Raphael Halevy

Procalcitonin as a marker of acute pyelonephritis in infants and children

Abstract In the absence of specific symptomatology in children, the early diagnosis of acute pyelonephritis is a challenge, particularly during infancy. In an attempt to differentiate acute pyelonephritis from lower urinary tract infection (UTI), we measured serum procalcitonin (PCT) levels and compared these with other commonly used inflammatory markers. We evaluated the ability of serum PCT levels to predict renal involvement, as assessed by dimercaptosuccinic acid (DMSA) scintigraphy. Serum C-reactive protein (CRP), leukocyte counts, and PCT levels were measured in 64 children admitted for suspected UTI. Renal parenchymal involvement was assessed by 99mTc-DMSA scintigraphy in the first 7 days after admission. In acute pyelonephritis, the median PCT level was significantly higher than in the lower UTI group (3.41, range 0.36–12.4 μg/l vs. 0.13, range 0.02–2.15 μg/l, P<0.0001). In these two groups, respectively, median CRP levels were 120 (range 62–249 mg/l) and 74.5 (range 14.5–235 mg/l, P=0.012) and leukocyte counts were 15,910/mm3 (range 10,200–26,900) and 14,600/mm3 (range 8,190–26,470, P=0.34). For the prediction of acute pyelonephritis, the sensitivity and specificity of PCT were 94.1% and 89.7%, respectively; CRP had a sensitivity of 100%, but a specificity of 18.5%. We conclude that serum PCT may be an accurate marker for early diagnosis of acute pyelonephritis.

Procalcitonin as a diagnostic aid in osteomyelitis and septic arthritis

Objectives: Plasma procalcitonin (PCT) increases rapidly during bacterial infections but remains low in viral infections and other inflammatory processes. High plasma PCT typically occurs in children with bacterial meningitis, severe bacterial infections, particularly in cases of septic shock or bacteremia, and in renal parenchymal damage. The aim of this study was to test the usefulness of plasma PCT analysis in the diagnosis of osteomyelitis, septic arthritis, and other skeletal inflammatory diseases in pediatric patients admitted because of fever and limping. Methods: White blood cell count, erythrocyte sedimentation rate, C-reactive protein, and PCT levels were measured in children admitted to the pediatric department with fever, limping, and suspected osteomyelitis or septic arthritis. PCT levels were measured by an immunochromatography assay, based on monoclonal and polyclonal antibodies against katacalcin. Results: Forty-four children were evaluated: 12 (27.3%) were diagnosed with osteomyelitis, 11 (25%) had septic arthritis, 5 children (11.4%) were diagnosed as a soft tissue infection, and transient synovitis or reactive arthritis was diagnosed in another 6 children (13.6%). Four children (9.1%) were diagnosed as having juvenile rheumatoid arthritis, and 6 (13.6%) with different diseases. PCT value was elevated in 7 patients (58.3%) with osteomyelitis, and only 3 children (27.2%) with the diagnosis of septic arthritis had a mildly elevated value. Among the children with other diagnosis, there were no positive PCT values (P < 0.001 between skeletal infection and all other diagnosis). Conclusions: In this study, PCT was found to be a useful marker in the diagnosis of osteomyelitis and not in septic arthritis. A larger group of patients needed to be studied to confirm our findings.

Procalcitonin is a Predictor for High-Grade Vesicoureteral Reflux in Children: Meta-Analysis of Individual Patient Data

OBJECTIVE To assess the predictive value of procalcitonin, a serum inflammatory marker, in the identification of children with first urinary tract infection (UTI) who might have high-grade (≥3) vesicoureteral reflux (VUR). STUDY DESIGN We conducted a meta-analysis of individual data, including all series of children aged 1 month to 4 years with a first UTI, a procalcitonin (PCT) level measurement, cystograms, and an early dimercaptosuccinic acid scan. RESULTS Of the 152 relevant identified articles, 12 studies representing 526 patients (10% with VUR ≥3) were included. PCT level was associated with VUR ≥3 as a continuous (P = .001), and as a binary variable, with a 0.5 ng/mL preferred threshold (adjusted OR, 2.5; 95% CI, 1.1 to 5.4). The sensitivity of PCT ≥0.5 ng/mL was 83% (95% CI, 71 to 91) with 43% specificity rate (95% CI, 38 to 47). In the subgroup of children with a positive results on dimercaptosuccinic acid scan, PCT ≥0.5 ng/mL was also associated with high-grade VUR (adjusted OR, 4.8; 95% CI, 1.3 to 17.6). CONCLUSIONS We confirmed that PCT is a sensitive and validated predictor strongly associated with VUR ≥3, regardless of the presence of early renal parenchymal involvement in children with a first UTI.

