Eosinophilic Esophagitis 

Eosinophilic Esophagitis – 6 Interesting Facts

  1. Eosinophilic esophagitis is a chronic immune-mediated inflammatory disease leading to esophageal dysfunction, caused by eosinophilic infiltration in esophageal mucosa 1
  2. Most common presentation in adults is solid food dysphagia. Children present with feeding difficulties and abdominal pain 2 3
  3. Endoscopy with esophageal biopsy is the only way to diagnose eosinophilic esophagitis and monitor disease activity 4
  4. Treatment options include medications, dietary modifications/restrictions, and in severe or recalcitrant cases, esophageal dilation 5
  5. Most common complications include food impaction and esophageal stricture; rarely, esophageal perforation is seen 6 7
  6. Symptoms improve with treatment, but recur upon discontinuation of therapy; most cases progress to fibrostenotic disease 8

Pitfalls

  • Reliable diagnosis of eosinophilic esophagitis requires confirmation on histologic analysis; endoscopic appearance alone is insufficient for diagnosis 10
  • There is no standard method of assessing disease activity in routine clinical practice other than through biopsy, which may require several endoscopies and biopsies to confirm diagnosis, ensure lack of response to proton pump inhibitor therapy, and monitor response to therapy 11

Introduction

  • Eosinophilic esophagitis is a chronic immune-mediated inflammatory disease that leads to esophageal dysfunction, caused by eosinophilic infiltration in esophageal mucosa 1
  • Typically triggered by food or environmental allergens
  • Most common in children and adolescents, but adults are affected as well
    • Manifests as feeding difficulties, vomiting, and abdominal pain in children; symptoms may be nonspecific and vary with age 3 12
    • Most often manifests as solid food dysphagia in adults 2
  • Formal pathologic definition: eosinophilic infiltration of esophageal mucosal layer with at least 15 eosinophils per high-power field on esophageal biopsy 13
  • Global pooled incidence and prevalence of eosinophilic esophagitis estimated at 5.31 cases per 100,000 inhabitant-years and 40.04 cases per 100,000 inhabitant-years, respectively; incidence and prevalence have increased substantially over the past several decades 14

Classification

  • I-SEE (Index of Severity for Eosinophilic Esophagitis) has been developed by the American Gastroenterological Association to classify severity of disease activity 15
    • Each of the following are scored:
      • Frequency of symptoms
        • Weekly: 1 point
        • Daily: 2 points
        • Multiple times daily: 4 points
      • Complications
        • Food impaction requiring emergency department visit or endoscopy (patient aged 18 years or older): 2 points
        • Food impaction requiring emergency department visit or endoscopy (patient aged younger than 18 years) or any disease-related hospitalization: 4 points
        • Esophageal perforation, malnutrition, or persistent inflammation requiring elemental diet or systemic therapy: 15 points
      • Inflammatory endoscopic features (edema, furrows, exudates)
        • Localized: 1 point
        • Diffuse: 2 points
      • Inflammatory histology
        • 15 to 60 eosinophils per high-power field: 1 point
        • Greater than 60 eosinophils per high-power field: 2 points
      • Fibrostenotic endoscopic features (rings, strictures)
        • Present but non-obstructive: 1 point
        • Present; minor obstruction: 2 points
        • Present; severe obstruction: 15 points
      • Fibrostenotic histology
        • Characteristic findings present: 2 points
    • Total score is used to assign severity:
      • Less than 1: inactive
      • 1 to 6: mild active
      • 7 to 14: moderate active
      • 15 or greater: severe active
    • I-SEE was developed in 2022 and validation studies are ongoing; early data indicate that I-SEE scores correlate with clinical features at baseline and improve with successful treatment, suggesting that scores can be used in practice to track disease severity and assess response to treatment 16

Diagnosis

Clinical Presentation

History

  • Symptoms in children 3
    • Infants and toddlers present with feeding difficulties
    • Children most often present with dyspepsia
    • Vomiting
    • Abdominal pain
    • Weight loss 17
    • Failure to thrive 17
  • Symptoms in adults 17
    • Solid food dysphagia (most common presenting symptom)
    • Heartburn
    • Food impaction
    • Chest pain, most often retrosternal and worse with swallowing

