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

Background: 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. Methods: Fifty-seven patients with a positive DPT occurring >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. Results: In total 25% (n = 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 (p < 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. Conclusion: 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.

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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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Non-immediate reactions to β-lactams: diagnostic value of skin testing and drug provocation test

Clinical & Experimental Allergy ◽

10.1111/j.1365-2222.2008.02961.x ◽

2008 ◽

Vol 38 (5) ◽

pp. 822-828 ◽

Cited By ~ 81

Author(s):

A. Padial ◽

C. Antunez ◽

N. Blanca-Lopez ◽

T. D. Fernandez ◽

J. A. Cornejo-Garcia ◽

...

Keyword(s):

Skin Testing ◽

Provocation Test ◽

Diagnostic Value ◽

Drug Provocation Test ◽

Immediate Reactions

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

Journal of Allergy and Clinical Immunology ◽

10.1016/j.jaci.2017.12.122 ◽

2018 ◽

Vol 141 (2) ◽

pp. AB37 ◽

Cited By ~ 3

Author(s):

Ana Prieto ◽

Inmaculada Doña ◽

Candelaria Muñoz ◽

María Salas ◽

Esther Barrionuevo ◽

...

Keyword(s):

Provocation Test ◽

Hypersensitivity Reactions ◽

Pediatric Age ◽

Immediate Hypersensitivity ◽

Drug Provocation Test

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Prospective study of 5-day challenge with penicillins in children

BMJ Paediatrics Open ◽

10.1136/bmjpo-2020-000734 ◽

2020 ◽

Vol 4 (1) ◽

pp. e000734

Author(s):

Birgitte Tusgaard Petersen ◽

Josefine Gradman

Keyword(s):

Prospective Study ◽

Children And Adolescents ◽

Provocation Test ◽

Specific Ige ◽

Hypersensitivity Reactions ◽

Skin Reactions ◽

Full Dose ◽

Culprit Drug ◽

Drug Provocation Test ◽

Registration Number

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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A comparison of six epicutaneous devices in the performance of immediate hypersensitivity skin testing

Journal of Allergy and Clinical Immunology ◽

10.1016/0091-6749(89)90321-7 ◽

1989 ◽

Vol 84 (2) ◽

pp. 168-174 ◽

Cited By ~ 42

Author(s):

Allen D. Adinoff ◽

Diane M. Rosloniec ◽

Lorma L. McCall ◽

Harold S. Nelson

Keyword(s):

Skin Testing ◽

Immediate Hypersensitivity ◽

Hypersensitivity Skin

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Azathioprine Hypersensitivity Syndrome during Treatment of Severe Interstitial Lung Disease with Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis

Case Reports in Pulmonology ◽

10.1155/2020/8852441 ◽

2020 ◽

Vol 2020 ◽

pp. 1-6

Author(s):

Eri Nakano ◽

Tomohiko Asakawa ◽

Mea Asou ◽

Eri Nohara ◽

Tomoyuki Seki ◽

...

Keyword(s):

Maintenance Therapy ◽

Clinical Symptoms ◽

Immunosuppressive Agents ◽

Provocation Test ◽

Hypersensitivity Syndrome ◽

Allergic Reactions ◽

Prednisolone Dose ◽

Anca Associated Vasculitis ◽

Drug Provocation Test ◽

The Relationship

Azathioprine is used to treat anti-neutrophil cytoplasmic antibody- (ANCA-) associated vasculitis. Azathioprine hypersensitivity syndrome is often missed. An 81-year-old man undergoing treatment for interstitial pneumonia developed a high fever and was diagnosed with ANCA-associated vasculitis based on an elevated myeloperoxidase- (MPO-) ANCA titer and renal biopsy findings. After induction therapy, his clinical symptoms improved, but his MPO-ANCA remained elevated (>300 U·L-1) and hematuria persisted. Prednisolone plus azathioprine was administered as maintenance therapy. Three exacerbations of the inflammatory response occurred during the subsequent 3 months. In each instance, we suspected opportunistic infection or a flare-up of vasculitis. The first exacerbation was treated with an increased prednisolone dose and antibiotics. At the onset of the second exacerbation, which was accompanied by systemic erythema, we stopped azathioprine and administered antibiotics. The third exacerbation, which occurred the day after restarting azathioprine, involved a fever with chills and an acute inflammatory reaction; we therefore suspected an azathioprine allergy. A drug provocation test was performed, and a hyperinflammatory response was observed. The patient received prednisolone (15 mg·day-1) monotherapy; no further fever was observed during the subsequent 2 months. We therefore diagnosed azathioprine hypersensitivity syndrome. Under treatment with prednisolone (5 mg·day-1) and mycophenolate mofetil (1 g·day-1) (replacing the azathioprine), no signs of relapse or infection have occurred for more than two years. Renal function and the pulmonary lesions are stable, although the high MPO-ANCA titer and hematuria persist. The diagnosis of azathioprine hypersensitivity is often delayed because of the difficulty in identifying the relationship between immunosuppressive agents and hypersensitivity and in distinguishing this from infection or relapse of the primary disease. The misdiagnosis of azathioprine hypersensitivity leads to unnecessary treatment; thus, clinicians should consider allergic reactions specific to azathioprine when switching from induction to maintenance therapy.

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