Acute hemorrhagic edema of infancy - is it really a mild, benign disease?

BACKGROUND: Acute hemorrhagic edema of infancy (AHEI) is a rare vasculitis, which presents dramatically as palpable purpuric skin lesions on the limb, face and auricles, with swelling of these parts and low-grade fever, in children up to 2 years of age. To date, approximately 400 cases have been described in the literature. The etiology remains mostly unknown. With or without treatment, AHEI goes to spontaneous recovery within 1-3 weeks, usually without any complications. To our knowledge, compartment syndrome as complication of AHEI has only been reported in one case. We present an unusual case of AHEI with serious complications due to compartment syndrome of the right-hand fingers. CASE: A 16-month-old male child presented with fever and sudden appearance and rapid spread of palpable, painless, non-itching ecchymotic hematomas on the thigh, cheeks, earlobes, forearms, dorsum of hands and feet, with mild edema of these regions. Complete systemic examination and all vital parameters were normal for age. There was no history of bleeding disorders in the family. Except low hemoglobin on complete blood count and increased D-dimer values, all other laboratory investigations were in the normal range. Changes on the right forearm and hand expanded on almost the entire dorsal side and all surfaces of the fingers, with pronounced swelling and formation of bullous lesions, which were spreading and cracking. Skin biopsy confirmed nonspecific small-vessel vasculitis. That required the use of Methylprednisolone, low-molecularweight heparin, antibiotics and debridement of necrotic eschar, with necrectomy of the affected fingers. CONCLUSIONS: Early recognition of AHEI is important to avoid unnecessary investigation and therapy. On the other hand, our reported case warns that unexpected complications may occur.

The Role of Presepsin Obtained from Tracheal Aspirates in the Diagnosis of Early Onset Pneumonia in Intubated Newborns.

OBJECTIVES: To investigate the role of presepsin obtained from tracheal aspirate of intubated newborns in the diagnosis of early neonatal pneumonia. METHODS: A cross-sectional observational study was performed on 60 intubated newborns during the two-year period. Tracheal aspirate for examination was taken in aseptic conditions in usual toilets, by lavage with 2 ml of 0.9% NaCl in Mucus suction set. On the same day, presepsin (blood) was measured. RESULTS: There were 34 newborns in the examined group (with pneumonia) and 26 in the control group. Patient groups were similar regarding demographic characteristics related to gender and Apgar score. The coefficients of simple linear correlation revealed the statistically significant connection between presepsin (from tracheal aspirate) and birth body weight, presepsin (plasma), maternal infection and pneumonia. Significant differences in the values of presepsin (from tracheal aspirate) (p < 0.001) and birth body weight (p = 0.036) were found. CONCLUSIONS: In intubated newborns, measurements of presepsin obtained from tracheal aspirate suggested that it can be used as a complementary marker in diagnosing early onset neonatal pneumonia.

Allergen specific sublingual immunotherapy in children with asthma and allergic rhinitis.

BACKGROUND: The incidence of asthma and allergic rhinitis (AR) is significantly increased, especially in younger children. Current treatment for children with asthma and allergic rhinitis include allergen avoidance, standard pharmacotherapy, and immunotherapy. Since standard pharmacotherapy is prescribed for symptoms, immunotherapy at present plays an important role in the treatment of allergic diseases. This article presents insights into the up-to-date understanding of immunotherapy in the treatment of children with allergic rhinitis and asthma. DATA SOURCES: PubMed articles published from 1990 to 2014 were reviewed using the MeSH terms "asthma", "allergic rhinitis", "children", and "immune therapy". Additional articles were identified by hand searching of the references in the initial search. RESULTS: Numerous studies have shown that sublingual application of allergen specific immunotherapy (SLIT) is an adequate, safe and efficient substitution to subcutaneous route of allergens administration (SCIT) in the treatment of IgE-mediated respiratory tract allergies in children. According to the literature, better clinical efficacy is connected with the duration of treatment and mono sensitized patients. CONCLUSIONS: At least 3 years of treatment and stable asthma before the immunotherapy are positive predictors of good clinical efficacy and tolerability of SLIT. SLIT reduces the symptoms of allergic diseases and the use of medicaments, and improves the quality of life of children with the diseases.

