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Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus that affects both children and adults. EoE is defined by symptoms of esophageal dysfunction (eg, dysphagia, vomiting, difficulty in feeding), with presentation varying depending on patient age.
The global incidence of EoE has increased in recent decades. In the United States alone, EoE is estimated to affect approximately 150,000 people and result in as much as $1.4 billion in annual healthcare costs.
There currently is no clear treatment hierarchy for EoE, and long delays between symptom onset and diagnoses are common.
Still, the knowledge base surrounding the disease is growing, and existing interventions have shown tremendous success at curbing symptoms and disease progression.
To help clinicians stay up to date on the latest information on this debilitating disease, here are five things to know about EoE.
1. EoE prevalence is increasing although not consistently around the globe.
EoE was first recognized as a distinct clinical entity in the early 1990s, when it was considered a relatively rare disease. Now, the incidence and prevalence rates of EoE are escalating at rates that cannot be explained by increased disease awareness and detection.
Although EoE has been diagnosed in Latin America, the Middle East, and Asia, such instances are relatively uncommon in comparison with the spiking rates noted in the United States; in Western Europe, including Denmark, the Netherlands, and Switzerland; and in Australia.
Emerging data suggest that climate and location may be a factor in the varying incidence rates of EoE. An analysis of 233,649 patients in a US pathology database reported that EoE was more common in cold and arid climate zones than in tropical zones. Another study suggests that EoE is more common in low-density, rural environments compared with urban settings.
2. Environmental and food exposures may trigger EoE, and genetics probably play a role.
The unequal geographic distribution of EoE lends credence to the theory that external triggers, which naturally differ in various locales, play an outsized role in its development.
Mice studies have indicated that the inhalation of allergens induces notable eosinophil infiltration and degranulation, and a pilot study conducted in New York City found that EoE symptoms peaked during the July-to-September period when grass pollen counts were at their highest.
Early-life factors that can result in alteration to the microbiome have also been identified as possibly influencing EoE development. They include cesarean delivery, preterm delivery, admission to a neonatal intensive care unit, infant formula use, and maternal or infant use of antibiotics. Conversely, evidence suggests that Helicobacter pylori infection may be protective against EoE due to immunomodulating effects that have not yet been sufficiently identified in the literature.
Yet, the clearest association between EoE and outside triggers is found with food exposures. In one analysis of pediatric patients, the items that were most commonly associated with elevated food-specific serum immunoglobulin E antibodies in patients with EoE were milk (78%), wheat (69%), eggs (64%), peanuts (54%), and soy (51%). Food allergies are also on the uptick in countries with rising EoE rates, suggesting that the two trends may be interrelated.
From a genetic standpoint, EoE is more likely to develop in those with first-degree relatives with the disease than in the general population. Thirty independent genes thought to be associated with EoE have been identified. EoE is also significantly more common in men than in women.
3. Diagnosis requires knowing the symptoms, excluding other disorders, and performing biopsy.
EoE can occur early in life, with approximately one third of children with the disease presenting under age 5 years. The prevalence rises with age, eventually peaking in those aged 35-45 years.
The presentation of EoE can be quite variable depending on patient age. Pediatric patients are significantly more likely to experience failure to thrive, vomiting, and heartburn, whereas their adult counterparts more often present with food impaction and dysphagia.
At the 2018 AGREE international consensus conference, researchers defined diagnostic criteria as presence of esophageal dysfunction symptoms; exclusion of non-EoE disorders, such as gastroesophageal reflux disease and achalasia; and esophageal biopsy findings of at least 15 eosinophils per high-power field (or approximately 60 eosinophils per mm2).
Endoscopic findings can also be crucial in diagnosing EoE because patients with this disease often present with inflammatory patterns recognizable in the form of exudates, furrows, and edema and/or fibrotic phenotypes such as the presence of rings and stenosis. Clinicians are advised to refer to the Endoscopic Reference Score proposed by Hirano and colleagues.
