Lymphocyte-rich inflammation of the esophageal mucosa has gained increased awareness among pathologists and clinicians recently. Patients usually present with symptoms of esophageal dysfunction, including dysphagia and food bolus impaction. Endoscopy may show changes similar to eosinophilic esophagitis but may also be entirely normal ('microscopic esophagitis'). Three morphological subtypes or variant forms have been described which include lymphocytic, lichenoid and lymphocyte-predominant esophagitis. These need to be discriminated against other distinct causes of esophageal lymphocytosis, such as gastro-esophageal reflux disease and Candida infection.

This review provides an overview of diagnostic criteria and clinical associations of the disorder and presents an algorithmic approach to diagnosis. A comprehensive literature review was conducted using PubMed, Medline and Google Scholar databases to identify articles related to lymphocyte-rich esophageal inflammation, published up to March 2024.

Lymphocyte-rich inflammation needs to be included in the differential diagnosis and clinical work-up of patients with esophageal dysfunction. There is currently considerable morphological overlap among published subtypes or variant forms. Follow-up studies of affected individuals are needed to formalize diagnostic parameters and identify the clinical course of disease in order to optimize treatment modalities.

Several features of drug-induced mucosal alterations have been observed in the upper gastrointestinal tract, i.e., the esophagus, stomach, and duodenum. These include pill-induced esophagitis, desquamative esophagitis, worsening of gastroesophageal reflux, chemotherapy-induced esophagitis, proton pump inhibitor-induced gastric mucosal changes, medication-induced gastric erosions and ulcers, pseudomelanosis of the stomach, olmesartan-related gastric mucosal inflammation, lanthanum deposition in the stomach, zinc acetate hydrate tablet-induced gastric ulcer, immune-related adverse event gastritis, olmesartan-asso-ciated sprue-like enteropathy, pseudomelanosis of the duodenum, and lanthanum deposition in the duodenum. For endoscopists, acquiring accurate knowledge regarding these diverse drug-induced mucosal alterations is crucial not only for the correct diagnosis of these lesions but also for differential diag-nosis of other conditions. This minireview aims to provide essential information on drug-induced mucosal alterations observed on esophagogastroduodenoscopy, along with representative endoscopic images.

Esophagitis dissecans superficialis (EDS) is a rare disease characterized by sloughing of the superficial esophageal mucosa and, histologically, by the bitonal appearance of the squamous epithelium secondary to necrosis of the most superficial layers. Etiology is uncertain, however, it has been associated with some medications, autoimmune diseases, esophageal stasis and endoscopic procedures. Here, two cases are presented, one of them which appeared in a woman after an episode of dysphagia and another one which occurred to a man with comorbidities and epigastric pain. This entity should be considered due to its self-limiting clinical course, compared to other entities with a more torpid evolution or that require more specific treatment.

Lichen planus (LP) is a frequent, chronic inflammatory disease involving the skin, mucous membranes and/or skin appendages. Esophageal involvement in lichen planus (ELP) is a clinically important albeit underdiagnosed inflammatory condition. This narrative review aims to give an overview of the current knowledge on ELP, its prevalence, pathogenesis, clinical manifestation, diagnostic criteria, and therapeutic options in order to provide support in clinical management. Studies on ELP were collected using PubMed/Medline. Relevant clinical and therapeutical characteristics from published patient cohorts including our own cohort were extracted and summarized. ELP mainly affects middle-aged women. The principal symptom is dysphagia. However, asymptomatic cases despite progressed macroscopic esophageal lesions may occur. The pathogenesis is unknown, however an immune-mediated mechanism is probable. Endoscopically, ELP is characterized by mucosal denudation and tearing, trachealization, and hyperkeratosis. Scarring esophageal stenosis may occur in chronic courses. Histologic findings include mucosal detachment, T-lymphocytic infiltrations, epithelial apoptosis (Civatte bodies), dyskeratosis, and hyperkeratosis. Direct immuno-fluorescence shows fibrinogen deposits along the basement membrane zone. To date, there is no established therapy. However, treatment with topical steroids induces symptomatic and histologic improvement in two thirds of ELP patients in general. More severe cases may require therapy with immunosuppressors. In symptomatic esophageal stenosis, endoscopic dilation may be necessary. ELP may be regarded as a precancerous condition as transition to squamous cell carcinoma has been documented in literature. ELP is an underdiagnosed yet clinically important differential diagnosis for patients with unclear dysphagia or esophagitis. Timely diagnosis and therapy might prevent potential sequelae such as esophageal stenosis or development of invasive squamous cell carcinoma. Further studies are needed to gain more knowledge about the pathogenesis and treatment options.

This review summarizes our current understanding of lymphocytic esophagitis (LE), a novel form of chronic esophagitis that incorporates distinctive histologic, clinical, and endoscopic features. First described as a histologic entity, a diagnosis of LE requires intraepithelial lymphocytosis without significant granulocytic inflammation and some evidence of epithelial damage; the rationale for and studies supportive of these histologic criteria are discussed within. Clinically, the majority of patients who present with histologically confirmed LE are older women or patients with underlying immunologic abnormalities, such as Crohn disease, rheumatologic disorders, or common variable immunodeficiency. The most common presenting symptom of LE is dysphagia, and the endoscopic findings can vary from normal mucosa to mucosal changes that resemble eosinophilic esophagitis: edema, rings, furrows, and plaques. The incidence of luminal strictures and the persistent dysphagia and/or lymphocytosis present in some patients provide evidence that LE is a chronic inflammatory disorder, at least within a subset of individuals. Several histologic mimics of LE are examined, as are disagreements surrounding the LE diagnosis.

