Pulmonary Langerhans Cell Histiocytosis: Diagnosis in Bronchoalveolar Lavage Liquid-based Cytology Samples.

INTRODUCTION: Pulmonary Langerhans Cell Histiocytosis (PLCH) is a rare interstitial lung disease characterized by the accumulation of Langerhans cells within the lung tissue. The diagnosis of PLCH traditionally involves clinical, radiological, and lung biopsy histopathological evaluations. CASE PRESENTATION: We present two cases where the diagnosis of PLCH was confirmed through the analysis of bronchoalveolar lavage (BAL) fluid cytology using immunoperoxdase technique, highlighting the significance of this minimally invasive technique in the diagnostic process. Clinical and radiological examination suggested advanced interstitial lung disease characterized by a fibrocystic pattern in both cases. The cytologic analysis of the BAL fluid revealed typical histiocytes with longitudinal grooves and eosinophils, which was better seen on liquid-based cytology (LBC) smears. ICC with a CD1a, Langerin, and S-100 confirmed the diagnosis of PLCH. CONCLUSION: Detecting PLCH through the examination of BAL cytology poses challenges, yet it is achievable, particularly with the assistance of LBC and ICC.

Epidemiology, Clinical Profile, Intensive Care Needs and Outcome in Children with SARS-CoV-2 Infection Admitted to a Tertiary Hospital During the First and Second Waves of the COVID-19 Pandemic in India.

OBJECTIVES: To compare the epidemiological, clinical profile, intensive care needs and outcome of children hospitalized with SARS-CoV-2 infection during the first and second waves of the pandemic. METHODS: This was a retrospective study of all children between 1 mo and 14 y, admitted to a dedicated COVID-19 hospital (DCH) during the first (1st June to 31st December 2020) and second waves (1st March to 30th June 2021). RESULTS: Of 217 children, 104 (48%) and 113 (52%) were admitted during the first and second waves respectively. One hundred fifty-two (70%) had incidentally detected SARS-CoV-2 infection, while 65 (30%) had symptomatic COVID-19. Comorbidities were noted in 137 (63%) children. Fifty-nine (27%) and 66 (30%) children required high-dependency unit (HDU) and ICU care respectively. Severity of infection and ICU needs were similar during both waves. High-flow oxygen (n = 5, 2%), noninvasive ventilation [CPAP (n = 34, 16%) and BiPAP (n = 8, 5%)] and invasive ventilation (n = 45, 21%) were respiratory support therapies needed. NIV use was more during the second wave (26% vs. 13%; p = 0.02). The median (IQR) length (days) of DCH stay among survivors was longer during the first wave [8 (6-10) vs. 5.5 (3-8); p = 0.0001]. CONCLUSIONS: Disease severity, associated comorbidities, PICU and organ support need and mortality were similar in the first and second waves of the pandemic. Children admitted during the second wave were younger, had higher proportion of NIV use and shorter length of COVID-19 hospital stay.

Serum Periostin Level in Children with Asthma.

OBJECTIVES: To determine the average serum periostin level in children with asthma between 6 and 16 y of age, and to find out if the levels correlated with markers of eosinophilic inflammation, asthma control, and severity. METHODS: Children under follow-up at a tertiary care centre were enrolled. Children with conditions causing elevated serum periostin other than asthma, or history of systemic steroid use in the past 6 mo were excluded. Serum total IgE and periostin were estimated by ELISA. RESULTS: The median (IQR) serum periostin level was 52.6 (45.4, 58.3) ng/mL. Levels did not vary with age, gender, duration of symptoms, positive family history, or history of exacerbations in the last 6 mo. There was no significant correlation with anthropometric parameters or their z scores, or markers of eosinophilic inflammation in blood including serum total IgE, eosinophil percentage or absolute eosinophil count. There was no difference in median periostin levels of children with different asthma symptom control or asthma severity. CONCLUSIONS: In a group of 26 Indian children with physician-diagnosed asthma, serum periostin showed no significant correlation to markers of eosinophilic inflammation.

Incidence of lymphadenitis following Bacillus Calmette-Guérin (BCG) vaccination in north Indian children.

