Got milk? Enzyme-linked immunosorbent assay analysis of casein proteins in methylprednisolone

Background: Sporadic reports have been published with regard to allergic reactions in patients with bovine milk allergy after receiving parenteral lactose-containing methylprednisolone. Persistent milk allergy is a risk factor for other atopic diseases, in which corticosteroids, e.g., methylprednisolone, are commonly an adjunctive treatment. Laboratory investigations to validate the presence of residual milk protein as the cause for reactions are scarce. Thus, individualized recommendations for the use of methylprednisolone in patients with milk allergy remain undefined. Objective: We hypothesized that excipient contaminants, e.g., residual caseins, may be responsible for these reactions. We sought to evaluate for the presence of casein proteins in lactose-containing methylprednisolone and provide recommendations with regard to its use in patients with milk allergy. Methods: To assess for incomplete purification of lactose from its bovine milk source, standardized enzyme-linked immunosorbent assay (ELISA) was performed from five vials across four lots of commercially available lactose-containing methylprednisolone to detect casein subtypes Bos d 9 and Bos d 11, the two most abundant milk proteins. Results: High-fidelity ELISA revealed no detectable Bos d 9 in any vials of lactose-containing methylprednisolone. Trace amounts of Bos d 11 were detected in all vials compared with Bos d 9 (p = 0.008). Molecular modeling revealed minimal similarity between Bos d 9 and Bos d 11. Conclusion: Undetectable Bos d 9 and trace Bos d 11 in lactose-containing methylprednisolone raises optimism but warrants further investigation of immunoglobulin E binding epitopes and the clinical relevance of casein subtypes. It is reassuring that milk protein eliciting doses are usually 10⁶-fold higher than the nanogram quantities of Bos d 11 detected in our study, although this is limited by exposure route. Vaccines and medications with possible trace milk proteins remain largely well tolerated in patients with milk allergy. Lactose-containing methylprednisolone can likely be used with low risk of adverse reaction in most patients with milk allergy.