What is the relationship between Mast Cell Activation Syndrome (MCAS) and Fibromyalgia?

Relationship Between Mast Cell Activation Syndrome and Fibromyalgia

Fibromyalgia-like pain is recognized as a non-specific clinical manifestation that may occur in patients with Mast Cell Activation Syndrome (MCAS), but it is not a precise diagnostic criterion for MCAS. 1

Diagnostic Distinctions

• MCAS is characterized by recurrent episodes of systemic anaphylaxis with concurrent involvement of at least 2 of 4 organ systems (cardiovascular, respiratory, dermatologic, and gastrointestinal), associated with acute increases in specific mast cell mediator levels 1
• Fibromyalgia symptoms such as chronic pain, fatigue, and cognitive dysfunction are listed among the clinical criteria that "lack precision" for diagnosing MCAS, despite being commonly reported by patients 1
• The diagnosis of MCAS requires laboratory confirmation with elevated mast cell mediators during symptomatic episodes and response to therapies targeting mast cell mediators 1

Potential Mechanistic Links

• Recent animal research demonstrates that peripheral mast cells are involved in experimental fibromyalgia models, with mast cell infiltration (mastocytosis) observed in plantar tissue of affected mice 2
• Depletion of mast cell mediators or stabilization of mast cell membranes prevented fibromyalgia-like symptoms in experimental models, suggesting a potential causal relationship 2
• Mast cells can release neurosensitizing proinflammatory substances (cytokines, preformed mediators, lipids) that may contribute to low-grade inflammation observed in fibromyalgia 3
• Mast cell-derived tumor necrosis factor (TNF) induces nerve growth factor (NGF) and participates in nerve fiber elongation in skin hypersensitivity, potentially explaining some fibromyalgia symptoms 3

Clinical Overlap and Comorbidities

• Both conditions can present with overlapping symptoms including fatigue, pain, and cognitive dysfunction 4, 3
• MCAS, fibromyalgia, and related conditions like Ehlers-Danlos syndrome (EDS) and Postural Orthostatic Tachycardia Syndrome (POTS) show significant comorbidity patterns 1
• In one prospective study of 139 patients with MCAS and refractory GI symptoms, 23.7% had EDS, which is also associated with fibromyalgia-like symptoms 1
• Patients with hypermobile EDS/hypermobility spectrum disorders (HSDs) who have concomitant POTS were more likely to have fibromyalgia, suggesting potential shared pathophysiological mechanisms 1

Diagnostic Approach

• When evaluating patients with suspected MCAS who have fibromyalgia-like symptoms, clinicians should:
  • Look for episodic symptoms affecting multiple organ systems rather than chronic persistent symptoms 1
  • Measure mast cell mediator levels at baseline and during acute episodes (serum tryptase, urinary N-methylhistamine, 11β-PGF2α, LTE4) 1
  • Consider that increases in serum tryptase of 20% above baseline plus 2 ng/mL are necessary to demonstrate evidence of mast cell activation 1
  • Evaluate response to therapies targeting mast cell mediators 1

Treatment Implications

• If MCAS is confirmed in patients with fibromyalgia-like symptoms, treatment should target mast cell mediators 1
• Options include H1 and H2 antihistamines, leukotriene receptor antagonists, and mast cell stabilizers 1
• Experimental evidence suggests that targeting specific receptors (PAR-2,5-HT2A, 5-HT3, H1, NK1) may help alleviate fibromyalgia-related symptoms when mast cell involvement is present 2
• Patients with MCAS may be more sensitive to medication excipients, which can complicate treatment of both conditions 5

Clinical Pitfalls to Avoid

• Avoid diagnosing MCAS based solely on fibromyalgia-like symptoms without evidence of episodic multi-system involvement and laboratory confirmation 1
• Do not assume all patients with fibromyalgia have MCAS or vice versa, as the relationship is complex and not fully established 1, 4
• Be aware that persistent symptoms (as seen in fibromyalgia) should direct clinicians to different underlying diagnoses rather than MCAS, which typically presents with episodic symptoms 1
• Recognize that both conditions require thorough evaluation for other comorbidities that may influence treatment approach 1, 6