SARS-CoV-2 brainstem encephalitis in human inherited DBR1 deficiency.

Inherited deficiency of the RNA lariat-debranching enzyme 1 (DBR1) is a rare etiology of brainstem viral encephalitis. The cellular basis of disease and the range of viral predisposition are unclear. We report inherited DBR1 deficiency in a 14-year-old boy who suffered from isolated SARS-CoV-2 brainstem encephalitis. The patient is homozygous for a previously reported hypomorphic and pathogenic DBR1 variant (I120T). Consistently, DBR1 I120T/I120T fibroblasts from affected individuals from this and another unrelated kindred have similarly low levels of DBR1 protein and high levels of RNA lariats. DBR1 I120T/I120T human pluripotent stem cell (hPSC)-derived hindbrain neurons are highly susceptible to SARS-CoV-2 infection. Exogenous WT DBR1 expression in DBR1 I120T/I120T fibroblasts and hindbrain neurons rescued the RNA lariat accumulation phenotype. Moreover, expression of exogenous RNA lariats, mimicking DBR1 deficiency, increased the susceptibility of WT hindbrain neurons to SARS-CoV-2 infection. Inborn errors of DBR1 impair hindbrain neuron-intrinsic antiviral immunity, predisposing to viral infections of the brainstem, including that by SARS-CoV-2.

COVID-19 Vaccination in Patients with Inborn Errors of Immunity Reduces Hospitalization and Critical Care Needs Related to COVID-19: a USIDNET Report.

BACKGROUND: The CDC and ACIP recommend COVID-19 vaccination for patients with inborn errors of immunity (IEI). Not much is known about vaccine safety in IEI, and whether vaccination attenuates infection severity in IEI. OBJECTIVE: To estimate COVID-19 vaccination safety and examine effect on outcomes in patients with IEI. METHODS: We built a secure registry database in conjunction with the US Immunodeficiency Network to examine vaccination frequency and indicators of safety and effectiveness in IEI patients. The registry opened on January 1, 2022, and closed on August 19, 2022. RESULTS: Physicians entered data on 1245 patients from 24 countries. The most common diagnoses were antibody deficiencies (63.7%). At least one COVID-19 vaccine was administered to 806 patients (64.7%), and 216 patients received vaccination prior to the development of COVID-19. The most common vaccines administered were mRNA-based (84.0%). Seventeen patients were reported to seek outpatient clinic or emergency room care for a vaccine-related complication, and one patient was hospitalized for symptomatic anemia. Eight hundred twenty-three patients (66.1%) experienced COVID-19 infection. Of these, 156 patients required hospitalization (19.0%), 47 required ICU care (5.7%), and 28 died (3.4%). Rates of hospitalization (9.3% versus 24.4%, p < 0.001), ICU admission (2.8% versus 7.6%, p = 0.013), and death (2.3% versus 4.3%, p = 0.202) in patients who had COVID-19 were lower in patients who received vaccination prior to infection. In adjusted logistic regression analysis, not having at least one COVID-19 vaccine significantly increased the odds of hospitalization and ICU admission. CONCLUSION: Vaccination for COVID-19 in the IEI population appears safe and attenuates COVID-19 severity.

Reliability of Agreement between Insulin, Clonidine, and Glucagon Stimulation Tests for the Diagnosis of Growth Hormone Deficiency in Children: A Retrospective Cohort Study.

