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Purpose: Inborn errors of immunity (IEI) are a heterogeneous group of diseases with variable clinical phenotypes. This study was conducted to describe the epidemiology, clinical presentations, treatment, and outcome of IEI in Jordanian children. Methods: A retrospective data analysis was conducted for children under 15 years diagnosed with IEI from the pediatric Allergy, Immunology, and Rheumatology Division-based registry at Queen Rania Children’s Hospital, Amman, Jordan, between 2010 and 2022. Results: A total of 467 patients, 263 (56.3%) males and 204 (43.7%) females, were diagnosed with IEI. The mean age at symptom onset was 18 months (1 week to 144 months), a positive family history of IEI was reported in 43.5%, and the consanguinity rate was 47.9%. The most common IEI category was immunodeficiencies affecting cellular and humoral immunity at 33.2%, followed by predominantly antibody deficiencies at 16.9%. The overall median diagnostic delay (range) was 6 (0-135) months; patients with a positive family history of IEI had a statistically significant shorter diagnostic delay. Pulmonary and gastrointestinal clinical features were the most common at 55.2% and 45.6%, respectively. The overall mortality was 33.2%; the highest rate was reported in severe combined immunodeficiency at 56.2%. Conclusions: The high minimal estimated IEI prevalence at 16.2/100,000 Jordanian children compared to the regional and worldwide data, with the diversities in clinical presentation and distribution of IEI categories in our cohort point to unique features of IEI in Jordanian children, call for national registry establishment, regional and international collaborative networks. [ABSTRACT FROM AUTHOR]

Kawasaki Disease (KD) is still the most common acquired heart disease in children below the age of five years; it has been well described in the developed world; however, data from the Arab world are limited to case reports or single-center case series. In an effort of optimizing KD research in the Arab world, a group of physicians and researchers established the KD Arab Initiative (Kawarabi) in 2021, and published the first survey, which showed disparities in the availability of intravenous immunoglobulin (IVIG); this had prompted Kawarabi to assess the access to care and therapy of KD patients in Arab countries. A 32 structured questions survey was conducted in thirteen Arab countries and addressed KD patients' access to healthcare in urban and rural settings. The survey results showed that access to care was uniform across large, mid-size cities and rural areas in 7/13 (54%) countries, while in 6/13 (46%) countries, it was in favor of large and mid-size cities over rural areas. The quality of medical services received by children with KD in large cities was rated as excellent in 6/13 or good in 7/13 countries compared to fair in 4/13 or poor in 4/13 countries in rural areas. Availability of IVIG was limited (23%) in mid-size cities and almost impossible (23%) in rural areas. The KD patients in mid-size cities and rural areas have limited access to standard healthcare in the Arab world. This survey laid the foundation for future Kawarabi endeavors to improve the care of children with KD. [ABSTRACT FROM AUTHOR]

Studies on Kawasaki disease (KD) in Arab countries are scarce, often providing incomplete data. This along with the benefits of multicenter research collaboratives led to the creation of the KD Arab Initiative [Kawarabi] consortium. An anonymous survey was completed among potential collaborative Arab medical institutions to assess burden of KD in those countries and resources available to physicians. An online 32-item survey was distributed to participating institutions after conducting face validity. One survey per institution was collected. Nineteen physicians from 12 countries completed the survey representing 19 out of 20 institutions (response rate of 95%). Fifteen (79%) institutions referred to the 2017 American Heart Association guidelines when managing a patient with KD. Intravenous immunoglobulin (IVIG) is not readily available at 2 institutions (11%) yet available in the country. In one center (5%), IVIG is imported on-demand. The knowledge and awareness among countries' general population was graded (0 to 10) at median/interquartiles (IQR) 3 (2–5) and at median/IQR 7 (6–8) in the medical community outside their institution. Practice variations in KD management and treatment across Arab countries require solid proactive collaboration. The low awareness and knowledge estimates about KD among the general population contrasted with a high level among the medical community. The Kawarabi collaborative will offer a platform to assess disease burden of KD, among Arab population, decrease practice variation and foster population-based knowledge. [ABSTRACT FROM AUTHOR]