Respiratory syncytial virus infection and bronchial hyperreactivity in children up to two years of age in correlation with atopy.

BACKGROUND/AIM: Bronchiolitis in early childhood caused by respiratory syncytial virus (RSV) is considered to be important risk factor of the recurrent wheezing and asthma development. The aim of this study was to examine the frequency of RSV infection and atopy in children up to two years of age and to determine their correlation with bronchial hyperreactivity. METHODS: The study included 175 children aged 5-24 months. The presence of RSV infection was identified by serum levels of IgA and IgG determined by ELISA. Bronchial hyperreactivity (BHR) has been defined as the existence of chronic bronchial disease and/or three or more previous suspected diagnosis of acute bronchial disease. Atopy was confirmed by detection of the specific serum IgE using quantitative multitest Phadiatop infant (cut off 0.35 kUA/L). RESULTS: The children with atopy were more frequently infected with RSV (43.3%) than those without atopy (22.8%; p = 0.02). The higher frequency of RSV infection was found in children with BHR in comparison with those without it but only in the group who also had atopy (77.8% vs. 28.6%, p = 0.018). In the female children, BHR and RSV infection were associated in 62.5% of cases, regardless the atopy. In the male children with atopy, RSV infection was associated with BHR in 83.3% of the cases, while in those without atopy, RSV infection with BHR was found in only 17.4% of the cases. CONCLUSION: Children up to two years of age with atopy are more frequently infected with RSV (43.3%) than nonatopic children. Every third child with atopy develops BHR and 77.8% of them also have RSV infection. Atopic children are at higher risk for development of BHR when infected with RSV also.

Rosai-Dorfman disease of vertebra: Case report and literature review.

Rosai-Dorfman disease is a rare benign histiocytic disorder that arises predominantly in lymph nodes with fever and malaise, but can affect various organs, with or without lymphadenopathy. Solitary extranodal skeletal lesions are extremely rare. Herein, we describe a case of isolated disease of thoracic spine, with vertebral body fracture. A 14-year-old girl presented with cervical back pain for about one month as the only symptom. There was no lymphadenopathy. Results of laboratory tests were within reference ranges. The radiological examinations revealed collapse, osteolytic lesion and compressive fracture, which reduced vertical diameter of C4 vertebral body. The patient made a complete recovery after a limited C4 laminectomy, spondylodesis C3/C5 vertebra and biopsy of the lesion. Histologically, nonspecific cellular milieu and atypical histiocytic proliferation with emperipolesis, with CD68 and S100 positivity, confirmed a diagnosis of Rosai-Dorfman disease. Isolated extranodal skeletal Rosai-Dorfman disease should be considered among the differential diagnoses of similar changes, such as Langerhans cell histiocytosis, Erdheim-Cheister disease, eosinophilic granuloma, osteomyelitis, metastasis and lymphoma.

Characteristics of norovirus infection in Serbia.

BACKGROUND/AIM: Norovirus (NoV), formerly Norwalk-like virus is the most common cause of acute gastroenteritis in humans of all ages. It is known that 90% of viral gastroenteritis and about 60-85% of all outbreaks of gastroenteritis, especially in the territory of United States of America, Europe and Japan are caused by this virus. For the countries of the northern hemisphere, individual cases and outbreaks of acute NoV gastroen teritis appear in seasonal pattern, mainly during the winter months. The aim of this study as to describe characteristics of acute gastroenteritis with the established NoV etiology in Serbia. METHODS: The study group included 88 patients with the symp toms of acute gastroenteritis, throughout the year 2010 and 2011. From all the patients, stool samples were taken less than three days from the onset of symptoms. Detection of NoV in stool samples was performed by commercial qualitative immunochromatography assay. Statistical analysis included application of x2 test, Mann-Whitney U-test, Kruskal-Wallis's test, Spearman's rank correlation test and logistic regression analysis. RESULTS: Outbreaks of acute gastroenteritis caused by NoV were recorded to be the most common in children with the incidence of infection of 50% in the age group 0-15 years. Analysis of individual symptoms in the NoV proven infection, showed that diarrhea was the most common symptom, followed by vomiting espe cially in small children, while abdominal pain was most common in elderly (> 65 years). The presence of frequent vomiting, more than 4 times/day, indicated NoV infection in the women, while for men the infection was always presented with diarrhea. CONCLUSION: The obtained results confirmed that small children and elderly are,the most susceptible to NoV infection and that outbreaks are more frequent in the winter months. Those who consumed food in restaurants and other public facilities were not at higher risk for NoV infection.