Growth hormone (GH) deficiency (GHD) is a rare disorder. The diagnosis of GHD requires a combination of two provocative GH tests. This study aimed to find agreement between commonly used medications to determine which combined tests have high reliability of agreement. This retrospective cohort included 201 children who underwent GH provocation testing from January 2012 to December 2022. The insulin tolerance test (ITT) with the clonidine stimulation test (CST) or glucagon stimulation test (GST) with the CST were performed. We calculated Cohen's kappa to determine the agreement between the test medications by considering the post-stimulation peak GH level with a cut-off value of 10 ng/mL as the primary outcome. A total of 151 patients underwent the two provocative tests and were included in the analysis. Of these patients, 119 underwent the ITT and CST and 54 (45.3%) were diagnosed with GHD. However, 32 patients underwent the GST and CST and 18 (56.2%) were diagnosed with GHD. The kappa value for ITT and CST was 0.258 (25.8%), indicating fair agreement between clonidine and insulin (p = 0.005). However, the kappa value for CST and GST was 0.178 (17.8%), representing slight agreement. The correlation coefficient revealed a very strong relationship between ITT and CST. Clonidine has fair agreement and a very strong correlation coefficient with ITT when used to diagnose GHD in children. Among the commonly used pharmacological tests for GH provocation in our unit, the CST was considered the best pharmacological test in terms of safety and reduced parental anxiety.

Adverse Drug Reactions (ADRs) of Montelukast in Children.

Montelukast is a leukotriene receptor antagonist (LTRA) commonly prescribed for asthma, allergic rhinitis and sleep-related breathing disorders. Recently, some studies have reported several adverse events, such as neuropsychiatric disorders and sleep disturbances, among children. OBJECTIVE: To obtain more insight into the safety profile of montelukast for children with asthma, allergic rhinitis and sleep-related breathing disorders. METHOD AND RESULTS: We retrospectively studied all adverse drug reactions to montelukast among 385 children 6 months or older in six tertiary centers over a two-year period. A total of 89.6% were asthmatic, 50% had allergic rhinitis and 13.6% had sleep-related breathing disorders; Singulair was the most common type of montelukast used (67.9%). This study reported a high prevalence of adverse drug reactions among 123 patients (31.9%), predominantly in those aged 4-9 years (52.8%), followed by adolescents (24.4%) and toddlers (22.8%). Two (ADRs) were reported in 9.8% of the children, while three or more were reported in 5.5%. Sleep disturbance was the most common (ADRs), affecting 15.1% of participants (overlap was common; 5.5% of children experienced sleep difficulties, 4.4% experienced sleep interruption and decreased sleep, and 1.82% experienced nightmares), followed by agitation (10.4%), pain (9.4%) and hyperactivity (6.8%). No serious (ADRs) were reported. Eleven percent of families faced difficulties in purchasing montelukast, and only 57% of families had insurance. Misconceptions were common (9.8% reported it to be a steroid, while 30.6% believed it to be a bronchodilator). Although 81% of the families believed it was an effective and preventive medication, 5.3% stopped the drug due to concern about side effects, especially agitation (3%) and nightmares (0.6%). CONCLUSION: These data demonstrate that montelukast is effective, but the associated adverse neuropsychiatric drug reactions are more prevalent than those reported in the literature. In particular, sleep disturbance, agitation, pain and hyperactivity were observed. Pediatricians should be aware of such (ADRs). Misconceptions about montelukast are still common, and parental counseling and urgent epidemiological studies are needed to quantify the risk for management plans.

Physicians' Understanding of the Role of the Microbiome in Allergies and Asthma: A Questionnaire-Based Study in Saudi Arabia.

Purpose: Allergies and asthma are two noncommunicable illnesses of increasing public health concern in Saudi Arabia. Nevertheless, little is known about knowledge of the microbiome and its relationship to asthma and allergy risks among healthcare professionals, such as pediatricians and family medicine practitioners, who are often involved in the care of patients suffering from these illnesses. Therefore, this study aimed to examine knowledge about microbiome science in these healthcare workers in the eastern region of the kingdom, where allergies and asthma are highly prevalent. Patients and Methods: The study survey consisted of 37 online questions in three topical domains, including microbiome science, dysbiosis, and probiotics, and was distributed to 203 participants in various demographic groups. Results: The survey analysis revealed that the mean knowledge score was 67.6%. The component scores were highest for the microbiome (75.6%) and lowest for dysbiosis (52.6%). Only 17.7% of the healthcare workers were prescribing probiotic food or drinks for most of their patients with allergies and/or asthma; and 37.8% of the healthcare workers were unaware of the reasons for prescribing pro-/prebiotics. Regression analysis revealed that older age (>45 years old), probiotic prescription experience, and positive beliefs about the importance of nutritional advice were independent predictors of higher microbiome knowledge. Conclusion: The analysis not only revealed existing gaps in microbiome knowledge among the participants, including those related to the role of the microbiome in allergy and asthma development but also identified predictors of higher microbiome knowledge. These observations provide an impetus for the rational design of continuing medical education curriculum and training to update healthcare professionals with emerging clinical application of microbiome knowledge for the management of microbiome-related illnesses.

