Immediate-Type Hypersensitivity to Succinylated Corticosteroids

Abstract

Background: Despite their frequent use, systemic corticosteroids have rarely elicited immediate-type reactions. Objective: We report two male patients, aged 26 and 70 years, respectively, with severe immediate-type hypersensitivity secondary to the administration of corticosteroids esterified with succinate. Methods: Skin tests, basophil activation tests and challenge tests were performed for diagnostic evaluation. Results: In both patients, immediate-type skin test reactions were found to methylprednisolone sodium hemisuccinate (MSH) and prednisolone sodium hemisuccinate (PSH). In contrast, nonsuccinylated corticosteroids (including methylprednisolone and prednisolone in one patient) yielded no test reactions. Basophils from one patient exhibited a stimulated expression of the activation marker CD63 upon in vitro incubation with PSH or hydrocortisone sodium succinate, but not with hydrocortisone. Skin tests and basophil activation tests were negative in controls. One patient was challenged with the incriminated drugs. He developed flush, conjunctivitis, tachycardia and dyspnea 2 min after injection of MSH, and dyspnea shortly after intravenous administration of PSH. Oral and intravenous challenge tests with nonsuccinylated corticosteroids were tolerated well by both patients. Conclusions: These case reports should alert clinicians to rare, but severe immediate-type reactions to corticosteroids, related to the succinate moiety in our patients. In case of allergic reactions to corticosteroids, it is mandatory to identify the causative agent and find safe alternatives.

Recent applications of basophil activation tests in the diagnosis of drug hypersensitivity

“…Hypersensitivity to other biologic agents such as rituximab [ 61 ] or infliximab [ 66 ] were examined by BAT, although the results warrant further confirmation. Among corticosteroids, methylprednisolone [ 62 , 67 ] and succinylated corticosteroids [ 68 - 70 ] have been tested. Hypersensitivity to anti-histamines such as cetirizine, desloratadine, ebastine, fexofenadine, or dexchlorpheniramine was also assessed by BAT [ 71 - 74 ].…”

Prednis-OH NO! – A Case of Anaphylaxis Induced by Prednisone

“…In contrast, there are also reports of positive skin testing to corticosteroids uniquely in the absence of ester conjugation [1]. Alternatively, corticosteroids may also contain preservatives or excipients which may result in sensitization and subsequent hypersensitivity reaction [7]. Some such examples include lactose, carboxymethylcellulose, polyethylene glycol, and hexylene glycol.…”

“…Furthermore, reactions may also be due to mimicry of anaphylaxis due to rapid infusion of large amounts of corticosteroids. In this scenario, α-adrenergic blockade and negative inotropy leads to cardiovascular collapse due to decreased cardiac output, resulting in clinical manifestations similar to those of anaphylaxis [7].…”

Flow-assisted basophil activation tests in immediate drug hypersensitivity: two decades of Antwerp experience

“…Whether passive sensitisation experiments using donor basophils as described in 39 or one of the recently developed human mast cell cultures 40,41 might broaden the application of flow-assisted diagnosis of IDHR remains to be investigated. H1-receptor antagonists 74,75 Heparin and low molecular weight heparins 76 Hyaluronidase 77 Hydroxyl ethyl starch 78 Infliximab 79 (Methyl)prednisolone 80,81 Ophalmologic atropine 82 Patent blue 83 Vaccines (e.g. recombinant hepatitis B) 84 …”