Identification of rare coding variants associated with Kawasaki disease by whole exome sequencing

Kawasaki disease (KD) is an acute pediatric vasculitis that affects genetically susceptible infants and children. To identify coding variants that influence susceptibility to KD, we conducted whole exome sequencing of 159 patients with KD and 902 controls, and performed a replication study in an independent 586 cases and 732 controls. We identified five rare coding variants in five genes (FCRLA, PTGER4, IL17F, CARD11, and SIGLEC10) associated with KD (odds ratio [OR], 1.18–4.41; p = 0.0027–0.031). We also performed association analysis in 26 KD patients with coronary artery aneurysms (CAAs; diameter > 5 mm) and 124 patients without CAAs (diameter < 3 mm), and identified another five rare coding variants in five genes (FGFR4, IL31RA, FNDC1, MMP8, and FOXN1), which may be associated with CAA (OR, 3.89–37.3; p = 0.0058–0.0261). These results provide insights into new candidate genes and genetic variants potentially involved in the development of KD and CAA.

Henoch Schönlein Purpura / Ig A Vasculitis in Children and Risk Factors for Renal Involvement

Objective: Henoch Schönlein Purpura also known as IgA vasculitis is the most common form of pediatric vasculitis and renal involvement is responsible for the mortality and long-term morbidity. We aimed to describe the epidemiological, clinical, and laboratory characteristics of patients with IgAV and analyze the predicting factors associated with renal involvement. Materials and Methods: This study included188 children diagnosed with IgA vasculitis. Demographical, and clinical data were retrospectively reviewed from the patient files. Results: Of the 188 IgA vasculitis patients, 51.6% were female. The mean±SD age at diagnosis was 8.49±3.35 years, and 66% of them were diagnosed before 10 years of age. All the patients had palpable purpura, 35.6% had arthritis, 34.6% had gastrointestinal system involvement, 12.2% had renal disorders, at the time of diagnosis. Besides 23(12.2%) patients presented with renal involvement, 42(22%) patients developed renal involvement at follow-up. Patients under 10 years of age had significantly more arthritis, patients over 10 years of age had significantly more renal involvement. Among laboratory work-up, erythrocyte sedimentation rate levels were found significantly higher in patients with renal involvement. In multivariate analysis, the occurrence of renal involvement was not associated with any of the defined demographic and clinical characteristics of the disease. Although erythrocyte sedimentation rate levels showed a higher risk ratio, it has only borderline significance. Conclusion: Although IgA vasculitis is a self-limiting disease, renal involvement can cause serious complications. In the presented study, being older than 10 years of age and having high levels of erythrocyte sedimentation rate at the time of diagnosis could serve as a possible predictor of renal involvement.

POS0082 PERFORMANCES OF THE RISK FACTORS AND PEDIATRIC VASCULITIS ACTIVITY SCORES FOR DISEASE SEVERITY IN CHILDREN WITH MULTISYSTEM INFLAMMATORY SYNDROME

