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INTRODUCTION: Growth modulation allows correction of progressive ulnar deviation of the distal radius in skeletally immature patients, which may occur as a consequence of various pathologies. The aim of this study is to evaluate the radiographic results and complication rate in a series of patients treated with minifragment plates. METHODS: The medical records of 12 patients who underwent guided growth with a minifragment plate on the radial aspect of the distal radius as a consequence of angular deformities in the distal radius were retrospectively reviewed. Demographic data, radiographic changes, and complication rate were analyzed. RESULTS: A total of 14 wrists and forearms were evaluated. The mean age at which surgery was performed was 10.5 years (interquartile range: 9.0 to 11.3). The average time between placement and removal of the material was 28.7 months (SD: 8,89). In each case, a general improvement of the radiographic parameters was obtained. There were 3 postoperative complications, but only 1 of them required reintervention (broken metaphyseal screw). CONCLUSIONS: Hemiepiphysiodesis using a minifragment plate is a treatment that respects the surgical anatomy and offers an alternative surgical option for angular deformities of the distal radius in children. LEVEL OF EVIDENCE: Level IV.
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Placas Óseas , Radio (Anatomía) , Humanos , Estudios Retrospectivos , Niño , Radio (Anatomía)/cirugía , Radio (Anatomía)/anomalías , Radio (Anatomía)/diagnóstico por imagen , Masculino , Femenino , Resultado del Tratamiento , Complicaciones Posoperatorias/etiología , Estudios de Seguimiento , Radiografía , Adolescente , Articulación de la Muñeca/cirugía , Articulación de la Muñeca/diagnóstico por imagen , Articulación de la Muñeca/anomalíasRESUMEN
Atopic dermatitis (AD) is an inflammatory skin disease characterized by intense itching and highly visible signs, representing a great burden to the patient. Despite its straightforward diagnosis, AD severity and burden can be underestimated in routine clinical practice. This review aims to determine the impact of AD on patients' lives, establish which domains of life are most affected, and identify symptom drivers of AD burden. A systematic literature review was conducted in Pubmed/Medline, Web of Science, and Scopus following Cochrane and PRISMA recommendations. Observational studies published in English or Spanish between January 1, 2018, and August 31, 2022, evaluating the impact of AD and its symptoms from the patient's perspective, were included. Reviewed studies were assessed for quality following the STrengthening the Reporting of OBservational studies in Epidemiology Checklist. A total of 28 observational studies evaluating the impact of AD and its symptoms from the patient's perspective were included in the review. All domains of the AD patient's life were found to be greatly affected, including health-related quality of life (HRQoL), emotional health, sleep disorders, work impairment, health care resource utilization, cognitive function, and development of comorbidities. The more severe the disease, the greater the impact, worsening in patients with moderate and severe AD. Pruritus and pain are reported to be the disease symptoms with the greatest impact. In conclusion, AD impacts several domains of patients' lives, especially HRQoL and mental health. Pruritus and pain are identified as the main drivers of AD impact, suggesting that optimal symptom control may reduce the burden and improve disease management.
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BACKGROUND: Tralokinumab was recently approved for the treatment of moderate-to-severe atopic dermatitis (AD) and is the first selective interleukin (IL)-13 inhibitor that specifically neutralizes IL-13 with high affinity. OBJECTIVES: To determine the real-life short-term effectiveness and safety of tralokinumab treatment in patients with moderate-to-severe AD. METHODS: A multicentre retrospective study was conducted including adult patients with moderate-to-severe AD who started tralokinumab treatment from 1 April to 30 June 2022 in 16 Spanish hospitals. Demographic and disease characteristics, severity and quality of life scales were collected at the baseline visit and at weeks 4 and 16. RESULTS: Eighty-five patients were included. Twenty-seven patients (32%) were non-naive to advanced therapy (biological or Janus kinase inhibitors inhibitors). All included patients had severe disease with baseline Eczema Area and Severity Index (EASI) scores of 25.4 (SD 8.1), Dermatology Life Quality Index (DLQI) 15.8 (5.4) and peak pruritus numerical rating scale (PP-NRS) 8.1 (1.8) and 65% had an Investigator's Global Assessment (IGA) of 4. At week 16, there was improvement on all scales. The mean EASI decreased to 7.5 (SD 6.9, 70% improvement), SCORing Atopic Dermatitis improved 64% and PP-NRS, 57%. Also, 82%, 58% and 21% of the patients achieved EASI 50, 75 and 90, respectively. The percentage of EASI 75 responders was significantly higher among the naive vs. non-naive groups (67% vs. 41%). The safety profile was acceptable. CONCLUSIONS: Patients, with a long history of disease and prior multidrug failure, showed a good response to tralokinumab, confirming clinical trial results.
