Reading Ability in Patients With Tuberous Sclerosis Complex: Results of Chinese Character Reading and Reading Comprehension Tests.

Background: Most tuberous sclerosis complex (TSC) patients have neurological disorders and are at high risk of academic difficulties. Among academic skills, reading ability is the most important academic skill. The study applied the Chinese character fluency test to measure the word recognition and reading comprehension of TSC children to observe whether they have the characteristics of reading disability, as an indicator of the spectrum of reading ability in TSC patients. Methods: The patients were assessed using the Chinese character fluency test and reading comprehension test to explore the differences in reading ability in terms of gender, age, epilepsy history, genotype, and intelligence level. Results: Of the 27 patients, the assessment of reading accuracy showed statistical differences between intellectual level > 80, PR (p = 0.024), and pass numbers (p = 0.018). For the fluency assessment, there was a difference between different intellectual level (p = 0.050). In the reading comprehension test, there was differences for intellectual level in positivity (p = 0.07) and pass numbers (p = 0.06). Conclusion: The Chinese character fluency and reading comprehension test measure the word recognition and reading comprehension and the spectrum of reading ability in TSC patients. All individuals with TSC, especially those with below average of intellectual ability, should be considered for potential academic difficulties.

Is Neonatal Hyperbilirubinemia Exposure Associated with a Risk of Autism Spectrum Disorder? A Nationwide Cohort Study.

OBJECTIVE: This study aimed to determine whether neonatal hyperbilirubinemia is associated with a risk of autism spectrum disorder (ASD) using a large population-based cohort. STUDY DESIGN: This retrospective cohort study used data from the children's database (2000-2012) of the National Health Insurance Research Database (1996-2012) in Taiwan. We included neonates who were born between 2000 and 2004 and aged <1 month diagnosed with and without hyperbilirubinemia. The primary outcome was physician-diagnosed ASD. At the end of 2012, multivariate Cox's regression analysis was used to estimate hazard ratios (HRs). RESULTS: A total of 67,017 neonates were included. The neonates with hyperbilirubinemia were associated with 1.28-fold increased risk of ASD (HR = 1.28, 95% confidence interval [CI]: 1.05-1.57) compared with those without hyperbilirubinemia. In subanalysis to determine how phototherapy and exchange transfusion treatment for hyperbilirubinemia were associated with ASD showed no association between treatment and ASD, suggesting the lack of a dose-response effect of hyperbilirubinemia on the risk of ASD. Boys had a nearly six-fold higher risk of ASD than girls (HR = 5.89, 95% CI: 4.41-7.86). Additionally, neonates born with preterm birth and low birth weight were associated with a risk of ASD (HR = 1.46, 95% CI: 1.00-2.13). CONCLUSION: We did not observe a dose-response effect of hyperbilirubinemia on ASD, but neonatal hyperbilirubinemia may be an independent risk factor for ASD if there is a residual confounding by other perinatal complications. Therefore, this study does not support a causal link between neonatal hyperbilirubinemia exposure and the risk of ASD.

Children with allergic rhinitis and a risk of epilepsy: A nationwide cohort study.

PURPOSE: Little is known about whether allergic disease is associated with a subsequent increased risk of childhood-onset epilepsy. We used a large, population-based cohort study to examine whether children with antecedent allergic rhinitis (AR) were associated with a subsequent increased risk of epilepsy. METHODS: This retrospective population-based cohort study was conducted by using data from the 2000-2012 Taiwan's National Health Insurance Research Database. We enrolled 67,537 children aged 0-18 years diagnosed with AR and 67,537 age- and gender-matched children without the diagnosis of AR. The incidence rate (per 10,000 person-years) of epilepsy was calculated. We used Cox proportional hazards regression analysis to estimate hazard ratios (HRs) and 95 % confident interval (CI). RESULTS: Of the 135,074 children included in the analyses, those with AR had a higher incidence rate of epilepsy (6.84 versus 3.95 per 10,000 person-years, p < 0.001) and an earlier age at diagnosis of epilepsy than those without AR [8.54 (4.90) versus 9.33 (5.40) years, p = 0.03)]. The Kaplan-Meier survival analysis demonstrated that the children with AR had a higher likelihood of developing epilepsy than those without AR (p < 0.001). After adjusting for confounding factors in multivariate model, children with AR had a 76 % increased risk of epilepsy (HR 1.76, 95 % CI 1.51-2.04) than those without AR. Boys had a 21 % increased risk of epilepsy (HR 1.21, 95 % CI 1.05-1.40) than girls. CONCLUSIONS: These results suggest that children with AR were associated with an increased subsequent risk of epilepsy.

