Pathogenesis and clinical approaches to anticonvulsant hypersensitivity syndrome: current state of knowledge.

Anticonvulsant hypersensitivity syndrome (AHS) is a rare, but severe and potentially fatal, adverse reaction that occurs in patients who are treated with commonly used older anticonvulsant drugs (phenytoin, carbamazepine and phenobarbital) and/or with some newer agents (lamotrigine). Paediatric patients are at an increased risk for the development of AHS for the higher incidence of seizure disorder in the first decade of life. Hypersensitivity reactions range from simple maculopapular skin eruptions to a severe life-threatening disorder. AHS is typically associated with the development of skin rash, fever and internal organ dysfunctions. Recent evidence suggests that AHS is the result of a chemotoxic and immunologically-mediated injury, characterized by skin and mucosal bioactivation of antiepileptic drugs and by major histocompatibility complex-dependent clonal expansion of T cells. Early recognition of AHS and withdrawal of anticonvulsant therapy are essential for a successful outcome. In vivo and vitro tests can be helpful for the diagnosis that actually depends essentially on clinical recognition

FeNO as a Marker of Airways Inflammation: The Possible Implications in Childhood Asthma Management

The aim of this study was to verify FeNO usefulness, as a marker of bronchial inflammation, in the assessment of therapeutic management of childhood asthma. We performed a prospective 1-year randomized clinical trial evaluating two groups of 32 children with allergic asthma: “GINA group”, in which therapy was assessed only by GINA guidelines and “FeNO group”, who followed a therapeutic program assessed also on FeNO measurements. Asthma Severity score (ASs), Asthma Exacerbation Frequency (AEf), and Asthma Therapy score (ATs) were evaluated at the start of the study (T1), 6 months (T2), and 1 year after (T3). ASs and AEf significantly decreased only in the FeNO group at times T2 and T3 (p[T1-T2] = 0.0001, and p[T1-T3] = 0.01; p[T1-T2] = 0.0001; and p[T1-T3] < 0.0001, resp.). After six months of follow-up, we found a significant increase of patients under inhaled corticosteroid and/or antileukotrienes in the GINA group compared to the FeNO group (P = .02). Our data show that FeNO measurements, might be a very useful additional parameter for management of asthma, which is able to avoid unnecessary inhaled corticosteroid and antileukotrienes therapies, however, mantaining a treatment sufficient to obtain a meaningful improvement of asthma

Applicazione clinica e studio di proteomica plasmatica in pazienti con insufficienza epatica in trattamento extracorporeo con il sistema FPSA (PROMETHEUS)