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Dermatitis Atópica , Adulto , Humanos , Dermatitis Atópica/tratamiento farmacológico , Calidad de Vida , Estudios Retrospectivos , Resultado del Tratamiento , Prurito/tratamiento farmacológico , Índice de Severidad de la Enfermedad , Método Doble CiegoRESUMEN
INTRODUCTION: Atopic dermatitis (AD) is a chronic, inflammatory skin disorder that impairs patients' quality of life (QoL). Physician assessment of AD disease severity is determined by clinical scales and assessment of affected body surface area (BSA), which might not mirror patients' perceived disease burden. METHODS: Using data from an international cross-sectional web-based survey of patients with AD and a machine learning approach, we sought to identify disease attributes with the highest impact on QoL for patients with AD. Adults with dermatologist-confirmed AD participated in the survey between July-September 2019. Eight machine learning models were applied to the data with dichotomised Dermatology Life Quality Index (DLQI) as the response variable to identify factors most predictive of AD-related QoL burden. Variables tested were demographics, affected BSA and affected body areas, flare characteristics, activity impairment, hospitalisation and AD therapies. Three machine learning models, logistic regression model, random forest and neural network, were selected on the basis of predictive performance. Each variable's contribution was computed via importance values from 0 to 100. For relevant predictive factors, further descriptive analyses were conducted to characterise those findings. RESULTS: In total, 2314 patients completed the survey with mean age 39.2 years (standard deviation 12.6) and average disease duration of 19 years. Measured by affected BSA, 13.3% of patients had moderate-to-severe disease. However, 44% of patients reported a DLQI > 10, indicative of a very large to extremely large impact on QoL. Activity impairment was the most important factor predicting high QoL burden (DLQI > 10) across models. Hospitalisation during the past year and flare type were also highly ranked. Current BSA involvement was not a strong predictor of AD-related QoL impairment. CONCLUSIONS: Activity impairment was the single most important factor for AD-related QoL impairment while current extent of AD did not predict higher disease burden. These results support the importance of considering patients' perspectives when determining the severity of AD.
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Interleukin 17 (IL-17) is an effector cytokine that plays a key role in the pathogenesis of both psoriasis and metabolic-associated fatty liver disease (MAFLD), a condition that is more prevalent and severe in patients with psoriasis. In liver inflammation, IL-17 is mainly produced by CD4+ T (TH17) and CD8+ T cells (Tc17), although numerous other cells (macrophages, natural killer cells, neutrophils and Tγδ cells) also contribute to the production of IL-17. In hepatocytes, IL-17 mediates systemic inflammation and the recruitment of inflammatory cells to the liver, and it is also implicated in the development of fibrosis and insulin resistance. IL-17 levels have been correlated with progression from MAFLD to steatohepatitis, cirrhosis, and even hepatocellular carcinoma. Clinical trials have shown that inhibiting IL-17A in patients with psoriasis could potentially contribute to the improvement of metabolic and liver parameters. A better understanding of the key factors involved in the pathogenesis of these chronic inflammatory processes could potentially lead to more efficient treatment for both psoriasis and MAFLD, and help to develop holistic strategies to improve the management of these patients.
