Mild to moderate hypersensitivity reactions to beta-lactams in children: a single-centre retrospective review

ObjectiveBeta-lactam (BL) antibiotics are the most reported drugs in hypersensitivity reactions in children. More than 90% of these children tolerate the suspected drug after diagnostic work-up. Skin tests (STs) show low sensitivity. Our aim was to assess the performance of drug provocation tests (DPTs) without previous ST in mild and moderate delayed reactions and to propose a new DPT protocol.Design of the studyCharts from 213 children under 15 years of age referred for suspected BL allergy from 2011 to 1013 were reviewed. Prick, intradermal and patch tests were performed with major determinant penicilloyl-polylysine, minor determinant mixture, amoxicillin (AMX), cefuroxime, penicillin G and AMX–clavulamate. Children with negative skin tests underwent DPT. After an initial full dose of antibiotic, DPT was carried on for 3 days at home in patients reacting within the first 3 days of treatment. If the reaction took place from day 4 on of treatment, patients took the antibiotic for 5 days.ResultsWe included 108 girls and 105 boys. Mean age at the time of reaction was 3.66±3.06 years. 195 patients (91.5%) reacted to one BL. 154 reactions (67.2%) were non-immediate. Mild to moderate skin manifestations were most frequently reported. AMX–clavulanate was the most frequently involved (63.4%). DPT confirmed the diagnosis of drug hypersensitivity in 17 (7.3%) cases. These 17 patients had negative ST.ConclusionIn mild and moderate cases of BL hypersensitivity, diagnosis can be performed by DPT without previous ST

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Early Biomarkers for Severe Drug Hypersensitivity Reactions

Current Pharmaceutical Design ◽

10.2174/1381612825666191107105440 ◽

2019 ◽

Vol 25 (36) ◽

pp. 3829-3839 ◽

Cited By ~ 1

Author(s):

Adriana Ariza ◽

Maria J. Torres ◽

Carmen Moreno-Aguilar ◽

Rubén Fernández-Santamaría ◽

Tahia D. Fernández

Keyword(s):

Drug Exposure ◽

Drug Hypersensitivity ◽

Clinical Manifestations ◽

Skin Tests ◽

Time Interval ◽

Hypersensitivity Reactions ◽

Early Biomarkers ◽

Immunological Mechanisms ◽

Drug Hypersensitivity Reactions ◽

Delayed Reactions

Drug hypersensitivity reactions (DHRs) are typically classified into immediate and delayed reactions based on the time interval between drug exposure and onset of symptoms. Clinical manifestations range from mild to severe and life-threatening reactions. The most severe clinical entities are anaphylaxis and anaphylactic shock for immediate reactions, and severe cutaneous adverse reactions such as Steven Johnson Syndrome and Toxic Epidermal Necrolysis for delayed reactions. The diagnosis is complex and challenging, as drug provocation tests and even skin tests can be very risky procedures, which makes them not recommended. Therefore, it is necessary to search for useful early biomarkers to manage the diagnosis of these reactions. These biomarkers could be useful to determine the clinical entity, but not to identify the culprit drug. Some of the currently available biomarkers are few genetic associations of drug allergy with polymorphisms of human leukocyte antigen (HLA), the detection of inflammatory and lipid mediators in serum, or the detection of cytokines, chemokines, and cytotoxic markers in skin biopsies. In this literature review, it has been summarize the immunological mechanisms involved in severe reactions, both immediate and delayed, and different early biomarkers: those currently used for the diagnosis of these reactions as well as possible early biomarkers that could be useful with further studies to standardize their clinical use.

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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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PATTERNS OF RESPONSE AND DRUGS INVOLVED IN HYPERSENSITIVITY REACTIONS TO BETA-LACTAMS IN CHILDREN.

10.22541/au.161635658.84094563/v1 ◽

2021 ◽

Author(s):

Isabel Torres-Rojas ◽

Diana Perez ◽

Maria Luisa Somoza-Alvarez ◽

Elisa Haroun Diaz ◽

Ana María Prieto-Moreno Pfeifer ◽

...

