Differential Diagnosis of Acute Liver Failure in Children: A Systematic Review.

PURPOSE: To develop a probability-based differential diagnosis for pediatric acute liver failure (PALF) based on age and socioeconomic status of the country of origin. METHODS: Comprehensive literature search using PubMed, EMBASE, and SCOPUS databases was performed. Children 0-22 years of age who met PALF registry criteria were included. Articles included >10 children, and could not be a case report, review article, or editorial. No language filter was utilized, but an English abstract was required. Etiology of PALF, age of child, and country of origin was extracted from included articles. RESULTS: 32 full text articles were reviewed in detail; 2,982 children were included. The top diagnosis of PALF in developed countries was acetaminophen toxicity (9.24%; 95% CredI 7.99-10.6), whereas in developing countries it was Hepatitis A (28.9%; 95% CredI 26.3-31.7). In developed countries, the leading diagnosis of PALF in children aged <1 year was metabolic disorder (17.2%; 95% CredI 10.3-25.5), whereas in developing countries it was unspecified infection (39.3%; CredI 27.6-51.8). In developed countries, the leading diagnosis in children aged >1 year was Non-A-B-C Hepatitis (8.18%; CredI 5.28-11.7), whereas in developing countries it was Hepatitis A (32.4%; CredI 28.6-36.3). CONCLUSION: The leading causes of PALF in children aged 0-22 years differ depending on the age and developmental status of their country of origin, suggesting that these factors must be considered in the evaluation of children with PALF.

Pediatric Syncope: A Systematic Review.

OBJECTIVES: The aims of the study were to perform the first systematic review of pediatric syncope etiologies and to determine the most common diagnoses with credible intervals (CredIs). METHODS: Review was performed within Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines and used Embase, Scopus, PubMed, and the Cochrane Controlled Trial databases. The following inclusion criteria for the articles were used: minimum of 10 patients, standard definition of syncope used, subjects who were 21 years or younger, and subjects who were either a consecutive retrospective group or a prospective group. No restrictions were made regarding language of the studies, but an English abstract was required. The following information was collected: purpose of the study, definition of syncope, number of patients, patient age range, inclusion/exclusion criteria, and etiologies of syncope. RESULTS: Of the 500 articles initially identified, 11 studies met the inclusion criteria and were the basis for this review. Three thousand seven hundred patients were included, ranging in age from 3 months to 21 years. The most common etiologies identified were vasovagal (52.2%; 95% CredI, 50.6-53.9), postural orthostatic tachycardia syndrome (13.1%; 95% CredI, 12.1-14.2), and cardiac causes (4.0%; 95% CredI, 3.39-4.65). A total of 18.3% (95% CredI, 17.0-19.5) of patients were found to have syncope of unknown cause. CONCLUSIONS: Syncope is a common pediatric complaint. Most cases seen are a result of benign causes, with only a small percentage because of serious medical conditions. In addition, most syncopal episodes in the pediatric population are diagnosed clinically or with minimally invasive testing, emphasizing the importance of a detailed history and physical examination.

The Differential Diagnosis of Vertigo in Children: A Systematic Review of 2726 Cases.

OBJECTIVES: Vertigo is a relatively common complaint in children with 5.3% of pediatric patients complaining of this symptom. Although the causes of vertigo have been well established in adults, the diagnoses in children have not been well described. The aims of this systematic review are to discover the current information regarding etiologies of vertigo in children and to determine the most common diagnoses that present with vertigo in pediatric patients. METHODS: PubMed, Scopus, and Embase were searched using the PRISMA guidelines. The inclusion and exclusion criteria were established a priori. All results were analyzed using a Bayesian methodology for point estimation and credible interval calculation. RESULTS: From the database searches, 1419 titles were reviewed. Twenty-two studies met inclusion criteria. From these studies, a total of 2726 children aged 2 months to 19 years were reported. The top 4 diagnoses associated with childhood vertigo include vestibular migraine (23.8%; credible interval, 22.3%-25.5%), benign paroxysmal vertigo of childhood (13.7%; credible interval, 12.4%-15%), idiopathic or no identified association (11.7%; credible interval, 10.5%-12.9%), and labyrinthitis/vestibular neuronitis (8.47%, credible interval, 7.46%-9.55%) accounting for approximately 57% of cases. Less common diagnoses included Meniere disease and central nervous system tumors. CONCLUSIONS: Although the most common causes of pediatric vertigo include vestibular migraine and benign paroxysmal vertigo of childhood, the etiologies are myriad. Rates and credible intervals are provided to permit a probabilistic diagnostic approach to these children.

Etiologies of Pediatric Cervical Lymphadenopathy: A Systematic Review of 2687 Subjects.

