Continuing Education Activity

Dysphagia is a common symptom with multiple possible etiological factors, one of which is diffuse intramural esophageal diverticulosis. This activity reviews this disease and shines a light on its different etiologic, pathophysiological, epidemiological, and clinical aspects for the interprofessional team.

Objectives:

• Summarize the etiology of diffuse intramural esophageal diverticulosis.
• Describe the presentation of a patient with diffuse intramural esophageal diverticulosis.
• Outline the main modes of management and when to intervene upon making the diagnosis of diffuse intramural esophageal diverticulosis.
• Review interprofessional strategies for health care providers to recall when evaluating patients with gastrointestinal symptoms from diffuse intramural esophageal diverticulosis.

Introduction

Diffuse intramural esophageal diverticulosis is a rare disease characterized by multiple tiny flask-shaped outpouching lesions of the esophageal wall. These outpouchings represent the ducts of submucosal glands of the esophagus, and for this reason, the disorder is also called esophageal intramural pseudodiverticulosis (EIP). It was first described by Mendl et al. in1960.[1] Usually, cases present with dysphagia and food impaction in association with a proximal esophageal stricture.[2] The diagnosis is usually made radiologically, endoscopically, and pathologically.[1] 

Etiology

While the exact etiology of the condition is unclear and needs to be further clarified, multiple studies have shown that alcohol consumption and tobacco smoking are the leading associated risk factors.[3] Furthermore, the first possible association with esophageal moniliasis was mentioned by Troupin, who suggested the causal relationship between the two.[4] Other correlations referred to in the literature are gastroesophageal reflux disease, whether with or without hiatal hernia, diabetes mellitus, corrosive ingestion, Plummer-Vinson syndrome, and esophageal carcinomas.[5][6][7] Several reports have suggested an association with motility disorders as a predisposing factor for the condition.[8]

Epidemiology

Diffuse intramural esophageal diverticulosis is a rare benign disease. It is suggested that there are only about 200 reports published all around the world. Moreover, in one study, which looked at 14,350 barium swallow esophagrams, this clinical entity was identified only in 21 patients who underwent the diagnostic procedure (that is about 0.15%).[6] The disease can affect any age. In a series of 97 cases reported, the age range was between 8 months and 86 years, with a mean age of 53.5 years. In that same series, it was found that 58% were males and 42% were females.[5] On the other hand, it was shown by other studies that this disease follows a bimodal pattern of age distribution affecting teenagers and patients in their 50s and 60s.[6]

Pathophysiology

The exact pathogenesis of diffuse intramural esophageal diverticulosis is unclear and controversial.[9] These diverticula or pseudodiverticula are composed of pathologically dilated submucosal glands with surrounding inflammatory cells, so it is postulated that inflammation plays an essential role in their pathogenesis.[6][10] Furthermore, given the association of esophageal intramural diverticulosis (EIP) with esophagitis and the fact that esophagitis is correlated with hypertensive lower esophageal sphincter, therefore, Bender et al. assumed that diverticular formation might have resulted from motility changes secondary to the inflammation in esophagitis.[6][8] Conversely, Creely and Trail performed manometric studies in esophageal intramural diverticulosis and found no signs of spasm or hyperperistalsis in the esophagus. Moreover, their cultured esophageal endoscopic washings came back negative for Candidiasis, which argues against EIP being caused by that fungus.[11]

As a result of the presence of Candida in some cases and its absence in others, it is suggested that esophageal candidiasis could be the cause or the result of EIP.[10] Likewise, esophageal strictures could be resulting in EIP, considering that they were present in many of the reported cases. Contrarily, other EIP reports showed a distribution of the diverticula distal to the stricture or complete absence of strictures, so one may argue that strictures are just the result of EIP rather than being the cause.[10]

History and Physical

Patients with diffuse intramural esophageal diverticulosis usually present with chronic dysphagia that is either constant, intermittent, or progressive and is usually for solids or less likely manifest with food impaction, which usually resolves spontaneously. Nonetheless, some patients are asymptomatic, and the condition is diagnosed accidentally during workup for other issues.[1][3][5] The mean time from the development of difficulty swallowing to diagnosis is usually 60.5 months (range two days to 26 years), as was reported in one of the studies.[5] Other manifestations include chest pain, chest tightness, odynophagia, and upper gastrointestinal bleed.[6][7]

Evaluation

Radiological examination using a single or double-contrast technique is more sensitive than the endoscopic exam in diagnosing esophageal intramural pseudodiverticulosis (EIP) because diverticular orifices can be tiny and hence difficult to visualize with endoscopy.[12] Radiologically, they are demonstrated by flask-shaped outpouchings that are few millimeters in size and are distributed either diffusely or segmentally.[13] Endoscopically, the diverticula may be missed given tiny orifices; however, when found, they look like small yellow-white mucosal elevations with or without fluid expressed from them.[5][13]

