What is the relationship between fibromyalgia and mast cell activation syndrome (MCAS)?

Relationship Between Fibromyalgia and Mast Cell Activation Syndrome

Fibromyalgia and Mast Cell Activation Syndrome (MCAS) have overlapping symptoms but are distinct conditions with limited evidence for a direct causal relationship; MCAS is frequently suspected but rarely confirmed in patients with fibromyalgia-like symptoms. 1, 2

Diagnostic Distinctions

• MCAS is characterized by recurrent episodic symptoms affecting multiple organ systems (cardiovascular, respiratory, dermatologic, and gastrointestinal) with laboratory-confirmed acute increases in mast cell mediators during symptomatic episodes 3, 1
• Fibromyalgia presents with chronic widespread pain, fatigue, and cognitive dysfunction, while MCAS typically presents with episodic symptoms rather than persistent ones 1, 4
• MCAS diagnosis requires:
  • Episodic symptoms affecting at least 2 organ systems
  • Laboratory confirmation with elevated mast cell mediators during symptomatic episodes (serum tryptase increase of 20% above baseline plus 2 ng/mL)
  • Response to therapies targeting mast cell mediators 3, 1

Pathophysiological Connections

• Research suggests mast cells may be involved in fibromyalgia pathophysiology:
  • Animal studies demonstrate increased mast cell infiltration (mastocytosis) in fibromyalgia models 5
  • Mast cells release proinflammatory cytokines, chemokines, and mediators that may contribute to pain sensitization 4, 6
  • Low-grade chronic inflammation mediated by mast cells has been observed in fibromyalgia patients 4

Clinical Overlap and Comorbidities

• MCAS, fibromyalgia, Ehlers-Danlos syndrome (EDS), and Postural Orthostatic Tachycardia Syndrome (POTS) show significant comorbidity patterns 1
• 23.7% of patients with MCAS and refractory GI symptoms have EDS 1
• Patients with hypermobile EDS/hypermobility spectrum disorders who have concomitant POTS are more likely to have fibromyalgia 1
• Despite symptom overlap, a prospective study found MCAS was confirmed in only 2% of patients with suspected MCAS, suggesting that mast cell activation is not driving symptoms in most patients with suspected MCAS 2

Diagnostic Approach

• When evaluating patients with fibromyalgia-like symptoms who might have MCAS:
  • Look for episodic rather than chronic persistent symptoms 3, 1
  • Measure mast cell mediator levels at baseline and during acute episodes 3
  • Test for serum tryptase increases of 20% above baseline plus 2 ng/mL during symptomatic episodes 3
  • Consider additional testing (urinary N-methylhistamine, leukotriene E4, 11β-prostaglandin F2) at specialized centers 3

Treatment Implications

• If MCAS is confirmed in patients with fibromyalgia-like symptoms, treatment should target mast cell mediators 1:
  • H1 and H2 antihistamines (may need higher than standard doses) 3, 1
  • Mast cell stabilizers like cromolyn sodium for gastrointestinal symptoms 3
  • Leukotriene receptor antagonists 3, 1
  • Aspirin for patients with increased urinary 11β-PGF2α levels (use with caution) 3
• Animal studies suggest mast cell membrane stabilizers like ketotifen may help with fibromyalgia-like symptoms 5

Clinical Pitfalls to Avoid

• Do not diagnose MCAS based solely on fibromyalgia-like symptoms without evidence of episodic multi-system involvement and laboratory confirmation 1
• Be aware that persistent symptoms (as seen in fibromyalgia) should direct clinicians to different underlying diagnoses rather than MCAS 3, 1
• Depression and anxiety are common comorbidities in patients with suspected MCAS and may contribute to symptom burden 2
• Despite frequent self-diagnosis, MCAS is confirmed in only a small percentage of patients with suspected MCAS 2