4. Treatment approaches rely on the ‘3 Ds.’
Although there is currently no leading strategy for the primary treatment of EoE, clinicians can avail themselves of suggested pathways.
The lack of a treatment hierarchy means that patients typically are very involved in selecting the therapy that works best for them. Physicians should be aware that patients researching EoE on their own might not find the information they need. A recent study found that the artificial intelligence tool ChatGPT was highly inaccurate when it came to providing answers about EoE.
The treatment strategies that clinicians and their patients can choose from revolve around the “3 Ds”: diet, drugs, and dilation.
Diet:
Three dietary interventions are available for EoE treatment:
- Elemental diet, in which patients consume only an amino-acid based formula that does not include any intact proteins
- Empiric elimination diet, which removes foods more commonly associated with food allergy regardless of whether there has been a positive allergy testing result
- Allergy testing-directed food elimination, which involves avoidance of all foods for which specific antibodies were detected or that tested positive on skin-prick tests
Each of these dietary interventions has clear advantages and drawbacks that should be discussed with patients. Elemental diets achieve robust histologic responses, yet their highly restrictive nature makes compliance difficult and can greatly impair patients’ quality of life.
Empiric elimination diets are the most popular choice and have shown high response rates. A common approach is to begin by removing six common foods (milk, wheat, egg, soy, nuts, and fish/seafood), which are then gradually reintroduced to identify the culprits. However, patients must be motivated to follow this process, and the likelihood it will be successful is greatly enhanced with assistance from a dietitian, which may not always be possible.
Last, allergy testing-guided food elimination diets have been reported to produce remissions rates of just under 50%, and the skin allergy tests they primarily rely on have been criticized for being unreliable.
Drugs:
The treatment of EoE experienced a significant advance in 2022 when dupilumab, a monoclonal antibody that binds to the interleukin (IL)–4 receptor alpha, became the first drug approved by the US Food and Drug Administration (FDA) for treating EoE in adults and pediatric patients aged 12 years or older. The drug was approved by the European Commission in 2023. In late January 2024, the FDA expanded dupilumab’s approval to children aged 1-11 years and weighing ≥ 15 kg after positive histologic remission and safety results were reported in the two-part phase 3 EoE KIDS trial.
In addition, the FDA approved budesonide, the first oral treatment for EoE, in February 2024.
These approvals have expanded treatment options beyond proton pump inhibitors (PPIs) and topical glucocorticosteroids, both of which received only nuanced recommendations for use under US and UK clinical guidelines.
A recent meta-analysis found that PPIs, off-label and EoE-specific topical steroids, and biologics had greater efficacy than did placebo in achieving histological remission. However, significant heterogeneity in the included studies’ eligibility criteria and outcome measures prevented development of a “solid therapeutic hierarchy,” the authors noted.
In addition, researchers are investigating therapies targeting IL-5 (eg, mepolizumab, reslizumab, and benralizumab) and other key inflammatory mediators in EoE, such as Siglec-8 (lirentelimab), IL-13 (cendakimab), and the sphingosine 1–phosphate receptor (etrasimod).
Dilation:
Finally, patients with significant strictures can benefit from dilation performed via through-the-scope balloons or Savary-Gilliard bougies, which can significantly and immediately improve symptoms even if they cannot address the underlying inflammation. Concerns that dilation would lead to increased complications, such as perforation and mucosal tears, do not appear to be borne out by recent data.
5. Reducing diagnosis delays is crucial for limiting EoE-associated morbidity.
Despite efforts to bring attention to EoE, evidence suggests that delays between symptom onset and diagnosis are common, and result in treatment delays. One study found a median lag time of 6 years.
The longer the delay in treatment, the more likely patients are to develop esophageal rings, a long narrowing in the esophageal caliber, or focal strictures. For example, diagnostic delays of more than 20 years result in prevalence rates of 70.8% for esophageal strictures, compared with 17.2% with delays of 0-2 years.
Simply put, the sooner one can identify EoE and begin treatment, the more likely patients are to be spared its worst effects.
A version of this article appeared on Medscape.com.
Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus that affects both children and adults. EoE is defined by symptoms of esophageal dysfunction (eg, dysphagia, vomiting, difficulty in feeding), with presentation varying depending on patient age.
The global incidence of EoE has increased in recent decades. In the United States alone, EoE is estimated to affect approximately 150,000 people and result in as much as $1.4 billion in annual healthcare costs.
There currently is no clear treatment hierarchy for EoE, and long delays between symptom onset and diagnoses are common.
Still, the knowledge base surrounding the disease is growing, and existing interventions have shown tremendous success at curbing symptoms and disease progression.
To help clinicians stay up to date on the latest information on this debilitating disease, here are five things to know about EoE.
1. EoE prevalence is increasing although not consistently around the globe.
EoE was first recognized as a distinct clinical entity in the early 1990s, when it was considered a relatively rare disease. Now, the incidence and prevalence rates of EoE are escalating at rates that cannot be explained by increased disease awareness and detection.
Although EoE has been diagnosed in Latin America, the Middle East, and Asia, such instances are relatively uncommon in comparison with the spiking rates noted in the United States; in Western Europe, including Denmark, the Netherlands, and Switzerland; and in Australia.
Emerging data suggest that climate and location may be a factor in the varying incidence rates of EoE. An analysis of 233,649 patients in a US pathology database reported that EoE was more common in cold and arid climate zones than in tropical zones. Another study suggests that EoE is more common in low-density, rural environments compared with urban settings.
2. Environmental and food exposures may trigger EoE, and genetics probably play a role.
The unequal geographic distribution of EoE lends credence to the theory that external triggers, which naturally differ in various locales, play an outsized role in its development.
Mice studies have indicated that the inhalation of allergens induces notable eosinophil infiltration and degranulation, and a pilot study conducted in New York City found that EoE symptoms peaked during the July-to-September period when grass pollen counts were at their highest.
Early-life factors that can result in alteration to the microbiome have also been identified as possibly influencing EoE development. They include cesarean delivery, preterm delivery, admission to a neonatal intensive care unit, infant formula use, and maternal or infant use of antibiotics. Conversely, evidence suggests that Helicobacter pylori infection may be protective against EoE due to immunomodulating effects that have not yet been sufficiently identified in the literature.
Yet, the clearest association between EoE and outside triggers is found with food exposures. In one analysis of pediatric patients, the items that were most commonly associated with elevated food-specific serum immunoglobulin E antibodies in patients with EoE were milk (78%), wheat (69%), eggs (64%), peanuts (54%), and soy (51%). Food allergies are also on the uptick in countries with rising EoE rates, suggesting that the two trends may be interrelated.
From a genetic standpoint, EoE is more likely to develop in those with first-degree relatives with the disease than in the general population. Thirty independent genes thought to be associated with EoE have been identified. EoE is also significantly more common in men than in women.
3. Diagnosis requires knowing the symptoms, excluding other disorders, and performing biopsy.
EoE can occur early in life, with approximately one third of children with the disease presenting under age 5 years. The prevalence rises with age, eventually peaking in those aged 35-45 years.
The presentation of EoE can be quite variable depending on patient age. Pediatric patients are significantly more likely to experience failure to thrive, vomiting, and heartburn, whereas their adult counterparts more often present with food impaction and dysphagia.
At the 2018 AGREE international consensus conference, researchers defined diagnostic criteria as presence of esophageal dysfunction symptoms; exclusion of non-EoE disorders, such as gastroesophageal reflux disease and achalasia; and esophageal biopsy findings of at least 15 eosinophils per high-power field (or approximately 60 eosinophils per mm2).
Endoscopic findings can also be crucial in diagnosing EoE because patients with this disease often present with inflammatory patterns recognizable in the form of exudates, furrows, and edema and/or fibrotic phenotypes such as the presence of rings and stenosis. Clinicians are advised to refer to the Endoscopic Reference Score proposed by Hirano and colleagues.
