Does dupilumab help with anaphylaxis and respiratory symptoms in MCAS (Mast Cell Activation Syndrome)?

Dupilumab for MCAS: Efficacy for Anaphylaxis and Respiratory Symptoms

Dupilumab is not currently recommended as a first-line treatment for anaphylaxis or respiratory symptoms in Mast Cell Activation Syndrome (MCAS), but may be considered as an off-label option for refractory cases when standard therapies have failed. 1

Understanding MCAS and Its Manifestations

• MCAS is characterized by recurrent episodes of systemic anaphylaxis concurrently affecting at least 2 organ systems, resulting from secreted mast cell mediators 2
• Common manifestations include:
  • Cardiovascular: hypotension, tachycardia, syncope 2
  • Respiratory: wheezing, shortness of breath, inspiratory stridor 2
  • Dermatologic: flushing, urticaria, pruritus, angioedema 2
  • Gastrointestinal: crampy abdominal pain, diarrhea, nausea, vomiting 2

First-Line Treatment Approach for MCAS

• H1 antihistamines (non-sedating preferred) are first-line for most symptoms and can be increased to 2-4 times the standard dose 3
• H2 antihistamines are recommended for gastrointestinal symptoms and to help attenuate cardiovascular symptoms 3
• Epinephrine autoinjectors should be prescribed for patients with history of systemic anaphylaxis or airway angioedema 3
• Leukotriene modifiers (montelukast, zileuton) may reduce bronchospasm and gastrointestinal symptoms 3
• Oral cromolyn sodium can help with gastrointestinal symptoms and possibly neuropsychiatric manifestations 3

Evidence for Biologics in MCAS

• Omalizumab is the most studied biologic for refractory MCAS:

  • Shown to reduce severity and frequency of allergic reactions 2
  • Can prevent spontaneous episodes of anaphylaxis in case reports 2
  • A systematic review found 61% of patients had partial response and 18% had complete response 4
  • Most effective for ameliorating anaphylaxis and allowing discontinuation of systemic glucocorticoids 4

• Dupilumab (evidence limited):

  • One case report showed near resolution of idiopathic anaphylaxis symptoms over a six-month period in a patient with recurrent episodes 1
  • The mechanism may involve targeting the Th2 pathway, which plays a role in mast cell activation 1
  • Currently considered an off-label option only when standard therapies and first-line biologics have failed 1

Treatment Algorithm for MCAS with Anaphylaxis and Respiratory Symptoms

1. First-line therapy:

   • H1 antihistamines (non-sedating) + H2 antihistamines 3
   • Epinephrine autoinjector for acute anaphylaxis 3
   • Albuterol for bronchospasm 3

2. Second-line therapy:

   • Add leukotriene modifiers (especially with elevated urinary LTE4) 3
   • Add oral cromolyn sodium 3
   • Consider aspirin if elevated prostaglandin levels (use with caution) 2

3. Third-line therapy for refractory cases:

   • Omalizumab (most evidence supports this as the first biologic option) 2, 4
   • Systemic corticosteroids (short-term use only) 3

4. Fourth-line therapy:

   • Consider dupilumab as an off-label option when other therapies have failed 1

Important Considerations and Pitfalls

• Diagnosis of MCAS requires objective documentation of elevated mast cell mediators during attacks 2
• Treatment should be guided by symptoms and specific elevated mediator levels 3
• Aspirin should be used with caution as it can trigger mast cell degranulation in some patients 2
• Long-term steroid use should be avoided due to side effects 3
• Dupilumab has very limited evidence for MCAS - only case reports are available 1
• Consider multidisciplinary management involving allergy specialists and other relevant specialists 3

Monitoring Response to Treatment

• Assess reduction in frequency and severity of anaphylactic episodes 3
• Monitor changes in respiratory symptoms (wheezing, shortness of breath) 3
• Track need for rescue medications (epinephrine, albuterol) 3
• For patients on biologics, evaluate at 3-6 months for clinical response 4