Delayed Influenza Treatment in Children With False-Negative Rapid Antigen Test: A Retrospective Single-Center Study in Korea 2016–2019

Background@#We aimed to examine the delay in antiviral initiation in rapid antigen test (RAT) false-negative children with influenza virus infection and to explore the clinical outcomes. We additionally conducted a medical cost-benefit analysis. @*Methods@#This single-center, retrospective study included children (aged < 10 years) with influenza-like illness (ILI), hospitalized after presenting to the emergency department during three influenza seasons (2016–2019). RAT-false-negativity was defined as RAT-negative and polymerase chain reaction-positive cases. The turnaround time to antiviral treatment (TAT) was from the time when RAT was prescribed to the time when the antiviral was administered. The medical cost analysis by scenarios was also performed. @*Results@#A total of 1,430 patients were included, 7.5% were RAT-positive (n = 107) and 2.4% were RAT-false-negative (n = 20). The median TAT of RAT-false-negative patients was 52.8 hours, significantly longer than that of 4 hours in RAT-positive patients (19.2–100.1, P< 0.001). In the multivariable analysis, TAT of ≥ 24 hours was associated with a risk of severe influenza infection and the need for mechanical ventilation (odds ratio [OR], 6.8, P = 0.009 and OR, 16.2, P = 0.033, respectively). The medical cost varied from $11.7–187.3/ILI patient. @*Conclusion@#Antiviral initiation was delayed in RAT-false-negative patients. Our findings support the guideline that children with influenza, suspected of having severe or progressive infection, should be treated immediately.

Pediatric Sarcoidosis Misdiagnosed as Hepatosplenic Abscesses: A Case Report and Review

Sarcoidosis is a systemic granulomatous disorder of unknown etiology characterized by granuloma formation. Due to the limited incidence of sarcoidosis in pediatric patients, little is known about the clinical course of this disease. A combination of clinical, radiologic, and pathologic examination is necessary to exclude other differential diagnoses (i.e., infection and granulomatous inflammatory disorder) and establish a diagnosis of sarcoidosis. Here, we report a case of histologically confirmed sarcoidosis initially misdiagnosed as hepatosplenic abscesses in an 11-year-old male. Treatment with corticosteroids improved his symptoms and resolved his skin and hepatosplenic lesions. A three-year follow-up was uneventful. This study emphasizes the importance of considering sarcoidosis in children presenting with findings of multi-organ involvement in the presence of histologic evidence of granuloma.

Two Cases of Tinea Faciei Mimicking Eczema Herpeticum in Siblings

Tinea faciei is a rare dermatophyte infection of the face that most often appears as a facial rash, followed by patches of small and raised bumps. Since it is uncommon in children and has similar rash patterns with various skin diseases, it is likely to be misdiagnosed as herpes simplex infection, contact dermatitis, disc-shaped lupus erythematosus, acne, and atopic dermatitis. In this case, siblings aged 3 and 4 were hospitalized due to skin rashes that occurred after traveling to Vietnam, and were administered antiviral drugs and systemic steroids under suspicion of herpes simplex infection with atopic dermatitis. Despite administration of these drugs, skin lesions did not show improvement. Serum beta-Dglucan assays were elevated in both patients, and after approximately 2 weeks, Trichophyton interdigitale was cultured in the older sister's skin fungal culture test. Both patients recovered after local and systemic antifungal therapy, without relapse or side effects. Skin lesions on the face, which do not respond to the existing treatment in children, should be checked for the possibility of tinea faciei through repeated fungal tests, and the beta-D-glucan assay can be a useful tool in diagnosing tinea faciei.

Evaluation of Interferon-gamma Release Assay in Children with Confirmed Tuberculosis