Campylobacter jejuni infection and IgE sensitization in up to 2-year-old infants.

BACKGROUND/AIM: The "hygiene hypothesis" addresses the correlation between the occurrence of atopy and the frequency of infections in the earliest age, explaining an increase in the incidence of atopic diseases by living in good, infection-free, hygienic conditions. The aim of our study was to determine the conection between atopy and Camplobacter infection, and to analyze the association between serum concentrations of total IgE and Campyobacter infection in relation to atopy in children up to two years. METHODS: A case control study was conducted with the sample of 98 infants of the average age of 8 months. Total serum IgE and Phadiatop infant multi-test were determined on Immunocap-100 (Phadia AB, Uppsala, Sweden). The presence of atopy was determined by detection of serum-specific IgE > 0.35 kUA/L (Phadiatop infant positive) and serum IgM, IgA, IgG levels against C j uni were determined by a quantitative immuno-enzyme test--SERION ELISA classic. RESULTS: Total IgE cut-off values > 15 kU/L point to atopy in infants, and tIgE cut-off values > or = 8.1 kU/L pointed to a Cj/uni infection in infants. Within the group of atopic children, tIgE levels > 29.8 kU/L point to C. jejuni infection, and within the group of non-atopic children, tIgE levels > or = 5.9 kU/L point to infection. Enteritis is not a predictor of C jejuni infection, because of a high frequency of asymptomatic cases of infection. The risk factors for C. jejuni infection are age and tIgE, and the protective factors are breastfeeding and atopy. CONCLUSION: C. jejuni infection increases the total serum IgE level, which is pre- dictive of infection, regardless of the presence of atopy. The presence of symptomatic C. jejuni infection reduces the risk of atopy in a child of the age of 5-24 months by the factor of 10.

Risk factors for brain metastases in surgically staged IIIA non-small cell lung cancer patients treated with surgery, radiotherapy and chemotherapy.

INTRODUCTION/AIM: Lung cancer is a leading cause of mortality among patients with carcinomas. The aim of this study was to point out risk factors for brain metastases (BM) appearance in patients with IIIA (N2) stage of nonsmall cell lung cancer (NSCLC) treated with three-modal therapy. METHODS: We analyzed data obtained from 107 patients with IIIA (N2) stage of NSCLC treated surgically with neoadjuvant therapy. The frequency of brain metastases was examined regarding age, sex, histological type and the size of tumor, nodal status, the sequence of radiotherapy and chemotherapy application and the type of chemotherapy. RESULTS: Two and 3-year incidence rates of BM were 35% and 46%, respectively. Forty-six percent of the patients recurred in the brain as their first failure in the period of three years. Histologically, the patients with nonsquamous cell lung carcinoma had significantly higher frequency of metastases in the brain compared with the group of squamous cell lung carcinoma (46%:30%; p = 0.021). Examining treatment-related parameters, treatment with taxane-platinum containing regimens was associated with a lower risk of brain metastases, than platinum-etoposide chemotherapy regimens (31%:52%; p = 0.011). Preoperative radiotherapy, with or without postoperative treatment, showed lower rate of metastases in the brain compared with postoperative radiotherapy treatment only (33%:48%; p = 0.035). CONCLUSION: Brain metastases are often site of recurrence in patients with NSCLC (IIIA-N2). Autonomous risk factors for brain metastases in this group of patients are non-squamous NSCLC, N1-N2 nodal status, postoperative radiotherapy without preoperative radiotherapy.

[Clinical manifestations of atopy in children up to two years of age].