Physical examination

  • No examination findings are specific to diagnosis 1

Causes and Risk Factors

Causes

  • Multifactorial disease involving environmental, genetic, and immunologic factors, leading to esophageal eosinophilia 10 18
  • In eosinophilic esophagitis, mucosa is infiltrated with eosinophils
  • Exact processes responsible for eosinophilic infiltrate in eosinophilic esophagitis are uncertain 10
    • Eosinophil infiltration of esophageal mucosa may be caused by an immune response to environmental or food antigens in genetically predisposed people
    • Abnormal cytokine and chemokine responses are also implicated in pathogenesis of disease

Risk factors and/or associations

Age
  • Bimodal distribution 19
    • Incidence in children increases with age, peaking at 12 years 19 20
    • Incidence peaks in adults aged 30 to 50 years 20
Sex
  • 3 times more common in males than in females 17 20
Genetics
  • High degree of heritability with strong familial clustering 21
    • Monozygotic twins exhibit high concordance rates, estimated at 40% 22
    • Sibling-risk ratio is 80 (having a sibling with disease increases risk of developing similar disease in other siblings 80-fold) 23
  • In genome-wide association studies, variants at 5 genetic loci have been associated with increased risk of disease 22
    • c11orf30
    • STAT6
    • TSLP
    • CAPN14
    • ANKRD27
Ethnicity/race
  • Occurs in all ethnic groups
  • More common in White populations 12
Other risk factors/associations
  • Strongly associated with other atopic diseases (eg, asthma, allergic rhinitis, IgE-mediated food allergy) 22
    • Rate of coexisting atopic disease is reported to be as high as 70% 22
  • Incidence higher in high-resource countries 14
  • Incidence higher in North America, as compared to Europe and Asia 14

Diagnostic Procedures

  • Endoscopic corrugated (ringed) appearance of esophagus in eosinophilic esophagitis.From Falk GW et al: Diseases of the esophagus. In: Goldman L et al, eds: Goldman-Cecil Medicine. 25th ed. Saunders; 2016:896-908, Figure 138-6.

Primary diagnostic tools

  • Diagnosis is generally based on the combination of typical symptoms along with specific histopathologic findings on specimens from esophageal biopsy taken during upper gastrointestinal endoscopy 41213
    • Consider diagnosis in patients presenting with food impaction or in those with upper endoscopy findings of unexplained esophageal strictures, narrowing, rings, furrows, exudates, edema, crepe paper–like mucosa, or spontaneous or endoscopic esophageal perforation 6 13
    • Suspicion should be increased in the presence of concomitant atopic conditions 13
  • International consensus diagnostic criteria 1213
    • Symptoms related to esophageal dysfunction
    • Eosinophil-predominant inflammation on esophageal biopsy, showing 15 or more eosinophils per high-power field
    • Mucosal eosinophilia is confined to esophageal mucosa
    • Exclusion of secondary causes or contributors of esophageal eosinophilia
  • Additional investigations (eg, CBC, total and food-specific IgE, allergy skin prick testing) may be useful but are not required to confirm diagnosis 18
    • Obtain general biochemistry, including vitamins and micronutrients, to assess the nutritional status
  • Positive response to trial of elimination diet or topical corticosteroids supports diagnosis, but is not required
  • Nonresponse (ongoing esophageal symptoms and histologic findings of esophageal eosinophilia) to a 2-month course of proton pump inhibitor therapy is no longer a diagnostic criterion 13
    • Responsiveness to proton pump inhibitor therapy characterizes a subtype of eosinophilic esophagitis described as proton pump inhibitor–responsive esophageal eosinophilia 13
  • esophageal eosinophilia 13

Laboratory

  • CBC
    • Shows eosinophilia in 50% of patients 18
  • Total IgE
    • Elevated levels in 80% of patients 18