Neonatal hyperbilirubinaemia is associated with a subsequent increased risk of childhood-onset type 1 diabetes.

Background: Type 1 diabetes (T1D) is one of the most common chronic diseases of childhood. Whether neonatal hyperbilirubinaemia increases the risk of T1D remains unclear.Aim: To estimate the association between neonatal hyperbilirubinaemia and phototherapy and the risk of T1D using a large nationwide population-based cohort.Methods: This retrospective study was conducted using data from the National Health Insurance Research Database in Taiwan from 2001 until 2005. Altogether, 23,784 neonates aged <30 days diagnosed with hyperbilirubinaemia and 47,568 neonates without hyperbilirubinaemia were enrolled and frequency-matched to the hyperbilirubinaemia group by gender, age, parental occupation and urbanisation. Cox regression analysis was performed to estimate hazard ratios (HRs) and 95% confidence intervals (CI).Results: Of the 71,352 neonates included, those with hyperbilirubinaemia had a higher incidence of T1D (4.76 vs 2.68 per 10,000 person-years, p < 0.001) and an earlier mean age at onset of T1D [4.13 (2.80) vs 5.80 (2.67) years, p < 0.001] than those without hyperbilirubinaemia. After adjusting for confounding factors in multivariable analysis, the neonates with hyperbilirubinaemia had a 66% increased risk of developing T1D (HR 1.66, 95% CI 1.26-2.18). Girls had a 1.41-fold (HR 1.41, 95% CI 1.10-1.82) greater risk of T1D than boys. Additionally, neonates with a history of perinatal complications (HR 1.66, 95% CI 0.99-2.80) and neonatal infections (HR 2.13, 95% CI 1.45-3.15) had an increased subsequent risk of T1D.Conclusions: The results suggest that neonatal hyperbilirubinaemia is associated with a subsequently increased risk of childhood-onset T1D.Abbreviations: T1D, type 1 diabetes; CI, confidence interval; NHI, national health insurance; NHIA, National Health Insurance Administration; NHIRD, National Health Insurance Research Database; ICD-9-CM, International Classification of Diseases, Ninth Revision, Clinical Modification; G6PD, glucose-6-phosphate dehydrogenase; LBW, low birthweight; HRs, hazard ratios.

Epithelial growth factor receptor tyrosine kinase inhibitors alleviate house dust mite allergen Der p2-induced IL-6 and IL-8.

Steroid-insensitive asthma-related airway inflammation is associated with the expression of epidermal growth factor receptor (EGFR) tyrosine kinase in asthmatic bronchial epithelium. Proinflammatory cytokines IL-6 and IL-8 are related to steroid-insensitive asthma. It is currently unknown how EGFR-tyrosine kinase inhibitors (EGFR-TKIs) affects house dust mite (HDM)-induced asthma in terms of inflammatory cytokines related to steroid-resistant asthma and further signaling pathway. Cytokine expressions and EGFR signaling pathway were performed by ELISA, reverse transcriptase PCR, real-time PCR, and Western blot in cell-line models. AMP-activated protein kinase (AMPK) pathway-related inhibitors were applied to confirm the association between EGFR-TKI and AMPK pathway. HDM induced IL-6 and IL-8 in a dose-dependent manner. Both Erlotinib (Tarceva) and Osimertinib (AZD-9291) reduced the levels of HDM-stimulated IL-6 and IL-8 levels in BEAS-2B cells. AZD-9291 was more effective than Erlotinib in inhibiting phospho-EGFR, and downstream phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) and phopho-signal transducer and activator of transcription 3 (p-STAT3) pathway signaling. In addition, AMPK pathway-related inhibitor, Calcium-/calmodulin-dependent protein kinase kinase ß (CaMKKß) inhibitor, down-regulated IL-8, but EGFR-TKI had no effect on AMPK pathway. Our findings highlight EGFR-TKIs, Tarceva, and AZD-9291, attenuate HDM-induced inflammatory IL-6 and IL-8 cytokines via EGFR signaling axis pathway, but not AMPK signaling pathway.

