Quantitative Analysis of Gamma Interferon Release Assay Response in Children with Latent and Active Tuberculosis.

The use of interferon gamma (IFN-γ) release assays (IGRAs) for the diagnosis of tuberculosis (TB) infection in children is still under debate because of concerns about the immature immune response in children. The aim of this study was to investigate quantitative values of the QuantiFERON-TB Gold In-Tube (QFT-IT) test, a commercially available IGRA, in a large cohort of children screened for TB infection. A retrospective analysis was conducted on samples from 517 children aged 0 to 14 years old at the Pediatric Unit of S. Orsola-Malpighi University Hospital of Bologna (Italy); quantitative responses to QFT-IT stimuli were analyzed according to diagnosis and age. Elevated IFN-γ values in the QFT-IT nil (background) tube were statistically associated with diagnosis of active TB. Quantitative IFN-γ response to Mycobacterium tuberculosis-specific antigens (TB Ag) was not significantly different in children with active TB compared to those with latent TB infection (LTBI), even though the median values were higher in the first group. When children were grouped by age, those less than 5 years old produced significantly higher levels of IFN-γ in response to TB Ag if they had active TB (median 10 IU/ml) than those with LTBI (median 1.96 IU/ml). IFN-γ response to mitogen increased with age. The overall rate of indeterminate results was low (3.9%), and no indeterminate QFT-IT values were observed in active or latent TB patients. In conclusion, quantitative QFT-IT values could provide further information to clinicians to manage TB in children, and these observations could be transferred to the new version of the test, QuantiFERON-TB Gold Plus, which to date lacks data from the pediatric population.

Quantiferon-TB Gold In-Tube Improves Tuberculosis Diagnosis in Children.

BACKGROUND: The diagnostic accuracy of Quantiferon-TB Gold In-Tube (QFT-IT) is uncertain in the pediatric population, while tuberculin skin test (TST) is still conventionally used despite its limitations. The aim of this study was to compare the performance of QFT-IT with TST in a large cohort of children screened for tuberculosis (TB) infection because of contact tracing, suspected TB, arrival from endemic country or immunosuppressive therapy. METHODS: A retrospective analysis was conducted on 517 children 0-14 years of age evaluated at the pediatric unit of the S. Orsola-Malpighi University Hospital of Bologna, Italy; 366 of them were also tested with TST. Results were analyzed for Calmette-Guérin bacillus vaccination, country of origin, reason for testing, diagnosis and age. RESULTS: The overall agreement between the 2 tests was 89.9%, but it was highly affected by Calmette-Guérin bacillus vaccination (P < .0001). According to diagnosis and age, QFT-IT detected latent tuberculous infection cases better than TST in all age groups. Sensitivity for diagnosing active TB in symptomatic children was higher for QFT-IT than TST (93.3% vs. 86.5%), especially in children younger than 2 years, while specificity was high for both tests (99.3% and 98.8%, respectively). Low rate of indeterminate QFT-IT results (3.9%) was not differently distributed among age groups, but was associated with diagnosis of TB exclusion (P < 0.0001), mainly pneumonia (35%), and to Italian children (P = 0.0024). CONCLUSIONS: Despite the concern about the use of QFT-IT in children because of their immature immune system, our results suggest the preferential use of QFT-IT as a support tool for diagnosis and management of TB, even in infants.

Growing Up with Type 1 Narcolepsy: Its Anthropometric and Endocrine Features.

STUDY OBJECTIVES: To evaluate the effect of type 1 narcolepsy (NT1) on anthropometric and endocrine features in childhood/adolescence, focusing on patterns and correlates of weight, pubertal development, and growth in treated and untreated patients. METHODS: We collected anthropometric (height, weight, body mass index (BMI) z-scores), pubertal, metabolic, and endocrine data from 72 NT1 patients at diagnosis and all available premorbid anthropometric parameters of patients from their pediatric files (n = 30). New measurements at 1-y reassessment in patients undergoing different treatments were compared with baseline data. RESULTS: We detected a high prevalence of overweight (29.2%), obesity (25%), metabolic syndrome (18.8%), and precocious puberty (16.1%), but no signs of linear growth alterations at diagnosis. According to anthropometric records, weight gain started soon after NT1 onset. At 1-y follow-up reassessment, sodium oxybate treatment was associated with a significant BMI z-score reduction (-1.29 ± 0.30, p < 0.0005) after adjusting for baseline age, sex, sleepiness, and BMI. CONCLUSIONS: NT1 onset in children/adolescents is associated with rapid weight gain up to overweight/obesity and precocious puberty without affecting growth. In our study, sodium oxybate treatment resulted in a significant weight reduction in NT1 overweight/obese patients at 1-y follow-up.

