Background: Hyaluronidase is an ubiquitous enzyme, present, among others, in hymenoptera venom and in medical formulations. The latter include use as an emergency treatment or to correct undesired outcomes of medical and aesthetic procedures using hyaluronic acid fillers.
Objectives: By performing detailed allergy work-ups including skin-prick tests (SPTs) we investigated whether patients with a history of allergic reaction to hymenoptera venom are also sensitized to medical grade hyaluronidase.
Methods: Ninety patients with a history of type-1 reaction to hymenoptera venom with and without a history of previous specific venom immunotherapy were included in the study. All underwent SPTs for medical hyaluronidase. All patients also underwent serological analysis for Api m2, the only commercially available IgE test for a hymenoptera hyaluronidase.
Results: Of the 90 patients with previous type-1 reactions to hymenoptera venom hyaluronidase included in the study, 60 had undergone previous venom immunotherapy; 30 did not. The majority (73 of 90) were allergic to wasps, followed by honeybees (14 of 90) and three were allergic to both. Neither patients having undergone previous immunotherapy nor those allergic to bees showed positive SPTs to medical hyaluronidase. Of those with a wasp allergy and naïve to immunotherapy, over 20% (5 of 23) showed positive SPTs to medical hyaluronidase. Healthy controls (0 of 30) without previous allergic reactions to hymenoptera did not show positive SPTs to medical hyaluronidase.
Conclusions: Sensitization to hyaluronidase is most common in wasp-allergic patients who have not had previous specific immunotherapy. As allergic reactions to medical hyaluronidase are reported to be scarce, this group is probably at the highest risk to develop anaphylaxis to medical hyaluronidase. While all patients with untreated anaphylaxis to hymenoptera venom should consult an allergy specialist, it is particularly important that those with untreated wasp allergies seek specialist advice before treatment with medical hyaluronidase is initiated.
Hyaluronidase is an enzyme that plays different roles in nature. Among others, it is a component of the venom found in stinging insects, like wasps and bees. It is also used medically: to facilitate the spreading of certain medications in tissues, to correct undesired outcomes of aesthetic hyaluronic acid filler treatments and as emergency medication if said fillers are accidentally injected into a blood vessel, causing an occlusion. However, due to their very similar nature, people who are allergic to the venom of stinging insects might also be allergic to hyaluronidase that is used medically. To investigate this, in our study all patients in a large university hospital who underwent skin testing for allergies to insect venom also underwent skin testing for medical hyaluronidase. We found that patients who had previously been treated for their respective allergies showed no sign of cross-reactivity, nor did patients who had shown allergic reaction to bee venom. Only a fraction of patients who had not undergone allergy treatment and who had shown allergic reaction to wasp venom showed reactions to medical hyaluronidase. Overall, our study findings suggest that all patients with an untreated allergy for stinging insects should consult an allergy specialist before treatment with hyaluronidase. However, those patients who have a (potential) allergy against wasp venom need to be examined by an allergy specialist before beginning treatment.
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