Procedures

  • Esophageal biopsy is required to diagnose eosinophilic esophagitis 1
  • In any patient for whom diagnosis is being considered, collect at least 6 biopsies from different locations in the proximal and distal esophagus, focusing on areas with endoscopic mucosal abnormalities 122024
    • In children, at initial consideration of diagnosis, obtain biopsies from antrum and duodenum to rule out other causes of esophageal eosinophilia 1
  • Holding proton pump inhibitors for at least 3 weeks before endoscopy and biopsy enhances accuracy of diagnosis 12
  • When diagnosis of eosinophilic esophagitis is suspected, perform esophageal biopsy regardless of endoscopic appearance 12 24
  • Suspected eosinophilic esophagitis
  • Esophageal perforation
  • On histopathologic analysis, diagnostic criteria require a minimum of 15 eosinophils per high-power field within esophageal epithelium 1
  • Endoscopy will also show visible abnormalities in most confirmed cases, though none are considered pathognomonic for eosinophilic esophagitis; 25 patterns include:
    • Linear furrows: 48% 26
    • Esophageal rings: 44% 26
    • Pallor/reduced vascularization: 41% 26
    • White plaques: 27% 26
    • Strictures: 21% 26
    • Narrow caliber: 9% 26
  • Endoscopic appearance is normal in 10% of cases, emphasizing the need for biopsy regardless of visual appearance 27

Other diagnostic tools

  • Allergy testing 1
    • Performed to identify a food or group of foods that allows a focused elimination diet specific to the patient
      • Consider if the patient is planning to undergo an elimination diet trial
    • Most common methods include skin prick testing and atopy patch testing
    • Include aeroallergens and the group of 6 foods (milk, wheat, soybean/legumes, egg, peanut/nuts, fish/shellfish) that are most frequently associated with eosinophilic esophagitis 18
    • Limitations
      • Helpful if the result is positive; however, negative result does not necessarily exclude a food culprit, owing to some discordance between testing results and response to food elimination in real practice
      • May be more helpful in children than in adults, especially in determining an elimination diet
      • Some recent guidelines now recommend against the use of allergy testing to determine an elimination diet 12

Differential Diagnosis

Most common

  • Dysphagia is a predominant symptom in eosinophilic esophagitis, while drug-induced, infectious, and caustic damages usually cause chest pain and odynophagia
  • Reflux esophagitis (Related: Gastroesophageal Reflux Disease in Adults)
    • Motility disorder caused by reflux of gastric contents into esophagus
    • Most common symptom is heartburn, without odynophagia
    • Acid exposure from gastroesophageal reflux can sometimes induce inflammatory, eosinophilic infiltrate in esophagus 10
      • Typically, the number of eosinophils seen in gastroesophageal reflux disease (if any) is less than 5 per high-power field 11
    • Eosinophilic infiltrate in gastroesophageal reflux disease usually resolves after proton pump inhibitor therapy and response to antireflux medication can be used to differentiate from eosinophilic esophagitis 28
    • Eosinophilic esophagitis and gastroesophageal reflux disease are not mutually exclusive and can both be present in the same patient 12
  • Infectious esophagitis (Related: Infectious Esophagitis29
    • Esophageal irritation caused by infection with fungi, yeast, or viruses
    • Presents with similar symptoms of dysphagia and retrosternal chest pain on swallowing, but odynophagia is a more prominent concern
    • Often accompanied by oral thrush and occasionally by oropharyngeal ulcers
    • Most often occurs in immunocompromised patients (eg, those with HIV infection or organ transplant, those undergoing glucocorticoid therapy)
    • On endoscopy, identifiable lesions are suggestive of underlying pathogen 29
      • Candida albicans: white mucosal plaques
      • HSV-1: well circumscribed, with slightly raised edges and volcanolike structure
      • Cytomegalovirus: large single ulcers in distal esophagus, linear/longitudinal, and deep on endoscopy
    • Differentiated from eosinophilic esophagitis by visual findings on endoscopy, results of biopsy, or favorable response to course of antimicrobial therapy
  • Esophageal involvement in Crohn disease (Related: Crohn Disease30
    • Typically occurs with concomitant ileocolonic disease; isolated esophageal Crohn disease is extremely rare
    • Almost all patients with upper gastrointestinal tract manifestations in Crohn disease also seek medical care for symptoms related to the lower intestine (ie, diarrhea, weight loss)
    • Symptoms of esophageal Crohn disease include heartburn and vague abdominal discomfort; in more advanced disease, symptoms of dysphagia, nausea, vomiting, and odynophagia predominate
    • Differentiated from eosinophilic esophagitis by endoscopy and biopsy
      • Endoscopic appearance of an esophagus affected by Crohn disease shows aphthous erosions and ulcerations usually localized far from esophagogastric junction 31
      • Histology in Crohn disease shows noncaseating granulomas 31
  • Esophagitis caused by drugs or corrosive materials 27
    • Direct toxic activity on mucosa or by production of caustic acidic or alkaline solutions
    • Symptoms of drug-induced esophagitis are like those of eosinophilic esophagitis, characterized by dysphagia, chest pain, or odynophagia
    • Most common pill offenders are NSAIDs, antibiotics, quinidine, potassium chloride, and bisphosphonates 32
    • Differentiated from eosinophilic esophagitis by endoscopy
      • Main endoscopic findings are ulcers or erosion that occurs in middle or lower third of esophagus 27
      • Other findings may include ulcer with bleeding, kissing ulcers (ulcers facing each other), coating with drug material, impacted pill fragments, and stricture 27
  • Other causes of esophageal eosinophilia 13
    • Eosinophilic gastritis, gastroenteritis, or colitis with esophageal involvement (Related: Bacterial Gastroenteritis)
    • Achalasia
    • Hypereosinophilic syndrome
    • Connective tissue disorders
    • Hypermobility syndromes
    • Autoimmune disorders and vasculitides
    • Dermatologic conditions with esophageal involvement (ie, pemphigus)
    • Drug hypersensitivity reactions
    • Graft-versus-host disease (Related: Graft-Versus-Host Disease)
    • Genetic disorders (eg, Marfan syndrome type II, hyper-IgE syndrome, PTEN hamartoma tumor syndrome) (Related: Marfan Syndrome)

