**4.1 Emergency endoscopy and food desimpaction**

The impaction of food in the esophagus is common in EoE patients and is, together with dysphagia, the clinical hallmark of the disease. Additionally, food impaction is the clinical manifestation which most frequently leads to diagnosis of EoE in adult patients, constituting a complication that must be urgently remedied. In this manner, 43.3% of the 30 adult patients studied in a Spanish series underwent endoscopy as an emergency treatment to resolve food impaction before being diagnosed with EoE (Lucendo et al., 2007). Furthermore, an analysis of 251 Swiss patients with EoE showed that 34.7% required extraction of the impacted bolus with the aid of flexible or rigid esophagoscopy, with the latter causing a 20% rate of transmural perforations (Straumann et al., 2008). Bolus removal by means of rigid endoscopy thus constitutes a high-risk procedure and should be avoided in EoE patients. Food impaction in pediatric forms of EoE seems to be uncommon, with no definitive explanation for this difference.

#### **4.2 Dilation treatment for EoE**

From the earliest documented cases, mechanical dilation with through-the-scope hydropneumatic balloons or Savary bougies has been employed as a treatment option for EoE, similar to the way it is used in other cases of rigid or fibrous esophageal stenosis resulting from the cicatrization of prolonged esophageal inflammatory processes such as GERD or after the ingestion of caustic substances. The chronic inflammatory phenomena which characterize EoE seem to cause subepithelial collagen deposition and fibrous remodeling, as recently shown in both childhood (Chehade et al., 2007; Aceves et al., 2007) and adult (Straumann et al., 2010, 2011) forms of the disease as well as in animal models (Mishra et al., 2008). Also, in recent years, various studies have addressed the relationship between EoE and GERD (Spechler et al., 2007), proving that both diseases can coexist in the same patient, causing dysmotility of the distal third of the esophagus, poor acid clearance, and the possibility of lesions – particularly Schatzki rings (Nurko et al., 2004) – from reflux. Several aspects should be considered before defining the real role of endoscopic treatment through dilation in EoE patients:

• There are no universally accepted therapeutic goals for EoE to date. Currently, treatment objectives range from merely controlling the symptoms to resolving the

Since the first descriptions of EoE appeared in the literature, the disease has been associated with alterations in the caliber of the esophagus, which specialists have sought to correct by means of endoscopic dilation. In this sense, endoscopic therapy has always been recognized as one of the main treatment modalities in EoE patients, together with systemic and topical

The efficacy of endoscopic treatment in EoE patients is clear in emergency situations, in which it is needed to resolve food impactions that block the esophageal lumen, and also in scheduled explorations of patients with esophageal symptoms, especially if these are accompanied by a reduced esophageal caliber. The characteristic fragility of the esophageal wall in these patients initially led several authors to consider endoscopic techniques to be a risky treatment option (Lucendo, 2007). We will discuss this assertion in greater depth after

The impaction of food in the esophagus is common in EoE patients and is, together with dysphagia, the clinical hallmark of the disease. Additionally, food impaction is the clinical manifestation which most frequently leads to diagnosis of EoE in adult patients, constituting a complication that must be urgently remedied. In this manner, 43.3% of the 30 adult patients studied in a Spanish series underwent endoscopy as an emergency treatment to resolve food impaction before being diagnosed with EoE (Lucendo et al., 2007). Furthermore, an analysis of 251 Swiss patients with EoE showed that 34.7% required extraction of the impacted bolus with the aid of flexible or rigid esophagoscopy, with the latter causing a 20% rate of transmural perforations (Straumann et al., 2008). Bolus removal by means of rigid endoscopy thus constitutes a high-risk procedure and should be avoided in EoE patients. Food impaction in pediatric forms of EoE seems to be uncommon, with no

From the earliest documented cases, mechanical dilation with through-the-scope hydropneumatic balloons or Savary bougies has been employed as a treatment option for EoE, similar to the way it is used in other cases of rigid or fibrous esophageal stenosis resulting from the cicatrization of prolonged esophageal inflammatory processes such as GERD or after the ingestion of caustic substances. The chronic inflammatory phenomena which characterize EoE seem to cause subepithelial collagen deposition and fibrous remodeling, as recently shown in both childhood (Chehade et al., 2007; Aceves et al., 2007) and adult (Straumann et al., 2010, 2011) forms of the disease as well as in animal models (Mishra et al., 2008). Also, in recent years, various studies have addressed the relationship between EoE and GERD (Spechler et al., 2007), proving that both diseases can coexist in the same patient, causing dysmotility of the distal third of the esophagus, poor acid clearance, and the possibility of lesions – particularly Schatzki rings (Nurko et al., 2004) – from reflux. Several aspects should be considered before defining the real role of endoscopic treatment

• There are no universally accepted therapeutic goals for EoE to date. Currently, treatment objectives range from merely controlling the symptoms to resolving the

**4. Endoscopic treatment for Eosinophilic Esophagitis (EoE)** 

steroids and changes in diet.

reviewing new evidence from the latest studies.

definitive explanation for this difference.

