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Background: Kawasaki disease (KD) is predominantly seen in young children (<5 years). Diagnosis of KD is often delayed in older children and adolescents, leading to a higher risk of coronary artery abnormalities (CAAs). There is a paucity of literature on KD in older children. Methods: Data were collated from a review of records of patients diagnosed with KD who were aged ≥10 years at the time of diagnosis, during the period from January 1994 to June 2019. Results: Eight hundred and sixty five patients were diagnosed with KD during this period. Of these, 46 (5.3%; 26 boys and 20 girls) were aged 10 years or older at the time of diagnosis. The median age at diagnosis was 11 years (range of 10-30 years). The median interval between the of fever and the diagnosis of KD was 12 days (range of 4-30 days). Eight patients (17.4%) presented with hypotensive shock. Coronary artery abnormalities (CAAs) were seen in six patients (13.04%), and three patients had myocarditis. Patients with CAAs were found to have significantly higher median platelet counts and higher median C-reactive protein levels. First-line treatment included intravenous immunoglobulin. Adjunctive therapy was given in five patients (infliximab in four patients and steroids in one patient). The median time between the onset of fever and the administration of IVIg was 13.5 days (range of 6-2). The total duration of follow up is 2,014.5 patient-months. Conclusion: Diagnosis of KD in children older than 10 years is usually delayed, and these patients are thus at a higher risk of CAAs., (Copyright © 2020 Jindal, Pilania, Guleria, Vignesh, Suri, Gupta, Singhal, Rawat and Singh.)

Background: More than 70% of human immunodeficiency virus (HIV)-positive children sustain respiratory diseases in their lifetime. Imaging plays an important role in establishing early and correct diagnosis., Objective: To evaluate the diagnostic accuracy of 3-Tesla (T) thorax MRI in HIV-positive children, using chest CT as the gold standard., Materials and Methods: We included 25 children with confirmed HIV-positive status and pulmonary complaints who were referred for chest CT. All children had 3-T thorax MRI using T2-W turbo spin-echo sequence, steady-state free precession gradient echo sequence, T2-W turbo spin-echo MultiVane XD sequence, and T1-weighted modified Dixon sequences. We evaluated the images for various pulmonary and mediastinal findings and calculated the sensitivity and specificity of 3-T thoracic MRI., Results: Sensitivity of 3-T MRI was 100% for detecting nodules >4 mm (95% confidence interval [CI] 66.3-100%), pleural effusion (CI 29.2-100%) and lymphadenopathy (CI 81.5-100%). It demonstrated a specificity of 100% for nodules >4 mm (CI 79.4-100%), pleural effusion (CI 84.6-100%) and lymphadenopathy (CI 59-100%). For consolidation/collapse, sensitivity and specificity were 93.8% (CI 69.8-99.8%) and 88.9% (CI 51.8-99.7%), respectively. The sensitivity and specificity for detecting bronchiectasis were 75% (CI 42.8-94.5%) and 100% (CI 75.3-100%), respectively, while for ground-glass opacity, sensitivity and specificity were 75% (CI 34.9-96.8%) and 94.1% (CI 71.3-99.9%), respectively. Nodules <4 mm were not well detected on MRI, with sensitivity of 35% (CI 15.4-59.2%)., Conclusion: Thoracic MRI at 3 T demonstrates a high sensitivity and specificity for detecting nodules >4 mm, effusion and lymphadenopathy in HIV-positive children.

Competing Interests: Disclosure The authors declare no conflicts or financial interest in any product or service mentioned in the manuscript, including grants, equipment, medications, employment, gifts, and honoraria. The authors had full access to all patient information in this report and take responsibility for the integrity and accuracy of the report.

Competing Interests: Competing interests: None declared.

Inflammatory bowel disease (IBD) is more common in adults than in children. Onset of IBD before 17 years of age is referred as pediatric onset IBD and is further categorized as very early onset IBD (VEO-IBD) for children who are diagnosed before 6 years of age, infantile IBD who had the disease before 2 years of age and neonatal onset IBD for children less than 28 days of life. Children presenting with early onset disease may have a monogenic basis. Knowledge and awareness of the clinical manifestations facilitates early evaluation and diagnosis. Next generation sequencing is helpful in making the genetic diagnosis. Treatment of childhood IBD is difficult; targeted therapies and hematopoietic stem cell transplantation form the mainstay. In this review we aim to summarize the genetic defects associated with IBD phenotype. We describe genetic location and functions of various genetic defect associated with VEO-IBD with their key clinical manifestations. We also provide clinical clues to suspect these conditions and approaches to the diagnosis of these disorders and suitable treatment options., (© 2019 Chongqing Medical University. Production and hosting by Elsevier B.V.)

