A Prospective Survey of Skin Manifestations in Children With Inborn Errors of Immunity From a National Registry Over 17 Years.

Background and Objectives: Reports on skin manifestations in inborn errors of immunity (IEI) are based on retrospective analysis, small series, or isolated case reports. The present prospective study aimed to determine the spectrum of skin manifestations in children with IEI and their relevance to specific molecular defects. Materials and Methods: The data were obtained from the Kuwait National Primary Immunodeficiency Disorders Registry during the period of 2004-2020. Results: A total of 313 pediatric cases of IEI, 71% diagnosed at molecular level, were registered with a cumulative follow-up period of 29,734 months. Skin manifestations were seen in 40.3% of the patients, and they were among the presenting manifestations in 33%. Patients with skin manifestations were older at both onset and diagnosis ages of IEI symptoms, but this was statistically significant for the latter only. The diagnosis delay was significantly longer in patients with skin manifestations. There was a statistically significant association between having skin manifestations and IEI category, being more common in patients with complement deficiencies, combined immunodeficiencies, and diseases of immune dysregulation. There was no statistically significant association between having skin manifestations and both gender and survival. Skin infections were the most frequent manifestations followed by eczema and autoimmune associations. Among IEI with more than 10 cases, skin lesions were a consistent finding in dedicator of cytokinesis 8 (DOCK8) deficiency, hyper IgE syndrome, ataxia-telangiectasia, and recombination activation gene (RAG)1 deficiency. Conclusions: Skin manifestations are common in IEI patients, and they had significant diagnosis delay and referral to specialists. Improvement of awareness about IEI is needed among pediatricians and dermatologists.

Frequency and Manifestations of Autoimmunity Among Children Registered in the Kuwait National Primary Immunodeficiency Registry.

Objectives: To present a prospective report on the characteristics of autoimmune manifestations in patients with primary immunodeficient children registered in the Kuwait National PIDs Registry (KNPIDR). Methods: The data were obtained from the Kuwait National Primary Immunodeficiency Disorders Registry during the period of January 2004 to December 2019. Results: A total of 286 PID children were registered in KNPIDR during the study period with a predominance of immunodeficiencies affecting cellular and humoral immunity followed by combined immunodeficiencies with associated syndromic features and diseases of immune dysregulation. Fifty-seven (19.9%) patients presented with a total of 107 autoimmune manifestations. There was no significant statistical association between autoimmune manifestations and gender. Patients with autoimmune manifestations were older at onset of PID symptoms compared to those with no such manifestations, but this did not reach level of significance. The diagnosis delay was longer in patients with autoimmune manifestations compared to those with no such manifestations (p = 0.038). Forty-seven percent of these manifestations were among the presenting symptoms while 53% were documented later during the course of the disease. Fifty-seven percent of the patients developed 1 autoimmune manifestation, 30% developed 2 such manifestations, and 16% had ≥3 autoimmune manifestations. The most common autoimmune manifestation was cytopenia, followed by gastrointestinal manifestations and manifestations of the skin, hair, and nails. Autoimmune cytopenia were more common in patients with immune dysregulation syndromes, while gastrointestinal and skin manifestations predominate in patients with immunodeficiencies affecting cellular and humoral immunity and endocrine manifestations were more common in immune dysregulation syndromes. There were significant statistical associations between developing autoimmune manifestations and death as well as PID categories, being more common in patients with immune dysregulation. The frequency of autoimmunity was high among patients with RAG, WAS, STAT5b, NF-κB2, Fas, FasL, LRBA, APECED, IL-10, and C4 deficiencies. Conclusions: Autoimmunity is frequent in patients with PIDs in Kuwait. This should prompt the suspicion of a PID in patients who present initially with autoimmunity, especially autoimmune cytopenia. Such patients should be managed with extra care since they are at a higher risk of death.

Determination of the elastic modulus of ascending thoracic aortic aneurysm at different ranges of pressure using uniaxial tensile testing.

