Małgorzata Pańczyk-Tomaszewska

Mycoplasma pneumoniae as a trigger for Henoch-Schönlein purpura in children.

Mycoplasma pneumoniae is one of the most common causes of respiratory tract infections in children. Extrapulmonary manifestations are seen in up to 25% of infected patients. Extrapulmonary complications are associated with the central nervous system, gastrointestinal tract, skin changes, myocarditis, pericarditis, hemolytic anemia, thrombocytopenia and thrombosis. The majority of extrapulmonary symptoms are associated with skin changes such as exanthematous skin eruptions, erythema nodosum, urticaria, Stevens-Jonson syndrome. M. pneumoniae stimulates production of the interleukins and tumor necrosis factor (TNF) α and can cause vasculitis. Henoch-Schönlein purpura (HSP) is a leucoclastic vasculitis that affects small vessels. Clinical manifestations of HSP include typical rash, arthritis, gastrointestinal and sometimes renal involvement. The main feature in HSP is abnormal IgA deposits in vessel walls. Circulating abnormal glycosylated IgA 1 and IgG antibodies form immune complexes: IgA1-IgG and anti-IgA 1. Immune complexes activate cytokines, parts of complement and influence directly the endothelium. We report cases of three children with Henoch-Schönlein purpura with prolonged and recurrent skin and joint changes. The serological analysis (positive serum IgM) confirmed Mycoplasma pneumoniae infection. Treatment with clarithromycin caused complete regression of disease. We suggest that in the case of prolonged symptoms of vasculitis due to Henoch-Schönlein purpura, Mycoplasma pneumonia infection may be a potential cause of exacerbation of the disease.

Markers of Bone Metabolism in Children with Nephrotic Syndrome Treated with Corticosteroids

The aim of the study was to assess bone mineral density, bone metabolism markers, and vitamin D level in children with idiopathic nephrotic syndrome in the course of 1-year observation. Twenty five children with nephrotic syndrome aged 5-17 years were enrolled into the study. The median number of relapses was 6 (range 1-22). All patients were treated with prednisone and vitamin D (800 IU/day). Bone mineral density of total body (TB-BMD) and lumbar spine (L-BMD), evaluated by dual energy X-ray absorptiometry (DXA) expressed as Z-score, and serum calcium, phosphorus, parathormone (iPTH), alkaline phosphatase (ALP), bone alkaline phosphatase (BAP), osteocalcin (OC), albumin, creatinine, 25(OH)D3, 1,25(OH)2D3 and urine calcium/creatinine ratio (uCa/Cr) were evaluated at the enrollment visit and after 1 year of therapy. After 1 year significant decreases of TB-BMD Z-score (from -0.24±1.34 to -0.74±1.31, p<0.05) and 25(OH)D3 serum level (from 31.7±16.3 to 23.7±9.3; p<0.05) were observed. No other appreciable differences were found. At the study onset, negative correlations were found between L-BMD Z-score and serum ALP, BAP, and phosphorus and between TB-BMD Z-score and urine uCa/Cr. After 1 year, L-BMD Z-score correlated negatively with serum BAP and OC, and positively with serum 25(OH)D3. Multivariate analysis showed that BAP was the strongest predictor of L-BMD Z-score (beta=-0.49; p<0.05). We conclude that children with nephrotic syndrome treated with corticosteroids are at risk of bone mass loss. Serum BAP concentration seems to be a good indicator of spongy bone metabolism in these children, who should be supplemented with vitamin D in an adjustable dose, possibly higher than 800 IU/24 h to prevent osteopenia.

Methods to evaluate arterial structure and function in children – State-of-the art knowledge

