Esophageal Intramural Pseudodiverticulosis Diagnosed by Combining Esophagogastroduodenoscopy, Esophagography, and High-resolution Manometry

Abstract

Esophageal intramural pseudodiverticulosis (EIPD) is a rare disease. A 78-year-old man with dysphagia presented to our hospital. The presence of diffuse esophageal spasm was suspected by his primary-care doctor. High-resolution manometry (HRM) showed no abnormal findings. The patient was diagnosed with EIPD and Candida esophagitis, by esophagogastroduodenoscopy (EGD) and esophagography. His symptoms improved after symptomatic treatment for Candida esophagitis with oral administration of an antifungal drug. EIPD should be considered in patients with dysphagia; EGD and esophagography should be performed when diagnosing EIPD.

Introduction

Esophageal intramural pseudodiverticulosis (EIPD) is characterized by the presence of outpouching flask-shaped lesions in the esophageal wall (1). This disease was first reported in 1960 by Mendl et al. (2); it is a relatively rare condition with a prevalence of 0.15% in patients who have undergone esophagography (3). Several well-known risk factors relevant to EIPD include diabetes mellitus, Candida infection, and gastroesophageal reflux disease (GERD) (4-6); however, the underlying etiology leading to the development of EIPD remains unclear.

To our knowledge, only three papers in the English literature have reported EIPD to have an association with esophageal motility disorders. One case report described a patient's lower esophageal sphincter relaxation to be normal, but the esophageal peristaltic contractions were considered to be stronger than those of normal people (7). Another case report mentioned increased esophageal pressure due to abnormal esophageal contractions as a mechanism for the development of EIPD (8). Nonetheless, the number of reported cases mentioned in association with EIPD and esophageal peristalsis is limited, and the relationship between EIPD and esophageal motility disorders remains unclear.

We herein report a case of EIPD in which high-resolution manometry (HRM) was performed to examine esophageal peristalsis and evaluate the pathogenesis of this morphologic change in the esophagus. In addition, we present our case to highlight the importance of performing esophagography and HRM for EIPD in addition to esophagogastroduodenoscopy (EGD).

Case Report

A 78-year-old man with dysphagia presented to our hospital to further evaluate his esophageal motility disorder. The patient had been diagnosed with Candida esophagitis nine years prior and was being treated with antifungal medication. Annual follow-up EGD was performed by his primary-care doctor, and diffuse esophageal spasm was suspected due to poor esophageal extensibility. He also had diabetes mellitus and dyslipidemia, both of which were being managed with oral treatment. His Eckardt score was 3 (dysphagia: 3; regurgitation: 0; retrosternal pain: 0; weight loss: 0).

A blood test showed slightly abnormal hemoglobin A1c levels (7.1%), but there were no other abnormal findings in the blood cell count and C-reactive protein levels. Tests for the specific IgE Candida antibody and antiscleroma 70-kD antibody were negative. EGD demonstrated stenosis of the upper thoracic esophagus 23 cm from the incisor that could not be passed with a normal-diameter endoscope (GIF-H290Z; Olympus, Tokyo, Japan) but could be passed with a small-diameter endoscope (GIF-XP290N; Olympus). In addition, multiple pinhole-like depressed lesions from the upper thoracic esophagus to the abdominal esophagus, and numerous white plaque patches in the esophagus between 22 and 43 cm from the incisors were revealed, including Candida esophagitis (Fig. 1). There was no obvious relaxation failure of the lower esophageal sphincter (LES). Esophagography showed multiple, tiny flask-shaped areas of outpouching in the upper thoracic esophagus (Fig. 2), although abnormal contraction of esophageal peristalsis was not observed. On HRM, esophageal peristalsis was normal and without abnormal contraction; the integrated relaxation pressure (IRP) was 13.1±2.4 mmHg, distal latency (DL) was 5.3±0.8 seconds, and the distal contractile integral (DCI) was 1,442.1±960.1 mmHg·s·cm (Starlet; STARMEDICAL, Tokyo, Japan) (Fig. 3).

Figure 1.