Flow cytometry has emerged as a useful technology that has facilitated our understanding of the human immune system. Primary immune deficiency disorders (PIDDs) are a heterogeneous group of inherited disorders affecting the immune system. More than 350 genes causing various PIDDs have been identified. While the initial suspicion and recognition of PIDDs is clinical, laboratory tools such as flow cytometry and genetic sequencing are essential for confirmation and categorization. Genetic sequencing, however, are prohibitively expensive and not readily available in resource constrained settings. Flow cytometry remains a simple, yet powerful, tool for multi-parametric analysis of cells. While it is confirmatory of diagnosis in certain conditions, in others it helps in narrowing the list of putative genes to be analyzed. The utility of flow cytometry in diagnosis of PIDDs can be divided into four major categories: (a) Enumeration of lymphocyte subsets in peripheral blood. (b) Detection of intracellular signaling molecules, transcription factors, and cytokines. (c) Functional assessment of adaptive and innate immune cells (e.g., T cell function in severe combined immune deficiency and natural killer cell function in familial hemophagocytic lymphohistiocytosis). (d) Evaluation of normal biological processes (e.g., class switching in B cells by B cell immunophenotyping). This review focuses on use of flow cytometry in disease-specific diagnosis of PIDDs in the context of a developing country., (Copyright © 2019 Rawat, Arora, Shandilya, Vignesh, Suri, Kaur, Rikhi, Joshi, Das, Mathew and Singh.)

Background & Aims: The development of non-invasive liver fibrosis tests may enable earlier identification of patients with non-alcoholic fatty liver disease (NAFLD) requiring referral to secondary care. We developed and evaluated a pathway for the management of patients with NAFLD, aimed at improving the detection of cases of advanced fibrosis and cirrhosis, and avoiding unnecessary referrals., Methods: This was a prospective longitudinal cohort study, with analyses performed before and after introduction of the pathway, and comparisons made to unexposed controls. We used a 2-step algorithm combining the use of Fibrosis-4 score followed by the ELF™ test if required., Results: In total, 3,012 patients were analysed. Use of the pathway detected 5 times more cases of advanced fibrosis (Kleiner F3) and cirrhosis (odds ratio [OR]5.18;95%CI2.97-9.04; p <0.0001), while reducing unnecessary referrals from primary care to secondary care by 81% (OR0.193; 95%CI 0.111-0.337; p <0.0001). Although it was used for only 48% of referrals, significant benefits were observed in practices exposed to the pathway compared to those which were not, with unnecessary referrals falling by 77% (OR0.23; 95% CI0.658-0.082; p = 0.006) and a 4-fold improvement in detection of cases of advanced fibrosis and cirrhosis (OR4.32; 95% CI1.52-12.25; p = 0.006). Compared to referrals made before the introduction of the pathway, unnecessary referrals fell from 79/83 referrals (95.2%) to 107/152 (70.4%), representing an 88% reduction in unnecessary referrals when the pathway was followed (OR0.12; 95%CI0.042-0.349; p <0.0001)., Conclusions: The use of non-invasive blood tests for liver fibrosis improves the detection of advanced fibrosis and cirrhosis, while reducing unnecessary referrals in patients with NAFLD. This strategy improves resource use and benefits patients., Lay Summary: Non-alcoholic fatty liver disease effects up to 30% of the population but only a minority of cases develop liver disease. Our study has shown that established blood tests can be used in primary care to stratify patients with fatty liver disease, leading to a reduction in unnecessary referrals by 80% and greatly improving the detection of cases of advanced fibrosis and cirrhosis., (Copyright © 2019 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: In some regions, multiple vitamin A (VA) interventions occur in the same target groups, which may lead to excessive stores. Retinol isotope dilution (RID) is a more sensitive technique than serum retinol to measure VA status., Objective: We evaluated VA status before and after a high-dose supplement in preschool children living in a region in South Africa with habitual liver consumption and exposed to VA supplementation and fortification., Methods: After baseline blood samples, subjects (46.7 ± 8.4 mo; n = 94) were administered 1.0 μmol [14,15]-13C2-retinyl acetate to estimate total liver retinol reserves by RID with a follow-up 14-d blood sample. Liver intake was assessed with a frequency questionnaire. In line with current practice, a routine 200,000 IU VA capsule was administered after the RID test. RID was repeated 1 mo later. Serum retinyl esters were evaluated using ultra-performance liquid chromatography., Results: At baseline, 63.6% of these children had hypervitaminosis A defined as total liver retinol reserves ≥1.0 μmol/g liver, which increased to 71.6% after supplementation (1.13 ± 0.43 to 1.29 ± 0.46 μmol/g; P < 0.001). Total serum VA as retinyl esters was elevated in 4.8% and 6.1% of children before and after supplementation. The odds of having hypervitaminosis A at baseline were higher in children consuming liver ≥1/mo (ratio 3.70 [95% CI: 1.08, 12.6]) and in children receiving 2 (4.28 [1.03, 17.9]) or 3 (6.45 [0.64, 65.41]) supplements in the past 12 mo. Total body stores decreased after the supplement in children in the highest quartile at baseline compared with children with lower stores, who showed an increase (P = 0.007)., Conclusions: In children, such as this cohort in South Africa, with adequate VA intake through diet, and overlapping VA fortification and supplementation, preschool VA capsule distribution should be re-evaluated. This trial was registered at https://clinicaltrials.gov/ct2/show/NCT02915731 as NCT02915731., (Copyright © American Society for Nutrition 2019.)

