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1.
Pharmaceuticals (Basel) ; 17(6)2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38931343

RESUMO

(1) Background: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are extremely severe cutaneous adverse drug reactions which are relatively rare in routine clinical practice. An analysis of a national pharmacovigilance database may be the most effective method of obtaining information on SJS and TEN. (2) Methods: Design-a retrospective descriptive pharmacoepidemiologic study of spontaneous reports (SRs) with data on SJS and TEN retrieved from the Russian National Pharmacovigilance database for the period from 1 April 2019 to 31 December 2023. Descriptive statistics was used to assess the demographic data of patients and the structure of suspected drugs. (3) Results: A total of 170 SRs on SJS and TEN were identified, of which 32.9% were SJS and 67.1%-TEN. In total, 30% were pediatric SRs, 21.2%-SRs of the elderly. There were 12 lethal cases, and all cases were TEN. The leading culprit drugs were anti-infectives for systemic use and nervous system agents. The top 10 involved drugs are as follows: lamotrigine (23.5%), ibuprofen (12.9%), ceftriaxone (8.8%), amoxicillin and amoxicillin with beta-lactam inhibitors (8.8%), paracetamol (7.6%), carbamazepine (5.9%), azithromycin (4.1%), valproic acid (4.1%), omeprazole (3.5%), and levetiracetam (3.5%). (4) Conclusions: Our study was the first study in Russia aimed at the assessment of the structure of the drugs involved in SJS and TEN on the national level.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38710408

RESUMO

A patient-reported outcome is directly reported by the patient without interpretation of the patient's response by anyone else. It refers to the patient's health (symptoms and feelings), quality of life, or functional status associated with health care or treatment. Patient-reported outcome measures (PROMs) are defined as the tools or instruments that are used to measure patient-reported outcomes. Health-related quality of life has been the most studied psychosocial PROM in food allergy, using validated questionnaires. In drug allergy, PROMs are useful in capturing patients' experiences of potential allergic reactions, including subjective symptoms such as headache, dizziness, or fatigue. Patient-reported outcome measures can also help differentiate true allergies from side effects or other nonallergic reactions and inform decisions about drug challenges and de-labeling strategies. Ensuring the chosen tool is validated for the specific allergy context is crucial for accurate data collection. Integrating patient-reported experiences alongside traditional methods can lead to more accurate assessments and personalized care.

3.
BMC Med Genomics ; 17(1): 101, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38654296

RESUMO

BACKGROUND: Allopurinol has been causing substantial morbidity and mortality particularly in Asian population by producing cutaneous adverse drug reactions (cADRs). Nonetheless, there are no data describing whether other genetics are a valid marker for prediction of allopurinol-induced cADRs patients in addition to HLA-B*58:01 allele. The goal of this study was to identify suitable single nucleotide polymorphisms (SNPs) for allopurinol induced cADRs among Thai patients. METHODS: We conducted a case-control association study after enrolling 57 Thai patients with allopurinol induced cADRs and 101 allopurinol-tolerant controls. The genetic biomarkers and associated SNPs located on chromosome 6p21 were examined by TaqMan® SNP genotyping assays in both the cases and the controls. RESULTS: Out of fifteen SNPs in nine genes, we found four combined SNPs (rs3099844 of HCP5, rs9263726 of PSORS1C1, rs9263733 of POLR2LP, and rs9263745 of CCHCR1) were significantly associated with allopurinol-induced cADRs compared to the tolerant controls (OR 73.2; 95% CI 24.2-266.8; P = 1.9 × 10- 24). The overall sensitivity, specificity, positive predictive value and negative predictive value of these combinations were 84%, 94%, 9%, and 100%, respectively. However, the variant alleles of these SNP combinations were detected in 89.5% (51/57) of the cases. Moreover, the HLA-B*58:01 allele was observed in 86.0% of patients with allopurinol-induced cADRs, but only in 4.0% of tolerant controls (OR: 137.2; 95% CI: 38.3-670.5 and p-value = 1.7 × 10- 27). CONCLUSIONS: Thus, this research confirms the association between the specific HLA-B*58:01 allele and all phenotypes of allopurinol-induced cADRs in Thais. Furthermore, there was found the combined four SNPs (rs3099844, rs9263726, rs9263733, and rs9263745) could be used as alternative novel biomarkers for predicting cADRs in patients taking allopurinol.


