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), though there appears to be a relationship between these conditions through shared pathophysiological mechanisms involving mast cell activation and neuroinflammation. 1

Diagnostic Distinctions and Overlaps

MCAS Definition and Diagnosis

• MCAS is characterized by:

  • Recurrent episodes of systemic anaphylaxis affecting at least 2 of 4 organ systems (cardiovascular, respiratory, dermatologic, gastrointestinal)
  • Acute increases in mast cell mediator levels during symptomatic episodes
  • Response to therapy with mast cell mediator blocking agents or stabilizers 1

• Precise MCAS diagnosis requires:

  • Documented increases in mast cell mediators (tryptase, histamine metabolites, prostaglandins)
  • Symptoms correlating with mediator increases
  • Response to targeted therapy 1

Fibromyalgia in Relation to MCAS

• Fibromyalgia-like pain is listed among clinical criteria that lack precision for diagnosing MCAS, alongside:
  • Fatigue
  • Dermographism
  • Chronic pain
  • Headache
  • Mood disturbances
  • Various other non-specific symptoms 1

Evidence for Relationship

Animal Model Evidence

Recent research (2024) demonstrates that peripheral mast cells are involved in fibromyalgia pathophysiology:

• In a mouse model of fibromyalgia, researchers found:
  • Mast cell infiltration (mastocytosis) in plantar tissue
  • Depletion of mast cell mediators or stabilization of mast cell membranes prevented mechanical and cold allodynia and muscle fatigue
  • Multiple receptors expressed on mast cells appear crucial in mediating fibromyalgia symptoms 2

Clinical Associations

• Both conditions frequently co-occur with:

  • Hypermobile Ehlers-Danlos Syndrome (hEDS)
  • Postural Orthostatic Tachycardia Syndrome (POTS)
  • Irritable Bowel Syndrome (IBS) 1

• In patients with MCAS and refractory GI symptoms:

  • 23.7% had Ehlers-Danlos Syndrome
  • 25.2% had POTS
  • 15.1% had both conditions 1

Pathophysiological Mechanisms

The relationship between MCAS and fibromyalgia likely involves:

1. Mast Cell-Mediated Inflammation:

   • Mast cells release multiple inflammatory mediators (histamine, cytokines, prostaglandins)
   • These mediators can sensitize pain pathways and contribute to widespread pain 2

2. Neuroinflammation:

   • Mast cell activation can trigger neurogenic inflammation
   • This may contribute to central sensitization seen in fibromyalgia 3

3. Shared Triggers:

   • Both conditions can be exacerbated by similar triggers:
     • Stress
     • Physical stimuli
     • Hormonal fluctuations 1

Clinical Implications

Diagnostic Approach

• When evaluating patients with fibromyalgia-like symptoms:
  • Consider MCAS if there are episodic symptoms affecting multiple organ systems
  • Look for cardinal features of MCAS (flushing, pruritus, hypotension, GI complaints)
  • Test for mast cell mediators during symptomatic episodes 1

Treatment Considerations

• Mast cell stabilizers and mediator blockers may benefit patients with overlapping symptoms:

  • H1 and H2 antihistamines
  • Mast cell stabilizers (ketotifen, cromolyn)
  • Leukotriene antagonists 4

• JAK inhibitors like tofacitinib have shown promise in treating MCAS and may potentially benefit patients with overlapping fibromyalgia symptoms 5

Pitfalls and Caveats

1. Diagnostic Confusion:

   • Avoid diagnosing MCAS based solely on fibromyalgia-like pain without evidence of mast cell activation
   • MCAS diagnosis requires documented increases in mast cell mediators during symptomatic episodes 1

2. Treatment Expectations:

   • Not all fibromyalgia patients will respond to mast cell-targeted therapies
   • Response to mast cell-directed therapy is part of MCAS diagnostic criteria 1

3. Comorbidity Management:

   • Even with confirmed MCAS, other conditions need to be correctly diagnosed and treated independently
   • A multidisciplinary approach is often necessary 1, 4

4. Evolving Understanding:

   • The relationship between these conditions is still being researched
   • Theoretical explanations exist, but experimental evidence of biological mechanisms is limited 1

In conclusion, while fibromyalgia and MCAS have distinct diagnostic criteria, emerging evidence suggests shared pathophysiological mechanisms involving mast cell activation. Recognizing this relationship may open new therapeutic avenues for patients with overlapping symptoms.