Lymphocytic Esophagitis: Navigating an Uncharted Territory

Abstract

Lymphocytic esophagitis (LE) is an uncommon subtype of esophagitis defined by persistent esophageal inflammation characterized by a high count of intraepithelial lymphocytes with scarce granulocytes. Although LE can present with atypical features such as chest pain, its clinical presentation can mimic that of gastroesophageal reflux disease or eosinophilic esophagitis, highlighting the importance of biopsy in diagnosing LE. Studies are still limited in understanding the pathophysiology behind this disease warranting further research. A 47-year-old female patient sought medical care with a chief complaint of recurrent substernal chest pain for the past year. An esophagogastroduodenoscopy was performed and showed patchy linear esophageal erosions and mucosal edema in the middle third of the esophagus with mild erythema. Biopsies revealed intraepithelial lymphocytosis with more than 40 lymphocytes per high-power field, corroborating a diagnosis of LE. Patient reported improvement after receiving high dose of proton pump inhibitor (PPI) on her first follow-up, advised to follow a low-acid diet and an annual endoscopy to monitor her response to treatment. Lymphocytic esophagitis often presents with symptoms that overlap with other esophageal diseases explaining the possible errors in underdiagnosing it as reason behind non-cardiac chest pain. This case plays an instrumental role in changing the way physicians translate unexplained chest pain, adding LE to their list of differential diagnosis as prompt detection slows us to start management with PPIs quicker and lessen the burden of symptoms on the patient. Standardized treatment approaches and further studies are required to clarify the connection between LE and non-cardiac chest discomfort.

Learning Points

• Lymphocytic esophagitis often presents with symptoms that overlap with other esophageal diseases explaining the possible errors in underdiagnosing it as reason behind non-cardiac chest pain.

• This case plays an instrumental role in changing the way physicians translate unexplained chest pain, adding lymphocytic esophagitis to their list of differential diagnosis as prompt detection slows us to start management with PPIs quicker and lessen the burden of symptoms on the patient.

• Standardized treatment approaches and further studies are required to clarify the connection between lymphocytic esophagitis and non-cardiac chest discomfort.

Introduction

Esophagitis is a chronic inflammation of the esophagus and it can be caused by several etiologies such as reflux, eosinophilic, infectious, medications induced, and rarely lymphocytic esophagitis (LE). Lymphocytic esophagitis is an important emerging topic that had not been studied extensively yet. ¹ After it was first reported by Aleem et al, ² LE has been considered to be a differential diagnosis among patients with esophagitis not matching the typical features of either gastroesophageal reflux disease (GERD) or eosinophilic esophagitis (EoE).^3,4

The clinical manifestation of LE coincides with several esophageal etiologies such as dysphagia, food impaction, and heart burn, making it difficult to differentiate among them clinically and leaving us with biopsy as the only gold standard of diagnosis. ⁵ To differentiate, LE is characterized by the presence of an increased number of intraepithelial lymphocytes (IELs) in the squamous mucosa of the esophagus on biopsy. ⁶ On the other hand, LE can present with atypical features that are infrequent but noteworthy symptoms.

For this, we herein describe the case of a 47-year-old female patient who was diagnosed with LE manifesting as non-cardiac chest pain.

Case Presentation

This is a case of a 47-year-old female patient, known to have hypertension and dyslipidemia that are well controlled with medications, presented for recurrent substernal chest pain for the past year. The pain was described as painful, squeezing feeling lasting for 10 to 20 minutes at rest which is exacerbated with inspiration and alleviated with leaning forward or drinking water. No other symptoms such as weight loss, dysphagia, diaphoresis, palpitations, and pain radiating to the jaw or left hand were reported. The patient is otherwise healthy with no history of neither smoking nor alcohol use. The patient had multiple visits to her cardiologist for her ongoing symptoms. Extensive cardiac workup such as electrocardiogram (ECG), chest x-ray, stress test, and coronary angiogram was done to rule out any coronary artery disease, but all revealed no abnormalities. The patient was referred to our gastroenterology clinic for further investigation of any possible esophageal pathologies for her non-cardiac chest pain.

Findings were normal with Barium swallow study that was made first to rule out any structural or anatomical abnormalities, strictures, tumors, or motility causes. Upper endoscopy showed patchy linear esophageal erosions and mucosal edema in the middle third of the esophagus with mild erythema (Figure 1A and 1B). Biopsies were taken from different levels of the esophagus. Histologically, biopsies revealed intraepithelial lymphocytosis with more than 40 lymphocytes per high-power field (HPF) (Figure 2). Immunohistochemistry showed lymphocytic predominance (CD3 + T cells) ruling out EoE and GERD.

Figure 1.

An endoscopic view revealing erythematous erosions in a linear fashion (black arrows) (A and B) interspersed with normal esophageal mucosa.

Figure 2.

A histopathological view of the biopsied esophageal mucosa revealing intraepithelial lymphocytosis with spongiosis and basal cell hyperplasia.

A diagnosis of LE was made. Thereafter, patient reported symptoms improvement and no severe episodes after receiving high dose of proton pump inhibitors (PPIs) twice daily on her first follow-up after 3 months. She was advised to follow a low-acid diet to avoid esophageal irritations and for annual endoscopy to monitor her response to treatment.

