Drug reexposure in children with severe mucocutaneous reactions

In pediatric patients, severe cutaneous adverse reactions (SCARs) frequently occur in the course of acute illnesses, mostly infections, which are usually treated with antibiotics or analgesics. The drug provocation test (DPT) is contraindicated in such situations, due to the risk of triggering a new severe reaction. As a consequence, lifelong avoidance is recommended. However, causation is uncertain in most cases. The dilemma arises when avoiding the drug is not harmless for the patient. We have attended three patients who were referred to our pediatric allergy unit with a history of SCAR related in time to simultaneous use of paracetamol and ibuprofen. Medical records and images of the patients were reviewed with the assistance of a dermatologist, and alternative diagnoses were considered in both cases. The ALDEN score for implicated drugs was calculated. After considering a high probability of ibuprofen tolerance and obtaining informed consent from the patients, we performed a sequential allergy workup including in vitro tests, skin tests, and finally DPT in two of the patients, confirming ibuprofen tolerance. In conclusion, although generally contraindicated, DPT may be considered for some useful drugs after careful evaluation of the risk–benefit balance, preceded by a sequential study including in vitro and skin tests.

Macrolide Allergy in Children and the Negative Predictive Value of Drug Provocation Tests in Mild Index Reactions

ABSTRACT Objective: Macrolide allergy is rarely reported, and there is limited knowledge of hypersensitivity reactions (HRs) in children. The negative predictive value (NPV) of drug provocation tests (DPTs) for macrolides is unresolved. We aim to evaluate the clinical features of macrolide allergy in children, and determine the NPV of macrolide DPTs. Materials and Methods: Pediatric patients who were referred to our allergy department with a suspicion of macrolide allergy were evaluated by DPTs with or without prior skin tests between 2011 and 2020. Characteristics of the HRs and patients, the results of skin and DPTs were recorded. At least three months after evaluation of the patients with allergy work up, telephone interviews were performed. Patients were asked whether they had reused the suspected macrolide or not. Patients who reported HR during subsequent drug intake were invited for reevaluation. Results: A total of 160 children (161 reactions) (55.6% male) with a suspicion of macrolide allergy were enrolled for the study, and all children had a mild index reaction. The median age was 48 (18-102) months, and the median time between the suspected allergic reaction and allergy work-up was 3 (2-8) months. The most frequently reported suspected agent was clarithromycin, in 151 patients (94.4%). Macrolide allergy was confirmed in 8 (5%) patients. Only one patient reported skin eruptions upon reuse despite a negative DPT and he was invited to be reevaluated. A second DPT was performed resulting in urticarial lesions. The NPV was found to be 97.4% for negative DPT with macrolides. Conclusion: Confirmed macrolide allergy is rare in children, and DPTs are the gold standard to assess suspected macrolide allergy. The NPV of macrolide provocation tests seems to be high in children. Keywords: Children, drug hypersensitivity, drug provocation test, macrolide, negative predictive value

Intradermal Testing Identifies 1 in 4 Patients with Nonimmediate Penicillin Allergy

<b><i>Background:</i></b> Intradermal testing with delayed reading (IDTdr), used routinely in many centers, may identify delayed reactions to penicillins. However, few studies have compared the results of IDTdr with drug provocation test (DPT). The aim of this study was to examine the proportion of provocation-positive patients testing positive on IDTdr. <b><i>Methods:</i></b> Fifty-seven patients with a positive DPT occurring &#x3e;2 h after intake of penicillin V, dicloxacillin, pivampicillin, or amoxicillin had an IDTdr with penicillin G, amoxicillin, ampicillin, and dicloxacillin. A control group included 18 patients with negative DPTs with the suspected penicillin. <b><i>Results:</i></b> In total 25% (<i>n</i> = 14) of provocation-positive patients tested positive on IDTdr. Among patients with positive IDTdr, 9/14 (64%) versus 11/43 (26%) in the IDTdr negative group (<i>p</i> &#x3c; 0.05) had required oral steroids to treat skin reactions following DPT. No other differences between IDTdr positive and negative groups were found. No controls had a positive IDTdr. <b><i>Conclusion:</i></b> Investigating with IDTdr would have identified 25% of patients with a DPT-verified allergy with delayed reactions. It is difficult to target subgroups who will test positive on IDTdr. There were more patients who tested positive on IDT who had received oral steroids after DPT, and this may be an indication that skin reaction severity plays a role in skin testing diagnostics. Further potential predictors for positivity of IDTdr, such as duration of skin symptoms, should be assessed in large studies in order to optimize the investigations of nonimmediate drug allergic reactions.

