76-godišnji bolesnik s legionarskom bolesti i osipom: prikaz slučaja

Legionella pneumophila is an important cause of atypical community- acquired pneumonia. Legionnaires’ disease usually manifests with high-grade fever and nonproductive cough, while the presence of diarrhoea, neurologic symptoms, hyponatremia and failure to respond to beta-lactam antibiotics can provide clues to diagnosis of Legionnaires\u27s disease. Cutaneous lesions in Legionnaires\u27 disease are very rare – a rash associated with the clinical manifestation of Legionella infection was described and evaluated in 10 cases according to literature. Herein we present a 76-year-old patient treated at the University Hospital for Infectious Diseases in Zagreb, Croatia because of Legionnaires\u27 disease and a petechial rash.Legionella pneumophila je važan uzročnik atipične domicilne pneumonije. Legionarska bolest najčešće se manifestira febrilitetom i suhim kašljem, a prisutnost dijareje, neuroloških manifestacija poput smetenosti, hiponatremije te neuspjeha terapije betalaktamskim antibioticima može uputiti na dijagnozu legionarske bolesti. Kožne manifestacije legionarske bolesti su izuzetno rijetke te je do sada opisano 10 takvih slučajeva u literaturi. U ovom smo radu prikazali 76-godišnjeg bolesnika s legionarskom bolesti koji je hospitaliziran u Klinici za infektivne bolesti zbog legionarske bolesti praćene petehijalnim osipom

TREATMENT GUIDELINES FOR PATIENTS WITH GENOTYPE 1 CHRONIC HEPATIS C INFECTION

Standard liječenja kroničnog hepatitisa C genotipa 1 do 2011. godine bila je kombinacija pegiliranog interferona-alfa 2a ili 2b (PEG IFN-α2) i ribavirina. Slijedom odobrenja novih, učinkovitijih lijekova tzv. prve generacije inhibitora virusnih proteaza boceprevira i telaprevira za kliničku primjenu u Europi i SAD-u 2011. g., postoji potreba osuvremenjivanja nacionalnih smjernica za liječenje kroničnog hepatitisa C genotipa 1 u Hrvatskoj. Pri donošenju novih preporuka za liječenje kroničnog hepatitisa C genotipa 1 u Hrvatskoj uzeli smo u obzir rezultate registracijskih studija za boceprevir i telaprevir, postojeće nacionalne smjernice u EU (Velika Britanija, Švedska, Njemačka, Francuska i Italija), preporuke EASL i AASLD te vlastita iskustva u dosadašnjem liječenju bolesnika s kroničnim hepatitisom C genotipa 1 dvojnom terapijom. U tekstu su navedene preporuke za prethodno neliječene kao i liječene bolesnike prema vrsti prethodnog virološkog odgovora. Kod neliječenih bolesnika s niskim stadijem fibroze, te povoljnim prediktorima virološkog odgovora preporuča se nadalje liječenje dvojnom terapijom. Liječenje trojnom terapijom preporuča se za neliječene bolesnike s visokim stadijem fibroze (F3 i F4), kao i one s umjerenim stadijem fibroze (F2) i kombinacijom nepovoljnih prediktora za izliječenje dvojnom terapijom (stariji >40 godina, non-CC IL28B genotip, non-RVR). U skupini prethodno liječenih bolesnika trojna terapija se preporuča za relapsere bez obzira na stadij fibroze, parcijalne respondere s visokim stadijem fibroze (F3 i F4), te individualni pristup u primjeni trojne terapije za nul-respondere.Dual therapy based on the combination of pegylated interferon-alpha 2a or 2b (PEG IFN-α2) and ribavirin has been considered standard-of-care treatment for chronic hepatitis C genotype 1 up to 2011. The first generation of protease inhibitors, boceprevir and telaprevir, have been approved for clinical use in Europe and USA since 2011. Therefore, national guidelines for the treatment of chronic hepatitis C genotype 1 have been updated to include new and more efficient therapeutic options. Croatian guidelines are based on the results of registration clinical trials for boceprevir and telaprevir, national guidelines of several EU countries (United Kingdom, Sweden, Germany, France and Italy), EASL and AASLD recommendations, as well as on the results of chronic hepatitis C genotype 1 treatment with dual therapy at the national level. The Croatian guidelines include recommendations for treatment-naïve and treatment-experienced patients (based on the type of virologic response to the first-line treatment). In treatment-naïve patients with mild fibrosis and favorable predictors of treatment outcome, dual therapy is the recommended treatment option. In treatment-naïve patients with advanced fibrosis (F3 and F4) as well as in patients with moderate fibrosis (F2) and unfavorable predictors of treatment outcome (age >40 years, non-CC IL-28B genotype, non-RVR), triple therapy is recommended. Triple therapy is also recommended for relapsers (irrespective of fibrosis stage) and partial responders with advanced fibrosis (F3 and F4). Lead-in treatment strategy during triple therapy is recommended for null-responders

