What is Syndrome de Gleich?

Syndrome de Gleich (Episodic Angioedema with Eosinophilia)

Syndrome de Gleich, also known as episodic angioedema with eosinophilia (EAE), is a rare disorder characterized by recurrent episodes of angioedema, hypereosinophilia, elevated serum IgM levels, and good response to corticosteroid therapy. 1

Clinical Characteristics

• Recurrent or non-recurrent episodes of angioedema, primarily affecting the face and upper limbs 1, 2
• Marked peripheral blood eosinophilia (typically >1,500 cells/μL) 1, 3
• Elevated serum IgM levels (observed in approximately 67% of patients) 2
• Weight gain during episodes (up to 12% of body weight) 4
• Fever may occur during acute episodes 1
• Urticaria in some cases, though not universally present 5
• Episodes typically last approximately 5.5 days (range 1-90 days) 2

Pathophysiology

• Elevated interleukin-5 (IL-5) levels during acute exacerbations, suggesting a key role in the pathogenesis 3
• Increased levels of chemokines CCL2 and CCL11 during acute phases 3
• CD3+ CD8- lymphocyte population with high frequency of IL-4, IL-5, and IL-13-producing cells 3
• Abnormal T-cell immunophenotypes detected in 40% of patients, with 17% showing evidence of clonal T-cell receptor gamma locus gene rearrangement 2

Diagnostic Approach

• Diagnosis is based on clinical presentation and laboratory findings 1
• Key laboratory findings include:
  • Marked peripheral eosinophilia during episodes 1, 3
  • Elevated serum IgM levels 1, 2
  • Elevated eosinophil cationic protein (ECP) levels 3
• Skin biopsy may show perivascular eosinophil infiltration 4
• Exclusion of other causes of hypereosinophilia is essential 4

Variants

• Classical (episodic) form as described by Gleich et al. with recurrent attacks 1
• Non-episodic angioedema with eosinophilia (NEAE), more commonly observed in Japan, characterized by:
  • Single episode without recurrence
  • Predominance in young females
  • Occurrence frequently in autumn
  • Arthritis in some patients
  • Increased serum LDH levels in some cases 5

Treatment

• Systemic corticosteroids are the mainstay of treatment, with excellent response in most patients 1, 4
• For acute episodes, prednisone 50-75 mg/day is typically effective 3
• Maintenance doses of prednisone (7.5-25 mg/day) may be required in some patients 3
• Anti-IL-5 therapy (mepolizumab) has shown efficacy in reducing:
  • Frequency of exacerbations
  • Eosinophil counts
  • ECP serum levels
  • Required corticosteroid doses 3
• Patients with abnormal T-cell populations have a shorter time to flare (hazard ratio 4.15) and may require more aggressive therapy 2
• Non-episodic forms may be treated with antiallergic drugs or simply observed, as spontaneous remission is common 5

Prognosis

• Generally favorable prognosis with good response to therapy 1
• At long-term follow-up (median 53 months):
  • 10% of patients were able to discontinue all treatments
  • 37% achieved clinical and biological remission on low-dose prednisone (<10 mg daily) 2
• Presence of abnormal T-cell phenotype is associated with shorter time to relapse 2