Drug-allergy investigation, provocation tests

The authors present the in vivo investigation options in drug allergy. In suspicion of drug induced hypersensitivity reaction prick testing, intradermal testing and patch testing are recommended according to the assumed immuno-mechanism. If these examinations are negative, the next step is the drug provocation test, which is the gold standard in the diagnosis of drug allergy. We summarize methods, indications and contraindications and the evaluationof each test, focusing on issues concerning antibiotics, perioperative medication, local anesthetics and biological agents. There are increasing number of patients presenting hypersensitivity reactions who require proper identification of the culprit drug.

Meloxicam and/or Etoricoxib Could Be Administered Safely in Two Equal Doses during an Open Oral Challenge in Patients with Nonsteroidal Anti-Inflammatory Drug Hypersensitivity

<b><i>Background:</i></b> Hypersensitivity reactions to nonsteroidal anti-inflammatory drugs (NSAIDs) are common. These patients require an effective and safe analgesic alternative. <b><i>Objective:</i></b> The aim of the study was to demonstrate the safety of meloxicam and etoricoxib administered by open oral challenge in 2 equal steps in patients with NSAID hypersensitivity. <b><i>Methods:</i></b> A cross-sectional, descriptive study of patients with a diagnosis of NSAID hypersensitivity who underwent an oral drug provocation test (DPT) with meloxicam or etoricoxib between January 2011 and August 2017 was conducted. The analysis was performed from a database in BD Clinic. <b><i>Results:</i></b> Two hundred and twenty-eight oral provocations were performed with an alternative NSAID (203 with meloxicam and 25 with etoricoxib) in 217 patients with hypersensitivity to NSAIDs. The median age was 38 years. Ninety-eight percent of meloxicam and 100% of etoricoxib DPTs were performed in 2 steps (without previous placebo), and 52% and 64% of meloxicam and etoricoxib DPTs, respectively, were performed with 50% of the therapeutic dose in each step. Tolerance to meloxicam was demonstrated in 192 patients (94.5%) and in 100% of patients receiving etoricoxib. <b><i>Conclusions:</i></b> Open oral provocation with meloxicam and etoricoxib carried out in 2 steps without placebo seems to be safe and implies less costs and less time expenditure. Also, it could be performed with 2 equal doses.

Fixed drug eruption and anaphylaxis induced concurrently by erdosteine: a case report

Background Erdosteine is used as a mucolytic agent and has a low incidence of adverse drug reactions, most of which are gastrointestinal and mild. Moreover, drug antigens rarely induce multiple simultaneous immunologic reactions. Only one previous case report has demonstrated hypersensitivity reaction induced by erdosteine. Here, we report a case of fixed drug eruption and anaphylaxis, which were concurrently induced by erdosteine. The association between the symptoms and erdosteine was proven by a drug provocation test. Case presentation A 35-year-old woman presented with recurrent angioedema and pruritic rash on the hands, which developed within 2 h following the administration of drugs, including erdosteine, for acute upper respiratory infection. Her rash was characterized by well-defined erythematous plaques, which recurred at the same site following the administration of the medications. She also experienced angioedema of the lips. Fixed drug eruption was considered after excluding other possible causes for the presented skin lesions. A drug provocation test confirmed that fixed drug eruption on both hands had occurred after administration of erdosteine, suggesting that erdosteine was the cause of the allergic reaction. However, she also experienced angioedema, isolated wheal, and laryngeal edema; thus, IgE-mediated type I hypersensitivity could also be concurrently occurring with the fixed drug eruption. Conclusions We report about a patient who was diagnosed with two different hypersensitivity reactions concurrently induced by erdosteine. We also demonstrate that patients may exhibit multiple simultaneous symptoms that usually arise from overlapping of different hypersensitivity mechanisms. Physicians should be aware of the possibility that some patients who are allergic to certain drugs could exhibit several symptoms caused by different mechanisms of hypersensitivity reactions simultaneously.