Continuous low-dose everolimus shrinkage tuberous sclerosis complex-associated renal angiomyolipoma: a 48-month follow-up study.

Tuberous sclerosis complex (TSC) is a rare disease that causes multisystem benign neoplasm, induced by dysregulation of the mammalian target of the rapamycin pathway (mTOR). This study aimed to examine the effects of continuous low-dose everolimus, a potent and selective inhibitor of mTOR, on the treatment of TSC-associated renal angiomyolipoma (AML). Between July 2013 and August 2017, 11 patients with TSC-AML were enrolled for an everolimus therapy protocol. An oral everolimus dose starting at 2.5 mg daily was gradually increased to 5.0 mg daily. All patients were evaluated using MRI or CT scanning at baseline, 12, 24, 36 and 48 months after the start of treatment for measuring changes of renal AML mass volume. Everolimus therapy resulted in significant shrinkage of TSC-AML volume after 48 months follow-up. Serum levels of everolimus were subdivided into group I (<8 ng/mL, n=6) and group II (>8 ng/mL, n=5). The volume reduction rates were 10.6%-65.2% in group I and 42.5%-70.6% in group II. To evaluate the response to treatment, three of six (50%) were responders in group I, and all the patients in group II (5/5, 100%) were responders. The differences in AML volume reduction between the groups were statistically significant at 12 months (p=0.011), 24 months (p=0006), 36 months (p=0.014) and 48 months (p=0.05). These results suggest that continuous low-dose everolimus therapy (2.5-5 mg daily) might be effective in shrinking TSC-AML volume and minimizes adverse effects and subsequent reducing medical costs.

Vancomycin-Induced Stevens-Johnson Syndrome in a Boy Under 2 Years Old: An Early Diagnosis by Granulysin Rapid Test.

Stevens-Johnson syndrome (SJS) is a life-threatening disease, which is mainly ascribed to drugs, such as sulfonamides and psychoepileptics. In this article, we present a pediatric case of vancomycin-induced SJS and an alternative diagnostic algorithm. The patient presented with multiple target-like rashes and vesicles throughout the whole body after receiving vancomycin. Despite the fact that skin biopsy remains the gold standard for diagnosing SJS, the granulysin rapid test by immunochromatographic assay is a non-invasive option for children. In this article, we describe our use of the Algorithm of Drug causality for Epidermal Necrolysis and a modified T-cell activation assay for granzyme B and interferon gamma to screen for the culprit drug. Moreover, we applied the granulysin rapid test as an early diagnosis method for children with drug-induced SJS.

Trend of seizure remission in patients with tuberous sclerosis complex: A retrospective medical review.

BACKGROUND: Seizures in tuberous sclerosis complex (TSC) tend to be intractable over time and become a subsequent psychological burden for the patients. The purpose of the current study was to describe the onset, phenotype, and factors associated with seizure remission in patients with TSC. METHODS: Patients diagnosed with TSC between 2009 and 2015 completed a questionnaire interview and underwent a systematic evaluation, including a medical review of their epilepsy history and neurobehavioral disorder assessment. RESULTS: Of the 61 patients, 50 patients (82.0%) had a positive seizure history. The active (n = 34) and seizure remission (n = 16) groups showed significant differences in age, neurobehavioral disorder, history of refractory epilepsy, and onset age (p < 0.001, p < 0.05, p < 0.05, and p < 0.05, respectively). The remission rates were 33.3% and 38.5% for those aged 6-18 years and over 18 years, respectively (p for trend = 0.01). CONCLUSION: Seizure remission can occur in adulthood. It shows a high correlation with patient age, minor refractory epilepsy, and neurobehavioral disorders.

Association between allergic disease, sleep-disordered breathing, and childhood nocturnal enuresis: a population-based case-control study.

