Revolution of Disturbed Bregs and Bmems Lymphocytes Homeostasis in Children With Chronic ITP After High-dose Dexamethasone Rescue Therapy.

SUMMARY: Dexamethasone is approved as second-line therapy in pediatric chronic immune thrombocytopenic purpura (ITP). Several B-cell abnormalities have been described in ITP pathogenesis.This study assessed the effects of high-dose dexamethasone (HD-DXM) on the percentages and absolute counts of CD19+CD24hiCD38hi regulatory (Bregs) and CD19+CD27+ memory B lymphocytes (Bmems) in children with chronic ITP during active bleeding.The study was a prospective case-control, included 20 children with chronic ITP and uncontrolled bleeding. Children received a single daily dose of HD-DXM for 4 days. Blood samples were withdrawn from patients just before HD-DXM therapy and on day 5 to evaluate the platelet counts and flow cytometric analysis of Bregs and Bmem. The patients' platelet counts significantly increased after 5 days of the initiation of therapy (P=0.0001). Bmems percentage and absolute counts were significantly higher in patients before treatment (P=0.0007), and decreased after HD-DXM therapy (P=0.97) compared with the controls. Bregs percentage and absolute counts were significantly lower before treatment (P=0.0003) and increased after HD-DXM (P=0.003). There is a negative correlation between platelet counts and Bregs percentage and absolute count Bmems percentage before and after HD-DXM, whereas a positive correlation between platelets and Bregs before and after dexamethasone has been reported. CONCLUSIONS: HD-DXM reestablishes the normal Bregs/Bmems balance. This finding discloses possible involvement of Bregs and Bmems in the pathogenesis of pediatric ITP and provides a novel vision for immune modulation and treatment perspectives.

Food sensitization in preschool Egyptian children with recurrent wheezing.

BACKGROUND: Food allergy is common in children with prevalence up to 10%. We assessed the clinico-laboratory characteristics and frequency of food sensitization to the commonly consumed food among upper Egyptian preschool children with recurrent wheezy chest. METHODS: This cross-sectional descriptive study was conducted on 100 preschool children with recurrent wheezy chest recruited from Emergency, Allergy, and Pulmonology units, Assiut University Children's Hospital, Egypt. All enrolled patients were subjected to history taking, through examination, chest X-ray, skin prick testing (SPT), and lab investigations. RESULTS: Family history of allergy was found in 66 patients, while history of other allergies was reported in 47 patients. History of food allergy was positive in 47% of the studied patients, and 28 patients had positive reaction by SPT. Sensitization to fish, milk, egg, and wheat was found in 15, 8, 5, and 4 patients, respectively. Eighteen out of the 28 patients who were sensitized by SPT gave positive history of food allergy, while ten patients had no suggestive history; also, history suggestive of food allergy was negative in 35.7% of sensitized patients versus 61.1% of non-sensitized patients. CONCLUSIONS: Food sensitization is common in preschool Egyptian children with recurrent wheezing. IMPACT: Food sensitization is common in children with prevalence up to 10%, and in atopic children up to 30%. Sensitization to fish was the most common type of sensitization observed among preschool children with recurrent wheezing, followed by milk, eggs, and wheat, respectively. SPT aided by history is a good screening tool to determine whether patients need to avoid some foods that can cause allergy in order to help in controlling their symptoms.

Nailfold capillaroscopic assessment in pediatric patients with autoimmune uveitis: a case-control study.

Uveitis is a major cause of visual impairment. Most uveitis cases have autoimmune etiology. Pediatric autoimmune uveitis may be associated with systemic diseases such as juvenile idiopathic arthritis or may arise as an isolated disorder. It may be accompanied by retinal vasculitis due to retinal microcirculation involvement. Nailfold capillaroscopy, a digital microscope, is a non-invasive tool for systemic microcirculation evaluation. We aimed to evaluate systemic microcirculation abnormalities in pediatric autoimmune uveitis. Twenty-five patients with pediatric autoimmune uveitis and 21 healthy children underwent detailed capillaroscopic evaluation. We assessed capillary density/mm, capillary morphology, capillary dimensions, and the presence or absence of microhemorrhages and avascular areas. The mean age of the study and control groups was 11.24 ± 3.03 and 9.9 ± 4.17 years, respectively. Most included patients had isolated uveitis and juvenile idiopathic arthritis (64% and 24%, respectively). The predominant uveitis subtype in the study was anterior uveitis (48%). A significant difference was found between cases and controls regarding mean capillary density (p-value = 0.0003) and the number of subjects having capillary density less than 7 (p-value = 0.002). Other capillaroscopic abnormalities did not show any significant difference between the studied groups. Mean capillary density did not correlate significantly with age, disease duration, or acute phase reactants. Children with autoimmune uveitis, whether isolated or as a part of systemic disease, may have systemic microcirculation involvement. Key Points • Idiopathic autoimmune uveitis is not always an isolated intraocular condition. • Systemic microcirculation involvement may occur in pediatric autoimmune uveitis, even in cases with isolated uveitis. • Nailfold capillaroscopy showed that capillary density in children with autoimmune uveitis is significantly reduced compared to healthy controls.