Treatment

Goals

  • Improve clinical symptoms and lessen eosinophilic infiltration in esophagus, to obtain complete regression of disease 4
  • Reduce incidence or recurrence of food impaction 17
  • Delay or prevent progression to fibrostenotic disease (esophageal rings, strictures)

Disposition

Recommendations for specialist referral

  • Refer to a gastroenterologist for esophagogastroduodenoscopy and esophageal biopsy 10
  • Refer to a nutritionist for counseling on dietary modifications; when dietary restriction is employed, consult to ensure that proper calories, vitamins, and micronutrients are maintained 6 10
  • Refer to an allergist or immunologist for formal allergy testing to document food triggers, aeroallergen sensitization, and seasonal variability 18 33

Treatment Options

Main treatment modalities include medications, dietary treatments, and endoscopic dilation 5 12 34

Pharmacologic treatment

  • Proton pump inhibitors are effective in some patients with eosinophilic esophagitis
    • Patients may prefer to trial proton pump inhibitor as a first line therapy before initiating corticosteroids or elimination diets 35
    • Assess for symptomatic and endoscopic improvement after an 8-week course of treatment 36
    • Overall histologic response rate of 42% in observational studies 37
    • Histological remission achieved in approximately 54% and symptoms improve in 65% of pediatric patients 35
    • Responsiveness to proton pump inhibitor therapy was previously used to distinguish eosinophilic esophagitis from a condition termed “proton pump inhibitor–responsive esophageal eosinophilia,” which was otherwise clinically, endoscopically, and histologically indistinguishable from eosinophilic esophagitis; these are now recognized to be the same disease 12
    • Optimal long-term management of children and adults with esophageal eosinophilia who respond to treatment with proton pump inhibitors has not been established; ongoing therapy appears effective in maintaining remission 12 37
  • Swallowed topical steroids are a mainstay of treatment 1638
    • Used for both initial and maintenance therapy 6
    • Budesonide and fluticasone best studied; as no topical steroid formulations have been approved specifically for eosinophilic esophagitis in the United States, treatment generally entails oral administration of preparations originally designed for inhalation use. Fluticasone spray can be swallowed directly while budesonide can be compounded into an oral viscous slurry 1
      • An orodispersible formulation of budesonide is available in Europe but has yet to be approved for use in the United States; oral formulations of fluticasone are currently under study 39
    • US guidelines do not recommend one agent over the other; recent analyses indicate no significant difference between budesonide and fluticasone in achieving histologic response 40
    • Most patients respond during short-term treatment period of 4 to 12 weeks: maintenance therapy is recommended after remission; however, the effects are less clear 37 38
    • Effectiveness
      • Fluticasone induces remission in approximately 50% of children and in approximately 60% of adults 41
      • Budesonide induces remission in approximately 50% to 80% in both children and adults 41
      • No prospective studies directly compare the 2 in response rates 41
      • A 2023 Cochrane systematic review reported that when used for medical treatment of eosinophilic esophagitis, compared to placebo, steroids: 42
        • May lead to slightly better clinical improvement, whether measured dichotomously or continuously
        • Lead to large histological improvement when measured dichotomously and may lead to histological improvement when measured continuously
        • May lead to little to no endoscopic improvement when measured dichotomously and may lead to endoscopic improvement when measured continuously
        • May lead to fewer withdrawals owing to adverse events