BACKGROUND/AIM: Atopic diseases such as atopic dermatitis, allergic rhinitis and asthma have had increased prevalence during the past decade and nowadays occur in every third child in developed countries. The aim of the study was to determine frequency and type of atopic diseases at the age of two, as well as the importance the total IgE antibodies concentrations have in diagnosis and prognosis of the disease. METHODS: The study involved 175 children up to two years of age. Allergy-like symptoms were found after surveying their parents and pediatric medical records. Using the fluorescence immunossay (FIA) method, total IgE antibodies concentrations and specific IgE antibodies (Phadiatop infant) were determined on an Immunocap 100 Dyagnostic System. RESULTS: One or more allergy-like symptoms accounted for 57.7% of findings in children under the age of two, whilst in 19.4% the existence of IgE-related allergic diseases was found. Atopic diseases usually have clinical manifestations of atopic dermatitis (11.4%), IgE-bound wheezing/asthma (10.8%) and food allergies (7.4%), and to much lesser extent those of allergic rhinitis (3.4%) and urticaria (1.7%). The significantly higher total IgE antibodies concentrations were found in children with allergy-like symptoms (p < 0.0005) (cut-off 15.15 kU/L, sensitivity 76.5% specificity 71.6%). CONCLUSION: Almost 20% of two-year-old children have any of clinically manifested allergic diseases, with atopic dermatitis and IgE wheeze/asthma being predominant. The higher total IgE antibodies concentration is a good marker for sensitization in children with allergy-like symptoms.

[Body mass index in asthmatic children before and after one year inhaled glucocorticosteroids therapy BMI].

INTRODUCTION: Asthma is the most frequent children's disease, with a tendency of further growth. Bearing in mind controversial data on obesity of asthmatic children and a possible effect of inhaled corticosteroids (ICS) on children's growth, the aim of our study was to determine the body mass index (BMI) in asthmatic children at the beginning of the therapy and to study the effect of the continuous application of ICS on growth and BMI during the period of 1 year. MATERIAL AND METHODS: The study included 100 children aged 7 to 18 diagnosed to have partly controlled and uncontrolled allergic asthma, who were continuously given ICS as a prevention against asthma attacks at Pediatric Clinic of the Clinical Center in Kragujevac for the period of 1 year. Children with BMI < p10 by their age and gender were considered to be underweight, children with p10-84 as of normal weight, children with p85-97 as overweight and children with BMI > p97 as obese. RESULTS: The highest percentage of children with asthma was within normal parameters (70%), 10% of the children were underweight (boys: n = 8/60, 13.3% vs. girls: n = 2/40, 5%), and 18% were overweight/obese. Monovariable analysis of variant with repeated measurements have shown a statistically significant difference in the height of children in all age groups after a year of continuous therapy of ICS (p = 0.000), except in girls aged 15-18, who did not show any significant difference in body height after the therapy (p > 0.05). CONCLUSION: Asthmatic children with partly controlled and uncontrolled asthma have mostly normal BMI and ICS can be safely administered in asthmatic children.

A case of acute tuberculous pleuropneumonia in a patient with acute lymphoblastic leukemia.

Respiratory system infections are the most common complications in immunocompromised cancer patients. We here report a 14-year-old male who was admitted to the hospital because of acute pneumonia, who had been diagnosed with acute lymphoblastic leukemia (ALL) when he was 12 years old. A diagnosis of acute tuberculous pleuropneumonia was made based on clinical and radiographical findings, and Mycobacterium tuberculosis was identified by Ziehl-Neelson acid-fast stain and culture on Löwenstein-Jensen medium. Twenty months before pneumonia onset, the patient had been treated with immunosupressive therapy (ALL IC-BFM 2002 protocol).

Heart rate variability in infants with central coordination disturbance.

Despite a remarkable medical progress in the field of Developmental Medicine and Child Neurology, early identification of infants at risk for permanent motor disabilities still presents challenge for both clinicians and researchers. As an indicator of cardiac autonomic control, it was shown that heart rate variability (HRV) might reflect not only sympathetic or parasympathetic activity but also functional integrity of the central nervous system (CNS). Furthermore a pattern of HRV was demonstrated to correlate with motor developmental outcome in high risk infants. The purpose of this study was to analyze the clinical usefulness as well as predictive value of time-domain HRV parameters in infants with central coordination disturbance. The study included 35 infants with central coordination disturbance and 37 healthy age and sex-matched controls. Time-domain HRV indices were analyzed from 24-h electrocardiography recordings. We found significantly lower values of SDNN, SDANN and RMSSD parameters in infants with central coordination disturbance compared to controls. Additionally, logistic regression analyses demonstrated independent predictive value of parameters SDNN and SDANN in infants who subsequently developed cerebral palsy (CP). By performing receiver operating characteristic (ROC) analyses, the optimal cut-off value of SDNN<=48ms predicted CP with a sensitivity of 68.7% (95% CI 41.4-88.9) and specificity of 84.2% (95 CI 60.4-96.4) while the optimal cut-off value of SDANN<=41ms predicted CP with a sensitivity of 87.5% (95% CI 61.6-98.1) and specificity of 57.9% (95 CI 33.5-79.7). We are in opinion that time domain HRV analysis could be helpful clinically as well as a prognostic tool in infants with central coordination disturbance.