**4.2 Dilation treatment for EoE** 

through dilation in EoE patients:

**4.1 Emergency endoscopy and food desimpaction** 

epithelial inflammatory infiltrate. A group of EoE experts have recommended treating asymptomatic cases of EoE to avoid the potential consequences of fibrous remodeling of the organ (Liacouras et al., 2011), although the long-term consequences are not really known. The experience of each center and the availability of techniques and studies also limit the treatment options and the objectives established in each case. However, we should keep in mind that if left untreated, EoE is a chronic disease involving persistent histological inflammation over time, with detrimental effects on a patient's quality-oflife (Straumann, 2008).


Fig. 3. Concentric esophageal short stricture, with fibrous appearance because of the absence of vascular pattern, before (a) and after (b) endoscopic dilation using a trough-the-scope balloon. A deep mucosal tear can be observed

Endoscopic Aspects of Eosinophilic Esophagitis: From Diagnosis to Therapy 71

bougies or through-the-scope balloons in a total of 363 dilation procedures (Dellon et al., 2010; Jung et al., 2011). In the first study, Dellon and coworkers observed an overall symptom improvement of 83% with a concomitant increase in esophageal caliber. The authors also observed a 7% complication rate, with 2 deep mucosal rents and 3 episodes of chest pain, but no transmural perforations. In the second study, Jung's group found that 9.2% of patients suffered deep mucosal tears while major bleeding and immediate perforation occurred in 0.3% and 1.0% of the patients, respectively. Complication rates from these two studies contrast with the high rates of perforation reported in earlier EoE literature. Moreover, none of the perforations reported in these two studies required

Several predictive factors for complications during dilation have been identified, including a long evolution of dysphagia, the existence of esophageal stenosis, and a high density of eosinophils (Cohen et al., 2007). Complications were also significantly associated with younger age and repeated procedures (Dellon et al., 2010), along with luminal narrowing in the upper and middle esophageal thirds, a luminal stricture incapable of being traversed

In spite of these data, it should be noted that because endoscopic dilation is a mechanical procedure with no effect on the underlying inflammatory process (Schoepfer et al., 2010), its efficacy is probably limited over time. In the case studies published to date, the duration of the effect cannot be appropriately estimated owing to the short monitoring period, although it usually ranges from 3 to 12 months. Still, it is common for patients to undergo repeated dilations, in some cases up to 9 times, to control their symptoms (Schoepfer et al., 2008; Dellon et al., 2010; Pasha et al., 2007). Also noteworthy is the fact that a proportion of patients undergoing endoscopic dilation also receive concomitant drug therapy, which may

Taking all this into account, endoscopic dilation should be considered as an alternative treatment for patients with EoE and esophageal stenosis when other measures (especially topical steroid treatment) have failed. It is also advisable that the procedure be used together with other therapy modalities in order to avoid complications derived from active eosinophilic inflammation of the organ. Further studies should be carried out to determine which patients are the best candidates for this kind of treatment due to their better clinical results and/or lower complication rates. This will probably require the definition of different patient subgroups or phenotypes according to several variables which are as yet unidentified.

As noted above, endoscopic dilation constitutes an effective treatment for EoE and should therefore be considered in those patients exhibiting a reduced esophageal caliber and persisting esophageal symptoms despite topical steroid treatment and/or dietary modifications. Dilation should preferably be done when the active inflammatory infiltrate has been banned or significantly reduced (Sgouros et al., 2006). Endoscopic dilation should be carried out by experienced endoscopists and under sedation to avoid provoking Boherhaave's syndrome if the technique is tolerated badly (Nantes et al., 2009). In order to minimize complications, the procedure should be carried out gently with medium-sized bougies, gradually increasing the caliber and never dilating fully to the larger calibers used

with a standard upper endoscope, and the use of Savary bougies (Jung et al., 2011).

mask the clinical effect of endoscopic therapy in and of itself (Dellon et al., 2010).

**4.4 Sustained efficacy of endoscopic dilation in EoE patients** 

**4.5 How endoscopic dilations should be done in EoE?** 

in the treatment of other forms of stenosis.

surgical intervention (Table 1).

