Society: AGA

Concomitant esophageal dysmotility can be present in up to 2/3 of patients with EoE and GERD. Esophageal dysmotility contribute to symptoms in these patients and can be a reason for a suboptimal response to therapy. Mechanisms for dysfunction of esophageal smooth muscle function in EoE and GERD have been studied in bench models of human esophageal tissues. Understanding and targeting these mechanisms therapeutically may improve symptomatic outcomes in what are otherwise considered mucosal esophageal diseases.

Background: Achalasia has been assumed to be an autoimmune disease that targets esophageal myenteric neurons. Recently, we proposed an alternative hypothesis that achalasia sometimes might be allergy-driven, caused by a form of eosinophilic esophagitis (EoE) in which activated eosinophils and/or mast cells infiltrating esophageal muscle release products that disrupt motility and damage myenteric neurons. To seek epidemiological support for this hypothesis, we identified achalasia patients in the Utah Population Database (UPDB), and explored their frequency of having EoE and other allergic disorders.
Methods: We used International Classification of Diseases (ICD) codes to identify patients with achalasia and allergic disorders including EoE, asthma, atopic dermatitis, contact dermatitis, allergic rhinitis, allergic conjunctivitis, hives/urticaria, and anaphylaxis. We validated our achalasia ICD code diagnostic accuracy by reviewing medical records of 100 randomly sampled patients in our database who had an ICD 9 or 10 diagnosis code for achalasia (validation review confirmed the diagnosis of achalasia by ICD codes in 87 of 100 cases). We calculated relative risk (RR) for each allergic disorder by comparing the number observed in achalasia patients to the expected number in control patients matched for birthyear and sex, and we performed sub-analyses for patients age ≤40 versus age >40 years.
Results: We identified a total of 844 achalasia patients for inclusion in our analyses (55% female, median age at diagnosis 58 years, Table 1). 355 (42%) had ≥1 allergic disorder(s), with contact dermatitis and asthma being the most frequent, affecting 24.5% and 23.9% of all achalasia patients, respectively. 64 achalasia patients had EoE, whereas only 1.17 EoE cases would have been expected (RR 54.5 [95% CI: 41.96-69.58], p<0.001), indicating a very strong association between the two disorders. 34 patients (54.8%) were diagnosed with achalasia and EoE during the same year, 14 (22.6%) were diagnosed with achalasia before EoE, and 14 (22.6%) were diagnosed with EoE before achalasia. The frequency of co-existing EoE was especially high in younger patients; in 208 achalasia patients age ≤40 years, the RR for EoE was 76.1 (95% CI 52.41-106.92, P<0.001). RR also was increased significantly for all other allergic disorders evaluated (all >3-fold above control, Table 2). Similarly increased rates of non-EoE allergic disorders were found in the younger and older achalasia patients with the exception of contact dermatitis, which occurred significantly more often in older patients (RR 4.77 [95% CI: 4.10-5.53]).
Conclusions: For patients in the UPDB, achalasia is strongly associated with EoE (~55-fold increased risk) and numerous other allergic disorders (all >3-fold increased risk).These data support the hypothesis that achalasia sometimes might have an allergic etiology.

Amiko Uchida

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