Background
IgA vasculitis (IgAV) is a common type of vascular inflammation that mainly affects children; however, its cause and pathogenesis remain poorly understood. It also affects adults, but the incidence of the disease is high in children (6–22 per 100,000 person-years). Although it usually has a favorable prognosis, the recurrence rate is high in children (2.7–66.2%)[
1]. The prevalence of IgAV is higher in males than females. It is most commonly seen in children aged 5–7 years. Moreover, the disease onset is more frequent in the winter season [
2,
3]. The main clinical manifestations of IgAV include nonthrombocytopenic purpura, arthritis or arthralgia, abdominal pain, gastrointestinal bleeding, and nephritis [
4], and the severity of kidney injury is the key determinant for the prognosis of IgAV in children [
4,
5]. Some studies have revealed that recurrence of IgAV in children can lead to kidney involvement or exacerbation of kidney injury [
6,
7]. Therefore, early prediction and interventions in recurrence of IgAV have important clinical implications.
Presently, there is no consensus regarding the findings on prediction of IgAV recurrence, and no specific routine laboratory test is available for the diagnosis of IgAV. Common laboratory indices, such as C-reactive protein (CRP), procalcitonin, white blood cell (WBC) count, and red blood cell (RBC) count are evaluated to rule out other diseases[
8]. Results of coagulation studies are usually in the normal range in IgAV patients. Few studies revealed platelet count and mean platelet volume (MPV) as the only laboratory indices related to IgAV recurrence. Low levels of platelet count and high MPV values were observed. Inflammatory markers, such as CRP and erythrocyte sedimentation rate (ESR) appear to be elevated [
9‐
15]. Inflammatory mechanisms play a major role in the etiology of vascular diseases.
Neutrophil/lymphocyte ratio (NLR) is a serum marker for inflammatory response and therefore, it is used in systemic inflammatory diseases. Moreover, NLR is inexpensive and easy to assess. Therefore, NLR is useful in evaluating the severity of the disease [
16]. Existing studies have shown that NLR and CRP have higher predictive value for IgAV recurrence in adults [
17]; however, few data are available on similar findings in children. Therefore, in the present study, we aimed to explore whether the common laboratory indices could predict IgAV recurrence in children and provide an accessible theoretical basis for early intervention to prevent recurrence of IgAV in children.
Data collection
In this study, we collected various demographic and clinical data of patients, including gender; age; duration of illness; use of CS; organ involvement; duration of treatment; presence of respiratory tract infection; and various clinical laboratory indices, such as WBC count, neutrophil (NEU) count, lymphocyte (LYM) count, platelet (PLT) count, MPV, RBC count, hemoglobin (HGB) level, monocyte (MONO) count, eosinophils (EOS) count, basophils (BAS) count, and CRP. Moreover, we calculated NLR and platelet/lymphocyte ratio (PLR).
Statistical analysis
Statistical analyses were performed using SPSS, version 25 (IBM Corp., Armonk, NY, USA). Normally distributed measurement data were presented as mean ± standard deviation and evaluated using the Student’s t test. Non-normally distributed data were presented as median and quartile M (P25, P75) and evaluated using the Mann–Whitney U test. Count data were presented as number (n) and percentage (%) and evaluated using the χ2 test. Multivariate logistic regression analysis (backward) was performed to establish the prediction model of IgAV recurrence. A receiver operating characteristic (ROC) curve was plotted to evaluate the performance of the prediction model by determining the optimal threshold with the highest sensitivity and specificity for predicting IgAV recurrence. A P-value <0.05 was considered statistically significant.
