Non-immediate reactions to β-lactams: diagnostic value of 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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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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Evaluation of immediate reactions to β lactam antibiotics using a comprehensive diagnostic protocol

International Journal of Basic & Clinical Pharmacology ◽

10.18203/2319-2003.ijbcp20174360 ◽

2017 ◽

Vol 6 (10) ◽

pp. 2366

Author(s):

Bhanuja Bhagwat ◽

Anuradha H. V.

Keyword(s):

Skin Prick Test ◽

Drug Hypersensitivity ◽

Tertiary Care ◽

Provocation Test ◽

Intradermal Test ◽

Care Hospital ◽

Prick Test ◽

Diagnostic Protocol ◽

Drug Provocation Test ◽

Immediate Reactions

Background: β lactam antibiotics are commonly prescribed groups of antibacterial drugs for various infections however the prevalence of its allergic effects is not clear in our country, hence the need for an effective diagnostic protocol to determine immediate hypersensitivity reactions. The objective was to formulate a diagnostic protocol for evaluating immediate drug hypersensitivity to β lactam antibiotics.Methods: A prospective study was conducted at a tertiary care hospital. Adults who were prescribed any class of β lactam antibiotic were included. Non irritating concentrations of the antibiotic as per The European Network on drug Allergy were used. A strict three step diagnostic algorithm with skin prick test followed by intradermal test and drug provocation test, with 20 minutes observation period between each step, to determine cutaneous allergic reactions was followed.Results: The most commonly prescribed drug was cefazolin, followed by ceftriaxone, and cefoperazone + sulbactam combination. The culprit drugs were ceftriaxone in 4 (4.7%) patients, followed by piperacillin + tazobactam combination in 3 (3.5%), amoxicillin + clavulanic acid in 2 (2.3%) and 1 (1.1%) each for cefotaxime and cefepime + tazobactam combination. No patients were positive for skin prick test; 2.4% were positive for intradermal test and 10.6% were positive for drug provocation test.Conclusions: This diagnostic protocol is apt to adequately diagnose immediate reactions to β lactam antibiotics and henceforth can be used effectively in India. However, the skin prick test may be excluded but the intradermal test and drug provocation test is crucial to identify these immediate reactions.

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Systemic reaction during intradermal skin tests with beta-lactams

BMJ Case Reports ◽

10.1136/bcr-2020-240050 ◽

2021 ◽

Vol 14 (3) ◽

pp. e240050

Author(s):

Joana Carvalho ◽

Georgeta Oliveira

Keyword(s):

Skin Testing ◽

Drug Hypersensitivity ◽

Systemic Reaction ◽

Skin Tests ◽

Beta Lactam ◽

Provocation Tests ◽

Maculopapular Eruption ◽

Intradermal Tests ◽

Amoxicillin Clavulanate ◽

Immediate Reactions

Beta-lactam (BL) antibiotics are the most frequent cause of drug hypersensitivity in children, inducing both immediate and non-immediate reactions. Here we report a case of a 4-year-old child with a disseminated maculopapular exanthema 7 days after the first dose of amoxicillin–clavulanate, referred to our paediatric allergy department. Skin prick tests were negative. Intradermal tests were performed and, after 10 hours, indurated wheals larger than 10×10 mm with progressive erythema and disseminated maculopapular eruption were developed, related to amoxicillin and amoxicillin–clavulanate. Systemic reactions to BL skin tests are rarely reported and the majority are immediate reactions. This case illustrates a rare example of a non-immediate systemic reaction to intradermal tests, underlying the importance of skin testing before drug provocation tests in cases of moderate to severe non-immediate reactions.

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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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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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