    • Relapse rates are high if treatment is withdrawn; maintenance therapy is recommended to prevent recurrence of symptoms and esophageal inflammation 12
  • Systemic corticosteroids are not routinely recommended for treatment; they can be considered if other agents including topical steroids are ineffective, or if rapid improvement is required 123843
    • Usually only used for acute exacerbations (eg, marked dysphagia, hospitalization, weight loss) on a short-term basis, and if topical steroids are ineffective
    • No study has evaluated optimal duration of steroid or therapy 33
  • Dupilumab has received FDA approval for use in the treatment of eosinophilic esophagitis; its role in management, particularly in relation to other treatment modalities, has yet to be fully defined 44
    • Human monoclonal antibody that inhibits IL-4 and IL-13 signaling
    • Previously approved for treatment of atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyposis, and prurigo nodularis
    • Received FDA approval for the treatment of eosinophilic esophagitis in adult and pediatric patients aged 12 years and older weighing at least 40 kg
    • Most common reported side effects include injection site reactions, upper respiratory tract infections, arthralgias, and herpes viral infections
    • FDA approval for eosinophilic esophagitis treatment indication was granted on the basis of a phase 3 trial demonstrating that approximately 60% of patients who received subcutaneous dupilumab either weekly or every 2 weeks up through 24 weeks achieved histologic remission, compared with approximately 5% of patients in the placebo groups; the final phase of the trial is still ongoing as of 2023 45
    • As FDA approval for this expanded indication was granted subsequent to the publication of recent consensus guidelines for the management of eosinophilic esophagitis, role of dupilumab has yet to be addressed in comprehensive guidelines
    • A recent expert opinion document suggested consideration of dupilumab in the following settings: 46
      • First line therapy in patients with:
        • Multiple comorbid atopic conditions meeting criteria for biologic therapy
        • Strong aversion to dietary treatments and swallowed topical steroids
        • Severe eosinophilic esophagitis disease
      • Step-up therapy in patients with:
        • Eosinophilic esophagitis that is difficult to treat
        • Significant weight loss, growth impairment, or failure to thrive due to disease
        • Frequent need of rescue therapies such as systemic steroids or esophageal dilations
        • Severe diet restrictions
        • Significant esophageal strictures or narrow caliber esophagus
        • Disease refractory to current therapy
        • Significant adverse effects to current therapy
  • Other agents such anti–IL-5, anti-IgE, anti-TNF and anti-integrin therapies, azathioprine, 6-mercaptopurine, cromolyn sodium, montelukast, and other novel biologics are not recommended for use at this time except in the context of a clinical trial 12 38

Dietary treatments 47

  • Rationale for dietary treatments is to control the disease by limiting exposure to food antigens that trigger allergy and subsequent immunologic response
  • 3 types of dietary treatments are available: empiric elimination of the most common allergen culprits, targeted elimination based on results of allergy testing, and elemental elimination; empiric elimination is the most commonly used approach
  • Elimination diets are effective in achieving remission in patients with eosinophilic esophagitis 12
  • Selection of a specific dietary approach is individualized to patient responses to allergy testing and/or preferences

Endoscopic treatments

  • Esophageal dilation is used to relieve dysphagia and treat fixed rings or strictures that persist despite medical or dietary therapy 38 41
  • Dilation is used in conjunction with medications, dietary approaches, or both

