Abdominal imaging and endoscopic characteristics of adult abdominal IgA vasculitis: a multicenter retrospective study.

BACKGROUND: IgA vasculitis (IgAV), previously known as Henoch-Schönlein purpura, is an IgA-mediated systemic small vessel vasculitis that tends to be more severe in adults than in children. Early diagnosis of IgAV involving the gastrointestinal tract remains difficult, especially in patients who present with gastrointestinal symptoms before purpura. This study aims to systematically analyze the abdominal imaging and endoscopic features of adult patients with abdominal IgAV, providing assistance to clinicians in the early recognition of this condition. PATIENTS AND METHODS: This multicenter retrospective study was conducted in three large tertiary hospitals in China from January 2017 to January 2024. A total of 108 adult patients with abdominal IgAV, who had complete abdominal imaging and/or endoscopy results, were enrolled. The clinical manifestations, abdominal imaging findings, endoscopic characteristics, and serological indicators of the patients were analyzed. RESULTS: The median age of the patients was 40 years (IQR: 26-55), with a male-to-female ratio of 2:1. Acute abdominal pain was the most common presenting symptom (100 patients, 92.59%). Bowel wall thickening was the most frequent finding on abdominal imaging (50/86 patients, 58.14%). Gastrointestinal endoscopy showed findings of congestion and erosion (32/67 patients, 47.76%), and erosion with ulcers (21/67 patients, 31.34%). Among patients with both imaging and endoscopic results, the duodenum (28/51 patients, 54.90%) and ileum (28/51 patients, 54.90%) were the most commonly affected sites. Laboratory findings revealed elevated white blood cell count (WBC), neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP), D-dimer and fibrinogen levels, along with decreased albumin level. Comparing patients with gastrointestinal symptoms versus purpura as the initial symptom, those with gastrointestinal symptoms had higher levels of WBC (p < 0.05) and NLR (p < 0.01). CONCLUSIONS: The most common symptom in adult abdominal IgAV patients is acute abdominal pain. In the early stage of the disease, most patients exhibit elevated levels of WBC, NLR, CRP, D-dimer, and fibrinogen, along with decreased albumin level. The duodenum and ileum are the most commonly affected sites. By integrating these findings, clinicians can identify abdominal IgAV patients earlier and more accurately.

Adult abdominal IgAV is prevalent in middle-aged adults, with abdominal pain being the main presenting symptom. Abdominal imaging and endoscopy suggest that the duodenum and ileum are particularly susceptible to involvement. Laboratory tests typically show elevated white blood cell count, neutrophil-to-lymphocyte ratio, C-reactive protein, D-dimer and fibrinogen levels, along with decreased albumin level. These findings can aid in the early recognition of IgAV and facilitate timely treatment, thereby improving patient prognosis.

Predicting renal damage in children with IgA vasculitis by machine learning.

BACKGROUND: Children with IgA Vasculitis (IgAV) may develop renal complications, which can impact their long-term prognosis. This study aimed to build a machine learning model to predict renal damage in children with IgAV and analyze risk factors for IgA Vasculitis with Nephritis (IgAVN). METHODS: 50 clinical indicators were collected from 217 inpatients at our hospital. Six machine learning algorithms-Logistic Regression, Linear Discriminant Analysis, K-Nearest Neighbor, Support Vector Machine, Decision Trees, and Random Forest-were utilized to select the model with the highest predictive performance. A simplified model was developed through feature importance ranking and validated by an additional cohort with 46 patients. RESULTS: The random forest model had the highest accuracy, precision, recall, F1 score, and area under the curve, with values of 0.91, 0.98, 0.70, 0.79 and 0.94, respectively. The top 11 features according to the importance ranking were anti-streptolysin O, corticosteroids therapy, antihistamine therapy, absolute eosinophil count, immunoglobulin E, anticoagulant therapy, C-reactive protein, prothrombin time, age at onset, D-dimer, recurrence of rash ≥ 3 times. A simplified model using these features demonstrated optimal performance with an accuracy of 84.2%, a sensitivity of 89.4%, and a specificity of 82.5% in external validation. Finally, we provided a web tool based on the simplified model, whose code was published on https://github.com/mulanruo/IgAVN_Prediction . CONCLUSION: The model based on the random forest algorithm demonstrates good performance in predicting renal damage in children with IgAV, providing a basis for early clinical diagnosis and decision-making.

