Evaluation of drug patch tests in children

Background: Patch tests are used to diagnose nonimmediate T-cell‐mediated drug hypersensitivity reactions. The aim of this study was to evaluate the results of patch tests performed with suspect drugs in children. Methods: Patients < 18 years of age who had a drug patch test at the pediatric allergy outpatient clinic of our hospital between January 2014 and January 2020 were included in the study. Age, sex, culprit drug(s), reaction characteristics, and patch test results were recorded from the patients' files. Results: A total of 105 drug patch tests were performed on 71 patients during the study period. The patients' median age was 7 years (interquartile range, 4‐11 years), and 57.7% (n = 41) were boys. Twenty-three patients (32.3%) had severe cutaneous adverse reaction (Stevens-Johnson syndrome in 11, drug reaction with eosinophilia and systemic symptoms in 9, and acute generalized exanthematous pustulosis in 3 patients), 45 (63.3%) had maculopapular rashes, and 3 (4.2%) had fixed drug eruption. A total of 20 patch test results (28%) were positive: 18 of 44 patch tests (40.9%) with antiepileptic drugs and 2 of 48 patch tests (4.1%) with antibiotics. Positive results were obtained in 23% of the patch tests (6/26) in 20 patients with severe cutaneous adverse reactions and in 17.7% of the patch tests (14/79) in 51 patients with mild cutaneous reactions. No adverse reactions occurred during or after the patch tests. Conclusion: In our study, patch test positivity was more common with antiepileptic drugs and in patients with severe cutaneous drug reaction.

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Role of in vivo and in vitro Tests in the Diagnosis of Severe Cutaneous Adverse Reactions (SCAR) to Drug

Current Pharmaceutical Design ◽

10.2174/1381612825666191107104126 ◽

2019 ◽

Vol 25 (36) ◽

pp. 3872-3880 ◽

Cited By ~ 3

Author(s):

Marcel M. Bergmann ◽

Jean-Christoph Caubet

Keyword(s):

Adverse Reactions ◽

Lymphocyte Transformation ◽

Stevens Johnson Syndrome ◽

In Vitro Tests ◽

High Morbidity ◽

Patch Tests ◽

Severe Cutaneous Adverse Reactions ◽

Cutaneous Adverse Reactions

Severe cutaneous adverse reactions (SCAR) are life-threatening conditions including acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS). Diagnosis of causative underlying drug hypersensitivity (DH) is mandatory due to the high morbidity and mortality upon re-exposure with the incriminated drug. If an underlying DH is suspected, in vivo test, including patch tests (PTs), delayed-reading intradermal tests (IDTs) and in vitro tests can be performed in selected patients for which the suspected culprit drug is mandatory, or in order to find a safe alternative treatment. Positivity of in vivo and in vitro tests in SCAR to drug varies depending on the type of reaction and the incriminated drugs. Due to the severe nature of these reactions, drug provocation test (DPT) is highly contraindicated in patients who experienced SCAR. Thus, sensitivity is based on positive test results in patients with a suggestive clinical history. Patch tests still remain the first-line diagnostic tests in the majority of patients with SCAR, followed, in case of negative results, by delayed-reading IDTs, with the exception of patients with bullous diseases where IDTs are still contra-indicated. In vitro tests have shown promising results in the diagnosis of SCAR to drug. Positivity is particularly high when the lymphocyte transformation test (LTT) is combined with cytokines and cytotoxic markers measurement (cyto-LTT), but this still has to be confirmed with larger studies. Due to the rarity of SCAR, large multi-center collaborative studies are needed to better study the sensitivity and specificity of in vivo and in vitro tests.

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Evaluation of Clinical Properties and Diagnostic Test Results of Cephalosporin Allergy in Children

International Archives of Allergy and Immunology ◽

10.1159/000513974 ◽

2021 ◽

pp. 1-7

Author(s):

Ozge Yilmaz Topal ◽

Ilknur Kulhas Celik ◽

Irem Turgay Yagmur ◽

Muge Toyran ◽

Ersoy Civelek ◽

...

