Eosinophil-associated diseases occur in all epithelial organs including the skin, upper and lower respiratory tract, gastrointestinal tract, urinary tract and the heart. A partial listing of eosinophil-associated diseases is as follows:

• Asthma
• Allergies including allergic conjunctivitis and allergic rhinitis
• Allergic inflammation, other
• Angiolymphoid hyperplasia with eosinophilia
• Atopic dermatitis
• Atopic diseases, other
• Bullous pemphigoid and other blistering skin diseases
• Capillary leak syndrome (Interleukin-2 associated)
• Churg Strauss syndrome
• Drug reactions, including drug hypersensitivity syndrome
• Eosinophilia myalgia syndrome
• Eosinophilic cellulitis (Wells’syndrome)
• Eosinophilic colitis
• Eosinophilic cystitis
• Eosinophil esophagitis
• Eosinophilic endomyocardial disease
• Eosinophilic enteritis
• Eosinophilic fasciitis
• Eosinophilic gastrointestinal disease (EGID)
• Eosinophilic gastroenteritis, other
• Eosinophilic pustular folliculitis
• Eosinophilic ulcer of the oral mucosa
• Eosinophilic vasculitis
• Episodic angioedema with eosinophilia (Gleich’s syndrome)
• Facial edema with eosinophilia
• Hypereosinophilic syndrome (HES), myeloproliferative variant
• Hypereosinophilic syndrome (HES), lymphocytic variant
• Hypereosinophilic syndromes (HES), overlap, undefined and familial
• Kimura’s disease
• Nodules, eosinophilia, rheumatism, dermatitis, swelling syndrome (NERDS)
• Parasitism, parasitic inflammation
• Toxic oil syndrome

Epidemiology

• Incidence
  • Eosinophilic vasculitis (EV) - rare
  • Eosinophilic esophagitis (EE) - 2-4/100,000
• Age
  • EE - often diagnosed in third decade; however, present from childhood-elderly
• Sex
  • EE - M>F

Classification

• EV is a disorder that involves eosinophilic infiltration of small blood vessels
• EE is characterized as eosinophilic infiltration of the epithelium of the esophagus

Risk Factors

• EV
  • Connective tissue disease
• EE
  • Positive family history
  • History of severe food allergies

Pathophysiology

• Eosinophilic activity
  • Eosinophilic activity is associated with allergies, parasitic diseases, multiple inflammatory diseases of epithelial organs and neoplastic disease
• Eosinophil major basic protein (eMBP)
  • Eosinophil major basic protein is a cationic protein that is toxic to mammalian cells and tissues
  • Extracellular eMBP in tissues represents eosinophilic activity in the presence or absence of intact eosinophils
  • Many diseases with eosinophilic association include eczematoid, urticarial, angioedema, vasculitis, blistering, fibrosis, airway inflammation, gastrointestinal inflammation, eosinophilic cystitis

Clinical Presentation

• EV
  • Pruritus
  • Erythematous purpuric plaques
  • Angioedema
• EE
  • Children <2 years old - feeding disorders, failure to thrive
  • Children 2-12 - emesis, abdominal pain
  • >12 years old - dysphagia, esophageal food impaction

Treatment

• EV - glucocorticoids, other glucocorticoid sparing agents
• EE
  • Elimination diets
  • Glucocorticoids, other glucocorticoid sparing agents

NOTE:  Eosinophil (eMBP), if mistakenly abbreviated MBP, will be confused with myelin basic protein - order appropriately.

Diagnosis

• Indications for testing
  • Known or suspected eosinophil involvement in disease, either in the presence or absence of identifiable intact eosinophils in tissue and/or peripheral blood
    • When eosinophils degranulate in disease, their presence and contribution to pathogenesis may not be identified by routine tissue staining
  • Specific disorders listed in Clinical Background which include the following
    • Eosinophilic vasculitis - compatible clinical presentation - purpuric papules and pruritus or angioedema
    • Eosinophilic esophagitis
      • Children - feeding disorders, failure to thrive, dysphagia
      • Adults - dysphagia
• Laboratory testing
  • CBC - with differential
    • Frequently will note blood eosinophilia (usually <2 fold)
  • Food allergy testing in EE with serum IgE specific tests or skin prick testing
    • Consideration in EE presenting in children
  • Disease specific testing for other eosinophil-associated disease—see references
  • Persistent, prolonged eosinophilia from any cause may be associated with eosinophilic endomyocardial disease and should be evaluated
  • Thrombotic events associated with hypereosinophilic syndromes mandate emergent evaluation
• Histology
  • Biopsy of appropriate tissue site with staining for eMBP
    • EV - angiocentric eMBP staining
    • EE - esophageal biopsy demonstrating >20 eosinophils in the epithelium/hpf
      • Extracellular eMBP also may be found in the biopsy staining