What is the treatment for a mast cell reaction?

Treatment of Mast Cell Reactions

Start with H1 antihistamines as first-line therapy, add H2 antihistamines for persistent symptoms, and ensure all patients have epinephrine autoinjectors for emergency use. 1

Emergency Management

• Administer epinephrine intramuscularly in a recumbent position immediately for hypotension, wheezing, laryngeal edema, or anaphylaxis. 1
• Epinephrine is the only appropriate first-line treatment for systemic anaphylaxis; antihistamines and steroids are adjunctive only. 1
• All patients with mast cell disorders must be prescribed epinephrine autoinjectors due to risk of life-threatening reactions. 1, 2
• For systemic hives with organ involvement (airway, gastrointestinal, neurologic, cardiovascular symptoms), use epinephrine first, then add H1/H2 antihistamines and corticosteroids as needed. 1

First-Line Pharmacologic Treatment

H1 Antihistamines

• Begin with H1 receptor antihistamines as the foundation of therapy for controlling pruritus, flushing, urticaria, and tachycardia. 1
• Both sedating (diphenhydramine, hydroxyzine) and non-sedating options (cetirizine, fexofenadine) are effective. 1
• Doses may need to be 2-4 times FDA-approved levels to achieve adequate symptom control. 2, 3
• First-generation antihistamines (diphenhydramine, hydroxyzine) cause significant sedation and cognitive decline, particularly in elderly patients, requiring cautious use. 2, 3
• High doses of H1 antihistamines carry risk of cardiotoxicity. 1

H2 Antihistamines

• Add H2 receptor antagonists (ranitidine, famotidine) when H1 antihistamines alone fail to control symptoms, particularly for gastrointestinal manifestations. 1
• Combined H1 and H2 therapy is more effective than monotherapy for controlling severe pruritus and wheal formation. 1, 2
• H2 antihistamines specifically target gastric hypersecretion and peptic ulcer disease associated with mastocytosis. 1

Second-Line Mast Cell Stabilizers

Oral Cromolyn Sodium

• Add oral cromolyn sodium for gastrointestinal symptoms including diarrhea, abdominal pain, nausea, and vomiting when antihistamines are insufficient. 1, 3
• Cromolyn sodium works by inhibiting mast cell degranulation and preventing mediator release. 4
• Despite low absorption, cromolyn sodium may also help cutaneous symptoms including pruritus. 1
• Introduce progressively to reduce side effects such as headache, sleepiness, irritability, abdominal pain, and diarrhea. 1
• It may take up to two weeks (or one month) of regular treatment at four times daily dosing to bring symptoms under control. 4
• The drug is poorly absorbed when swallowed and must be administered properly (nebulized for respiratory symptoms, oral solution for GI symptoms). 4

Additional Mediator-Blocking Agents

Leukotriene Inhibitors

• Add cysteinyl leukotriene inhibitors (montelukast) or 5-lipoxygenase inhibitors (zileuton) if symptoms persist despite first-line therapy, especially if urinary LTE4 levels are elevated. 2, 3

Cyproheptadine

• Consider cyproheptadine, which functions as both an H1 blocker and serotonin receptor antagonist, particularly effective for diarrhea and nausea. 2, 3

Proton Pump Inhibitors

• Use proton pump inhibitors when H2 antihistamines fail to control gastrointestinal symptoms. 1, 5

Aspirin

• Aspirin may reduce flushing and hypotensive episodes from prostaglandin D2 secretion in select patients. 1, 5
• Aspirin must be introduced only in a controlled clinical setting with emergency equipment available, as it can paradoxically trigger mast cell activation in some patients. 1, 5

Refractory Cases

Omalizumab

• Consider omalizumab (anti-IgE monoclonal antibody) for mast cell activation symptoms insufficiently controlled by conventional therapy. 1
• Omalizumab is particularly effective for recurrent anaphylaxis and skin symptoms, more so than for gastrointestinal, musculoskeletal, and neuropsychiatric symptoms. 1

Corticosteroids

• Short courses of oral corticosteroids (prednisone 0.5 mg/kg/day with slow taper over 1-3 months) may be used for refractory symptoms. 3
• Systemic corticosteroids help acute episodes but should be tapered quickly to limit adverse effects. 5

PUVA Therapy

• PUVA therapy has proven effective for bullous diffuse cutaneous mastocytosis, even with life-threatening mediator release episodes. 1, 5
• PUVA is most effective in non-hyperpigmented diffuse cutaneous mastocytosis; response is usually poor in nodular or plaque forms. 1

Critical Implementation Considerations

Trigger Avoidance

• Control temperature extremes (hot and cold) as these can activate mast cells and worsen symptoms. 1, 2
• Avoid anxiety and stress when possible. 1
• Identify and avoid specific triggers including certain foods, medications, insect stings, and physical stimuli. 1

Medication Introduction

• Introduce all medications cautiously as some patients experience paradoxical reactions to standard therapies. 2, 5
• Medication trials should be conducted in controlled settings with emergency equipment available. 5

Monitoring

• Serum tryptase levels above 20 μg/L indicate increased mast cell burden and require close observation, evaluation, and possibly hospitalization. 1, 2
• Elevated tryptase levels are a risk factor for anaphylaxis. 1

Special Situations

Perioperative Management

• Pre-treat with antihistamines before surgery, imaging procedures with contrast dyes, and dental work to prevent life-threatening episodes. 1, 2
• If opioids are needed for pain, use fentanyl or remifentanil rather than morphine or codeine, as the latter can trigger mast cell activation. 2, 3
• Pre-treat with antihistamines and mast cell stabilizers before administering opioids. 2

Hymenoptera Venom Allergy

• Venom immunotherapy (VIT) is effective for IgE-mediated Hymenoptera venom anaphylaxis and significantly reduces risk of anaphylaxis after re-sting. 1
• VIT is recommended for all patients with positive skin test or positive Hymenoptera-specific IgE antibodies and history of venom anaphylaxis. 1

Treatment Algorithm by Severity

Mild symptoms: Start H1 antihistamines alone at standard or increased doses. 5

Moderate symptoms: Add H2 antihistamines and consider cromolyn sodium for gastrointestinal symptoms. 5

Persistent symptoms: Add leukotriene antagonists; consider aspirin in controlled setting; ensure epinephrine autoinjector prescribed. 5

Refractory symptoms: Consider omalizumab, short-term systemic corticosteroids, or PUVA therapy for cutaneous disease. 5

Patient and Caregiver Education

• Education of parents and care providers is essential, particularly for pediatric cases. 1
• Community communication (teachers, nurses, daycare workers) protects children and prevents life-threatening episodes. 1
• Clarify that cutaneous mastocytosis is not contagious. 1
• Provide informational materials containing protocols for specific situations including fever, vaccinations, dental work, imaging procedures, and surgery. 1