Why are individuals with Ehlers-Danlos Syndrome (EDS), Mast Cell Activation Syndrome (MCAS), and Dysautonomia more prone to iron deficiency?

Iron Deficiency in Ehlers-Danlos Syndrome, MCAS, and Dysautonomia

Individuals with Ehlers-Danlos Syndrome (EDS), Mast Cell Activation Syndrome (MCAS), and Dysautonomia are prone to iron deficiency primarily due to gastrointestinal dysfunction, bleeding abnormalities, and inflammatory processes that impair iron absorption.

Mechanisms of Iron Deficiency in These Conditions

1. Gastrointestinal Dysfunction

• Small intestinal dysmotility: Patients with EDS often have gastrointestinal dysmotility that can impair nutrient absorption, including iron 1
• Malabsorption: Disrupted gut function in EDS and MCAS can lead to poor absorption of iron and other nutrients 1
• Celiac disease association: There is a higher prevalence of celiac disease in these patient populations, which directly impairs iron absorption through duodenal villous atrophy 1

2. Bleeding Abnormalities

• Platelet dysfunction: Up to 90% of EDS patients have platelet function abnormalities that contribute to bleeding risk 2
• Vascular fragility: The connective tissue defects in EDS lead to increased vascular fragility and susceptibility to bleeding 2
• Occult blood loss: Patients may experience chronic, low-grade gastrointestinal bleeding that can be difficult to detect but contributes to iron deficiency over time 1

3. Inflammatory and Immune-Mediated Processes

• Mast cell activation: MCAS causes release of inflammatory mediators that can damage the gastrointestinal mucosa and impair iron absorption 3
• Chronic inflammation: Inflammatory processes can increase hepcidin production, which blocks iron absorption and mobilization from stores 1
• Dysautonomia effects: Autonomic dysfunction can alter gut motility and blood flow, further compromising nutrient absorption 4

Clinical Implications and Management

Diagnostic Approach

• Monitor ferritin and transferrin saturation regularly in these patients, as they are at high risk for iron deficiency 1
• Consider that in the presence of inflammation (common in MCAS), serum ferritin levels up to 100 μg/L may still reflect iron deficiency 1
• Evaluate for occult GI bleeding, especially when iron deficiency is recurrent or refractory to treatment 1

Treatment Considerations

• Oral iron supplementation may be poorly tolerated due to gastrointestinal symptoms that are already prevalent in these conditions 1
• Intravenous iron therapy may be necessary when oral iron is not tolerated or is ineffective 1
• Address underlying mechanisms:
  • Optimize management of MCAS to reduce inflammation and GI symptoms
  • Consider nutritional supplementation beyond iron alone, as these patients often have multiple deficiencies 5
  • Manage dysautonomia to improve gut function and blood flow

Special Considerations

Comorbid Conditions

• The triad of EDS, MCAS, and Dysautonomia represents a complex clinical picture where each condition can exacerbate the others 1, 4
• These conditions frequently overlap with other disorders that can contribute to iron deficiency:
  • Postural Orthostatic Tachycardia Syndrome (POTS) 1
  • Gastrointestinal dysmotility disorders 1
  • Small intestinal bacterial overgrowth

Monitoring and Follow-up

• Regular monitoring of iron status is essential, particularly in women of childbearing age with these conditions 1
• Iron deficiency may persist despite treatment, requiring ongoing management and periodic reassessment 1
• Consider the impact of menstruation in female patients, which can further deplete iron stores 1

By understanding these mechanisms, clinicians can better anticipate, diagnose, and manage iron deficiency in patients with EDS, MCAS, and Dysautonomia, potentially improving quality of life and reducing complications associated with chronic iron deficiency.