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NAVIGATE clinical trial demonstrated a higher rate of Psoriasis Assesment Severity Index (PASI)90 response in patients treated with guselkumab when compared to ustekinumab and an improved response in those who switched from ustekinumab to guselkumab due to partial response. The objective of the study is to describe ustekinumab to guselkumab switching in clinical practice. Observational, multicentric, descriptive study including 54 psoriasis patients who switched to guselkumab after treatment with ustekinumab from March 2019 to February 2021. Mean basal PASI with ustekinumab (16.7) was higher than with guselkumab (7.2). Up to 49.01% of patients were able to reach PASI90 with ustekinumab and up to 21.56% had a less frequent dosage regime vs. summary of product characteristics. Main reason to start guselkumab was a loss of ustekinumab cutaneous or articular response (82.36%) but up to 17.64% were switched in order to increase dosage regime efficiency. Six months after starting guselkumab, the absolute PASI was lower than 2 in 72% of patients and 38.5% of them were treated with a reduced dosage regime. Guselkumab doses used by our cohort were 19.5% lower than the expected according to the summary of product characteristics. No adverse events reported. There is no real-world evidence regarding patients who switched from ustekinumab to guselkumab. A short paragraph in the article by Fougerousse et al, reported 63 patients with a mean basal PASI of 5.3 and similar efficacy rate at week 16 to NAVIGATE. Our study adds practical information regarding efficacy, safety and efficiency through dose optimization in a real-world cohort.
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Anticuerpos Monoclonales Humanizados , Psoriasis , Ustekinumab , Anticuerpos Monoclonales Humanizados/uso terapéutico , Ensayos Clínicos como Asunto , Humanos , Psoriasis/tratamiento farmacológico , Resultado del Tratamiento , Ustekinumab/uso terapéuticoRESUMEN
Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a life-threatening hypersensitivity reaction to medications characterized by keratinocyte apoptosis and skin detachment. IL-15 serum levels have been associated with severity and prognosis of SJS/TEN. We have measured IL-15 concentrations in serum and blister fluid (BF) from patients with SJS/TEN by ELISA and used quantitative RT-PCR to analyze the expression of IL15 and IL15RA (encoding for IL-15 Receptor-α chain) genes in peripheral blood and BF cells, including isolated monocytes, and in affected skin. A positive correlation was found between IL-15 serum levels and a percent of detached skin. BF concentrations were higher, but no correlation was found. Higher IL15 and IL15RA gene expression levels were found in skin-infiltrating blister fluid cells compared to peripheral mononuclear cells. Moreover, IL15RA transcripts were barely detected in healthy skin, being the highest expression levels found in samples from two SJS/TEN patients who did not survive. The cutaneous expression of IL-15Rα in SJS/TEN may provide an explanation to the tissue-specific immune cytotoxic response in this clinical entity, and the results suggest that the effects of IL-15 in SJS/TEN patients may be dependent on the expression of its private receptor IL-15Rα in affected skin.
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BACKGROUND: Additional long-term treatments are needed for moderate-to-severe atopic dermatitis (AD). An ongoing, open-label, 5-year extension trial, ECZTEND (NCT03587805), assesses tralokinumab plus optional topical corticosteroids in participants from previous tralokinumab parent trials (PTs) with moderate-to-severe AD. OBJECTIVE: To evaluate the safety and efficacy of up to 2 years tralokinumab treatment in a post hoc interim analysis. METHODS: Safety analyses included adults from completed PTs enrolled in ECZTEND, regardless of tralokinumab exposure duration. Efficacy analyses included adult participants treated with tralokinumab in ECZTEND for ≥1 year and subgroup analyses of those on tralokinumab for 2 years (1 year from PT, 1 year in ECZTEND). Primary end point was the number of adverse events with additional efficacy end points. RESULTS: Participants on tralokinumab had an exposure-adjusted rate of 237.8 adverse events/100 patient-years' exposure (N = 1174) in the safety analysis set. Exposure-adjusted incidence rates of common adverse events were comparable to PTs, although at lower rates. With 2 years of tralokinumab, improvements in extent and severity of AD were sustained, with Eczema Area and Severity Index (EASI-75) in 82.5% of participants (N = 345). LIMITATIONS: Possible selection bias; no placebo arm; some participants experienced treatment gaps between PTs and ECZTEND. CONCLUSION: Over 2 years, tralokinumab was well tolerated and maintained long-term control of AD signs and symptoms.
