Introduction
The presence of esophageal rings used to be a strong indicator for eosinophilic esophagitis
(EoE) [1 ]. In 2006, however, Rubio and colleagues described 20 unique cases of chronic esophagitis
postulating a new entity, lymphocytic esophagitis (LyE) [2 ]. Subsequent studies of LyE have noted endoscopic features similar to EoE, including
esophageal rings, esophagitis, esophageal stricture, erythema, nodularity, plaques,
furrows and webs [3 ]
[4 ]
[5 ]
[6 ]. Histology of LyE is characterized by a chronic inflammation of the mid and distal
esophagus with epithelial lymphocytic infiltration, particularly involving the peripapillary
fields, distinct from other forms of chronic esophagitis where lymphocytes predominate
in the interpapillary fields [2 ]. The relative absence of granulocytes is a notable feature of this disease entity.
Since its description, there have been numerous publications supporting this condition
as a distinct clinical entity [3 ]
[4 ]
[5 ]
[6 ]
[7 ]
[8 ]
[9 ]
[10 ]. Few have commented on the presence of esophageal rings. Here we aim to contribute
to the limited literature by describing three cases of lymphocytic esophagitis with
esophageal rings.
Patients and methods
This is a retrospective report of 3 consecutive patients with esophageal rings on
endoscopy diagnosed with lymphocytic esophagitis between October 2015 and August 2016
at Northwell Health System, New Hyde Park, New York, United States. Institutional
Review Board approval was obtained to abstract patient information from the medical
chart. Informed consent was obtained for each procedure. Charts were reviewed and
clinical data was abstracted.
Case Reports
Patient 1
An 81-year-old male presented with 6 months of dysphagia to solid food, episodes of
regurgitation, and 18-lb weight loss. Medical and surgical history was significant
for bladder cancer status post-bladder resection and ileal conduit. Medications included
rabeprazole and multivitamins. There were no environmental or drug allergies. The
patient quit smoking 30 years prior, with a 15-pack-year history. He reported daily
alcohol intake (1 – 2 drinks/day). The patient underwent an upper endoscopy, which
showed esophageal concentric rings ([Fig. 1 ]), a proximal web, pseudodiverticula and a distal Schatzki’s ring. Histology showed
squamous epithelium with reactive changes infiltrated by 70 lymphocytes per high power
field (400-fold magnification), particularly in the peripapillary regions. No intraepithelial
eosinophils, neutrophils, or other granulocytes were identified ([Fig. 2 ]). Gastric and duodenal biopsies were without lymphocytic involvement. Endoscopy
1 year later demonstrated the same endoscopic and histologic findings. The patient
required endoscopic dilation of the esophageal web during both endoscopies and was
started on oral fluticasone 220 micrograms twice daily with improvement of symptoms
including resolution of his symptoms of dysphagia to solid foods and no further episodes
of regurgitation over the subsequent 6-month follow-up.
Fig. 1 Endoscopy from a patient with lymphocytic esophagitis showing a narrowed esophagus
with rings.
Fig. 2 Histology from the patient in [Fig. 1 ] that showed squamous epithelium with reactive changes, infiltrated by intraepithelial
lymphocytes, particularly in the peripapillary regions. No intraepithelial eosinophils
or neutrophils were identified.
Patient 2
A 67-year-old female presented with complaints of a globus sensation for several months.
She denied weight loss, regurgitation, vomiting, chest or abdominal pain. Medical,
surgical, and family history were noncontributory including no autoimmune diseases.
Medications included simvastatin, levothyroxine, and fexofenadine. She noted environmental
allergies, including grass, ragweed and tree pollen, and denied drug allergies. The
patient reported a distant smoking history and denied alcohol intake. Upper endoscopy
was notable for concentric rings in the mid-esophagus ([Fig. 3 ]) and evidence of distal esophageal erythema, just proximal to a 3-cm hiatal hernia.
Pathology of the middle and distal esophagus demonstrated 48 lymphocytes per high
power field concentrated around the squamous papillae, without granulocytes. The patient
was started on a proton pump inhibitor with near complete resolution of her globus
sensation at 1 year follow up.
Fig. 3 A patient with lymphocytic esophagitis with concentric rings on endoscopy.