Esophagogastroduodenoscopy (EGD) before treatment. Multiple pinhole-shaped depressions (arrows) and numerous white lichen deposits along the entire length of the esophagus were observed in the upper esophagus.

Figure 2.

Esophagography. Multiple cystic, capillary, and bridging projections (arrows) were observed in the upper esophagus.

Figure 3.

High resolution manometry. Esophageal peristalsis was normal without abnormal contraction.

The patient was diagnosed not with esophageal motility disorder but rather EIPD and Candida esophagitis and was treated with an oral antifungal drug (miconazole 100 mg/dose, twice daily) for Candida esophagitis. Follow-up was performed six weeks after the start of treatment, and he no longer complained of dysphagia. Follow-up EGD showed the disappearance of esophageal candida, although there was no significant change in the pseudodiverticulosis of the esophagus (Fig. 4). Stenosis at the upper thoracic esophagus was still present and could not be passed with a normal-diameter endoscope, although no apparent exacerbation was present. Antifungal medication was discontinued, as the patient's symptoms improved, and no recurrence of symptoms was indicated one month after stopping the medication.

Figure 4.

Esophagogastroduodenoscopy after treatment with an oral antifungal drug. Disappearance of Candida esophagitis was noted, with no significant changes in the esophageal intraluminal pseudodiverticulum.

Discussion

EIPD is a relatively rare condition with a prevalence of 0.15% in patients who underwent esophagography (3). EIPD causes slow progressive stenosis of the esophagus, which leads to dysphagia in approximately 90% of patients (4). Umlas et al. suggested that stenosis of the esophagus in EIPD is due to fibrosis of the submucosa associated with esophageal inflammation, not due to hypertrophy of the intrinsic muscular layer (9); however, the underlying etiology of this pathological condition remains unknown. The imaging findings of EIPD are characteristic in achieving a diagnosis of this disease, including a small flask-like protrusion on esophagography and a diverticulum-like depression of several millimeters in size on EGD (4,10). Symptomatic therapy is often selected as the treatment of EIPD, including an antifungal medication for Candida esophagitis, an antacid for GERD, and dilation for esophageal stenosis. Surgical treatment, such as an esophagectomy, might be required when the symptoms are not improved with symptomatic therapy (11).

In our case, yearly follow-up EGD was performed by the patient's primary-care doctor, and diffuse esophageal spasm was suspected; however, the presence of EIPD was uncertain. We performed esophagography in addition to EGD to detect not only esophageal motility disorders but also any disease that had not yet been diagnosed. As a result, EIPD was detected, while esophageal motility disorder was negative. In a typical case of EIPD, esophagography shows multiple, tiny flask-shaped areas of outpouching, which are characteristic of EIPD (5). EGD is relatively easy to perform in screening the upper gastrointestinal tract; this examination can be performed at approximately 5,000 medical facilities in Japan, which is equivalent to approximately 5% of medical institutions, including clinics.

However, esophagography is not often performed, and an X-ray irradiator is required to perform this examination. In the diagnosis of esophageal diseases, continuous esophagography has a complementary role (12). As our case demonstrates the importance of esophagography, not only EGD but also esophagography is needed to detect esophageal diseases, especially for patients with dysphagia. When esophagography shows many diverticula, it is important to be able to diagnose EIPD appropriately.

According to previous case reports of EIPD, 91% of patients with EIPD in Western countries had dysphagia with stenosis of the esophagus, with stenosis developing in the cervical or upper esophagus in 44% of cases, and 56% had stenosis in the middle or lower esophagus (4). To clarify the characteristics of EIPD in Japanese patients, we reviewed a total of 48 cases with EIPD reported in Japan, including our case (Table). Among Japanese patients with EIPD, 72% of patients complained of dysphagia resulting from stenosis of the esophagus, 67% of whom had stenosis in the cervical or upper esophagus, and 33% had stenosis in the middle and lower esophagus. The results of the previously mentioned studies indicate that the stenotic region of the esophagus differs between Western and Japanese EIPD patients. Some reports have described GERD as a risk factor for EIPD (4-6), and the proportion of patients with GERD is higher in Western countries than in Japan (4,13,14). In Western patients with EIPD, GERD was present in 70% of patients (4), whereas our review indicated that there was only one case of GERD in Japanese patients with EIPD. Therefore, the site of stenosis in Western patients with EIPD seems to be more commonly located in the lower esophagus, due to the higher morbidity rate of GERD than in Japanese patients. In Western EIPD patients, the administration of antireflux medication was performed in 14 cases, and this treatment was successful in 85.7% (12 cases) (4).

