Clinical characteristics of hospitalized adults and adolescents with herpes zoster in Croatia: more than 20 years of a single-center experience.

AIM: To evaluate the clinical characteristics of adult and adolescent Croatian patients hospitalized for herpes zoster over a period of 21 years in the largest national center for infectious diseases (catchment area approximately 25% of the Croatian population). METHODS: This retrospective chart review included all patients older than 15 years hospitalized for herpes zoster at the University Hospital for Infectious Diseases "Dr. Fran Mihaljevic" between January 1, 1996 and December 31, 2016. RESULTS: The study enrolled 1755 patients (uniform annual hospitalizations), 50% of whom suffered from complicated forms of herpes zoster, mostly generalized zoster (22.0%), infected lesions (14.8%), and meningitis/encephalitis (10.4%). A low percentage of patients experienced Ramsey-Hunt syndrome (3.0%), keratitis (1.5%), and visceral dissemination (0.2%). The majority of patients were older than 55 years (80%, median 70 years). Overall, 61.6% of patients suffered from at least one comorbidity (most frequent: diabetes 14.6%, cardiovascular incidents 24.4%, malignancy 13.0%, other infection 12.9%), and 28.2% suffered from ≥2 comorbidities. All-cause in-hospital mortality was 0.9%. The proportion of patients with any complicated form and of patients with meningitis/encephalitis steadily decreased over time, while the proportion of patients with comorbidities increased. This coincided also with steadily increasing age. No association was observed between comorbidities and complicated forms of zoster. Pharmacological immunosuppression was associated with generalized zoster; younger age was associated with meningitis/encephalitis; and older age was associated with generalized zoster and infected lesions. CONCLUSION: The patients most frequently hospitalized for herpes zoster are elderly people burdened with comorbidities, not necessarily patients with complicated forms of the disease.

A case report of severe recurrent varicella in an ankylosing spondylitis patient treated with adalimumab - a new side effect after 15 years of usage.

BACKGROUND: Tumor necrosis factor-α (TNF-α) antagonists, most of which are monoclonal antibodies, became a widespread treatment for autoimmune diseases such as rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel diseases, psoriasis, psoriatic arthritis, hidradenitis suppurativa and uveitis. Their use is based on the blockage of TNF-α, which plays an important role in granulomas formation, development of phagosomes, activation and differentiation of macrophages, immune response against viral pathogens. The multiple adverse effects of TNF-α inhibition have been identified, including a two-to four-fold increased risk of active tuberculosis and other granulomatous conditions and an increased occurrence of some other serious bacterial, fungal and certain viral infections. CASE PRESENTATION: A 34-year-old male patient with disseminated varicella and pneumonitis was admitted to our hospital. The diagnosis of varicella was established serologically by enzyme immunoassay (EIA) and by polymerase chain reaction confirmation of the virus in vesicular fluid. The patient has been receiving adalimumab and methotrexate for the last 3 years due to ankylosing spondylitis and was seropositive to varicella zoster virus prior to the introduction of TNF-α antagonists. Acyclovir was administered for 10 days with the resolution of clinical illness and radiological signs of pneumonitis. CONCLUSION: Due to the use of biological agents, particularly TNF-α inhibitors, as a well-established therapy for some autoimmune diseases, new potential adverse events can be expected in the future and we wanted to point out one of them. To our knowledge this is the first case of recurrent disseminated varicella in a patient taking TNF-α antagonists.

Albendazolesulphoxide concentrations in plasma and hydatid cyst and prediction of parasitological and clinical outcomes in patients with liver hydatidosis caused by Echinococcus granulosus.