Patient 3
A 53-year-old male with a history of Crohn’s disease managed on adalimumab, budesonide
and mesalamine presented with 1 year of dysphagia to solid foods. Medical history
was significant for asthma requiring albuterol and a small bowel resection. He denied
environmental or drug allergies. The patient was a former smoker. Endoscopy demonstrated
a distal esophageal ring ([Fig. 4 ]). Histology showed absence of granulocytes and presence of 75 lymphocytes per high
power field, with highest concentrations in the peripapillary region of the esophageal
squamous mucosa, consistent with lymphocytic esophagitis. An esophageal motility study
was consistent with mechanical obstruction in the distal esophagus. The patient underwent
a repeat endoscopy with balloon dilation of the lower esophageal ring with immediate
improvement in his complaints of dysphagia to solids. The patient was started on oral
fluticasone 220 mcg twice daily with maintenance in resolution of symptoms at 5-month
follow-up.
Fig. 4 A patient with lymphocytic esophagitis with a distal esophagus ring on endoscopy.
Summary of case series
All 3 cases reported here show esophageal rings, which were previously thought to
be suggestive of EoE. However, rings can be associated with LyE and cause symptoms
of dysphagia. Other features reported in this series were esophageal erythema, pseudodiverticula
and a web. Successful endoscopic dilation in 2 of the cases demonstrates its safety
in this patient population. Two of the patients in this series were prescribed oral
fluticasone, a medication prescribed in EoE. Although the benefit is extrapolated
from EoE, both patients responded to this treatment.
Discussion
Clinical findings for LyE are non-specific. The overall pattern of inflammation, distribution
of lymphocytes within the squamous epithelium, and clinical presentation are important
in making a diagnosis. LyE is a pathologic diagnosis characterized as having the following:
1) a large number of lymphocytes in the peripapillary region of the esophageal squamous
epithelium; 2) frequent absence of granulocytes (i. e. eosinophils, neutrophils) [2 ]; and 3) marked intracellular edema/spongiosis [3 ]
[4 ]. In contrast, biopsies in patients with gastroesophageal reflux disease (GERD) demonstrate
minimal, if any, reactive histologic changes. There has been no association identified
between LyE and lymphocytic infiltration at other sites in the gastrointestinal tract
[3 ].
The lymphocytes identified on biopsy of patients with LyE expressed CD3, CD4, CD8
and rarely granzyme B, without T-cell intracytoplasmic antigen 1 [2 ]. No granulocytes were present in 60 % of biopsies meeting diagnostic criteria for
lymphocytic esophagitis, and only occasional granulocytes were seen in the remaining
40 %. In contrast, many granulocytes were present in the other forms of esophagitis,
including grade 2 and 3 gastroesophageal reflux and Candida albicans esophagitis [2 ].
In a study of 119 cases of LyE, patients presented with similar symptoms as patients
with EoE, most commonly dysphagia (LyE: 53 % vs. EoE: 63 %) [4 ]. Across 4 studies of patients with LyE, complaints of dysphagia and heartburn were
noted in 43 – 70 % and 18.5 – 47 % of patients respectively [3 ]
[4 ]
[5 ]
[6 ]. Additional symptoms include odynophagia, abdominal pain, chest pain, nausea, vomiting,
regurgitation, and heartburn ([Table 1 ]). Notable complications of LyE include food impactions [7 ].
Table 1
Symptoms and endoscopic findings in patients with lymphocytic esophagitis across 4
studies.
Purdy et al. [3 ] (%)
Haque et al. [4 ] (%)
Cohen et al. [5 ] (%)
Pasricha et al. [6 ] (%)
Clinical manifestations
Dysphagia
43
52.9
66.7
70
Heartburn/reflux
26
18.5
46.9
26
Abdominal/chest pain
–
–
44.4
–
Abdominal pain
–
–
–
15
Chest pain
–
–
–
19
Nausea/vomiting
–
–
29.6
19
Odynophagia
–
–
12.3
4
All esophageal symptoms
57
–
–
–
Endoscopic impressions
Normal
31
22.6
29.6
18
Esophagitis
24
18.5
16.0
33
Eosinophilic esophagitis
–
33.6
–
–
Esophageal rings
12
–
19.8
26
Stricture
–
10.1
8.6
37
Motility disorder
–
5.0
–
–
Schatzki's ring
–
2.5
–
–
Candida
–
1.6
–
15
Achalasia
–
0.8
–
–
Hiatal hernia
10
–
–
26
Narrow caliber
–
–
–
44
Overall, LyE was detected in ~ 0.1 %, or 1 in 1000, of all patients who underwent
esophageal biopsies for any cause [4 ]. LyE predominantly affects older women (60 %) with a median age of 63. In contrast,
EoE tends to affect younger men (66 %) with a median age of 43 [4 ]. The majority of LyE patients are white (86 %) [5 ]. When compared to patients with normal esophageal biopsies, GERD and EoE, patients
with LyE were more likely to use tobacco, had comparable rates of drug and food allergies,
and were less likely to have allergic rhinitis [6 ].