Purpose of Review: We describe the clinical and genetic findings in four patients from a single family who presented with refractory psoriatic arthritis and were hemizygous in the forkhead box protein 3 (FOXP3) gene (c.1222G>A). Recent Findings: We report four siblings with hemizygous mutation in the FOXP3 gene (c.1222G>A) who presented with type 1 diabetes mellitus and psoriatic arthritis poorly responsive to treatment. Our findings expand the phenotype spectrum of FOXP3 mutations. Summary: Immune dysregulation, polyendocrinopathy, and enteropathy, X-linked (IPEX) syndrome is a rare disorder caused by mutations in FOXP3 gene, which lead to early onset of constellation of autoimmune manifestations. This report highlights the influence of immune dysregulation in juvenile arthritis. [ABSTRACT FROM AUTHOR]

To define the spectrum and phenotypic characteristics of systemic autoinflammatory diseases (SAIDs) other than familial Mediterranean fever (FMF) in Arab children and to delineate diagnostic evaluation. Data retrospectively collected on patients with clinical and/or genetically proven SAIDs other than FMF at 10 tertiary Arab pediatric rheumatology clinics from 1990 to 2018. The collected data comprised the clinical findings and diagnostic evaluation including genetic testing, the provided treatment and the accrual damage related to SAIDs. A total of 144 patients (93 female) with a median age at onset of 2.5 (range 0.1–12) years were enrolled. The initial diagnosis was inaccurate in 49.3%. Consanguinity rate among parents was 74.6%. The median time-to-diagnosis for all SAIDs was 2.5 (range 0.1–10) years. There were 104 patients (72.2%) with a confirmed diagnosis and 40 patients with suspected SAIDs. Seventy-two had monogenic and 66 patients with multifactorial SAIDs while six patients had undifferentiated SAIDs. The most frequent monogenic SAIDs were LACC1 mediated monogenic disorders (n = 23) followed by CAPS (12), TRAPS (12), HIDS (12), and Majeed's syndrome (6). The most frequent multifactorial SAIDs was CRMO (34), followed by PFAPA (18), and early onset sarcoidosis (EOS) (14). Genetic analysis was performed in 69 patients; 50 patients had genetically confirmed disease. Corticosteroid used for 93 patients while biologic agents for 96 patients. Overall, growth failure was the most frequent accrual damage (36%), followed by cognitive impairment (13%). There were three deaths because of infection. This study shows a heterogenous spectrum of SAIDs with a high number of genetically confirmed monogenic diseases; notably, LACC1 associated diseases. Hopefully, this work will be the first step for a prospective registry for SAIDs in Arab countries. [ABSTRACT FROM AUTHOR]

B-cell linker (BLNK) protein is a non-redundant adaptor molecule in the signaling pathway activated by (pre) B-cell antigen receptor signals. We present two siblings with a homozygous deleterious frameshift mutation in BLNK, resulting in a block of B cell development in the bone marrow at the preB1 to preB2 stage, absence of circulating B cells and agammaglobulinemia. This is the first description of an enteroviral infection associated arthritis and dermatitis in a patient with BLNK deficiency. [ABSTRACT FROM AUTHOR]

To evaluate giant aneurysms (GiAn) prevalence in Arab countries and examine contributing factors; and to review Kawasaki disease (KD) publication trends and collaborations among Arab nations. A scoping literature review was conducted to analyze the publications across the Arab world, spanning 16 countries from 1978 to 2023. The collected articles were a combination of database search with a call on Kawasaki Disease Arab Initiative (Kawarabi) members to share non-PubMed publications. Over 45 years, 50 articles originated from the Arab Countries with a 30% average annual growth rate in KD research output. Publications were evenly split between case reports (42%) and institutional series (52%). Research productivity lagged in developing nations with UAE, KSA and Egypt, contributed to 64% of total publications. Among 26 institutional series, 256 coronary artery aneurysms (CAA) from a total of 1264 KD cases were reported. Of those, 25 CAA were GiAn (prevalence 1.43% [range 0–12.5%]). The initial KD misdiagnosis rate was 4%, and incomplete KD (iKD) averaged 10.6%. Series (38.5%) that did not report iKD correlated with a higher prevalence of CAA, but not of GiAn. Longer fever duration emerged as a pivotal factor for GiAn (OR 5.06, 95%CI 1.51–17). This review unveils the research landscape of KD in the Arab world over 45 years. Initial misdiagnosis, untreated cases, delayed diagnosis and underreporting of iKD are contributing factors for an underestimated epidemiology, explaining the higher GiAn prevalence. This calls for strategic interventions to enhance KD research in these countries, aligning with Kawarabi’s mission. [ABSTRACT FROM AUTHOR]