A specific diagnostic metabolome signature in adult IgA vasculitis.

INTRODUCTION: IgA vasculitis diagnosis relies primarily on clinical features and is confirmed by pathological findings. To date, there is no reliable noninvasive diagnostic biomarker. OBJECTIVE: We aimed to explore the baseline serum metabolome of adult patients with IgA vasculitis to identify potential diagnostic biomarkers. METHODS: We performed a study comparing the serum metabolome of patients with IgA vasculitis to that of patients with inflammatory condition, namely spondyloarthritis. Serum analyses were performed by high-performance liquid chromatography-mass spectrometry. RESULTS: Fifty-five patients with IgA vasculitis and 77 controls with spondyloarthritis (age- and sex-matched) were included in this study. The median age of IgA vasculitis patients was 53 years. Two-thirds of patients were female (n = 32). At the time of vasculitis diagnosis, 100% of patients had skin involvement and 69% presented with glomerulonephritis (n = 38). Joint and digestive involvement were observed in 56% (n = 31) and 42% (n = 23) of patients. Four discriminative metabolites between the two groups were identified: 1-methyladenosine, L-glutamic acid, serotonin, and thymidine. The multivariate model built from the serum metabolomes of patients with IgA vasculitis and spondyloarthritis revealed an accuracy > 90%. As this model was significant according to the permutation test (p < 0.01), independent validation showed an excellent predictive value of the test set: sensitivity 98%; specificity 98%, positive predictive value 97% and negative predictive value 98%. CONCLUSION: To our knowledge, this study is the first to use the metabolomic approach for diagnostic purposes in adult IgA vasculitis, highlighting a specific diagnostic metabolome signature.

Insight into the Interplay of Gd-IgA1, HMGB1, RAGE and PCDH1 in IgA Vasculitis (IgAV).

The pathogenesis of IgAV, the most common systemic vasculitis in childhood, appears to be complex and requires further elucidation. We aimed to investigate the potential role of galactose-deficient immunoglobulin A1 (Gd-IgA1), high-mobility group box 1 (HMGB1), receptor for advanced glycation end products (RAGE) and protocadherin 1 (PCDH1) in the pathogenesis of IgAV. Our prospective study enrolled 86 patients with IgAV and 70 controls. HMGB1, RAGE, Gd-IgA1 and PCDH1 in serum and urine were determined by the enzyme-linked immunosorbent assay (ELISA) method at the onset of the disease and after a six-month interval in patients and once in the control group. Serum concentrations of HMGB1, RAGE and PCDH1 and urinary concentrations of HMGB1, RAGE, Gd-IgA1 and PCDH1 were significantly higher in patients with IgAV than in the control group (p < 0.001). Concentrations of HMGB1 (5573 pg/mL vs. 3477 pg/mL vs. 1088 pg/mL, p < 0.001) and RAGE (309 pg/mL vs. 302.4 pg/mL vs. 201.3 pg/mL, p = 0.012) in the serum of patients remained significantly elevated when the disease onset was compared with the six-month follow-up interval, and thus could be a potential marker of disease activity. Urinary concentration of HMGB1 measured in the follow-up period was higher in patients with nephritis compared to IgAV without nephritis (270.9 (146.7-542.7) ng/mmol vs. 133.2 (85.9-318.6) ng/mmol, p = 0.049) and significantly positively correlated with the urine albumine to creatinine ratio (τ = 0.184, p < 0.05), the number of erythrocytes in urine samples (τ = 0.193, p < 0.05) and with the outcome of nephritis (τ = 0.287, p < 0.05); therefore, HMGB1 could be a potential tool for monitoring patients with IgAV who develop nephritis. Taken together, our results imply a possible interplay of Gd-IgA1, HMGB1, RAGE and PCDH1 in the development of IgAV. The identification of sensitive biomarkers in IgAV may provide disease prevention and future therapeutics.