Keyword(s):

Drug Reaction ◽

Diagnostic Test ◽

Pediatric Patients ◽

Drug Hypersensitivity ◽

Maculopapular Rash ◽

Test Results ◽

Pediatric Allergy ◽

Fixed Drug ◽

Drug Hypersensitivity Reactions ◽

Immediate Reactions

Introduction: Beta-lactams (BLs) are one of the most frequent causes of drug hypersensitivity reactions (HRs), and cephalosporins are a widely used subclass of BLs, especially in children. The aim of this study was to evaluate the clinical features and diagnostic test results of pediatric patients evaluated for suspected cephalosporin allergy. Methods: This study included patients who presented to our pediatric allergy clinic with a history of reactions attributed to cephalosporins between January 1, 2011, and December 31, 2019, and whose diagnostic tests were completed for the diagnosis. Results: This study included 120 pediatric patients and 69 (57.5%) of them were girls. The median age was 38.63 (interquartile range 10.5–85.7) months. Reactions occurring within 1 h of drug intake were reported in 33 patients (27.5%). Reactions were maculopapular rash in 55 (45.8%) patients, urticaria and/or angioedema in 49 (40.8%), anaphylaxis in 11 (9.2%), severe cutaneous drug reaction in 4 (3.3%), and fixed drug reaction in 1 patient (0.83%). The most frequently suspected agent was cefixime in 41 patients (34.2%). In total, 30 (25%) patients were diagnosed as having cephalosporin hypersensitivity. Confirmation of HRs was also significantly more frequent among patients who were older (p: 0.000), who had taken the drug parenterally (p: 0.000) and with immediate reactions (p: 0.000). Conclusion: Cephalosporin allergy has been confirmed in approximately one-fourth of the patients evaluated for suspected cephalosporin allergy. Confirmation of HRs was significantly more common among patients who were older, had immediate reactions, and had taken the drug parenterally.

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The association between HLA-B*15:02 and phenytoin-induced severe cutaneous adverse reactions: a meta-analysis

Pharmacogenomics ◽

10.2217/pgs-2021-0126 ◽

2021 ◽

Author(s):

Thanh Huong Phung ◽

Khanh Ngoc Cong Duong ◽

Mac Ardy Junio Gloria ◽

Thien Khac Nguyen

Keyword(s):

Drug Reaction ◽

Adverse Reactions ◽

Meta Analysis ◽

Stevens Johnson Syndrome ◽

Random Effects Model ◽

Systemic Symptom ◽

Anticonvulsant Agent ◽

Johnson Syndrome ◽

Severe Cutaneous Adverse Reactions ◽

Cutaneous Adverse Reactions

Aim: Phenytoin (PHT) is a common anticonvulsant agent known for inducing severe cutaneous adverse reactions (SCARs). HLA-B*15:02 as a risk factor of PHT-induced SCARs was reported in numerous studies with inconsistent results. This meta-analysis aimed to establish pooling evidence of this association. Materials & methods: Pooled odds ratios (ORs) with 95% CIs were estimated using a random-effects model. Results: A total of 11 studies on 1389 patients, were included for the analyses. There was a significant association between HLA-B*15:02 and PHT-induced SCAR (pooled OR = 2.29, 95% CI: 1.25–4.19, p = 0.008). Furthermore, there was a significant association regarding Stevens–Johnson syndrome/toxic epidermal necrolysis (OR = 3.63, 95% CI: 2.15–6.13, p < 0.001) but no association regarding drug reaction with eosinophilia and systemic symptom. Conclusion: The results supported the recommendations of HLA-B*15:02 screening before treatment with PHT.

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TOXIC EPIDERMOLYSIS CAUSED BY ANTIEPILEPTIC DRUGS: CLINICAL OBSERVATIONS

PEDIATRIA Journal named after G N SPERANSKY ◽

10.24110/0031-403x-2021-100-1-282-287 ◽

2021 ◽

Vol 100 (1) ◽

pp. 282-287

Author(s):

M.A. Ufimtseva ◽

◽

M.A. Zakharov ◽

O.Yu. Averyanov ◽

O.V. Kozhevnikova ◽

...

Keyword(s):

Adverse Drug Reaction ◽

Drug Reaction ◽

Toxic Epidermal Necrolysis ◽

Antiepileptic Drugs ◽

Stevens Johnson Syndrome ◽

International Literature ◽

Emergency Medical Care ◽

Clinical Observations ◽

Johnson Syndrome

Toxic epidermal necrolysis (Lyell's syndrome) and Stevens–Johnson syndrome are severe types of toxicodermia and require emergency medical care. The pathophysiology of toxicoderma is associated with an adverse drug reaction. The article provides data from Russian and international literature on the role of antiepileptic drugs in these diseases occurrence. It also presents clinical cases of toxic epidermal necrolysis in children caused by anticonvulsants intake.

