What is the first line treatment for urticaria and angioedema in patients with Systemic Mastocytosis (SM)?

First-Line Treatment for Urticaria and Angioedema in Systemic Mastocytosis

The first-line treatment for urticaria and angioedema in patients with Systemic Mastocytosis (SM) is a combination of H1 and H2 antihistamines, with non-sedating H1 antihistamines preferred for daytime use. 1

Initial Treatment Approach

Step 1: Antihistamine Therapy

• H1 Antihistamines:

  • Start with non-sedating H1 antihistamines (e.g., cetirizine, loratadine) 1
  • Can be increased to 2-4 times the standard dose for better symptom control 2
  • Consider adding a sedating H1 antihistamine (e.g., hydroxyzine 10-50 mg) at night if needed for sleep 1

• H2 Antihistamines:

  • Add H2 receptor antagonists (e.g., ranitidine, famotidine) concurrently 2, 1
  • Particularly helpful for gastrointestinal symptoms and can enhance the effect of H1 antihistamines for cardiovascular symptoms 2

Step 2: For Inadequate Response

If symptoms persist despite optimal antihistamine therapy:

• Add Cromolyn Sodium:
  • Particularly effective for gastrointestinal symptoms (bloating, diarrhea, cramps) 2, 3
  • May also benefit neuropsychiatric manifestations 1
  • Start at lowest dose and gradually increase to 200 mg four times daily before meals and at bedtime 1
  • Clinical improvement typically occurs within 2-6 weeks of treatment initiation 3

Advanced Treatment Options

For Refractory Symptoms:

1. Leukotriene Receptor Antagonists:

   • Consider montelukast when urinary LTE4 levels are elevated 1
   • Most effective for respiratory and dermatologic symptoms 1
   • Works best in conjunction with antihistamines 1

2. Omalizumab:

   • Consider for antihistamine-resistant symptoms 1
   • Reduces severity and frequency of allergic reactions 1
   • Particularly effective for recurrent anaphylaxis and skin symptoms 2

3. Corticosteroids:

   • For short-term management of severe symptoms 2, 1
   • Initial oral dosage of 0.5 mg/kg/day with slow taper over 1-3 months 1
   • Not recommended for long-term use due to side effects 1

4. Aspirin:

   • May reduce flushing and hypotension, particularly with elevated urinary prostaglandin metabolites 1
   • Use with caution as it can trigger mast cell activation in some patients 2, 1
   • Contraindicated in those with allergic reactions to NSAIDs 1

Emergency Preparedness

• All patients should carry two epinephrine auto-injectors for emergency management of anaphylaxis 2, 1
• Instruct patients to assume a supine position for hypotensive episodes 2
• Consider albuterol for bronchospasm symptoms 1

Important Considerations

Trigger Avoidance

• Identify and avoid triggers such as:
  • Insect venoms
  • Temperature extremes
  • Mechanical irritation
  • Alcohol
  • Certain medications (e.g., aspirin, radiocontrast agents, anesthetic agents) 2
  • Foods that may trigger symptoms

Monitoring

• Assess symptom response to treatment regularly
• Monitor for medication side effects, particularly with higher doses of antihistamines or long-term corticosteroid use

Special Situations

• For patients with SM sensitive to insect venom, consider lifelong venom immunotherapy 2
• Premedication protocols should be considered before procedures/surgery 1

Treatment Pitfalls to Avoid

1. Delayed treatment initiation: Early intervention with antihistamines is crucial to prevent symptom escalation.

2. Inadequate dosing: Standard antihistamine doses may be insufficient; higher doses (2-4× standard) may be necessary 2.

3. Monotherapy: Combination therapy with H1 and H2 antihistamines is more effective than either alone.

4. Overlooking trigger identification: Failure to identify and avoid triggers can lead to persistent symptoms despite optimal medical therapy.

5. Neglecting emergency preparedness: All patients should be equipped with epinephrine auto-injectors and educated on their use.

6. Long-term corticosteroid use: While effective for acute management, long-term use should be avoided due to significant side effects.