Investigating the comparative effect of vitamin D level with the type of complications in Henoch Schönlein purpura and Kawasaki disease.

INTRODUCTION AND OBJECTIVES: Henoch Schönlein purpura (HSP) and Kawasaki disease (KD) are two main inflammatory diseases among childhood vasculitis. Considering the anti-inflammatory effects of 25-hydroxyvitamin D3, we decided to investigate the association of serum 25-hydroxy vitamin D3 level with the type and severity of these conditions. MATERIALS AND METHODS: The present study was performed as a historical cohort of 254 affected children with KD and HSP vasculitis. The required data were extracted, using a researcher-made questionnaire from patients' electronic file, and then they were analyzed after collecting information of the patients. RESULTS: In HSP group, 54% of participants were boys. Similarly, in KD group, boys were more affected than girls. The comparative 25-hydroxyvitamin vitamin D3 level in HSP patients with and without renal involvement (P=0.02), hematuria (P=0.14), and in two groups with and without heart disease, and also with and without coronary artery dilatation in KD patients (P<0.001) were significant. DISCUSSION AND CONCLUSIONS: The findings showed that insufficient level of vitamin D3 were significantly associated with the exacerbation of complications of both diseases, and therefore it seems that vitamin D deficiency can be an effective predictive factor of severity in HSP and KD patients.

Comparison of clinical and laboratory data of adult patients with cutaneous IgA vasculitis and non-IgA vasculitis.

BACKGROUND: Immune complex vasculitides may be subdivided into adult IgA small vessel vasculitis (aIgA-SVV; i.e. adult Henoch-Schönlein purpura) and non-IgA-SVV (hypersensitivity vasculitis, etc.). OBJECTIVES: To evaluate the clinical and laboratory parameters of inpatients fulfilling the diagnostic criteria for aIgA-SVV and non-IgA-SVV. METHODS: Twenty-nine adults aged ≥ 20 years with aIgA-SVV [according to the European League Against Rheumatism/Paediatric Rheumatology International Trials Organisation/Paediatric Rheumatology European Society (EULAR/PRINTO/PRES) criteria] and 53 adults with non-IgA-SVV (according to the 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides) were compared with respect to a variety of clinical and laboratory parameters by uni- and multivariable analyses. RESULTS: Compared with patients with aIgA-SVV, the platelet-to-lymphocyte ratio was significantly higher in patients with non-IgA-SVV. Serum C3 levels and mean corpuscular haemoglobin concentration in patients with non-IgA-SVV were significantly lower compared with patients with aIgA-SVV. Proteinuria and haematuria were significantly more common in patients with aIgA SVV, and were significantly correlated with systemic immune-inflammation biomarkers only in patients with aIgA-SVV. In patients with aIgA-SVV, higher lactate dehydrogenase and C-reactive protein were strong independent predictors for the presence of proteinuria and proteinuria. In patients with non-IgA-SVV, female sex was a protective factor for proteinuria, while skin lesions on the upper extremities proved to be a significant independent predictor of haematuria. CONCLUSIONS: We detected several clinical and laboratory differences between patients with aIgA-SVV and non-IgA-SVV. Distinct predictors for renal involvement were not observed in either group, indicating that aIgA-SVV and non-IgA-SVV are similar conditions but do not appear to represent the same entity.

Neutrophil-to-lymphocyte Ratio: A Biomarker for Predicting Systemic Involvement in Henoch-Schonlein Purpura.

