What is the treatment for mast cell activation?

Treatment for Mast Cell Activation

Begin treatment with H1 and H2 antihistamines as first-line therapy, combined with oral cromolyn sodium for gastrointestinal symptoms and prevention of mast cell degranulation. 1, 2

Acute Management of Mast Cell Activation Episodes

• Intramuscular epinephrine is the primary treatment for acute severe mast cell activation events, particularly when hypotension, laryngeal angioedema, or bronchospasm occurs 1
• Patients should assume the supine position immediately during hypotensive episodes before administering epinephrine 1
• All patients at risk for severe activation events must carry two epinephrine autoinjectors at all times 1
• Bronchospasm can alternatively be treated with inhaled albuterol if epinephrine is not immediately needed 1
• After epinephrine administration, transport to the emergency department by ambulance while maintaining supine position 1
• Benzodiazepines, corticosteroids, and fluid resuscitation serve as adjunctive therapies during acute episodes 1

First-Line Preventive Pharmacotherapy

H1 Antihistamines

• Nonsedating H1 antihistamines are preferred and can be increased to 2-4 times the standard FDA-approved dose to achieve adequate symptom control 1
• First-generation H1 antihistamines (diphenhydramine, hydroxyzine) may cause drowsiness, impair driving ability, and lead to cognitive decline, particularly in elderly patients 1
• Doxepin, a potent dual H1/H2 antihistamine with tricyclic antidepressant activity, may reduce central nervous system manifestations but carries similar sedation and cognitive risks 1

H2 Antihistamines

• H2 receptor antagonists should be used as first-line therapy for gastrointestinal symptoms and may enhance cardiovascular symptom control when combined with H1 antihistamines 1

Mast Cell Stabilizers

• Oral cromolyn sodium is FDA-approved for mastocytosis and reduces abdominal bloating, diarrhea, cramps, flushing, headaches, vomiting, urticaria, abdominal pain, nausea, and itching 2
• Cromolyn sodium inhibits histamine and leukotriene release from mast cells by preventing degranulation 2
• Use divided dosing with weekly upward titration to the target dose to improve tolerance and adherence 1
• Benefits may extend to neuropsychiatric manifestations 1
• Only 0.28-0.50% of oral cromolyn is absorbed systemically, with the remainder excreted in feces 2

Second-Line and Adjunctive Therapies

Leukotriene Modifiers

• Montelukast or zileuton should be added when urinary LTE4 levels are elevated or when response to antihistamines is inadequate 3

Aspirin Therapy

• Aspirin can inhibit prostaglandin synthesis but must be used with extreme caution as it may trigger mast cell activation in some patients 1, 3
• Consider aspirin only if prostaglandin levels are documented to be elevated 3

Corticosteroids

• Corticosteroids are useful for reducing frequency and severity of mast cell activation symptoms, particularly during pregnancy and the postpartum period 1
• Prolonged episodes of mast cell activation may require corticosteroid therapy 3

Treatment Algorithm for Indolent and Smoldering Systemic Mastocytosis

• Manage symptomatic patients with anti-mediator drug therapy using the agents described above 1
• Monitor with history and physical examination plus laboratory studies every 6-12 months 1
• Assess symptom burden and quality of life using validated tools 1
• DEXA scans every 1-3 years for patients with osteopenia/osteoporosis 1
• Cladribine and pegylated interferon-alfa are reserved for advanced systemic mastocytosis but may be considered for selected patients with severe, refractory mediator symptoms or bone disease unresponsive to standard therapy 1

Treatment for Aggressive Systemic Mastocytosis

• Midostaurin is the preferred cytoreductive agent for aggressive disease 1
• Alternative cytoreductive options include cladribine, interferon-alfa preparations (interferon alfa-2b, peginterferon alfa-2a, or peginterferon alfa-2b) with or without prednisone 1
• Imatinib should only be used if KIT D816V mutation is negative or unknown, or if eosinophilia with FIP1L1-PDGFRA fusion gene is present 1
• Referral to specialized centers with mastocytosis expertise is strongly recommended 1
• Consider evaluation for allogeneic hematopoietic cell transplantation in appropriate candidates 1

Critical Trigger Avoidance and Special Considerations

• Identify and avoid specific triggers including insect venoms, temperature extremes, mechanical irritation, alcohol, aspirin, radiocontrast agents, and certain anesthetic agents 1
• Patients with systemic mastocytosis who are sensitive to insect venom require lifelong venom immunotherapy 1
• Omalizumab during venom immunotherapy reduces the risk of anaphylaxis to the immunotherapy itself 1

Opioid Use

• Opioids such as morphine and codeine should be used with caution due to their potential to trigger mast cell activation 1, 4
• However, opioids should not be withheld when needed, as pain itself can trigger mast cell degranulation 1, 4
• Fentanyl and remifentanil are safer opioid alternatives compared to morphine or codeine 4
• Intravenous administration is preferred over oral administration to ensure reliable delivery and minimize gastrointestinal exposure 4
• Pre-treatment with antihistamines (H1 and H2 blockers) and mast cell stabilizers before opioid administration reduces activation risk 4

Perioperative Management

• The risk of anaphylaxis during the perioperative period is higher in patients with systemic mastocytosis compared to the general population 1
• Multidisciplinary collaboration with anesthesiologists is essential for procedures and surgery 1
• Have emergency medications (epinephrine, corticosteroids, additional antihistamines) readily available when administering potentially triggering medications 4

Pregnancy Considerations

• Systemic mastocytosis is not a contraindication to pregnancy 1
• Management requires a multidisciplinary team including high-risk obstetricians and anesthesiologists 1
• Avoidance of triggers and prophylactic anti-mediator therapy (corticosteroids, antihistamines, epinephrine) are standard during pregnancy and early postpartum 1
• Interferon-alfa can be considered for pregnant women with severe refractory symptoms 1
• Cladribine, imatinib, and midostaurin are not recommended during pregnancy 1

Common Pitfalls to Avoid

• Do not eliminate additives in compounded drugs used to treat anaphylaxis, as additive allergies have been ruled out in controlled challenges 1
• Do not rely solely on plasma or urine histamine levels for diagnosis, as histamine metabolites are preferred 1
• Chromogranin A and heparin are not validated biomarkers of mast cell activation and should not be used 1
• Serum tryptase should be measured within 30-120 minutes of symptom onset and again after full recovery to document acute mast cell activation 1