Keyword(s):

Clavulanic Acid ◽

Skin Testing ◽

Drug Hypersensitivity ◽

Penicillin G ◽

Hypersensitivity Reactions ◽

Beta Lactams ◽

Provocation Tests ◽

Drug Challenge ◽

Immediate Reactions

Background Beta-lactams generate different allergenic determinants that induce selective or cross-reactive drug hypersensitivity reactions (DHRs). We aimed to identify the drugs involved, the selectivity of the response, the mechanism, and the value of the different diagnostic tests for establishing a diagnosis in children evaluated for DHRs to beta-lactams. Methods Prospective study evaluating children aged under 16 years reporting DHRs to beta-lactams. Reactions were classified as immediate and nonimmediate reactions. The work-up included sIgE, skin testing and drug provocation tests (DPTs) for immediate reactions and patch testing and DPTs for nonimmediate ones. Results Of the 510 included children, 133 were evaluated for immediate reactions and confirmed in 8.3%. Skin test/in vitro IgE contributed to diagnosing half of the cases. Selective reactions occurred with amoxicillin (63%), followed by common penicillin determinants (27%) and cephalosporins (0.9%). Among nonimmediate reactions (11,4% of the 377 children evaluated), most required DPTs, 52.7% of which were positive at 6–7 days of drug challenge. Selective reactions were identified with amoxicillin (80%), penicillin G (7.5%), cephalosporins (7.5%), and clavulanic acid (5%). Urticaria and maculopapular exanthema were the most frequent entities. Conclusions There were few confirmed cases of either type of reaction. Skin testing proved less valuable in nonimmediate reactions, over half of which would also have been lost in a short DPT protocol. Selective responders to amoxicillin were more likely to have nonimmediate reactions, while clavulanic acid-selectivity was exclusive to the nonimmediate typology. Over half the cases with DPTs required 6-7 days of treatment for DHR confirmation.

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Diagnosing and Managing Patients with Reactions to Radiocontrast Media

Current Treatment Options in Allergy ◽

10.1007/s40521-021-00287-x ◽

2021 ◽

Vol 8 (3) ◽

pp. 210-221

Author(s):

Knut Brockow

Keyword(s):

Skin Testing ◽

Drug Hypersensitivity ◽

Skin Tests ◽

Hypersensitivity Reactions ◽

Positive Skin ◽

Provocation Tests ◽

Ring Molecules ◽

Allergic Skin ◽

Drug Hypersensitivity Reactions ◽

Drug Provocation Tests

Abstract Purpose of the review Iodinated radio contrast media (RCM) belong to the most common elicitors of drug hypersensitivity reactions (HR). Urticaria or anaphylaxis may occur ≤ 1(−6) hour(s) (immediate HR) and exanthems (non-immediate HR) develop > 6 h after application of RCM. Evidence for an immunologic mechanism of RCM HR against the different RCM benzene ring molecules and the benefit of allergological testing in patients with previous hypersensitivity reactions is progressively increasing. Recent findings Positive skin tests can confirm allergy in patients with previous reactions to RCM and help to select alternative better tolerated RCMs. Severe hypersensitivity reactions are mainly caused by an allergic mechanism, whereas the majority of non-severe reactions appear to be non-allergic. Skin testing is highly recommended to help identify allergic hypersensitivity reactions and to select alternatives. Using structurally different RCM is more effective than premedication for the prevention of future reactions. Drug provocation tests to RCM have been increasingly used, but are not yet standardized among different centers. Summary In patients with previous severe hypersensitivity reactions to RCM, skin testing is recommended. For future RCM-enhanced examinations in patients with previous reactions, structurally different, skin test-negative preparations should be applied. Drug provocation tests do confirm or exclude RCM hypersensitivity or may demonstrate tolerability of alternative RCMs.

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The Contradiction of Drug Allergy in Patients with Cystic Fibrosis and Review of the Literature

10.22541/au.161538684.40504015/v1 ◽

2021 ◽

Author(s):

Gokcen Dilsa Tugcu ◽

Nagehan Emiralioğlu ◽

Ebru Yalçın ◽

Umit Sahiner ◽

Deniz Doğru ◽

...