Blood utilization and quality indicators at a university hospital in the Eastern Province of Saudi Arabia.

BACKGROUND: Blood transfusion is a common, essential procedure when treating many different medical and surgical conditions. Efficient utilization of blood bank facilities by frequent auditing is crucial; however, few studies have examined blood utilization in Saudi Arabia. We aimed to review the blood ordering patterns and transfusion practices, and blood bank audit effectiveness at a single center in Saudi Arabia and compare our results with those of a similar study performed in the same center 20 years ago. MATERIALS AND METHODS: This study was a retrospective descriptive chart review of all healthy blood donors and recipients from January 1, 2016, to December 31, 2020. We evaluated the crossmatching-to-transfusion ratio (C/T) as an indicator of blood bank utilization and compared the findings with those of the previous study. We also evaluated changes in blood bank utilization during the coronavirus disease 2019 pandemic. RESULTS: Findings from 27,414 donors (men, 94.9%; mean age, 32.2 + 9.6 years) showed a 71% increase in blood donations compared to that of 2000. The donations gradually increased over the years, peaking just before COVID-19 pandemic started in March 2020. For 3,836 patients, 13,324 units of blood were crossmatched (average, 3.47 crossmatch/patient), with 23% of the crossmatch requests from surgical departments. The average C/T ratio, transfusion index, and transfusion probability (T%) were 1.37, 2.55, and 73.2%, respectively. The C/T ratio decreased by 54% between 2000 and 2020. During the pandemic, crossmatching decreased by 26% between 2019 and 2020, but with comparable C/T ratio in 2019 (1.45) and 2020 (1.39). CONCLUSION: Our hospital blood bank utilization improved over the past 20 years, showing increased donations, reduced C/T ratio, and increased T%. This improvement emphasizes the importance of blood donation campaigns, blood bank auditing, restrictive transfusion guidelines, and physician education.

Evaluating the knowledge on microbiome and dysbiosis in allergic diseases among medical sciences students in Saudi Arabia.

BACKGROUND: Microbiome science deals with the development of diseases that are derived from the interaction between the host immune system and microbes. Microbiome disturbance or dysbiosis has been increasingly recognized as an important contributor to the pathogenesis of allergic diseases. Thus, this field is pivotal in the management of allergic disorders. Despite the increasing prevalence of allergic disorders in Saudi Arabia, medical students lack knowledge of microbiome science. Therefore, this study aimed to assess the level of knowledge of medical sciences students on the human microbiome, dysbiosis, and management of the impaired microbiome with a focus on allergic diseases and asthma. METHODS: An online survey was designed, validated, and distributed to 100 final-year students and interns majoring in clinical nutrition, public health, and clinical laboratory sciences at a single university in Saudi Arabia. The study period was from November 2020 to January 2021. RESULTS: The overall knowledge of the human microbiome was adequate among the participants, but their understanding of dysbiosis and management of the impaired microbiome was low to moderate. Knowledge of dysbiosis management was significantly higher in students majoring in clinical nutrition than in those majoring in public health and clinical laboratory sciences. CONCLUSIONS: Collectively, this study provides the first evidence that knowledge of specific domains of microbiome science among a cohort of medical sciences students in Saudi Arabia is insufficient. Large-scale studies are warranted to confirm these observations at a national level, and specific curriculum modifications are necessary to improve the knowledge of future healthcare professionals about clinical applications of microbiome science.