Background: Kawasaki disease (KD) is emerging as the most common medium vessel vasculitis in children. Recurrence of KD (0.8%-3.0%) is unusual and not commonly reported., Objective: To study the clinico-laboratory profile of children with recurrent KD., Methods: Case records of 714 children with KD, registered from January 1994 to April 2018 in the Pediatric Rheumatology Clinic at the Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research Chandigarh, were reviewed and data were analyzed for children having had recurrent KD., Results: Seven (0.98%) children (five boys; two girls) had recurrent KD in our cohort of 714 patients. Mean age at diagnosis was 4.3 years (range, 2-9 years). Six (85.7%) had recurrence of KD within 1.5 years. Incomplete KD was more common during recurrence (71.4%) as compared to the first episode (33.3%). Five children with recurrent KD developed desquamation during the first week of illness. Laboratory investigations did not show any significant difference during the two episodes of KD. Six of the seven children in the first episode received treatment with intravenous immunoglobulin (IVIG). Five of the seven children received IVIG during recurrence. One child had transient left main coronary artery ectasia during the first episode of KD as well as during recurrence and it normalized after treatment on both occasions., Conclusion: Recurrences in KD are unusual. Over a period of 24 years the recurrence rate in our cohort of children with KD was 0.98%. Further, children with recurrences tended to have milder and incomplete form of the disease., (© 2019 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Competing Interests: Competing interests: None declared.

Kawasaki disease (KD) has replaced acute rheumatic fever as the most common cause of acquired heart disease in children in the developed world and is increasingly being recognized from several developing countries. It is a systemic vasculitis with a predilection for coronary arteries. The diagnosis is based on a constellation of clinical findings that appear in a temporal sequence. Quite understandably, this can become a problem in situations wherein the clinical features are not typical. In such situations, it can be very difficult, if not impossible, to arrive at a diagnosis. Several biomarkers have been recognized in children with acute KD but none of these has reasonably high sensitivity and specificity in predicting the course of the illness. A line up of inflammatory, proteomic, gene expression and micro-RNA based biomarkers has been studied in association with KD. The commonly used inflammatory markers e.g. erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and total leucocyte counts (TLC) lack specificity for KD. Proteomic studies are based on the identification of specific proteins in serum, plasma and urine by gel electrophoresis. A host of genetic studies have identified genes associated with KD and some of these genes can predict the course and coronary outcomes in the affected individuals. Most of these tests are in the early stages of their development and some of these can predict the course, propensity to develop coronary artery sequelae, intravenous immunoglobulin (IVIg) resistance and the severity of the illness in a patient. Development of clinical criteria based on these tests will improve our diagnostic acumen and aid in early identification and prevention of cardiovascular complications.

Lymphocyte subsets of long-term non-progressor (LPNT) HIV-infected children is a less studied aspect of HIV infection. Evaluation of different lymphocyte subsets was done in HIV-infected children ≥8 years of age. Subjects were divided in two groups-group 1 (LTNP), treatment-naive with CD4 ≥ 500 cells/μL ( n  = 20); group 2, non-long-term non-progressor (nLTNPs) receiving antiretroviral therapy (ART) with CD4 count ≤500 on at least one occasion ( n  = 21). Group 3 comprised age-, sex-matched healthy controls (HCs, n  = 20). Lymphocyte subsets were acquired with a flow cytometer (Navios; Beckman Coulter), and data were analyzed using Kaluza flow analysis software. The mean ages were 12.1 (±2.4 SD) and 12.5 (±2.7) years with mean duration of follow-up of 6.8 (±3.4) and 5.6 (±1.95) years in LTNP and nLTNP subjects, respectively. The mean duration of ART was 5.17 years for group 2. Absolute count and percentage of CD4 + T cells was lower in nLTNPs than in LTNPs. Cytotoxic T cells were high in both HIV-infected groups compared with HCs. Natural killer (NK) cells were found to be significantly lower in LTNP and nLTNP groups compared with HCs ( p  ≤ .000003 and p  ≤ .00003, respectively). Naïve B cells were more in HIV-infected individuals than in HCs. NK cells were significantly lower in LTNP and nLTNP groups. Immune reconstitution was comparable in children initiated with ART early versus long-term HIV-infected children receiving no ART.