AIM: To investigate the relationship between plasma and cyst concentrations of albendazolesulphoxide (ASO) and their effects on parasitological findings and disease recurrence in patients with liver hydatidosis. METHODS: The study was conducted at the University Hospital for Infectious Diseases Dr. Fran Mihaljevic, Zagreb, Croatia, between August 2006 and January 2011. Consecutive patients (N=48, age 6-77 years) were treated with albendazole (3×5 mg/kg/d) over 28 days before surgical cyst removal (n=34) or percutaneous evacuation (PAIR) (n=14). Plasma ASO was determined on days 10 and 28 of treatment and cyst concentrations at surgery/PAIR. RESULTS: Disease recurred in 3 surgically treated patients. Variability of ASO concentrations was substantial. Plasma concentrations on day 10 were higher than on day 28 (geometric means ratio [GMR] 2.00; 95%CI 1.38-2.91, P<0.001) and higher than cyst concentrations at the time of treatment (GMR=1.58, 1.01-2.34, P=0.045). Higher cyst (but not plasma) concentrations were independently associated with lower odds of protoscolex motility (OR=0.23, 0.01-0.70, P<0.001) and higher odds of protoscolex destruction (OR=1.17, 1.04-1.46, P<0.001). With adjustment for age and protoscolex motility, higher day 10 plasma concentrations (but not cyst concentrations) were associated with lower odds of disease recurrence (OR=0.49, 0.09-0.97, P=0.035). Plasma concentrations did not predict cyst concentrations. CONCLUSION: Viability of protoscolices progressively decreased with increasing ASO concentrations in the cyst. Data strongly suggested that higher plasma concentrations reduced the risk of disease recurrence.

Parental administration of antipyretics to children with upper respiratory tract infections without consultation with a physician.

AIM: To evaluate the administration of antipyretics to children with upper respiratory tract infections (URTI) by their parents or guardians without consultation with physicians, and compare epidemiological and clinical characteristics of patients who received antipyretics and of untreated patients. METHODS: A prospective observational study was performed in three pediatric clinics in Zagreb, Croatia, from March to June 2002. A total of 171 children aged from 2 to 14 years with symptoms and signs of URTI lasting more than 2 days and fever above 38 °C lasting more than 2 days were included in the study. Data were collected on the usage of antipyretics, patients' demographic and epidemiological characteristics, and clinical signs and symptoms. RESULTS: Antipyretics, predominantly paracetamol, were used in 29.8% of patients. Their usage was less frequent in children attending day-care centers (49% of treated and 70% of untreated children, P = 0.014) and in children with reiterated URTIs (33.3% of treated and 55.8% of untreated children, P = 0.008). However, it was more frequent in children with recent URTIs in the family (33.3% of treated and 7.5% of untreated children, P < 0.001). Overall, most clinical signs and symptoms of URTI were notably less pronounced in patients treated with antipyretics. CONCLUSIONS: Antipyretics use correlated with less pronounced clinical signs and symptoms of infection, which indicates their anti-inflammatory activity, but also with negative effects such as lethargy. It is necessary to educate parents on the positive and negative aspects of antipyretics use and on the optimal choice of an antipyretic drug.

[Relapsing polychondritis--case report]. / Ponavljani polihondritis--prikaz bolesnika.

Relapsing polychondritis (RP) is a rare systemic inflammatory disease in which recurrent episodes of cartilage inflammation result in destruction of ears, nose and tracheobronchal tract. The joints, eyes, audiovestibular system and cardiovascular system can also be involved. About 30% of patients with RP have coexisting autoimmune disease, or malignant disease like colon, breast, and lung carcinoma, or malignant lymphoma. Pathogenesis is still unknown, and there is no consistent laboratory parameter specific for RP, which makes the diagnosis mainly clinical. Glucocorticoids are a mainstay of medical treatment of RP, whereas newer studies show positive effects of biological therapy. The course of RP is characterized by recurrent episodes of cartilage inflammation, and the prognosis has been recently improved because of improved medical and surgical treatment. We present a case of a patient with RP who was diagnosed 1 month after the development of first symptoms and responded well to glucocorticoid therapy.

Unusual presentations of actinomycosis: a case series and literature review.

