Eosinophilic Esophagitis: Asthma of the Esophagus?

Abstract

The question whether eosinophilic esophagitis (EoE) might be an ‘asthma of the esophagus' is reasonable. There are a number of similarities between the two diseases: EoE and asthma, as well as other atopic diseases, are frequently associated and have a number of similarities in their pathogenesis. Thus, investigating differences and similarities between the diseases might be a worthwhile endeavor. Both EoE and asthma are chronic immune-mediated conditions characterized by inflammatory changes in the mucosa and submucosa with a characteristic and diagnostic infiltration of eosinophils. They result in organ dysfunction with considerable morbidity and (in the case of asthma) even mortality. Asthma and EoE affect all ages, but frequently start in childhood or adolescence. While asthma has seen a large increase in its prevalence in the past 50 years, EoE was first described in the 1970s. Since then the frequency of the diagnosis of EoE has increased significantly. The prevalence for both diseases seems to be highest in the Western world. In contrast to asthma, where females are more often affected, EoE is more frequent in males. Asthma in children, however, is also more common in boys, but this changes after puberty. EoE is frequently associated with asthma, and up to 80% of patients with EoE are atopic, similar to childhood asthma. Adult-onset asthma is not necessarily associated with atopy (termed intrinsic asthma) and similar observations have been made for EoE. Endoscopically, asthmatic airway mucosa as well as esophageal mucosa in EoE can appear normal, and biopsies are required for diagnosis. Long-standing disease in asthma has been associated with ‘remodeling' compared to predominantly reversible inflammatory changes early in the course of the disease. Similar observations have been made in EoE. Toxic proteins derived from eosinophils such as major basic protein, eosinophil-derived neurotoxin and eosinophil cationic protein can be found in the mucosa of both diseases, which are also characterized by a thickening of the lamina propria or basement membrane, respectively. Despite these histologic and immunochemistry findings, asthma as well as EoE remain clinical diagnoses, and diagnosing either condition can be challenging. Therapeutically, both diseases respond well to corticosteroids. Ironically, corticosteroids for inhalation are deliberately swallowed in EoE to reach the esophageal mucosa. Allergen/food avoidance can improve symptoms in asthma and EoE. Taken together, allergic asthma and EoE have a number of common features which make a common pathogenesis manifested in different organs for reasons not yet fully understood likely. Combining allergological research with gastroenterologic and pneumologic expertise with a focus on similarities between these diseases might be a way forward.

Enhanced activation of eosinophils in peripheral blood and implications for eosinophilic esophagitis diagnosis

“…Activated eosinophils are effector cells with proinflammatory and destructive capabilities. Eosinophils with activation phenotypes are observed in the specimens of esophagus of patients with EoE, and deposition of eosinophil products is readily seen in these patients' affected tissues . They have been suggested to participate in the damaging process .…”

“…Eosinophil degeneration was significantly lower in the group with EoE, suggesting that eosinophils showed a greater half‐life in these patients. This is possibly due to the influence of cytokines released by the esophageal epithelium, such as IL‐5, IL‐23, leukotrienes, and eotaxin‐3, which prolong the half‐life of eosinophils by inactivating molecules that lead to apoptosis, like Fas and FasL …”

“…Eosinophils with activation phenotypes are observed in the specimens of esophagus of patients with EoE, and deposition of eosinophil products is readily seen in these patients' affected tissues. 7 They have been suggested to participate in the damaging process. 6 Eosinophils abounding and degranulating in esophageal tissue are also believed to have pathogenic roles in EoE.…”

“…5 Furthermore, esophageal changes are not limited to the number of eosinophils and might also depend on the extracellular content of eosinophil granule proteins, which might have a functional role in EoE 6 and have been suggested to participate in the damaging process. 7 Major basic protein has been found around eosinophilic cells, showing that degranulation of eosinophils in the esophageal wall occurs. The intensity of degranulation was not correlated with the number of eosinophils in the esophageal epithelium, suggesting that the absolute number of eosinophils has little relationship with disease severity.…”

“…However, eosinophilia is detected in blood only in 50% of patients with EoE . Furthermore, esophageal changes are not limited to the number of eosinophils and might also depend on the extracellular content of eosinophil granule proteins, which might have a functional role in EoE and have been suggested to participate in the damaging process . Major basic protein has been found around eosinophilic cells, showing that degranulation of eosinophils in the esophageal wall occurs.…”