DPT is considered the “gold standard” in the diagnosis of DHR to many drugs including nonsteroidal anti-inflammatory drugs (NSAIDs), due to the absence of reliable skin tests (or in-vitro tests), except for certain IgE mediated reactions. Because of a variety of clinical presentation of NSAIDs DHR (respiratory, cutaneous or anaphylaxis, and single or multiple reactors) [
13], reliability of clinical history is difficult to assess, and most patients require DPT to confirm or refute diagnosis. The upmost interest of a DPT is to rule out the responsibility of a drug. Indeed, in our pioneer work [
6] involving 1372 DPTs performed using various drugs, including ß-lactams (30.3%), aspirin (14.5%), other NSAIDs (11.7%), paracetamol (8.9%), macrolides (7.4%), and quinolones (2.4%), there were only 241 (17.6%) positive results. While being a diagnostic tool, confirming the role of NSAIDs in 13.4% [
14] to 85.7% [
15] of the suspicions, DPT holds an intrinsic scientific value, since it generates precious knowledge. In this respect, we [
16] used data collected from a large database in 980 patients gathered over a 10-year period (using both the clinical history and the results of the DPTs) to put forward a new classification of NSAIDs DHR. The objective was to demonstrate whether or not patterns of NSAIDs reactivity are well defined with little or no overlap and to have the possibility of identifying patients at a high risk, with a rather high probability, according to clinical history and clinical manifestations. Based on our cohort of 122 (12.5%) positive patients, accounting for 307 positive DPTs and 105 negative challenges for finding an alternative drug, we were able to design a new classification, encompassing all our patients (some of which could not be included in the groups previously described by others) [
13,
14,
17]. We chose to group the conditions comprising asthma/rhinosinusitis and/or urticaria/angioedema in one single entity of underlying diseases, because we noticed that the same clinical forms,
i.e. immediate reactions (occurring immediately or up to 6 h after drug exposure) such as asthma/rhinitis and/or urticaria/angioedema can be seen with or without any underlying disease. Another major clinical innovation of our analysis is the highlighting of non-immediate angioedema (occurring between 6 to 24 h after exposure) as a form of non-immediate reaction to NSAIDs, which was not included in the previous classifications. This classification provides immediate application in clinical practice, since it offers an insight into the management of these patients, making it easier to decide which steps need to be followed to choose the drug to be tested (same drug, alternative drug from another NSAID family, or a COX-2 inhibitor directly).