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Dermatitis Atópica , Adulto , Anticuerpos Monoclonales/efectos adversos , Dermatitis Atópica/tratamiento farmacológico , Método Doble Ciego , Glucocorticoides/uso terapéutico , Humanos , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
INTRODUCTION: Previous drug survival studies of dupilumab in atopic dermatitis (AD) show that many patients continue treatment through 1 year, suggesting that patients experience clinically relevant benefits with long-term treatment. METHODS: This post hoc analysis included data through week 100 from 391 adult patients from the dupilumab open-label extension (OLE) study who had not achieved the endpoints of at least 75% improvement from baseline in the Eczema Area and Severity Index (EASI-75) or an Investigator's Global Assessment (IGA) score of 0 or 1 with short-term (16 weeks, 300 mg qw or q2w) dupilumab treatment in the parent SOLO 1 or 2 studies. All patients received dupilumab 300 mg qw in the OLE study, irrespective of whether they received qw or 2qw dosing in the parent study. RESULTS: Among those who had not achieved EASI-75 or IGA 0/1 during the 16-week parent study, the proportion of patients achieving EASI-75 by week 100 was 91%. The proportion achieving IGA 0 or 1 at week 100 was 45% for patients initially on q2w week dosing and 49% for those on initial qw dosing. CONCLUSION: Long-term dupilumab treatment may be associated with improvement in AD in patients with suboptimal responses during the initial 16 weeks of treatment. CLINICAL TRIAL REGISTRATION: LIBERTY AD SOLO 1: ClinicalTrials.gov identifier NCT02277743; EudraCT 2014-001198-15. LIBERTY AD SOLO 2: ClinicalTrials.gov identifier NCT02277769; EudraCT 2014-002619-40. LIBERTY AD OLE: ClinicalTrials.gov Identifier NCT01949311; EudraCT 2013-001449-15.
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INTRODUCTION: Atopic dermatitis (AD) can have a profound negative impact on the quality of life (QoL) of patients. We analyzed the long-term changes in AD symptoms, QoL, and patient assessment of treatment effect in adults with moderate-to-severe AD treated for 2 years with dupilumab. METHODS: LIBERTY AD OLE (NCT01949311) is a multicenter, open-label extension (OLE) study in adults with moderate-to-severe AD who previously participated in dupilumab clinical trials (parent studies). Patients received dupilumab 300 mg weekly. Patient-Oriented Eczema Measure (POEM), Dermatology Life Quality Index (DLQI), EQ-5D-3L, and the Patient Global Assessment of Treatment Effect (PGATE) were assessed at weeks 48 and 100. RESULTS: A total of 2677 patients were included in the OLE, and 1028 completed week 100. By weeks 48 and 100, 94.1% and 95.6% of patients achieved a ≥ 4-point change in POEM from the parent study baseline (PSBL), respectively, and 93.3% and 93.4% of patients had achieved a ≥ 4-point change in DLQI from PSBL, respectively. At week 100, 35.1% of patients had a POEM score ≤ 2 (AD clear/almost clear) compared with 0.1% at PSBL, and 49.9% had a DLQI score of 0 or 1 (no effect at all on patient's life) compared with 1.5% at PSBL. At week 100, 74.5-97.3% of patients reported no effect of AD on the individual EQ-5D-3L domains, and 93.8% rated the effect of dupilumab treatment as "excellent," "very good," or "good" according to PGATE. CONCLUSION: In adults with moderate-to-severe AD, dupilumab treatment over 2 years resulted in sustained improvements in patient-reported symptoms and QoL and a favorable patient perception of treatment effect. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01949311. Supplementary material 1 (MP4 552250 kb).
Atopic dermatitis is a common skin disease that causes scaly, itchy skin. It can have a profoundly negative effect on a patient's quality of life (QoL). In short-term clinical trials, dupilumab treatment resulted in significant improvements in signs and symptoms of atopic dermatitis, and in the QoL reported by patients, together with acceptable safety. In this study, adults with moderate-to-severe atopic dermatitis who had completed one of the short-term clinical trials continued dupilumab treatment, including those who had taken placebo. This study allowed researchers to continue to evaluate how dupilumab worked in the long term, including its impact on patient-reported outcomes, which measure the success of treatment from the patient's own perspective. The results were evaluated at approximately 1 and 2 years of this open-label extension study and were compared with the period just before the patient was first treated with dupilumab so that the effect of dupilumab could be seen. At approximately 1 and 2 years, most patients had achieved clinically meaningful improvements in two measures: Patient Oriented Eczema Measure, a tool used by patients to self-report the severity of their symptoms, and Dermatology Life Quality Index, which allows patients to report the effect of the disease on their QoL. Additionally, in this open-label extension study, most patients described their experience of being treated with dupilumab as "excellent," "very good," or "good" using the Patient Global Assessment of Treatment Effect questionnaire. Dupilumab treatment resulted in sustained improvements in atopic dermatitis and was regarded favorably by patients.