Aim: To report our experience on complex percutaneous interventions of the abdominal aorta and its branches in six children with Takayasu arteritis (TA)., Methods: A review of records of children with TA, who underwent percutaneous interventions of the abdominal aorta and its major branches., Results: In this analysis, we included six children with TA who underwent intervention of the abdominal aorta and its major branches. The endovascular interventions were performed mostly for treatment-resistant renovascular hypertension and mesentery artery ischemia. Mean age (±SD) at time of intervention was 10.6 ± 2.5 years (four boys and two girls). Percutaneous interventions included stenting of abdominal aorta (n = 2), renal arteries (n = 4), mesenteric arteries (n = 2), repeat stenting for renal artery in-stent restenosis (n = 1), and renal autotransplantation (n = 4). All 13 interventions were successful and enabled us to obtain good control of blood pressure., Conclusion: We hereby report six children with TA who were successfully managed with complex percutaneous interventions of the abdominal aorta and its major branches. Balloon dilatation and stent placement constitutes the mainstay of management of TA with stenosis of the large vessels., (© 2018 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Purpose: To assess the safety and efficacy of intraoperative intravitreal dexamethasone implant in patients of juvenile idiopathic arthritis (JIA)-associated uveitis undergoing phacoemulsification with posterior chamber intraocular lens (PCIOL) implantation., Methods: Retrospectively, data of patients with JIA-associated uveitis undergoing phacoemulsification with PCIOL implantation with intraoperative dexamethasone implant injection were analyzed. Patients with a minimum follow-up of 6 months were included. Primary outcome measures were ocular inflammation, intraocular pressure (IOP), best-corrected visual acuity (BCVA), and worsening of uveitis., Results: 8 eyes of 6 patients were included. BCVA was significantly improved at 1, 3, and 6 months postoperatively 0.20 ± 0.09, P = 0.008; 0.18 ± 0.11, P = 0.008; and 0.24 ± 0.11, P = 0.01, respectively. No statistical difference noted in mean IOP at various follow-up visits. None developed worsening of uveitis or Cystoid macular edema., Conclusion: Intraoperative intravitreal dexamethasone implant is a safe and effective in preventing and managing the postoperative inflammation in children with JIA-associated uveitic cataract., Competing Interests: None

There is a paucity of literature on renal diseases associated with HIV infection in Asian countries. Renal disease in HIV-infected children can involve the glomerulus, interstitium, tubules or blood vessels of the kidney. In this case series, five HIV-infected children with various forms of renal disease are reported. The renal pathology included HIV-associated nephropathy, collapsing focal segmental glomerulosclerosis without tubular changes, tubule-interstitial nephritis and minimal change disease (MCD). Case five fulfilled the classification criteria for childhood polyarteritis nodosa (PAN). It is important to screen all HIV-infected children for renal disease to enable detection at an early stage.

We report two children with systemic lupus erythematosus (SLE) having severe bleeding manifestations and lupus anticoagulant hypoprothrombinemia syndrome (LAHPS) along with a review of published cases of childhood SLE and LAHPS. We report clinical and laboratory profile of two children diagnosed with childhood SLE and LAHPS. We also conducted literature search to identify similar published cases and a review was performed. An 8-year-old girl had presented with fever, arthralgia, alopecia, anasarca and bleeding from multiple sites. She was diagnosed to have SLE based on laboratory investigations which showed anemia, thrombocytopenia, low complements, positive anti-nuclear antibody (ANA) and double standard DNA (dsDNA) antibodies. She was also found to have prolonged prothrombin time (PT) and activated partial thromboplastin time (aPTT), positive lupus anticoagulant (LA) and low factor II levels. She was diagnosed to have SLE with LAHPS and treated with intravenous methylprednisolone, intravenous immunoglobulin and cyclophosphamide with good outcome. Patient 2 was a 7-year-old-boy who was diagnosed to have SLE when he presented with fever, anasarca, malar rash, arthritis and bleeding from skin and mucosa. Laboratory investigations revealed anemia, proteinuria, low complements, positive ANA and anti-dsDNA titre. Coagulation studies showed deranged PT and aPTT, positive LA and low factor II levels. He was diagnosed to have SLE with LAHPS and was treated with intravenous methylprednisolone and oral mycophenolate mofetil. Review of literature of cases with childhood SLE and LAHPS showed that there are 32 cases have been reported till date which have been summarized. LAHPS is an uncommonly identified cause of bleeding in patients with SLE and must be suspected while evaluating these children.