Assuntos
Alopurinol , Polimorfismo de Nucleotídeo Único , Humanos , Alopurinol/efeitos adversos , Masculino , Feminino , Tailândia , Pessoa de Meia-Idade , Estudos de Casos e Controles , Idoso , Adulto , Farmacogenética , Antígenos HLA-B/genética , Predisposição Genética para Doença , Variantes Farmacogenômicos , População do Sudeste Asiático
4.
Cureus ; 16(3): e55318, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38562325

RESUMO

Cutaneous adverse drug reactions (CADRs) are one of the most broadly studied and rigorously researched conditions in recent dermatological advancements. Also termed as "toxidermia," they are heavily involved and are of utmost importance to be understood and studied in the modern healthcare industry. In simple terms, they are dermatological manifestations which result from systemic drug administration to patients. Since allopathy is influenced by the medicines and drugs provided to the patients, cutaneous skin eruptions are a common occurrence in recent times. It is a need of the hour to understand the causative factors for such skin eruptions and the correct management and handling of such disorders to provide better healthcare to patients. The withdrawal of the causative drug which induces the reaction plays a key role in treatment. The risk factors are to be thoroughly studied, and dosages must be in accordance with the patient's situation. They are some of the common public health problems. The age group which is affected is highly variable as people from all age groups can be affected. Those who are affected comprise approximately 10% of all hospitalized patients, and it is also observed in about 1-4% of people who are on multiple medications.

5.
J Dermatol ; 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38605448

RESUMO

Drug causality assessment in severe cutaneous adverse reactions (SCARs) remains challenging. We investigated the usefulness of in-vivo drug patch tests (PT), ex-vivo interferon (IFN)-γ enzyme-linked immunospot (ELISpot) assay, and lymphocyte transformation test (LTT) in 30 SCARs patients within the past 36 months. Drug PT yielded a 20% positivity rate (n = 6), while IFN-γ ELISpot and LTT showed positive rates of 56.67% (n = 17) and 41.38% (n = 12), respectively. Combining the three tests resulted in an overall positive rate of 66.67% (n = 20) of cases. IFN-γ ELISpot offered additional positivity, especially with oxypurinol. Employing a combined diagnostic approach may enhance the chances of obtaining a positive result.

6.
Indian J Dermatol ; 69(1): 106, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38572036

RESUMO

Background: Adverse drug reactions (ADRs) are major problems in the drug therapy. Cutaneous adverse drug reactions (CADRs) are the most common ADRs. The pattern of CADRs differs among various drugs. Aims: To record various morphological patterns of CADRs and their causal relationships among patients attending in a tertiary care centre. Materials and Methods: An observational, cross-sectional, clinical study was conducted for a duration of one and a half years in a tertiary care centre in eastern India. Patients presenting with suspected CADRs were included if drug identity could be ascertained. Clinical profiling and drug history were recorded, and causality assessment was carried out as per the Naranjo scale. Result: The commonest CADR in our study was fixed drug eruption (FDE) 48.61%, followed by SJS-TEN spectrum 16.66%, maculopapular rash 11.11% and so on. Severe cutaneous adverse drug reactions (SCARs) such as SJS, TEN, SJS-TEN Overlap, AGEP and DRESS accounted for 18 cases (25%). The most common culprit drugs were antimicrobials (54.16%), followed by nonsteroidal anti-inflammatory drugs (15.27%) and anticonvulsants (12.5%). Most of the CADRs were in probable category. Conclusion: The pattern of CADRs and the drugs causing them in our study population are similar to some previous studies but somewhat different from most of the previous Indian studies. The incidence of SCARs was significantly higher than in previous other studies in India and abroad.

