Risk of Anaphylaxis in Opioid Dependent Persons: Effects of Heroin Versus Substitution Substance

Background: Across Europe, illicit drug-related mortality has not declined despite ever increasing prevention measures. The cause of these deaths has traditionally been associated with overdose. Previous findings have revealed the appearance of non-lethal opioid concentrations, leading us to investigate a further cause of death. The symptoms of heroin intoxication with asphyxia and/or cardiovascular involvement resemble anaphylaxis, and therefore it has been speculated that such deaths might be caused by an allergic reaction. The study´s aims were to investigate levels of allergic mediators in long-term injecting drug users (IDU) compared to healthy controls and to determine if oral opioid substitution therapy (OST) resulted in similar allergic symptoms to those reported by IDU after intravenous (IV) heroin use.

Methods: We quantified the concentrations of histamine, diamine oxidase (DAO), tryptase and lipoprotein-associated phospholipase A2 (LpPLA2) at baseline and 1 h after administration of Substitol®retard (482 ± 220 mg) in 56 patients at a withdrawal centre (Austria) and compared them with healthy controls (n = 103). Questionnaires and face-to-face interviews were used to assess allergic symptoms and side effects in IDU. Descriptive statistical analyses of quantitative data were performed by using SPSS.

Results: Baseline histamine, tryptase and LpPLA2 were significantly elevated in IDU compared to the healthy control group, while DAO decreased. Blood levels showed no significant change after oral substitution uptake. Self-reported allergic symptoms and side effects after IV heroin use were reported in 55 cases (98.2%), minimal symptoms were documented after OST (12.5%, 7/56).

Conclusions: This study revealed that baseline histamine concentrations were elevated in chronic IDU, although only relatively small changes in tryptase plasma levels occurred. After IV heroin application the reported allergic symptoms were mostly mild and did not lead to clinically relevant side effects. The substitution substance was clearly better tolerated than IV administered heroin. Elevated levels of allergic mediators such as histamine in IDUs may place them at greater risk of severe or fatal anaphylaxis when exposed to heroin; however, this requires further investigation.