Patients with LyE can have a variety of endoscopic findings ([Table 1 ]). Across 4 studies, the appearance of a normal esophagus in LyE ranged from 18 %
to 31 % [3 ]
[4 ]
[5 ]
[6 ]. Esophageal rings were present in 19.8 % of patients (vs. 18.8 % of patients with
EoE) [5 ]. In contrast to EoE, patients with LyE had fewer esophageal strictures (8.6 % vs.
16.3 %) [5 ], however the incidence of strictures in LyE ranged from 8.6 % to 37 % [4 ]
[5 ]
[6 ]. Overall, based on the endoscopic appearance of the esophagus, EoE was suspected
by physicians in one third of LyE cases [4 ], demonstrating that these clinically distinct entities have overlapping features.
Thirty-seven cases of LyE with esophageal rings have been reported in the literature
to date. With this case series, there are now 40 reported cases. There is no identifiable
unifying feature that would allow postulation of an associated condition or patient
characteristic ([Table 2 ]). Two of the 3 patients in this case series underwent balloon dilation of their
esophageal rings with symptomatic improvement in their dysphagia.
Table 2
Summary of literature on lymphocytic esophagitis with esophageal rings
Purdy et al. [3 ]
Haque et al. [4 ]
Cohen et al. [5 ]
Pasricha et al. [6 ]
Mandaliya et al. [7 ]
Kasirye et al. [8 ]
Niewiarowski et al. [9 ]
Zhang et al. [10 ]
Pleet et al.
# patients with LyE, n
42
119
81
27
1
1
1
1
3
# patients with LyE and esophageal rings, n
5 (12 %)
5 (4 %)
16 (20 %)
7 (26 %)
1
1
1
1
3 (100 %)
Men, n
–
47 (40 %)
37 (46 %)
10 (37 %)
1
0
0
0
2 (67 %)
Age, years
45 (median)
62 (median)
51 (median)
56 (mean)
74
60
82
66
67 (median)
Caucasian, n
–
–
69 (85 %)
16 (59 %)
–
–
–
–
3 (100 %)
Tobacco use, n
–
–
24 (30 %)
13 (48 %)
–
–
–
1
3 (100 %)
Lye, lymphocytic esophagitis
Treatment with proton pump inhibitors, alterations in eating habits, and topical steroids
are of unknown benefit. Anecdotal evidence supporting the use of proton pump inhibitors
is conflicting. Currently there is insufficient evidence to recommend lifestyle changes
or medical therapy for LyE. Patients with LyE and webs, rings or strictures can benefit
from mechanical dilation, though symptoms can recur.
The clinical course of LyE is largely unknown. In one study, almost 90 % of patients
were still living 3 years after diagnosis and reported good quality of life at follow
up [5 ]. Repeat upper endoscopy on patients with previously diagnosed LyE demonstrated persistent
LyE in 41 % of cases, with the remaining cases showing normal or alternative diagnoses
[5 ]. Nearly 60 % of this cohort of LyE patients reported improvement in initial symptoms,
largely attributed to escalation of medical management (70.6 % of cases), usually
with a proton pump inhibitor [5 ].
Since it was first described in 2006, the diagnosis of LyE has risen drastically [5 ]. While it’s clinical presentation may overlap with other forms of chronic esophagitis,
particularly EoE, it is histologically distinct. As our case series shows, patients
with LyE may present with esophageal rings. Further research is needed to determine
the cause, clinical course and effective treatment options for this disease entity.