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Exantema , Antígenos HLA-A , Alelos , Anticonvulsivantes , Exantema/inducido químicamente , Antígenos HLA-A/genética , Humanos , NitroimidazolesRESUMEN
Numerous epidemiology studies confirm the increasing prevalence of non-alcoholic fatty liver disease in severe psoriasis, with more than double the risk reported for patients without psoriasis (odds ratio [OR] 2.15). Liver disease is more severe in patients with psoriasis than in controls without psoriasis and is associated with the severity. Similarly, patients with fatty liver disease have more severe psoriasis. This harmful synergy has a common pathogenic origin, resulting from the frequent association between both diseases, insulin resistance and the metabolic syndrome. The disease manifests with a greater intensity when both conditions co-occur than when each manifests separately. Furthermore, psoriasis and fatty liver also have a common cytokine-mediated inflammatory background, which involves an imbalance between pro-inflammatory and anti-inflammatory cytokines. In fact, each disease plays a role in the course of the other. The dermatologist should usually detect liver disease after a specific assessment of patients who present with the metabolic syndrome. The hepatologist should be aware of the more severe condition of these patients. Various medications, such as acitretin, cyclosporine and methotrexate may prove harmful for patients with liver disease. Biologics have proven to be safe in patients with chronic liver disease. Hepatologists and dermatologists should work together to ensure the careful evaluation of the optimal therapy for each patient depending on the severity of both diseases, taking care to avoid, where possible, hepatotoxic drugs and select options that may even have a shared benefit for both diseases.
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Enfermedad del Hígado Graso no Alcohólico/complicaciones , Psoriasis/complicaciones , Citocinas/metabolismo , Humanos , Inmunosupresores/efectos adversos , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Psoriasis/tratamiento farmacológico , Psoriasis/epidemiología , Psoriasis/metabolismoRESUMEN
Cyclooxygenase-2 (COX-2) and its metabolic product prostaglandin E2 (PGE2 ) are induced in response to growth factors, inflammatory cytokines, tumor promoters, activated oncogenes, and, in the skin, ultraviolet (UV) radiation. Accumulating evidence suggests a role for the COX-2/PGE2 pathway in tumorigenesis in various tissue types including cutaneous squamous cell carcinoma. There is also strong evidence for a role in the development of actinic keratoses (AKs) - common dysplastic lesions of the skin associated with UV radiation overexposure - considered as part of a continuum with skin cancer. Non-steroidal anti-inflammatory drugs (NSAIDs) exert their anti-inflammatory, analgesic, and antipyretic effects by reversibly or irreversibly acetylating COX isoforms, inhibiting downstream prostaglandins, and may have a chemopreventive role in malignancies, including skin cancer. Topical treatment of AK lesions with the NSAID diclofenac sodium 3% in combination with hyaluronic acid 2.5% has been shown to be effective and well tolerated, although the mechanism of action remains to be elucidated.