4. Treatment approaches rely on the ‘3 Ds.’
Although there is currently no leading strategy for the primary treatment of EoE, clinicians can avail themselves of suggested pathways.
The lack of a treatment hierarchy means that patients typically are very involved in selecting the therapy that works best for them. Physicians should be aware that patients researching EoE on their own might not find the information they need. A recent study found that the artificial intelligence tool ChatGPT was highly inaccurate when it came to providing answers about EoE.
The treatment strategies that clinicians and their patients can choose from revolve around the “3 Ds”: diet, drugs, and dilation.
Diet:
Three dietary interventions are available for EoE treatment:
- Elemental diet, in which patients consume only an amino-acid based formula that does not include any intact proteins
- Empiric elimination diet, which removes foods more commonly associated with food allergy regardless of whether there has been a positive allergy testing result
- Allergy testing-directed food elimination, which involves avoidance of all foods for which specific antibodies were detected or that tested positive on skin-prick tests
Each of these dietary interventions has clear advantages and drawbacks that should be discussed with patients. Elemental diets achieve robust histologic responses, yet their highly restrictive nature makes compliance difficult and can greatly impair patients’ quality of life.
Empiric elimination diets are the most popular choice and have shown high response rates. A common approach is to begin by removing six common foods (milk, wheat, egg, soy, nuts, and fish/seafood), which are then gradually reintroduced to identify the culprits. However, patients must be motivated to follow this process, and the likelihood it will be successful is greatly enhanced with assistance from a dietitian, which may not always be possible.
Last, allergy testing-guided food elimination diets have been reported to produce remissions rates of just under 50%, and the skin allergy tests they primarily rely on have been criticized for being unreliable.
Drugs:
The treatment of EoE experienced a significant advance in 2022 when dupilumab, a monoclonal antibody that binds to the interleukin (IL)–4 receptor alpha, became the first drug approved by the US Food and Drug Administration (FDA) for treating EoE in adults and pediatric patients aged 12 years or older. The drug was approved by the European Commission in 2023. In late January 2024, the FDA expanded dupilumab’s approval to children aged 1-11 years and weighing ≥ 15 kg after positive histologic remission and safety results were reported in the two-part phase 3 EoE KIDS trial.
In addition, the FDA approved budesonide, the first oral treatment for EoE, in February 2024.
These approvals have expanded treatment options beyond proton pump inhibitors (PPIs) and topical glucocorticosteroids, both of which received only nuanced recommendations for use under US and UK clinical guidelines.
A recent meta-analysis found that PPIs, off-label and EoE-specific topical steroids, and biologics had greater efficacy than did placebo in achieving histological remission. However, significant heterogeneity in the included studies’ eligibility criteria and outcome measures prevented development of a “solid therapeutic hierarchy,” the authors noted.
In addition, researchers are investigating therapies targeting IL-5 (eg, mepolizumab, reslizumab, and benralizumab) and other key inflammatory mediators in EoE, such as Siglec-8 (lirentelimab), IL-13 (cendakimab), and the sphingosine 1–phosphate receptor (etrasimod).
Dilation:
Finally, patients with significant strictures can benefit from dilation performed via through-the-scope balloons or Savary-Gilliard bougies, which can significantly and immediately improve symptoms even if they cannot address the underlying inflammation. Concerns that dilation would lead to increased complications, such as perforation and mucosal tears, do not appear to be borne out by recent data.
5. Reducing diagnosis delays is crucial for limiting EoE-associated morbidity.
Despite efforts to bring attention to EoE, evidence suggests that delays between symptom onset and diagnosis are common, and result in treatment delays. One study found a median lag time of 6 years.
The longer the delay in treatment, the more likely patients are to develop esophageal rings, a long narrowing in the esophageal caliber, or focal strictures. For example, diagnostic delays of more than 20 years result in prevalence rates of 70.8% for esophageal strictures, compared with 17.2% with delays of 0-2 years.
Simply put, the sooner one can identify EoE and begin treatment, the more likely patients are to be spared its worst effects.
A version of this article appeared on Medscape.com.
Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus that affects both children and adults. EoE is defined by symptoms of esophageal dysfunction (eg, dysphagia, vomiting, difficulty in feeding), with presentation varying depending on patient age.
The global incidence of EoE has increased in recent decades. In the United States alone, EoE is estimated to affect approximately 150,000 people and result in as much as $1.4 billion in annual healthcare costs.
There currently is no clear treatment hierarchy for EoE, and long delays between symptom onset and diagnoses are common.
Still, the knowledge base surrounding the disease is growing, and existing interventions have shown tremendous success at curbing symptoms and disease progression.
To help clinicians stay up to date on the latest information on this debilitating disease, here are five things to know about EoE.
1. EoE prevalence is increasing although not consistently around the globe.
EoE was first recognized as a distinct clinical entity in the early 1990s, when it was considered a relatively rare disease. Now, the incidence and prevalence rates of EoE are escalating at rates that cannot be explained by increased disease awareness and detection.
Although EoE has been diagnosed in Latin America, the Middle East, and Asia, such instances are relatively uncommon in comparison with the spiking rates noted in the United States; in Western Europe, including Denmark, the Netherlands, and Switzerland; and in Australia.
Emerging data suggest that climate and location may be a factor in the varying incidence rates of EoE. An analysis of 233,649 patients in a US pathology database reported that EoE was more common in cold and arid climate zones than in tropical zones. Another study suggests that EoE is more common in low-density, rural environments compared with urban settings.
2. Environmental and food exposures may trigger EoE, and genetics probably play a role.
The unequal geographic distribution of EoE lends credence to the theory that external triggers, which naturally differ in various locales, play an outsized role in its development.
Mice studies have indicated that the inhalation of allergens induces notable eosinophil infiltration and degranulation, and a pilot study conducted in New York City found that EoE symptoms peaked during the July-to-September period when grass pollen counts were at their highest.
Early-life factors that can result in alteration to the microbiome have also been identified as possibly influencing EoE development. They include cesarean delivery, preterm delivery, admission to a neonatal intensive care unit, infant formula use, and maternal or infant use of antibiotics. Conversely, evidence suggests that Helicobacter pylori infection may be protective against EoE due to immunomodulating effects that have not yet been sufficiently identified in the literature.
Yet, the clearest association between EoE and outside triggers is found with food exposures. In one analysis of pediatric patients, the items that were most commonly associated with elevated food-specific serum immunoglobulin E antibodies in patients with EoE were milk (78%), wheat (69%), eggs (64%), peanuts (54%), and soy (51%). Food allergies are also on the uptick in countries with rising EoE rates, suggesting that the two trends may be interrelated.
From a genetic standpoint, EoE is more likely to develop in those with first-degree relatives with the disease than in the general population. Thirty independent genes thought to be associated with EoE have been identified. EoE is also significantly more common in men than in women.
3. Diagnosis requires knowing the symptoms, excluding other disorders, and performing biopsy.
EoE can occur early in life, with approximately one third of children with the disease presenting under age 5 years. The prevalence rises with age, eventually peaking in those aged 35-45 years.
The presentation of EoE can be quite variable depending on patient age. Pediatric patients are significantly more likely to experience failure to thrive, vomiting, and heartburn, whereas their adult counterparts more often present with food impaction and dysphagia.
At the 2018 AGREE international consensus conference, researchers defined diagnostic criteria as presence of esophageal dysfunction symptoms; exclusion of non-EoE disorders, such as gastroesophageal reflux disease and achalasia; and esophageal biopsy findings of at least 15 eosinophils per high-power field (or approximately 60 eosinophils per mm2).
Endoscopic findings can also be crucial in diagnosing EoE because patients with this disease often present with inflammatory patterns recognizable in the form of exudates, furrows, and edema and/or fibrotic phenotypes such as the presence of rings and stenosis. Clinicians are advised to refer to the Endoscopic Reference Score proposed by Hirano and colleagues.