Perception of Saudi Undergraduate Students Towards Professionalism in Medicine.

OBJECTIVES: Professionalism has garnered immense attention in medical education due to increased societal accountability and focus on excellence in healthcare. However, less attention has been given to identifying attitudes about professionalism in medical students who are the future advocates of the healthcare system. This study aimed to assess perceptions of Saudi undergraduate medical students towards professionalism. METHODS: A cross-sectional survey was carried out among second and sixth year students of the College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia, in September 2018. A self-administered professionalism questionnaire was anonymously completed. Students were asked to provide their level of agreement with 18 survey items using a 5-point Likert scale. RESULTS: Overall, 288 students participated in the study (males: 49.3% and females: 50.7%), with a response rate of 90%. The median professionalism score was high (71.0; range: 64-76) regardless of age, gender or level of education. Similar high scores were noted in the following subscales: Excellence, 20.0 (range: 18-21); Respect for Others, 17.0 (14-18); Altruism, 12.0 (10-13); Duty, 8.0 (7-9); Accountability, 7.0 (6-8) and Honour and Integrity, 8.0 (7-10). No gender differences were observed in the majority of subscales. However, males demonstrated higher scores in the Duty subscale (males: 9.0 versus females: 8.0; P = 0.026). CONCLUSION: Medical students demonstrated high professionalism scores. Future studies are needed to assess the impact of the course curriculum on their level of professionalism over time.

Maternal Blood Group and Routine Direct Antiglobulin Testing in Neonates: Is There a Role for Selective Neonatal Testing?

Recommendations for the screening of hemolytic disease of the newborn (HDN) advise taking a selective approach in using the direct antiglobulin test (DAT) for mothers with blood group O or RhD-negative. This study assessed the relation of DAT results to maternal and neonatal blood groups and evaluated the risk of HDN. A retrospective analysis of all healthy newborns admitted during 2018 was performed. Of 1463 newborns, 4.4% had a positive DAT. There were 541 (37%) maternal-neonatal pairs with ABO incompatibility, most commonly born to mothers with blood group O. The cohort of neonates born to mothers with blood group O was divided into three groups: the O-A and O-B groups and the O-O group as a control. The DAT was positive in 59 (8.3%) neonates; most were in the O-B group (49.2%), whereas 13.6% were in the control group (p < 0.01). While the neonates in the O-B group were more likely to require phototherapy (p = 0.03), this finding was not related to DAT results. We found that selective testing of mothers with blood group O, mothers with blood group O or RhD-negative, neonates with blood group B, and neonates with blood group B born to mothers with blood group O or RhD-negative was ineffective in detecting phototherapy requirements. Our results indicate no difference regarding the need for phototherapy in neonates born to mothers with different blood types regardless of the DAT results.

Clinicians' Perceptions of Picture Archiving and Communication System (PACS) Use in Patient Care in Eastern Province Hospitals in Saudi Arabia.

PURPOSE: The picture archiving and communication system (PACS) is one of the most important tools used in patient care in many hospitals worldwide. It allows clinicians to remotely communicate and consult with other clinicians on patient cases and view diagnostic images from different angles, thus facilitating patient diagnosis and treatment. Several studies have been conducted in Saudi Arabia to evaluate different aspects of PACS use; however, no comprehensive study has been conducted in its Eastern Province. This study aimed to investigate clinicians' perceptions of the advantages and disadvantages of the use of PACS in Eastern Province hospitals in Saudi Arabia and identify the factors that affect their perceptions and its use. In addition, it aimed to gather recommendations of clinicians for improving the system and its implementation. METHODS: A qualitative approach with grounded theory method was employed. A sample of 18 residents, radiologists, and consultants from three Eastern Province hospitals in Saudi Arabia participated in the study. Data were collected using semi-structured interviews over a period of 7 months. RESULTS: The perceived advantages of PACS included providing quality images and the ability to manipulate their resolution, whereas the perceived barriers included low-speed internet connections and technical problems. Participants recommended providing clinicians remote access to the system and implementing a mobile PACS application. The theory that emerged from the analysis revealed that demographic, system-related, and hospital-related factors affected participants' perspectives of PACS and its use. CONCLUSION: The results of this study and its theoretical model can help identify areas of improvement and inform policy and strategic planning for the effective implementation of PACS in patient care in Saudi Arabia.