7.
Front Allergy ; 5: 1330517, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38384771

RESUMO

Drug hypersensitivity reactions (DHR) in children have a significant impact on clinical practice and public health. Both under-diagnosis (due to under-reporting) and over-diagnosis (due to the overuse of the term "allergy") are potential issues. The aim of this narrative review is to describe the most recent findings of DHR in children/adolescents and gaps regarding epidemiology, antibiotic allergy, antiepileptic hypersensitivity, vaccine allergy, and severe cutaneous adverse reactions (SCAR) in this age group.

9.
Therapie ; 79(2): 239-270, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37980248

RESUMO

Cutaneous adverse drug reactions (ADRs) represent a heterogeneous field including various clinical patterns without specific features suggesting drug causality. Maculopapular exanthema and urticaria are the most common types of cutaneous ADR. Serious cutaneous ADRs, which may cause permanent sequelae or have fatal outcome, may represent 2% of all cutaneous ADR and must be quickly identified to guide their management. These serious reactions include bullous manifestations (epidermal necrolysis i.e. Stevens-Johnson syndrome and toxic epidermal necrolysis), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalized exanthematous pustulosis (AGEP). Some risk factors for developing cutaneous ADRs have been identified, including immunosuppression, autoimmunity or genetic variants. All drugs can cause cutaneous ADRs, the most commonly implicated being antibiotics (especially aminopenicillins and sulfonamides), anticonvulsants, allopurinol, antineoplastic drugs, non-steroidal anti-inflammatory drugs and iodinated contrast media. Pathophysiology is related to immediate or delayed "idiosyncratic" immunologic mechanisms, i.e., usually not related to dose, and pharmacologic/toxic mechanisms, commonly dose-dependent and/or time-dependent. If an immuno-allergic mechanism is suspected, allergological explorations (including epicutaneous patch testing and/or intradermal test) are often possible to clarify drug causality, however these have a variable sensitivity according to the drug and to the ADR type. No in vivo or in vitro test can consistently confirm the drug causality. To determine the origin of a rash, a logical approach based on clinical characteristics, chronologic factors and elimination of differential diagnosis (especially infectious etiologies) is required, completed with a literature search. Reporting to pharmacovigilance system is therefore essential both to analyze drug causality at individual level, and to contribute to knowledge of the drug at population level, especially for serious cutaneous ADRs or in cases involving newly marketed drugs.


Assuntos
Pustulose Exantematosa Aguda Generalizada , Síndrome de Stevens-Johnson , Humanos , Pele , Síndrome de Stevens-Johnson/epidemiologia , Síndrome de Stevens-Johnson/etiologia , Síndrome de Stevens-Johnson/diagnóstico , Antibacterianos/efeitos adversos , Pustulose Exantematosa Aguda Generalizada/diagnóstico , Pustulose Exantematosa Aguda Generalizada/epidemiologia , Pustulose Exantematosa Aguda Generalizada/etiologia , Anti-Inflamatórios não Esteroides/efeitos adversos
10.
Med J Armed Forces India ; 79(Suppl 1): S209-S216, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38144617

RESUMO

Background: The term severe cutaneous adverse reactions to drugs (SCAR) comprises of acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms complex (DRESS), Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS-TEN) and drug-induced erythroderma or exfoliative dermatitis (ED). The present study aims at describing the epidemiological and clinical profile, probable cause and the extent of morbidity and mortality in patients with severe cutaneous adverse drug reactions. Methods: An observational study of all cases of SCAR presenting to our centre during the period from Jun 2018 to July 2019 was carried out. Results: A total of 24 SCAR patients were studied. Most of the patients were in the age group of 11-20 years. The commonest reactions observed were SJS-TEN (54.2%) followed by DRESS (42%). Antibiotics are the most common cause of SJS-TEN, whereas almost all the drug groups were implicated equally in DRESS. No causative drug could be found in two of the SJS-TEN patients. These patients had raised atypical targetoid lesions as well as evidence of viral reactivation which could have been the probable trigger for the SCAR. A total of five patients (20.8%) died during treatment in hospital, and the percentage mortality was highest in SJS-TEN. Conclusion: Nondrug aetiologies for SJS-TEN are on the rise, and this was observed in this study too. Viral reactivation may be the commonest aetiology in such cases, and the morphology of the rash can give a clue to such cases.