Table.

Review Summary of Cases with Esophageal Intramural Pseudodiverticulosis.

	Western		Japanese
	(n=97)		(n=48)
The number of patients with dysphagia accompanied with stenosis of the esophagus (%)	88	(90.7%)	41	(85.4%)
The site of stenosis
Cervical or upper esophagus	39	(44.3%)	12	(66.7%)
Middle or lower esophagus	49	(55.7%)	6	(33.3%)
Intercurrent disease
Gastroesophageal reflux disease	68	(70.1%)	1	(2.1%)
Candida esophagitis	15	(15.5%)	24	(50.0%)
Treatment*
Antifungal medication	6	(6.2%)	14	(29.2%)
Antireflux medication	14	(14.4%)	4	(8.3%)
Balloon dilatation	40	(41.2%)	11	(22.9%)
Surgical operation	12	(12.4%)	8	(16.7%)
Other treatment	3	(3.1%)	5	(10.4%)
No treatment given	19	(19.6%)	7	(20.8%)
Not described	8	(8.2%)	6	(12.5%)

*Treatment includes duplicate cases.

Regarding Candida esophagitis, another risk factor for EIPD, 41% of Western patients and 65% of Japanese patients were diagnosed. Candida is a fungus normally present in the oral cavity (15) and might have caused the stenosis of the upper esophagus, as Candida seems to be easily transferred to the upper esophagus by swallowing. Antifungal drugs were administered to 14 patients (58.3%) of the 24 Japanese EIPD patients with Candida esophagitis. Among these patients, five with severe stenosis of the esophagus underwent balloon dilatation as well as antifungal drug administration, suggesting that additional intervention other than drug treatment might be needed in those patients. In recent years, the number of patients with GERD has been increasing in Japan (16); the site where esophageal stenosis is likely to occur in Japanese patients with EIPD might therefore change in the future.

Regarding surgical treatment, in Western EIPD patients, 12 cases (12.4%) underwent an operation, such as antireflux surgery or resection/bypass of stricture (4), whereas esophagectomy was performed in 8 (16.7%) Japanese EIPD patients. Among the Japanese EIPD patients who underwent surgery, esophagectomy was performed in seven cases due to accompanying or high suspicion of esophageal cancer, and surgery was performed in one case due to perforation of the esophagus.

The number of reports on the association between esophageal peristalsis and EIPD is limited. To date, there have been only three reports of HRM being performed for patients with EIPD. One case reported a patient with a proximal peristaltic defect in the esophageal body (17), and another case demonstrated that EIPD is a comorbid disease of Jackhammer's esophagus (18). Another report stated that an increased esophageal pressure due to abnormal esophageal contractions may be one of the mechanisms underlying the development of EIPD (7). In our case, abnormal esophageal contractions could not be detected on HRM, and esophageal peristalsis was normal, including IRP, DL, and DCI. Although increased esophageal pressure may be associated with esophageal motility disorder, which is a factor in the pathogenesis of EIPD, it should be considered that EIPD can occur even if the esophageal intraluminal pressure is normal, such as in our case. The presence of EIPD might induce increased esophageal pressure or abnormal esophageal contraction.

Nevertheless, the relationship between esophageal motility disorder and EIPD remains unclear, including whether EIPD is a cause or a consequence of esophageal motility disorders. Therefore, the implementation of HRM for patients with EIPD is needed to clarify these associations.

In conclusion, the presence of EIPD should be considered in patients with dysphagia, since dysphagia might result from stenosis of the esophagus, accompanied by EIPD. To adequately diagnose EIPD, not only EGD but also esophagography should be performed.

The authors state that they have no Conflict of Interest (COI).