Background:Multisystem Inflammatory Syndrome in Children (MIS-C) is observed by hyperinflammation and cytokine storm. The spectrum of severity ranged from standard hospitalization to pediatric intensive care unit management. There is no specific activity score that predicts whether this hyperinflammatory state will be severe or result in mortality in pediatric patients. There are activity scores used in KD and other vasculitis such as Kobayashi score (KS) and Pediatric Vasculitis Activity Score (PVAS) that determine the severity of the disease in children.Objectives:Based on the clinical similarity of MIS-C to these disease groups, we wanted to evaluate the performance of these disease activity scores. Also, we aimed to identify the factors associated with the disease severity of patients with MISCMethods:We retrospectively enrolled a single-center cohort of 45 consecutive pediatric patients with MISC admitted to Umraniye Training and Resrach Hospital, Pediatric Rheumatology Clinic, Istanbul, Turkey, from April 20 to December 31, 2020. Medical information of each patient including demographic data, clinical characteristics, laboratory results, and outcomes was extracted retrospectively through review of electronic medical records. We analyzed all score systems including KS, PVAS, NLR, cHIS, and C-reactive protein/albumin ratio (CAR) as assessment factors for diagnosis for severe disease and evaluation of disease activity in MISC. All scores were compared between two groups and receiver operating characteristic (ROC) curve analysis was performed to evaluate diagnostic utility.Results:We reported 45 patients (10 female, 35male) with MISC. Their mean age was 9.65±4.93 years (7 months-18 years). All patients had fever (median 4 days), 71 % patients had acute gastrointestinal symptoms, 37.8 % of patient’s conjunctivitis and only 5 patients had respiratory findings at admission. Twenty-four (46.7%) patients met criteria for classic KD. Macrophage activation syndrome and myocardial dysfunction with or without cardiogenic shock were seen 14 and 10 patients respectively. All the patients had positive serology for SARS-CoV-2, abnormal complete blood counts and coagulation tests, and elevated inflammatory markers.We divided the disease severity into a moderate or severe group based on admission on intensive care unit (ICU). There were 15 patients with severe illness (33%). The median age of these patients was significantly older (11.3 years vs 9.16 years, p=0.05). The median hospital stay period was 10 days. The median need for intensive care was on the first day (1-14th days), and the median lasted 5 (1-9) days. The majority of MISC patients were on Intravenous immunoglobulin (IVIG) (89%), and corticosteroid (73.3%). A total of 12 patients received anakinra.In the severe group, all patients had higher values of KD, PVAS, NLR, cHIS, and CAR than the patients in moderate group. For severe MISC, the area under receiver operating characteristic curve (AUC) was 0.864 (95% confidence interval [CI], 0.729–1) for the PVAS, 0.911 (95% CI, 0.827–0.995) for the NLR, and 0.853 (95% CI, 0.744–0.963) for the CAR, with optimal cut-off values of 3.5, 9.05, and 4.86, respectively. Thirty-eight (84.4%) of the 45 patients met two or more cHIS criteria at the time of their hospitalization; 39% of these patients were identified as severe group (OR 1.62, 95% CI 1.27-2.13, p=0.04). At the time of diagnosis, 29 patients with a Kobayashi score greater than 4 were detected, of which 15 required intensive care (OR 2.07, 95% CI 1.42-3.0, p=0.00).Conclusion:This study demonstrated that both inflammatory scores (CAR and NLR) and disease activity scores (KS, PVAS and cHIS) can be used to aid the assessment for severity of MISCReferences:[1]Webb BJ, et al Lancet Rheumatol. 2020 Dec;2(12):e754-e763.[2]Feldstein LR et al N Engl J Med. 2020;383(4):334-346Disclosure of Interests:None declared.

Lower CMV and EBV Exposure in Children With Kawasaki Disease Suggests an Under-Challenged Immune System

Background: Kawasaki Disease (KD) is a pediatric vasculitis of which the pathogenesis is unclear. The hypothesis is that genetically pre-disposed children develop KD when they encounter a pathogen which remains most often unidentified or pathogen derived factors. Since age is a dominant factor, prior immune status in children could influence their reactivity and hence the acquisition of KD. We hypothesized that systemic immune responses early in life could protect against developing KD. With this study we tested whether the incidence of previous systemic cytomegalovirus (CMV) or Epstein-Barr virus (EBV) infection is lower in children with KD compared to healthy age-matched controls.Methods and Results: We compared 86 KD patients with an age-matched control group regarding CMV and EBV VCA IgG measurements (taken before or 9 months after IVIG treatment). We found that both CMV and EBV had an almost 2-fold lower seroprevalence in the KD population than in the control group.Conclusions: We suggest that an under-challenged immune system causes an altered immune reactivity which may affect the response to a pathological trigger causing KD in susceptible children.

MODERN DIAGNOSTIC CRITERIA FOR KAWASAKI DISEASE IN CHILDREN

Kawasaki disease (KD) is a pediatric vasculitis with coronary artery aneurysms as its main complication, often occurs in children under 5 years of age. The diagnosis is based on the presence of persistent fever and clinical features including exanthema, lymphadenopathy, bilateral conjunctivitis, and changes to the mucosae and extremities. Although the etiology is still unknown, it is believed that it is probably caused by an infectious trigger that initiates an inadequate immune response in genetically predisposed children. The article discusses the diagnostic criteria of not only the full form of KD, but also of partial one, taking into account the results of general and biochemical blood tests. Cardiological findings are described.There are presented infectious and somatic diseases, with which differential diagnosis should be carried out. Timely diagnosis and treatment of KD can improve the prognosis of the disease, prevent the development of coronary artery aneurysms.

Henoch-Schonlein purpura in pregnancy: A case report

Henoch-Schonlein purpura is a relatively common pediatric vasculitis. Very few cases of Henoch-Schonlein purpura during pregnancy have been described. Henoch-Schonlein purpura is variable in its presentation, from completely benign to possibly catastrophic complications. This rarely encountered condition in adults can also be a recurrence of a previous childhood disease. We present a case of a pregnant 40-year-old woman with Henoch-Schonlein purpura, resulting in a viable birth with no fetal complications. Her presentation is discussed in detail and a general presentation of Henoch-Schonlein purpura is explored, with particular attention to its rare onset during pregnancy.