BACKGROUND: Little is known about the associations between allergic disease, sleep-disordered breathing (SDB), and childhood nocturnal enuresis (NE). We examined whether allergic disease and SDB were associated with childhood NE. METHODS: Data were assessed from the 2007-2012 Taiwan National Health Insurance Research Database. We enrolled 4308 children aged 5-18 years having NE diagnosis and age- and sex-matched 4308 children as the control group. The odds ratios of NE were calculated to determine an association with preexisting allergic disease and SDB. RESULTS: A total of 8616 children were included in the analysis. Prevalence of allergic diseases and SDB was significantly higher for the NE group than the control group (all p < 0.001). After adjusting odds ratios for potential confounding factors, except asthma, children with allergic rhinitis, atopic dermatitis, allergic conjunctivitis, and obstructive sleep apnea (OSA) had significantly higher odds of NE compared with children never diagnosed. With stratification for sex, girls with allergic rhinitis, atopic dermatitis, allergic conjunctivitis, OSA, and snoring had significantly higher odds of NE, compared with girls never diagnosed. Only boys with allergic rhinitis and OSA were associated with increased odds of NE. With stratification for age, children aged 5-12 years with allergic rhinitis, atopic dermatitis, allergic conjunctivitis, and OSA had significantly higher odds of NE compared with those never diagnosed. Odds of NE increased with the number of comorbid allergic diseases. CONCLUSIONS: Allergic diseases and SDB are associated with increased odds of childhood NE. The odds of NE increased with the number of comorbid allergic diseases present.

Evaluation of efficacy and safety of Lactobacillus rhamnosus in children aged 4-48 months with atopic dermatitis: An 8-week, double-blind, randomized, placebo-controlled study.

OBJECTIVE: The main objective of this study was to evaluate the efficacy and safety of Lactobacillus rhamnosus in children aged 4-48 months with atopic dermatitis. METHODS: The design of this study was a two-center, double-blind, randomized, and placebo-controlled study with two parallel groups to evaluate the efficacy and safety profile of L. rhamnosus in children aged 4-48 months with atopic dermatitis diagnosed using Hanifin and Rajka criteria and with a Scoring of Atopic Dermatitis (SCORAD) ≥ 15 at enrollment. The duration of this study was 8 weeks with a total of five visits. The enrolled patients were allocated into either a treatment group (one ComProbi capsule containing L. rhamnosus a day) or a control group (one capsule of placebo a day) at a ratio of 1:1. The primary endpoint was to compare the mean change from baseline in SCORAD after 8 weeks of treatment. The other secondary end points were to compare the following: the mean changes from baseline in SCORAD at postbaseline visits, the frequency and total amount of the use of corticosteroids during the 8-week treatment, the frequency of atopic dermatitis and the symptom-free duration, the mean changes from baseline in Infant Dermatitis Quality of Life Questionnaire at Week 4 and Week 8, and the mean changes from baseline in the Dermatitis Family Impact Questionnaire at Week 4 and Week 8. RESULTS: The mean changes in SCORAD from baseline at Week 8 was -21.69 ± 16.56 in the L. rhamnosus group and -12.35 ± 12.82 in the placebo group for the intent-to-treat population (p = 0.014). For the per-protocol population, the mean change of SCORAD from baseline was -23.20 ± 15.24 in the L. rhamnosus group and -12.35 ± 12.82 in the placebo group (p = 0.003). Significant differences were demonstrated between groups at Week 8 in intensity in the intent-to-treat population and per-protocol population. Throughout the period, the amount of topical corticosteroids used showed no difference between groups. No significant difference was noted in the overall symptom-free durations compared with the placebo group. Infant Dermatitis Quality of Life Questionnaires and Dermatitis Family Impact Questionnaires scores improved significantly at Week 4 and Week 8 but did not reach statistical significance. Adverse events were documented in 14/33 patients in the L. rhamnosus group (42.42%, 35 events) and in 15/33 placebo patients (45.45%, 37 events). CONCLUSIONS: The results of this study indicated that L. rhamnosus was effective in decreasing symptoms of atopic dermatitis after an 8-week treatment by comparing the mean change of SCORAD from baseline with a placebo (p < 0.05). The reduction in SCORAD resulted from a consistent decrease in all components of SCORAD. Patients who took L. rhamnosus for 8 weeks expressed less SCORAD in the three components: area of affected skin, intensity of atopic dermatitis, and patient symptoms, with a significant decrease in the mean change of intensity from baseline compared with placebo.

Trend of nocturnal enuresis in children with attention deficit/hyperactivity disorder: a nationwide population-based study in Taiwan.