BACKGROUND With increasing rates of hypertension, obesity, and diabetes in the pediatric population, wide available, and reproducible methods are necessary to evaluate arterial structure and function in children and adolescents. METHODS MEDLINE/Pubmed was searched for articles published in years 2012-2017 on methodology of, current knowledge on, and limitations of the most commonly used methods to evaluate central, proximal and coronary arteries, as well as endothelial function in pediatric patients. RESULTS Among 1528 records screened (including 1475 records from years 2012 to 2017) 139 papers were found suitable for the review. Following methods were discussed in this review article: ultrasound measurements of the intima-media thickness, coronary calcium scoring using computed tomography, arterial stiffness measurements (pulse wave velocity and pulse wave analysis, carotid artery distensibility, pulse pressure, and ambulatory arterial stiffness index), ankle-brachial index, and methods to evaluate vascular endothelial function (flow-mediated vasodilation, peripheral arterial tonometry, Doppler laser flowmetry, and cellular and soluble markers of endothelial dysfunction). CONCLUSIONS Ultrasonographic measurement of carotid intima-media thickness and measurement of pulse wave velocity (by oscillometry or applanation tonometry) are highly reproducible methods applicable for both research and clinical practice with proved applicability for children aged ≥6 years or with height ≥120cm. Evaluation of ambulatory arterial stiffness index by ambulatory blood pressure monitoring is another promising option in pediatric high-risk patients. Clearly, further studies are necessary to evaluate usefulness of these and other methods for the detection of subclinical arterial damage in children.

Levamisole therapy in children with frequently relapsing and steroid-dependent nephrotic syndrome: a single-center experience

Introduction Numerous studies suggest that levamisole, an antihelmintic agent with an immunomodulatory effect, reduces the number of relapses in children with frequently relapsing and steroid-dependent nephrotic syndrome (FRNS/SDNS). The aim of the study was to present a single center’s experience in treatment of FRNS and SDNS with levamisole. Material and methods Among 72 children with FRNS/SDNS treated in our department with levamisole in the years 1984-2011 we studied in detail 53 patients (mean age: 6.5 ±3.0 years), in whom the medication was administered for at least 6 months. In these 53 patients we evaluated: the course of the disease before levamisole, the renal biopsy result, medications used, prednisone dose on levamisole initiation, duration of levamisole treatment, time to first relapse and number of relapses on levamisole, and levamisole side effects. Results The duration of nephrotic syndrome was 3.4 ±2.9 years, and the number of relapses before levamisole treatment was 6.0 ±3.4. The dose of prednisone on initiation of levamisole treatment was 1.2 ±0.6 mg/kg/24 h, and the duration of levamisole treatment was 15.0 ±7.3 months. During levamisole treatment proteinuria relapsed in 34/53 (64.2%) children, and the time to first relapse was 8.8 ±8.1 months. During levamisole therapy relapses of the disease decreased significantly (2.7 ±2.0 vs. 1.8 ±2.1 relapses/year, p = 0.02). Time to first relapse correlated with total number of relapses (R = –0.59, p < 0.001) and number of relapses in one year during levamisole treatment (R = –0.60, p < 0.001). Conclusions Levamisole is effective in reducing the number of relapses in children with frequently relapsing and steroid-dependent nephrotic syndrome. Early relapse of proteinuria on levamisole treatment in children with FRNS/SDNS suggests low efficacy of further treatment.

Urine interleukin-6, interleukin-8 and transforming growth factor β1 in infants with urinary tract infection and asymptomatic bacteriuria

Introduction Urinary tract infection (UTI) occurs in 1.1% of girls and 1.4% of boys during the first year of life. Asymptomatic bacteriuria (ABU) is usually detected incidentally in 0.9% of girls and 2.5% of boys at this age. The aim of the study was to assess the usefulness of measurement of pro-inflammatory urine interleukin (IL)-6 and IL-8 concentrations and anti-inflammatory transforming growth factor β1 (TGF-β1) level in infants with febrile UTI, non-febrile UTI and ABU. Material and methods A total of 35 children, mean age 6.14 ±3.47 months, were divided into three groups: group I – febrile UTI (n = 13), group II – non-febrile UTI (n = 13) and group III – ABU (n = 9). At the time of enrollment urine IL-6, IL-8, TGF-β1 and serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and white blood cell count (WBC) were measured. Renal ultrasound was performed in all children, 99mTc-dimercaptosuccinic acid scintigraphy (DMSA) and voiding cystourethrography in children with UTI. Results Urine concentrations of IL-6 and IL-8 were significantly higher in febrile UTI compared to those with non-febrile UTI and ABU (p < 0.5, p < 0.01) and positively correlated with CRP, ESR and WBC (p < 0.01). Urine levels of TGF-β1 were significantly higher in children with febrile UTI compared to those with ABU (p < 0.05) and positively correlated with WBC (p < 0.01). Inflammatory changes in the DMSA scan were detected in 66.6% of children with UTI. No significant difference in frequency of an abnormal DMSA scan compared to a normal scan was found in groups with febrile and non-febrile UTI. No relations between urine cytokines, systemic inflammatory markers and changes in DMSA scan were observed. The cutoff value for detection of inflammatory changes in the DMSA scan for IL-8 was 120 pg/mg creatinine (Cr) and 40 pg/mg Cr for TGF-β1. Based on this value, the sensitivity for IL-8 was 58.3%, specificity 100% and for TGF-β1 66.7% and 83.7%, respectively. Conclusions We found significant differences in children with febrile UTI and ABU regarding urine IL-6, IL-8 and TGF-β1 levels. Urine cytokines and systemic inflammatory markers do not differentiate between upper and lower UTI in infants.