Keyword(s):

Cystic Fibrosis ◽

Drug Allergy ◽

Drug Hypersensitivity ◽

Skin Tests ◽

Beta Lactam ◽

Provocation Tests ◽

Maculopapular Eruption ◽

Drug Hypersensitivity Reactions ◽

Amoxicillin Clavulanic Acid ◽

Multiple Drugs

Background: Cystic fibrosis (CF) is reported to be a risk factor for drug hypersensitivity. However, there is conflicting data about true prevalence of drug allergy in children with CF. Methods: The suspicious drug hypersensitivity reactions (DHR) of children with CF were enquired by European Network for Drug Allergy (ENDA) questionnaire and skin tests and/or drug provocation tests were performed according to established guidelines. Results: Two hundred and nineteen children (48.9% boys; median [IQR] age, 8.4 years [4.8-12.4 years]) with cystic fibrosis were included in the study, from whom 22 patients with 24 suspected DHRs were evaluated. Most of the suspected DHRs were non-immediate (n=16, 66.6%) type and the offending drugs were amoxicillin clavulanic acid (n=7), macrolides (n=4), trimethoprim sulfamethoxazole (TMP/SMX) (n=2), piperacillin tazobactam (n=1), pancrelipase (n=1) and ursodeoxycholic acid (n=1). Eight (33.3%) of the DHRs were classified as immediate [ceftriaxone (n=2), ceftazidim (n=2), meropenem (n=1), ambisome (n=2), vancomycin (n=1)]. The main presenting clinical presentations were maculopapular eruption (41.6%) and urticaria (37.5%), accompanied by angioedema (8.3%), flushing (12.5%) and vomiting (8.3%). Nine skin tests (with beta-lactam protocol in 6 patients) and 24 DPTs were performed and none of the skin tests revealed a positive result, however 2 DPTs with TMP/SMX were positive. Conclusion: Actual drug allergy was demonstrated in 2 of 219 patients (0.9%) with nonbeta-lactam antibiotics. These results conflict with previous researches that showed higher drug allergy rates but were consistent with some recent studies. Numerous and long-term use of multiple drugs during management of cystic fibrosis may contribute to tolerance development.

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PERIOPERATIVE IMMEDIATE DRUG HYPERSENSITIVITY: CLINICAL FEATURES, DIAGNOSTICS, RISK ASSESSMENT

Rossiiskii Allergologicheskii ZHurnal ◽

10.36691/rja486 ◽

2014 ◽

Vol 11 (6) ◽

pp. 9-19

Author(s):

D G Zhukova ◽

E S Fedenko ◽

A A Yudin ◽

O Y Rakhimova

Keyword(s):

Clinical Features ◽

Clinical Symptoms ◽

Drug Hypersensitivity ◽

Clinical Manifestations ◽

Diagnostic Algorithm ◽

Respiratory Arrest ◽

Skin Tests ◽

Hypersensitivity Reactions ◽

Cutaneous Manifestations ◽

Provocation Tests

Background. To evaluate clinical features and to develop the diagnostic algorithm of perioperative drug’s hypersensitivity reactions. Methods. 40 patients who presented perioperative immediate drug’s hypersensitivity reactions were studied in the Central Clinical hospital of the Russian Academy of sciences during 2010-2012. The diagnostic protocol consisted of 2 steps: at the 1 step (during the acute clinical manifestation period) a case history, grade of severity of immediate hypersensitivity reactions, serum tryptase levels have been studied; at the 2 step (6-12 weeks after symptoms were over) inhibition test of natural emigration of leukocytes by Ado, sublingual, skin tests and drug provocation tests have been performed. Results. Clinical manifestations of drugs hypersensitivity were as follows: hypersensitivity reactions grade I (isolated cutaneous manifestations) - in 20 patients (50%), anaphylactic-type reactions - in 20 patients (50%): grade II (moderate anaphylaxis) - in 13 patients (32,5%), grade III (severe life-threatening anaphylaxis) - in 6 (15%), and grade IV (cardiac and respiratory arrest) - in 1 patient (2,5%). Positive tests at least with 1 drug had 28 patients (70%): neuromusculars blockers (22,5%); antibiotics (22,5%); lidocaine (10%); amidotrizoate (7,5%); NSAID (7,5%). Other 12 patients had negative tests (30%) with all suspected agents and moderate clinical symptoms if to compare with others 28 patients (p

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Hypersensitivity reactions to low molecular weight heparins: different patterns of cross-reactivity in 3 patients

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2017-0246 ◽

2018 ◽

Vol 96 (4) ◽

pp. 428-432 ◽

Cited By ~ 1

Author(s):

Danica Juricic Nahal ◽

Ivana Cegec ◽

Viktorija Erdeljic Turk ◽

Ksenija Makar Ausperger ◽

Iva Kraljickovic ◽

...