Posterior reversible encephalopathy syndrome associated with licorice consumption: a case report in a 10-year-old boy.

BACKGROUND: Posterior reversible encephalopathy syndrome is characterized by a combination of clinical-radiological findings and pathophysiologically by localized brain vasogenic edema. Many clinical illnesses may trigger the onset of posterior reversible encephalopathy syndrome and hypertension is present in about 80% of patients. METHODS: We describe a child with high consumption of licorice toffees who developed systemic hypertension followed by posterior reversible encephalopathy syndrome. RESULTS: This boy was hospitalized following a cluster of generalized tonic-clonic seizures. Monitoring his clinical parameters, we detected constant high blood pressure and a brain magnetic resonance scan showed a localized vasogenic edema; these symptoms suggested posterior reversible encephalopathy syndrome. He had been eating licorice toffees for a period of 4 months, consuming an estimated 72 mg of glycyrrhizic acid per day; this led to our assumption of the reason for his hypertension. CONCLUSION: There are several reported examples of posterior reversible encephalopathy syndrome-induced licorice hypertension in adults, but none related to children. Our report examines a possible link between licorice consumption and hypertension/posterior reversible encephalopathy syndrome in children.

Diagnosis and management of acute mastoiditis in a cohort of Italian children.

OBJECTIVE: The Italian Society for Pediatric Infectious Diseases created a registry to determine the management of pediatric acute mastoiditis (AM) in Italy. METHODS: A cross-sectional survey of paediatricians was conducted to evaluate hospitalization due to AM in Italian pediatric wards between 1 January 2002, and 31 December 2013. RESULTS: A total of 913 children (561 males, 61.4%) were included in this study. The annual number of AM cases significantly increased during the study period (30 in 2002 and 98 in 2013) but only among older children (≥ 4 years old; p = 0.02). AM complications occurred in 69 (7.6%) of the children and sequelae were observed in 13 (1.4%) patients. CONCLUSION: The annual number of pediatric AM cases admitted to Italian pediatric wards increased in the past few years; this increase was strictly age-related. The risk of severe AM complications appeared relatively low, and most AM cases could be treated conservatively.

Mycoplasma pneumoniae-induced recurrent Stevens-Johnson syndrome in children: a case report.

Mycoplasma pneumoniae, the major pathogen of primary atypical pneumonia, is reported as the most common infectious agent associated with Stevens-Johnson syndrome (SJS) in children. For that reason it is important to consider mycoplasma infection also in the absence of classical pulmonary symptoms. SJS is a rare and acute, self-limited disease, characterized by severe inflammation and necrosis of two or more mucous membranes. We report the case of a 12-year-old boy with a diagnosis of SJS induced by M. pneumoniae infection. The patient's SJS relapsed 8 months after discharge. When the condition is recurrent, it is important early on to identify the cause of a single episode to optimize care and therapeutic choices.

High prevalence of precocious puberty and obesity in childhood narcolepsy with cataplexy.

STUDY OBJECTIVES: We analyzed the potential predictive factors for precocious puberty, observed in some cases of childhood narcolepsy with cataplexy (NC) and for obesity, a much more common feature of NC, through a systematic assessment of pubertal staging, body mass index (BMI), and metabolic/endocrine biochemical analyses. DESIGN: Cross-sectional on consecutive recruitment. SETTING: Hospital sleep center and pediatric unit. PATIENTS: Forty-three children and adolescents with NC versus 52 age-matched obese children as controls. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Patients underwent clinical interview, polysomnographic recordings, cerebrospinal fluid hypocretin-1 measurement, and human leukocyte antigen typing. Height, weight, arterial blood pressure, and Tanner pubertal stage were evaluated. Plasma lipid and glucose profiles were analyzed. When an altered pubertal development was clinically suspected, plasma concentrations of hypothalamic-pituitary-gonadal axis hormones were determined. Children with NC showed a high prevalence of overweight/obesity (74%) and a higher occurrence of precocious puberty (17%) than obese controls (1.9%). Isolated signs of accelerated pubertal development (thelarche, pubic hair, advanced bone age) were also present (41%). Precocious puberty was significantly predicted by a younger age at first NC symptom onset but not by overweight/obesity or other factors. In addition, overweight/obesity was predicted by younger age at diagnosis; additional predictors were found for overweight/obesity (short disease duration, younger age at weight gain and lower high-density lipoprotein cholesterol), which did not include precocious puberty. NC symptoms, pubertal signs appearance, and body weight gain developed in close temporal sequence. CONCLUSIONS: NC occurring during prepubertal age is frequently accompanied by precocious puberty and overweight/obesity, suggesting an extended hypothalamic dysfunction. The severity of these comorbidities and the potential related risks require a multidiagnostic approach and a tailored therapeutic management.

