Intraepithelial eosinophils (IEEs) are a specific finding in medical pathology signaling an underlying inflammatory or allergic disease process. The term describes eosinophils, a type of white blood cell, that have abnormally migrated from the deeper connective tissue layer (lamina propria) and infiltrated the surface lining (epithelium) of an organ. Their presence in certain tissues, particularly the esophagus, is not a normal finding and serves as a diagnostic marker for specific conditions. Identifying and counting these cells within a tissue sample is a primary task for pathologists investigating immune-mediated disorders.
The Biological Role of Eosinophils
Eosinophils belong to a group of white blood cells called granulocytes, characterized by granules filled with potent biological chemicals. These cells develop in the bone marrow and circulate before migrating into various tissues. Their primary function involves defending the body against parasitic infections by releasing toxic granule contents. In developed nations, however, eosinophils are primarily associated with Type 2 inflammatory responses, such as allergic reactions.
Normally, eosinophils reside in the connective tissues beneath the epithelium of the gastrointestinal tract, lungs, and skin, acting as immune sentinels. Their presence in these deeper layers is a regulated state and not a sign of disease. The medically significant finding is their movement across the basement membrane and into the epithelium itself (the “intraepithelial” location). This migration is often triggered by inflammatory signaling molecules, such as Interleukin-5 (IL-5), which recruit and activate these cells at the site of exposure to an allergen.
Eosinophilic Esophagitis: The Primary Association
The most common and clinically relevant condition associated with a high number of intraepithelial eosinophils is Eosinophilic Esophagitis (EoE). This chronic, immune-mediated disease is characterized by inflammation limited to the esophagus, typically driven by an allergic reaction to foods or environmental allergens. This leads to the sustained infiltration of eosinophils into the esophageal lining.
Symptoms of EoE often include difficulty swallowing (dysphagia) and food impaction. Chronic inflammation from persistent IEEs leads to tissue remodeling, causing structural changes like rings, furrows, and narrowing of the esophageal lumen. Diagnosis requires both clinical symptoms of esophageal dysfunction and the histological finding of eosinophil-rich inflammation.
To confirm the diagnosis, a gastroenterologist performs an endoscopy and takes biopsies from the esophagus. A pathologist examines these samples to count the IEEs within a high-power field (hpf). Current guidelines define EoE by the presence of at least 15 eosinophils per hpf in the biopsy, along with the exclusion of other causes of esophageal eosinophilia. This specific numerical threshold distinguishes EoE from conditions like gastroesophageal reflux disease (GERD), which may cause a lower eosinophil count. This quantification is fundamental for definitive diagnosis, guiding subsequent management and monitoring treatment response.
IEEs in Other Gastrointestinal and Organ Systems
Beyond the esophagus, intraepithelial eosinophils can be present in other segments of the digestive tract, resulting in Eosinophilic Gastrointestinal Disorders (EGIDs). These include Eosinophilic Gastritis (EoG) in the stomach, Eosinophilic Enteritis (EoN) in the small intestine, and Eosinophilic Colitis (EoC) in the large intestine. These conditions cause symptoms like abdominal pain, nausea, vomiting, and diarrhea, differing from the swallowing issues of EoE.
Unlike the esophagus, the stomach, small intestine, and colon naturally contain a baseline population of eosinophils. Consequently, the diagnostic thresholds for non-esophageal EGIDs are significantly higher and specific to the organ segment. For example, diagnosis in the stomach and small intestine often requires counts of 30 or more and 50 or more eosinophils per high-power field, respectively.
EGIDs are rarer than EoE and can affect multiple sites simultaneously. Outside the digestive system, eosinophils contribute to chronic allergic conditions like eosinophilic asthma, where their presence drives inflammation and tissue damage in the bronchial lining.
Detecting and Managing Eosinophilic Inflammation
The detection of intraepithelial eosinophils begins with an upper endoscopy, where a flexible tube with a camera is passed into the digestive tract. The physician obtains small tissue samples (biopsies) from the affected area, such as the esophagus. These biopsies are processed and stained in the pathology laboratory to make the eosinophils visible for cell counting.
Management strategies focus on reducing inflammation by eliminating the immune trigger or suppressing the eosinophil response. One common treatment involves dietary elimination, often targeting common food allergens. This approach requires subsequent endoscopies to confirm if the removal of the specific food has successfully reduced the IEE count.
Pharmaceutical interventions are widely used to reduce tissue inflammation. Swallowed topical corticosteroids, which act locally with minimal systemic absorption, are a standard first-line treatment for EoE. Proton pump inhibitors (PPIs), which reduce stomach acid, are also frequently used, as they can reduce esophageal eosinophilia through anti-inflammatory mechanisms.
For severe or refractory cases, newer biologic therapies are available that specifically target inflammatory pathways responsible for eosinophil recruitment. These medications, such as monoclonal antibodies that block Interleukin-5, effectively lower eosinophil counts in the blood and affected tissues. The goal of management is to achieve histological remission—the reduction of intraepithelial eosinophils below the diagnostic threshold—to alleviate symptoms and prevent long-term tissue damage.