Lupus nephritis in children – 10 years’ experience

Systemic lupus erythematosus (SLE) in children is usually more severe than it is in adults and there is a higher incidence of renal involvement. We described 18 children (16 girls, 2 boys) with lupus nephritis (LN), whose average age was 14.4 ±1.81 years. Disease activity was assessed according to SLEDAI (SLE Disease Activity Index). Renal biopsy was classified according to the INS/RPS (International Society of Nephrology/Renal Pathology Society). The patients were treated with steroids (100%) and pulses of cyclophosphamide (88.9%) or mycophenolate mofetil (11.1%), next azathioprine or mycophenolate mofetil with prednisone in reduced doses. In children with renal/multi-organ insufficiency and/or septicaemia, renal replacement therapy (27.8%), and plasmapheresis (22.2%) were used in the initial treatment. The SLEDAI initial activity was high in 44.4% and moderate in 55.6% of children. LN manifested as: nephrotic syndrome (83.3%), microhaematuria (100%), leukocyturia (60%), hypertension (72.2%), and acute renal injury (83.3%); mean GFR was 54.55 ±33.09 ml/min/1.73 m2. In the renal biopsy, class IV LN according to INS/RPS was mainly diagnosed (82%). At the end of follow-up, mean observation time 32.1±23.36 months: mean GFR was 90.87 ±12.13 ml/min/1.73 m2, proteinuria disappeared in 66.7% and decreased in 33.3% of children to the average of 1.7 g/day (range: 0.5-4.0 g/day), hypertension was observed in 83.4% of children. Intensive immunosuppressive treatment with pulses of cyclophosphamide in early stage of LN in children is very effective.

Effect of perinatal risk factors on neutrophil gelatinase-associated lipocalin (NGAL) level in umbilical and peripheral blood in neonates

Introduction Acute kidney injury biomarkers are opening a new era in diagnosing kidney failure. The requirement for a specific and sensitive marker of kidney function is highly desirable in neonates because the diagnostic possibilities in this age group are not sufficient. Recent research show that neutrophil gelatinase-associated lipocalin (NGAL) can have a great potential but there is a wide range of medical conditions, that may influence their expression. The aim of the study was to evaluate the impact of perinatal risk factors on NGAL level in neonates. Material and methods NGAL was measured in umbilical cord blood and peripheral blood in full term neonates with perinatal risk factors during the first days of life. Results We found significantly higher umbilical cord blood NGAL levels in neonates with perinatal risk factors (117.69 ng/ml) compared to the control group (64.37 ng/ml). No significant difference in peripheral blood NGAL level was shown between the two groups. Umbilical cord blood NGAL level correlated positively with peripheral blood NGAL level (r = 0.36, p < 0.01). Umbilical cord blood NGAL level was significantly higher in neonates with fetal distress and infection compared to neonates with other perinatal risk factors. Peripheral blood NGAL level was significantly higher in neonates with infection compared to neonates with other perinatal risk factors. Significantly higher umbilical cord blood NGAL levels were seen in neonates born by operative delivery compared to born by natural delivery.