X-linked hyper IgM Syndrome (XLHIGM), the most frequent form of the Hyper IgM syndromes is a primary immune deficiency resulting from a mutation in the CD40 ligand gene (CD40LG). We analyzed the clinical and laboratory features of ten patients with XLHIGM, who were diagnosed at a tertiary care hospital in North India. Most common infections were sinopulmonary infections (80%) and diarrhea (50%). Sclerosing cholangitis and necrotising fasciitis were noted in one patient each. Three novel mutations in CD40LG (c.429&#95;429 delA, p. G144DfsX5; c.500 G > A, p.G167E and c.156 G > C, p.K52 N) were detected. In addition, we found one missense mutation, two splice site mutations and two large deletions, which have been previously reported. Four (4) patients had expired at the time of analysis. We report the first series of XLHIGM from North India where we have documented unique features such as pulmonary alveolar proteinosis and infections with Mycobacterium sp., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Cryptococcal meningitis is an opportunistic fungal infection commonly seen in immunocompromised individuals. Information on cryptococcal meningitis is scarce in immunocompetent children. The authors report an 8-year-old immunocompetent boy with cryptococcal meningitis and bilateral vision loss. The role of repeated therapeutic lumbar puncture in the management of raised intracranial pressure in cryptococcal meningitis is discussed.

The efficacy and duration of memory storage is regulated by neuromodulatory transmitter actions. While the modulatory transmitter serotonin (5-HT) plays an important role in implicit forms of memory in the invertebrate Aplysia, its function in explicit memory mediated by the mammalian hippocampus is less clear. Specifically, the consequences elicited by the spatio-temporal gradient of endogenous 5-HT release are not known. Here we applied optogenetic techniques in mice to gain insight into this fundamental biological process. We find that activation of serotonergic terminals in the hippocampal CA1 region both potentiates excitatory transmission at CA3-to-CA1 synapses and enhances spatial memory. Conversely, optogenetic silencing of CA1 5-HT terminals inhibits spatial memory. We furthermore find that synaptic potentiation is mediated by 5-HT4 receptors and that systemic modulation of 5-HT4 receptor function can bidirectionally impact memory formation. Collectively, these data reveal powerful modulatory influence of serotonergic synaptic input on hippocampal function and memory formation., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Neurologic manifestations of HIV infection are not uncommon. However, stroke secondary to Moyamoya syndrome has rarely been described in children with HIV infection. We report a 10-year-old boy with perinatally acquired HIV-1 infection, who presented with recurrent strokes while on antiretroviral therapy.

Background: Cytomegalovirus (CMV) results in significant morbidity and mortality in Human Immunodeficiency Virus (HIV)-infected individuals. There is paucity of literature on paediatric CMV disease, especially from developing countries., Methods: A retrospective review of records of all HIV-infected children with evidence of CMV disease was done., Results: A total of 15 children were found to have CMV disease (retinitis in all, pneumonia in two and invasive gastrointestinal disease in one). Median CD4+ T cell count and percentage at diagnosis of CMV disease was 64.5 cells/µl and 3.6%, respectively. Intravenous ganciclovir was used in patients with active CMV disease. Of the 15 children, three died while two were lost to follow-up. Symptomatic patients had poor visual outcome and almost all children who were diagnosed on active screening attained normal vision., Conclusion: Retinitis is the most common CMV disease in HIV-infected children. Early detection by active screening and initiation of systemic ganciclovir reduces the morbidity.

The objective of this study was to report four children having juvenile dermatomyositis (JDM) with inverse Gottron sign along with a brief review of literature of similarly published cases. This is a retrospective review of case records of all children diagnosed with JDM at a single tertiary care centre in North India. Children who were found to have Gottron papules over palmar surface were identified. A total of 127 children were diagnosed with JDM in the last 24 years (1994-2017). Out of these 127 patients, 4 were found to have Gottron papules over palmar surface. The median age at presentation of these four patients was 9 years (range 8-10). The distribution for inverse Gottron papules was over the palmar aspect of proximal and distal interphalangeal joints, palmar creases and lateral aspects of proximal and distal interphalangeal joints. One child also had features of systemic scleroderma overlap and one patient had patchy lipoatrophy. ANA were positive in two patients. High-resolution computed tomography (HRCT) chest was carried out in all four patients and three of them were found to have changes consistent with interstitial lung disease. Prednisolone was used for all patients, methotrexate in three, azathioprine in two and cyclophosphamide in one patient. Inverse Gottron papule is a hitherto uncommonly recognized cutaneous manifestation of JDM. The clinical implications of this sign are yet not clear in children with JDM. Children with JDM with palmar Gottron papules may be screened for ILD as this may change their management and prognosis.