Factors to consider in selecting a treatment

  • Topical corticosteroids and dietary therapies are roughly equivalent from an efficacy standpoint 48
  • Topical corticosteroids allow ingestion of multiple food triggers and improve quality of life, but symptom relapse occurs in approximately 45% of patients upon discontinuation, usually within 6 weeks 49
  • Systemic side effects of topical corticosteroids in the context of long-term treatment for patients with eosinophilic esophagitis have not been consistently observed 12
  • Dietary restriction therapies allow identification of food triggers, but depending upon the specific diet employed, they can be difficult to implement owing to difficulty with adherence and need for extensive allergy testing
  • Combination therapy
    • Some experts recommend avoiding combined use of corticosteroids with diet therapy initially, reserving this approach for treatment failure 1247
      • Immunosuppressive effects of corticosteroids can obscure histologic responses observed during various phases of an elimination diet, making it difficult to identify a food trigger during the food reintroduction process
    • Some clinicians opt to start a combination of diet and steroid therapy simultaneously; however, there are no data that evaluate superiority of single versus dual therapy 33
  • Proton pump inhibitors, topical corticosteroids, or elimination diets may be continued as maintenance therapy based on risk of recurrence and patient preference 38
  • Dupilumab is an option for first line treatment in severe disease, when patients have other indications for biologic therapy, or when patients are not amenable to diet or steroid therapy; it can be used as step-up therapy in other situations 46

Drug therapy

  • Proton pump inhibitors
    • Esomeprazole 18
      • Esomeprazole Magnesium Powder for Oral suspension; Children and Adolescents: 1 mg/kg/dose (Max: 40 mg/dose) PO twice daily for 8 to 12 weeks, then reduce dose to the lowest dose that maintains remission.
      • Esomeprazole Magnesium Oral capsule, gastro-resistant pellets; Adults: 20 to 40 mg PO twice daily for 8 to 12 weeks, then reduce dose to the lowest dose that maintains remission.
    • Omeprazole 18
      • Omeprazole Magnesium Oral suspension; Children and Adolescents: 1 mg/kg/dose (Max: 40 mg/dose) PO twice daily for 8 to 12 weeks, then reduce dose to the lowest dose that maintains remission.
      • Omeprazole Gastro-resistant tablet; Adults: 20 to 40 mg PO twice daily for 8 to 12 weeks, then reduce dose to the lowest dose that maintains remission.
  • Topical corticosteroids
    • Budesonide 50
      • Budesonide Nebulizer suspension; Children and Adolescents: 0.5 mg PO (swallowed) twice daily for 8 weeks, then reduce dose to the lowest dose that maintains remission.
      • Budesonide Nebulizer suspension; Adults: 1 mg PO (swallowed) twice daily for 8 weeks, then reduce dose to the lowest dose that maintains remission.
    • Fluticasone 1
      • Fluticasone Propionate Pressurized inhalation, suspension; Children and Adolescents: 88 (2 actuations of 44 mcg/actuation) to 440 mcg (2 actuations of 220 mcg/actuation) PO (swallowed) 2 to 4 times daily for 8 weeks, then reduce dose to the lowest dose that maintains remission.
      • Fluticasone Propionate Pressurized inhalation, suspension; Adults: 440 (2 actuations of 220 mcg/actuation) to 880 mcg (4 actuations of 220 mcg/actuation) PO (swallowed) twice daily for 8 weeks, then reduce dose to the lowest dose that maintains remission.
  • Systemic corticosteroids
    • Prednisone
      • Prednisone Oral solution; Children and Adolescents: 1 mg/kg/dose PO once or twice daily.
      • Prednisone Oral tablet; Adults: 1 mg/kg/dose PO once or twice daily.
  • Interleukin-4 receptor alpha antagonist
    • Dupilumab
      • Dupilumab Solution for injection; Children and Adolescents 1 to 17 years weighing 40 kg or more: 300 mg subcutaneously once weekly.
      • Dupilumab Solution for injection; Adults: 300 mg subcutaneously once weekly.

