Different Patterns of Response in Hypersensitivity Reactions to Arylpropionic Acid Derivatives.

BACKGROUND: Ibuprofen and other arylpropionic acid derivatives (APs) are among the most consumed nonsteroidal anti-inflammatory drugs worldwide at all age ranges; however, little is known about drug hypersensitivity reactions (DHRs) they induce. OBJECTIVE: To characterize in detail patients reporting DHRs to APs. METHODS: We prospectively evaluated patients with symptoms suggestive of AP-DHRs and analyzed their clinical characteristics, reported reactions, and diagnostic approaches. RESULTS: Six hundred sixty-two patients confirmed as hypersensitive to APs were included: 489 with cross-reactive reactions (CRs) (73.86%) and 173 with selective reactions (SRs) (26.13%). The percentage of subjects reporting reactions to ibuprofen and dexketoprofen was higher in CRs (P = .005 and P = .01, respectively), whereas naproxen and ketoprofen were more frequently involved in SRs (P = .0002 and P = .00001, respectively). The most frequent symptoms induced by ibuprofen, dexketoprofen, and naproxen were isolated angioedema and urticaria, combined or not with angioedema in both CRs and SRs. The result of nasal provocation test with lysine acetylsalicylate was positive in 156 cases (77.14% in patients showing exclusively respiratory symptoms, and in 68.18% of those with both cutaneous and respiratory involvement). To confirm diagnosis, drug provocation test with acetylsalicylic acid was required in 246 CR patients (50.3%), whereas in 28 SR patients (16.18%) drug provocation test with the culprit AP was required. CONCLUSIONS: Skin is the organ most commonly involved in AP-DHRs, with ibuprofen and dexketoprofen inducing most frequently CRs, and naproxen and ketoprofen SRs. More studies are necessary to clarify the underlying mechanism in DHRs induced by APs.

Hypersensitivity to gadolinium-based contrast.

PURPOSE OF REVIEW: The use of contrast media is increasing in recent decades. Although gadolinium-based contrast agents (GBCAs) are generally well tolerated, adverse reactions, including hypersensitivity reactions (HSRs), although infrequent, may occur. It is important to perform a thorough allergological evaluation in patients with suspected GBCA-HSRs to avoid potentially serious reactions in subsequent exposures. RECENT FINDINGS: Data on GBCA-HSRs are scarce. Most published articles dealing with skin tests and drug provocation tests (DPTs) with GBCAs are case series and small cohorts. Controversies exist about the role of premedication for preventing HSRs on subsequent exposures. Selection of well tolerated alternatives is based on potential cross-reactivity among GBCAs; however, the extent of cross-reactivity among them remains unclear. SUMMARY: As premedication is not useful because breakthrough reactions are frequent in patients with GBCA-HSRs in subsequent exposures, an allergological evaluation is required. Available data suggest a high negative predictive value of skin tests, being crucial for guiding the selection of an alternative GBCA. However, DPTs are still necessary to confirm or exclude the diagnosis or find alternative GBCAs. Cross-reactivity is high among GBCAs belonging from the same group, mainly among macrocyclic compounds, so this must be taken into account for selecting alternatives.

Resensitization in suspected penicillin allergy.

BACKGROUND: The diagnosis of allergic reactions to penicillins (AR-PEN) is very complex as there is a loss of sensitization over time, which leads to negative skin tests (STs) and specific IgE in serum, and even to tolerance to the drug involved. However, STs may become positive after subsequent exposure to the culprit drug (resensitization), with the risk of inducing potentially severe reactions. The exact rate of resensitization to penicillins is unknown, ranging from 0% to 27.9% in published studies. OBJECTIVES: To analyze the rate of resensitization in patients with suggestive AR-PEN by repeating STs (retest) after an initial evaluation (IE). MATERIAL AND METHODS: Patients with suspected AR-PEN were prospectively evaluated between 2017 and 2020. They underwent STs, and a randomized group also underwent a drug provocation test (DPT) with the culprit. Only patients with negative STs and/or DPT were included. All included cases were retested by STs at 2-8 weeks. RESULTS: A total of 545 patients were included: 296 reporting immediate reactions (IRs) and 249 non-immediate reactions (NIRs). Eighty (14.7%) cases had positive results in retest (RT+): 63 (21.3%) IRs and 17 (6.8%) NIRs (p < 0.0001). The rate of RT+ was higher in anaphylaxis compared with all other reactions (45.8% vs 9.1%, p < 0.0001). The risk of RT+ was higher from the fifth week after IE (OR: 4.64, CI: 2.1-11.6; p < 0.001) and increased with the patient's age (OR: 1.02; CI: 1.01-1.04; p = 0.009). CONCLUSIONS: Due to the high rate of resensitization, retest should be included in the diagnostic algorithm of IRs to penicillins after an initial negative study, especially in anaphylaxis, to avoid potentially severe reactions after subsequent prescriptions of these drugs.

Antibiotic Allergy De-Labeling: A Pathway against Antibiotic Resistance.

Antibiotics are one of the most frequently prescribed drugs. Unfortunately, they also are the most common cause for self-reported drug allergy, limiting the use of effective therapies. However, evidence shows that more than 90% of patients labeled as allergic to antibiotics are not allergic. Importantly, the label of antibiotic allergy, whether real or not, constitutes a major public health problem as it directly impacts antimicrobial stewardship: it has been associated with broad-spectrum antibiotic use, often resulting in the emergence of bacterial resistance. Therefore, an accurate diagnosis is crucial for de-labeling patients who claim to be allergic but are not really allergic. This review presents allergy methods for achieving successful antibiotic allergy de-labeling. Patient clinical history is often inaccurately reported, thus not being able to de-label most patients. In vitro testing offers a complementary approach but it shows limitations. Immunoassay for quantifying specific IgE is the most used one, although it gives low sensitivity and is limited to few betalactams. Basophil activation test is not validated and not available in all centers. Therefore, true de-labeling still relies on in vivo tests including drug provocation and/or skin tests, which are not risk-exempt and require specialized healthcare professionals for results interpretation and patient management. Moreover, differences on the pattern of antibiotic consumption cause differences in the diagnostic approach among different countries. A multidisciplinary approach is recommended to reduce the risks associated with the reported penicillin allergy label.