Background: Hyper-IgE syndrome (HIES) caused by loss-of-function (LOF) mutations in STAT3 gene (STAT3 LOF HIES) is associated with dental and facial abnormalities in addition to immunological defects. The role of STAT3 in the pathogenesis of the dental/facial features is, however, poorly elucidated., Objectives: Since mechanism of cellular resorption of mineralized tissues such as bone and teeth are similar, we attempted to study the expression of genes involved in bone homeostasis in STAT3 LOF HIES., Methods: Peripheral blood mononuclear cells from healthy controls (HCs), STAT3 LOF HIES patients, STAT3 -/- PC-3 cells and STAT3 +/+ LNCaP cells were stimulated with IL-6 and quantitative PCR array was performed to study the relative mRNA expression of 43 pre-selected genes. PCR array finding were further evaluated after stattic induced STAT3 inhibition., Results: Osteopontin (OPN) gene was seen to be significantly upregulated after IL-6 stimulation in HC (mean fold change 18.6, p  = 0.01) compared with HIES subjects. Inhibition of STAT3 signaling by stattic followed by IL-6 stimulation abrogated the OPN response in HCs suggesting that IL-6-induced STAT3 signaling regulates OPN expression. Bioinformatics analysis predicted the presence of STAT3 response element TTCCAAGAA at position -2005 of the OPN gene., Conclusion: Regulation of OPN gene through IL-6-mediated STAT3 activation and its significant dysregulation in STAT3 LOF HIES subjects could make OPN a plausible candidate involved in the pathogenesis of dental/facial manifestations in HIES.

Background: Complement system plays a crucial role in the pathogenesis of systemic lupus erythematosus (SLE). Excessive activation of complement causes tissue injury and SLE occurrence is typically associated with congenital deficiencies of the early components of the classical complement pathway. Mannose-binding lectin (MBL) is recognized as important causative factor in the etio-pathogenesis of SLE and MBL-2 gene has evolved as a candidate gene for SLE susceptibility., Aim: This study was done to assess the functional MBL (fMBL) level in SLE patients in remission and its co-relation with disease severity and outcome., Methods: Functional MBL levels were compared with age and sex matched healthy controls and were correlated with duration of illness,complement levels and anti-double- stranded DNA antibody levels., Results: Mean fMBL level in patients was found to be 696.19 ± 408.98 U/mL and 579.52 ± 393.87 U/mL in the control group. Four children had very low fMBL levels (< 40 U/mL). Functional MBL levels were higher in patients with SLE even when the disease was in remission as compared to healthy controls, although not statistically significant., Conclusion: Large variation exists in fMBL levels in patients with SLE even when in remission. Very low fMBL levels were found in some children with younger age of onset of SLE, multisystem involvement and severe course of the disease. Positive correlation of MBL levels with anti-ds DNA titers suggest that its values vary with activity and could be a potential biomarker of the disease., (© 2018 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Objectives: Kawasaki disease (KD) is a multisystemic vasculitis with predominant mucocutaneous manifestations. Pulmonary involvement in KD is distinctly uncommon and is not commonly recognized. We describe our experience of managing children with KD wherein the initial presentation was predominantly pulmonary., Methods: Six hundred and two children have been diagnosed with KD during the period January 1993 to May 2017 in the Allergy Immunology Unit, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh. Data were collected from inpatient records in Allergy Immunology Unit and follow-up files in the Pediatric Rheumatology Clinic., Results: Of 602 children, 11 (1.83%) had a predominant pulmonary presentation of KD. Mean age at diagnosis of KD was 2.5 years. Fever, cough and respiratory distress were the presenting complaints in all patients. First sign of KD was noted at a mean duration of 14.5 days from the onset of symptoms. Periungual desquamation was the most common clinical sign (72.7%). Persistent fever in spite of antimicrobials, thrombocytosis, and elevated erythrocyte sedimentation rate and C-reactive protein levels pointed toward a diagnosis of KD in our patients. Parenchymal consolidation was evident on chest X-ray in all patients, pleural effusion in six, empyema in three, and pneumothorax in two patients. Coronary artery abnormalities were evident in three patients. Intravenous immunoglobulin was given after a mean period of 22.4 days of onset of fever., Conclusions: The diagnosis of KD is often delayed in children who have a predominantly pulmonary presentation. This can have adverse clinical consequences., (© 2017 Wiley Periodicals, Inc.)

Purpose: To analyze the clinical features, course, management, and outcomes of tubercular (TB) uveitis in the pediatric population and assess the response to anti-tubercular therapy (ATT)., Methods: Hospital records of children (≤16 years) from a large tertiary-care institute between January 2001 and December 2015 were reviewed., Results: A total of 32 children (mean age: 10.7 ± 4.27 years; range 2-16) were diagnosed with TB-associated uveitis. The most common presentation was posterior uveitis (n = 14, 43.75%) and panuveitis (n = 14, 43.75%), followed by intermediate uveitis (n = 2, 6.25%) and anterior uveitis (n = 2, 6.25%); 14 children had probable intraocular tuberculosis (IOTB) (43.75%) and 17 (53.13%) had possible IOTB. Despite ATT and corticosteroids, 29.63% patients showed suboptimal response or worsening of disease requiring additional immunosuppression., Conclusions: TB is an important cause of pediatric uveitis in endemic countries. The manifestations of the disease resemble adult TB-related uveitis. However, higher inflammatory response in children may require more aggressive therapy with corticosteroids/immunosuppression.

