A Reply to "Spanish Society of Allergology and Clinical Immunology (SEAIC) Vision of Drug Provocation Tests".

To the Editor: We read with interest the guideline on drug provocation tests (DPTs) by Audicana et al [1] on behalf of the Drug Allergy Committee of the Spanish Society of Allergology and Clinical Immunology that was published in the Journal of Investigational Allergology and the Clinical Immunology (JIACI) in October 2021. However, we are surprised that DPTs with iodinated contrast media (ICM) are now discouraged. This statement contradicts a previous proposal of the same Committee, which recommended DPTs with ICM when studying hypersensitivity reactions to these drugs. This advice was included in the "Practical Guide for the Diagnosis and Management of Hypersensitivity Reactions to Contrast Media" published in JIACI in 2016 [2]. In the new guideline, the contraindication to DPTs with ICM is based on potential toxicity. However, in our opinion, this is not a compelling reason. In fact, the same authors consider that DPTs with potentially more toxic drugs, such as nonsteroidal anti-inflammatory drugs, biologics, and cytostatic drugs, are indicated. Kidney damage is the most frequent toxicity reaction produced by ICM. However, the existence of contrast-induced nephropathy is currently questioned [3] and, in any case, is avoidable using a nephroprotective protocol adjusted to a renal risk score [4,5]. In other words, while many drugs are potentially toxic, the toxicity of ICM can be prevented using nephroprotective measures, especially if the patient is properly hydrated. In recent years, the lack of efficacy of premedication in preventing hypersensitivity reactions to ICM [6] has led to allergy studies including DPTs. These studies were performed by influential research groups, several of which were Spanish, with successful results [7-9]. Moreover, DPTs with ICM were also recommended by the EAACI in a recent position paper [10]. Therefore, we think that DPTs with ICM are a safe and necessary tool, both for establishing a diagnosis of drug allergy (in the case of inconclusive results with ICM in skin tests) and for confirming tolerance to an alternative ICM with previous negative skin test results. Perhaps the greatest difficulty in generalizing the use of DPTs with ICM is the lack of standardized protocols. Therefore, further studies are necessary to search for the most appropriate methodology. In conclusion, in the study of hypersensitivity reactions to ICM, we believe that DPTs should be the gold standard, as in any other drug allergy study.