Evaluating the time-varying risk of hypertension, cardiac events, and mortality following Kawasaki disease diagnosis.

BACKGROUND: This study evaluated the risk of hypertension, major adverse cardiac events (MACE), and all-cause mortality in Kawasaki disease (KD) patients up to young adulthood. METHODS: An inception cohort of 1169 KD patients between 1991 and 2008 from a tertiary-level hospital in Ontario, Canada was linked with health administrative data to ascertain outcomes up to 28 years of follow-up. Their risk was compared with 11,690 matched population comparators. The primary outcome was hypertension and secondary outcomes were MACE and death. RESULTS: After a median follow-up of 20 years [IQR: 8.3], the cumulative incidence of hypertension and MACE in the KD group was 3.8% (95% CI: 2.5-5.5) and 1.2% (95% CI: 0.6-2.4%), respectively. The overall survival probability in the KD group was 98.6% (95% CI: 97.2-99.3%). Relative to comparators, KD patients were at an increased risk for hypertension [aHR: 2.2 (95% CI: 1.5-3.4)], death [aHR: 2.5 (95% CI: 1.3-5.0)], and MACE [aHR: 10.7 (95% CI: 6.4-17.9)]. For hypertension and MACE, the aHR was the highest following diagnosis and then the excess risk diminished after 16 and 13 years of follow-up, respectively. MACE occurred largely in KD patients with coronary aneurysms [cumulative incidence: 12.8%]. CONCLUSIONS: KD patients demonstrated a reassuring cardiac prognosis up to young adulthood with low events and excellent survival. KD patients were at increased risk for hypertension, but this excess risk occurred early and declined with time. IMPACT: With the current standard of care, KD patients demonstrated favorable cardiac prognosis, with low events of hypertension, MACE, and excellent survival. Hypertension and MACE risk appear to be highest around the time of KD diagnosis. MACE occurred primarily in KD patients with coronary aneurysms. Our findings are reassuring to KD patients, families, and their providers. Our study demonstrated an association between KD exposure and hypertension. This association is relatively novel. Previous studies have remained conflicting if KD contributes to long-term atherosclerotic risk.

Higher concentrations of vitamin D in Canadian children with juvenile idiopathic arthritis compared to healthy controls are associated with more frequent use of vitamin D supplements and season of birth.

A number of studies have demonstrated that patients with autoimmune disease have lower levels of vitamin D prompting speculation that vitamin D might suppress inflammation and immune responses in children with juvenile idiopathic arthritis (JIA).  The objective of this study was to compare vitamin D levels in children with JIA at disease onset with healthy children. We hypothesized that children and adolescents with JIA have lower vitamin D levels than healthy children and adolescents. Data from a Canadian cohort of children with new-onset JIA (n= 164, data collection 2007-2012) were compared to Canadian Health Measures Survey (CHMS) data (n=4027, data collection 2007-2011). We compared 25-hydroxy vitamin D (25(OH)D) concentrations with measures of inflammation, vitamin D supplement use, milk intake, and season of birth. Mean 25(OH)D level was significantly higher in patients with JIA (79 ± 3.1 nmol/L) than in healthy controls (68 ± 1.8 nmol/L P <.05). Patients with JIA more often used vitamin D containing supplements (50% vs. 7%; P <.05). The prevalence of 25(OH)D deficiency (<30 nmol/L) was 6% for both groups. Children with JIA with 25(OH)D deficiency or insufficiency (<50 nmol/L) had higher C-reactive protein levels. Children with JIA were more often born in the fall and winter compared to healthy children. In contrast to earlier studies, we found vitamin D levels in Canadian children with JIA were higher compared to healthy children and associated with more frequent use of vitamin D supplements. Among children with JIA, low vitamin D levels were associated with indicators of greater inflammation.

Long-term use and remission of granulomatosis with polyangiitis with the oral C5a receptor inhibitor avacopan.

Granulomatosis with polyangiitis (GPA) is a rare antineutrophil cytoplasm antibody-associated vasculitis. Several therapeutic advances have occurred over the past two decades, but relapse rate remains high and refractory cases are not uncommon. Here, we present the case of a female patient diagnosed with GPA at the age of 9 years with a severe, multirelapsing disease course which failed to adequately respond to conventional therapies. Avacopan, a novel C5a receptor inhibitor, was started based on phase II studies that showed promise as a steroid-sparing adjunct. The patient was able to successfully reduce her glucocorticoid dose and reduce her immunosuppressive treatments without another flare. She has been on avacopan for 35 months, had no adverse events that required its discontinuation, and her disease is in sustained remission.

Is multisystem inflammatory syndrome in children on the Kawasaki syndrome spectrum?

An alarming increase in children presenting with fever, hyperinflammation, and multiorgan dysfunction frequently requiring intensive care has been observed after severe acute respiratory syndrome coronavirus 2 infection. The illness resembles Kawasaki disease (KD), with coronary dilatation and aneurysm occurring in some. However, the cardiovascular manifestations were typically on the severe end of the KD spectrum, with cardiogenic shock a common presentation together with other features. This led to defining a unique syndrome named multisystem inflammatory syndrome in children (MIS-C). In this issue of the JCI, Lee and Day-Lewis et al. and Diorio et al. explored the clinical profiles associated with coronavirus disease 2019 in children. We posit that while splitting MIS-C into a separate disease may aid clinical management decisions, lumping it into the KD pot may better serve to understand pathobiology.

Increased serum levels of TGFbeta1 in children with localized scleroderma.

BACKGROUND: There are neither sensitive nor specific laboratory tests for measuring disease activity in localized scleroderma (LS). Monitoring is done almost exclusively by clinical assessment. Our aim was to determine whether serum concentrations of TGFbeta1 are a good biomarker of disease activity in children with LS. METHODS: 55 pediatric patients with LS were divided into sub-types according to their main lesion; morphea, generalized morphea, linear scleoderma affecting a limb or the face. The lesions were further categorized by overall clinical assessment into active, inactive, and indeterminate groups according to disease activity. Serum TGFbeta1 concentration levels were measured by enzyme linked immunosorbent assay (ELISA), analyzed and correlated with disease subtypes and disease activity. RESULTS: The mean TGFbeta1 concentration were significantly higher in the patient group (51393 +/- 33953 pg/ml) than in the control group (9825 +/- 5287 pg/ml) (P < 0.001). The mean concentration were elevated in all the disease subtypes, and did not correlate with disease duration or activity. CONCLUSION: Serum concentration of TGFbeta1 were elevated in patients with all subtypes of LS irrespective of clinical disease activity. Although TGFbeta1 may play an important role in the pathogenesis of local skin fibrosis, circulating blood levels of molecules known to act locally may not be useful biomarkers of disease activity.