Anti-Amoxicillin Immunoglobulin E, Histamine-2 Receptor Antagonist Therapy and Mast Cell Activation Syndrome Are Risk Factors for Amoxicillin Anaphylaxis

Abstract

Background: β-Lactam antibiotics (mainly amoxicillin, AX) are the drugs that most frequently induce systemic drug allergy reactions. Objective: We attempted to identify the risk factors associated with systemic reactions to AX. Methods: All patients who were referred to our department for suspected hypersensitivity reactions to AX over a 6-month period were evaluated for anti-AX immunoglobulin E (IgE) levels and skin-test positivity for β-lactams. Age, sex, concomitant diseases, therapies, total IgE, serum tryptase levels and signs and symptoms suggesting mast cell activation syndrome (MCAS) were analyzed in relation to the severity of the reaction in accordance with the Mueller classification. Results: Sixty-seven patients were selected: 39 with mild reactions such as cutaneous or gastrointestinal symptoms (grades I and II) and 28 with severe systemic reactions (grades III and IV). Anti-AX IgE levels and total IgE were significantly higher in severe reactions than in mild ones (p < 0.00005, p = 0.0037). Treatment with histamine-2 receptor antagonists (anti-H2) was significantly related to severe reactions (p = 0.007). No significant correlations were found between the severity of the reactions and dyslipidemia or levels of angiotensin-converting enzyme and tryptase. Conclusion: Anti-AX IgE levels were the most significant immunological parameter distinguishing patients who presented with severe reactions to AX and those with mild reactions. Higher values of total IgE, the use of gastroprotective drugs and signs and symptoms suggesting an MCAS significantly increased the odds ratio of having a severe reaction. The risk of serious adverse reactions to AX increased in older patients and in males, but this trend was not significant.

Diagnostic workup including CD203c‐based basophil activation test in immediate hypersensitivity due to metronidazole and ornidazole and evaluation of cross‐reactivity in between

“…53 On the other hand, in some studies elevated tIgE levels were defined as a risk factor in patients who had anaphylaxis due to quinolones 54 and amoxicillin. 55 In another study, serum tIgE level was found higher in patients with quinolone hypersensitivity and atopy was observed in 50% of these patients. 56 In the present study, serum tIgE level was higher in patients with confirmed diagnosis (P = .023) and only 2 of these patients had atopy.…”

“…In a recent study, elevated tIgE levels were reported in non‐atopic aspirin‐exacerbated respiratory disease patients 53 . On the other hand, in some studies elevated tIgE levels were defined as a risk factor in patients who had anaphylaxis due to quinolones 54 and amoxicillin 55 . In another study, serum tIgE level was found higher in patients with quinolone hypersensitivity and atopy was observed in 50% of these patients 56 .…”

Evaluation of the Potential Risk Factors for Drug-Induced Anaphylaxis in Adult Patients

“…Previously, our group reported that the total IgE level was higher in quinolone-induced anaphylaxis [30] and Pastorello et al [53] reported that higher total IgE level was associated with severity in amoxicillin-induced anaphylaxis. However, in this study, serum total IgE levels were not associated with anaphylaxis in the general study population, and also not in β-lactam- or NSAID-hypersensitive patients.…”

Nonclonal Mast Cell Activation Syndrome

“…Not surprisingly, allergic disorders and specific IgE-mediated allergies to environmental factors and foods are prominent in NC-MAS patients and should be weighed in the context of the presenting manifestations to decide whether secondary mast cell activation due to allergy is the more appropriate diagnosis. Furthermore, the presence of NC-MCAS may increase the severity of allergic reactions as was shown in a cohort of patients with NC-MCAS and allergy to amoxicillin (33).…”