INTRODUCTION: Bacillus Calmette-Guerin (BCG) vaccination is given as a part of the national immunization schedule in India and its most common complication is BCG lymphadenitis. The reported incidence of BCG lymphadenitis ranges from 0.1 to 9.9% in various studies. In our country, though most babies get BCG vaccination during the neonatal period, the incidence of BCG lymphadenitis is not studied well. AIMS: To study the incidence of lymphadenitis following BCG vaccination at tertiary care hospital in North India. METHODS: It was a prospective longitudinal observational study. All newborns weighing ≥1.5 kg at birth without any significant illness who received BCG vaccination at our institute were enrolled and followed up for 16 weeks after vaccination. Babies were examined at 6, 10 and 14 weeks for the development of lymphadenopathy. Meta-analysis of studies evaluating incidence of BCG adenitis in children was also performed. RESULTS: Out of 817 babies vaccinated during the enrolment period, 605 babies could be followed up till 16.2 ± 0.9 weeks post BCG vaccination. One case of BCG lymphadenitis was detected at 14 weeks. Thus, the observed incidence of BCG lymphadenitis was 0.16% (95% CI of 0.004%-0.92%). Meta-analysis of 21 studies showed mean incidence estimate of 0.336% (95% CI: 0.315%-0.358%) using fixed effect model whereas random effect model showed mean incidence of 4.45% (95% CI: 3.02%-6.15%). CONCLUSION: The lower incidence of lymphadenitis in our study can probably be attributed to a less immunogenic vaccine (Danish 1331), proper technique, experience of the vaccinator and good storage facilities available at our institute.

Flexible Fibreoptic Bronchoscopy and Bronchoalveolar Lavage for Confirmation of Pulmonary Hydatid Disease in Children: A Case Series.

Hydatid disease of the lungs is common in endemic regions. It can be suspected clinically by non-specific respiratory symptoms in children living in endemic regions, especially when they are close to sheep or dogs. Chest imaging X-ray or computed tomography may show characteristic cysts in some cases, but typical findings are absent in many children. Hydatid serology may contribute to the diagnosis, but does not have sufficient sensitivity for pulmonary cysts. Thus, there is no confirmatory diagnostic test, other than surgical excision and histopathologic examination. Hence, there is a need for more reliable diagnostic tests. We present a series of children, both with and without suspected pulmonary hydatid, wherein flexible fibreoptic bronchoscopy (FFOB) performed under conscious sedation, revealed hydatid membranes in the airways. Bronchoalveolar lavage (BAL) analysis revealed hydatid in most of them. Thus the diagnosis could be confirmed even before surgical excision of cysts was performed. We propose that FFOB with BAL could be useful to confirm the diagnosis of pulmonary hydatid in children. This will be particularly helpful in children without characteristic radiological or serological findings. To the best of our knowledge, this is a completely novel approach to the condition with potential to alter the diagnostic paradigm Lay summary Hydatid disease of the lungs is commonly encountered in endemic regions. However, there is no confirmatory diagnostic test for pulmonary hydatid cyst, other than surgical excision and histopathologic examination. Imaging including chest X-ray and computed tomography may not be typical, especially in complicated cysts and hydatid serology does not have a satisfactory sensitivity for diagnosing lung cysts. Thus, there is a need for more reliable diagnostic tests. We present a series of children, both with and without suspected pulmonary hydatid, wherein flexible fibreoptic bronchoscopy (FFOB) under conscious sedation, revealed hydatid membranes in the airways. Bronchoalveolar lavage (BAL) analysis confirmed hydatid in most of them. We propose FFOB with BAL as a useful diagnostic modality to confirm pulmonary hydatid in children, prior to surgical excision. To the best of our knowledge, this is a completely novel approach to the condition with potential to alter the diagnostic paradigm.

Plasma and Urinary Amino Acid Profile in Children with Infantile Tremor Syndrome.

BACKGROUND: Infantile Tremor Syndrome (ITS) is a disorder of infancy, and characterized by developmental delay and/or regression, pallor, skin hyperpigmentation and hypopigmented hair. It is commonly seen in infants in whom exclusive breastfeeding is given inappropriately for longer durations than recommended. ITS is predominantly reported from the Indian subcontinent and in children from a lower socioeconomic background. It is a clinical diagnosis and vitamin B12 deficiency is the most commonly accepted etiology of this entity. OBJECTIVES: The primary objectives of study were to compare the plasma and urine amino acid levels among children with ITS spectrum with those of healthy children. The secondary objectives were to compare the plasma and urine amino acid levels among children with ITS and Pre-ITS. STUDY DESIGN: This cross-sectional, observational study was carried out at a tertiary care hospital in North India. PARTICIPANTS: A total of 50 children aged < 36 months with ITS/Pre-ITS were enrolled. Children with Pre-ITS and ITS were compared with healthy age-matched study subjects. RESULTS: Thirty-nine (78%) cases and twelve (24%) healthy children had low serum vitamin B12 levels. Folate levels were normal in all the controls, while only one case had folate deficiency. There were significant differences (p < 0.05) in the values of 32 amino acids in plasma. Among 44 urinary amino acids, levels of 30 amino acids were significantly different in the cases compared with the controls (p < 0.05). CONCLUSIONS: Several changes in amino acids in the children suffering from ITS were observed. These changes may be a reflection of the metabolic derangements in ITS.