Lung function outcome at school age in very low birth weight children.

OBJECTIVE: The aim of this study was to assess pulmonary function and its predictors in very low birth weight (birth weight ≤1,500 g) children (VLBWc) with or without bronchopulmonary dysplasia (BPD), born at gestational age ≤32 weeks at a single tertiary center during 1996-1999, after the introduction of surfactant therapy. METHODS: Of the 120 surviving VLBW children, 48 (40%) VLBWc (22 with prior-BPD) at age 8.5 ± 1.0 years and 46 age-matched controls (8.8 ± 1.4 years) born at term, underwent lung function study. RESULTS: Adjusted values (z-score) of forced vital capacity (z-FVC), forced expiratory volume in 1 sec (z-FEV1), forced expiratory flow 25-75% (z-FEF25-75), carbon monoxide lung diffusion capacity (z-DLCO), and DLCO/alveolar volume (z-DLCO/VA) were significantly lower than controls (mean difference, 95% CI: -1.35, -1.81 to -0.90, P < 0.001; -1.31, -1.73 to -0.90, P < 0.001; -0.87, -1.29 to -0.46, P < 0.001; -0.98, -1.72 to -0.23, P < 0.001; -0.70, -1.22 to -0.18, P < 0.05; respectively). Residual volume (z-RV) and RV/total lung capacity (RV/TLC) ratio (%) were significantly higher in VLBWc than controls (mean difference, 95% CI: 1.06, 0.44 to 1.68, P < 0.001; 9.54%, 5.73 to 13.3%, P < 0.001; respectively). No differences were found in lung function between VLBWc (no-BPD vs. BPD) with the exception of a significant higher RV/TLC ratio in the BPD-subgroup (mean difference, 95% CI: 7.0%, 0.4 to 13%, P = 0.03). Lung function abnormalities were found in 30 (63%) VLBWc with evidence of airway obstruction and diffusing capacity impairment. A weak relationship was observed between gestational age with z-FVC (r = 0.30, P = 0.04), birth weight with z-FEV1 (r = 0.30, P = 0.04) and RV/TLC ratio (r = -0.49, P = 0.001). The duration of oxygen treatment correlated negatively with the z-DLCO/Va (r = -0.5, P = 0.02). No differences were found in FeNO levels between VLBWc and controls. CONCLUSION: VLBWc at school age showed lung function abnormalities characterized by airway obstruction, hyperinflation, and diffusion impairment. Neonatal lung damage together with preterm birth may play a role in worsening the functional respiratory outcome.

A mesenteric hernia complicated with a triple necrotic volvulus.

A 6-year-old girl was admitted to the paediatric emergency department with colicky abdominal pain. She had a significant medical history, with four previous admissions due to recurrent abdominal pain in the past year. On examination the abdomen was soft, there was no rebound tenderness and Rovsing's sign was negative. Her blood tests revealed a raised white cells count, although her C reactive protein was within the normal range. Abdominal x-ray revealed small bowel obstruction. During her assessment the patient rapidly deteriorated and seemed to go into shock. Her clinical state in addition to the radiological findings meant that she was taken to theatre for surgical exploration. This showed a triple volvulus with necrotic bowel loops that had herniated through a mesenteric defect. The necrotic bowel was subsequently resected.

Gastrointestinal lesions in parvovirus B19 infection.

A 13-year-old girl with persistent fever, pharyngitis, acute anaemia, peripheral blood and bone marrow positive for parvovirus B19 DNA.Microscopic findings of gastrointestinal biopsy showed diffuse vacuolar alteration of the cytoplasma of duodenal enterocytes and virological analysis demonstrated the presence of parvovirus in lymphocytes of the duodenal wall's epithelial layer.In unexplained gastrointestinal pathologies, the role of parvovirus B19 infection should be investigated.

Intravenous high-dose immunoglobulin treatment in recent onset childhood narcolepsy with cataplexy.

We report on the outcome of intravenous high-dose immunoglobulin (IVIg) treatment in four children with narcolepsy and cataplexy, in whom the early diagnosis and the extreme disease severity were indications for this potentially efficacious therapy. One of four patients showed an objective and persistent improvement in clinical features during and after IVIg treatment. Our data partially support the recent report of the efficacy of IVIg treatment in early diagnosed narcolepsy with cataplexy and support the need for a controlled multicenter clinical trial on IVIg in narcolepsy.

Airway inflammation and lung function decline in childhood post-infectious bronchiolitis obliterans.