Keyword(s):

Molecular Weight ◽

Challenge Test ◽

Cross Reactivity ◽

Skin Tests ◽

Delayed Type Hypersensitivity ◽

Low Molecular Weight ◽

Hypersensitivity Reactions ◽

Low Molecular Weight Heparins ◽

Safe Alternative ◽

Delayed Reactions

Low molecular weight heparins (LMWHs) are used for a variety of indications. The most common type of hypersensitivity reactions to LMWHs are delayed-type hypersensitivity reactions (DHR). Immediate-type hypersensitivity reactions (IHR) occur only sporadically. Cross-reactivity of different LMWHs is a common and unpredictable problem. We present 2 cases of patients who developed DHR to nadroparin and enoxaparin, respectively. The third case presents a patient who developed IHR to nadroparin. Skin tests confirmed the hypersensitivity in all cases. In the cases of DHR, a skin test negative LMWH was identified and was tolerated in a challenge test. In the IHR case, cross-reactivity to all tested LMWHs was established. We hypothesize that the degree of cross-reactivity might depend on the type of hypersensitivity reaction with immediate reactions linked to more extensive cross-reactivity than delayed reactions. This is important to consider because, at least in some cases, a safe alternative LMWH can be identified.

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Converter Phenotype: A New Profile That Is Not Exclusive to Taxanes

Frontiers in Allergy ◽

10.3389/falgy.2021.785259 ◽

2022 ◽

Vol 2 ◽

Author(s):

Teodorikez Wilfox Jimenez-Rodriguez ◽

Francisco Manuel Marco de la Calle ◽

Inmaculada Lozano-Cubo ◽

Rosa Ana Montoyo-Anton ◽

Victor Soriano-Gomis ◽

...

Keyword(s):

Clinical Characteristics ◽

Drug Exposure ◽

Drug Hypersensitivity ◽

Skin Tests ◽

Hypersensitivity Reactions ◽

Test Results ◽

Drug Reactions ◽

Immediate Hypersensitivity ◽

Drug Hypersensitivity Reactions ◽

Median Interval

Introduction: Phenotype I hypersensitivity reactions are the most commonly reported drug reactions; however, precision medicine has made it possible to characterize new phenotypes. A recent communication proposed the existence of a “converter phenotype,” which would affect patients who present non-immediate hypersensitivity reactions and in subsequent exposures develop immediate hypersensitivity reactions. This study aimed to describe the clinical characteristics of converter phenotype reactions and their evolution during desensitization to chemotherapeutic drugs and monoclonal antibodies.Methods: We retrospectively reviewed our database of patients undergoing desensitization to chemotherapy or biological agents and selected those with a converter phenotype. Demographic and clinical characteristics of the patients, the results of skin tests, tryptase and IL-6 levels, and desensitization outcomes were assessed.Results: Of 116 patients evaluated, 12 (10.3%) were identified as having a converter phenotype. The median interval between drug exposure and reaction was 90.6 h (range 8-288 h). After the conversion, phenotype I was the most frequent (58.3%), followed by cytokine release reactions (33.3%). Fifty-one desensitizations were undertaken and all treatments completed, with 10 (19.6%) breakthrough reactions. No new changes in the phenotype were detected.Conclusions: The symptoms of non-immediate drug hypersensitivity reactions may indicate the need for an early allergological evaluation to assess the risk of future immediate drug reactions. Clinical characteristics, skin test results, and biomarkers can help predict responses to rapid drug desensitization, guiding clinicians on how to optimize therapy delivery while maintaining patient safety.