BACKGROUND: Henoch-Schonlein purpura (HSP) is one of the commonest entities included within the category of cutaneous vasculitis (CV). Our work is purposed to explore the predictive value of neutrophil-to-lymphocyte ratio (NLR) for systemic involvement in Henoch- Schonlein purpura patients. This ratio is known as an inflammatory marker, and is used to assess the systemic inflammation associated with various diseases. Our objective is to establish whether it can be applied for the prediction of renal and gastrointestinal (GI) or purely renal involvement in Henoch-Schonlein purpura. AIM: To determine the relationship between neutrophil-to-lymphocyte ratio and systemic involvement in Henoch-Schonlein purpura Methods: This is a retrospective review of the patients who were diagnosed with Henoch-Schonlein purpura in our hospital between 2012 and 2018. RESULTS: A total of 57 patients met our inclusion criteria. Pre-treatment neutrophil-to-lymphocyte ratio was significantly associated with renal and/or GI manifestations of the disease (p<0.001). The optimal cut-off value of this ratio for predicting systemic involvement was 2.48, with a 95% specificity and a 94% sensitivity. In addition, pretreatment ratio was also found to be significantly correlated with the severity of relevant systemic manifestations of Henoch-Schonlein purpura (r=0.831; p<0.01). LIMITATIONS: The small number of patients recruited for our research, its retrospective design, and the inclusion of patients attending the same hospital. CONCLUSION: This study suggests that neutrophil-to-lymphocyte ratio is suitable as a potential indicator for predicting the systemic involvement in Henoch-Schonlein purpura.

The Involvement of Neutrophil Extracellular Traps in Disease Activity Associated With IgA Vasculitis.

Objectives: This aim of this study was to determine whether neutrophil extracellular traps (NETs) are involved in the pathogenesis of IgA vasculitis (IgAV) and investigate whether the circulating NETs levels are associated with disease activity in children. Methods: We performed a case-control study and collected blood samples from 193 children with different stages of IgAV (61 were at the onset stage, 64 at the remission stage, 43 at the active stage, and 25 were undergoing drug withdrawal). A total of 192 healthy children were recruited as controls. Circulating cell free DNA (cf-DNA) was obtained from the plasma and quantified by using the Quant-iT PicoGreen DNA quantification kit. NETs-associated myeloperoxidase-DNA (MPO-DNA), citrullinated-histone H3 (cit-H3), neutrophil elastase (NE), and the deoxyribonuclease I (DNase I) concentrations were measured using enzyme-linked immunosorbent assays. The presence of NETs in the kidney and gastrointestinal tissues of onset and active IgAV patients was determined by multiple immunofluorescence staining in 15 IgAV nephritis patients and 9 IgAV patients without IgAV nephritis, respectively. NETs degradation potency of collected sera samples from IgAV patients were checked in vitro. Relationships between circulating levels of cf-DNA with MPO-DNA, NE, and DNase I and the patients were analyzed. Results: Circulating levels of cf-DNA in onset and active IgAV patients were significantly higher than those in remission and drug withdrawal patients as well as healthy controls. The results were similar for MPO-DNA and NE. The levels of circulating cf-DNA correlated significantly with MPO-DNA, NE and DNase I. A significantly decreased degradation of NETs from the onset and active IgAV patients was observed, but was normal in healthy controls. Furthermore, presence of NETs was also confirmed in all renal and gastrointestinal tissues obtained from the onset and active IgAV patients but not control samples. Conclusions: Our data showed that NETs were released into the circulation of IgAV patients and are involved in the disease activity. The circulating levels of NETs maybe used to assess disease severity in children with IgAV.

Correlations of Serological Markers with Development of Systemic Involvement in Adult Immunoglobulin A Vasculitis: A Retrospective Study of 259 Patients in Central China.

OBJECTIVE: Although relatively rare, adult immunoglobulin A vasculitis (IgAV) can lead to severe complications and longer hospitalization, and result in poor prognosis, when compared to childhood IgAV. Hence, early identification and prevention for patients prone to develop systemic involvement are essential. The purpose of this study was to explore the correlations of common serological markers with the development of systemic involvement in adult IgAV. METHODS: A retrospective analysis was performed for adult IgAV patients, who were hospitalized in Wuhan Union Hospital between January 2016 and December 2019. A total of 259 patients were enrolled, and the pre-treatment serological markers were comprehensively assessed. RESULTS: In the present study, 49.0% and 33.2% of patients developed renal and gastrointestinal (GI) involvement, respectively. Furthermore, the elevated levels of white blood cells count, D-Dimer (D-D), C-reactive protein (CRP) and neutrophil granulocyte ratio (NE%) >60% were significantly associated with GI involvement in the univariate analysis, while the decrease in high density lipoprotein level, and the elevated D-D and CRP levels were significantly associated with renal involvement (P<0.05). Moreover, a prediction model that combined multiple markers was established by performing a logistic regression analysis, and this presented a more favorable value of prediction than the individual serological markers. CONCLUSION: The present study suggests that common serological markers have close correlations with systemic involvement in adult IgAV, and that the establishment of a prediction model for systemic involvement may be helpful in facilitating personalized therapeutic strategies and clinical management for IgAV patients.

