Delayed type hypersensitivity reaction to oral intake of trometamol

ABSTRACT

Case report Trometamol (tromethamine, tris(hydroxymethyl)aminomethane (TRIS)) is an excipient frequently used as buffer in fluids and semisolid agents, including many drugs such as antibiotics, iodinated contrast agents and the COVID-19 vaccine mRNA-1273. Here, we report the first case of a delayed-type hypersensitivity after oral intake of trometamol. A 64-year- old female patient presented to our emergency department with generalized erythematous rash, pruritus and swelling of the face five hours after the intake of one tablet of fosfomycin trometamol for a urinary tract infection. Further medical history revealed a previous erythematous rash five to six hours after administration of the iodinated contrast agent iopromide. We performed skin prick and intradermal tests with trometamol, fosfomycin trometamol and various iodinated contrast agents, including iopromide, iomeprol, iobitridol, iopamidol and iodixanol. These tests showed no reactions initially. However, 48 hours after intradermal testing, macular erythematous lesions developed at the sites tested with trometamol 0.1%, trometamol 0.01% and all sites tested with iodinated contrast agents. Furthermore, when we performed a lymphocyte transformation test with trometamol, fosfomycin trometamol and iopromide, we recorded a positive reaction with cytokine release after stimulating T cells with trometamol and iopromide. In contrast, basophil activation testing showed a negative result for these agents. Based on these results and our patient's history, we diagnosed a clinically relevant type IV sensitization to trometamol. There are only a few case reports about immediate-type allergic reactions to gadolinium contrast agents caused by the excipient trometamol. There are some published cases which report contact dermatitis after topical administration of trometamol-containing agents. To our knowledge, ours is the first case to report a delayed hypersensitivity reaction to oral administration of trometamol. Excipients are indispensable for drugs, vaccines and other products since they stabilize and preserve the active agents. Nevertheless, excipients should always be considered during an allergy workup, especially if the patient reports prior drug reactions that cannot be explained by a chemical cross-reaction. In our case, we diagnosed delayed-type hypersensitivity to the excipient trometamol. This is a consequential diagnosis for the patient, because trometamol is contained in many drugs and in the COVID-19 vaccine mRNA-1273.