We present a detailed study of thermal and electrical transport behavior of single crystal titanium disulphide flakes, which belong to the two dimensional, transition metal dichalcogenide class of materials. In-plane Seebeck effect measurements revealed a typical metal-like linear temperature dependence in the range of 85-285 K. Electrical transport measurements with in-plane current geometry exhibited a nearly T 2 dependence of resistivity in the range of 42-300 K. However, transport measurements along the out-of-plane current geometry showed a transition in temperature dependence of resistivity from T 2 to T 5 beyond 200 K. Interestingly, Au ion-irradiated TiS 2 samples showed a similar T 5 dependence of resistivity beyond 200 K, even in the current-in-plane geometry. Micro-Raman measurements were performed to study the phonon modes in both pristine and ion-irradiated TiS 2 crystals.

A cross-sectional study from a tertiary care center in India was undertaken to assess and compare the prevalence of blood glucose and lipid profile aberrations in children who received first-line antiretroviral therapy (ART; n = 63) and in children who were naïve to ART (n = 46). Impaired fasting blood glucose values were found in 7 children in ART-experienced group but none in ART-naïve group (P = 0.02). Low concentrations of high-density lipoprotein cholesterol were more prevalent in the ART-naïve group compared with ART-experienced group (54.3% vs. 22.2%; P = 0.001). Hypertriglyceridemia was noted in a significant proportion of both ART-naïve (43.5%) and ART-experienced children (39.7%). Incidence of clinical lipodystrophy was 47.7%, and there was no significant association noted between lipid profile abnormalities and lipodystrophy.

Aim: Primary membranous nephropathy (PMN) accounts for only 1-2% of nephrotic syndrome in children. Antibodies to m-type phospholipase A2 receptor (aPLA 2 R) is seen in 70% of adult PMN cases. The present study was undertaken to study m-type phospholipase A 2 receptor (PLA 2 R) status and clinical behavior in adolescent PMN cases., Methods: The present prospective observational study included adolescent (10-19 years) onset biopsy proved PMN. Patients were followed on a monthly basis with urine protein, serum albumin and creatinine. Serum aPLA 2 R was done at baseline and at 6 and 12 months of starting treatment. Patients were treated as per unit's protocol., Results: During the study period a total of 18 patients were enrolled. The mean age of the cases was 16.27 ± 2.39 (11-19) years. Seventeen (94.44%) patients presented with nephrotic syndrome. The mean proteinuria and serum albumin was 4.52 ± 1.93 (2.43-9.20) g/day and 2.1 ± 0.6 (1.1-3.4) g/dL respectively. PMN was PLA 2 R related in 83%. aPLA2R and enhanced staining for PLA 2 R in glomeruli was seen in 14 (77.78%) and 13 (72.22%), respectively. Clinical remission at the end of 6 and 12 months of therapy was seen in 11 (61.11%) and 9 (50%) subjects respectively. There was a significant association of aPLA 2 R to clinical remission/ resistance., Conclusion: Primary membranous nephropathy in adolescent population is aPLA 2 R related in over three-quarters of the cases and the response to therapy is seen in only half of them. aPLA 2 R monitoring is clinically relevant and should be incorporated in the management of adolescent onset PMN., (© 2016 Asian Pacific Society of Nephrology.)

An association of X-linked agammaglobulinemia (XLA) with Kawasaki disease (KD) is very uncommon. Only two case reports are available so far in pediatric literature. Patients with XLA have recurrent infections and physical examination have absent lymph nodes and tonsils. Laboratory investigations reveal hypogammaglobulinemia and reduced or absent B cells on flow cytometry. KD is a medium vessel vasculitis. Here, we report a 12 year old boy with X-linked agammaglobulinemia on regular replacement intravenous immunoglobulin who developed KD on follow-up. This is an uncommon occurrence.

Competing Interests: Competing interests: None declared.