Herpes simplex virus (HSV) and cytomegalovirus (CMV) immunohistochemical stains (IHC) are frequently applied on esophageal biopsies. Our aims were to identify IHC use patterns in viral esophagitis (VE), and clinicopathologic features of VE that could guide IHC use.

We included 58 VE cases and 60 controls, defined as patients with negative HSV/CMV IHC between January 2006 and July 2017. Biopsies were reviewed and histologic features and clinical data recorded.

Thirteen cases required IHC for diagnosis. IHC was performed in 13 HSV and 5 CMV cases where diagnostic viral inclusions were present. VE patients were more likely to have endoscopic ulcer (P=0.002) and be immunocompromised (P<0.001). Pretest clinical concern for VE was common (P=0.006). Histologically, VE patients were more likely to have ulcer (P=0.004), ulcer exudate rich in neutrophils and histiocytes (P=0.001), neutrophils in squamous mucosa (P<0.001), histiocyte aggregates >15 (P<0.001) and spongiosis (P<0.001). Controls had frequent eosinophils, alone (P=0.008) or admixed with other inflammatory cells (P<0.0001).

IHC is used in VE biopsies despite definite viral inclusions on hematoxylin and eosin and in patients without concerning histology or clinical concern for VE. History, endoscopic findings, and histology can be used to better target IHC use in VE.

This review summarizes recent literature pertaining to infectious oesophagitis.

Infectious oesophagitis is an uncommon condition of the oesophagus caused by viral, bacterial or fungal agents. A compromised immune system is the most important risk factor for the development of infectious oesophagitis and HIV or AIDS and solid organ transplant patients are particularly at risk. Common symptoms of infectious oesophagitis include odynophagia and dysphagia, but it can be difficult to distinguish infectious oesophagitis from other causes of oesophagitis based on patient symptoms alone. Definitive diagnosis requires esophagoscopy with biopsy for histologic and microbiologic evaluation. Endoscopic findings differ based on cause. Overall, Candida albicans is the most common cause of infectious oesophagitis. Treatment of infectious oesophagitis is based on host immune status, the severity of infection and risk of complications. When seemingly adequate treatment is unsuccessful, alternative diagnoses should be entertained and additional biopsies and/or diagnostics obtained.

Recent research in infectious oesophagitis involves identifying preventive strategies for at-risk populations. Prevention may include use of probiotics, prophylactic medications and/or treatment of underlying immune dysfunction and could be important for susceptible individuals.

Among the many inflammatory processes that may account for esophageal symptoms, infection represents an important etiologic category with numerous clinically relevant subdivisions. While features of the history and physical exam are informative, diagnosis often hinges on endoscopic visualization and histopathologic analysis. This chapter will review in series the most clinically relevant causative agents for infectious esophagitis, with specific diagnostic and therapeutic features of note divided into one of two immune milieus. Our discussion focuses primarily on Candida species, herpes simplex virus, and cytomegalovirus as the most common causes of infectious esophagitis while also addressing a number of less common pathogens worth keeping in mind.

The non-steroid anti-inflammatory drugs (NSAIDs) are among the drugs that can commonly cause injury in the esophagus, such as non-reflux oesophagitis, with important clinical consequences. This injury may be 'silent' and therefore often overlooked. Recently, we established that hydrogen sulfide (H2S) is a critical mediator of esophageal mucosal protection and repair. The aim of the study was to determine the effect of naproxen, the most commonly used NSAIDs, on the oesophagus and oesophagogastric junction and its relation with suppression or stimulation of endogenous H2S synthesis during naproxen-induced oesophageal injury.

Rats were treated with vehicle (control) or naproxen, with or without being subjected to water immersion restricted stress (Takagi et al. Chem Pharm Bul 12:465-472, 1964). Subgroups of rats were pre-treated with an inhibitor of H2S synthesis cystathionine γ-lyase (CSE) or cystathionine β-synthase (CBS), or with the Sodium sulphide (NaHS), which spontaneously generates H2S in solution. Damage of the oesophageal mucosa and oesophagogastric junction was estimated and scored using a histological damage index.

Treatment with naproxen increased the thickness of the corneal and epithelial layers of the oesophagus, as well as producing disorganization of the muscle plate and irregular submucosal oedema. Both injury factors, stress and suppression of H2S synthesis resulted in the development of severe esophagitis and damage to the oesophagogastric junction. The damage was exacerbated by inhibitors of H2S biosynthesis, and attenuated by treatment with NaHS.

Inhibition of endogenous H2S synthesis provides a novel experimental model that can be useful in preclinical studies NSAID-related non-reflux oesophagitis. H2S contributes significantly to mucosal defence in the oesophagus.