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

Relationship Between Mast Cell Activation Syndrome and Fibromyalgia

Fibromyalgia-like pain is considered a non-specific clinical criterion that lacks precision for diagnosing Mast Cell Activation Syndrome (MCAS), although there is emerging evidence suggesting mast cells play a role in fibromyalgia pathophysiology. 1

Diagnostic Relationship

MCAS Diagnostic Criteria

MCAS is diagnosed based on three specific criteria:

• Recurrent episodes affecting ≥2 organ systems (cardiovascular, dermatologic, respiratory, gastrointestinal)
• Documented increase in validated mast cell mediators during symptomatic episodes
• Response to medications targeting mast cell mediators 2

Fibromyalgia in MCAS Context

• Fibromyalgia-like pain is listed among clinical criteria that lack precision for diagnosing MCAS 1
• This appears alongside other non-specific symptoms such as:
  • Fatigue
  • Dermographism
  • Chronic low back pain
  • Headache
  • Mood disturbances
  • Anxiety

Pathophysiological Connections

Mast Cell Involvement in Fibromyalgia

Recent research suggests potential mechanisms linking these conditions:

• Mast cells release proinflammatory cytokines, chemokines, and mediators that may contribute to fibromyalgia symptoms 3

• In fibromyalgia models, there is evidence of:

  • Increased mast cell infiltration (mastocytosis) in tissues 4
  • Elevated levels of TNF (produced by mast cells) 3
  • Low-grade chronic inflammation mediated by mast cells 5

• A 2024 experimental study demonstrated that:

  • Mast cell depletion or stabilization prevented fibromyalgia-like symptoms in mice
  • Antagonists of receptors expressed on mast cells reversed allodynia and fatigue 4

Clinical Implications

Diagnostic Considerations

• When evaluating patients with overlapping symptoms:
  • Focus on established diagnostic criteria for each condition separately
  • Avoid using fibromyalgia as a primary diagnostic criterion for MCAS
  • Document objective increases in mast cell mediators during symptomatic episodes for MCAS diagnosis 2

Treatment Approach

If both conditions are present:

1. Treat MCAS according to established protocols targeting specific mediators
2. Address fibromyalgia symptoms with standard fibromyalgia treatments
3. Consider mast cell stabilizers that might benefit both conditions 4

Comorbidity Patterns

The conditions may co-occur within a broader spectrum of disorders:

• MCAS, Ehlers-Danlos Syndrome (EDS), and Postural Orthostatic Tachycardia Syndrome (POTS) show significant overlap 1
• In one prospective study of patients with MCAS and refractory GI symptoms:
  • 23.7% had EDS
  • 25.2% had POTS
  • 15.1% had both EDS and POTS 1
• Patients with these overlapping conditions were more likely to have fibromyalgia 1

Cautions and Pitfalls

• Avoid diagnosing MCAS based solely on fibromyalgia symptoms without meeting established MCAS criteria
• Recognize that chronic symptoms without episodic pattern should direct clinicians to different diagnoses 1
• Remember that persistent symptoms (rather than episodic) are more characteristic of fibromyalgia than MCAS
• Ensure that other conditions are correctly diagnosed and treated independently, even when MCAS is present 1

Future Research Directions

The American Academy of Allergy, Asthma, and Immunology notes that more research is needed to understand:

• The relationship between MCAS and other manifestations of genetic conditions 1
• The role of IL-37 as a potential therapeutic target for inhibiting inflammation in fibromyalgia 3, 5
• The precise mechanisms by which mast cells contribute to pain and fatigue in fibromyalgia 4