How to treat fibromyalgia with mast cell activation syndrome (MCAS)?

Treatment of Fibromyalgia with Mast Cell Activation Syndrome

A multidisciplinary approach combining mast cell stabilization therapy with standard fibromyalgia treatments is required for effective management of patients with both fibromyalgia and MCAS. 1

Understanding the Connection

Recent research suggests a potential pathophysiological link between mast cell activation and fibromyalgia symptoms:

• Mast cells release neuro-sensitizing molecules (histamine, IL-1β, IL-6, TNF, CGRP) that can stimulate pain pathways 2
• Peripheral mast cell infiltration (mastocytosis) has been demonstrated in experimental fibromyalgia models 3
• Mast cell mediators contribute to neuroinflammation that may worsen fibromyalgia symptoms 2

Treatment Algorithm

Step 1: Control Mast Cell Activation

1. H1 and H2 Antihistamines

   • First-line therapy to block histamine-mediated symptoms
   • Examples: cetirizine, fexofenadine (H1) combined with famotidine (H2)
   • Schedule: Daily administration rather than as-needed

2. Mast Cell Stabilizers

   • Oral cromolyn sodium - FDA-approved for mastocytosis; improves diarrhea, flushing, headaches, urticaria, abdominal pain, and itching 4
   • Ketotifen fumarate - Has shown efficacy in preventing mechanical and cold allodynia in experimental models 3

3. Trigger Avoidance

   • Identify and avoid individual MCAS triggers (foods, medications, temperature extremes, stress)
   • Maintain consistent sleep schedule and stress management

Step 2: Treat Fibromyalgia Symptoms

1. Pharmacological Management (based on EULAR recommendations) 1

   a. First-line medications:

   • Antidepressants (Level of evidence: Ib, Strength: A)
     • Amitriptyline, duloxetine, milnacipran
     • Note: Use caution with TCAs as they may exacerbate MCAS symptoms in some patients

   b. Second-line medications:

   • Pregabalin (Level of evidence: Ib, Strength: A) 5
     • Effective for pain reduction and improvement in function
     • Start at low doses (75mg BID) and titrate slowly

   c. For breakthrough pain:

   • Tramadol (Level of evidence: Ib, Strength: A) 1
     • Use with caution as opioids can trigger mast cell degranulation
     • Avoid stronger opioids and corticosteroids

2. Non-Pharmacological Approaches 1

   a. Physical therapies:

   • Heated pool therapy (Level of evidence: IIa, Strength: B)
   • Individually tailored exercise programs (Level of evidence: IIb, Strength: C)
     • Start with gentle, progressive exercise
     • Monitor for post-exertional symptom flares

   b. Cognitive-behavioral therapy (Level of evidence: IV, Strength: D)

   • Addresses pain catastrophizing and improves coping strategies

   c. Complementary approaches:

   • Relaxation techniques
   • Mindfulness meditation
   • Gentle yoga or tai chi

Special Considerations for Combined MCAS and Fibromyalgia

1. Medication Sensitivities

   • Start all medications at lower doses than typically prescribed
   • Gradually titrate while monitoring for mast cell activation symptoms
   • Be aware that NSAIDs may trigger mast cell degranulation in some patients

2. Pain Management Challenges

   • Pain itself can trigger mast cell activation, creating a vicious cycle 1
   • Address both mast cell activation and central pain sensitization

3. Gastrointestinal Symptoms

   • Common in both conditions and may require specific management 6
   • Consider specialized diets (low histamine) if food triggers are identified

4. Sleep Disturbances

   • Prioritize sleep hygiene and management of sleep disorders
   • Poor sleep can worsen both fibromyalgia pain and mast cell activation

Monitoring and Follow-up

• Regular assessment of both fibromyalgia symptoms (using validated tools like FIQ) and MCAS symptoms
• Monitor for changes in mast cell mediator levels when symptoms change significantly
• Adjust treatment based on symptom control and tolerability

Pitfalls to Avoid

1. Overlooking MCAS triggers that may be exacerbating fibromyalgia symptoms
2. Using medications that worsen MCAS (certain muscle relaxants, NSAIDs in sensitive individuals)
3. Focusing solely on pain management without addressing underlying mast cell activation
4. Overreliance on opioids which may worsen mast cell activation in some patients
5. Dismissing symptoms as "just fibromyalgia" when they may represent mast cell activation requiring specific treatment

By addressing both conditions simultaneously with this structured approach, patients with comorbid fibromyalgia and MCAS can experience significant improvement in quality of life and symptom control.