Referral Patterns to Pediatric Rheumatology From Primary Care Physicians and General Pediatrics at a Single Pediatric Rheumatology Center in Saudi Arabia.

Objective This study aims to investigate referral patterns to pediatric rheumatology and assess the correctness of referrals from primary care physicians and pediatric specialties. Methodology A cross-sectional, retrospective study was conducted on all patients who were referred to the Pediatric Rheumatology Department since 2015 (N = 282) at King Abdullah Specialized Children's Hospital (KASCH), Pediatric Rheumatology Clinic. Age, gender, reason for referral, clinical features, referring department, and final diagnosis were taken as variables. Data were collected through the documents and records of the cases (referrals) in the electronic medical records system of the hospital (BestCare). Then Excel was used for data entry, and JMP statistical software, version 14.0.0 (SAS Institute Inc., Cary, NC, USA) was used for data analysis. Results In a total of 282 patients across the Pediatric Rheumatology Clinic, KASCH, the most common reason for referral to the clinic was joint pain (112, 43%) and the least common reason was rash (6, 2.3%). The most common diagnosis was juvenile idiopathic arthritis (JIA) (24, 26.6%). The majority of patients referred to the rheumatology department did not have a rheumatological disease (169, 65%). The majority of the referrals were from pediatrics subspecialties (168, 65%). The least referred department was primary care ( 21, 8%). Conclusions To our knowledge, this is the first study showing the referral pattern, accuracy, and profile of a pediatric rheumatology clinic population in Saudi Arabia. Expectedly, the most common reason for referral was arthralgia. The most common diagnosis was JIA. According to the results, most of the referrals were inaccurate as they did not end up with a rheumatological diagnosis. Pediatric subspecialties should be more aware of the nature of rheumatological disease to avoid over-referrals. Finding a pattern of referrals to pediatric rheumatology is an excellent modality to accomplish early diagnosis and the best possible prognosis.

Consensus clinical approach for a newly diagnosed systemic juvenile idiopathic arthritis among members of the pediatric rheumatology Arab group.

BACKGROUND: Systemic juvenile idiopathic arthritis (sJIA) is a diagnosis of exclusion. The complex nature and clinical variety of the disease, as well as the vast clinical variation of disease presentation, may lead to difficulties in disease detection and subsequent delays in treatment. AIM: To provide a consensus guidance on the management of newly diagnosed sJIA patients among pediatric rheumatologists in Arab countries. METHODS: This work was conducted in two phases. The first phase utilized an electronic survey sent through an email invitation to all pediatric rheumatologists in Arab countries. In the second phase, a Task Force of ten expert pediatric rheumatologists from Arab countries met through a series of virtual meetings. Results obtained in phase one were prioritized using a nominal group and Delphi-like techniques in phase two. RESULTS: Seven overarching principles and a set of recommendations were approved by the Task Force to form the final consensus. CONCLUSION: This is the first consensus on a clinical approach for pediatric rheumatic diseases among Arab pediatric rheumatologists. It is presented as a guidance on the clinical approach to sJIA that requires further evidence, and future updates are anticipated.

A web-based collection of genotype-phenotype associations in hereditary recurrent fevers from the Eurofever registry.

BACKGROUND: Hereditary recurrent fevers (HRF) are a group of rare monogenic diseases leading to recurrent inflammatory flares. A large number of variants has been described for the four genes associated with the best known HRF, namely MEFV, NLRP3, MVK, TNFRSF1A. The Infevers database ( http://fmf.igh.cnrs.fr/ISSAID/infevers ) is a large international registry collecting variants reported in these genes. However, no genotype-phenotype associations are provided, but only the clinical phenotype of the first patient(s) described for each mutation. The aim of this study is to develop a registry of genotype-phenotype associations observed in patients with HRF, enrolled and validated in the Eurofever registry. RESULTS: Genotype-phenotype associations observed in all the patients with HRF enrolled in the Eurofever registry were retrospectively analyzed. For autosomal dominant diseases (CAPS and TRAPS), all mutations were individually analyzed. For autosomal recessive diseases (FMF and MKD), homozygous and heterozygous combinations were described. Mean age of onset, disease course (recurrent or chronic), mean duration of fever episodes, clinical manifestations associated with fever episodes, atypical manifestations, complications and response to treatment were also studied. Data observed in 751 patients (346 FMF, 133 CAPS, 114 MKD, 158 TRAPS) included in the Eurofever registry and validated by experts were summarized in Tables. A total of 149 variants were described: 46 TNFRSF1A and 27 NLRP3 variants, as well as various combinations of 48 MVK and 28 MEFV variants were available. CONCLUSIONS: We provide a potentially useful tool for physicians dealing with HRF, namely a registry of genotype-phenotype associations for patients enrolled in the Eurofever registry. This tool is complementary to the Infevers database and will be available at the Eurofever and Infevers websites.

Erlotinib in wild type epidermal growth factor receptor non-small cell lung cancer: A systematic review.

BACKGROUND: Targeting epidermal growth factor receptors (EGFR) is an innovative approach to managing non-small cell lung cancer (NSCLC) which harbors EGFR mutation. However, the efficacy of these agents like erlotinib in patients without the mutation is not known. METHODS: This systematic review included Phase III randomized clinical trials that compared single agent erlotinib to other management options in the setting of NSCLC with reported outcome data on patients with EGFR wild type (EGFRWT) tumors. Outcome data include overall survival (OS), progression free survival (PFS) and response rate (RR). Random effects meta-analysis was used to pool outcomes across studies. RESULTS: Three studies met the inclusion criteria. These studies included a total of 2044 patients with outcome data on 674 patients with EGFRWT tumors (33%). Meta-analysis revealed a statistically significant improvement in OS with erlotinib (hazard ratio of 0.780; 95% confidence interval: 0.654-0.930, P = 0.006). Data were not available to perform PFS or RR analysis. The quality of this evidence is considered to be moderate to high. CONCLUSION: Our study revealed a significant benefit of erlotinib in patient with EGFRWT tumors compared with other approaches. These findings add another therapeutic option to patients generally considered difficult to treat.

DOCK8 deficiency impairs CD8 T cell survival and function in humans and mice.

In humans, DOCK8 immunodeficiency syndrome is characterized by severe cutaneous viral infections. Thus, CD8 T cell function may be compromised in the absence of DOCK8. In this study, by analyzing mutant mice and humans, we demonstrate a critical, intrinsic role for DOCK8 in peripheral CD8 T cell survival and function. DOCK8 mutation selectively diminished the abundance of circulating naive CD8 T cells in both species, and in DOCK8-deficient humans, most CD8 T cells displayed an exhausted CD45RA(+)CCR7(-) phenotype. Analyses in mice revealed the CD8 T cell abnormalities to be cell autonomous and primarily postthymic. DOCK8 mutant naive CD8 T cells had a shorter lifespan and, upon encounter with antigen on dendritic cells, exhibited poor LFA-1 synaptic polarization and a delay in the first cell division. Although DOCK8 mutant T cells underwent near-normal primary clonal expansion after primary infection with recombinant influenza virus in vivo, they showed greatly reduced memory cell persistence and recall. These findings highlight a key role for DOCK8 in the survival and function of human and mouse CD8 T cells.