Renal function in children with β-thalassemia major and thalassemia intermedia

In β-thalassemia, profound anemia and severe hemosiderosis cause functional and physiological abnormalities in various organ systems. In recent years, there have been few published studies demonstrating proteinuria, aminoaciduria, low urine osmolality, and excess secretion of the tubular damage markers, such as urinary N-acetyl-D-glucosaminidase (UNAG) and β2 microglobulin, in patients with thalassemia. The object of this study was to analyze renal tubular and glomerular function in pediatric patients with β-thalassemia and to correlate the renal findings to iron overload. Thirty-seven patients with β-thalassemia major and 11 with thalassemia intermedia were studied. Twelve children without iron metabolism disorders or renal diseases served as a control group. No difference in blood urea nitrogen (BUN), serum creatinine, creatinine clearance, electrolytes, fractional excretion of sodium and potassium, and tubular phosphorus reabsorption was found. Serum uric acid was equal in the two groups, but its urine excretion was significantly higher in the thalassemic group. UNAG and UNAG to creatinine ratio (UNAG/CR) were elevated in all patients with thalassemia compared with the control group (p < 0.001) and were directly correlated to the amount of transfused iron but not to actual ferritin level. We found that renal tubular function is impaired in children with β- thalassemia major and intermedia. It is not known whether these functional abnormalities would have any long-term effects on the patients. Further studies are needed, and means of preventing these disturbances should be sought.

Acute mastoiditis in children: Pseudomonas aeruginosa as a leading pathogen

OBJECTIVE Acute mastoiditis is a serious bacterial infection of the temporal bone and is the most common complication of otitis media. The goal of this study is to assess the clinical features, pathogens, management, and outcome of acute mastoiditis in children in northern Israel. METHODS A systematic review of medical records of all children who were admitted with acute mastoiditis from January 1990 through December 2000. RESULTS Fifty-seven children were included. Median was age: 36 months. In 26 patients (45.6%) mastoiditis complicated the first episode of acute otitis media (AOM). Twenty-five children (44%) received antibiotic treatment prior to admission. Frequent symptoms included mastoid area erythema in 54 children (94.7%), proptosis of the auricle in 52 children (91.2%) and fever in 43 children (75.4%). Middle ear, and subperiostal culture yielded growth of pathogen in 30 children (75%), two cultures yielded more then one pathogen. The most frequent pathogens were: Pseudomonas aeruginosa in 10 children (25%), Streptococcus pneumoniae in eight children (20%), Group A streptococcus in six children (15%). The highest incidence of Streptococcus pneumoniae was found in children who did not suffer from AOM before admission (35 vs. 5%). Fifty-two (91.2%) children were cured with antibiotic treatment alone. Seventeen children underwent computed tomography (CT) of the mastoid. Mastoid bone destruction was demonstrated in six children and subperiostal abscess in eight. Mastoidectomy was performed in five children. CONCLUSIONS The diagnosis of acute mastoiditis can be made on clinical basis alone requiring CT only when complications are suspected. Half of the children admitted with acute mastoiditis had no previous history of recurrent AOM. In those children S. pneumoniae was the leading pathogen while P. aeruginosa was more prevalent in children with recurrent AOM. Most of the children recovered with medical therapy alone, without surgical intervention.

Community-Acquired Urinary Tract Infection in Hospitalized Children Etiology and Antimicrobial Resistance. A Comparison Between First Episode and Recurrent Infection

Urinary tract infection (UTI) is common in infants and children, and Escherichia coli is the leading pathogen. The aims of this study were to compare first episode of UTI with recurrent infection, reveal organisms that cause UTI, uropathogen resistance, and presence of bacteria producing extended-spectrum β-lactamase (ESBL). The first-UTI group included 456 children. E coli was the leading pathogen (80.5%), and Pseudomonas aeruginosa was found in 1.5%. The uropathogens were resistant to gentamicin (3.41%) and cefuroxime (5.71%), and highly resistant to cefamezin (37.39%). The recurrent-infection group included 106 children. E coli was also the leading pathogen, but 7.5% of the isolates were P aeruginosa (P = .002 compared with first-episode group); 6.6% were ESBL-producing bacteria compared with 1.1% in the first-episode group (P = .002). E coli is the leading pathogen in both groups. P aeruginosa and ESBL-producing bacteria were more common in the recurrent infection group.

