Tryptase in Acute Appendicitis: Unveiling Allergic Connections through Compelling Evidence

Abstract

The aetiology of acute appendicitis (AA), the most frequent abdominal surgical emergency, is still unclarified. Recent epidemiologic, clinical and laboratorial data point to an allergic component in the pathophysiology of AA. Mastocytes participate in the Th2 immune response, releasing inflammatory mediators from their granules upon stimulation by IgE-specific antigens. Among the well-known mediators are histamine, serotonin and tryptase, which are responsible for the clinical manifestations of allergies. We conducted a prospective single-centre study to measure histamine and serotonin (commercial ELISA kit) and tryptase (ImmunoCAP System) concentrations in appendicular lavage fluid (ALF) and serum. Consecutive patients presenting to the emergency department with a clinical diagnosis of AA were enrolled: 22 patients with phlegmonous AA and 24 with gangrenous AA The control group was composed of 14 patients referred for colectomy for colon malignancy. Appendectomy was performed during colectomy. Tryptase levels were strikingly different between histological groups, both in ALF and serum (p < 0.001); ALF levels were higher than serum levels. Tryptase concentrations in ALF were 109 times higher in phlegmonous AA (APA) (796.8 (194.1–980.5) pg/mL) and 114 times higher in gangrenous AA (AGA) (837.4 (272.6–1075.1) pg/mL) than in the control group (7.3 (4.5–10.3) pg/mL. For the diagnosis of AA, the discriminative power of serum tryptase concentration was good (AUC = 0.825), but discriminative power was weak (AUC = 0.559) for the differential diagnosis between APA and AGA. Mastocytes are involved in AA during clinical presentations of both phlegmonous and gangrenous appendicitis, and no significant differences in concentration were found. No differences were found in serum and ALF concentrations of histamine and serotonin between histological groups. Due to their short half-lives, these might have elapsed by the time the samples were collected. In future research, these determinations should be made immediately after appendectomy. Our findings confirm the hypersensitivity type I reaction as an event occurring in the pathogenesis of AA: tryptase levels in ALF and serum were higher among patients with AA when compared to the control group, which is in line with a Th2 immune response and supports the concept of the presence of an allergic reaction in the pathogenesis of acute appendicitis. Our results, if confirmed, may have clinical implications for the treatment of AA.

Compilation of Evidence Supporting the Role of a T Helper 2 Reaction in the Pathogenesis of Acute Appendicitis

“…There were differences between tryptase serum levels, but these were not as striking as those from ALF. In serum, tryptase levels were 6.5 times higher in APA and 11 times higher in AGA, when compared to the levels of the control group [54].…”

“…ALF tryptase levels were higher than serum levels, and these differences could reflect an intense inflammatory local reaction in the appendicular lumen. Tryptase concentrations in ALF were 109 times higher in APA and 114 times higher in AGA than in the control group [54].…”

“…Several recent studies have reinforced the hypothesis that there is a Th2 immune reaction in AA [19,45,47,[49][50][51][52][53][54][55][56][57][58][59] (Table 1).…”

“…Mast cells s are key factors in the Th2 immune response by releasing inflammatory mediators from their granules upon stimulation by IgE-specific antigens [54]. Elevated serum tryptase concentrations have been observed in several diseases, such as systemic allergic reactions [88].…”

“…A single prospective study simultaneously evaluated tryptase levels in blood and ALF in patients with AA and the control group, which was comprised of patients submitted to right colectomy for right-side colon cancer [54].…”