Liver transplantation has become the standard treatment for patients with terminal liver failure. The different forms of liver injury (acute, subacute, acute on chronic, chronic) are characterized by high mortality rates. The natural course of chronic liver injury is often complicated by acute episodes of potentially reversible decompensation, triggered by a sudden event such as infection or gastrointestinal bleeding. These episodes are defined as acute on chronic liver injury. The willingness to carry out transplants is limited by the shortage of organs resulting in longer waiting times for patients on the transplant list. In 2002, in Western Europe, more than 4,000 liver transplants were made, and the waiting list were more than 5000 patients. The extracorporeal liver support therapies have the aim of preparing the patient for transplantation and provide two different approaches: a biological one and non-organic one type. While biological approaches use hepatocytes or a whole organ (both animal and human), non-biological ones use filtration dialytic techniques and sorption. The aim of our study is to evaluate clinical efficacy of the Prometheus system liver for detoxification, improvement of the indices of nitrogen retention and improvement of the MELD score. We have dealt, with the Prometheus system, 7 patients with acute liver failure, we studied consecutively, for a total of 18 treatments. Primary outcome of treatment with the Prometheus system is to achieve optimal serum bilirubin levels. Was estimated plasma concentration of cytokines in patients treated with the Bio-Plex Suspension Array System. Our experience has confirmed that the Prometheus, while causing achieving the primary outcome to get a significant reduction in serum bilirubin, it does not affect the mortality of patients with terminal liver disease but must be viewed as an important tool in preparation for liver transplantation. The trend of plasma concentrations of cytokines measured by us showed that the prolongation of therapy involves the modulation of a greater number of cytokines, in particular the down-regulation of pro-inflammatory ones, such as IP10, IL-6, IL-8, PDGF bb and RANTES accompanied by a decrease in apoptosis. The system optimization and further results, still being processed, could be developed on two fronts: · Implementation of knowledge on the pathophysiological mechanisms that relate to the inflammatory process metabolic decompensation in the course of acute liver failure from chronic liver disease · Final implementation of the Prometheus system as a bridge to liver transplantation in face of increasingly significant mismatch between the pool of available donors and the number of waiting list patients for liver transplantationIl trapianto di fegato è diventato il trattamento standard per pazienti con insufficienza epatica terminale. Le differenti forme di danno epatico (acuto, subacuto, acuto su cronico, cronico) sono caratterizzate da alti tassi di mortalità. Il corso naturale del danno epatico cronico è complicato spesso da episodi acuti di scompenso, potenzialmente reversibili, innescati da un evento improvviso quale un’infezione o un sanguinamento gastrointestinale, episodi che vengono definiti come danno epatico acuto su cronico. La disponibilità ad effettuare i trapianti è limitata dalla scarsa disponibilità di organi con conseguente allungamento dei tempi d’attesa per i pazienti in lista di trapianto. Nel 2002 sono stati effettuati, in Europa occidentale, oltre 4000 trapianti di fegato e in lista d’attesa erano presenti più di 5000 pazienti. Le terapie di supporto epatico extracorporeo hanno la scopo di preparare il paziente al trapianto e prevedono due diversi approcci: uno di tipo biologico e uno di tipo non biologico. Mentre quelli di tipo biologico utilizzano epatociti o l’organo intero (sia di origine animale che umana), quelli non biologici utilizzano tecniche dialitiche di filtrazione e adsorbimento. Lo scopo del nostro studio è la valutazione dell’efficacia clinica del sistema Prometheus per la detossificazione epatica, il miglioramento degli indici di ritenzione azotata e miglioramento del MELD score. Abbiamo trattato con il sistema Prometheus 7 pazienti con insufficienza epatica acuta, consecutivamente giunti alla nostra osservazione, per un totale di 18 trattamenti. Outcome primario dei trattamenti con il sistema Prometheus consiste nel raggiungimento di valori sierici di bilirubina ottimali. E’ stata valutata la concentrazione plasmatica delle citochine nei pazienti trattati con il sistema Bio-Plex Suspension Array System. La nostra esperienza ha confermato che il sistema Prometheus, pur determinando il raggiungimento dell’outcome primario di ottenere una importante riduzione dei livelli sierici di bilirubina, non incide sulla mortalità dei pazienti epatopatici terminali ma va considerato come un importante strumento di preparazione al trapianto di fegato. L’andamento delle concentrazioni plasmatiche delle citochine da noi dosate ha evidenziato che il prolungamento della terapia comporta la modulazione di un numero maggiore di citochine, in particolare la down-regolazione di quelle pro-infiammatorie, come IP10, IL-6, IL-8, PDGF bb e RANTES accompagnata da una diminuzione della apoptosi. La ottimizzazione del sistema e gli ulteriori risultati ancora in fase di elaborazione potranno svilupparsi su due fronti: - implementazione delle conoscenze sui meccanismi fisiopatologici che correlano il processo flogistico allo scompenso metabolico in corso di insufficienza epatica acuta da epatopatia cronica - applicazione definitiva del Sistema Prometheus come bridge al trapianto epatico, a fronte del sempre più rilevante mismatch tra il pool dei donatori disponibili e il numero dei pazienti in lista in attesa di trapianto epatico

Anticonvulsant drugs and hematological disease

Many antiepileptic drugs (AEDs) are associated with hematological disorders that range from mild thrombocytopenia or neutropenia to anemia, red cell aplasia, until bone marrow failure. Fortunately, potentially fatal hematological disorders such as aplastic anemia are very rare. This review investigates hematological effects associated with classic and newer AEDs: a PubMed search indexed for MEDLINE was undertaken to identify studies in adults, children and animals using the name of all anticonvulsant drugs combined with the terms "hematological disease" and "hematological abnormalities" as key words. The most common hematological alterations occur with older AEDs than newer. Indeed, careful hematological monitoring is needed especially using carbamazepine, phenytoin and valproic acid. The pathogenetic mechanisms are still unknown: they seem to be related to an immunological mechanism, but drugs pharmacokinetics and pharmacodynamics interactions may also play an important role. Further research is needed to assess the real pathogenetic mechanism at the basis of hematological complications caused by AEDs. © 2014 Springer-Verlag

Topiramate-induced weight loss: a review.

BACKGROUND: Weight loss can occur during topiramate (TPM) treatment and it should be evaluated by clinicians, especially in children, whose growth could be compromised. In international literature, the reported body weight loss incidences linked to TPM therapy vary widely and, in some cases, are very conflicting. AIMS: The aims of this review are to quantify TPM-induced weight loss, analyze the pathogenetic mechanisms and evaluate its clinical implications in patients with epilepsy. RESULTS: The amount of weight loss appears to be related to some factors such as the duration of the treatment and a high baseline body mass index (BMI), while the role of daily dosage and gender of patients is controversial. The mechanism through which TPM may induce weight loss is still unclear. INTERPRETATION: TPM is able to induce weight loss, especially in high baseline BMI patients, not strictly depending on daily dosage and perhaps not influenced by gender. This makes TPM a good choice, especially in obese patients suffering from seizures. However, TPM can make nutritionally vulnerable children or adult patients, with epilepsy associated with other neuropsychiatric diseases, who cannot voluntarily increase their caloric intake