Defining Criteria for Disease Activity States in Systemic Juvenile Idiopathic Arthritis Based on the Systemic Juvenile Arthritis Disease Activity Score.

OBJECTIVE: Our objective was to develop and validate cutoff values in the systemic Juvenile Arthritis Disease Activity Score 10 (sJADAS10) that distinguish the states of inactive disease (ID), minimal disease activity (MDA), moderate disease activity (MoDA), and high disease activity (HDA) in children with systemic juvenile idiopathic arthritis, based on subjective disease state assessment by the treating pediatric rheumatologist. METHODS: The cutoff definition cohort was composed of 400 patients enrolled at 30 pediatric rheumatology centers in 11 countries. Using the subjective physician rating as an external criterion, six methods were applied to identify the cutoffs: mapping, calculation of percentiles of cumulative score distribution, the Youden index, 90% specificity, maximum agreement, and receiver operating characteristic curve analysis. Sixty percent of the patients were assigned to the definition cohort, and 40% were assigned to the validation cohort. Cutoff validation was conducted by assessing discriminative ability. RESULTS: The sJADAS10 cutoffs that separated ID from MDA, MDA from MoDA, and MoDA from HDA were ≤2.9, ≤10, and >20.6, respectively. The cutoffs discriminated strongly among different levels of pain, between patients with and without morning stiffness, and among patients whose parents judged their disease status as remission or persistent activity or flare or were satisfied or not satisfied with current illness outcome. CONCLUSION: The sJADAS cutoffs revealed good metrologic properties in both definition and validation cohorts and are therefore suitable for use in clinical trials and routine practice.

Detection of multiple extensively-drug resistant hypervirulent Klebsiella pneumoniae clones from patients with ventilator-associated pneumonia in Egypt.

Introduction. Hypervirulent-K. pneumoniae (hvKP) is an evolving pathotype that is more virulent than the classical-K. pneumoniae (cKP) and causes serious fatal illnesses.Hypothesis/Gap Statement. Although there are few reports on hvKP isolated from Egyptian patients, the molecular characteristics and clonal relatedness of MDR-hvKP have not been adequately investigated.Aim. To investigate the microbiological and genetic characteristics as well as the epidemiology of hvKP induced ventilator-associated pneumonia (VAP).Methodology. A retrospective study of 59 K. pneumoniae inducing VAP was conducted at Assiut University Hospitals from November 2017 to January 2019. All K. pneumoniae were tested for resistance phenotype, capsular genotype (K1 and K2), virulence gene profile (c-rmpA, p-rmpA, iucA, kfu, iroB, iroN), and the presence of resistance genes (blaNDM-1, blaCTX-M-3-like, blaCTX-M-14-like). Clonal relatedness was assessed by Pulsed field gel electrophoresis (PFGE).Result. HvKP accounted for 89.8 % (53/59) of K. pneumoniae isolates with ~95 % exhibiting extensively-drug resistant (XDR) phenotype. Hypermucoviscous phenotype was detected in 19 (35.8 %) hvKP and K2 capsular gene was identified in 18 (33.9 %) of hvKP. Regarding the virulence genotype of hvKP strains, iucA was the most prevalent virulence gene (98.1%), while p-rmpA and kfu were detected in 75.4 and 52.8 % of hvKP strains, respectively. Resistance genes were highly prevalent in both cKP and hvKP with blaCTX-M-3-like being more prevalent in hvKP (100 % vs 94.3 % for blaNDM-1, 50 % vs 62.2 % for blaCTX-M-3-like and 83.3 % vs 69.8 % for blaCTX-M-14 -like, respectively). PFGE typing of 29 representative K. pneumoniae revealed 15 pulsotypes, with identical hvKP pulsotypes isolated from different ICUs at different times and several hvKP and cKP isolates belonged to the same pulsotype.Conclusion. This study highlights the dominance and clonal spread of XDR-hvKP strains at Assiut University Hospital in Egypt. Physicians should be aware of the increased risk of hvKP induced-VAP and support further epidemiologic studies.