Value of the Direct Antiglobulin Test in Predicting the Need for Phototherapy in Newborns.

PURPOSE: Guidelines for managing neonatal hemolytic disease of the newborn (HDN) recommend a selective approach in the use of direct antiglobulin test (DAT). In Saudi Arabia, many hospitals still perform routine DAT for all newborns. This study assessed the need for phototherapy in relation to DAT results in full-term healthy newborns. PATIENTS AND METHODS: A retrospective analysis of all healthy newborns admitted during 2018 was performed. The primary outcome was the association of positive DAT results with phototherapy. RESULTS: There were 1463 newborns born during the study period. The DAT was positive at 4.4%. The 24-hour bilirubin levels were higher in DAT-positive cases (P=0.06); however, peak bilirubin levels were not correlated with the DAT results (P=0.717). Thirty-six neonates (2.46%) required phototherapy, and the need was similar among DAT-positive and DAT-negative cases (P=0.271). The most common indication for phototherapy was clinical jaundice in 22 neonates (61.1%), followed by DAT positivity in 12 (33.3%) and hospital protocol in 2 patients (5.6%) (P <0.01 by chi-square overall comparison). CONCLUSION: Our results indicate that factors other than DAT positivity are important in assessing the need for phototherapy in newborns. Clinical signs of jaundice were indicators of high serum bilirubin levels and subsequent phototherapy, further indicating that the DAT test was overused in predicting the need for phototherapy.

Clinical spectrum and outcome of immunoglobulin A vasculitis in children: A 10-year clinical study.

BACKGROUND: Immunoglobulin A (IgA) vasculitis is the most common vasculitides of childhood. The aim of this study was to characterise the disease and identify clinical and laboratory factors associated with renal involvement. METHODS: Medical records of children aged ≤18 years with the diagnosis of IgA vasculitis according to the EULAR/PRES criteria were retrospectively reviewed for demographic data, clinical manifestations and laboratory tests. Factors associated with renal involvement were determined using multivariable logistic regression analysis. RESULTS: A total of 113 patients were involved in the study. There were 57.5% of males (male: female ratio of 1.4:1). The mean (SD) age was 7.1 (3.0) years. Most of the patients presented during the fall (37.2%) and winter (29.2%). The most common presenting complaints were skin rash (83.2%) and arthralgia (9.7%). The most frequent presentation of the skin was palpable purpuric rash, except for two patients (1.8%) presenting with blistering eruptions in the form of hemorrhagic bullae and ecchymoses of both extremities. We have encountered one patient with pulmonary-renal syndrome. Renal involvement was found in 27.4% of the patients. In the multivariate analysis, the strongest factors associated with renal involvement were older age and elevated creatinine level. Factors that improved model fit were higher platelet and lower white blood cell counts, elevated anti-streptolysin O and a history of preceding infection. CONCLUSION: The clinical profile of the disease in our cohort was similar to other reports. However, we have encountered a few severe and rare atypical presentations. Over a quarter of children in our setting had renal involvement. Children presenting with these risk factors need to be closely monitored and long-term follow-up is recommended.

Dynamic Interplay Between Microbiota and Mucosal Immunity in Early Shaping of Asthma and its Implication for the COVID-19 Pandemic.

