What is the primary treatment approach for managing symptoms of mastocytosis?

Primary Treatment Approach for Mastocytosis

The primary treatment for managing symptoms of mastocytosis is anti-mediator drug therapy with H1 antihistamines as first-line agents, adding H2 antihistamines for persistent gastrointestinal symptoms, and reserving cytoreductive therapy for advanced disease or refractory cases. 1

First-Line Anti-Mediator Therapy

H1 Antihistamines

• Start with H1 receptor antihistamines as the cornerstone of symptom management for dermatologic manifestations, tachycardia, pruritus, flushing, and abdominal discomfort 1, 2
• Both sedating (diphenhydramine, hydroxyzine) and non-sedating (cetirizine) options are effective 1, 2
• Doses may need to be 2-4 times higher than FDA-approved levels for adequate symptom control, though this requires careful monitoring for cardiotoxicity 1, 2

H2 Antihistamines

• Add H2 receptor antihistamines (ranitidine, famotidine) when gastrointestinal symptoms persist despite H1 antihistamine monotherapy 1, 2
• H2 blockers are particularly effective for gastric hypersecretion and peptic ulcer disease 1
• Combined H1 and H2 therapy is superior to monotherapy for controlling severe pruritus and wheal formation 1, 2

Second-Line Mast Cell Stabilizers

Cromolyn Sodium

• Oral cromolyn sodium is the preferred second-line agent for gastrointestinal symptoms including diarrhea, abdominal pain, nausea, and vomiting 1, 3
• FDA-approved specifically for mastocytosis management, with documented improvement in diarrhea, flushing, headaches, vomiting, urticaria, abdominal pain, and itching 3
• Clinical improvement typically occurs within 2-6 weeks of treatment initiation at 200 mg four times daily 3
• Progressive introduction reduces side effects such as headache, sleepiness, and irritability 1

Additional Mediator-Blocking Agents

Targeted Symptom Management

• Cyproheptadine for persistent diarrhea and nausea 1
• Proton pump inhibitors when H2 antihistamines fail to control gastrointestinal symptoms 1
• Aspirin may reduce flushing and hypotensive episodes from prostaglandin D2 secretion, but must be introduced only in a controlled clinical setting due to risk of paradoxical mast cell activation 1

Emergency Preparedness

Anaphylaxis Management

• All patients with systemic mastocytosis or history of anaphylaxis must be prescribed epinephrine autoinjectors 1, 2
• Epinephrine must be administered intramuscularly in a recumbent position for hypotension, wheezing, laryngeal edema, or cyanotic episodes 1, 2
• Have emergency medications (epinephrine, corticosteroids, additional antihistamines) readily available 4

Acute Episode Management

• Systemic corticosteroids may help acute episodes but should be tapered quickly to limit adverse effects 1
• Additional options include fluid resuscitation, intravenous epinephrine, and discontinuation of suspected triggering agents 5

Disease-Specific Treatment Algorithms

Indolent Systemic Mastocytosis (ISM) and Smoldering Systemic Mastocytosis (SSM)

• Continue anti-mediator drug therapy for patients experiencing adequate response 5
• Switch to cytoreductive therapy if inadequate response, loss of response, or progression to advanced disease 5

Advanced Systemic Mastocytosis (ASM, SM-AHN, MCL)

• Initiate cytoreductive therapy as primary treatment 5
• Evaluate for allogeneic hematopoietic cell transplantation in patients with adequate response to cytoreductive therapy and suitable donors identified 5
• Switch to alternate cytoreductive therapy not previously received if inadequate response or loss of response 5

Refractory Disease Management

• Consider omalizumab when mast cell activation syndrome is resistant to standard mediator-targeted therapies 1
• PUVA therapy has proven effective for bullous diffuse cutaneous mastocytosis, even with life-threatening mediator release episodes 1

Critical Implementation Considerations

Medication Introduction

• Introduce all medications cautiously as some patients experience paradoxical reactions 1
• Medication trials should be conducted in controlled settings with emergency equipment available 1

Trigger Avoidance

• Temperature control is essential as mast cells are activated by hot temperatures and, to a lesser extent, cold temperatures 1, 2
• Avoid anxiety and stress, which can trigger mast cell activation 1, 2
• Pain control is crucial since pain itself triggers mast cell activation, though opioids like morphine and codeine should be used with caution 5, 4
• Fentanyl and remifentanil are safer opioid options compared to morphine or codeine 4, 2

Special Populations

Perioperative Management

• Multidisciplinary management is mandatory involving surgical, anesthesia, and perioperative medical teams 5
• Pretreatment with benzodiazepines, antihistamines (H1 and H2 blockers), and corticosteroids is probably helpful in reducing perioperative mast cell activation 5
• The risk of anaphylaxis in the perioperative period is higher in patients with systemic mastocytosis relative to the general population 5

Pregnancy

• Systemic mastocytosis is not a contraindication to pregnancy 5
• Pregnant women with systemic mastocytosis should be managed by a multidisciplinary team including a high-risk obstetrician and anesthesiologist 5
• Spontaneous miscarriages and worsening of mast cell activation symptoms occur in 20-30% of pregnant women with mastocytosis 5

Response Assessment

• Response assessment should be based on improvement of mast cell activation symptoms and organ damage at the discretion of the clinician, rather than strict research criteria 5
• Restaging studies are recommended before starting additional therapy in patients with inadequate response 5