[Neurotoxicity during induction treatment of childhood acute lymphoblastic leukaemia--two case reports].

INTRODUCTION: During chemotherapy of acute lymphoblastic leukaemia (ALL), children sometimes exhibit neurological disturbances. Chemiotherapeutic regimens include methotrexate, administered either intravenously or via intrathecal route. Although multiple drugs are used in addition to methotrexate, the acute neurotoxicity reported in patients is usually attributed to methotrexate. The acute neurotoxicity usually results in stroke-like symptoms such as aphasia, weakness, sensory deficits, ataxia and seizures. OUTLINE OF CASES: From 2002 until January 2008, 32 children with ALL were diagnosed and treated at the Children's Hospital in Nis. The patients' age ranged from 1.5 to 16 years. They were treated in accordance with the protocol ALL IC-BFM 2002 (ALL Intercontinental Berlin Frankfurt Münster 2002). Two of the patients (6.25%) exhibited neurotoxicity. After the occurrence of neurological symptoms, the patients were ophthalmologically and neurologically examined. In addition, the magnetic resonance (MR) imaging, computerized tomography and electroencephalography were applied. The paper presents two patients, aged 9 and 15 years respectively, who exhibited acute neurotoxicity--methotrexate encephalopathy during ALL treatment. Both patients had tonic-clonic seizures and neurological symptoms in the course of the induction therapy. Neurotoxicity occurred 7 days after the third, and 3 days after the fourth intrathecal methotrexate therapy. MR images confirmed multi-focal morphological changes of brain density in one of the patients, while the other patient had normal CT reading. Even though the development significantly differed, the changes were reversible in both patients. CONCLUSION: The neurotoxicity in patients with ALL can be combined with significant structural changes of the brain, but also morphological changes can be absent. Several questions concerning aetiology and treatment of neurological events are raised.

[Correlation between neurological finding and gestational maturity of newborns determined by neurosonography].

INTRODUCTION: Maturity is a complex functional condition influenced especially by the development of the vital functions of a fetus, primarily by the degree of the development of its central nervous system. The aim of this investigation was to establish the gestational maturity of the nervous system by neurosonography and neurological status. MATERIAL AND METHODS: The parameter of the neurological maturity, compared in this research are a neurological status and the degree of girification established by the ultrasound. RESULTS: All the coefficients of correlation between the gestation age determined by the ultrasound and the establishing of the gestation based on the neurological findings show a statistically significant correlation for p < 0.01. Of particular parametres of the neurological evaluation , the most appropriate ones appeared to be reflexes (the reflex of crossed extension, Moro reflex and the reflex of the main points), then volar flexion of a hand and the poplietal corner as the indicator of the passive tonus, whereas within the area of the evaluation of the active tonus, the motility was the most valid for establishing the maturity of a neonatal. The lowest coefficients of the correlations were in the automatic walk and the active tonus of the neck flexor, which are the ones of the most common neurological indicators of hypoxic ischemic encephalopathy of a neonatal. CONCLUSIONS: Bearing in mind that the premature babies are a risky group for existence of perinatal brain damages, we believe the neurosonographic establishing of the gestation age to be a precise and comfortable indicator of the maturity of the nervous system.

Polyamine oxidase activity in peripheral blood of newborn infants with neonatal hyperbilirubinemia: is bilirubin an antioxidant?