Comparison of performances of loop-mediated isothermal amplification, XPERT MTB/RIF and BACTEC MGIT in the diagnosis of childhood tuberculosis.

AIM: Key to the successful management of paediatric pulmonary tuberculosis (PTB) lies in the early detection and proper treatment. We evaluated the performances of modern diagnostic tests: loop-mediated isothermal amplification (LAMP-IS6110), Xpert MTB/RIF (Cepheid) and mycobacteria growth indicator tube (BACTEC MGIT 960 culture) against a modified version of international consensus diagnostic definition (i.e. composite reference standard (CRS)). METHODS: A cross-sectional analytical study was conducted in a tertiary care hospital in North India from July 2016 to December 2017 involving 100 children <14 years with suspected PTB. Respiratory specimens (sputum, gastric lavage and/or bronchoalveolar lavage) were collected and subjected to LAMP-IS6110, Xpert MTB/RIF and BACTEC MGIT 960 culture assay. RESULTS: Fifty-five children had confirmed and probable TB according to the CRS (prevalence = 58.5%). The sensitivity of BACTEC MGIT 960 culture, Xpert MTB/RIF and LAMP-IS6110 assay was 14%, 9.1% and 10.91%, respectively, when compared against the predefined CRS. The specificity for all these tests was 100%. When compared with BACTEC MGIT 960 culture as the gold standard, the LAMP-IS6110 assay and Xpert MTB/RIF assay had the sensitivity of 85.71% (95% CI: 42.13-99.64%) and 71.43% (95% CI: 29.04-96.33%), respectively. The specificity of both assays was 100%. CONCLUSIONS: We noted that LAMP-IS6110 performed better than Xpert MTB/RIF (Cepheid) in terms of sensitivity when compared against BACTEC MGIT 960 culture as reference standard, though specificity of both the tests was comparable. The diagnostic performance of BACTEC MGIT 960 culture was better than LAMP-IS6110 and Xpert MTB/RIF in paediatric PTB, when compared against CRS.

Fibrosing Mediastinitis Associated With Tuberculosis in Children.

Two children developed fibrosing mediastinitis following past tuberculosis disease. Both were microbiologically negative for tuberculosis at presentation. One was treated with steroids and supportive therapy, but developed active tuberculosis with complications. He ultimately succumbed to healthcare-associated infection. The other recovered with steroids, administered along with antituberculosis treatment.

Coronavirus disease 2019 in children: Clinical & epidemiological implications.

Despite the global spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, there are limited data emerging in children. This review provides an update on clinical features, diagnosis, epidemiology, management and prevention of coronavirus disease 2019 (COVID-19) in children. Specific characteristics noted in children and their implications in disease management as well as transmission control are highlighted. Besides respiratory symptoms, gastrointestinal and atypical features such as chilblains, neurological symptoms and multisystem inflammation are also reported. Younger infants and those with comorbidity were found to be at risk of severe illness. Infected pregnant women and neonates were reported to have good prognosis. It is possible to manage the children with mild disease at home, with strict infection prevention control measures; severely affected require respiratory support and intensive care management. There are anecdotal reports of using antiviral and immunomodulatory drugs, benefit of which needs to be confirmed in clinical trials. A significant percentage of asymptomatic infection in children has epidemiological implication as these may act as links in transmission chain in the community. There is a need for systematic data on extra-pulmonary manifestations and atypical features, risk factors of severity, role of imaging and biomarkers, testing and management strategies and trials with antivirals and immunomodulatory drugs in children. The psychosocial effects of quarantine, closure of schools, lack of play activities and impact of lockdown need to be addressed. Understanding the biological basis for the profound age-dependent differential outcome of COVID-19 infection is important. Elucidating the protective mechanisms in children may aid in developing novel treatment strategies.

Loop-mediated isothermal amplification (LAMP) in the respiratory specimens for the diagnosis of pediatric pulmonary tuberculosis: A pilot study.

