Value of drug provocation test in non-immediate hypersensitivity reactions to betalactams in pediatric age

ObjectivesTo examine if a 5-day challenge with penicillin improves the diagnostic sensitivity compared with a single full dose in children with mild skin reactions.DesignSubjects referred with suspected allergy to penicillin were consecutively included. Irrespectively of the morphology of the index reaction and the result of specific IgE, all subjects underwent a two-step titrated drug provocation test (DPT) with the culprit drug followed by a 5-day challenge at home.ParticipantsChildren and adolescents aged 0–18 years referred to allergic workup for penicillin hypersensitivity at two paediatric Danish centres. Only subjects with non-severe skin reactions were included.ResultsA total of 305 subjects were included and 22 (7%) of the DPTs were positive. Three subjects reacted within 1 hour of the first full dose and nine reacted 1–8 hours after the first full dose. Additional 10 positive reactions were observed during the prolonged provocation. Seven subjects reacted after the second full dose and three reacted after 3–6 days. Only mild skin rashes were observed. Eighteen subjects had a specific IgE to a penicillin >0.1 kU/L. Only one of these had a positive DPT.ConclusionIn children, a DPT with penicillins should include at least two full doses. In children with mild hypersensitivity reactions it may be safe to perform DPTs despite a low specific IgE.Trial registration numberNCT04331522

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Hypersensitivity Reactions to Monoclonal Antibodies in Children

Medicina ◽

10.3390/medicina56050232 ◽

2020 ◽

Vol 56 (5) ◽

pp. 232

Author(s):

Francesca Mori ◽

Francesca Saretta ◽

Annamaria Bianchi ◽

Giuseppe Crisafulli ◽

Silvia Caimmi ◽

...

Keyword(s):

Monoclonal Antibodies ◽

Therapeutic Option ◽

Provocation Test ◽

Type I ◽

Hypersensitivity Reactions ◽

Biologic Drugs ◽

Type Iv ◽

Drug Provocation Test

Biologic drugs are widely used in pediatric medicine. Monoclonal antibodies (mAbs) in particular are a therapeutic option for rheumatic, autoinflammatory and oncologic diseases. Adverse drug reactions and hypersensitivity reactions (HSR) to mAbs may occur in children. Clinical presentation of HSRs to mAbs can be classified according to phenotypes in infusion-related reactions, cytokine release syndrome, both alpha type reactions and type I (IgE/non-IgE), type III, and type IV reactions, all beta-type reactions. The aim of this review is to focus on HSRs associated with the most frequent mAbs in childhood, with particular attention to beta-type reactions. When a reaction to mAbs is suspected a diagnostic work-up including in-vivo and in-vitro testing should be performed. A drug provocation test is recommended only when no alternative drugs are available. In selected patients with immediate IgE-mediated drug allergy a desensitization protocol is indicated. Despite the heavy use of mAbs in childhood, studies evaluating the reliability of diagnostic test are lacking. Although desensitization may be effective in reducing the risk of reactions in children, standardized pediatric protocols are still not available.

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DRUG PROVOCATION TEST AS A DIAGNOSTIC APPROACH FOR HYPERSENSITIVITY REACTION TO ANTITUBERCULOSIS DRUGS: A REPORT OF TWO CASES

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2020.v13i5.37248 ◽

2020 ◽

pp. 1-4 ◽

Cited By ~ 1

Author(s):

KETUT SURYANA

Keyword(s):

Therapeutic Approach ◽

Patient Adherence ◽

Drug Hypersensitivity ◽

Public Health Problem ◽

Provocation Test ◽

Hypersensitivity Reactions ◽

Increased Risk ◽

Drug Provocation Test ◽

Drug Hypersensitivity Reactions ◽

Degrees Of Severity

Pulmonary tuberculosis (PTB) continues to be a public health problem, especially in developing countries. The necessity use of multidrug regimens of antituberculosis drug (ATD) in PTB treatment has been associated with increased risk of drug hypersensitivity reactions (DHRs). DHR is a type of unpredictable reaction, refers to immunologically mediated hypersensitivity reactions. It is observed more frequently in the intensive phase of the PTB treatment with varying degrees of severity. DHR can lead to reduce the patient adherence, thereby leading to stoppage of the drugs by the patient. The definite diagnosis based on drug provocation test (DPT) that should be performed at a hospital. The recommended therapeutic approach is rapid desensitization by reintroducing drugs in safety and optimal under threshold dose until usual daily dose is reached. We present two cases of DHR to ATD, DPT as the diagnosis and rapid desensitization as the therapeutic approach.