Background. Cervical lymphadenopathy in children is common and its etiologies diverse. No systematic review of the differential diagnosis of pediatric cervical lymphadenopathy has been conducted. Objective. To determine the prevalence rate of specific etiologies of pediatric cervical lymphadenopathy. Data Sources. EMBASE, PubMed, and SCOPUS were searched electronically. Bibliographies of select studies were reviewed as well. Study Selection. (1) Any clinical trial, observational study, or cross-sectional case series with 10 or more subjects that included delineation of etiologies and/or associated conditions with lymphadenopathy; (2) subjects aged 0 to 21 years with enlarged lymphoid tissue on body; (3) lymphadenopathy was confirmed by clinical evaluation; and (4) no specific diagnoses were excluded. Data Extraction. Year and location of publication, definition of lymphadenopathy, percentage of lymphadenopathy that was cervical, total number of subjects, gender distribution of subjects, age range of patients, and specific etiologies. Results. Of the 1790 studies, 7 studies that were combined resulted in 2687 subjects that were selected. Nonspecific benign etiology was the most common diagnosis occurring at a rate of 67.8%. Epstein-Barr virus was the next most prevalent (8.86%), followed by malignancy (4.69%) and granulomatous disease (4.06%). The most common malignancy etiology was non-Hodgkin's lymphoma (46.0%), and the most common granulomatous disease was tuberculosis (73.4%). Conclusions. This systematic review and meta-analysis provides a rate-based differential diagnosis of pediatric cervical lymphadenopathy. Although the most common causes of pediatric cervical lymphadenopathy are nonspecific, the etiologies are diverse. Rates and credible intervals are provided to enable a probability-based diagnostic approach to palpable cervical lymphadenopathy in this age group.

The Effects of Inhaled Steroids on Recurrent Wheeze After Acute Bronchiolitis: A Systematic Review and Meta-Analysis of 748 Patients.

Background. Acute bronchiolitis infection during infancy is associated with an increased risk of asthma later in life. The objective of this study was to determine if inhaled steroids are effective in preventing the development of recurrent wheeze or asthma following acute bronchiolitis. Methods. Multiple databases and bibliographies of selected references were searched. Inclusion required (a) a randomized controlled trial of inhaled steroids and control group, (b) at least 2 weeks duration of therapy started during the acute phase of disease, and (c) identification of the rate of recurrent wheeze or asthma at least 6 months after therapy. Results. Of 1410 studies reviewed, 8 reports were included in this meta-analysis (748 patients). The overall odds ratio for developing recurrent wheeze or asthma with treatment versus without treatment was 1.02 (95% confidence interval = 0.58-1.81). Conclusions. A course of inhaled steroids after acute bronchiolitis is not effective in preventing recurrent wheeze or asthma.

Utility of adjunctive macrolide therapy in treatment of children with asthma: a systematic review and meta-analysis.

BACKGROUND: The purpose of this study was to investigate macrolides as an adjunct to an asthma controller regimen in children with asthma. METHODS: Prospective clinical trials of macrolide therapy in children with asthma using outcome measures of change in forced expiratory volume in one second (FEV(1)) and/or oral corticosteroid requirement were searched for in PubMed up to December 2009. The reference lists of studies were also included in the analysis, as well as those listed in published meta-analyses. RESULTS: The literature search yielded 116 studies, six of which were included in this meta-analysis. The change in FEV(1) from baseline with adjunctive use of macrolide therapy in all children was not significant (0.25% predicted; 95% confidence interval [CI] -0.37, 0.86 predicted, P = 0.43); however, the change in FEV(1) among children receiving daily oral corticosteroids was significant (3.89% predicted; 95% CI -0.01, 7.79, P = 0.05). Addition of macrolide therapy to the treatment of children with oral corticosteroid-dependent asthma resulted in a statistically significant decrease in daily corticosteroid dosage (-3.45 mg/day; 95% CI -5.79, -1.09 mg/day, P = 0.004). This reduction in daily corticosteroid dosage was directly proportional to the duration of macrolide therapy (-0.17 mg methylprednisolone per week of macrolide therapy; 95% CI -0.33, -0.021, P = 0.025). CONCLUSION: Addition of macrolides to the treatment regimen of children with oral corticosteroid-dependent asthma improves FEV(1) and decreases the daily dosage of corticosteroids required for control in these children. The degree of dose reduction is directly related to the duration of macrolide therapy. Additional large, randomized, placebo-controlled trials of adjunctive macrolide use in children with oral corticosteroid-dependent asthma are required to verify this observation.

Polymorphous hemangioendothelioma in a child with acquired immunodeficiency syndrome (AIDS).

Polymorphous hemangioendotheliomas (PH) are rare and borderline malignant tumors that are among the wide range of vascular tumors. We report here a 13-year-old male presenting with a history of weight loss, opportunistic infections, and lymphadenopathy. He was determined to be HIV positive and to have acquired immunodeficiency syndrome (AIDS). A biopsy of a femoral node was diagnostic of PH. His systemic lymphadenopathy appeared to resolve with anti-retroviral therapy. This tumor should be considered within the differential diagnoses of pediatric and immunocompromised patients.