What are the treatment options for mast cell disorders?

Treatment of Mast Cell Disorders

H1 antihistamines are the cornerstone first-line treatment for mast cell disorders, with H2 antihistamines added for gastrointestinal symptoms and refractory cases. 1

Initial Pharmacologic Management

First-Line Therapy

• H1 receptor antihistamines should be initiated immediately to control dermatologic manifestations (pruritus, flushing, urticaria), tachycardia, and abdominal discomfort 1

  • Both sedating (diphenhydramine, hydroxyzine) and non-sedating (cetirizine, fexofenadine) options are effective 2
  • Doses may need to be 2-4 times FDA-approved levels for adequate symptom control 3
  • Caution: First-generation antihistamines cause significant sedation and cognitive decline, particularly in elderly patients 1

• H2 receptor antihistamines (ranitidine, famotidine) should be added when gastrointestinal symptoms persist, particularly for gastric hypersecretion and peptic ulcer disease 2, 1

• Combined H1 and H2 antihistamine therapy has proven effective for controlling severe pruritus and wheal formation when monotherapy fails 2

Second-Line Mast Cell Stabilizers

• Oral cromolyn sodium is particularly effective for gastrointestinal symptoms including diarrhea, abdominal pain, nausea, and vomiting 2, 1

  • Despite low absorption, it may also help cutaneous symptoms and pruritus 2
  • Progressive introduction reduces side effects (headache, sleepiness, irritability, abdominal pain) 2

• Leukotriene receptor antagonists (montelukast) or 5-lipoxygenase inhibitors (zileuton) should be added for dermatologic symptoms unresponsive to antihistamines 1

Additional Mediator-Blocking Agents

• Cyproheptadine is specifically recommended for diarrhea and nausea 1

• Aspirin may reduce flushing and hypotensive episodes from prostaglandin D2 secretion, but must be introduced in a controlled clinical setting due to potential paradoxical mast cell activation 1

• Proton pump inhibitors should be used when H2 antihistamines fail to control gastrointestinal symptoms 2

Emergency Management

Acute Mast Cell Activation

• Epinephrine must be administered intramuscularly in recumbent position for hypotension, wheezing, laryngeal edema, cyanotic episodes, or recurrent anaphylactic attacks 2

• All patients with history of systemic anaphylaxis must be prescribed epinephrine autoinjectors 1

• Systemic corticosteroids may help acute episodes but should be tapered quickly to limit adverse effects 1

Refractory and Severe Cases

Advanced Pharmacotherapy

• Omalizumab should be considered when MCAS is resistant to standard mediator-targeted therapies 1

• PUVA therapy (oral methoxypsoralen with ultraviolet A radiation) has proven effective for bullous diffuse cutaneous mastocytosis, even with life-threatening mediator release episodes 2

Cytoreductive Therapy

• Imatinib is FDA-approved for aggressive systemic mastocytosis 4

  • May provide benefits even in KIT-D816V-negative mast cell disorders due to other unknown mutations 5
  • Reserved for aggressive variants with life-threatening symptoms 2

• Continuous diphenhydramine infusion represents an option for severe, therapy-refractory cases with frequent anaphylactic reactions, particularly in intensive care settings 5

Critical Implementation Considerations

Medication Introduction Protocol

• Medications must be introduced cautiously as some patients experience paradoxical reactions 1

• Medication trials should be conducted in controlled settings with emergency equipment available 1

Trigger Management

• Temperature control (avoiding hot and cold extremes through rational use of baths, showers, swimming pools, air conditioning) decreases symptoms and antihistamine requirements 2

• Anxiety and stress avoidance is essential 2

• Careful trigger identification and avoidance is crucial alongside pharmacologic interventions 1

Patient and Caregiver Education

• Education of parents and care providers is essential for pediatric cases 2

• Community communication (teachers, nurses, day care workers, pediatricians) protects children and prevents life-threatening episodes during surgery, imaging procedures with dyes, and dental work 2

• Clarify that cutaneous mastocytosis is not contagious 2

Treatment Algorithm by Severity

Mild symptoms: Start H1 antihistamines alone 1

Moderate symptoms: Add H2 antihistamines and consider cromolyn sodium for GI symptoms 2, 1

Persistent symptoms: Add leukotriene antagonists, consider aspirin in controlled setting 1

Refractory symptoms: Consider omalizumab, systemic corticosteroids (short-term), or PUVA therapy 2, 1

Aggressive/life-threatening disease: Cytoreductive therapy with imatinib or other targeted agents 4, 5