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Use of Rapid Drug Desensitization in Delayed Hypersensitivity Reactions to Chemotherapy and Monoclonal Antibodies

Frontiers in Allergy ◽

10.3389/falgy.2021.786863 ◽

2022 ◽

Vol 2 ◽

Author(s):

Arantza Vega ◽

M. Isabel Peña ◽

Inés Torrado

Keyword(s):

Monoclonal Antibodies ◽

Drug Hypersensitivity ◽

Hypersensitivity Reactions ◽

Short Period ◽

Drug Hypersensitivity Reactions ◽

Facial Edema ◽

Delayed Reactions ◽

Hospital Visits ◽

To Receive ◽

Maculopapular Exanthema

Background:Rapid drug desensitization (RDD) allows first-line therapies in patients with immediate drug hypersensitivity reactions (DHR) to chemotherapeutic drugs (ChD) and monoclonal antibodies (mAb). Desensitization in delayed drug reactions has traditionally used slow protocols extending up to several weeks; RDD protocols have been scarcely reported.Patients and Method:We retrospectively analyzed the patients referred to the Allergy Department, who had experienced a delayed DHR (> 6 h) related to a ChD or mAb and underwent an RDD protocol. The rate of successful administration of the offending drug and the presence of adverse reactions were evaluated.Results:A total of 93 RDDs were performed in 11 patients (including 6 men and 5 women, with a median age of 61 years). The primary DHR were maculopapular exanthema (MPE) (8), generalized delayed urticaria (1), MPE with pustulosis and facial edema (1), and facial edema with desquamative eczema (1). The meantime for the onset of symptoms was 3 days (range 1–16 days). RDD was performed using a protocol involving 8–13 steps, with temozolomide (25), bendamustine (4), rituximab (9), infliximab (24), gemcitabine (23), and docetaxel (8), within 4.6–6.5 h. Sixteen breakthrough reactions were reported during the RDD (17.2 %) in 5 patients; all were mild reactions including 11 delayed and 5 immediate reactions. All patients completed their treatment.Conclusions:RDD is a potentially safe and effective procedure in patients suffering from delayed reactions to ChD and mAb. It allows them to receive full treatment in a short period, thereby reducing time and hospital visits.

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Hypersensitivity reactions to non-steroidal anti-inflammatory drugs: results of an Austrian cohort study

Allergo Journal International ◽

10.1007/s40629-020-00134-6 ◽

2020 ◽

Vol 29 (7) ◽

pp. 227-232

Author(s):

Teresa Bangerl ◽

Brigitte Zahel ◽

Andrea Lueger ◽

Emmanuella Guenova ◽

Irena Angelova-Fischer ◽

...

Keyword(s):

Skin Testing ◽

Drug Hypersensitivity ◽

Provocation Test ◽

Clinical History ◽

University Hospital ◽

Skin Tests ◽

Hypersensitivity Reactions ◽

Culprit Drug ◽

Inflammatory Drugs ◽

Anti Inflammatory

Summary Background Hypersensitivity to non-steroidal anti-inflammatory drugs (NSAIDs) is the second most common cause of drug hypersensitivity. Despite the importance of NSAIDs in routine analgesia only few studies have systematically addressed the question of tolerability in hypersensitive patients. Methods The authors retrospectively analysed 398 patients that were treated at the Department of Dermatology, Kepler University Hospital Linz, Austria, in the period 2012–2016 with a clinical history of NSAID hypersensitivity. Skin tests (skin prick and intracutaneous tests) to common NSAIDs were performed, followed by single-blinded, placebo-controlled drug challenge with either the culprit drug or an alternative NSAID. Results A total of 361 patients were subjected to skin testing. Of these, 25 patients (6.3%) showed a positive reaction to the culprit drug. According to the severity of the reaction in the medical history, 87 patients were exposed orally to the culprit drug (oral provocation test, OPT) after negative skin test and 255 patients received OPT with alternative NSAIDs according to established protocols. OPT with the culprit drug resulted in hypersensitivity reactions in 12 patients (13.79%). In terms of alternative NSAID testing, the three most commonly tested drugs were lornoxicam (192 OPTs), acetaminophen (156 OPTs) and celecoxib (133 OPTs) with tolerability rates in respectively 88.54% (hypersensitivity reactions, 11.46%), 92.31% (hypersensitivity reactions, 7.69%) and 91.73% (hypersensitivity reactions, 8.27%) of cases. Conclusion OPT with alternative NSAIDs are useful in patients with NSAID hypersensitivity as tolerability varies between the individual substances.

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