BACKGROUND: Loop-mediated isothermal amplification (LAMP) assay is a novel molecular diagnostic technique that can be used for the diagnosis of tuberculosis (TB). It is most suited for developing countries as it is rapid, inexpensive, highly sensitive, requiring minimal infrastructure, training and manpower. Studies in pediatric TB are lacking. We evaluated LAMP in the diagnosis of pediatric pulmonary TB. METHODOLOGY: This was a cross-sectional analytical study conducted at a tertiary care teaching hospital in North India from July 2014 to June 2015 involving 60 children with suspected pulmonary TB. Respiratory specimens (sputum, gastric lavage, bronchoalveolar lavage and/or endotracheal aspirates) were collected and subjected to BACTEC MGIT 960 culture, IS6110 PCR, and LAMP assay targeting IS6110 gene of Mycobacterium tuberculosis. RESULTS: Thirty seven children had confirmed and probable TB according to the composite reference standard (CRS). Among all the 3 tests used for diagnosis of Pulmonary TB, LAMP had highest sensitivity (37.8%) followed by PCR (27%), and culture (21.6%) when compared against the predefined CRS. Culture had maximum specificity of 100%; and PCR, and LAMP had specificity of 95-96%. The sensitivity, specificity, PPV, and NPV of LAMP against culture as reference standard were 75%, 72.4%, 42.9%, and 91.3% respectively. Similarly sensitivity, specificity, PPV, and NPV of PCR against culture as reference standard were 75%, 86.2%, 60%, and 86.2% respectively. On combining LAMP with culture, sensitivity increased to 45.7% (7.8% increase, p = 0.04). CONCLUSION: We noted that LAMP had highest sensitivity when compared to culture and PCR and comparable specificity.

Infantile Tremor Syndrome or a Neurocutaneous Infantile B12 Deficiency (NIB) Syndrome?

OBJECTIVES: To prospectively study the clinical and developmental profile; hematological profile and the B-12 status using multiple parameters in children with Infantile tremor syndrome (ITS). METHODS: In this observational study (NCT02762682) (July 2015 through December 2016) children (and their mothers) with a clinical diagnosis of ITS were evaluated clinically; and development was assessed by CAPUTE scales. A complete blood count (CBC); peripheral blood smear examination; markers of vitamin B12 status (serum B12, homocysteine, folate); acylcarnitines [using Tandem mass spectrometry (TMS)] and urine methylmalonic acid (MMA) [Gas chromatography mass spectrometry (GCMS)] were estimated. A control group of children and their mothers were sampled for comparison. RESULTS: A total of 286 individuals were enrolled for this study. One-hundred-ten children with ITS were screened and 92 (20 with tremors; age 12.7 ± 5 mo, 61 boys) children and their mothers were enrolled. Fifty-one children and their mothers were enrolled as controls. The median clinical linguistic & auditory milestone-developmental quotient (CLAM-DQ) was 32 (IQR 20.6-45.5) and median cognitive adaptive test-developmental quotient (CAT-DQ) was 36.2 (IQR 18.7-49.0). All babies except 9 (ovo-veg) had vegetarian mothers. Head circumference below 2 SD (WHO standards) was seen in 84% and below 3 SD in 58%. The CBC findings were; Hb- 8.3 ± 1.6 g/dl, Thrombocytopenia-29 (32%), mean corpuscular volume (MCV)- 92.2 ± 13.4, MCV- more than 95 fL-38(42%), Red cell distribution width (RDW)- 21.6 ± 6.5, and macrocytes on peripheral smear in 68%. In 89 (97%) out of 92 children had laboratory features of deficient B12 status. Two-thirds of the mothers also had evidence of B12 deficiency. CONCLUSIONS: ITS is, in all likelihood is a consequence of vitamin B12 defeciency. It has a significant impact on head growth and development of affected infants.

Trace Element Status in Children with Infantile Tremor Syndrome: An Inductively Coupled Plasma-Mass Spectrometry Based Study.

The primary objective of the study was to compare the trace element status in children with infantile tremor syndrome (ITS) with healthy controls. Blood counts, serum vitamin B12, plasma homocysteine, plasma ferritin and trace elements - magnesium, zinc and selenium were compared. Twenty-six children (11 with tremors, 14 boys, mean age 11.5 ± 3.5 mo) and 19 controls were enrolled for this study. Low vitamin B12 levels (67% vs. 5%) and elevated plasma homocysteine 96% vs. 26%) was significantly more (P < 0.001) in cases. Eight controls had hypoferritinemia, while none with ITS had it (p < 0.001). None of the children in either group had low serum levels of zinc or magnesium. Low levels of selenium were seen in six cases and five controls. This study did not show any association between the studied nutrients/ trace elements and ITS while, it showed a strong association of ITS with vitamin B12 deficiency supporting that it is a Neurocutaneous Infantile B-12 deficiency (NIB) syndrome.

An Infant with Interstitial Lung Disease.

Interstitial lung disease in infants, unlike older children and adults, has diverse etiology, including infective, metabolic, autoimmune, genetic, malignant and idiopathic causes. Clinical recognition of the interstitial pattern of lung involvement is important as the etiology and management is entirely different from that of recurrent or chronic lung parenchymal pathologies. We discuss the clinical and pathological findings of an infant with interstitial pneumonia, who succumbed to hospital-acquired sepsis.