What is the treatment for mast cell activation?

Treatment of Mast Cell Activation

Treatment of mast cell activation is highly individualized and targets both acute episodes and chronic symptom prevention through a stepwise approach: H1 antihistamines as first-line therapy, adding H2 antihistamines for gastrointestinal symptoms, oral cromolyn sodium for refractory cases, and maintaining epinephrine autoinjectors for emergency use. 1, 2

Acute Management of Mast Cell Activation Episodes

Acute mast cell activation attacks should be managed identically to systemic anaphylaxis. 1

• Hypotensive episodes require immediate supine positioning followed by intramuscular epinephrine administration. 1
• Laryngeal angioedema necessitates intramuscular epinephrine, while bronchospasm can be treated with either intramuscular epinephrine or inhaled albuterol. 1
• All patients at risk for severe activation events must carry an epinephrine autoinjector to avoid potentially life-threatening delays in treatment. 1, 2
• After epinephrine administration, patients should be transported to the emergency department by ambulance while remaining supine. 1
• Adjunctive therapy includes fluid resuscitation, corticosteroids, and antihistamines (H1 and H2 blockers), along with discontinuation of any suspected triggering drug or anesthetic agent. 1

Chronic Preventive Pharmacotherapy

First-Line: H1 Antihistamines

• Nonsedating H1 antihistamines (cetirizine, loratadine, fexofenadine) are preferred as initial therapy and can be increased to 2-4 times the standard FDA-approved dose for adequate symptom control. 1, 2
• Sedating H1 antihistamines (diphenhydramine, hydroxyzine) may acutely impair driving ability and chronically lead to cognitive decline, particularly in elderly patients. 1
• These agents effectively control itching, flushing, skin rashes, and tachycardia. 2

Second-Line: H2 Antihistamines

• H2 antihistamines (famotidine, ranitidine) should be added when gastrointestinal symptoms persist despite H1 antihistamine monotherapy. 1, 2
• Combined H1 and H2 therapy is particularly effective for controlling severe pruritus and wheal formation when monotherapy fails. 2
• H2 blockers can also help H1 antihistamines attenuate cardiovascular symptoms. 1

Third-Line: Mast Cell Stabilizers

• Oral cromolyn sodium is FDA-approved for mastocytosis and can reduce abdominal bloating, diarrhea, cramps, and potentially neuropsychiatric manifestations. 1, 3
• Cromolyn sodium inhibits the release of histamine and leukotrienes from mast cells but has no intrinsic vasoconstrictor, antihistamine, or glucocorticoid activity. 3
• Less than 1% of orally administered cromolyn is absorbed from the gastrointestinal tract, with the remainder excreted in feces. 3
• Divided dosing with weekly upward titration to reach the target dose improves tolerance and adherence. 1

Alternative Agents

• Doxepin, a potent H1 and H2 antihistamine with tricyclic antidepressant activity, may reduce central nervous system manifestations but carries risks of drowsiness, cognitive decline in the elderly, and increased suicidal tendencies in children and young adults with depression. 1
• Leukotriene modifiers can be considered based on urinary leukotriene E4 levels. 4

Trigger Identification and Avoidance

The first step in preventing future mast cell activation events involves identifying and strictly avoiding triggers. 1

• Common triggers include insect venoms, temperature extremes, mechanical irritation, alcohol, aspirin, radiocontrast agents, and certain anesthetic agents. 1, 2
• Pain itself can trigger mast cell activation, creating a challenging cycle where inadequate pain control worsens symptoms. 5
• Anxiety and stress can also trigger mast cell activation and should be managed appropriately. 2
• Temperature control is particularly important, as mast cells are activated by hot temperatures and, to a lesser extent, cold temperatures. 2

Special Considerations for Opioid Use

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 when needed since pain itself can trigger mast cell degranulation. 1, 5

• Fentanyl and remifentanil are considered safer opioid options compared to morphine or codeine. 1, 5, 2
• Intravenous administration of opioids is generally preferred over oral administration to ensure reliable drug delivery and minimize gastrointestinal exposure. 5
• Pre-treatment with antihistamines (H1 and H2 blockers) and mast cell stabilizers before administering opioids reduces the risk of mast cell activation. 5
• Emergency medications (epinephrine, corticosteroids, additional antihistamines) should be readily available when administering opioids to patients with mast cell activation disorders. 5

Perioperative Management

Patients with systemic mastocytosis have an estimated higher risk of anaphylaxis in the perioperative period compared to the general population. 1

• Safer perioperative drugs include propofol for anesthetic induction, sevoflurane or isoflurane for inhalational anesthesia, fentanyl or remifentanil for analgesia, lidocaine or bupivacaine for local anesthesia, and povidone-iodine for skin antisepsis. 1
• Agents to avoid include muscle relaxants atracurium and mivacurium (rocuronium and vecuronium may be safer) and succinylcholine. 1
• Prophylactic anti-mediator drug therapy with corticosteroids, antihistamines, and available epinephrine should be standard during the perioperative period. 1

Venom Immunotherapy

Patients with systemic mastocytosis who are sensitive to insect venom, particularly those with a history of systemic anaphylaxis to a prior insect sting, should undergo lifelong venom immunotherapy. 1

• Omalizumab during immunotherapy appears to reduce the risk of anaphylaxis to venom immunotherapy. 1

Diagnostic Workup After Activation Events

Following any anaphylaxis or mast cell activation event, a full allergic workup should be initiated. 1

• Serum tryptase level should be measured within 30-120 minutes of symptom onset and again after full recovery to establish baseline comparison. 1, 4
• Identification of IgE-mediated hypersensitivity to drugs requires detection of specific IgE antibodies and skin testing (skin prick and intradermal tests). 1

Pregnancy Considerations

Systemic mastocytosis is not a contraindication to successful pregnancy, though management requires a multidisciplinary team including high-risk obstetrics and anesthesia. 1

• Avoidance of triggers, prophylactic antihistamines, as-needed corticosteroids, and epinephrine on demand for anaphylaxis are standard approaches during pregnancy and the early postpartum period. 1
• For severe cases refractory to conventional therapy, cytoreductive therapy with interferon-alfa can be considered during pregnancy. 1
• Use of cladribine, imatinib, and midostaurin is not recommended during pregnancy. 1

Common Pitfalls

• Eliminating additives in drugs used to treat or prevent anaphylaxis by compounding them is not recommended, as single- and double-blind challenges have ruled out additive allergies in patients with chronic urticaria who complained of such sensitivities. 1
• Neither plasma nor urine histamine levels are recommended over histamine metabolites for diagnostic purposes due to insufficient sensitivity and specificity. 1
• Chromogranin A resides in neuroendocrine cells but not in mast cells and should not be used as a biomarker of mast cell activation. 1