This was a retrospective cohort study conducted at the Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, in Bangkok, Thailand. Our center is the largest tertiary academic referral center in the region. All data from diagnosis to follow up were retrieved from January 2010 to December 2022 via an electronic medical record using the International Classification of Diseases, Tenth Revision code D69.0. The research protocol for this study obtained ethical approval from the Siriraj Institutional Review Board (COA) number Si 537/2023, in accordance with the Declaration of Helsinki. Because this study was retrospective, the requirement for informed consent and assent was waived.

Participants in this study were patients ≤18 years of age diagnosed with IgAV according to EULAR/PRINTO/PReS classification criteria [21]; the presence of purpura and at least one of the following 4 symptoms: abdominal pain, arthritis or arthralgia, leukocytoclastic vasculitis with predominant IgA deposits/proliferative glomerulonephritis with predominant IgA deposits in histopathology, or renal involvement. The age cut-point for childhood-onset at <10 years and adolescent-onset at 10–19 years was defined in accordance with the definition for adolescence by the World Health Organization [22].

Demographic and clinical phenotypes included sex, age at diagnosis, family history of IgAV, preceding infection within 1 month, weight, height, duration of the disease. Clinical features; skin, MSK, GI, renal, scrotal, pulmonary, and central nervous system were collected. Laboratory results included complete blood count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), urinalysis, antinuclear antibody, complement and stool occult blood were recorded. Imaging studies were obtained comprising abdominal ultrasound and computed tomography if performed. Histopathological results were obtained if performed. Renal biopsy was performed in patients with glomerular filtration rate (GFR) <90 mL/min/1.73m², nephrotic-range proteinuria (UPCR >2 mg/mg), or persistent subnephrotic-range proteinuria >2–4 weeks [23,24]. Treatment of nonsteroidal anti-inflammatory drugs, acetaminophen, corticosteroids, intravenous immunoglobulin, colchicine, dapsone, azathioprine, cyclophosphamide, mycophenolate mofetil, biologics, and enalapril were gathered. Corticosteroids are indicated for patients with severe abdominal pain, GI bleeding, orchitis, hemorrhagic bullae, severe organ- or life-threatening vasculitis, and moderate to severe IgAV nephritis. Prednisolone is administered at 1–2 mg/kg/day for 1–2 weeks, followed by tapering over 4–6 weeks based on clinical response. Other disease-modifying antirheumatic drugs, including mycophenolate mofetil, azathioprine, calcineurin inhibitor or cyclophosphamide, may be used for refractory disease or inability to wean from corticosteroids. The pediatric vasculitis activity score (PVAS) was evaluated to determine disease severity [25].

Our protocol for the follow-up patient with IgAV encompassed clinical features, weight, height, vital signs including blood pressure measurement and urinalysis as follows; every 2 weeks during the first month of the disease, then monthly for 5 months, then every 2 months thereafter for 6 months, then every 3 months twice, every 6 months once and then yearly. Our protocol is comparable to the recommendations endorsed by international associations [11,12,23].

The recurrence of IgAV was classified by the reappearance of purpuric/petechiae rash [11,26] or other features that reappeared after a period of at least one month without symptoms. Proteinuria was defined as spot UPCR >0.2 mg/mg. Hematuria was classified as red blood cell >5/high-power field. Hypertension was defined if blood pressure >95th percentile according to age and sex. The GFR was calculated using a modified Schwartz formula [27]. CKD was defined as GFR<60 m L/min/1.73 m² for >3 months [28]. IgAV with nephritis was classified according to the international study of kidney disease in children [29].

All statistical analyzes were performed with IBM SPSS Statistics ver. 20.0 (IBM Co., USA). Descriptive statistics were used for analysis. Categorical data were reported as frequencies with percentages. Continuous data were presented as either mean±standard deviations for normally distributed data or median with interquartile range (IQR) for nonnormally distributed data. Comparison of differences in clinical characteristics and investigation findings between childhood-onset IgAV and adolescent-onset IgAV were analyzed using an independent samples t test (for normally distributed data) and Mann-Whitney U test (for nonnormally distributed data) for continuous variables, while categorical variables underwent via the chi-square test and Fisher exact test. The time from diagnosis to recurrent IgAV was analyzed using Kaplan-Meier survival analysis. The data was censored if there was no recurrence or if the subject was lost to follow-up. Factors associated with recurrent IgAV were assessed using Cox proportional hazards regression analysis. Variables with P value <0.2 from the univariable analysis were entered into the multivariable Cox proportional hazards regression analysis. The PVAS was also entered into the multivariable Cox proportional hazards regression analysis to adjust for potential confounder of disease severity. Predictors were reported as the hazard ratio (HR) and the 95% confidence interval (CI). Variables with a P value less than 0.05 were considered statistically significant.