Nondrug and supportive care

Dietary treatments 12 51 52

  • Empiric elimination
    • Foods that account for most food allergies are eliminated; no allergy testing is required
    • There are several elimination diet variants in use, with varying degrees of food restriction: 38
      • 6-food elimination diet removes milk products, soy, wheat, peanuts and tree nuts, eggs, and fish/shellfish
      • 4-food elimination diet removes milk products, wheat, egg, and legumes
      • 2-food elimination diet removes milk products and wheat
      • 1-food elimination diet removes milk products
    • Elimination diet protocols generally entail baseline endoscopy and esophageal mucosal biopsy with repeat endoscopy performed 8 to 12 weeks later 52
      • All food groups for the diet are eliminated initially; if histological remission is achieved upon repeat endoscopy then foods are reintroduced one at a time for at least 8 to 12 weeks with each food, and endoscopy is repeated after each reintroduction to establish trigger food(s)
      • Foods not definitively proved to be antigenic can be restored to the diet, with careful observation for recurrence 6
      • Foods demonstrated to trigger disease may need to be eliminated from the diet indefinitely 6
    • There is practice variation in terms of preferred first line elimination diet regimen
      • Until recently, the 6-food elimination diet was considered the standard approach to diet therapy for most patients; use of this diet remains common 47
        • Response rate (symptomatic and histologic improvement) of the 6-food elimination diet is approximately 52% to 73% in adults and 70% to 74% in children 52
      • 2020 US consensus guidelines suggested use of an empiric 6-food elimination diet over no treatment, commenting that the effectiveness of 1-, 2-, and 4-food elimination diets appeared to be lower 38
      • 2022 UK guidelines also stated the 6-food elimination diet results in higher rates of histologic remission compared to less restrictive diets, but is associated with lower compliance 12
      • More recent studies support the use of less restrictive diets for first line dietary management
        • A 2023 systematic review and meta-analysis assessing the efficacy of different elimination diet regimens reported an overall histological remission rate of 53.8% for all diets 53
          • Individual response rates:
            • 61.3% for 6-food elimination
            • 49.4% for 4-food elimination
            • 51.4% for 1-food elimination
            • 45.7% for targeted elimination (ie, based on results of allergy testing)
          • Authors concluded that results supported use of less restrictive elimination diets for first line treatment
        • A 2023 multicenter, randomized, open-label trial comparing a 6-food elimination diet with a 1-food elimination diet for the treatment of eosinophilic esophagitis in adults reported that improvement in histological and endoscopic findings and rates of histological remission were similar with either diet; 40% of patients in the 6-food elimination diet group had histological remission at 6 weeks, compared to 34% in the 1-food elimination diet group 54
      • Step-wise approaches to dietary restriction are now commonly employed, as they are cost-effective and improve compliance compared to initial selection of a 6-food elimination diet 51
        • On the basis of recent studies, some experts now conclude that eliminating animal milk alone (ie, 1-food elimination) is a reasonable approach to initial dietary management of eosinophilic esophagitis; non-responders can proceed to a 6-food elimination diet
          • In the 2023 trial comparing 6-food and 1-food elimination diets, 43% of participants who did not achieve histological response to 1-food elimination and proceeded to 6-food elimination subsequently reached remission 54
        • Other step-wise approaches, such as starting with a 2-food elimination diet and proceeding to a 4-food and then 6-food elimination diet in case of no response, have also been studied and appear viable 55
  • Targeted elimination diet
    • After testing for food allergies, those foods that elicit a positive result are identified and eliminated
      • Allergy testing usually involves a combination of skin-prick testing and atopy-patch testing to predict specific foods that may trigger disease in a patient
    • Upper endoscopy with biopsy is performed approximately 6 weeks after diet restriction to determine histologic response 52
    • Response rates of targeted elimination diet are approximately 65% in children 56 and approximately 45% in adults 57
    • Recently, this dietary method has lost appeal owing to imprecision, poor predictive value of allergy tests, and findings of comparable or superior histologic and clinical response with empiric elimination diets; recent guidelines now recommend against use of allergy testing to determine the type of elimination diet for disease management 12 47 58
  • Elemental diet
    • Diet exclusively consists of an amino acid–based formula from which all allergenic food peptides are removed (complete removal of table foods)
    • Generally maintained for approximately 6 weeks, after which table foods are gradually reintroduced
    • Effective in relieving symptoms and inducing histologic remission in most patients (approximately 90%), but not a permanent solution for many 57 59 60
    • Many patients have difficulty adhering to diet due to palatability, nutritional concerns, practicality, adverse effect on quality of life, and cost 38
    • Limited role in disease management owing to poor tolerability; may be an option for patients refractory to other treatments 12
    • Primarily used in infants and young children because adherence in older children and adults is poor 35
  • Among the dietary therapies, elemental formula is most effective for inducing resolution or near resolution of disease, but is limited by poor tolerance and adherence 61
  • Effects of dietary restriction on process of esophageal fibrosis is unknown