Purpose@#This study aimed to evaluate the diagnostic value of the QuantiFERON-TB Gold InTube (QFT-GIT) in children with confirmed tuberculosis (TB). @*Methods@#We retrospectively reviewed the medical records of children aged ≤18 years who underwent both QFT-GIT and Mycobacterium tuberculosis culture between 2006 and 2017.Confirmed TB was defined as the presence of at least one positive specimen for M. tuberculosis on culture or a nucleic acid amplification test. @*Results@#Of the 582 patients included in the analysis, 48 were confirmed to have TB. The sensitivity and specificity of QFT-GIT for the diagnosis of confirmed TB were 85.4% and 95.5%, respectively. Among children with confirmed TB, the proportion in the immunocompromised state was higher in the QFT-GIT negative group than in the QFT-GIT positive group (50.0% vs. 5.7%, P=0.010). The median age at sampling was lower in the QFTGIT indeterminate group than in the QFT-GIT positive group (7 years vs. 17 years, P=0.008), and the proportion of immunosuppression was higher in the QFT-GIT indeterminate group than in the QFT-GIT positive group (42.9% vs. 5.7%, P=0.017). The interferon gamma response to mitogen control was significantly higher in the 10–18 years group than in the 0–9 years group (P<0.001), and was significantly higher in the immunocompetent group than in the immunocompromised group (P=0.001). @*Conclusion@#The QFT-GIT results should be interpreted carefully in immunocompromised or younger children suspected of having TB.

A case of neonatal lupus presenting with fever and skin rash in a 47-day-old girl

Neonatal lupus (NL) is a passively acquired autoimmune disease that occurs in infants born from asymptomatic mothers having anti-SSA or anti-SSB antibody. Infants with NL may show symptoms of systemic lupus erythematosus, including skin rash, congenital heart block, hepatic dysfunction, and hematological abnormalities. Mothers of the infants are asymptomatic or diagnosed with autoimmune diseases. When infants born to asymptomatic mothers who have never been diagnosed with the diseases show symptoms of NL, they may be mistaken for having infections. We report an NL case of a 47-day-old girl who presented to the emergency department with fever and skin rash.

Two Cases of Tinea Faciei Mimicking Eczema Herpeticum in Siblings

Tinea faciei is a rare dermatophyte infection of the face that most often appears as a facial rash, followed by patches of small and raised bumps. Since it is uncommon in children and has similar rash patterns with various skin diseases, it is likely to be misdiagnosed as herpes simplex infection, contact dermatitis, disc-shaped lupus erythematosus, acne, and atopic dermatitis. In this case, siblings aged 3 and 4 were hospitalized due to skin rashes that occurred after traveling to Vietnam, and were administered antiviral drugs and systemic steroids under suspicion of herpes simplex infection with atopic dermatitis. Despite administration of these drugs, skin lesions did not show improvement. Serum beta-Dglucan assays were elevated in both patients, and after approximately 2 weeks, Trichophyton interdigitale was cultured in the older sister's skin fungal culture test. Both patients recovered after local and systemic antifungal therapy, without relapse or side effects. Skin lesions on the face, which do not respond to the existing treatment in children, should be checked for the possibility of tinea faciei through repeated fungal tests, and the beta-D-glucan assay can be a useful tool in diagnosing tinea faciei.

Evaluation of Interferon-gamma Release Assay in Children with Confirmed Tuberculosis

Purpose@#This study aimed to evaluate the diagnostic value of the QuantiFERON-TB Gold InTube (QFT-GIT) in children with confirmed tuberculosis (TB). @*Methods@#We retrospectively reviewed the medical records of children aged ≤18 years who underwent both QFT-GIT and Mycobacterium tuberculosis culture between 2006 and 2017.Confirmed TB was defined as the presence of at least one positive specimen for M. tuberculosis on culture or a nucleic acid amplification test. @*Results@#Of the 582 patients included in the analysis, 48 were confirmed to have TB. The sensitivity and specificity of QFT-GIT for the diagnosis of confirmed TB were 85.4% and 95.5%, respectively. Among children with confirmed TB, the proportion in the immunocompromised state was higher in the QFT-GIT negative group than in the QFT-GIT positive group (50.0% vs. 5.7%, P=0.010). The median age at sampling was lower in the QFTGIT indeterminate group than in the QFT-GIT positive group (7 years vs. 17 years, P=0.008), and the proportion of immunosuppression was higher in the QFT-GIT indeterminate group than in the QFT-GIT positive group (42.9% vs. 5.7%, P=0.017). The interferon gamma response to mitogen control was significantly higher in the 10–18 years group than in the 0–9 years group (P<0.001), and was significantly higher in the immunocompetent group than in the immunocompromised group (P=0.001). @*Conclusion@#The QFT-GIT results should be interpreted carefully in immunocompromised or younger children suspected of having TB.

