Relationship Between Mast Cell Activation Syndrome and Fibromyalgia

Diagnostic Criteria

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, according to the Journal of Allergy and Clinical Immunology 1, 2
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, as stated by the Journal of Allergy and Clinical Immunology 1, 3
The diagnosis of MCAS requires laboratory confirmation with elevated mast cell mediators during symptomatic episodes and response to therapies targeting mast cell mediators, as recommended by the Journal of Allergy and Clinical Immunology 3

MCAS, fibromyalgia, and related conditions like Ehlers-Danlos syndrome (EDS) and Postural Orthostatic Tachycardia Syndrome (POTS) show significant comorbidity patterns, with 23.7% of patients with MCAS and refractory GI symptoms having EDS, according to Clinical Gastroenterology and Hepatology 4, 5, 6
Patients with hypermobile EDS/hypermobility spectrum disorders (HSDs) who have concomitant POTS were more likely to have fibromyalgia, suggesting potential shared pathophysiological mechanisms, as reported by Clinical Gastroenterology and Hepatology 6

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, and measure mast cell mediator levels at baseline and during acute episodes, as recommended by the Journal of Allergy and Clinical Immunology 1, 3
Increases in serum tryptase of 20% above baseline plus 2 ng/mL are necessary to demonstrate evidence of mast cell activation, according to Clinical Gastroenterology and Hepatology 7

If MCAS is confirmed in patients with fibromyalgia-like symptoms, treatment should target mast cell mediators, including options like H1 and H2 antihistamines, leukotriene receptor antagonists, and mast cell stabilizers, as stated by the Journal of Allergy and Clinical Immunology 3, 8

Avoid diagnosing MCAS based solely on fibromyalgia-like symptoms without evidence of episodic multi-system involvement and laboratory confirmation, as warned by the Journal of Allergy and Clinical Immunology 1, 2
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, according to the Journal of Allergy and Clinical Immunology 2, 3