The crosstalk between host immunity and the external environment in the mucous membranes of the gastrointestinal and respiratory tracts in bronchial asthma has recently been scrutinized. There is compelling evidence that the microbiota at these sites may play an important role in the pathogenesis of this chronic airway disease. The appearance of bacteria early in life in the gut before dissemination to the airways plays a pivotal role in shaping mucosal immunity. Loss of microbial diversity or dysbiosis can result in aberrant immune-mediated inflammation and mucosal barrier disruption, which coincides clinically with the successive development of the "allergic march" in asthma. Microbial manipulation may be effective in curbing asthma development by indirectly preserving homeostatic epithelial barrier functions. The protective effects and mechanisms of immunity-microbiome crosstalk at mucosal sites require further investigation to identify therapeutic and preventive measures in asthma. This topical review aims to highlight new evidence that compromised epithelial barrier function, which results in deregulated crosstalk between the microbiome and host mucosal immune system, is an important disease mechanism in asthma. In the light of current COVID-19 pandemic, the collective findings on the impact of mucosal microbiota on the suceptibility to SARS-CoV-2 infection and severity of COVID-19 is explored. The possible therapeutic implications to target these abnormalities are further discussed.

Childhood Asthma Awareness in Saudi Arabia: Five-Year Follow-Up Study.

BACKGROUND: Bronchial asthma is a chronic inflammatory airway disease that is characterized by reversible airway obstruction due to bronchial hyperresponsiveness. It is one of the most common chronic diseases. In Saudi Arabia, asthma affects 2 million people with asthma frequency in children markedly higher than adults with regional variations ranging from 9% to 33.7%. OBJECTIVE: The aim of this study is to measure asthma awareness and knowledge of study participants during the ongoing annual Saudi asthma awareness campaigns and compare them with previous survey data conducted in 2014. METHODS: A cross-sectional study was carried out in the form of a survey distributed across three major cities in Saudi Arabia, Jeddah, Riyadh and Dammam, during the National Asthma Awareness Campaign in major regional shopping centers in April 2019. Asthma knowledge scores across different demographic groups were generated from surveyed data. Descriptive and correlative statistical analyses were performed to identify factors associated with changes in asthma knowledge. Scores were compared to previous survey results. RESULTS: The mean score for asthma knowledge was 15.6 out of 25. Asthma knowledge significantly correlated with age (P=0.002), asthma status of the participants (P=0.001), having children with asthma (P=0.005) or knowing friends or family with asthma (P=0.029) but not with other socioeconomic factors such as gender, marital status, occupation, level of education and number of children in the family (P > 0.05). There was a significant difference in the asthma scores from 2014 (M= 63%, SD=26) to 2019 (M= 70%, SD= 26) conditions; t (24) = -2.106, p=0.046. CONCLUSION: Further educational campaigns are necessary to enhance and measure general public awareness of asthma, its differential diagnosis against other respiratory infections, environmental triggers, risk factors as well as treatment options.

A novel variant in the neutrophil cytosolic factor 2 (NCF2) gene results in severe disseminated BCG infectious disease: A clinical report and literature review.

BACKGROUND: Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disorder (PID) affecting NADPH oxidase activity. The rarest form of the disease is considered to be caused by NCF2 gene bi-allelic variant. Here, we report the clinical and molecular characterization of a patient presenting with early-onset severe disease due to bi-allelic NCF2 variant. METHODS: Gene mutational analysis was performed by whole-exome and Sanger sequencing. RESULTS: The patient presented with a history of fever and rash since the age of 1 month, followed by destructive osteomyelitis and necrotizing lymphadenopathy. The patient received the Bacillus Calmette-Guérin (BCG) vaccine at birth; she was subsequently diagnosed with disseminated BCG infection. Whole-exome sequencing identified a private (unreported) homozygous variant in NCF2 (c.290C > A) that results in a nonconservative change, p.Ala97Asp, in the p67phox protein. The variant is located in the third helix of the TRP domain, which is crucial for the binding of GTPase RAC2 to the NADPH oxidase complex. CONCLUSION: We identified a novel NCF2 variant located in the region interacting with RAC2 that is linked to a severe and early CGD phenotype in the setting of disseminated BCG infection. Our findings support postponing BCG vaccination until 6-12 months of age and after PID assessment.

