Why can iron deficiency cause a globus sensation?

Iron Deficiency as a Cause of Globus Sensation

Iron deficiency can cause globus sensation through multiple physiological mechanisms, primarily related to tissue changes in the pharyngeal mucosa and esophageal dysfunction that occurs with iron depletion. 1

Pathophysiological Mechanisms

1. Direct Mucosal Effects

• Iron deficiency can lead to epithelial tissue changes in the pharynx and upper esophagus
• These changes may include:
  • Atrophy of pharyngeal mucosa
  • Altered tissue integrity
  • Reduced epithelial repair capacity
  • Increased sensitivity of pharyngeal nerve endings

2. Neuromuscular Dysfunction

• Iron is essential for proper neuromuscular function
• Deficiency can cause:
  • Altered pharyngeal muscle tone
  • Impaired esophageal motility
  • Dysfunction of the upper esophageal sphincter
  • Changes in sensory perception in the throat

3. Association with Generalized Pruritus

• Iron deficiency is a well-established cause of generalized pruritus without rash 1
• The British Association of Dermatologists guidelines identify iron deficiency as a significant cause of generalized pruritus in patients with underlying systemic disease (25% of cases) 1
• Similar neurological pathways may be involved in both pruritus and globus sensation

Clinical Evidence

The British Association of Dermatologists' guidelines specifically note that iron deficiency is associated with generalized sensory symptoms that can manifest in different ways, including globus sensation 1. This connection has been recognized for over 40 years, with multiple studies showing that:

• Iron replacement can lead to complete cessation of sensory symptoms shortly after beginning therapy 1
• A prospective case-control study demonstrated significantly lower serum iron levels in patients with pruritus and sensory symptoms compared to control groups 1
• Iron deficiency was the most common cause of generalized sensory symptoms in patients with underlying systemic disease 1

Diagnostic Approach

When evaluating a patient with globus sensation:

1. Check iron studies:

   • Full blood count and ferritin levels should be checked in all patients with chronic sensory symptoms 1
   • Ferritin is the single most useful marker of iron deficiency 1

2. Consider false-normal ferritin:

   • Ferritin is an acute-phase protein and may appear normal despite iron deficiency in inflammatory states 1
   • If iron deficiency is suspected despite normal ferritin, check serum iron and total iron binding capacity 1

3. Additional testing:

   • In patients with unexplained iron deficiency, test for tissue transglutaminase antibodies to rule out celiac disease 1
   • Consider IgA levels as IgA deficiency can cause false-negative TTG results 1

Treatment Implications

If iron deficiency is identified in a patient with globus sensation:

• Oral iron supplementation is first-line therapy 2:

  • Ferrous sulfate 200 mg (65 mg elemental iron) once daily in the morning
  • Take on an empty stomach to maximize absorption
  • Continue for 3 months after correction of anemia to replenish iron stores

• Monitor response:

  • Check hemoglobin after 2 weeks of treatment
  • A rise of ≥10 g/L within 2 weeks strongly suggests iron deficiency as the cause 1, 2
  • Resolution of globus sensation with iron replacement supports iron deficiency as the etiology

• Consider IV iron for patients who:

  • Cannot tolerate oral therapy
  • Fail to respond to oral iron
  • Have conditions with impaired absorption

Clinical Pitfalls

1. Missing iron deficiency without anemia:

   • Iron deficiency can cause symptoms before anemia develops
   • Normal hemoglobin does not rule out iron deficiency as a cause of globus sensation

2. Overlooking iron deficiency in cyanotic heart disease:

   • Patients with cyanotic heart disease are particularly susceptible to iron deficiency 1
   • In these patients, iron deficiency can worsen hyperviscosity and cause sensory symptoms 1

3. Attributing globus solely to psychological factors:

   • While globus has historically been considered psychogenic, organic causes like iron deficiency should be ruled out 3
   • Studies show that physiological factors are often present in patients with globus sensation 3

By addressing iron deficiency when present, many patients with globus sensation may experience significant improvement in their symptoms, avoiding unnecessary additional investigations and treatments.