Upregulation of Cytotoxic T-cells in pediatric patients with Gaucher disease.

Cytotoxic (CD8) T-cells and natural killer (NK) cells have a significant immune function role. The ongoing stimulation of immunity and the excessive release of proinflammatory cytokines observed in pediatric patients with Gaucher disease (GD) can affect immune cells. Few studies have looked at the proportion of cytotoxic CD8 T-cells and their subsets in children with GD. A prospective case-control study was performed involving twenty pediatric patients with type 1 GD and twenty healthy age-matched controls. All patients received regular enzyme replacement therapy (ERT) for at least 6 months before the study. Complete blood count and flow cytometric analyses of CD8 T, Tc1, Tc2, NK, and NK T-cells were performed. GD patients showed significantly increased of CD8 T, Tc1 and significantly decreased NK cells frequencies when compared to healthy controls. However, no significant difference in Tc2 and NK T-cells was found between the studied groups. GD patients on regular ERT have increased CD8+ T-cell frequencies, predominantly Tc1, together with a reduction in NK cells than in healthy controls. These crucial immunological changes may contribute to some extent to the pathogenesis and the progression of GD.

Physicians' knowledge and practice concerning diagnosis and management of anaphylaxis: The situation in Egypt.

INTRODUCTION: Early recognition of an anaphylaxis event is crucial for instituting lifesaving management. We sought to explore knowledge and practice towards anaphylaxis in a sample of physicians from ten Egyptian governorates. METHODS: An eighteen question-based questionnaire was developed by expert allergists to evaluate the knowledge and practice towards anaphylaxis, based on the World Allergy Organization guidelines for the assessment and management of anaphylaxis. The questionnaires were distributed, and the answered forms collected via emails, and data were tabulated, and analysed. RESULTS: In this cross-sectional study, a total of 242 physicians completed the survey (183 (75.6%) paediatricians, 32 (13.2%) internists, 22 (9.1%) intensivists and five (2.1%) anaesthetists). Only 91 participants (37.6%) identified all the four proposed anaphylaxis clinical scenarios while 70, 45 and 36 identified three, two and one scenario, respectively. Loss of consciousness and abdominal symptoms were not recognised as possible presentations of anaphylaxis by 64.5% and 80.2% of the participants, respectively. Epinephrine was considered the first line treatment by 98 (40.5%), corticosteroids by 77 (31.8%) and antihistamines by 25 (10.3%). 75 (31%) responders identified the right dose of epinephrine while 119 (49.2%) identified the proper route. Concerning practice, 83 physicians (39.2%) used epinephrine for all cases of anaphylaxis, 88 (41.5%) used it for refractory cases only whereas 41 (19.3%) did not use epinephrine at all. DISCUSSION: Our survey shows that the knowledge of Egyptian physicians and their practice towards anaphylaxis are still inadequate. The current situation reinforces the need to disseminate and encourage the adoption of the international guidelines for anaphylaxis diagnosis and treatment.

Consensus evidence-based recommendations for treat-to-target management of immunoglobulin A vasculitis.

IgA vasculitis (IgAV), formerly known as Henoch-Schönlein purpura, is the most common cause of systemic vasculitis in childhood. Given its potential life-threatening systemic complications, early and accurate diagnosis as well as management of IgAV represent a major challenge for health care professionals. This study was carried out to attain an evidence-based expert consensus on a treat-to-target management approach for IgAV using Delphi technique. The preliminary scientific committee identified a total of 16 key clinical questions according to the patient, intervention, comparison, and outcomes (PICO) approach. An evidence-based, systematic, literature review was conducted to compile evidence for the IgAV management. The core leadership team identified researchers and clinicians with expertise in IgAV management in Egypt upon which experts were gathered from different governorates and health centers across Egypt. Delphi process was implemented (two rounds) to reach a consensus. An online questionnaire was sent to expert panel (n = 26) who participated in the two rounds. After completing round 2, a total of 20 recommendation items, categorized into two sections were obtained. Agreement with the recommendations (rank 7-9) ranged from 91.7-100%. Consensus was reached (i.e. ⩾75% of respondents strongly agreed or agreed) on the wording of all the 20 clinical standards identified by the scientific committee. Algorithms for the diagnosis and management have been suggested. This was an expert, consensus recommendations for the diagnosis and treatment of IgAV and IgA vasculitic nephritis, based on best available evidence and expert opinion. The guideline presented a strategy of care with a pathway to achieve a state of remission as early as possible. PLAIN LANGUAGE SUMMARY: Given its potential life-threatening systemic complications, early and accurate diagnosis of immunoglobulin A vasculitis represents a major challenge for health care professionals. This work provided cornerstone principles for the management of the condition. Adopting PICO approach and implementing Delphi process a consensus was reached on evidence-based treat-to-target treatment recommendations. This will endorse enhancement and consistency of care of this cohort of patients in standard practice.