11.
SAGE Open Med Case Rep ; 11: 2050313X231210390, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37954539

RESUMO

Cutaneous adverse drug reactions are known side effects of first-line antitubercular therapy, which ranges from mild pruritus to life-threatening toxic epidermal necrolysis. Severe cutaneous adverse drug reactions can lead to antitubercular therapy discontinuation and further complicates tuberculosis treatment. Here we present the case of a 49-year-old obese male who developed a generalized maculopapular rash within 24 hours of initiation of therapy followed by bullae over palms in 3 days. Antitubercular therapy was immediately discontinued, and he was managed with antihistamines, intravenous fluid, and electrolyte supplementation. He was discharged on antihistamines, a short course of systemic steroids, moxifloxacin, and bedaquiline (second-line antitubercular therapy (ATT)). Proper guidelines about rechallenge therapy will enormously aid in managing cutaneous adverse drug reactions, and efficient treatment of tuberculosis in these patients, and ceasing its progression to multisystemic complications. This article aims to discuss the presentation and management of cutaneous adverse drug reactions in the setting of Nepal.

12.
Cureus ; 15(9): e44812, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37809172

RESUMO

Toxic epidermal necrolysis (TEN) is a life-threatening, blistering dermatitis. It is characterized by fever and the development of mucocutaneous lesions, which lead to necrosis and sloughing of the epidermis. It is commonly triggered by medications and infections. We present the case of a 75-year-old male who presented to the hospital with a fever and widespread exfoliating skin rash involving 41% of his body surface area (BSA). He has a past medical history of gout, hypertension, asthma, and depression. He was recently started on allopurinol by his general practitioner (GP) for hyperuricemia. The condition also involved oral, eye, and pharynx mucosae. He was diagnosed with toxic epidermal necrolysis and was managed with intravenous (IV) hydrocortisone, steroid and antibiotic eye drops, and steroid and antibiotic topical creams. Due to the weak available evidence supporting the use of ciclosporin and intravenous immunoglobulins, this patient was managed with steroid use only. His rash initially worsened, but ultimately, he made a full recovery without any sequelae. The patient was reviewed in the dermatology clinic four weeks post-discharge, and he did not have any residual disease.

13.
Pharmacogenomics ; 24(8): 459-474, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37503628

RESUMO

Aim: Examining the association between HLA-A/B alleles and different carbamazepine (CBZ)-induced cutaneous adverse reactions in the Chinese population. Methods: A systematic review and meta-analysis of case-control studies was conducted. A systematic search was conducted of PubMed, Embase, the Cochrane Library, National Knowledge Infrastructure, the Chinese Biomedical Literature database and Wanfang Digital Periodicals. Results: 23 studies with a total of 1174 patients were included. In the Han population, HLA-B*15:02 is significantly associated with the increased risk of CBZ-related Stevens-Johnson syndrome/toxic epidermal necrolysis, and this correlation was not related to geographic distribution. HLA-A*31:01, B*38:02 are associated with CBZ-related maculopapular eruption in South Han population. HLA-A*31:01 is associated with CBZ-DRESS in Taiwan Han population. Conclusion: HLA-B*15:02, A*31:01 and B*38:02 genes were found to be involved in the occurrence of CBZ cutaneous adverse reactions in Han Chinese.