A novel mutation in NCF2 resulting in very-early-onset colitis and juvenile idiopathic arthritis in a patient with chronic granulomatous disease.

BACKGROUND: Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disorder caused by a defect in the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex. The disease primarily presents with recurrent infections, and patients may also present with inflammatory conditions, including noninfectious colitis, and an increased frequency of autoimmunity. We report here a patient with CGD in whom the presentation, unlike the classical presentation of CGD, was predominantly of an inflammatory and autoimmune phenotype. CASE PRESENTATION: A 3-year-old Pakistani female presented with bloody diarrhea since the age of 7 days, followed by the development of perianal abscesses and fistula. There was no other history of recurrent infections. The patient subsequently developed joint pain and stiffness with persistently elevated inflammatory markers and elevated anti-cyclic citrullinate peptide (anti-CCP) antibody titer. She was diagnosed with oligoarticular juvenile idiopathic arthritis and colitis. The diagnosis of CGD was later made and was based on the absence of NADPH oxidase activity in the patient's neutrophils upon phorbol myristate acetate (PMA) stimulation using the dihydrorhodamine-1,2,3 (DHR) flow cytometry test. Targeted next-generation sequencing revealed an unreported deletion mutation in exon 10 as a homozygous loss-of-function variant of the human neutrophil oxidase factor 2 (NCF2) (NCF2: NM_001190789, nucleotide change: c.855_856del:p.T285fs). The gene encodes a protein subunit, p67phox, in the NADPH enzyme complex. CONCLUSIONS: The case emphasizes the importance of maintaining high clinical suspicion of immunodeficiency and CGD in patients with very-early-onset colitis and autoimmune disorders. This case is important due to its rarity and because it might represent a previously undiscovered mutation, which is possibly more common in the patient's ethnic group. Other mutations in NCF2 have been linked to inflammatory bowel disease and autoimmunity, but without CGD, suggesting similarities in the pathogenesis.

Sensitization to Common Aeroallergens in Asthmatic Children in the Eastern Region of Saudi Arabia.

BACKGROUND: Allergic disorders, particularly bronchial asthma, are one of the most common chronic childhood diseases. Bronchial asthma is more prevalent among children of the Eastern Province of Saudi Arabia compared with the other provinces. Environmental factors play major roles in the disease pathogenesis in genetically predisposed hosts. In this study, we characterize the pattern of allergenicity in asthmatic children in the Eastern Province of Saudi Arabia. MATERIALS AND METHODS: This study is a retrospective, cross-sectional analysis of skin sensitization profiles of 100 Saudi asthmatic children living in Al-Khobar, Saudi Arabia. The group compromised 32 females and 68 males, aged 5-14 years with a mean age of 8.98 ± 2.93 years. Skin prick tests were performed in a regional tertiary center, in the period between January 2011 and December 2012, using a variety of indoor and outdoor allergens. RESULTS: The most common indoor sensitizing allergens found were the house dust mite (54%), cat fur (53%) and the German cockroach (26%). Among outdoor allergens, Salsola kali was the most common (48%), followed by Timothy grass (23%) and Chenopodium album (23%). Among trees, Prosopis glandulosa was found to be the most prevalent sensitizer (19%). Among the molds, Alternaria and Aspergillus species were the most prevalent (21% each). CONCLUSION: A high rate of sensitization to aeroallergens was found in asthmatic children living in Al-Khobar city. The pattern of sensitization found in our study reflects the newly altered nature of an ancient humid desert that has been influenced by the recent artificial modernization of the region.

Genetic, immunological, and clinical features of patients with bacterial and fungal infections due to inherited IL-17RA deficiency.

