5

Perioperative Management

The risk of anaphylaxis in the perioperative period is higher in patients with systemic mastocytosis compared to the general population. 1

• Perioperative drugs are not contraindicated, though certain drugs are considered safer based on anecdotal reports 1
• In the event of anaphylaxis or other mast cell activation event, initiate a full allergic workup including skin tests or detection of specific IgE antibodies 1
• Measure serum tryptase level within 30 to 120 minutes of symptom onset and again after full recovery 1

Pregnancy Considerations

Systemic mastocytosis is not a contraindication to pregnancy, but requires multidisciplinary management. 1

• Pregnant women with systemic mastocytosis should be managed by a team including a high-risk obstetrician and anesthesiologist 1
• Avoidance of known triggers and prophylactic anti-mediator drug therapy (corticosteroids, antihistamines, and epinephrine) are standard approaches during pregnancy and early postpartum 1
• Cytoreductive therapy with interferon-alfa can be considered for pregnant women with severe symptoms refractory to conventional therapy 1
• Cladribine, imatinib, and midostaurin are not recommended during pregnancy 1

Common Pitfalls to Avoid

• Do not eliminate additives in drugs used to treat or prevent anaphylaxis by compounding them, as this is not recommended 1
• Do not stop taking cromolyn sodium or skip doses without consulting a physician 3
• Do not use cromolyn sodium if it contains a precipitate or becomes discolored 3
• Cromolyn sodium is poorly absorbed when swallowed and is not effective by the oral route for systemic symptoms 3
• When respiratory function is impaired during severe asthma exacerbations, a temporary increase in corticosteroids may be required 3