Candida spp. and gingivitis in children with nephrotic syndrome or type 1 diabetes

BackgroundDiabetes and Nephrotic syndrome (NS) promote plaque-related gingivitis and yeast-like fungal infections.The study assesses the impact of Candida spp. and general disease- or treatment-related factors on plaque-related gingivitis severity in children and adolescents with Nephrotic syndrome /diabetes.MethodsBody mass index (BMI), BMI standard deviation score, and oral cavity (Plaque Index – PLI, Gingival Index – GI, mucosa status, presence and Candida enzymatic activity) were assessed in 96 patients (32 with NS: 30- immunosuppressive treatment, 35 - type 1 diabetes, and 29 generally healthy), aged; 3–18 years. Laboratory included cholesterol and triglyceride measurements; in diabetic subjects– glycated haemoglobin, in NS: total protein, albumin, creatinine, haemoglobin, haematocrit, white cell count, urinary protein excretion. Medical records supplied information on disease duration and treatment. A statistical analysis was performed; Kendall Tau coefficient, chi-square test, t-test, and multiple regression analysis ( P < 0.05).ResultsCandida spp. often occurred in healthy patients, but oral candidiasis was found only in the NS and diabetes groups (9.37% and 11.43%). Gingivitis occurred more frequently in patients with NS/diabetes. Gingivitis severity was correlated with PLI, age, and yeast enzyme activity in NS – to with immunosuppressive treatment with >1 drug, drug doses, treatment duration, lipid disorders, and BMI; in diabetes, with blood glucose and glycated haemoglobin >8%.ConclusionPoor hygiene control is the main cause of gingivitis. Gingivitis severity is most likely related to age, lipid disorders and increase in body mass. Candida spp., in uncompensated diabetes and in those using immunosuppressive treatment, might intensify plaque-related gingivitis.

Serum GDIgA1 levels in children with IgA nephropathy and Henoch-Schönlein nephritis

Introduction GDIgA1 (galactose deficient IgA1) plays a significant role in the pathogenesis of IgA nephropathy (IgAN) and Henoch-Schönlein nephritis (HSN). Aim of the study The aim of this study was to assess the relevance of serum GDIgA1 level as a prognostic marker in children with IgAN and HSN. Material and methods 41 children were included to the study group (15 IgAN, 26 HSN) and 22 to the control group. The following parameters were evaluated at baseline and endpoint: proteinuria, erythrocyturia, serum creatinine, serum IgA, GFR. A kidney biopsy was performed in all patients and evaluated according to the Oxford Classification (1 – present, 0 – absent: M – mesangial hypercellularity; E– endocapillary hypercellularity; S – segmental sclerosis/adhesion; T – tubular atrophy/interstitial fibrosis), and was calculated as the total score (sum of M, E, S, T). At the end of follow-up, the serum GDIgA1 concentration was measured. Results The serum GDIgA1 concentration in patients with IgAN and HSN was significantly higher than in the control group. No significant differences in mean proteinuria, erythrocyturia, GFR, MEST score, or GDIgA1 in serum, as well as the duration of follow-up between IgAN and HSN were observed. Baseline serum IgA concentration and time to kidney biopsy were significantly higher in children with IgAN than in children with HSN. We observed a positive correlation between GDIgA1 and IgA levels (r = 0.53), and GDIgA1 and serum creatinine levels (r = 0.5), as well as negative correlation between GDIgA1 and GFR (r = –0.37). Conclusions Serum GDIgA1 level may have a prognostic value in children with IgAN and HSN; however, to fully elucidate its clinical potential further studies performed in larger patient cohorts are required.

7-day compared with 10-day antibiotic treatment for febrile urinary tract infections in children: protocol of a randomised controlled trial

Introduction The optimal duration of antibiotic therapy in children with febrile urinary tract infections (UTIs) is still a matter of debate. Current guidelines recommend treating children with febrile UTIs with antimicrobials for 7 to 14 days. We aim to compare the efficacy and safety of 7-day versus 10-day course of oral or sequence therapy (intravenous with a switch to oral) with cefuroxime/cefuroxime axetil for febrile UTIs in children. Methods and analysis A non-inferiority, double-blind, randomised, controlled trial will be conducted. Two hundred twenty-one patients aged 3 months to 7 years with febrile UTIs (defined as a combination of fever and leucocyturia in urine sediment) will be randomly assigned to a 7-day treatment arm (7 days of cefuroxime/cefuroxime axetil followed by 3 days of blinded placebo) or a 10-day treatment arm (7 days of cefuroxime/cefuroxime axetil followed by 3 days of blinded cefuroxime axetil). The primary outcome measure will be frequencies of recurrence and reinfection of UTI during the 6 months after the intervention. Ethics and dissemination The Bioethics Committee approved the study protocol. The findings of this trial will be submitted to a peer-reviewed paediatric journal. Abstracts will be submitted to relevant national and international conferences. Date and protocol version identifier 04/09/2017 Trial registration number NCT03221504.