Attention-deficit/hyperactivity disorder (ADHD) and nocturnal enuresis are common disorders with extensive psychosocial suffering in affected children, and healthcare burden on parents. Whether the childhood psychological disorders and nocturnal enuresis are factors contributing to ADHD have not been clearly established. This study conducted a population-based case-control study using data sets from the National Health Research Insurance database, and identified 14 900 children diagnosed with ADHD. Risk factors that have been associated with or possibly related to ADHD development were included in this study. Performance of in groups of ADHD with enuresis was compared with controls. With adjustment for potential covariates, participants with enuresis exhibited a 2.24-fold greater risk of subsequent ADHD development compared with controls (95% CI 1.84 to 2.73). Participants with enuresis and comorbidity had a significantly greater risk of ADHD than those with no enuresis and no comorbidity (adjusted OR=8.43, 95% CI 4.38 to 16.2). Children who are assessed for ADHD should be evaluated for the presence of enuresis or other neurobehavioral comorbidities. Multidisciplinary treatment may benefit children with ADHD and minimize psychological burden on parents.

Effects of everolimus on tuberous sclerosis complex-associated renal angiomyolipoma: A preliminary report.

AIM: Tuberous sclerosis complex (TSC) presents with multisystem benign neoplasm induced by dysregulation of the mammalian target of rapamycin pathway. This study aimed to examine the effects of oral everolimus at either 2.5 or 5.0 mg daily on the treatment of TSC-associated renal angiomyolipoma (AML). METHODS: Between July 2012 and August 2015, patients with TSC-associated renal AML were selected for everolimus therapy protocol. An oral everolimus starting dose at 2.5 mg was administered daily, and was gradually increased to 5.0 mg daily. All patients were evaluated using magnetic resonance imaging or computed tomography scanning at baseline, 12, 24, and 36 months after the start of treatment for measuring the changes of renal AML mass volume. RESULTS: Eight patients were finally enrolled for analysis in this study. Everolimus treatment had a statistically significant effect on the renal AML volume reduction during follow-up (P < 0.05). Renal AML mass volume reduction rates were 10.5-45.3% in four patients with everolimus 2.5 mg and 40.7-73.1% in four patients with everolimus 5.0 mg daily; the difference was statistically significant between the two groups (P < 0.05). Longitudinal follow-up for response to everolimus showed volume reduction rates to be around 10.5-73.1% in the initial 6-24 months after everolimus treatment, which remained stable during follow-up up to 36 months. CONCLUSION: The results suggest that an oral everolimus is effective and provides a non-invasive way to treat TSC-associated renal AML, and patients are likely to require maintenance therapy to continue to derive benefit.

Antimicrobial Resistance and Diagnostic Imaging in Infants Younger Than 2 Months Old Hospitalized With a First Febrile Urinary Tract Infection: A Population-based Comparative Study.

BACKGROUND: Data on urinary tract infection (UTI) in infants ≤2 months of age are limited. We examined clinical characteristics, antimicrobial resistance, imaging findings and clinical outcomes in infants ≤2 months of age and children 2-24 months of age hospitalized with the first febrile UTI. METHODS: Children ≤24 months of age hospitalized with their first-diagnosed febrile UTI were prospectively studied. Renal ultrasonography, Tc-dimercaptosuccinic acid scanning and voiding cystourethrography were performed in all children. RESULTS: Of the 388 children analyzed (255 boys and 133 girls), 61 patients were ≤2 months of age, representing 15.7% of the whole population, whereas 327 patients were 2-24 months of age. Escherichia coli was the predominant bacterium, with similar antimicrobial resistance in the 2 groups, and associated E. coli bacteremia occurred in 9 patients (2.3%). Renal ultrasonography showed abnormal findings in 130 patients (33.5%), but there was no difference in the rate of abnormal findings between the groups. Vesicoureteral reflux (VUR) was present in 130 children (33.5%), including 93 (24%) with grades III-V VUR. VUR was more prevalent in the infants ≤2 months of age (P = 0.007), but there was no difference in the prevalence of grades III-V VUR between the groups. The incidence of renal scarring was 28.6% (111/388), and it did not differ between the groups. CONCLUSIONS: There are similarities in clinical characteristics, antimicrobial resistance, imaging findings and clinical outcomes after a first UTI between the young infants ≤2 months and children 2-24 months of age. The same guidelines for the diagnosis and management after the first febrile UTI can be applied to children who are ≤24 months of age.

Association between the growth rate of subependymal giant cell astrocytoma and age in patients with tuberous sclerosis complex.