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Penicillin and cephalosporin cross-reactivity: role of side chain and synthetic cefadroxil epitopes

Clinical and Translational Allergy ◽

10.1186/s13601-020-00368-1 ◽

2020 ◽

Vol 10 (1) ◽

Cited By ~ 1

Author(s):

Gador Bogas ◽

Cristobalina Mayorga ◽

Ángela Martín-Serrano ◽

Rubén Fernández-Santamaría ◽

Isabel M. Jiménez-Sánchez ◽

...

Keyword(s):

Provocation Test ◽

Cross Reactivity ◽

Side Chain ◽

Immediate Hypersensitivity ◽

Drug Provocation Test ◽

Group A ◽

Unique Factor ◽

Group B

Abstract Background Analysis of cross-reactivity is necessary for prescribing safe cephalosporins for penicillin allergic patients. Amoxicillin (AX) is the betalactam most often involved in immediate hypersensitivity reactions (IHRs), and cefadroxil (CX) the most likely cephalosporin to cross-react with AX, since they share the same R1 side chain, unlike cefuroxime (CO), with a structurally different R1. We aimed to analyse cross-reactivity with CX and CO in patients with confirmed IHRs to AX, including sIgE recognition to AX, CX, CO, and novel synthetic determinants of CX. Methods Fifty-four patients with confirmed IHRs to AX based on skin test (ST) and/or drug provocation test (DPT) were included. Serum sIgE to AX and benzylpenicillin was determined by Radioallergosorbent test (RAST). Two potential determinants of CX, involving intact or modified R1 structure, with open betalactam ring, were synthesised and sIgE evaluated by RAST inhibition assay. Results Tolerance to CX (Group A) was observed in 64.8% cases and cross-reactivity in 35.2% cases (Group B). Cross-reactivity with CO was only found in 1.8% cases from Group B. ST to CX showed a negative predictive value of 94.6%. RAST inhibition assays showed higher recognition to CX as well as to both synthetic determinants (66% of positive cases) in Group B. Conclusions Cross-reactivity with CX in AX allergic patients is 35%, being ST not enough for prediction. R1, although critical for recognition, is not the unique factor. The synthetic determinants of CX, 1-(HOPhG-Ser-Bu) and 2-(pyrazinone) are promising tools for determining in vitro cross-reactivity to CX in AX allergic patients.

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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

International Archives of Allergy and Immunology ◽

10.1159/000512072 ◽

2021 ◽

pp. 1-7

Author(s):

Dolly Vanessa Rojas-Mejía ◽

Diana Lucía Silva Espinosa ◽

Diana Marcela Martínez ◽

Luis Fernando Ramírez Zuluaga ◽

Carlos Daniel Serrano Reyes

Keyword(s):

Drug Hypersensitivity ◽

Provocation Test ◽

Descriptive Study ◽

Oral Challenge ◽

Oral Drug ◽

Hypersensitivity Reactions ◽

Cross Sectional ◽

Drug Provocation Test ◽

Inflammatory Drugs ◽

Anti Inflammatory

Background: Hypersensitivity reactions to nonsteroidal anti-inflammatory drugs (NSAIDs) are common. These patients require an effective and safe analgesic alternative. Objective: 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. Methods: 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. Results: 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. Conclusions: 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.

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M056 SUSPECTED OCRELIZUMAB-INDUCED IMMEDIATE HYPERSENSITIVITY: NEGATIVE SKIN TESTING AND DRUG PROVOCATION TEST

Annals of Allergy Asthma & Immunology ◽

10.1016/j.anai.2021.08.230 ◽

2021 ◽

Vol 127 (5) ◽

pp. S74

Author(s):

K. Reddy ◽

I. Carrillo-Martin ◽

A. Lopez-Chiriboga ◽

A. Gonzalez-Estrada

Keyword(s):

Skin Testing ◽

Provocation Test ◽

Immediate Hypersensitivity ◽

Drug Provocation Test

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

Allergy Asthma & Clinical Immunology ◽

10.1186/s13223-021-00517-6 ◽

2021 ◽

Vol 17 (1) ◽

Author(s):

Da Woon Sim ◽

Ji Eun Yu ◽

Young-Il Koh

Keyword(s):

Case Report ◽

Drug Eruption ◽

Provocation Test ◽

Skin Lesions ◽

Laryngeal Edema ◽

Type I ◽

Hypersensitivity Reactions ◽

Fixed Drug Eruption ◽

Fixed Drug ◽

Drug Provocation Test

Abstract 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.

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