Discussion
IgAV is an IgA-mediated systemic vasculitis occurring mainly in children. The IgA deposition in the small blood vessels results in the symptoms of IgAV, affecting the kidneys, skin, and joints. Usually, IgAV has an excellent outcome in children. However, renal involvement (IgA vasculitic nephritis) at disease onset is the most severe complication of IgAV, affecting its prognosis. This renal involvement can result in end-stage kidney disease in children. Kidney injury has a higher incidence rate in children with recurrent IgAV than that in children with the initial episode of IgAV [
2,
19‐
21]. Therefore, reducing IgAV recurrence is the need of the hour. In this retrospective study, we explored the association between common laboratory indices and IgAV recurrence in children for evaluating the predictors for IgAV recurrence. Findings of this study revealed that the duration of illness (OR: 1.198, 95% CI: 1.092–1.315) and joint involvement (OR: 2.596, 95% CI: 1.097–6.147) were independent predictors for IgAV recurrence in children. However, no significant differences were observed in any of the studied laboratory indices (
P > 0.05). AUC of the prediction model was 0.766 (
P < 0.05) with sensitivity of 74.4% and specificity of 68.8%.
Numerous foreign studies have confirmed that IgAV recurrence can result in kidney injury in children with IgAV and the recurrence rate ranges from 10.25 to 25% [
11,
12,
22]. In the present study, we found that the recurrence rate was 20.2%, which was consistent with previous findings. Under no difference in treatment, the present study suggested that the duration of illness on initial diagnosis in the recurrence group was longer than that in the non-recurrence group, which was an independent risk factor for IgAV recurrence (
P = 0.000), and consistent with findings of many other studies [
23‐
26]. The reason for this finding may be that in autoimmune diseases, early treatment can promote the transformation from immune response involved by non-specific T cells and antibodies to that involved by specific T cells and antibodies as soon as possible, avoiding further tissue injury resulting from excessive activation of immune cells and release of more inflammatory factors [
27].
The pathogenesis of IgAV in children remains unclear. Some studies have demonstrated that older age is a high risk factor for recurrence in the ethnic Chinese population; however, there are differences in the non-ethnic Chinese population [
28]. In the present study, we did not observe the correlation between age and IgAV recurrence, which may be due to the limited small sample size or differences in allocation. Additionally, some studies have shown a correlation between different locations/systems, such as skin, kidney, joint, and gastrointestinal tract, or different numbers of these systems and IgAV recurrence [
12]. In the present study, joint involvement was an independent predictive factor for IgAV recurrence (OR: 2.596, 95% CI: 1.097–6.147;
P < 0.05). No other statistically significant differences were observed in location/systems involved and IgAV recurrence (
P > 0.05), which may be because the clinical manifestations are only the result of immune inflammation, and its presence or absence and severity depend on the severity of the immune inflammation [
15,
29‐
31]. Several studies reveal that infection, especially the upper respiratory tract infection, is a risk factor for patients with new-onset or recurrent IgAV [
22]; however, in the present study, no correlation was observed between the presence of respiratory tract infection and IgAV recurrence in children (
P > 0.05). Moreover, the present study suggested that there was no correlation between duration of treatment and IgAV recurrence (
P > 0.05), which may be because IgAV is a self-limiting disorder, and its treatment only relieved symptoms or delayed the disease course.
Blood parameters, including NEU, PLT, LYM, monocyte (MONO), NLR, PLR, and monocyte/lymphocyte ratio (MLR), have been shown to be indices for systemic inflammation and infection [
32]. Studies have shown that PLT and MPV are the only laboratory indices associated with IgAV recurrence in children [
11]; however, the present study found that these common laboratory indices, on initial diagnosis in the recurrence group, did not differ significantly from those in the non-recurrence group (
P > 0.05). Maybe because HSP is an IgA-mediated immune inflammation and not an inflammation caused by infection. Therefore, further research on differences in IgA and other immunoglobulinsare required to study the recurrence of IgAV in children.
This study has some limitations. First, the sample size was small. Second, the severity and duration of organ involvement have not been analyzed in detail. Therefore, further research is warranted to explore the association of IgA and other immunoglobulinswith the recurrence of IgAV in children.
In conclusion, the present retrospective study explored the predictive factors for IgAV recurrence in children. The recurrence rate was consistent with that of previous literature. The common laboratory indices were not associated with the recurrence of IgAV in children. The duration of illness and joint involvement were proved independent risk factors for IgAV recurrence. The duration of illness in the recurrence group was observed to be longer than that in the non-recurrence group. Therefore, clinical follow-up should focus on children with a duration from the onset of symptoms to admission of more than 4 days on initial diagnosis, and prevent IgAV recurrence.
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