Discussion

Chronic esophagitis is divided into various subtypes, among the latter, LE, which is a rare form that has been progressively rising in diagnosis over the years as biopsy has become the gold standard to distinguish these subtypes. ⁷

Lymphocytic esophagitis is commonly defined by the latter histological observation: lymphocytosis in the peripapillary epithelium, spongiosis, and a scant existence of intraepithelial granulocytes in the absence of infection. ⁸

In the esophageal mucosa of a healthy individual, in the peripapillary epithelium, resides a few lymphocytes, known as IELs, with an approximate count of 10 IELs/HPF, normally consisting of cytotoxic CD8+ T cells. ⁹ Whereas the lamina propria is the primary site of Helper CD4+ T cells and B lymphocytes. ¹⁰

Nevertheless, the type of lymphocyte elevated may differ despite the normal distribution of CD8+ T cells, CD4+ T cells, and B lymphocytes. ⁵ Whereby, in one study, it was noted that the intraepithelial lymphocytosis was CD4+ T-cell prevalent when LE was associated with esophageal motility disorder, ¹¹ while CD8+ T-cell prevalence was noted in association with GERD. ¹² There is no necessary minimum of IEL/HPF to confirm diagnosis, ² yet a threshold of ≥20 IEL/HPF frequently applied. ⁷ Hence, the biopsy results of our patient met the standards used with more than 40 IEL/HPF with CD3+ predominance and negligible granulocyte count including eosinophils and neutrophils making the diagnosis of EoE unfavorable.

In addition, EoE is typically identified in younger adult males. ² This common association with an age group gender do not apply to the patient at hand as well.

The exact pathophysiology and etiology of LE remain unclear. The onset of this inflammatory condition could be linked to inflammatory bowel disease, ⁷ celiac disease, ⁷ gastroesophageal reflux, hypothyroidism, ⁶ rheumatological disease, lichen planus,^1,5 and primary motility disorders such as achalasia. ⁸ Remarkably, our patient does not have a past or present history of any of these conditions. The latter was confirmed upon thorough examination in aim to rule out esophageal structural or functional disorders with Barium swallow study.

Moreover, patients with a positive diagnosis usually fit the profile of a female, age above 60, allergies, history of smoking, autoimmune disease, and use of certain medications.^2,9 The only pertinent similarities with the profile of our patient are gender and the use an antihypertensives and statin to control her hypertension and dyslipidemia, respectively.

In regard to clinical presentation, the commonly reported symptoms accompanying this diagnosis include abdominal pain, odynophagia, and heartburn with dysphagia being the most common.^6,9,10 However, our patient came to the emergency department with the single complaint of a squeezing chest pain sensation of almost 15 minutes duration that improved with change in position. This presentation warranted a cardiac workup as first differential that was ultimately unremarkable and excluded the attribute of pain to a cardiac origin.

In regard to endoscopic findings, LE has a variety of presentations and features ranging from normal esophageal mucosa, to the presence of strictures, rings, linear furrows, erosive esophagitis, esophageal swelling, or white plaques.^11,12 According to the systematic review by Habbal et al., a normal endoscopic appearance was observed in 120 out of 387 individuals (31%) previously diagnosed with LE. ¹⁰ Furthermore, Tanaka et al, by using narrow-band imaging magnifying endoscopy (NBI-ME), were able to differentiate the gross endoscopic features of LE, GERD, and EoE. The evaluated traits were comprised of hidden submucosal vessels, beige-colored esophageal lining, and an increased number of congested dot-like intrapapillary loops. All 3 features were present in only 82% of the LE group in comparison to the EoE group with a presence of 100%.^1,11,12 Similarly, the endoscopic images do not comply with the 82% aforementioned as the sole pertinent findings depicted patchy linear esophageal erosions and mucosal edema in the middle third of the esophagus with mild erythema.

Many other esophageal disorders are included in the differential diagnosis of LE. These include peptic strictures, esophageal neoplasms, IgG4-related esophagitis, erosive esophagitis, Candida esophagitis, EoE, esophageal lichen planus, and achalasia or non-achalasia esophageal motility problems. ² Every one of these disorders has specific clinical characteristics, making a correct diagnosis critical for effective management and treatment.

Concerning the treatment of LE, there is no clear algorithmic protocol as compared to the treatment of EoE. ⁷ However, as they have a similar presentation, LE may be managed in a similar way. ⁶ Therefore, the therapeutic plan focuses on symptomatic management where PPIs have proven to be helpful whether or not a reflux-associated lymphocytosis is present taken twice daily for 12 weeks.^2,12 Once the course is complete, an assessment should be made based on symptoms and endoscopic findings to talk about the next step in management. Similar to PPIs, there is an apparent clinical benefit with topical steroid as shown in a case report by Kasirye et al. whereby after taking 2 puffs of fluticasone (220 μg aerosol) 3 times a day, a patient with LE no longer had solid food dysphagia after 6 months. ¹¹ However, if symptomatic esophageal strictures or rings persist in patients with LE despite medical treatment, it is recommended to undergo endoscopic therapeutic interventions consisting of serial endoscopic dilatations. ¹² Fortunately, our patient noticed a substantial improvement in her chest pain after taking PPIs for 3 months that did not warrant further management.

It is worth highlighting that what makes our case distinctive is that our patient reported with chest discomfort as an early symptom rather than more common presentations such as dysphagia, odynophagia, or heartburn. This fact therefore gives our case uniqueness and novelty.

Conclusions

Lymphocytic esophagitis is an unusual condition and LE manifesting as non-cardiac chest pain is extremely rare entity that is not studied well in literature. This case report emphasizes that physicians should take LE into consideration when examining a patient with non-cardiac chest pain. The association between LE and non-cardiac chest pain remains unclear, thus this article should target future research to disclose the relation between these 2 entities.