Performances of the risk factors and pediatric vasculitis activity scores for disease severity in children with multisystem inflammatory syndrome

Sözeri, B.; Çaǧlayan, Ş Akyol A.; Ulu, K.; Coşkuner, T.; Hasbal Akkuş, C.; Demir, F.

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 MISC Methods: 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 SARSCoV-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 MISC.