Post-infectious bronchiolitis obliterans (PBO) is a rare form of chronic obstructive lung disease in children with few data on the pulmonary function outcome and underlying inflammatory process. The aim of this study was to determine the change in lung function over time and to investigate by bronchoalveolar lavage (BAL) the inflammatory characteristics of pulmonary involvement. Eleven Caucasian children with PBO were evaluated to estimate the average rate of change in lung function indices using a mixed model. The differential cytology and lymphocyte subsets of BAL fluid were analyzed. The median follow-up was 10.2 (IQR 3.2-12) years. The estimated forced expiratory volume in 1 sec (FEV1) had a baseline intercept of 57% predicted (62% predicted after bronchodilator) at 10 years of age which fell at a rate of 1.01% per year whereas the estimated forced expiratory flow 25-75 (FEF25-75) had a baseline intercept of 36% predicted (42% predicted after bronchodilator) at 10 years of age which fell at a rate of 1.04% per year. The estimated FEV1/FVC ratio had a baseline intercept of 70% (74% after bronchodilator) at 10 years of age which declined with an average slope of 1.02% per year (-1.10% per year after bronchodilator). Although the baseline and post-bronchodilator level of estimated FVC was abnormal (68% and 69% predicted, respectively) it did not change significantly with time. The median disease duration at BAL evaluation was 3.7 (IQR 0.7-8) years. The percentage differential cell counts were characterized by a significant increase in neutrophils (median 50%, IQR 1-66%), and a slight increase of lymphocytes (median 14%, IQR 7.5-15%). In conclusion, pulmonary function in childhood PBO is characterized by significant airway obstruction which deteriorates over time. The presence of an ongoing inflammatory process could explain the decline in lung function over time.

A case of furuncular myiasis associated with systemic inflammation.

Cutaneous myiasis is a common travel-associated dermatosis caused by fly larvae. We report an unusual case of furuncular myiasis caused by Dermatobia hominis that was associated with signs of systemic inflammation. In this case study, morphological and novel molecular approaches were used to identify and characterize the larvae responsible for human infestation.

Lung function in children with diabetes mellitus.

A cross-sectional study design was undertaken to assess pulmonary function in children with insulin-dependent diabetes mellitus (IDDM), and to establish if there is any relationship with diabetic factors and complications. Thirty-eight children (10 +/- 1.8 years) with IDDM and without clinical or radiological evidence of lung involvement, and 41 healthy age-matched reference subjects, underwent a pulmonary function study. Thirteen (34%) of 38 subjects with IDDM were studied at the onset of their disease. Adjusted values expressed as SD score of forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV(1)), and the transfer factor for carbon monoxide (TLCO) were found to be significantly lower than in controls (-0.54 +/- 0.87 vs. 0.40 +/- 1.10, P = 0.0008; -0.11 +/- 0.96 vs. 0.52 +/- 1.07, P = 0.01; -1.60 +/- 1.07 vs. -0.57 +/- 1.28, P = 0.001, respectively). These differences also existed in the group investigated at onset of diabetes. Residual volume (RV) and RV/total lung capacity ratio (RV/TLC) were significantly higher in the whole group of patients with IDDM than in controls (-0.20 +/- 0.83 vs. -0.80 +/- 0.88, P = 0.003; and 26 +/- 6.2 vs. 21 +/- 5.0, P = 0.0002, respectively). Seventeen patients (45%) had abnormal pulmonary function (SD score, less than -1.64): 16 subjects had reduced TLCO, 4 had reduced FVC, and in 3 of the 17, both functional indices were abnormal. There was no significant relationship between pulmonary function indices and diabetic factors or complications. The only significant association was between abnormal TLCO and females (P = 0.03), suggesting that sex may be a predisposing factor for the development of pulmonary complications. This study supports the view that the lung is functionally involved in children with IDDM early on in the course of the disease.

Clinico-pathological evaluation of ciliary dyskinesia: diagnostic role of electron microscopy.

From November 1995 to May 2002, the authors studied 59 children with suspected primary ciliary dyskinesia (PCD). Samples of ciliated respiratory epithelium were obtained by nasal brushing from 44 patients and by biopsy of bronchial mucosa from 15 patients. Thirty-four/Fifty-nine samples were suitable to obtain a qualitative-quantitative evaluation of ultrastructural ciliary abnormalities. Many ciliary and axoneme alterations were described. This study revealed that quantitative and qualitative ultrastructural assessment of respiratory epithelial cilia plays an important role in the differentiation between primary, secondary, and borderline ciliary abnormalities. Early diagnosis of PCD with appropriate clinical follow-up and treatment is important to prevent irreversible lung tissue damage, namely bronchiectasis.