INTRODUCTION: To review unusual actinomycosis cases that appeared as a diagnostic and therapeutic challenge at our institution and to present a literature review on the usual clinical presentations. METHODOLOGY: This retrospective review included all patients hospitalized for actinomycosis in a 10-year period at the University Hospital for Infectious Diseases "Dr. Fran Mihaljevic", Zagreb, Croatia. RESULTS: A total of 15 patients were hospitalized during the observed period, 9 (60%) females and 6 (40%) males. The localizations of actinomycosis were: pelvis (5), lungs (3), blood stream (2), colon (1), penis (1), stomach (1), skin (1), cervicofacial region (1). We present four unusual cases: subcutaneous actinomycotic abscess, actinomycosis of the stomach with underlying non-Hodgkin lymphoma, sepsis due to Actinomyces neslundii originated from chronic asymptomatic periapical tooth abscesses and actinomycosis of the distal part of the penile shaft. CONCLUSIONS: Actinomycosis was a very rare clinical problem in our clinical practice (0.032% of all hospitalizations and 0.0034% of all outpatients) but among those cases classical clinical presentations were also very rare.

Single oral dose of azithromycin versus 5 days of oral erythromycin or no antibiotic in treatment of campylobacter enterocolitis in children: a prospective randomized assessor-blind study.

OBJECTIVE: To evaluate efficacy of a single oral azithromycin dose versus standard oral erythromycin regimen or no antibiotic for Campylobacter enterocolitis in children younger than or equal to 12 years of age. PATIENTS AND METHODS: Randomized parallel group assessor-blind trial testing for inequality in efficacy between treatments was done. Patients (N = 120) were enrolled at less than or equal to 48 hours since disease onset to receive erythromycin 50 mg kg day for 5 days, single-dose azithromycin 20 mg/kg or 30 mg/kg, or no antibiotic (no treatment control) (1: 1: 1: 1). Antibiotics were commenced 8 to 10 hours after enrollment. Patients were assessed at 24-hour intervals for 6 days. RESULTS: In the intent-to-treat analysis, Campylobacter eradication was achieved in 20 of 30 controls and in all of the patients treated with antibiotic. Incidence of clinical cure during the observed period was 15 of 30 in the control, 14 of 30 in the erythromycin, 20 of 30 in the lower, and 25 of 30 in the higher azithromycin dose group. With adjustment for age, sex, baseline disease severity, and disease duration before enrollment, only azithromycin 30 mg/kg was superior to no treatment: incidence ratio (IR) 1.76 (95% confidence interval [CI] 1.11-2.87). It was also superior to erythromycin (IR 1.80, 97.5% CI 1.13-2.84). Regarding time to clinical cure, only azithromycin 30 mg/kg was superior to no treatment (adjusted hazard ratio [HR] 4.90, 95% CI 2.44-9.84). It was also superior to erythromycin (HR 4.17, 97.5% CI 1.91-9.09). All treatments were well tolerated. CONCLUSIONS: The administration of single oral dose of azithromycin 30 mg/kg early after disease onset effectively eradicates the pathogen and accelerates clinical cure in childhood Campylobacter enterocolitis. It is clinically superior to an early commenced 5-day erythromycin regimen, which apparently conveys no clinically relevant benefit over no antibiotic treatment.

[ISKRA guidelines on sore throat: diagnostic and therapeutic approach--Croatian national guidelines]. / Smjernice iskra za grlobolju: dijagnosticki i terapijski pristup--Hrvatske nacionalne smjernice.

