Epidemiological and clinical aspects of immunoglobulin A vasculitis in childhood: a retrospective cohort study

Background A retrospective study was conducted in order to investigate and describe the characteristics of Immunoglobulin A vasculitis (IgAV), previously known as Henoch-Schӧnlein purpura, in the paediatric population of a community-based healthcare delivery system in the Italian region of Abruzzo. Methods This is a population-based retrospective chart review of the diagnosis of IgAV in children ages 0 to 18, admitted to the Department of Paediatrics of Chieti and Pescara between 1 January 2000 and 31 December 2016. All children enrolled presented with clinical symptoms and laboratory findings and met the EULAR/PRINTO/PRES 2008 criteria. Results Two-hundred-eight children met the criteria for IgAV, with the highest incidence reported among children below 7-years of age. A correlation with recent infections was found in 64% of the cohort; the onset was more frequently during the winter and fall. Purpura had a diffuse distribution in the majority of patients; joint impairment was the second most frequent symptom (43%), whereas the gastrointestinal tract was involved in 28% of patients. Conclusions Hereby, we confirm the relative benignity of IgAV in a cohort of Italian children; with regards to renal involvement, we report a better outcome compared to other studies. However, despite the low rate of renal disease, we observed a wide use of corticosteroids, especially for the treatment of persistent purpura.

Predicting Severe Renal and Gastrointestinal Involvement in Childhood Immunoglobulin A Vasculitis with Routine Laboratory Parameters

<b><i>Background:</i></b> Immunoglobulin A vasculitis (IgAV) is the most common vasculitis in children. Although childhood IgAV is generally considered as a self-limited disease, progressive course and poor prognosis could occur in some cases which mostly result from severe renal involvement and gastrointestinal (GI) involvement. <b><i>Methods:</i></b> We performed a retrospective study of pediatric patients diagnosed as IgAV in our institution from 2016 to 2019. Patients were divided into groups based on the occurrence and severity of GI and renal involvement. Analysis of variance (ANOVA) and Kruskal-Wallis test were used to compare results of laboratory parameters among groups and prediction models were built by using logistic regression analysis. <b><i>Results:</i></b> A total of 286 patients were enrolled. GI involvement occurred in 148 (51.7%) patients, 30 (20.3%) of which were severe cases. Renal involvement developed in 120 (42.0%) patients, 22 (18.3%) of which were severe cases. Compared with patients with only cutaneous manifestations, white blood cell (WBC) count, neutrophil-to-lymphocyte ratio (NLR), and D-dimer levels were higher in those with GI involvement, and D-dimer level was found to be positively associated with severity. Increased NLR and lower complement 3 (C3) were found in patients with renal involvement, but only C3 was relevant in distinguishing moderate and severe cases. The prediction model for severe renal involvement was: Logit (P) = 6.820 + 0.270 (age) + 0.508 (NLR) − 16.130 (C3), with an AUC of 0.914. The prediction model for severe GI involvement was: Logit (P) = −5.459 + 0.005 (WBC) + 1.355 (D-dimer) – 0.020 (NLR), with an AUC of 0.849. <b><i>Conclusion:</i></b> Our data suggest C3 to be an exclusive predictor for severe renal involvement and D-dimer level to be positively associated with the severity of GI involvement. Prediction models consisting of the above parameters were built for obtaining prognostic information in the early phase of IgAV.

Role of the IL33 and IL1RL1 pathway in the pathogenesis of Immunoglobulin A vasculitis

Cytokines signalling pathway genes are crucial factors of the genetic network underlying the pathogenesis of Immunoglobulin-A vasculitis (IgAV), an inflammatory vascular condition. An influence of the interleukin (IL)33- IL1 receptor like (IL1RL)1 signalling pathway on the increased risk of several immune-mediated diseases has been described. Accordingly, we assessed whether the IL33-IL1RL1 pathway represents a novel genetic risk factor for IgAV. Three tag polymorphisms within IL33 (rs3939286, rs7025417 and rs7044343) and three within IL1RL1 (rs2310173, rs13015714 and rs2058660), that also were previously associated with several inflammatory diseases, were genotyped in 380 Caucasian IgAV patients and 845 matched healthy controls. No genotypes or alleles differences were observed between IgAV patients and controls when IL33 and IL1RL1 variants were analysed independently. Likewise, no statistically significant differences were found in IL33 or IL1RL1 genotype and allele frequencies when IgAV patients were stratified according to the age at disease onset or to the presence/absence of gastrointestinal (GI) or renal manifestations. Similar results were disclosed when IL33 and IL1RL1 haplotypes were compared between IgAV patients and controls and between IgAV patients stratified according to the clinical characteristics mentioned above. Our results suggest that the IL33-IL1RL1 signalling pathway does not contribute to the genetic network underlying IgAV.