TREATMENT GUIDELINES FOR PATIENTS WITH GENOTYPE 1 CHRONIC HEPATIS C INFECTION

Standard liječenja kroničnog hepatitisa C genotipa 1 do 2011. godine bila je kombinacija pegiliranog interferona-alfa 2a ili 2b (PEG IFN-α2) i ribavirina. Slijedom odobrenja novih, učinkovitijih lijekova tzv. prve generacije inhibitora virusnih proteaza boceprevira i telaprevira za kliničku primjenu u Europi i SAD-u 2011. g., postoji potreba osuvremenjivanja nacionalnih smjernica za liječenje kroničnog hepatitisa C genotipa 1 u Hrvatskoj. Pri donošenju novih preporuka za liječenje kroničnog hepatitisa C genotipa 1 u Hrvatskoj uzeli smo u obzir rezultate registracijskih studija za boceprevir i telaprevir, postojeće nacionalne smjernice u EU (Velika Britanija, Švedska, Njemačka, Francuska i Italija), preporuke EASL i AASLD te vlastita iskustva u dosadašnjem liječenju bolesnika s kroničnim hepatitisom C genotipa 1 dvojnom terapijom. U tekstu su navedene preporuke za prethodno neliječene kao i liječene bolesnike prema vrsti prethodnog virološkog odgovora. Kod neliječenih bolesnika s niskim stadijem fibroze, te povoljnim prediktorima virološkog odgovora preporuča se nadalje liječenje dvojnom terapijom. Liječenje trojnom terapijom preporuča se za neliječene bolesnike s visokim stadijem fibroze (F3 i F4), kao i one s umjerenim stadijem fibroze (F2) i kombinacijom nepovoljnih prediktora za izliječenje dvojnom terapijom (stariji >40 godina, non-CC IL28B genotip, non-RVR). U skupini prethodno liječenih bolesnika trojna terapija se preporuča za relapsere bez obzira na stadij fibroze, parcijalne respondere s visokim stadijem fibroze (F3 i F4), te individualni pristup u primjeni trojne terapije za nul-respondere.Dual therapy based on the combination of pegylated interferon-alpha 2a or 2b (PEG IFN-α2) and ribavirin has been considered standard-of-care treatment for chronic hepatitis C genotype 1 up to 2011. The first generation of protease inhibitors, boceprevir and telaprevir, have been approved for clinical use in Europe and USA since 2011. Therefore, national guidelines for the treatment of chronic hepatitis C genotype 1 have been updated to include new and more efficient therapeutic options. Croatian guidelines are based on the results of registration clinical trials for boceprevir and telaprevir, national guidelines of several EU countries (United Kingdom, Sweden, Germany, France and Italy), EASL and AASLD recommendations, as well as on the results of chronic hepatitis C genotype 1 treatment with dual therapy at the national level. The Croatian guidelines include recommendations for treatment-naïve and treatment-experienced patients (based on the type of virologic response to the first-line treatment). In treatment-naïve patients with mild fibrosis and favorable predictors of treatment outcome, dual therapy is the recommended treatment option. In treatment-naïve patients with advanced fibrosis (F3 and F4) as well as in patients with moderate fibrosis (F2) and unfavorable predictors of treatment outcome (age >40 years, non-CC IL-28B genotype, non-RVR), triple therapy is recommended. Triple therapy is also recommended for relapsers (irrespective of fibrosis stage) and partial responders with advanced fibrosis (F3 and F4). Lead-in treatment strategy during triple therapy is recommended for null-responders

Paraneoplastički neurološki sindrom uz karcinom bubrega – dijagnostički zavaravajuća smrt miša

Neurologic symptoms secondary to a paraneoplastic syndrome (PNS) may be the presenting manifestation of a previously undiagnosed cancer. This case highlights the potential complexity of the PNS associated with renal cell carcinoma, confusion and delay of diagnosis due to positive mouse bioassay, latter presentation as encephalitic syndrome, positive outcome associated with initial treatment with total plasma exchange, as well as absence of recurrence of neurologic symptoms after complete surgical removal of tumor.Neurološki simptomi mogu predstavljati i paraneoplastički sindrom (PNS) uslijed nedijagnosticiranog tumora. Ovaj prikaz bolesnika ističe potencijalnu složenost PNS-a povezanog s karcinomom bubrega, zabunu i kašnjenje dijagnoze zbog pozitivnog biološkog testa na mišu, kliničku prezentaciju u obliku sindroma encefalitisa, pozitivnog ishoda povezanog s početnim liječenjem plazmaferezom, kao i odsutnost recidiva neuroloških simptoma nakon potpunog kirurškog uklanjanja tumora

Liječenje starijih bolesnika s kroničnim hepatitisom C: retrospektivno kohortno istraživanje