Chronic mucocutaneous candidiasis (CMC) is defined as recurrent or persistent infection of the skin, nails, and/or mucosae with commensal Candida species. The first genetic etiology of isolated CMC-autosomal recessive (AR) IL-17 receptor A (IL-17RA) deficiency-was reported in 2011, in a single patient. We report here 21 patients with complete AR IL-17RA deficiency, including this first patient. Each patient is homozygous for 1 of 12 different IL-17RA alleles, 8 of which create a premature stop codon upstream from the transmembrane domain and have been predicted and/or shown to prevent expression of the receptor on the surface of circulating leukocytes and dermal fibroblasts. Three other mutant alleles create a premature stop codon downstream from the transmembrane domain, one of which encodes a surface-expressed receptor. Finally, the only known missense allele (p.D387N) also encodes a surface-expressed receptor. All of the alleles tested abolish cellular responses to IL-17A and -17F homodimers and heterodimers in fibroblasts and to IL-17E/IL-25 in leukocytes. The patients are currently aged from 2 to 35 y and originate from 12 unrelated kindreds. All had their first CMC episode by 6 mo of age. Fourteen patients presented various forms of staphylococcal skin disease. Eight were also prone to various bacterial infections of the respiratory tract. Human IL-17RA is, thus, essential for mucocutaneous immunity to Candida and Staphylococcus, but otherwise largely redundant. A diagnosis of AR IL-17RA deficiency should be considered in children or adults with CMC, cutaneous staphylococcal disease, or both, even if IL-17RA is detected on the cell surface.

CNS vasculitis and stroke as a complication of DOCK8 deficiency: a case report.

BACKGROUND: Primary immunodeficiency disorders associated with autoimmunity are poorly understood. Central nervous system (CNS) vasculitis can complicate the courses of such entities, but it is underappreciated. Deletion of the dedicator of cytokinesis 8 (DOCK8) gene is considered to be the autosomal recessive form of hyperimmunoglobulin E syndrome which is a rare type of primary immunodeficiency disease characterized by elevated levels of IgE antibody, eczema, and recurrent staphylococcal infections. DOCK8 deletion is associated with fatal CNS vasculitis. However, descriptions of such cases and their outcomes are scarce in the literature. CASE PRESENTATION: This report describes a young female with a DOCK8 gene deletion presenting acutely with squint, fatigue and visual hallucinations. The patient was diagnosed as having neuritis of the third oculomotor nerve and encephalitis, which were thought to be related to her underlying immune deficiency, however, she subsequently was diagnosed with CNS vasculitis based on brain magnetic imaging and magnetic resonance angiography findings. We provide here a comprehensive description of the patient's clinical outcome and outline an effective treatment approach that may be useful for similar patients and includes the use of steroids and mycophenolate mofetil (MMF). The treatment was well tolerated and enabled the patient to recover most of her neurological deficits. However, despite the initial improvement, she later developed stroke. CONCLUSIONS: To the best of our knowledge, this is the first report in the literature of a case of primary immunodeficiency complicated by CNS vasculitis demonstrating a successful outcome. Our observations indicate that the combination of MMF and steroids is an effective treatment for CNS vasculitis associated with DOCK8 deficiency. However, lack of awareness of the neurological comorbidities associated with primary immunodeficiencies and the delay in diagnosis likely contributed to the development of acute cerebral infarction. Early treatment and aggressive control of the disease's initial inflammation is essential for preventing catastrophic stroke.

Approach to the child with recurrent infections.

Children with a history of recurrent, severe, or unusual infections present a diagnostic challenge. It is important to maintain a high index of suspicion for the diagnosis of immunodeficiency, for early diagnosis and treatment can improve outcome. Differentiation between infections caused by common risk factors, or immune dysfunction should be based on a detailed history and physical examination and, if indicated, followed by appropriate laboratory studies. This paper aims at providing guidelines for the evaluation of children with recurrent infections. It provides an overview of the diagnostic approach including important details required from the history, physical examination, and an appropriate choice of screening test to be ordered.