Assuntos
Carbamazepina , Síndrome de Stevens-Johnson , Humanos , Carbamazepina/efeitos adversos , Anticonvulsivantes/efeitos adversos , População do Leste Asiático , Antígenos HLA-B/genética , Síndrome de Stevens-Johnson/genética , Antígenos HLA-A/genética
14.
Front Pharmacol ; 14: 1088841, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37324461

RESUMO

Background: Data on traditional medicine-induced cutaneous adverse drug reactions (ADRs) is very scarce. The current secondary analysis based on the WHO database (VigiBase) of individual case safety reports (ICSRs) focuses on the suspected cutaneous ADRs linked to traditional medicines (TMs). Methods: All the ICSRs reported between 1st January 2016 and 30th June 2021 from the UN Asia region in VigiBase where at least one TM was suspected to cause cutaneous ADRs were included in the study. Data regarding demographic details, suspected drug, adverse reaction as per MedDRA term, the seriousness of the reaction, de-challenge, re-challenge, and clinical outcome for suspected cutaneous ADRs associated with TM were obtained from VigiBase and analyzed for frequency of reported events and suspected medicines. Findings: Total 3,523 ICSRs with 5,761 ADRs related to "skin and subcutaneous tissue disorders" were included in the analysis. Amongst these, 6.8% of ICSRs were reported as serious. Pruritus (29.6%), rash (20.3%), urticaria (18.9%), and hyperhidrosis (3.3%) were commonly reported ADRs. Artemisia argyi H.Lév. and Vaniot. (14.9%), Ginkgo biloba L. (5.1%), Vitis vinifera L. (4%), Vitex agnus-castus L. (3.8%), Silybum marianum (L.), Gaertn (3.5%), and Viscus album L. (2.7%) were some commonly suspected TMs for cutaneous ADRs. There were 46 cases of Stevens-Johnson syndrome and toxic epidermal necrolysis reported with TMs during the study period. Death was reported in 5 ICSRs. Interpretation: TMs are linked with various cutaneous ADRS ranging from pruritus to toxic epidermal necrolysis which may have serious consequences. TMs listed as suspected offending agents in this analysis, should be kept in mind while dealing with suspected cutaneous ADRs. Clinicians should be more vigilant in detecting and reporting events associated with TMs.

15.
Indian J Dermatol ; 68(1): 34-40, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37151259

RESUMO

Background: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are some of the less common cutaneous adverse drug reactions with significant mortality. Objectives: This study was undertaken with the objective of studying the demographics and clinical profile of SJS/TEN and identifying parameters associated with mortality. Materials and Methods: All patients with SJS/TEN over 10 years (2010-2020) were included in the study. Data obtained from in-patient and out-patient records were analysed. Results: A total of 82 patients with SJS/TEN were admitted to our centre over a period of 10 years. Patients with SJS were significantly younger than those with TEN, with a male: female ratio >1 in SJS and <1 in TEN. The most commonly implicated drugs were antiepileptics (n = 29, 35.4%), antibiotics (n = 20, 24.4%). and Non-steroidal antiinflammatory drugs (NSAIDs) (n = 7, 8.5%). The mortality rate in the TEN group was 16% (n = 8). Certain factors such as cutaneous lesions preceding mucosal lesions at onset, high mean Body surface area (BSA) of denudation and a transfer to intensive care unit (ICU) more than 7 days after admission were significantly associated with higher mortality. There was no difference between survivors and deaths in terms of delay in hospitalisation, total disease duration, implicated drug, delay in initiation of therapy, the onset of re-epithelialisation, Severity-of-illness score for TEN (SCORTEN) and total duration of hospital stay. Conclusion: Factors significantly associated with increased mortality in TEN were cutaneous onset of lesions, mean BSA of involvement and transfer to the intensive care unit (ICU) beyond day 7 of admission.

