Food‐dependent NSAID‐induced hypersensitivity (FDNIH) reactions: Unraveling the clinical features and risk factors

Abstract

Background In up to 70%–80% of patients with a suspected non‐steroidal anti‐inflammatory drug hypersensitivity (NSAIDH), challenge tests with the culprit drug yield negative results. On the other hand, there could be a NSAIDH overdiagnosis when anaphylaxis is the clinical manifestation. We hypothesize that some negative NSAID challenge tests and an overdiagnosis of NSAIDH occur in patients with food‐dependent NSAID‐induced hypersensitivity (FDNIH). Methods We studied 328 patients with a suspected acute NSAIDH. FDNIH was diagnosed in patients meeting all the following: (1) tolerance to the food ingested more temporally closed before the reaction, later the episode, (2) respiratory or cutaneous symptoms or anaphylaxis related to NSAID, (3) positive skin prick test to foods and/or specific IgE to food allergens (Pru p 3, Tri a 19, Pen a 1) involved in the reaction, and (4) negative oral provocation test to the culprit NSAID. Results 199 patients (60%) were diagnosed with NSAIDH and 52 (16%) with FDNIH. Pru p 3 was involved in 44 cases (84.6%) and Tri a 19 in 6 cases (11%). FDNIH subjects were younger (p < .001), with a higher prevalence of rhinitis (p < .001) and previous food allergy (p < .001), together with a higher proportion of subjects sensitized to pollens (p < .001) and foods (p < .001). Using just four variables (Pru p 3 sensitization, Tri a 19 sensitization, anaphylaxis, and any NSAID different from pyrazolones), 95.3% of cases were correctly classified, with a sensitivity of 92% and specificity of 96%. Conclusion Evaluation of FDNIH should be included in the diagnostic workup of NSAIDH.

NSAID Hypersensitivity in the Pediatric Population: Classification and Diagnostic Strategies

“…NSAIDs may act as a co-factor inducing or aggravating food-dependent exercise-induced urticaria/angioedema or anaphylaxis, and the related phenotype is now defined as food-dependent NSAID-induced hypersensitivity (FDNIH) and classified as a subgroup of NSAID-H for adults. 81,118 In this case, food or an NSAID does not induce a reaction exclusively; however, exercise 4 to 6 hours preceded by simultaneous ingestion of the specific food and the NSAID induces the reaction. In some cases, solitary food ingestion would result in a mild reaction such as oral allergy syndrome or contact urticaria.…”

Advances and highlights in biomarkers of allergic diseases

“…157 Improvements in genomics have facilitated assessing the rela- ) and NSAIDs hypersensitivity (Figure 7 ). 156 Recently, Sanchez-Lopez et al 161 have reported that 16% of patients with suspected NSAID hypersensitivity could be further diagnosed as suffering from food-dependent NSAID-induced hypersensitivity, with LTP and gliadin being the main culprit food allergens.…”

“…Recent advances have facilitated the analysis of the complete transcriptome, revealing associations between different gene expression (POSTN, CNKSR, SPTBN2, ADORA3) and NSAIDs hypersensitivity (Figure7) 156. Recently, Sanchez-Lopez et al161 have reported that 16% of patients with suspected NSAID hypersensitivity could be further diagnosed as suffering from food-dependent NSAID-induced hypersensitivity, with LTP and gliadin being the main culprit food allergens.Non-immediate reactions are characterized by a wide range of clinical manifestations driven by different mechanisms. The heterogeneity of NIDHR makes it essential to identify biomarkers for accurate diagnosis.…”

Mechanisms of human drug-induced anaphylaxis

“…93 In contrast, sensitization to some cereal and peach allergens (lipid transfer protein) is a high-risk factor to nonsteroidal anti-inflammatory drugs anaphylaxis, without any cross-reactivity identified. 94 The first-line treatment of any type of anaphylaxis, whatever the mechanism, is adrenaline (epinephrine). As far as therapeutic tools are concerned, the avoidance of the drug is the only efficient action when possible.…”