In this context, endoscopic dilation can be restricted to two well-established subgroups of EoE patients: those unresponsive to medical therapy and those with a persistent or definitive stricture (Schoepfer et al., 2008). The identification of such patients should be made prior to endoscopic therapy, which in clinical practice implies not using endoscopic dilation as an initial treatment.

#### **4.3 Safety of esophageal dilation in EoE patients**

A review of the literature indicates that esophageal dilation is an efficient treatment for EoE, providing immediate relief of symptoms (Zuber-Jerger et al., 2006; Roberts-Thomson, 2009), which is why many authors regard it as a front-line treatment (Vasilopoulos et al., 2002; Straumann, 2010). However, initial reports on the use of esophageal dilation in EoE patients also found a high rate of complications ranging from chest pain to esophageal perforation, which appeared in 7% and 5% of all reported cases, respectively (Furuta et al., 2007; Hirano, 2010). These rates are substantially higher than those for esophageal dilation for other benign strictures. Most described cases of esophageal perforation (spontaneous or after endoscopic procedures) only led to pneumomediastinum (Eisenbach et al., 2006; Rajagopalan & Triadafilopoulos, 2009), but in some cases, an emergency esophagectomy by means of thoracotomy or esophagogastroplasty was required (Lucendo et al., 2011; Riou et al., 1996; Liguori et al., 2008). Although no patient fatalities have been reported to date, the seriousness of these complications has led some researchers to warn that endoscopic dilation poses a higher risk of complications in patients with EoE. That, along with the efficacy and proved safety of dietary modification and topical steroids for this disease, has caused several authors to recommend that dilations not be performed until the presence of an eosinophilic infiltrate has been ruled out (Lucendo & De Rezende, 2007). A trial with corticosteroids before dilation has been also proposed in order to reduce active inflammation and the risk for complications (Sgouros et al., 2006).

The exact cause of the extreme fragility described for esophageal mucosa in EoE has not been clearly established, but it seems to be directly related to the inflammatory infiltrate and the cytotoxic effect of eosinophils. These eosinophils contain several cytotoxic proteins in their cytoplasmic granules capable of damaging tissues (Rothenberg et al., 2001), the risk of which is likely to be higher in patients with a high density of eosinophils and long-term symptoms (Straumann et al., 2008). Multiple evidence obtained from patients (Landres et al., 1978) and from animal models of EoE (Mishra et al., 2001) has shown that the inflammatory infiltrate penetrates deeply into the esophageal wall, reaching the muscle layers. Indeed, fibrous remodeling of the esophageal wall, which reduces the elastic properties of its components, has also been described in EoE patients (Aceves et al., 2004; Straumann et al., 2011). In this sense, esophageal distensibility, which alters the mechanical properties of the esophageal wall (Kwiatek et al., 2011), has been shown to be significantly reduced in adult EoE patients in comparison to controls. Accordingly, both the resistance and distension of the organ may be impaired in EoE, leading to increased fragility during endoscopic dilation procedures (Lucendo & De Rezende, 2007) and in traction movements around the gastroesophageal junction in cases of nausea and vomiting. Thus, a simple brush of the endoscope may give rise to mucosal rents, with cases of spontaneous esophageal perforation (Prasad & Arora, 2005) and Boerhaave's syndrome (Lucendo et al, 2011) having been reported in EoE patients after the mere passage of the endoscope (Kaplan et al., 2003). For these patients especially, then, the various endoscopic procedures must be performed gently. Two recent retrospective, uncontrolled studies developed in adult EoE patients and

published in 2010 and 2011 attempted to assess the safety of esophageal dilation with

In this context, endoscopic dilation can be restricted to two well-established subgroups of EoE patients: those unresponsive to medical therapy and those with a persistent or definitive stricture (Schoepfer et al., 2008). The identification of such patients should be made prior to endoscopic therapy, which in clinical practice implies not using endoscopic