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Cephalosporin-Induced Atypical DRESS Syndrome; a Tale of Two Cases

Journal of Skin and Stem Cell ◽

10.5812/jssc.112575 ◽

2021 ◽

Vol 8 (1) ◽

Author(s):

Ravindranath Brahmadeo Chavan ◽

Vasudha Abhijit Belgaumkar ◽

Nitika S. Deshmukh ◽

Amruta Patil ◽

Vijay Deepak Joshi

Keyword(s):

Drug Reaction ◽

Adverse Reactions ◽

Stevens Johnson Syndrome ◽

Standard Group ◽

Erythematous Rash ◽

Dress Syndrome ◽

Drug Induced ◽

Severe Cutaneous Adverse Reactions ◽

Systemic Symptoms ◽

Cutaneous Adverse Reactions

Introduction: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare, idiosyncratic subset of drug-induced hypersensitivity syndrome manifesting as skin eruption, fever, lymphadenopathy, hematologic abnormalities, and multi-organ involvement. It presents usually after a latent period of 2 to 6 weeks as a diffuse erythematous rash with systemic symptoms and facial edema. It is now recognized as one of the severe cutaneous adverse reactions (SCAR) associated with high mortality, chiefly because of derangement of renal or liver functions. The cutaneous morphologies can be myriad, encompassing maculopapular, exfoliative dermatitis-like, pustular, erythema multiforme-like, Stevens-Johnson syndrome-like, and toxic epidermal necrolysis-like presentations. Case Presentation: We hereby report two young males who developed pruritic exfoliating erythematous rash after taking cephalosporin with paradoxical worsening despite drug withdrawal. They were diagnosed with ‘atypical DRESS syndrome’ according to the Japanese study group severe cutaneous adverse reactions (J-SCAR) criteria and treated successfully with systemic steroids and emollients. The J-SCAR scoring and the concept of atypical DRESS are useful in situations, where either all clinical and laboratory criteria are not present simultaneously, or typical clinical presentations wherein human herpes virus-6 (HHV-6) reactivation cannot be documented. Conclusions: These two cases were used to illustrate the hitherto obscure concept of atypical DRESS syndrome that presented with compatible clinical features but did not satisfy all the requisite criteria. We also highlight cephalosporins (one of the most commonly prescribed standard group of drugs) as a plausible but infrequently reported cause of this severe adverse cutaneous drug reaction.

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HLA-A*24:02 as a common risk factor for antiepileptic drug–induced cutaneous adverse reactions

Neurology ◽

10.1212/wnl.0000000000004008 ◽

2017 ◽

Vol 88 (23) ◽

pp. 2183-2191 ◽

Cited By ~ 48

Author(s):

Yi-Wu Shi ◽

Fu-Li Min ◽

Dong Zhou ◽

Bin Qin ◽

Juan Wang ◽

...

Keyword(s):

Risk Factor ◽

Antiepileptic Drug ◽

Antiepileptic Drugs ◽

Adverse Reactions ◽

Han Chinese ◽

Stevens Johnson Syndrome ◽

Drug Induced ◽

Maculopapular Eruption ◽

Johnson Syndrome ◽

Cutaneous Adverse Reactions

Objective:To investigate the involvement of human leukocyte antigen (HLA) loci in aromatic antiepileptic drug–induced cutaneous adverse reactions.Methods:A case-control study was performed to detect HLA loci involved in aromatic antiepileptic drug–induced Stevens-Johnson syndrome in a southern Han Chinese population. Between January 1, 2006, and December 31, 2015, 91 cases of Stevens-Johnson syndrome induced by aromatic antiepileptic drugs and 322 matched drug-tolerant controls were enrolled from 8 centers. Important genotypes were replicated in cases with maculopapular eruption and in the meta-analyses of data from other populations. Sequence-based typing determined the HLA-A, HLA-B, HLA-C, and HLA-DRB1 genotypes.Results:HLA-B*15:02 was confirmed as strongly associated with carbamazepine-induced Stevens-Johnson syndrome (p = 5.63 × 10−15). In addition, HLA-A*24:02 was associated significantly with Stevens-Johnson syndrome induced by the aromatic antiepileptic drugs as a group (p = 1.02 × 10−5) and by individual drugs (carbamazepine p = 0.015, lamotrigine p = 0.005, phenytoin p = 0.027). Logistic regression analysis revealed a multiplicative interaction between HLA-B*15:02 and HLA-A*24:02. Positivity for HLA-A*24:02 and/or HLA-B*15:02 showed a sensitivity of 72.5% and a specificity of 69.0%. The presence of HLA-A*24:02 in cases with maculopapular exanthema was also significantly higher than in controls (p = 0.023). Meta-analysis of data from Japan, Korea, Malaysia, Mexico, Norway, and China revealed a similar association.Conclusions:HLA-A*24:02 is a common genetic risk factor for cutaneous adverse reactions induced by aromatic antiepileptic drugs in the southern Han Chinese and possibly other ethnic populations. Pretreatment screening is recommended for people in southern China.

