Background/Objective: The purpose of this study was to evaluate the prevalence and severity of skin involvement in children with IgA vasculitis (IgAV) and its relationship with clinical and biochemical parameters and the risk of developing IgA vasculitis nephritis (IgAVN), the only cause of long-term morbidity and the main prognostic factor in IgAV patients. Methods: This national multicenter retrospective study included 611 patients under the age of 18 years with IgAV referred to five Croatian tertiary hospitals between 2009 and 2019. Patient data were collected from a database with systematic analysis of IgAV patients in the Croatian population. Results: Among the 611 children, 205 (33.55%) had purpura on the lower extremities, in 207 (33.88%) the rash extended on the trunk, in 149 (24.39%) it extended to the upper extremities, in 32 (5.24%) the rash was generalized, while 15 (2.47%) had the most severe skin symptoms: bullae, ulcerations, and necroses. IgAVN developed in 130 (21.28%) and persistent IgAVN (present for >3 months) in 48 (7.86%) children. Multivariate logistic regression found that presence of ulcerations and necroses (OR 3.20 [95% CI 1.03–9.91]), persistent purpura (OR 2.89 [95% CI 1.71–4.88]), and higher age (OR 1.16 [95% CI 1.09–1.23]) were significant predictors of IgAVN, whereas persistent purpura (OR 20.11 [95% CI 1.09–372.52]), male sex (OR 3.32 [95% CI 1.13–9.80]), and higher age (OR 1.15 [95% CI 1.00–1.30]) were predictors of persistent IgAVN. Among the laboratory parameters, higher serum urea (OR 1.43 [95% CI 1.03–2.00]) and reduction in activated partial thromboplastin time (OR 0.83 [95% CI 0.74–0.93]) were shown to have a significant impact on increasing the risk of persistent IgAVN. Conclusion: With increasing severity and duration of cutaneous manifestations in IgAV, the risk of developing IgAVN increases, making the prognosis worse, with a greater likelihood to need more aggressive treatment.

Objective : To detect stress in newborns by observing heart rate (HR) variability utilizing an asymmetric detrended fluctuation analysis (ADFA), we sought to determine the fractal structure of the series of inter-beat intervals, so as to distinguish the periods of acceleration of the HR from decelerations. Thus, two scaling exponents, α ⁺ and α ⁻ , representing decelerations and accelerations respectively, are obtained. Approach : Forty healthy term newborns were included in this study, undergoing two different types of stress stimuli: routine heel lance blood sampling for metabolic screening purposes, and its simulation by applying dull pressure on the heel. Main results : It appears that when newborns face stress, the scaling exponent related to accelerations significantly increases and becomes higher than the deceleration scaling exponent. To test the diagnostic properties of the scaling exponents, an ROC curve analysis was applied; α ⁻ showed good diagnostic performance with an AUC between 0.626 and 0.826, depending on the length of the time series. The joint use of α ⁺ and α ⁻ further increased the diagnostic performance, in particular for shorter series of RR intervals, with an AUC between 0.691 and 0.833. Significance : ADFA, particularly of the acceleration scaling exponent, may be a useful clinical diagnostic tool for monitoring neonatal stress.

Studies concerning the genetic background of IgA vasculitis (IgAV), a small-vessel vasculitis occurring predominantly in childhood, have confirmed that the HLA-DRB1 gene showed a strong association with disease susceptibility. The objective was to investigate human leukocyte antigen (HLA) polymorphisms among Croatian patients with IgAV and their influence on disease susceptibility and clinical heterogeneity. Thus, 130 children with IgAV and 202 unrelated healthy individuals were enrolled in the study. Genomic DNA was extracted from whole peripheral blood, and HLA-A, -B, -DRB1 and -DQB1 gene polymorphism analysis was performed. HLA-A*03 (21.4% vs. 12.38%, p = 0.0092), HLA-B*37 (2.9% vs. 0.2%, p = 0.0054) and HLA-DRB1*12 (3.1% vs. 0.7%, p = 0.0216) alleles were significantly more frequent in IgAV patients than in controls. High-resolution typing revealed significantly higher frequency of HLA-DRB1*10:01 and -DRB1*11:03 among IgAV patients with gastrointestinal manifestations of the disease in comparison to controls (p = 0.0021 and p = 0.0301, respectively), while HLA-DRB1*14:01P occurred significantly more often in the group of patients who developed nephritis during the course of the disease (17.5% vs. 4.5%, p = 0.0006). Our results demonstrated that there is an association of HLA-A*03, HLA-B*37 and HLA-DRB1*12 alleles with susceptibility to IgAV in the examined Croatian pediatric population. Studies which aim to determine the HLA profile may contribute to the elucidation of the genetic background of autoimmune diseases, including IgAV.

Heart rate variability (HRV) has been analysed using linear and nonlinear methods. In the framework of a controlled neonatal stress model, we applied tone–entropy (T–E) analysis at multiple lags to understand the influence of external stressors on healthy term neonates. Forty term neonates were included in the study. HRV was analysed using multi-lag T–E at two resting and two stress phases (heel stimulation and a heel stick blood drawing phase). Higher mean entropy values and lower mean tone values when stressed showed a reduction in randomness with increased sympathetic and reduced parasympathetic activity. A ROC analysis was used to estimate the diagnostic performances of tone and entropy and combining both features. Comparing the resting and simulation phase separately, the performance of tone outperformed entropy, but combining the two in a quadratic linear regression model, neonates in resting as compared to stress phases could be distinguished with high accuracy. This raises the possibility that when applied across short time segments, multi-lag T–E becomes an additional tool for more objective assessment of neonatal stress.

Endothelial cell injury is a hallmark of IgA vasculitis (IgAV), possibly associated with various factors, including oxidative stress. Certain single nucleotide polymorphisms (SNPs) of glutathione S-transferases (GST) genes have been shown to increase susceptibility to oxidative stress. The objective of our study was to evaluate the gene polymorphisms of GSTM1, GSTT1, GSTP1, and GSTA1 in patients with IgAV. DNA was extracted from the blood of 124 children with IgAV and 168 age-matched healthy controls. A higher frequency of the GSTM1 null genotype was observed in patients with gastrointestinal (GI) system involvement compared to those without GI system involvement (51.5% vs. 28.6%, p = 0.011). Additionally, the GSTM1 null genotype was less prevalent (30.8% vs. 69.2%, p = 0.032), while the GSTP1 Val/Val genotype was significantly more prevalent in patients who developed urogenital complications (scrotal swelling) during the course of the disease (60% vs. 40%, p = 0.039). This study is the first to suggest an association between GSTM1 and GSTP1 polymorphisms and various phenotypes observed during the clinical course of IgAV in the pediatric population. However, it was performed on a national and likely single ethnic cohort, too small for definitive conclusions, so larger studies are needed to confirm this association.