There were 361 patients with IgAV included in this study; 192 females (53.2%) and 169 males (46.8%) with a mean age of 7.7±3.9 years. The median duration of follow-up (IQR) from diagnosis was 16.5 (2.4–58.3) months. Ninety-five patients (26.3%) had preceding infection prior to IgAV diagnosis.

All IgAV patients had skin manifestation; 277 patients (76.7%) developed palpable purpura, 27 patients (7.5%) developed petechiae, and 152 patients (42.1%) had nonblanchable rash. Subcutaneous edema and hemorrhagic bullae were found in 9 (2.5%) and 7 patients (1.9%), respectively. GI involvement was found in 214 patients (59.3%) with abdominal pain being the most common manifestation at 189 (52.4%). GI bleeding occurred in 62 (17.2%). No intussusception or bowel perforation was detected in our cohort. MSK features were reported in 219 patients (60.7%). Arthritis and arthralgia were observed in 103 (28.5%) and 116 patients (32.1%), respectively. Oligoarticular involvement of the lower extremities was the most common joint distribution. Orchitis was observed in 12 patients (3.3%). Renal involvement was observed in 82 patients (22.7%). Fifty-five patients (15.2%) underwent a renal biopsy. Half of patients required hospitalization at the time of IgAV diagnosis (184 patients, 51%). Corticosteroids was prescribed in 228 patients (63.2%) and 11 patients also received pulsed intravenous methylprednisolone. The median duration of corticosteroids was 51 days (25.5–120 days).

The prevalence of childhood-onset (<10 years) IgAV and adolescent-onset IgAV (10–19 years) was 269 (74.5%) and 92 (25.5%), respectively. Childhood-onset IgAV had significant GI manifestation (P=0.010), MSK features (P=0.002), and required hospitalization (P=0.004). In contrast, those with adolescent-onset IgAV had significantly renal involvement (P<0.001) and required longer duration of corticosteroids treatment (P<0.001). The clinical features of all patients and the clinical features compared between childhood-onset IgAV and adolescent-onset IgAV are shown in Table 1.

Twenty-seven patients were lost to follow-up after the initial visit and 334 patients were analyzed for the recurrence of IgAV. There were 119 patients (35.6%) with recurrent IgAV. The clinical features compared between patients with recurrent IgAV and nonrecurrent IgAV are demonstrated in Table 2. Univariable Cox proportional hazards regression analysis found that preceding infection, ESR >20 mm/hr and corticosteroids treatment were associated with the recurrence of IgAV (all P<0.2). However, based on the multivariable Cox proportional hazards regression analysis, the significant factor associated with the recurrence of IgAV was corticosteroids treatment (HR, 1.99; 95% CI, 1.266–3.157; P=0.003). The factors associated with the recurrence of IgAV are shown in Table 3. Subgroup analysis of factors associated with the recurrence of IgAV in patients with GI involvement or renal involvement are shown in the Supplementary Table 1. The overall time from IgAV diagnosis to the time of recurrence of IgAV is shown in Fig. 1. The time of recurrence of IgAV between patients with renal and without renal involvement was not statistically different (Fig. 2). There were significant differences in the time of recurrence of IgAV between those with and without corticosteroids treatment (P<0.001) (Fig. 3). There were 98 patients (27.1%) with recurrent IgAV during 12-month follow-up at a median time of 1.9 months (IQR, 1.2–4.8 months). The outcomes and complications of patients with IgAV are described in Table 4. The majority (345, 95.6%) went into complete remission. CKD >stage 2 was observed in 8 patients (2.2%). There were 4 patients who received dialysis; 2 with hemodialysis and 2 with continuous ambulatory peritoneal dialysis. None received kidney transplantation. There were no significantly different outcomes between childhood-onset IgAV and adolescent-onset IgAV (P>0.05). Two patients were subsequently diagnosed with systemic lupus erythematosus. One patient with IgAV with end-stage renal disease died of intracranial hemorrhage secondary to a hypertensive crisis.