Prior drug allergies are associated with worse outcome in patients with idiosyncratic drug-induced liver injury: A machine learning approach for risk stratification.

The impact of prior drug allergies (PDA) on the clinical features and outcomes of patients who develop idiosyncratic drug-induced liver injury (DILI) is largely unknown. We aimed to assess the clinical presentation and outcomes of DILI patients based on the presence or absence of PDA and explore the association between culprit drugs responsible for DILI and allergy. We analysed a well-vetted cohort of DILI cases enrolled from the Spanish DILI Registry. Bootstrap-enhanced least absolute shrinkage operator procedure was used in variable selection, and a multivariable logistic model was fitted to predict poor outcomes in DILI. Of 912 cases with a first episode of DILI, 61 (6.7%) had documented PDA. Patients with PDA were older (p = 0.009), had higher aspartate aminotransferase (AST) levels (p = 0.047), lower platelet count (p = 0.011) and higher liver-related mortality than those without a history of drug allergies (11% vs. 1.6%, p < 0.001). Penicillin was the most common drug associated with PDA in DILI patients (32%). A model including PDA, nR-based type of liver injury, female sex, AST, total bilirubin, and platelet count showed an excellent performance in predicting poor outcome in patients from the Spanish DILI Registry (area under the ROC curve [AUC] 0.887; 95% confidence interval [CI] 0.794 - 0.981) and the LATINDILI Network (AUC 0.932; 95% CI 0.884 - 0.981). Patients with suspected DILI should be screened for PDA as they would require a close monitoring for early detection of worsening clinical course.

The Need for the Closer Monitoring of Novel Drugs in MS: A Siponimod Retrospective Cohort Study (Realhes Study).

BACKGROUND: Severe cases of lymphopenia have been reported during siponimod clinical trials, which may negatively impact its benefit/risk profile. OBJECTIVE: We aimed to evaluate the incidence of lymphopenia following the initiation of siponimod treatment in clinical practice. The secondary objectives included the analysis of factors predisposing to and the clinical relevance of lymphopenia events. METHODS: In this multicenter retrospective cohort study, information collected from the medical records of 129 patients with MS from 15 tertiary hospitals in Spain who initiated treatment with Siponimod were followed-up for at least 3 months, including at least one lymphocyte count evaluation per patient. RESULTS: Of the 129 patients, 121 (93.6%) reported lymphopenia events, including 110 (85.3%) with grade ≤ 3 and 11 (8.5%) with grade 4 lymphopenia, higher than those reported in the pivotal clinical trial (73.3% and 3.3% for grade ≤ 3 and grade 4 lymphopenia, respectively). The study included an unexpectedly high proportion of male subjects (72.9%), which might have led to an underestimation of the actual magnitude of the risk. CONCLUSIONS: In this study, the incidence and severity of lymphopenia after starting siponimod treatment were higher than those reported in previous clinical trials. Therefore, our results reinforce the need for the closer monitoring of novel MS drugs in clinical practice, as well as larger and longer follow-up studies to properly characterize this risk.

Clinical presentation, causative drugs and outcome of patients with autoimmune features in two prospective DILI registries.

BACKGROUND & AIMS: Idiosyncratic drug-induced liver injury (DILI) with autoimmune features is a liver condition with laboratory and histological characteristics similar to those of idiopathic autoimmune hepatitis (AIH), which despite being increasingly reported, remains largely undefined. We aimed to describe in-depth the features of this entity in a large series of patients from two prospective DILI registries. METHODS: DILI cases with autoimmune features collected in the Spanish DILI Registry and the Latin American DILI Network were compared with DILI patients without autoimmune features and with an independent cohort of patients with AIH. RESULTS: Out of 1,426 patients with DILI, 33 cases with autoimmune features were identified. Female sex was more frequent in AIH patients than in the other groups (p = .001). DILI cases with autoimmune features had significantly longer time to onset (p < .001) and resolution time (p = .004) than those without autoimmune features. Interestingly, DILI patients with autoimmune features who relapsed exhibited significantly higher total bilirubin and transaminases at onset and absence of peripheral eosinophilia than those who did not relapse. The likelihood of relapse increased over time, from 17% at 6 months to 50% 4 years after biochemical normalization. Statins, nitrofurantoin and minocycline were the drugs most frequently associated with this phenotype. CONCLUSIONS: DILI with autoimmune features shows different clinical features than DILI patients lacking characteristics of autoimmunity. Higher transaminases and total bilirubin values with no eosinophilia at presentation increase the likelihood of relapse in DILI with autoimmune features. As the tendency to relapse increases over time, these patients will require long-term follow-up.

Potential benefit and lack of serious risk from corticosteroids in drug-induced liver injury: An international, multicentre, propensity score-matched analysis.