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Diclofenaco/administración & dosificación , Ácido Hialurónico/administración & dosificación , Queratosis Actínica/tratamiento farmacológico , Administración Cutánea , Animales , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/farmacología , Carcinoma de Células Escamosas/prevención & control , Inhibidores de la Ciclooxigenasa 2/administración & dosificación , Inhibidores de la Ciclooxigenasa 2/farmacología , Diclofenaco/farmacología , Humanos , Queratosis Actínica/patología , Neoplasias Cutáneas/prevención & controlRESUMEN
BACKGROUND AND OBJECTIVE: Multi-criteria decision analysis (MCDA) is a tool that systematically considers multiple factors relevant to health decision-making. The aim of this study was to use an MCDA to assess the value of dupilumab for severe atopic dermatitis compared with secukinumab for moderate to severe plaque psoriasis in Spain. METHOD: Following the EVIDEM (Evidence and Value: Impact on DEcision Making) methodology, the estimated value of both interventions was obtained by means of an additive linear model that combined the individual weighting (between 1 and 5) of each criterion with the individual scoring of each intervention in each criterion. Dupilumab was evaluated against placebo, while secukinumab was evaluated against placebo, etanercept and ustekinumab. A retest was performed to assess the reproducibility of weights, scores and value estimates. RESULTS: The overall MCDA value estimate for dupilumab versus placebo was 0.51 ± 0.14. This value was higher than those obtained for secukinumab: 0.48 ± 0.15 versus placebo, 0.45 ± 0.15 versus etanercept and 0.39 ± 0.18 versus ustekinumab. The highest-value contribution was reported by the patients' group, followed by the clinical professionals and the decision makers. A fundamental element that explained the difference in the scoring between pathologies was the availability of therapeutic alternatives. The retest confirmed the consistency and replicability of the analysis. CONCLUSIONS: Under this methodology, and assuming similar economic costs per patient for both treatments, the results indicated that the overall value estimated of dupilumab for severe atopic dermatitis was similar to, or slightly higher than, that of secukinumab for moderate to severe plaque psoriasis.
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Anticuerpos Monoclonales , Toma de Decisiones Clínicas/métodos , Técnicas de Apoyo para la Decisión , Dermatitis Atópica/tratamiento farmacológico , Psoriasis/tratamiento farmacológico , Anticuerpos Monoclonales/economía , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados , Enfermedad Crónica , Humanos , Índice de Severidad de la Enfermedad , Resultado del TratamientoAsunto(s)
Trastornos del Desarrollo Sexual 46, XX/complicaciones , Hernia Diafragmática/complicaciones , Conductos Paramesonéfricos/anomalías , Trastornos del Desarrollo Sexual 46, XX/diagnóstico por imagen , Anomalías Múltiples/diagnóstico por imagen , Adolescente , Anomalías Congénitas/diagnóstico por imagen , Femenino , Hernia Diafragmática/diagnóstico por imagen , Humanos , Conductos Paramesonéfricos/diagnóstico por imagenRESUMEN
The high prevalence of psoriasis and the high spending on pharmaceuticals motivate a more evidence-based and cost-effective usage of biopharmaceuticals. A growing body of evidence exists that the implementation of therapeutic drug monitoring for biopharmaceuticals in psoriasis patients optimizes patient management and clinical outcome and enhances their efficacy. Therefore, the aim of this review was to give an overview of the literature on therapeutic drug monitoring of biopharmaceuticals in the treatment of psoriasis and to provide the useful information to dermatologists to improve health care in psoriasis patients.
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Productos Biológicos/sangre , Productos Biológicos/uso terapéutico , Monitoreo de Drogas/métodos , Psoriasis/sangre , Psoriasis/tratamiento farmacológico , Adalimumab/sangre , Adalimumab/uso terapéutico , Animales , Antiinflamatorios/sangre , Antiinflamatorios/uso terapéutico , Biofarmacia/métodos , Biofarmacia/tendencias , Monitoreo de Drogas/tendencias , HumanosRESUMEN