BACKGROUND: Neonatal hyperbilirubinemia can be physiological and pathological and most frequently is a consequence of faster erythrocytes (RBC) hemolysis. Free unconjugated bilirubin is a highly toxic compound, especially for the central nervous system. The most abundant polyamines circulating in blood are spermidine (Spd) and spermine (Sp), which are mainly localized in RBC, where they control membrane permeability. Polyamine oxidase (PAO) exerts an important activity in the plasma and erythrocytes of newborn infants with hyperbilirubinemia, catalyzing the oxidative deamination of Sp and Spd, producing potentially toxic agents that induce apoptosis of mammalian cells. The present study investigated polyamine metabolism by measuring PAO activity in the blood of newborn infants with hyperbilirubinemia and explored the possible antioxidant function of bilirubin through monitoring malondialdehyde (MDA) levels. METHODS: The study included 43 newborns, 10 in the control and 33 in the diseased group. Blood PAO activity and bilirubin and MDA levels were measured using spectrophotometric methods. RESULTS/DISCUSSION: Our results indicate that bilirubin, at physiologic concentrations, protects neonatal erythrocytes against oxidative stress. The positive correlation between PAO activity and MDA levels with high bilirubin concentrations (> 200 micromol/L) in newborn infants indicates that in pathological conditions, bilirubin cannot exert its antioxidant function. CONCLUSION: Investigating the function of polyamines in erythrocytes and the importance of PAO related to hemolysis and bilirubin synthesis is necessary to shed light on the functions of PAO and its metabolites on the permeability of the erythrocyte membrane.

[Hashimoto's thyroiditis in children and adolescents].

INTRODUCTION: Hashimoto's thyroiditis (HT) is a common cause of goitre and hypothyroidism in children and adolescents. Spontaneous remission may occur in up to 50% patients, but the development of hypothyroidism is possible. OBJECTIVE: We investigated the clinical manifestations, course and long-term outcome of HT. METHOD: We reviewed charts of 43 children (36 females) with HT, mean age at presentation 12.3 years, and mean follow-up duration 4.6 years. RESULTS: HT is five times more common in females. The common complaints leading to referral were goitre in 19 children (44.3%), diffuse in 17 children (89.5%). As to the prevalence of goitre, it accounted for significantly more referrals in females (14 girls, and 5 boys; 73.7% vs 26.3%, t-test; p < 0.005). Goitre was either isolated in 15 (34.4%) or associated with other complaints in 4 children: anaemia in 7 (16.2%), fatigue in 5 (11.8%), increased appetite in 4 (9.7%), weight gain in 3 (7.0%), growth retardation in 2 children (4.7%), at irregular menses in 3 pubertal girls. Hypothyroidism was present in 18 patients (41.1%), 7 (38.8%) on initial admission, and 11 (61.8%) had the mean follow-up duration of 4.6 years. There were 25 euthyroid HT patients (59.9%). The family history of the thyroid disease was positive in 16 children (37.1%) and 12 of them (71.4%) had hypothyroidism. There were 6 patients (13.9%) in whom the disease was associated with some other autoimmune disease. CONCLUSION: HT is five times more common in females. The usual complaints leading to referral were diffuse goitre, which accounted for significantly more referrals in females. A positive family history of autoimmune thyroid disease is associated with a higher risk of hypothyroidism in children with HT. Hypothyroid patients may appear in higher percentage of children and adolescents than previously reported.

[Molecular epidemiology of rotaviruses in preschool children].

Numerous epidemiological studies, conducted in both developed and developing countries, have shown that the rotavirus is an important aetiological agent in severe diarrhoeal diseases among preschool children. In recent years, different biochemical techniques for the genetic and phenotypic analysis of rotaviruses have been developed. The aim of this study was to define the biological and genetic differences among rotaviruses isolated from the faeces of affected children, by using the Polyacrylamide Gel Electrophoresis technique, as well as to type the viruses and establish the number of strains circulating within our population. In total, 124 faeces samples from children up to 5 years of age were analysed. With the use of the ELISA test, rotaviruses were isolated in 10.3% of cases. The extraction of viral RNA was carried out directly from the faeces samples, which was followed by electrophoresis, and finally observation using a UV lamp, and documentation with a photo camera. The analysis of viral RNA, using Polyacrylamide Gel Electrophoresis (PAGE), revealed equal mobility in all segments of the genome. The results of our analysis demonstrated that the same strains of rotaviruses do circulate within our population. Such a result can be explained as a consequence of our years-long isolation as well as of the decreased mobility of our population. However, the results do not signify that the rotavirus genome in this region will not be susceptible to variations and that, consequently, new strains will not be created.