PURPOSE: The most common neurological complications associated with tuberous sclerosis complex (TSC) include intractable seizures that begin in infancy and subependymal giant cell astrocytoma (SEGA) complicated by hydrocephalus with increasing age. Information on SEGA growth of TSC patients is limited. This study aimed to examine the TSC-SEGA growth rates by periodic neuroimaging. METHODS: This study evaluated the TSC-SEGA growth rates by serial neuroimaging. Fifty-eight patients with TSC underwent systematic evaluation, including a review of medical history and serial brain neuroimaging. RESULTS: While magnetic resonance imaging was more sensitive in detecting cortical tubers than computed tomography (73.1 vs. 0 %, p < 0.001), its efficacy in identifying intracranial lesions was comparable to that of computed tomography (96.2 vs. 100 %, p = 0.658). Significant tumor growth was observed in children (p = 0.012) and adults (p = 0.028) during follow-up periods, respectively (median for children 23.5 months, interquartile range 18-40 months and median for adults 23 months, interquartile range 12-34 months). Further, the SEGA growth rate in children was significantly higher than that in adults (75.6 vs. 16.5 %, p = 0.03). CONCLUSIONS: The results of the study show that SEGA has a significantly higher growth rate in children using serial follow-up brain imaging, suggesting the importance of performing follow-up neuroimaging at yearly intervals in childhood to identify and prevent potential comorbidities.

Role of Renal Ultrasonography in Predicting Vesicoureteral Reflux and Renal Scarring in Children Hospitalized with a First Febrile Urinary Tract Infection.

BACKGROUND: This study was designed to examine the capability of renal ultrasonography (US) for predicting vesicoureteral reflux (VUR) and renal scarring (RS), and to assess, using initial US, the significant urologic abnormalities that impact on management of children hospitalized with a first febrile urinary tract infection (UTI). METHODS: Hospitalized children aged ≤ 2 years with a first febrile UTI were prospectively evaluated using imaging studies, including (99m)Tc dimercaptosuccinic acid (DMSA) scan, US, and voiding cystourethrography. RESULTS: Of the 310 children analyzed (195 boys and 115 girls), 105 (33.9%) had abnormal US. Acute DMSA scans were abnormal in 194 children (62.6%), including 89 (45.9%) with concomitant abnormal US. There was VUR in 107 children (34.5%), including 79 (25.5%) with Grades III-V VUR. The sensitivity and negative predictive values of US were 52.3% and 75.1%, respectively, for Grades I-V VUR and 68.4% and 87.8%, respectively, for Grades III-V VUR. Eighty-five children (27.4%) had RS, including 55 (64.7%) with abnormal US. Of the 105 children with abnormal US, 33 (31.4%) needed subsequent management (surgical intervention, parental counseling, or follow up of renal function). Nephromegaly on initial US and Grades III-V VUR were risk factors of RS. CONCLUSION: Abnormal US may carry a higher probability of Grades III-V VUR and RS, and can affect subsequent management in a significant number of children. Nephromegaly on initial US and Grades III-V VUR are strongly associated with an increased risk for RS. Thus, US should be performed on children after a first febrile UTI and children with normal US may not require voiding cystourethrography.

Necrotizing pneumonia and acute purulent pericarditis caused by Streptococcus pneumoniae serotype 19A in a healthy 4-year-old girl after one catch-up dose of 13-valent pneumococcal conjugate vaccine.

Streptococcus pneumoniae is a common cause of infectious diseases in children that may lead to life-threatening complications. Acute purulent pericarditis is an uncommon complication of S. pneumoniae in the antibiotic era. A healthy 4-year-old girl was admitted with pneumonia and pleural effusion. She had received one catch-up dose of 13-valent pneumococcal conjugate vaccine at 2 years of age. She rapidly developed necrotizing pneumonia, complicated by bronchopleural fistula presenting as subcutaneous emphysema and pneumothorax and acute purulent pericarditis. S. pneumoniae serotype 19A was subsequently identified from blood, empyema and pericardial fluid cultures. After appropriate antibiotic therapy and a right lower lobectomy, her condition stabilized and she promptly recovered. This case highlights two rare potential clinical complications of pneumococcal disease in a child: necrotizing pneumonia and acute purulent pericarditis. This is the first report of a child who received just one catch-up dose of 13-valent pneumococcal conjugate vaccine at 2 years of age, as per the United States' Advisory Committee on Immunization Practice's recommendations, but who still developed severe invasive pneumococcal disease with life-threatening complications caused by S. pneumoniae serotype 19A.