A case of neonatal lupus presenting with fever and skin rash in a 47-day-old girl

Neonatal lupus (NL) is a passively acquired autoimmune disease that occurs in infants born from asymptomatic mothers having anti-SSA or anti-SSB antibody. Infants with NL may show symptoms of systemic lupus erythematosus, including skin rash, congenital heart block, hepatic dysfunction, and hematological abnormalities. Mothers of the infants are asymptomatic or diagnosed with autoimmune diseases. When infants born to asymptomatic mothers who have never been diagnosed with the diseases show symptoms of NL, they may be mistaken for having infections. We report an NL case of a 47-day-old girl who presented to the emergency department with fever and skin rash.

Flow Cytometry for the Diagnosis of Primary Immunodeficiency Diseases: A Single Center Experience

PURPOSE: While there is an urgent need for diagnosis and therapeutic intervention in patients with primary immunodeficiency diseases (PIDs), current genetic tests have drawbacks. We retrospectively reviewed the usefulness of flow cytometry (FCM) as a quick tool for immunophenotyping and functional assays in patients suspected to have PIDs at a single tertiary care institute.METHODS: Between January 2001 and June 2018, patients suspected of having PIDs were subjected to FCM tests, including lymphocyte subset analysis, detection of surface- or intracellular-target proteins, and functional analysis of immune cells, at Samsung Medical Center, Seoul, Korea. The genetic diagnosis was performed using Sanger or diagnostic exome sequencing.RESULTS: Of 60 patients diagnosed with definite or probable PID according to the European Society of Immune Deficiencies criteria, 24 patients were provided with useful information about immunological dysfunction after initial FCM testing. In 10 patients, the PID diagnosis was based on abnormal findings in FCM testing without genetic tests. The FCM findings provided strong evidence for the diagnosis of severe combined immunodeficiency (n = 6), X-linked chronic granulomatous diseases (CGD) (n = 6), leukocyte adhesion deficiency type 1 (n = 3), X-linked agammaglobulinemia (n = 11), autoimmune lymphoproliferative syndrome-FASLG (n = 1), and familial hemophagocytic lymphohistiocytosis type 2 (n = 1), and probable evidence for autosomal recessive-CGD (n = 2), autosomal dominant-hyper-immunoglobulin E (IgE)-syndrome (n = 1), and STAT1 gain-of-function mutation (n = 1). In PIDs derived from PIK3CD (n = 2), LRBA (n = 2), and CTLA4 mutations (n = 3), the FCM test provided useful evidence of immune abnormalities and a tool for treatment monitoring.CONCLUSIONS: The initial application of FCM, particularly with known protein targets on immune cells, would facilitate the timely diagnosis of PIDs and thus would support clinical decisions and improve the clinical outcome.

Epidemiology and Clinical Features of Coronavirus disease 2019 in Children

Coronavirus disease 2019 (COVID-19), which started in Wuhan, China, in December 2019 and declared a worldwide pandemic on March 11, 2020, is a novel infectious disease that causes respiratory illness and death. Pediatric COVID-19 accounts for a small percentage of patients and is often milder than that in adults; however, it can progress to severe disease in some cases. Even neonates can suffer from COVID-19, and children may spread the disease in the community. This review summarizes what is currently known about COVID-19 in children and adolescents.

Clinical Features of and Antibiotic Resistance in Recurrent Urinary Tract Infection in Children with Vesicoureteral Reflux

Purpose@#This study aimed to investigate the clinical features of recurrent urinary tract infection (UTI) in children with vesicoureteral reflux (VUR) and to compare the causative uropathogen and antibiotic susceptibility between the first and recurrent UTI episodes. @*Methods@#We retrospectively reviewed the medical records of children with VUR who had recurrent UTI. Group 1 included patients in whom the same pathogen caused the first and recurrent UTI episodes. Group 2 included patients in whom different pathogens caused the first and recurrent UTI episodes. @*Results@#During a 13-year study period (2005–2018), 77 children with VUR experienced at least one episode of UTI. Among these, 47 patients (61.0%) had recurrent UTI. Of the children with recurrent UTI, 19 (40.4%) were in group 1 and 28 (59.6%) were in group 2. Escherichia coli was the most commonly isolated uropathogen (n=37; 39.4%) in both episodes of recurrent UTIs, followed by Klebsiella pneumoniae (n=18; 19.1%), Enterococcus faecalis (n=14; 14.9%), and Enterobacter aerogenes (n=7; 7.4%). Although the difference was not significant, the rate of resistance to the antibiotics ceftazidime, piperacillin/tazobactam, and trimethoprim-sulfamethoxazole increased in patients with the second episode of E. coli recurrence in group 1, and that to cefotaxime, ceftazidime, piperacillin/tazobactam, and meropenem increased in children with the second episode of E. aerogenes recurrence in group 1. @*Conclusions@#When selecting empirical antibiotics for recurrent UTI in children with VUR, it is important to consider that the pathogen and antimicrobial susceptibility of the previous UTI are not always the same in recurrent UTIs.

