Epidemiology

• Rare disorder
• Sex: M: F ratio is 9: 1
• Age: average onset usually in 30’s

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Classification of Hypereosinophilic Syndrome (Hypereosinophilic Diseases Working Group of the International Eosinophil Society, 2010) [MEDLINE]

Myeloproliferative Type

• Myeloproliferative Hypereosinophilic Syndrome
  • PDGFRA Rearrangements
  • PDGFRB Rearrangements
  • FGFR1 Rearrangements
  • JAK Point Mutation/Translocation
  • Deletion of 4q12 –> FIPIL1-PDGFRA Fusion
• Chronic Eosinophilic Leukemia (see Chronic Eosinophilic Leukemia)
  • Clinical: clonal eosinophilia

Lymphocytic Type

• General Comments
  • Physiology: aberrant T-cells which produce IL-5
• Clonal T-Cells
• No T-Cell Clone

Familial Hypereosinophilic Syndrome

• Epidemiology: autosomal dominant
• Physiology: mapped to 5q 31-33
• Clinical: asymptomatic eosinophilia present from birth

Organ-Restricted Eosinophilic Disorders

• General Comments
  • Clinical: peripheral eosinophilia with single organ involvement (with eosinophilic organ infiltration)
• Chronic Eosinophilic Pneumonia (see Chronic Eosinophilic Pneumonia, Chronic Eosinophilic Pneumonia)
• Eosinophilic-Associated Gastrointestinal Disorders (EGID)
  • Eosinophilic Esophagitis (see Eosinophilic Esophagitis, Eosinophilic Esophagitis)
  • Eosinophilic Gastroenteritis (see Eosinophilic Gastroenteritis, Eosinophilic Gastroenteritis)
• Eosinophilic Dermatitis (Wells Syndrome)
• Eosinophilic Intrinsic Asthma (see Asthma, Asthma)
• Eosinophilic Sinus Disease

Associated Hypereosinophilic Syndrome

• General Comments
  • Clinical: marked peripheral eosinophilia
• Episodic Angioedema with Eosinophilia (Gleich Syndrome) (see Gleich Syndrome, Gleich Syndrome)
  • Clinical
    • Elevated Serum IgM
    • Episodic Angioedema (see Angioedema, Angioedema)
    • Fever (see Fever, Fever)
    • Leukocytosis with Maked Peripheral Eosinophilia (see Peripheral Eosinophilia, Peripheral Eosinophilia)
    • Pruritus (see Pruritus, Pruritus)
    • Urticaria (see Urticaria, Urticaria)
    • Weight Gain (see Weight Gain, Weight Gain)
• Inflammatory Bowel Disease
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• Churg-Strauss Syndrome (Eosinophilic Granulomatosis with Polyangiitis, EGPA) (see Churg-Strauss Syndrome, Churg-Strauss Syndrome)

Idiopathic Hypereosinophilic Syndrome

• Clinically Variable

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Physiology

• Eosinophilic Infiltration of Various Organs
  • Tissue Damage is More Likely to Occur with Peripheral Eosinophilia >1500 Eosinophils Per uL: however, the degree of peripheral eosinophilia does not accurately predict the risk of organ damage
• Increased Eosinophil Cationic Protein Present within Eosinophils

Mechanisms of Eosinophil Damage to Tissues

• Eosinophil Release of Toxic Granule Products: major basic protein, eosinophil-derived neurotoxin, eosinophil peroxidase, eosinophil cationic protein –> damage to epithelial cells and nerves
• Eosinophil Synthesis of Lipid Mediators: sulfide peptide leukotrienes, platelet activating factor –> smooth muscle contraction and recruitment of inflammatory cells
• Eosinophil Release of Cytokines: GM-CSF, TGF-alpha, TGF-beta, interleukins –> tissue remodeling and fibrosis

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Pathologic Patterns

• Eosinophilic pneumonia: absence of arteritis (excludes Churg-Strauss Syndrome as the cause)

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Diagnosis

The hypereosinophilic syndrome (HES) is characterized by the presence of marked unexplained blood and tissue eosinophilia associated with a variety of clinical manifestations. Since 1975, 3 criteria have been used to define HES: (1) blood eosinophilia ≥1500/mm3 for longer than 6 months (or death before 6 months associated with signs and symptoms of hypereosinophilic disease), (2) lack of evidence for parasitic, allergic, or other known causes of eosinophilia, and (3) presumptive signs of organ involvement, such as heart failure, gastrointestinal dysfunction, central nervous system abnormalities, fever, or weight loss.1

Old definition: idiopathic hypereosinophilic syndrome
– Blood eosinophilia of greater than 1500/mm3 for at least 6 mo
– Unknown trigger of eosinophilia
– Signs and symptoms of organ involvement

Proposed new definition: HES [MEDLINE]
– Blood eosinophilia of greater than 1500/mm3 on at least 2 occasions or evidence of prominent tissue eosinophilia associated with symptoms and marked blood eosinophilia
– Exclusion of secondary causes of eosinophilia, such as parasitic or viral infections, allergic diseases, drug-induced or chemical-induced eosinophilia, hypoadrenalism, and neoplasms

• Pleural fluid:
  • Cell count: eosinophilia
• CXR/Chest CT patterns:
  • Alveolar Infiltrates: may be peripheral
  • Pleural Effusion:
• Serum IgE: elevated
• CBC: marked eosinophilia (range: 20,000-180,000/mm3)
  • Typically higher eosinophil counts than those seen in Churg-Strauss Syndrome
  • Smear shows increased vacuolization of eosinophils
• BM Bx: increased eosinophil precursors

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Clinical

Lung Involvement (50%)

• Pneumonia-Like Process: cough
• Pleural Effusion (see Pleural Effusion-Exudate)

Cardiac Involvement (60%)

• Arrhythmias:
• Cardiomyopathy:
• Tricuspid or Mitral Regurgitation:
• Cardiogenic Thrombi:

Renal Involvement

• HTN
• Proteinuria

Neuro Involvement

• Peripheral neuropathy:
• Intellectual deterioration:
• CVA: due to thromboemboli or CNS vasculitis

GI Involvement

• Abdominal Pain

Rheum Involvement

• Polyarthropathy:

Derm Involvement

• Rash
• Purpura

Constitutional

• Fever
• Anorexia
• Weight loss:

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Treatment

• Steroids: usually initial response
  • Steroid response is predicted by presence of pulmonary eosinophilia, CHF, purpura, and elevated IgE
• Hydroxyurea: for steroid-resistant cases
• Anticoagulation: for cases with thromboemboli

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Prognosis

• High morbidity and mortality

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References

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