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Missed Diagnosis of Epilepsy-Associated Scald Burns: Two Cases Initially Diagnosed as Bullous Dermatosis

Journal of Burn Care & Research ◽

10.1093/jbcr/iraa184 ◽

2020 ◽

Author(s):

Laura Giraud-Kerleroux ◽

Chloé Charpentier ◽

Charlotte Bernigaud ◽

Nicolas Ortonne ◽

Camille Hua ◽

...

Keyword(s):

Adverse Reactions ◽

Stevens Johnson Syndrome ◽

Fixed Drug Eruption ◽

Antiepileptic Treatment ◽

Bullous Dermatosis ◽

Johnson Syndrome ◽

Fixed Drug ◽

Epileptic Attack ◽

Missed Diagnosis ◽

Cutaneous Adverse Reactions

Abstract Thermal burns can occur during seizure. This diagnosis can be difficult in case of atypical lesions, even more if the epilepsy is unknown and in case of seizures with loss of consciousness and/or an unwitnessed epileptic attack. We report two cases of cutaneous bullous lesions initially misdiagnosed as severe acute cutaneous adverse reactions (generalized bullous fixed drug eruption and Stevens–Johnson syndrome). In the two cases, the clinical aspect, necrotic evolution, and absence of obvious attributable medication allowed to revert to the diagnosis of burns due to boiling water revealing previously unknown epilepsy. For both, surgical management with skin graft was performed, and antiepileptic treatment was introduced. Facing unexplained burns, occult epilepsy should be investigated. Questioning of patient and relatives is crucial.

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Pattern of adverse drug reaction to antiepileptic drugs in a tertiary care hospital

International Journal of Basic & Clinical Pharmacology ◽

10.18203/2319-2003.ijbcp20173748 ◽

2017 ◽

Vol 6 (9) ◽

pp. 2219

Author(s):

Suchitra D. Akalu ◽

Niveditha G. Belavadi

Keyword(s):

Adverse Drug Reaction ◽

Drug Reaction ◽

Antiepileptic Drugs ◽

Vascular System ◽

Tertiary Care ◽

Stevens Johnson Syndrome ◽

Care Hospital ◽

Entire Study ◽

Monitoring Centre ◽

Post Marketing Surveillance

Background: Adverse drug reactions (ADRs) are a major cause of morbidity and mortality, and are the leading cause of hospital admission. The overall rate of ADRs is estimated to be 6.5% and 28% of these ADRs are preventable. Antiepileptic drugs (AEDs) are authorized for several therapeutic indications and are highly prescribed. ADRs due to AEDs range from minor maculopapular exanthem (MPE) to severe life-threatening reactions like Drug reaction eosinophilia and systemic symptoms (DRESS) and Stevens-Johnson syndrome (SJS). Objective of the study was to evaluate the pattern of ADRs reported with AEDs in an adverse drug reaction monitoring centre (AMC) of a tertiary care hospital.Methods: Retrospective analysis of the records was done for a period 48 months from January 2013 to December 2016. During this period, all the ADRs caused by AEDs reported to the AMC were included in the study. The study evaluated the pattern of ADRs due to AEDs. The study also assessed the gender-wise distribution, predilection for various systems, causality, severity, and preventability of ADRs. Data was analysed using descriptive statistics.Results: A total of 319 ADRs were reported by spontaneous reporting during the entire study period. Out of the total 319 ADR reports received, antiepileptic drugs related ADRs were 35 (11%). Antiepileptic drugs which caused the ADRs included phenytoin, carbamazepine, clobazam and lorazepam. The most common system affected was dermatological (60%), followed by gastrointestinal system (17.14%), vascular system (11.42%), blood (5.8%), respiratory system (5.8%) and central nervous system (2.9%). Among the dermatological ADRs, SJS accounted for 11 cases of which 10 cases were due to phenytoin and one case was due to carbamazepine. DRESS syndrome due to phenytoin was documented in one case.Conclusions: AEDs are the most commonly prescribed drugs for various indications. Uses of AEDs are accompanied by ADRs which vary from mild rashes and itching to SJS and DRESS/TEN. Post-marketing surveillance of the AEDs is important for compliance, therapeutic efficacy and ultimately safety of the patient.

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