Page 663 - Clinical Immunology_ Principles and Practice ( PDFDrive )

CHaPter 46 Eosinophil-Associated Gastrointestinal Disorders 637

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eosinophilic infiltrate of the mucosa (e.g., GERD). Several biopsies
should be taken in EoE: tissue eosinophils can be patchily dis- Drugs
tributed in EoE, whereas eosinophils appear superficially along Acid suppression with proton pump inhibitors (PPI) is not usually
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the luminal surface. Because white exudates correspond to effective in relieving symptoms and resolving eosinophilic
eosinophil aggregations and microabscesses (Fig. 46.3), biopsies inflammation in patients with EoE. However, patients with
should preferably be taken from these areas. concomitant GERD, and a subgroup of EoE patients with “PPI-
responsive” EoE, may respond to treatment with PPI. Therefore
Treatment PPI therapy should not be considered as first-line treatment but
As a result of recent advances in the understanding of the natural instead used as cotherapy in patients with secondary or coexisting
course of the disease, at least three reasons have been determined GERD. 4,8
to treat EoE: (a) improvement of quality of life after resolution Systemic and topical corticosteroids show comparable effective-
of the swallowing disturbances; (b) reduction of the risk of severe ness in resolving signs and symptoms of active EoE in both
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esophageal injury by preventing long-lasting food impactions; children and adults. As topical steroids have fewer side effects,
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and (c) prevention of esophageal remodeling. The current they are recommended as first-line therapy. Short-term use of
treatment options can be summarized as the three D’s (Drugs, systemic corticosteroids may be limited to emergent cases, such
Diet, and Dilatation) and are presented in Table 46.3. as dysphagia requiring hospitalization, patients with dehydration
due to swallowing difficulties, or patients with symptoms refrac-
tory to topical steroids. Discontinuation of topical and systemic
corticosteroids is usually followed by recurrence of the disease
TABLE 46.3 Current treatment Options within a few weeks. 8
for eosinophilic esophagitis: the three D’s Antiallergic drugs have been found largely ineffective in EoE
(Drugs, Diet, and Dilatation) treatment. Cromolyn sodium has no apparent therapeutic effect,
and although leukotriene receptor antagonists have been shown
tHeraPeUtiC OPtiONS to induce symptomatic relief, they do not affect esophageal
Drugs eosinophilia.
• Swallowed topical corticosteroids (budesonide, fluticasone) Only limited data are available for targeted therapy with novel
• Systemic corticosteroids (prednisone)
• Biologicals (monoclonal antibodies against interleukin [IL]-13, IL-5) biological agents or immunosuppressants. The most impressive
• Immunosuppressants (azathioprine, 6-mercaptopurine) effect on symptoms, inflammation, and molecular abnormalities
• Antiallergic agents (CRTH2 blockers) has been demonstrated with QAX576, a monoclonal anti-IL-13
antibody. Mepolizumab (anti-IL-5) significantly reduced esopha-
Diets geal eosinophils in adult EoE patients with only minimal effects
7,8
• Targeted elimination diets (individualized based on results of allergic on clinical improvement. Treatment of EoE patients with the
testing) anti-TNF-α antibody infliximab did not reduce eosinophilic
• Empiric “6-Food” elimination diet (milk, soy, wheat, nuts, eggs, tissue infiltration or improve symptoms, even though massive
seafood)
• Elemental diet (protein-free formulas) expression of TNF-α has been shown in the squamous epithelium
of the esophagus in active EoE. The immunosuppressants aza-
Dilatation thioprine and 6-mercaptopurine were effective in inducing and
• For strictures maintaining remission in three corticosteroid-refractory EoE
patients. However, further evaluation of these alternatives for
corticosteroid-refractory EoE is needed before they can be
implemented into daily clinical practice.

Diet
Several prospective uncontrolled trials have been conducted to
assess the potential of three different diets in treating EoE.
Individually tailored so-called targeted elimination diets, empirical
six-food elimination diets (removal of the six most common
allergenic foods such as dairy, eggs, wheat, soy, peanuts, fish/
shellfish), and a protein-free elemental diet have all shown efficacy
7-9
in active EoE. The choice of a specific dietary therapy requires
that the patient’s lifestyle and family resources be considered.
So far, dietary treatment has been more effective in children
than in adults. Overall, the value and the feasibility of dietary
therapy require further evaluation.
Dilatation
Esophageal dilatation leads to long-lasting symptom relief but
does not influence the underlying inflammation. It should
fiG 46.3 Histopathological Findings in Eosinophilic Esopha- therefore be reserved for patients who present with functional
gitis (EoE). Representative histological pictures of active eosino- esophageal narrowing (strictures, stenosis) that is refractory to
philic esophagitis showing a dense infiltration of the squamous drug therapy. Endoscopic dilatation should be performed with
epithelium with eosinophils forming microabscesses. caution, as it carries a risk of esophageal injury, although recently