17.
HLA ; 102(3): 269-277, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37002612

RESUMO

In this observational case-control study, 107 cutaneous adverse reaction (CAR) cases (CAR+) manifesting up to 12 weeks after the start of treatment with antiseizure medication (ASM) were identified. Control groups consisted of 98 epilepsy patients without a history of CAR (CAR-) and 3965 healthy individuals in the Brazilian National Registry of Bone Marrow Donors. All participants were HLA typed by high-resolution Next Generation Sequencing for HLA-A, B, C, DQB1 and DRB1; HLA-DPA1, DPB1, DQA1, DRB3, DRB4 and DRB5 were also sequenced in samples from CAR+ and CAR- individuals. The relationship between the carrier frequency of each allele, CAR type and ASM for all participants was investigated. The ASMs most frequently associated with CAR were carbamazepine (48% of CAR+ subjects), lamotrigine (23%), phenytoin (18%), phenobarbital (13%) and oxcarbazepine (5%). The main alleles associated with a risk of CAR were HLA-A*02:05 (OR = 6.28; p = 0.019, carbamazepine or oxcarbazepine); HLA-DPA1*02:02 (OR = 4.16, p = 0.003, carbamazepine); HLA-B*53:01 (OR = 47.9, p = 0.014, oxcarbazepine), HLA-DPA1*03:01/DPB1*105:01 (OR = 25.7, p = 0.005, phenobarbital); HLA-C*02:10 (OR = 25.7, p = 0.005, phenobarbital) and HLA-DRB1*04:02 (OR = 17.22, p = 0.007, phenytoin). HLA-A*03:01 increased the risk for phenytoin-induced maculopapular exanthema 4.71-fold (p = 0.009), and HLA-B*35:02 was associated with a 25.6-fold increase in the risk of carbamazepine-induced Stevens-Johnson syndrome (p = 0.005). None of the 4170 subjects carried the HLA-B*15:02 allele, and HLA-A*31:01 was not associated with CAR. Hence, HLA-A*31:01 and HLA-B*15:02 were not associated with CAR in this population. Although other HLA class I and II alleles tested were associated with a risk of CAR, none of these associations were strong enough to warrant HLA testing before prescribing ASM.


Assuntos
Antígenos HLA-B , Fenitoína , Humanos , Alelos , Brasil , Oxcarbazepina , Estudos de Casos e Controles , Antígenos HLA-B/genética , Carbamazepina/efeitos adversos , Antígenos HLA-A/genética , Fenobarbital
18.
Dermatology ; 239(2): 241-247, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36599331

RESUMO

BACKGROUND: Drug patch test to identify cutaneous adverse drug reactions (CADRs) has been widely reported. Appropriate vehicles can improve the ability of drug delivery and significantly increase positive reaction of drug patch tests. OBJECTIVE: The aim of this study was to evaluate the efficacy of drug patch tests using 0.9% saline vehicle in comparison with other traditional vehicles in CADRs. METHOD: All patients were patch tested with suspected drugs using 10-30% concentration of the commercialized form of drugs diluted in 0.9% saline, petrolatum, and water. RESULT: Of 100 patients with CADRs, 54 of those had at least one positive drug patch test. In terms of vehicles used, 43 patients had positive drug patch test with saline as compared to 35 with water (p = 0.485) and 25 with petrolatum (p = 0.007). Among CADRs subgroup, saline rendered significantly higher positive rate when compared with petrolatum in drug rash with eosinophilia and systemic symptom (DRESS) (70% vs. 20%, p = 0.025), maculopapular rash (MP) (52.4% vs. 31%, p = 0.046), and lichenoid drug eruption (46.7% vs. 0.0%, p = 0.002). 12/54 (22.2%) of CADRs patients had positive reaction with saline alone. Among these patients, 4/12 (33.3%) were lichenoid drug reaction, 3/12 (25%) were DRESS, and 2/12 (16.7%) were MP rash. Allopurinol was the drug giving positive patch test only with saline. CONCLUSION: Appropriate vehicles are essential to obtain the positive drug patch test. Using saline as a vehicle can increase the positive reaction of drug patch test, particularly in lichenoid drug eruption. We recommend the use of saline as another traditional vehicle in drug patch test.