Furthermore, endoscopy is important in diagnosing or excluding coexisting conditions like strictures, Barret esophagus, esophagitis, or cancer by direct visualization and/or biopsy.[13] On computed tomography, the esophageal wall might appear hypertrophied with some irregular luminal narrowing.[6] Other studies used manometry to evaluate the condition, and they found out a range of motility issues, including local or diffuse aperistalsis, decreased amplitude with normal peristalsis, decreased amplitude with aperistalsis, high amplitude contractions, diffuse esophageal spasms, or normal amplitude with synchronous tertiary contractions.[5][6][8]

Treatment / Management

The treatment is directed toward the accompanying medical conditions and symptoms relief, with approximately 10% of cases not necessitating any interventions.[6][14] Therefore, antireflux medications for patients with coexisting gastroesophageal reflux disease or esophagitis and treating associated esophageal Candidiasis, when present, have been shown to improve symptoms.[6][8] Moreover, mechanical dilatation of the accompanying esophageal strictures has shown to result in considerable clinical response and, in some cases, resulted in a reduction in the number of or even complete disappearance of the diverticula.[6][12][14][15]

Differential Diagnosis

Other conditions that fall in the differential diagnoses of diffuse intramural esophageal diverticulosis are other causes of dysphagia. Furthermore, many of these conditions usually coexist with EIP and are considered risk factors for it. These include gastroesophageal reflux disease, esophagitis, esophageal stricture due to other causes, esophageal carcinoma, or motility disorders.[6][8]

Prognosis

The diverticula themselves may have no clinical importance, and whether or not they disappear with treatment has no relationship to the patients' clinical outcome.[13] Nonetheless, they can be an indicator of underlying or co-existing conditions as most of the complications are usually not the direct result of the diverticulosis but may be resulted from similar underlying pathophysiology, so the overall nature of the condition is benign, but there is a reported correlation with esophageal cancer.[5]

Complications

The most common complication that a patient with diffuse intramural esophageal diverticulosis suffers from is developing an esophageal stricture that can be observed in up to 76% to 90% of patients and is mostly found in the upper esophagus, followed by the lower esophagus then the middle esophagus.[3][6][12] There is an increased prevalence of EIP in patients diagnosed with esophageal cancer; however, the association is not clear and requires further confirmation. In other words, EIP could be the cause of or the result of esophageal cancer, or could both share the same etiologic and pathogenic factors.[12] Another reported rare fatal complication is fistula formation with the anterior mediastinum.[5]

Deterrence and Patient Education

Although diffuse intramural esophageal diverticulosis is a rare condition, physicians should keep it in the back of their minds when evaluating a patient with dysphagia. On the other hand, patients should be educated that dysphagia is never normal, and they should seek help as soon as possible.

Enhancing Healthcare Team Outcomes

Diffuse intramural esophageal diverticulosis is one of the causes of gastrointestinal symptoms, especially dysphagia. Health care providers need to consider it whenever dealing with a patient with dysphagia. Since dysphagia is the usual presentation for our subject of interest and since all health care providers must diagnose and intervene when a patient presents with dysphagia, we will describe below some recommendations to deal with patients who present with dysphagia.

Dysphagia is defined as difficulty in swallowing. It can be divided into oropharyngeal versus esophageal. The first indicates difficulty initiating swallowing and is mostly due to motility disorders, while the latter denotes the inability to transport food down the esophagus with a feeling of food stuck in the esophagus. Furthermore, esophageal dysphagia can be attributed to motility disorders like achalasia and esophageal spasms. Other causes can be structural issues like esophageal cancer, esophagitis, esophageal webs and rings, diverticulosis, or strictures.[16][17]

Below are recommendations are taken from "Clinical Practice Guidelines for the Assessment of Uninvestigated Esophageal Dysphagia" published in Journal of the Canadian Association of Gastroenterology, 2018 [17]:

1. In patients presenting with dysphagia, it is recommended to use history and physical exam to identify oropharyngeal causes.[17] 
2. In patients with esophageal dysphagia, it is recommended to use history to differentiate structural and motility disorders of the esophagus.[17]
3. In patients presenting with esophageal dysphagia, it is recommended to use history and physical exam, including alarm features like vomiting, gastrointestinal bleeding, unexplained weight loss, abdominal mass, or anemia, to ensure timely management especially need for urgent investigations.[17]
4. In patients with esophageal dysphagia, endoscopy is recommended over barium esophagram to improve structural esophageal disease diagnosis. On the other hand, barium esophagram is chosen over endoscopy whenever there is limited local access to endoscopy with efforts for timely referral for endoscopy at other facilities.[17]
5. For patients under the age of 50 who present with esophageal dysphagia and reflux with no alarm features, it is recommended to investigate after the patient failed a trial of oral proton pump inhibitors (PPI), taken twice daily for 4 weeks.[17]
6. Esophageal manometry is used in evaluating persistent dysphagia after excluding structural causes as it is considered the gold standard for diagnosing esophageal motility disorders.[17]