Coping mechanisms 33

  • Dysphagia and feeding dysfunction
    • Avoid highly textured foods (eg, meats) and bulky foods (eg, bagels)
    • Cut food into small pieces and chew extensively
    • Lubricate foods before eating with liquids or butter
    • Wash food down with liquids
  • Food impaction
    • Wash food down with liquids
    • Raise hands above head or jump up and down, waiting for food to dissolve or to pass
  • Chest pain
    • Avoid foods or liquids that exacerbate pain (eg, highly textured or bulky foods, alcohol, acidic drinks)
Procedures
Esophageal dilation 24 62

General explanation

  • Endoscopic procedure performed to mechanically expand luminal diameter of esophagus when narrowed by stricture
  • Typically performed in adults, as strictures are uncommonly found in children
  • Requires conscious sedation
  • Combine endoscopic dilation with effective antiinflammatory therapy (ie, with swallowed topical steroids) to optimize patient outcomes 12

Indication

  • Esophageal stricture with dysphagia
  • Severe esophageal stenosis (diameter less than 10 mm)
  • Nonresponse to pharmacologic and/or dietetic therapy

Contraindications

  • Suspected esophageal perforation
  • Suspected underlying malignant stricture

Complications

  • Postprocedural chest pain (common; counsel patients that this is expected as part of successful dilation) 63
  • Esophageal perforation (rare, less than 1%) 8

Interpretation of results

  • Symptomatic improvement in dysphagia lasting up to 6 months occurs in approximately 85% of patients 64
  • Remission can last several months, but multiple sessions separated by several weeks are needed to achieve an optimal dilation, especially in those with more fibrostenotic disease 65
    • Serial dilations are required within 1 to 2 years 41

Monitoring

  • Regular scheduled follow-up facilitates assessment of treatment changes, disease response, and adverse effects, and encourages adherence 66
  • Monitor symptoms and esophageal abnormalities (particularly luminal area) with regularly scheduled endoscopy, regardless of specific treatment employed 24 47
  • Follow-up (including endoscopy with biopsy) is recommended 8 to 12 weeks after the initiation of new treatment or any major treatment changes 66
  • Regular clinical follow-up every 12 to 24 months is reasonable in patients with stable disease; frequency of endoscopy for these patients can be individualized 66
  • Frequency of endoscopy for patients in other circumstances (eg, patients with recurrent or worsening symptoms despite treatment, concern for development of complications) can be individualized 12 66
  • I-SEE (Index of Severity for Eosinophilic Esophagitis) can be used as a standardized tool to track disease severity and response to interventions 15 16

Complications and Prognosis

Complications

  • Food impaction (food retention requiring endoscopic extraction; 30%-55% of patients) 6
    • Typically presents with odynophagia, retrosternal chest pain, nausea, and salivation
    • Chest radiograph can help to exclude other foreign bodies and assist with alternative diagnoses
    • May require immediate gastroenterologist consultation to perform emergent endoscopic disimpaction
  • Esophageal perforation 7
    • Rare, but very morbid complication associated with eosinophilic esophagitis
      • Eosinophilic esophagitis is the most common cause of spontaneous esophageal perforation, which usually occurs in the setting of a food bolus obstruction 12
      • Perforation may also occur as a rare (less than 1%) iatrogenic complication of esophageal dilation procedures
    • Typically presents with chest or neck pain after vomiting, with appearance of subcutaneous emphysema
    • Plain radiographs can support diagnosis
      • Lateral cervical spine radiograph, posterior and lateral chest radiographs, and upright abdominal series may show free air, air in fascial planes, or air-fluid level
    • If perforation is suspected, obtain surgical consultation
    • Additional imaging studies (esophagram with water-soluble contrast medium or CT scan) will be required before thoracotomy, drainage, repair, and possible resection
    • Partial perforations may be managed conservatively
  • Strictures (11%-31% of patients) 6
  • Narrow caliber esophagus (approximately 10% of patients) 6
  • Esophageal remodeling associated with fibrosis 67

Prognosis

  • Chronic and relapsing condition; currently cannot be cured, but disease remission is possible with treatment 20 66
  • Associated with persistent symptoms and inflammation resulting in esophageal stricture formation and functional abnormalities, if untreated 20
  • Symptoms usually improve with dietary treatment and/or topical corticosteroids but likely to recur after discontinuing treatment 1
  • Effective treatment likely reduces development of associated complications 66
  • Delay in diagnosis is associated with greater risk for esophageal stenosis 8
  • Long-term treatment may be required indefinitely, particularly in patients with severe symptoms and/or endoscopic manifestations 68

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