BACKGROUND: The use of corticosteroids to treat patients with idiosyncratic drug-induced liver injury (DILI) relies on empirical clinical decisions. AIM: To investigate the relationship between corticosteroids and risk of acute liver failure (ALF) in patients with DILI and to assess if corticosteroid therapy was associated with improved outcomes in DILI patients. METHODS: We analysed bona fide idiosyncratic DILI cases from the Spanish DILI Registry and Indiana University School of Medicine. Patients treated with corticosteroids were compared to those who did not receive any treatment. Nearest neighbour propensity score matching analyses were conducted. RESULTS: We enrolled 724 patients, 106 under corticosteroid therapy, in whom there was over-representation of more severe injury and autoimmune features, and 618 who did not receive any treatment. In an analysis of 80 pairs of propensity score-matched patients, corticosteroid administration was not associated with an increased risk of developing ALF (odds ratio = 0.65; 95% confidence interval [CI]: 0.18-2.40; p = 0.518). Furthermore, in an additional analysis, a Cox regression model that included 41 propensity score-matched pairs showed that patients receiving corticosteroids had a significantly higher normalisation rate of liver enzymes than untreated patients (hazard ratio [HR] = 1.84; 95% CI: 1.02-3.32; p = 0.043), particularly in patients with serious injury who did not resolve within 30 days (HR = 2.79; 95% CI: 1.20-6.50; p = 0.018). CONCLUSION: Corticosteroid therapy did not worsen outcome in DILI patients. Indeed, corticosteroid administration was associated with a greater rate of normalisation of liver enzymes in patients with serious DILI.

Lesiones melanocíticas en el pie. Diagnóstico diferencial / Differential diagnostic

El melanoma maligno es una de las principales causas de muerte entre el cáncer de piel en adultos jóvenes. Su incidencia esta incrementándose dramáticamente. El control de los factores de riesgo, así como un diagnóstico precoz, son fundamentales para el pronóstico de este tipo de lesiones. La exposición a las radiaciones solares, las quemaduras solares, el fototipo de la piel y la existencia de múltiples nevus atípicos son algunos de los factores que intervienen en su etiopatogenia. Ante la presencia de una lesión pigmentada en la piel, ya sea desde el nacimiento o de nueva aparición, deberemos tener en cuenta una serie de parámetros clínicos, como la regla ABDCE, que serán muy importante en el diagnóstico precoz, así como una historia clínica integral. Los nevus, las lesiones melanocíticas precancerosas y los diferentes tipos de melanomas descritos son abordados en este artículo (AU)

Duplicidad ungueal: a propósito de un caso

El propósito de este artículo es mostrar la opción terapéutica adoptada en un caso clínico de una malformación congénita de duplicidad ungueal; a la vez que mostrar una revisión de las afecciones, que al igual que la duplicidad ungueal, cursan con la aparición de dos uñas completas en un mismo dedo.Para realizar un diagnóstico diferencial entre la polisindáctilia, la polioniquia y la duplicidad ungueal el examen de la estructura ósea resulta imprescindible, la aparición de elementos óseos duplicados en todo el dedo, caracterizaría la polisindactília; la existencia de falanges distales bífidas o bipartitas sería característico de la polioniquia y la ausencia de elementos óseos supernumerarios el determinante de la duplicidad ungueal, si bien muchos autores denominan la aparición de uñas supernumerarias polioniquia sin realizar diferenciación. Por ello mostramos el análisis de las radiografías realizadas en el caso clínico, que resultaron concluyentes para el diagnóstico definitivo. La aparición de dos unidades ungueales completas, lateralizadas hacía los bordes medial y lateral del segundo dedo del pie derecho, producía una deformidad en el dedo desde el nacimiento. A pesar de que el paciente asistió por primera vez a consulta a los 15 meses de edad, optamos por esperar 6 meses para analizar si alguna de las dos unidades ungueales adoptaba una posición dorsal y un mayor tamaño para realizar las funciones biomecánicas de la uña. El buen resultado en un caso tratado con anterioridad, en el que existía la misma deformidad, fue determinante para realizar una resección total de la uña situada en el borde lateral y al mismo tiempo realizar una resección de los tejidos circundantes, que dotaban al dedo de mayor volumen en la zona distal. Los objetivos de la intervención eran restablecer la función biomecánica de la uña, posibilitar el uso de calzado normal, mejorar la estética del pie y prevenir futuras afecciones. El resultado de la intervención quirúrgica fue satisfactorio, sin embargo la lateralización hacia medial de la única uña existente y la ausencia de osificación de la falange distal nos hacen prever la necesidad de aplicación de tratamientos quiropodológicos y ortopodológicos en un futuro (AU)