A review of the literature indicates that esophageal dilation is an efficient treatment for EoE, providing immediate relief of symptoms (Zuber-Jerger et al., 2006; Roberts-Thomson, 2009), which is why many authors regard it as a front-line treatment (Vasilopoulos et al., 2002; Straumann, 2010). However, initial reports on the use of esophageal dilation in EoE patients also found a high rate of complications ranging from chest pain to esophageal perforation, which appeared in 7% and 5% of all reported cases, respectively (Furuta et al., 2007; Hirano, 2010). These rates are substantially higher than those for esophageal dilation for other benign strictures. Most described cases of esophageal perforation (spontaneous or after endoscopic procedures) only led to pneumomediastinum (Eisenbach et al., 2006; Rajagopalan & Triadafilopoulos, 2009), but in some cases, an emergency esophagectomy by means of thoracotomy or esophagogastroplasty was required (Lucendo et al., 2011; Riou et al., 1996; Liguori et al., 2008). Although no patient fatalities have been reported to date, the seriousness of these complications has led some researchers to warn that endoscopic dilation poses a higher risk of complications in patients with EoE. That, along with the efficacy and proved safety of dietary modification and topical steroids for this disease, has caused several authors to recommend that dilations not be performed until the presence of an eosinophilic infiltrate has been ruled out (Lucendo & De Rezende, 2007). A trial with corticosteroids before dilation has been also proposed in order to reduce active inflammation

The exact cause of the extreme fragility described for esophageal mucosa in EoE has not been clearly established, but it seems to be directly related to the inflammatory infiltrate and the cytotoxic effect of eosinophils. These eosinophils contain several cytotoxic proteins in their cytoplasmic granules capable of damaging tissues (Rothenberg et al., 2001), the risk of which is likely to be higher in patients with a high density of eosinophils and long-term symptoms (Straumann et al., 2008). Multiple evidence obtained from patients (Landres et al., 1978) and from animal models of EoE (Mishra et al., 2001) has shown that the inflammatory infiltrate penetrates deeply into the esophageal wall, reaching the muscle layers. Indeed, fibrous remodeling of the esophageal wall, which reduces the elastic properties of its components, has also been described in EoE patients (Aceves et al., 2004; Straumann et al., 2011). In this sense, esophageal distensibility, which alters the mechanical properties of the esophageal wall (Kwiatek et al., 2011), has been shown to be significantly reduced in adult EoE patients in comparison to controls. Accordingly, both the resistance and distension of the organ may be impaired in EoE, leading to increased fragility during endoscopic dilation procedures (Lucendo & De Rezende, 2007) and in traction movements around the gastroesophageal junction in cases of nausea and vomiting. Thus, a simple brush of the endoscope may give rise to mucosal rents, with cases of spontaneous esophageal perforation (Prasad & Arora, 2005) and Boerhaave's syndrome (Lucendo et al, 2011) having been reported in EoE patients after the mere passage of the endoscope (Kaplan et al., 2003). For these patients especially, then, the various endoscopic procedures must be performed gently. Two recent retrospective, uncontrolled studies developed in adult EoE patients and published in 2010 and 2011 attempted to assess the safety of esophageal dilation with

dilation as an initial treatment.

**4.3 Safety of esophageal dilation in EoE patients** 

and the risk for complications (Sgouros et al., 2006).

bougies or through-the-scope balloons in a total of 363 dilation procedures (Dellon et al., 2010; Jung et al., 2011). In the first study, Dellon and coworkers observed an overall symptom improvement of 83% with a concomitant increase in esophageal caliber. The authors also observed a 7% complication rate, with 2 deep mucosal rents and 3 episodes of chest pain, but no transmural perforations. In the second study, Jung's group found that 9.2% of patients suffered deep mucosal tears while major bleeding and immediate perforation occurred in 0.3% and 1.0% of the patients, respectively. Complication rates from these two studies contrast with the high rates of perforation reported in earlier EoE literature. Moreover, none of the perforations reported in these two studies required surgical intervention (Table 1).

Several predictive factors for complications during dilation have been identified, including a long evolution of dysphagia, the existence of esophageal stenosis, and a high density of eosinophils (Cohen et al., 2007). Complications were also significantly associated with younger age and repeated procedures (Dellon et al., 2010), along with luminal narrowing in the upper and middle esophageal thirds, a luminal stricture incapable of being traversed with a standard upper endoscope, and the use of Savary bougies (Jung et al., 2011).

#### **4.4 Sustained efficacy of endoscopic dilation in EoE patients**

In spite of these data, it should be noted that because endoscopic dilation is a mechanical procedure with no effect on the underlying inflammatory process (Schoepfer et al., 2010), its efficacy is probably limited over time. In the case studies published to date, the duration of the effect cannot be appropriately estimated owing to the short monitoring period, although it usually ranges from 3 to 12 months. Still, it is common for patients to undergo repeated dilations, in some cases up to 9 times, to control their symptoms (Schoepfer et al., 2008; Dellon et al., 2010; Pasha et al., 2007). Also noteworthy is the fact that a proportion of patients undergoing endoscopic dilation also receive concomitant drug therapy, which may mask the clinical effect of endoscopic therapy in and of itself (Dellon et al., 2010).