Assuntos
Toxidermias , Exantema , Líquen Plano , Humanos , Testes do Emplastro , Solução Salina , Toxidermias/diagnóstico , Toxidermias/etiologia , Preparações Farmacêuticas
19.
Dermatology ; 239(3): 328-333, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36702114

RESUMO

BACKGROUND: Acute generalized exanthematous pustulosis (AGEP) is a potentially severe adverse cutaneous drug reaction, which typically occurs within 24-48 h after the intake of the culprit drug. SUMMARY: AGEP is characterized by numerous sterile subcorneal pustules on erythematous skin and in less than a third of cases it can be associated with organ manifestations possibly leading to life-threatening symptoms (e.g., cholestasis, nephritis, and lung and bone marrow involvement). In contrast to generalized pustular psoriasis, it can involve mucosal regions and typically resolves rapidly if the culprit drug is removed, and adequate therapy with topical or systemic steroids administered. Diagnosis based on patient history, clinical signs, and characteristic cutaneous histology is rarely challenging. Identification of the culprit drug may be aided by patch testing or lymphocyte transformation tests that are of limited value. KEY MESSAGES: Recent experimental data reviewed herein are supportive of an early role of drug-induced innate immune activation and innate cytokines such as interleukin (IL)-1, IL-36, and IL-17 in the pathogenesis of AGEP. This explains the rapid onset and neutrophilic character of the cutaneous inflammation, but also provides new avenues for in vitro tests aimed at better identifying the culprit drug.


Assuntos
Pustulose Exantematosa Aguda Generalizada , Humanos , Pustulose Exantematosa Aguda Generalizada/diagnóstico , Pustulose Exantematosa Aguda Generalizada/etiologia , Pustulose Exantematosa Aguda Generalizada/terapia , Pele/patologia , Administração Cutânea
20.
Front Pharmacol ; 13: 954596, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36506572

RESUMO

Vancomycin is a commonly used antibiotic; however, it can cause life-threatening severe cutaneous adverse reactions, such as drug reaction with eosinophilia and systemic symptoms (DRESS). A previous study has reported a strong association between HLA-A*32:01 and vancomycin-induced DRESS in European ethnicity. Herein, we aim to investigate the genetic predisposition of vancomycin-induced DRESS in the Han-Chinese population. In this study, we enrolled a total of 26 patients with vancomycin-induced DRESS, 1,616 general population controls, and 51 subjects tolerant to vancomycin. In vitro granulysin-based lymphocyte activation tests (LAT) were conducted among 6 vancomycin-induced DRESS patients who were concomitantly receiving other medicines. HLA-A and HLA-B genotypes were determined by sequencing-based typing. Our results found that vancomycin-induced DRESS was associated with HLA-A*32:01 [odds ratio (OR) = 7.8, 95% confidence interval (CI) = 1.7-35.8; p-value = 0.035], HLA-B*07:05 (OR = 32.3, 95% CI = 2.8-367.7; p-value = 0.047), HLA-B*40:06 (OR = 4.7, 95% CI = 1.3-16.1; p-value = 0.036) and HLA-B*67:01 (OR = 44.8, 95% CI = 7.2-280.4; p-value = 0.002) when comparing the vancomycin-induced DRESS patients with the general population controls. LAT results showed that granulysin significantly increased in the vancomycin-induced DRESS patients upon vancomycin stimulation (4.7 ± 3.7 fold increased), but not upon other co-medicines. This study identified that, in addition to HLA-A*32:01, HLA-B*07:05, HLA-B*40:06, and HLA-B*67:01 were also genetic markers for vancomycin-induced DRESS in the Han-Chinese population. Associations of ethnic variances in HLA with vancomycin-DRESS were observed.

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