Prediction of moderate and high grade vesicoureteral reflux after a first febrile urinary tract infection in children: construction and internal validation of a clinical decision rule.

PURPOSE Urinary tract infection leads to a diagnosis of moderate or high grade (III or higher) vesicoureteral reflux in approximately 15% of children. Predicting reflux grade III or higher would make it possible to restrict cystography to high risk cases. We aimed to derive a clinical decision rule to predict vesicoureteral reflux grade III or higher in children with a first febrile urinary tract infection. MATERIALS AND METHODS We conducted a secondary analysis of prospective series including all children with a first febrile urinary tract infection from the 8 European participating university hospitals. RESULTS A total of 494 patients (197 boys, reflux grade III or higher in 11%) were included. Procalcitonin and ureteral dilatation on ultrasound were significantly associated with reflux grade III or higher and then combined into a prediction model with an ROC AUC of 0.75 (95% CI 0.69-0.81). Given the prespecified constraint of achieving at least 85% sensitivity, our model led to the clinical decision rule, for children with a first febrile urinary tract infection cystography should be performed in cases with ureteral dilatation and serum procalcitonin level 0.17 ng/ml or higher, or without ureteral dilatation (ie ureter not visible) when serum procalcitonin level is 0.63 ng/ml or higher. The rule had 86% sensitivity (95% CI 74-93) with 47% specificity (95% CI 42-51). Internal cross-validation produced 86% sensitivity (95% CI 79-93) and 43% specificity (95% CI 39-47). CONCLUSIONS A clinical decision rule was derived to enable a selective approach to cystography in children with urinary tract infection. The rule predicts high grade vesicoureteral reflux with approximately 85% sensitivity and avoids half of the cystograms that do not find reflux grade III or higher. Further validation is needed before its widespread use.

Severe Thrombocytopenia and Dermonecrosis after Loxosceles Spider Bite in a 3-Year-Old Child

3-year-old girl was admitted for sudden onset of 12 hours of high fever, vomiting, malaise, and skin rash the day prior to admission, with no history of trauma or drugs. The patient showed a petechial and morbilliform rash, swelling, redness and a dry dark blue-purple lesion on the right big toe (Figure). Blood tests showed thrombocytopenia (18 10 9 /L), high C-reactive protein, and no signs of disseminated intravascular coagulation. A presumptive diagnosis of loxoscelism was made, based on the clinical picture in an endemic area during the warm season. The patient was treated with antibiotics until blood and wound cultures appeared negative and prednisone for 5 days, and was discharged after 4 days with resolution of the systemic symptoms and laboratory improvement. The dermonecrosis underwent desquamation and healing within 3 weeks. Loxoscelism describes the reactions and lesions caused by bites from spiders of the genus Loxosceles. 1-3 In Israel, certified bites of L rufescens have been reported and many cases of loxoscelism have been described. 1,4 Most bites are benign, but local and/or systemic reactions can appear. The typical local manifestation is dermonecrosis. Systemic symptoms include morbilliform rash, fever, chills, nausea, vomiting, malaise, arthralgia, and myalgia; hemolytic anemia and leukocytosis; less frequent thrombocytopenia, disseminated intravascular coagulation, renal failure, multiorgan failure, and even death, more commonly in children than in adults. 1-3 Loxosceles venom contains enzymes (hyaluronidase, alkaline phosphatase, esterase, and sphingomyelinase D2) responsible for tissue destruction and cytotoxicity. 1-3 The diagnosis is rarely based on identification of the spider. A presumptive diagnosis is made clinically, based on

Chronic recurrent multifocal osteomyelitis in infancy: A case report

Ch hronic recurrent multifocal osteomyelitis (CRMO) is a rare disorder characterized by a chronic inflammatory musculoskeletal process that presents with lytic lesions of the multiple bones with pain and swelling of the affected areas. The disorder has a varying course with exacerbations and spontaneous remissions. The etiology of the disorder is unknown, but it is theorized that there is either an au-

Steroid responsive nephrotic syndrome associated with bilateral renal dysplasia.

Abstract Renal dysplasia is characterized by hypoplastic kidneys that contain elements of primitive tubules. Patients may develop end-stage renal failure early in life. Nephrotic syndrome is one of the most common renal diseases in childhood and may occur in association with renal dysplasia. We report a case of a child with bilateral dysplastic kidneys and steroid responsive nephrotic syndrome (SRNS). An association between renal dysplasia with chronic renal failure and SRNS has not previously been reported in the English literature.