The prevalence of chronic hepatitis C increases in elderly patients. The aims of this study were to identify the factors associated with hepatocellular carcinoma (HCC) and end-stage liver disease development and to evaluate the efficacy and safety of pegylated interferon (PEG-IFNα) plus ribavirin (RBV) therapy in elderly patients. A retrospective cohort study included all consecutive patients with hepatitis C virus (HCV) infection treated with PEG-IFNα+RBV between 2003 and 2013. Elderly patients had a higher frequency of poor prognostic factors including genotype 1 infection, high fibrosis, and high fibrosis index based on four factors (FIB-4) score. The sustained virologic response (SVR) rate for genotype 1 was significantly lower (35.8% vs. 57.1%), while the frequency of PEG-IFNα (27.2% vs. 7.8%), RBV dose reduction (19.6% vs. 9.7%) and treatment discontinuation (13.0% vs. 4.1%) was significantly higher in elderly patients. However, age was not associated with SVR in multivariate analysis, and comparable SVR rates were achieved when adjusted for fibrosis score (Ishak ≤3: 66.7% vs. 69.8%). During the follow-up, HCC was diagnosed in 18 elderly patients (3 SVR+, 4 SVR- and 9 untreated patients). In conclusion, selected elderly patients can achieve comparable SVR rates as younger patients, but with a higher rate of side effects. Since complications of HCV infection occur more frequently in elderly patients, they should be given priority for antiviral therapy.Učestalost kroničnog hepatitisa C (KHC) raste u starijim dobnim skupinama. Ciljevi ovoga istraživanja bili su utvrditi čimbenike povezane s razvojem hepatocelularnog karcinoma (HCC) i dekompenzirane jetrene bolesti te procijeniti učinkovitost i sigurnost terapije pegiliranim interferonom (PEG-IFNα) i ribavirinom (RBV) u starijih bolesnika. Retrospektivna kohortna studija je uključila sve bolesnike s KHC koji su liječeni PEG-IFNα + RBV između 2003. i 2013. godine u Klinici za infektivne bolesti “Dr. Fran Mihaljević”. Bolesnici u dobi od >65 godina češće su imali nepovoljne prognostičke čimbenike, tj. HCV-1 genotip, uznapredovali stadij fibroze i viši zbir indeksa fibroze zasnovan na četiri čimbenika (fibrosis index based on four factors, FIB-4). Trajni virusološki odgovor (sustained virologic response, SVR) je bio značajno niži (35,8% prema 57,1%), dok je učestalost smanjenja doze PEG-IFNα (27,2% prema 7,8%), RBV (19,6% prema 9,7%) i prekida liječenja (13,0% prema 4,1%) bila značajno češća u starijih bolesnika. Dob nije bila povezana sa SVR u multivarijatnoj analizi, a stariji bolesnici su imali podjednaki SVR kao i mlađi bolesnici ovisno o stadiju fibroze (Ishak ≤3: 66,7% prema 69,8%). Tijekom praćenja HCC je dijagnosticiran u 18 bolesnika u dobi od >65 godina (3 SVR+, 4 SVR-, 9 neliječenih). Zaključno, stariji bolesnici imaju podjednaku vjerojatnost postizanja SVR kao i mlađi, ali uz češće nuspojave. Budući da se komplikacije infekcije virusom hepatitisa C češće javljaju u ovoj populaciji, stariji bolesnici trebaju imati prednost u primjeni antivirusne terapije

Treatment of chronic hepatitis C in Croatian war veterans: experiences from Croatian reference center for viral hepatitis

Aim. To examine the risk factors, comorbidity, severity of liver disease, treatment course, and outcome in Croatian war veterans with chronic hepatitis C, especially those suffering from posttraumatic stress disorder (PTSD). ----- Methods. We collected medical records of 170 adult men diagnosed with chronic hepatitis C who started treatment with a combination of pegylated interferon-alpha and ribavirin between January 2003 and June 2009 at the Croatian Reference Centre for Viral Hepatitis. ----- Results. Participants' mean age was 43±9 years. Among 170 participants, there were 37 war veterans (22%). The main risk factor in veteran patients were operative procedures with transfusions (46% vs 5% in non-veterans; P<0.001) and in non-veteran patients intravenous drug use (42.1% vs 13%; P<0.001). The average duration of infection was longer in war veterans (14.5±3.4 vs 12.2±7.2 years; P=0.020). The percentage of PTSD comorbidity in the whole group was 11% (18/170) and in the war veterans group 49% (18/37). The prevalence of sustained virological response in patients with PTSD was 50% and in patients without PTSD 56%. Treatment reduction in patients with PTSD (33%) was higher than in patients without PTSD (12%; P=0.030). ----- Conclusion. Croatian war veterans are a group with high risk of chronic hepatitis C infection because many of them were wounded during the Croatian War 1991-1995. Considerations about PTSD as a contraindication for interferon treatment are unjustified. If treated, patients with PTSD have an equal chance of achieving sustained virological response as patients without PTSD