Successful Sirolimus Treatment for Korean Patients with Activated Phosphoinositide 3-kinase δ Syndrome 1: the First Case Series in Korea

Activated phosphoinositide 3-kinase δ syndrome (APDS)1 is caused by gain-of-function mutations in PIK3CD, which encodes the catalytic p110δ subunit of phosphoinositide 3 kinase. We describe three patients with APDS1, the first thereof in Korea. Therein, we investigated clinical manifestations of APDS1 and collected data on the efficacy and safety profile of sirolimus, a mammalian target of rapamycin inhibitor and pathway-specific targeted medicine. The same heterozygous PIK3CD mutation was detected in all three patients (E1021K). After genetic diagnosis, all patients received sirolimus and experienced an excellent response, including amelioration of lymphoproliferation and improvement of nodular mucosal lymphoid hyperplasia in the gastrointestinal tract. The median trough level of sirolimus was 5.5 ng/mL (range, 2.8–7.5) at a dose of 2.6–3.6 mg/m2. Two patients who needed highdose, short-interval, immunoglobulin-replacement treatment (IGRT) had a reduced requirement for IGRT after initiating sirolimus, and the dosing interval was extended from 2 and 3 weeks to 4 weeks. The IgG trough level after sirolimus treatment (median, 594 mg/dL; range, 332–799 mg/dL) was significantly higher than that before sirolimus treatment (median, 290 mg/dL; range, 163–346 mg/dL) (p<0.001). One episode of elevated serum creatinine with a surge of sirolimus (Patient 2) and episodes of neutropenia and oral stomatitis (Patient 1) were observed. We diagnosed the first three patients with APDS1 in Korea. Low-dose sirolimus may alleviate clinical manifestations thereof, including hypogammaglobulinemia.

Incidence and Characteristics of Clostridioides difficile Infection in Children

Purpose@#We evaluated the incidence and characteristics of Clostridioides difficile infection (CDI) in Korean children. @*Methods@#Medical records of patients aged 2–18 years and diagnosed with CDI at a tertiary hospital between 2009 and 2018 were analyzed. The patients were classified into three CDI groups: community-acquired (CA), community onset-health care facility-associated (COHCFA), and healthcare facility onset (HO). @*Results@#The incidence of CDI increased from 1.00 to 10.01 cases per 10,000 admissions from 2009 to 2018 (P<0.001). As compared to the CA group, the HO group had a higher frequency of operation and malignancy as predisposing factors (40.4% vs. 0.0%, P=0.001; and 27.7% vs. 0.0%, P=0.027, respectively), frequency and number of previous antibiotic use (97.9% vs. 31.3%, P<0.001; and 2 vs. 0, P<0.001, respectively), and median postdiagnosis hospital stay (13 vs. 5 days, P=0.008). The CO-HCFA group had a lower median age and higher frequency of malignancy than the CA group (5 vs. 13 years, P=0.012; and 30.8% vs.0.0%, P=0.030, respectively). As compared to the HO group, the CA group had a higher frequency of abdominal pain and hematochezia (56.3% vs. 10.6%, P=0.001; and 50.0% vs. 10.6%, P=0.002, respectively), inflammatory bowel disease (68.8% vs. 2.1%, P=0.001), and intravenous metronidazole treatment (37.5% vs. 2.1%,P=0.001). @*Conclusions@#With the increasing incidence of pediatric CDI, awareness regarding its epidemiology and clinical characteristics is important to manage nosocomial infections.

