Background This study aimed to analyze the potential etiopathogenic role of a type I hypersensitivity reaction in the development of overall acute appendicitis (AA), non-complicated acute appendicitis (NCAA), and complicated acute appendicitis (CAA).

Methods This review was prospectively registered in PROSPERO (CRD42024516547). We included both prospective and retrospective original clinical studies that examined the role of immunoallergic processes in the development of acute appendicitis (AA). A comprehensive search was conducted in PubMed, Web of Science, Scopus, and OVID, using the following search terms and keywords: (allergy OR allergic OR immunoallergy OR immunoallergic OR immunomediated) AND (appendicitis OR appendectomy) AND (IgE OR IgE-mediated OR hypersensitivity OR type I). Two independent reviewers meticulously selected the articles and extracted relevant data. The methodological quality of the studies was rigorously assessed using the Newcastle-Ottawa index. A synthesis of the results, a standardization of the metrics, and seven random-effect meta-analyses were performed.

Results This review included nineteen studies. A random-effects meta-analysis including six articles (6370 patients with NCAA and 2000 patients with CAA) showed that patients with any documented history of IgE-mediated allergy had a lower risk of developing CAA (OR 0.52, 95%CI [0.38-0.72], p<0.0001). The random-effect meta-analysis for serum Interleukin-9 (NCAA vs. CAA) included two articles (177 patients with NCAA and 101 patients with CAA) and resulted in a significant mean difference [95% CI] of -0.38 [-0.67,-0.08] pg/mL (p=0.01). The random-effect meta-analysis for serum Interleukin-13 (NCAA vs. CAA) included two articles (177 patients with NCAA and 101 patients with CAA) and resulted in a significant mean difference [95% CI] of -11.32 [-13.90,-8.75] pg/mL (p=<0.001). The random-effect meta- analysis for total eosinophil count (NCAA vs. CAA) included three articles (455 NCAA and 303 CAA) and resulted in a significant mean difference [95% CI] of -0.06 [-0.10,-0.02] eosinophils x 109/L (p=0.002).

Conclusions The present study demonstrates an association between a type I hypersensitivity reaction and the development of NCAA. Additionally, our meta-analytic model shows significantly higher levels of eosinophils peripheral blood in patients with NCAA than in patients with CAA. These findings suggest a potential immunoallergic mediation in the development of NCAA. Future prospective studies must validate these findings since these patients may benefit from specific therapeutic targets.

Registration PROSPERO (CRD42024516547).

The authors have declared no competing interest.

This study did not receive any funding

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