OBJECTIVE: The purpose of this study is to provide measurements of the elastic modulus of the aortic wall of ascending thoracic aortic aneurysms for different ranges of pressure (physiologic, hypertensive). In addition, pre-failure stress, taken as the peak stress obtained before specimen failure, was recorded for each test. METHODS: Ninety-seven aortic samples freshly excised from 13 patients with ascending thoracic aortic aneurysms were obtained from greater and lesser curvatures and tested uniaxially in circumferential and longitudinal orientations. RESULTS: The maximum elastic moduli, overall, and particularly in the lesser curvature were significantly higher in the circumferential orientation (9.19 MPa) than in the longitudinal (3.13 MPa). Results of peak stress showed positive correlation with maximum elastic modulus and inverse correlation with tissue wall thickness. CONCLUSIONS: This study provides new data on the elastic modulus in the physiologic and hypertensive range that can be used in computational analysis and the design of bench-top models. The accuracy of computational analysis and bench-top models strongly depends on the knowledge of the elastic properties of the aortic wall. The mechanical properties presented in this study, with specific values for 2 locations (greater and lesser curvature) and 2 directions (circumferential, longitudinal), will increase our understanding of the mechanisms that precede rupture of an ascending aortic aneurysm.

Performance status and deaths among children registered in Kuwait National Primary ImmunoDeficiency Disorders Registry.

Children with primary immunodeficiency disorders (PIDD) have an increased risk of suffering from physical, social, and psychological problems. The aim of this study was to evaluate the performance status and mortality of children with PIDD in Kuwait and to determine the variables and co-morbidities that may affect their performance and risk of death. The data for the children were obtained from Kuwait National Primary Immunodeficiency Disorders Registry describes the patients' characteristics, comorbidities and their treatment regimens. Each patient was scored using the Lansky Play Performance Scale (LPPS), and we evaluated the number of deaths among the children and the effects of different variables on their LPPS scores and mortality. We examined 98 pediatric patients with a mean delay in diagnosis of 21.2 months. Antimicrobial prophylaxis was administered to 57.2% of the patients, whereas intravenous immunoglobulin (IVIG) therapy was used in 44%. Eight patients underwent bone marrow transplants. The mean LPPS score for all the patients was 65.5, and there was a significant disparity in the mean LPPS scores across PIDD categories. Twenty-one patients died. The variables that were found to have a significant effect on both the LPPS score and the risk of death were an age of onset of less than 6 months, a history of CMV infection, parental consanguinity, the use of antimicrobial prophylaxis and IVIG therapy. In conclusion, patients with PIDD have a poor performance status and a high rate of mortality. Early diagnosis and aggressive therapeutic interventions directed at patients with early onset of symptoms and CMV infections can help improve the quality of life of patients with PIDD.

Primary immunodeficiency disorders: survey of pediatricians in Kuwait.

INTRODUCTION: Early diagnosis of primary immunodeficiency disorders (PID) is critical so life saving interventions can be implemented to avoid significant morbidity and mortality. Unfortunately, they are frequently misdiagnosed, which results into significant delay in diagnosis. This study aimed to determine the knowledge and practice of pediatricians in Kuwait about PID. MATERIALS AND METHODS: A 66-item self-administered questionnaire was designed and distributed to the pediatricians working at all six governmental hospitals to measure their knowledge and practice about PID. A total of 244 pediatricians (78.4%; 143 males and 101 females) participated in the study. The mean age of participants was 40 years, and the mean number of years working in pediatrics was 13 years. The mean overall score was 59.6%, whereas the mean score in clinical presentation section was 63%, in associated diseases and syndromes section 58%, and in laboratory investigations section 51%. Only 26% of the participants answered correctly at least 2/3 of the questions (67% of the questions). CONCLUSION: This survey demonstrates that there is universal deficiency in both the knowledge and practice of pediatricians in the field of PID. Implementation of strategies to improve the awareness of pediatricians about PID is critical so early therapeutic interventions can be done to improve the health and prevent morbidity and mortality.