Taking all this into account, endoscopic dilation should be considered as an alternative treatment for patients with EoE and esophageal stenosis when other measures (especially topical steroid treatment) have failed. It is also advisable that the procedure be used together with other therapy modalities in order to avoid complications derived from active eosinophilic inflammation of the organ. Further studies should be carried out to determine which patients are the best candidates for this kind of treatment due to their better clinical results and/or lower complication rates. This will probably require the definition of different patient subgroups or phenotypes according to several variables which are as yet unidentified.

#### **4.5 How endoscopic dilations should be done in EoE?**

As noted above, endoscopic dilation constitutes an effective treatment for EoE and should therefore be considered in those patients exhibiting a reduced esophageal caliber and persisting esophageal symptoms despite topical steroid treatment and/or dietary modifications. Dilation should preferably be done when the active inflammatory infiltrate has been banned or significantly reduced (Sgouros et al., 2006). Endoscopic dilation should be carried out by experienced endoscopists and under sedation to avoid provoking Boherhaave's syndrome if the technique is tolerated badly (Nantes et al., 2009). In order to minimize complications, the procedure should be carried out gently with medium-sized bougies, gradually increasing the caliber and never dilating fully to the larger calibers used in the treatment of other forms of stenosis.

Endoscopic Aspects of Eosinophilic Esophagitis: From Diagnosis to Therapy 73

2 adults Both cases No No No.

1 adult Asymptomatic Repeated

improvement for 3

improved over an average 6-month

improved for 6 months

Overall clinical response in 20 (83%)

Not specified Mean no. of

Not specified Mean of 2.07

Table 1. Summary of published cases of dilations, their results and complications

Efficiency Repeated sessions Perfora-

recurred.

esophageal dilation

Yes, after dysphagia

Mean number of dilations was 2 (range, 1-5)

Mean number of dilations was 2.7 (range, 1-5)

Two dilations in a 6 week period

dilations per patient

dilations per patient

1.8±1.4

No definitive data exist with regard to which dilation technique(s) should be used. Some clinicians prefer using through-the-scope balloons to dilate EoE patients since this method allows the endoscopist a direct visualization of the mucosa during the procedure (Dellon et al., 2010), but the use of Savary bougies has also been reported to be a safe method (Swan et

Multiple strictures are also possible in patients with EoE, but a common strategy in such cases has likewise yet to be established. Inflating a balloon segmentally in multiple areas can dilate the entire esophagus quickly if necessary while maintaining direct visualization at all times (Dellon et al., 2010), but the final method employed should preferably depend on the

Eosinophilic esophagitis is a rapidly emerging disease which has become a common pathology in clinical practice. A wide range of endoscopic findings typical of EoE has been described in the literature, but none of them is pathognomonic for the disease. If a patient

Mean no. of dilations per patient 1.9 (range 1-9).

tion

Yes No.

No No.

Other complications

No Superficial mucosal

of dilations.

No Severe pain during the subsequent 24- 48-hour period.

No 5 complications reported: 2 deep mucosal rents and 3 episodes of chest pain, on of them needing hospitalization.

Yes Deep mucosal tear in 9,2% of dilations and major bleeding in 0,3% of dilations.

No 2 cases admitted with postdilatation pain.

postprocedural odynophagia for 1-3

No Transient

days.

tears occurred in 31%

Author and year

Cantù P. et al., 2005

Eisenbach C. et al., 2006

Zuber-Jerger I. et al., 2006

Pasha SF. et al., 2007

Schoepfer AM. et al., 2008

Rajagopalan J. et al., 2009

Dellon ES. et al., 2010

Jung KW. et al., 2011

Swan MP. et al., 2011

al., 2011).

36 patients

161 patients

29 patients

endoscopist's experience.

**5. Conclusion** 

Patients dilated

1 adult Clinical

years

13 adults 11/13 clinically improved

10 adults 10/10 clinically

period

1 adult Symptoms



Table 1. Summary of published cases of dilations, their results and complications

No definitive data exist with regard to which dilation technique(s) should be used. Some clinicians prefer using through-the-scope balloons to dilate EoE patients since this method allows the endoscopist a direct visualization of the mucosa during the procedure (Dellon et al., 2010), but the use of Savary bougies has also been reported to be a safe method (Swan et al., 2011).

Multiple strictures are also possible in patients with EoE, but a common strategy in such cases has likewise yet to be established. Inflating a balloon segmentally in multiple areas can dilate the entire esophagus quickly if necessary while maintaining direct visualization at all times (Dellon et al., 2010), but the final method employed should preferably depend on the endoscopist's experience.