Incidence and Characteristics of Clostridioides difficile Infection in Children

Purpose@#We evaluated the incidence and characteristics of Clostridioides difficile infection (CDI) in Korean children. @*Methods@#Medical records of patients aged 2–18 years and diagnosed with CDI at a tertiary hospital between 2009 and 2018 were analyzed. The patients were classified into three CDI groups: community-acquired (CA), community onset-health care facility-associated (COHCFA), and healthcare facility onset (HO). @*Results@#The incidence of CDI increased from 1.00 to 10.01 cases per 10,000 admissions from 2009 to 2018 (P<0.001). As compared to the CA group, the HO group had a higher frequency of operation and malignancy as predisposing factors (40.4% vs. 0.0%, P=0.001; and 27.7% vs. 0.0%, P=0.027, respectively), frequency and number of previous antibiotic use (97.9% vs. 31.3%, P<0.001; and 2 vs. 0, P<0.001, respectively), and median postdiagnosis hospital stay (13 vs. 5 days, P=0.008). The CO-HCFA group had a lower median age and higher frequency of malignancy than the CA group (5 vs. 13 years, P=0.012; and 30.8% vs.0.0%, P=0.030, respectively). As compared to the HO group, the CA group had a higher frequency of abdominal pain and hematochezia (56.3% vs. 10.6%, P=0.001; and 50.0% vs. 10.6%, P=0.002, respectively), inflammatory bowel disease (68.8% vs. 2.1%, P=0.001), and intravenous metronidazole treatment (37.5% vs. 2.1%,P=0.001). @*Conclusions@#With the increasing incidence of pediatric CDI, awareness regarding its epidemiology and clinical characteristics is important to manage nosocomial infections.

Non-Mandatory Influenza Vaccination Rates among Healthcare Workers during the 2017–2018 Influenza Season: a Multicenter Study in Korea

PURPOSE: Annual influenza vaccination is the best strategy to prevent healthcare-associated influenza transmission. Influenza vaccination rates among healthcare workers (HCWs) vary by country, region, and year. We investigated the influenza vaccination rates for HCWs during the 2017–2018 influenza season in South Korea, where a non-mandatory vaccination campaign was conducted.METHODS: We retrospectively investigated factors affecting the influenza vaccination rate among HCWs during the 2017–2018 influenza season in three tertiary hospitals in Goyang City, where the non-mandatory influenza vaccination program is conducted.RESULTS: Consequently, 6,994 of 7,180 HCWs (97%) were included, and the overall vaccination rate was 85%. Nurses had the highest rate with 92%, followed by health technicians (88%), physicians (84%), and non-medical HCWs (79%, P<0.001). Vaccination rates differed, depending on the frequency of contact with patients in the non-medical HCWs (frequent contact vs. less-frequent contact; 90% vs. 73%, P<0.001).CONCLUSIONS: The influenza vaccination rate among HCWs during the 2017–2018 influenza season in Korea was 85%, which is among the highest rates compared with previously reported non-mandatory vaccination rates in other countries. The vaccination rate may vary depending on the HCW's occupational characteristics, including the extent of contact with the patient. Therefore, a multifaceted strategy is needed to increase the vaccination rate of HCWs.

Intraventricular Vancomycin Therapy for Intractable Bacillus cereus Ventriculitis

Bacillus cereus causes serious central nervous system infections, especially in immunocompromised patients. Successful treatment requires adequate antimicrobial concentrations in the cerebrospinal fluid; however, in some cases, achieving this with systemic treatment alone is difficult. We treated intractable B. cereus ventriculitis with intraventricular vancomycin, with no major adverse events.

Changes in Cytomegalovirus Seroprevalence in Korea for 21 Years: a Single Center Study