4. Treatment approaches rely on the ‘3 Ds.’
Although there is currently no leading strategy for the primary treatment of EoE, clinicians can avail themselves of suggested pathways.
The lack of a treatment hierarchy means that patients typically are very involved in selecting the therapy that works best for them. Physicians should be aware that patients researching EoE on their own might not find the information they need. A recent study found that the artificial intelligence tool ChatGPT was highly inaccurate when it came to providing answers about EoE.
The treatment strategies that clinicians and their patients can choose from revolve around the “3 Ds”: diet, drugs, and dilation.
Diet:
Three dietary interventions are available for EoE treatment:
- Elemental diet, in which patients consume only an amino-acid based formula that does not include any intact proteins
- Empiric elimination diet, which removes foods more commonly associated with food allergy regardless of whether there has been a positive allergy testing result
- Allergy testing-directed food elimination, which involves avoidance of all foods for which specific antibodies were detected or that tested positive on skin-prick tests
Each of these dietary interventions has clear advantages and drawbacks that should be discussed with patients. Elemental diets achieve robust histologic responses, yet their highly restrictive nature makes compliance difficult and can greatly impair patients’ quality of life.
Empiric elimination diets are the most popular choice and have shown high response rates. A common approach is to begin by removing six common foods (milk, wheat, egg, soy, nuts, and fish/seafood), which are then gradually reintroduced to identify the culprits. However, patients must be motivated to follow this process, and the likelihood it will be successful is greatly enhanced with assistance from a dietitian, which may not always be possible.
Last, allergy testing-guided food elimination diets have been reported to produce remissions rates of just under 50%, and the skin allergy tests they primarily rely on have been criticized for being unreliable.
Drugs:
The treatment of EoE experienced a significant advance in 2022 when dupilumab, a monoclonal antibody that binds to the interleukin (IL)–4 receptor alpha, became the first drug approved by the US Food and Drug Administration (FDA) for treating EoE in adults and pediatric patients aged 12 years or older. The drug was approved by the European Commission in 2023. In late January 2024, the FDA expanded dupilumab’s approval to children aged 1-11 years and weighing ≥ 15 kg after positive histologic remission and safety results were reported in the two-part phase 3 EoE KIDS trial.
In addition, the FDA approved budesonide, the first oral treatment for EoE, in February 2024.
These approvals have expanded treatment options beyond proton pump inhibitors (PPIs) and topical glucocorticosteroids, both of which received only nuanced recommendations for use under US and UK clinical guidelines.
A recent meta-analysis found that PPIs, off-label and EoE-specific topical steroids, and biologics had greater efficacy than did placebo in achieving histological remission. However, significant heterogeneity in the included studies’ eligibility criteria and outcome measures prevented development of a “solid therapeutic hierarchy,” the authors noted.
In addition, researchers are investigating therapies targeting IL-5 (eg, mepolizumab, reslizumab, and benralizumab) and other key inflammatory mediators in EoE, such as Siglec-8 (lirentelimab), IL-13 (cendakimab), and the sphingosine 1–phosphate receptor (etrasimod).
Dilation:
Finally, patients with significant strictures can benefit from dilation performed via through-the-scope balloons or Savary-Gilliard bougies, which can significantly and immediately improve symptoms even if they cannot address the underlying inflammation. Concerns that dilation would lead to increased complications, such as perforation and mucosal tears, do not appear to be borne out by recent data.
5. Reducing diagnosis delays is crucial for limiting EoE-associated morbidity.
Despite efforts to bring attention to EoE, evidence suggests that delays between symptom onset and diagnosis are common, and result in treatment delays. One study found a median lag time of 6 years.
The longer the delay in treatment, the more likely patients are to develop esophageal rings, a long narrowing in the esophageal caliber, or focal strictures. For example, diagnostic delays of more than 20 years result in prevalence rates of 70.8% for esophageal strictures, compared with 17.2% with delays of 0-2 years.
Simply put, the sooner one can identify EoE and begin treatment, the more likely patients are to be spared its worst effects.
A version of this article appeared on Medscape.com.