Aromatic antiepileptic drugs (AEDs) are among the drugs most frequently involved in severe cutaneous adverse reactions (SCARs), such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reactions with eosinophilia and systemic symptoms (DRESS). This study investigated the associations between the genetic polymorphisms of HLA class-I and AED-induced SCARs in the Spanish population. HLA class-I genotypes were determined in AED (phenytoin[PHT],lamotrigine[LTG],carbamazepine[CBZ],phenobarbital[PB])-induced SJS/TEN (n=15) or DRESS (n=12) cases included in the Spanish SCAR registry, PIELenRed. There were 3 control groups: (A)tolerant to a single AED, (B)tolerant to any AED, and (C)Spanish population controls. For SJS/TEN, concomitant HLA-A*02:01/Cw15:02 alleles were significantly associated with PHT-cases compared to control groups B and C [(B)odds ratio(OR):14.75, p=0.009;(C)OR:27.50, p<0.001], and were close to significance with respect to control group A (p=0.060). The genotype frequency of the HLA-B*38:01 was significantly associated with PHT-LTG-cases compared with the 3 groups of controls [(A)OR:12.86, p=0.012;(B)OR:13.81; p=0.002;(C)OR:14.35, p<0.001], and with LTG-cases [(A)OR:147.00, p=0.001;(B)OR:115.00, p<0.001;(C)OR:124.70, p<0.001]. We found the HLA-B*15:02 allele in a Spanish Romani patient with a CBZ-case. The HLA-A*11:01 was significantly associated with CBZ-cases [(A)OR:63.89, p=0.002;(B)OR:36.33, p=0.005;(C)OR:28.29, p=0.007]. For DRESS, the HLA-A*24:02 genotype frequency was statistically significant in the PHT-LTG-cases [(A)OR:22.56, p=0.003;(B)OR:23.50. p=0.001; (C)OR:33.25, p<0.001], and in the LTG-cases [(A),OR:49.00, p=0.015;(B)OR:27.77, p=0.005; (C)OR:34.53, p=0.002]. HLA-A*31:01 was significantly associated with the CBZ-cases [(A)OR:22.00, p=0.047;(B)OR:29.50, p=0.033;(C)OR:35.14, p=0.006]. In conclusion, we identified several significant genetic risk factors for the first time in the Spanish Caucasian population: HLA-A*02:01/Cw*15:02 combination as a risk factor for PHT-induced SJS/TEN, HLA-B*38:01 for LTG- and PHT- induced SJS/TEN, HLA-A*11:01 for CBZ-induced SJS/TEN, and HLA-A*24:02 for LTG- and PHT- induced DRESS. The strong association between HLA*31:01 and CBZ-DRESS in Europeans was confirmed in this study.
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Anticonvulsivantes/efectos adversos , Síndrome de Hipersensibilidad a Medicamentos/genética , Genes MHC Clase I/genética , Predisposición Genética a la Enfermedad/genética , Síndrome de Stevens-Johnson/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Síndrome de Hipersensibilidad a Medicamentos/etiología , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo Genético , Factores de Riesgo , España , Síndrome de Stevens-Johnson/etiología , Población Blanca/genética , Adulto JovenRESUMEN
AIM: We conducted a prospective evaluation of all eosinophilic drug reactions (EDRs) through the Prospective Pharmacovigilance Program from Laboratory Signals at Hospital to find out the incidence and distribution of these entities in our hospital, their causative drugs, and predictors. METHODS: All peripheral eosinophilia >700 × 106 cells l-1 detected at admission or during hospitalisation, were prospectively monitored over 42 months. The spectrum of the localised or systemic manifestation of EDR, the incidence, the distribution of causative drugs, and the predictors were analysed. RESULTS: The incidence of EDR was 16.67 (95% Poisson confidence interval [CI]: 9.90-25.98) per 10 000 admissions. Of 274 cases of EDR, 154 (56.2%) cases in 148 patients were asymptomatic hypereosinophilia. In the remaining 120 (43.8%) cases, there was other involvement. Skin and soft tissue reactions were detected in 36 (13.1%) cases; visceral EDRs in 19(7.0%) cases; and drug-induced eosinophilic cutaneous and visceral manifestations were detected in the remaining 65 (23.7%) cases, 64 of which were potential drug reaction with eosinophilia and systemic symptoms (DRESS). After adjusting for age, sex, and hospitalisation wards, predictors of symptomatic eosinophilia were earlier onset of eosinophilia (hazard ratio [HR], 10.49; 95%CI: 3.13-35.16) higher eosinophil count (HR, 8.51; 95%CI: 3.28-22.08), and a delayed onset of corticosteroids (HR, 1.34; 95%CI: 1.01-1.73). A higher eosinophil count in patients with DRESS was significantly associated with greater impairment of liver function, prolonged hospitalisation, higher cumulative doses of corticosteroids, and if hypogammaglobinaemia was detected, a reactivation of human-herpesvirus 6 was subsequently detected. CONCLUSIONS: Half (53.3%, 64/120 cases) of symptomatic EDRs were potential DRESS. The main predictor of severity of EDR was an early severe eosinophilia.