PURPOSE: Cytomegalovirus (CMV) infection is mostly asymptomatic but can be detrimental to certain hosts. We investigated changes of CMV seroprevalence in Koreans before and after the year 2000. METHODS: We reviewed laboratory values of patients who were tested for CMV immunoglobulin G (IgG) at Samsung Medical Center, Seoul, Korea, from January 1995 to December 2015. Changes in seroprevalence were analyzed by gender, age, region, and tested year period (period 1, 1995–2005 vs. period 2, 2006–2015). RESULTS: Overall CMV seropositivity was 94.1% (10,900/11,584). There was no significant difference for CMV seropositivity among the two periods (94.2% vs. 94.1%) (P=0.862). CMV seropositivity in the 11 to 20-year age group in period 2 (78.8%) was significantly lower than that of period 1 (89.9%) (P=0.001). The seropositivity of individuals aged 31–40 years (97.4%) was significantly higher than that of younger age groups (P < 0.001) and lower than that of older age groups (P < 0.001). Of 2,441 females of reproductive age (from 15 to 49), CMV seropositivity was 97% (2,467/2,441). The seropositivity in women aged 20–24-years was higher than that of men in the same age group (97.6% vs. 85.6%, P=0.003). No significant difference was observed among different regions. CONCLUSIONS: Overall CMV seropositivity of Koreans was estimated to be 94% and the average seropositivity of reproductive women was 97%. Monitoring of the changes in seroprevalence including the reproductive age group is needed in the future.

Etiology and clinical characteristics of fever of unknown origin in children: a 15-year experience in a single center / 소아과

PURPOSE: Fever is one of the most common symptoms in children. In previous studies, infectious disease was the most common cause of pediatric fever of unknown origin (FUO). The aim of this study is to investigate the etiology, clinical characteristics and prognosis of pediatric FUO in 21 century with more diagnostics available and to analyze the factors for certain disease categories. METHODS: Among the children under 18 years old who were hospitalized at Samsung Medical Center from January 2000 to December 2014, the patients who met the criteria including fever of ≥38.0℃ for longer than ≥14 days and failure to reach a diagnosis after one week of investigations were included. RESULTS: Total 100 patients were identified. Confirmed diagnosis was achieved in 57 patients (57%). Among them, infectious diseases (n=19, 19%) were most common, followed by connective tissue diseases (n=15, 15%), necrotizing lymphadenitis (n=8, 8%), and malignancies (n=7, 7%). Children with fever duration over 28 days had a trend for higher frequency of connective tissue diseases (28.3%) except undiagnosed etiology. The symptoms such as arthritis, lymph node enlargement and only fever without other symptoms were significantly related with connective tissue diseases, necrotizing lymphadenitis and undiagnosed respectively (P<0.001). Ninety-two patients have become afebrile at discharge and 1 patient died (1%). CONCLUSION: Almost half of our patients were left without diagnosis. Although it has been known that infectious disease was most common cause of pediatric FUO in the past, undiagnosed portion of FUO have now increased due to development of diagnostic techniques for infectious diseases.

Importance of Specimen Type and Quality in Diagnosing Middle East Respiratory Syndrome

No abstract available.

The First Newborn Screening Study of T-Cell Receptor Excision Circle and κ- Deleting Recombination Excision Circle for Severe Combined Immunodeficiency in Korea: A Pilot Study

PURPOSE: Severe combined immunodeficiency (SCID) is the most serious form of primary immunodeficiency. Infants with SCID are susceptible to life-threatening infections. To establish newborn screening for SCID in Korea, we performed a screening test for T-cell receptor excision circle (TREC) and κ-deleting recombination excision circle (KREC) in neonates and investigated the awareness of SCID among their parents. METHODS: Collections of dried blood spots from neonates and parent surveys were performed at the Samsung Medical Center and Cheil General Hospital & Women's Healthcare Center in Korea. The amplification crossing point (Cp) value 39.0 was defined as negative. RESULTS: For TREC/KREC screening, 141 neonates were enrolled; 63 (44.7%) were male. One hundred forty neonates (99.3%) had positive TREC/KREC results at the time of the initial test; 82.3% and 75.9% were positive and 17.0% and 23.4% were weakly positive for TREC and KREC, respectively. In one neonate (0.7%), the initial TREC/KREC test result was negative. However, repeated tests obtained and confirmed a positive result. For an awareness survey, 168 parents were engaged. Only 2% of parents (3/168) knew that the newborn screening test for SCID had been introduced and performed in other countries. Eighty-four percent of parents (141/168) replied that nationwide newborn SCID screening should be performed in Korean newborns. CONCLUSIONS: In this study, newborn SCID screening was performed along with assessment of public awareness of the SCID test in Korea. The study results showed that newborn SCID screening can be readily applied for clinical use at a relatively low cost in Korea.