Sore throat is most commonly caused by viruses, but when caused by bacteria, the most important is group A streptococcus (GAS). The aim of these guidelines is to determine optimal treatment for streptococcal sore throat and reasonable indications for tonsillectomy, as well as recommend how to differentiate streptococcal infection for which antibiotics are justified, from numerous other sore throats where antibiotics wont have a significant effect on disease course, but might contribute to bacterial resistance to antibiotics. The development of the guidelines was initiated by the Interdisciplinary Section for Antibiotic Resistance Control (ISKRA) of the Croatian Ministry of Health and Social Welfare in accordance with the principles of AGREE (Appraisal of Guidelines for Research and Evaluation) methodology which means that the guidelines are the result of consensus between all interested professional societies and institutions. For streptococcal sore throat diagnostics, the Working Group recommends evaluation of clinical presentation according to Centor criteria and for patients with Centor score 0-1, antibiotic therapy is not recommended nor bacteriological testing, while for patients with Centor score 2-4 bacteriological testing is recommended (rapid test or culture) as well as antibiotic therapy in case of positive result. The drug of choice for the treatment of streptococcal tonsillopharyngitis is oral penicillin taken for ten days (penicillin V) or in case of poor patient compliance benzathine penicillin G can be administered parenterally in a single dose. Other antibiotics (macrolides, clindamycin, cephalosporins, co-amoxiclav) are administered only in case of hypersensitivity to penicillin or in recurrent infections. Tonsillectomy is a widely accepted surgical procedure that decreases the number of sore throats in children and should be performed only if indications for this procedure are established. Absolute indications include five or more streptococcal infections per year, tonsillitis complications, permanent respiratory tract obstruction, obstructive sleep apnea syndrome and suspected tonsillar malignancy. Relative indications include chronic tonsillitis and occlusion disturbances.

Combined Albenazole-Praziquantel Treatment in Recurrent Brain Echinococcosis: Case Report.

We present a 40-year-old woman with a history of relapsing echinococcosis who had undergone a number of surgical procedures for cyst removal (right pulmectomy, cardiac surgery and 6 subsequent brain surgeries and two gamma knife procedures) and was admitted to University Hospital for Infectious Diseases "Fran Mihaljeviæ", Zagreb, Croatia in 2014 for pre-operative medical treatment of brain hydatidosis in the right parietal region. We aimed to attain a high cyst albendazole sulphoxide (ASO) concentration in order to achieve a more pronounced protoscolex inactivation and a high serum ASO concentration (reflecting the tissue concentrations) to reduce the risk of disease recurrence. The patient was treated with a higher dose of albendazole (15 mg/kg/day for 4 wk) that we had found effective in patients with liver hydatidosis, and combined with praziquantel over the last 14 d at a dose that is typically used to treat neurocysticercosis with an intention to improve ASO bioavailability. Neither serum nor cerebrospinal fluid concentrations on day 10 apparently differed from those on day 24 indicating a lack of an effect of praziquantel on ASO bioavailability. Intra-cystic ASO concentration was below the lower limit of quantification, but above the limit of detection. After the 7th episode of the disease and combined albendazole-praziquantel and surgery treatment, the patient achieved a 3-year remission. With the apparent lack of a meaningful pharmacokinetic praziquantel-albendazole interaction, this is most likely ascribable to the use of a higher albendazole dose than previously.

An unusual outcome in a child with hepatosplenic cat-scratch disease.

Typical cat-scratch disease (Bartonella henselae infection) in an immunocompetent child is usually associated with a history of scratch, bite or intimate contact with a cat. Most patients develop a non-tender papule in the scratch line after three to ten days. This may persist for only a few days or as long as two to three weeks. During the next two weeks or more, regional lymph nodes that drain the area gradually enlarge and then slowly resolve in more than 10% of patients. The nodes develop overlying erythema and may suppurate. Atypical forms of cat-scratch disease occur in a minority of cases and are characterized by ocular or neurological manifestations, hepatosplenic involvement, vertebral osteomyelitis, endocarditis etc. Immunocompromised individuals with B. henselae infection may develop bacillary angiomatosis, bacillary peliosis, and relapsing bacteremia. There have been several reports of hepatosplenic granulomas caused by B. henselae in immunocompetent children. We report a case of a 6-year-old boy with the hepatosplenic form of cat-scratch disease. Despite early diagnosis and long-term antimicrobial treatment, splenectomy could not be avoided.