Development passes through sensitive periods, during which plasticity allows for genetic and environmental factors to exert indelible influence on the maturation of the organism. In the context of central nervous system (CNS) development, such sensitive periods shape the formation of neuro-circuits that mediate, regulate, and control behavior. This general mechanism allows for development to be guided by both the genetic blueprint, as well as the environmental context. While allowing for adaptation, such sensitive periods are also windows of vulnerability during which external and internal factors can confer risk to brain disorders by derailing adaptive developmental programs. Our group has been particularly interested in developmental periods that are sensitive to serotonin (5-HT) signaling, and impact behavior and cognition relevant to psychiatry. Specifically, we review a 5-HT-sensitive period that impacts fronto-limbic system development, resulting in cognitive, anxiety, and depression-related behaviors. We discuss preclinical data to establish biological plausibility and mechanistic insights. We also summarize epidemiological findings that underscore the potential public health implications resulting from the current practice of prescribing 5-HT reuptake inhibiting antidepressants during pregnancy. These medications enter the fetal circulation, likely perturb 5-HT signaling in the brain, and may be affecting circuit maturation in ways that parallel our findings in the developing rodent brain. More research is needed to better disambiguate the dual effects of maternal symptoms on fetal and child development from the effects of 5-HT reuptake inhibitors on clinical outcomes in the offspring. Birth Defects Research 109:924-932, 2017. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Background: Severe combined immunodeficiency (SCID) is fatal unless treated with hematopoietic stem cell transplant. Delay in diagnosis is common without newborn screening. Family history of infant death due to infection or known SCID (FH) has been associated with earlier diagnosis., Objective: The aim of this study was to identify the clinical features that affect age at diagnosis (AD) and time to the diagnosis of SCID., Methods: From 2005 to 2016, 147 SCID patients were referred to the Asian Primary Immunodeficiency Network. Patients with genetic diagnosis, age at presentation (AP), and AD were selected for study., Results: A total of 88 different SCID gene mutations were identified in 94 patients, including 49 IL2RG mutations, 12 RAG1 mutations, 8 RAG2 mutations, 7 JAK3 mutations, 4 DCLRE1C mutations, 4 IL7R mutations, 2 RFXANK mutations, and 2 ADA mutations. A total of 29 mutations were previously unreported. Eighty-three of the 94 patients fulfilled the selection criteria. Their median AD was 4 months, and the time to diagnosis was 2 months. The commonest SCID was X-linked ( n  = 57). A total of 29 patients had a positive FH. Candidiasis ( n  = 27) and bacillus Calmette-Guérin (BCG) vaccine infection ( n  = 19) were the commonest infections. The median age for candidiasis and BCG infection documented were 3 months and 4 months, respectively. The median absolute lymphocyte count (ALC) was 1.05 × 10 9 /L with over 88% patients below 3 × 10 9 /L. Positive FH was associated with earlier AP by 1 month ( p  = 0.002) and diagnosis by 2 months ( p  = 0.008), but not shorter time to diagnosis ( p  = 0.494). Candidiasis was associated with later AD by 2 months ( p  = 0.008) and longer time to diagnosis by 0.55 months ( p  = 0.003). BCG infections were not associated with age or time to diagnosis., Conclusion: FH was useful to aid earlier diagnosis but was overlooked by clinicians and not by parents. Similarly, typical clinical features of SCID were not recognized by clinicians to shorten the time to diagnosis. We suggest that lymphocyte subset should be performed for any infant with one or more of the following four clinical features: FH, candidiasis, BCG infections, and ALC below 3 × 10 9 /L.

Purpose: Deficiency of interleukin-1 receptor antagonist (DIRA) is a rare life-threatening autoinflammatory disease caused by autosomal recessive mutations in IL1RN. DIRA presents clinically with early onset generalized pustulosis, multifocal osteomyelitis, and elevation of acute phase reactants. We evaluated and treated an antibiotic-unresponsive patient with presumed DIRA with recombinant IL-1Ra (anakinra). The patient developed anaphylaxis to anakinra and was subsequently desensitized., Methods: Genetic analysis of IL1RN was undertaken and treatment with anakinra was initiated., Results: A 5-month-old Indian girl born to healthy non-consanguineous parents presented at the third week of life with irritability, sterile multifocal osteomyelitis including ribs and clavicles, a mild pustular rash, and elevated acute phase reactants. SNP array of the patient's genomic DNA revealed a previously unrecognized homozygous deletion of approximately 22.5 Kb. PCR and Sanger sequencing of the borders of the deleted area allowed identification of the breakpoints of the deletion, thus confirming a homozygous 22,216 bp deletion that spans the first four exons of IL1RN. Due to a clinical suspicion of DIRA, anakinra was initiated which resulted in an anaphylactic reaction that triggered desensitization with subsequent marked and sustained clinical and laboratory improvement., Conclusion: We report a novel DIRA-causing homozygous deletion affecting IL1RN in an Indian patient. The mutation likely is a founder mutation; the design of breakpoint-specific primers will enable genetic screening in Indian patients suspected of DIRA. The patient developed anaphylaxis to anakinra, was desensitized, and is in clinical remission on continued treatment.