Emergence of Cronobacter sakazakii in Cases of Neonatal Sepsis in Upper Egypt: First Report in North Africa.

BACKGROUND AND AIM: Cronobacter sakazakii (C. sakazakii) has attracted considerable attention as an emerging neonatal pathogen and has been associated with outbreaks of life-threatening septicemia, necrotizing enterocolitis, and meningitis in neonates and infants globally. No data about the role of C. sakazakii as a cause of neonatal sepsis in North Africa is availale. Herein, we aimed to study the incidence of C. sakazakii in cases of neonatal sepsis, its distribution in different food samples in Egypt, antimicrobial profile, and the ability of the strains to form biofilms. METHODS: A total of 100 positive blood cultures from cases of neonatal sepsis admitted to the neonatal ICU at Assiut University Children's Hospital, Egypt, were analyzed. In addition, 1,100 food samples, including 400 powdered infant formula (PIF), 500 herbs, and 200 water samples were screened for the presence of C. sakazakii. We evaluated the antimicrobial profile and the ability of the strains to form biofilms. RESULTS: Cronobacter sakazakii was detected in 12 out of 100 cases of neonatal sepsis. The organism was also isolated from PIF, herbs, and water in percentages of 17.5, 9.2, and 7.5%, respectively. Regarding the antimicrobial sensitivity, all strains were resistant to ampicillin, amoxicillin, ampicillin/sulbactam, clindamycin, cephalothin, and cephalexin. In addition, C. sakazakii strains showed the ability to form biofilms, but with variable degrees of cell density. CONCLUSION: We reported, for the first time, cases of neonatal sepsis caused by the emerging life-threatening pathogen C. sakazakii in Egypt. The organism was also detected in contaminated PIF, herbs, and water, which may be sources of infection for neonates, especially in countries where natural herbs are widely used as an alternative medicine. Finally, collective efforts by the parents, manufacturers of PIF, and healthcare personnel are essential to prevent serious infections caused by C. sakazakii, particularly in infants.

Peripheral Blood B and T Cell Profiles in Children with Active Juvenile Idiopathic Arthritis.

Juvenile idiopathic arthritis (JIA) is one of the most common autoimmune diseases in children. Our study aimed to evaluate the peripheral blood B and T lymphocyte subpopulations in children with JIA. This case-control study included 20 children with JIA as well as 20 healthy children with matching age and sex as a control group. All patients included in the study were in activity as determined by visual analog scale. In addition to complete clinical evaluation, basic investigations, peripheral blood B and T lymphocyte subpopulations were done to all participants by flow cytometry. JIA patients displayed a significant decrease in IgM memory B lymphocytes, switched memory B lymphocytes, and total memory B lymphocytes when compared to the healthy controls. The percentages of naïve B lymphocytes were significantly increased in JIA patients than in controls. Total T lymphocytes, CD8+CD28null cells, and CD4+CD28null cells were significantly increased in JIA patients as compared to controls. In conclusion; JIA patients have an alteration in both B and T lymphocytes with the predisposition of memory cells which may have a role in sustaining the JIA disease activity.

Effects of royal jelly supplementation on regulatory T cells in children with SLE.

BACKGROUND AND OBJECTIVE: To our knowledge, no previous studies have focused on the immunomodulatory effects of fresh royal jelly (RJ) administration on systemic lupus erythematosus (SLE) in humans. Our aim was to study the effect of fresh RJ administration on the disease course in children with SLE with some immunological markers (CD4+ and CD8+ regulatory T cells and T lymphocytes apoptosis). METHODS: This was an open-label study in which 20 SLE children received 2 g of freshly prepared RJ daily, for 12 weeks. RESULTS: The percentages of CD4+ CD25+high FOXP3+cells (CD4+ regulatory T cells) and CD8+CD25+high FOXP3+cells (CD8+ regulatory T cells) were significantly increased after RJ treatment when compared with baseline values. Apoptotic CD4 T lymphocytes were significantly decreased after RJ therapy when compared with baseline values and the control group. CONCLUSION: This is the first human study on the effect of RJ supplementation in children with SLE. Our results showed improvements with 3-month RJ treatment with regard to the clinical severity score and laboratory markers for the disease. At this stage, it is a single study with a small number of patients, and a great deal of additional wide-scale randomized controlled studies are needed to critically validate the efficacy of RJ in SLE.