Serum VEGF-A and VEGFR-1 levels in patients with adult immunoglobulin A vasculitis.

AIM: Immunoglobulin A vasculitis (IgAV) is classified as a leukocytoclastic vasculitis characterized by immune deposits in endothelial walls of small vessels causing vascular endothelial injury. The aim of the present study is to evaluate levels of vascular endothelial growth factor-A (VEGF-A) and VEGF receptor-1 (VEGFR-1) levels in adult IgAV patients. METHOD: Thirty-seven adult IgAV patients admitted to the Rheumatology Clinic meeting the IgAV American College of Rheumatology (ACR) criteria and 32 control subjects were enrolled in the study. Disease activity was categorized as "remission" or "active" according to Birmingham Vasculitis Activity Score (BVAS). Serum VEGF-A, VEGFR-1 levels and VEGFR-1/VEGF-A ratio were evaluated in patient and control groups. RESULTS: Serum median VEGF-A, VEGFR-1 and VEGFR-1/VEGF-A ratios were significantly higher in the patient group when compared to controls (235.9 [155-308.4] pg/mL vs. 78.8 [29.7-210.3] pg/mL, 400 [277.2-724.3] pg/mL vs. 31.5 [12.5-214.4] pg/mL and 1.85 [0.57-2.97] vs. 0.46 [0.38-0.63] respectively, all P values <.001). VEGFR-1 had the strongest predictive value with a cut-off value of 0.6 with 75% sensitivity and 73% specificity (P < .001). CONCLUSION: This study is the first report indicating elevated serum VEGF-A, VEGFR-1, and more importantly VEGFR-1/VEGF-A ratio can be good representatives of the inflammatory processes together with vascular endothelial injury in adult IgAV patients. VEGFR-1 seems to be a more important indicator of the ongoing inflammation.

Meta-analysis of the neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios in Henoch-Schonlein purpura and its complications.

OBJECTIVE: The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are associated with the severity of Henoch-Schonlein purpura (HSP). Therefore, we conducted a meta-analysis to evaluate the clinical significance of NLR and PLR in HSP and its complications. METHODS: A comprehensive literature search was conducted by searching the PubMed, EMBASE, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang, VIP, and SinoMed databases from their inception to September 31, 2020. We used the standard mean difference (SMD) with a 95% confidence interval (CI) to estimate the pooled effect and used subgroup analysis to investigate heterogeneity. RESULTS: A total of 1,691 HSP patients and 563 healthy controls (HCs) from 15 studies were included in the analysis. The NLR value was significantly higher in 431 HSP patients with gastrointestinal complications (HSP-GCs) than that in 833 HSP patients without GCs (SMD = 1.09, 95% CI: 0.62-1.57, P < 0.001); in 83 HSP adult patients with renal involvement (HSP-RI) than that in 131 adult HSP patients without RI (SMD = 0.33, 95% CI: 0.05-0.60, P = 0.021); and in 831 HSP patients than that in 563 HCs (SMD = 0.70, 95% CI: 0.51-0.89, P < 0.001). The PLR was significantly higher in 417 HSP patients than that in 264 HCs (SMD = 0.39, 95% CI: 0.06-0.71, P = 0.02). CONCLUSIONS: NLR could serve as a useful biomarker to predict GCs and RI in patients with HSP. However, further well-designed and large cohort studies are warranted to confirm these findings.

Clinical relevance of neutrophil-to-lymphocyte ratio and mean platelet volume in pediatric Henoch-Schonlein Purpura: a meta-analysis.

The association of neutrophil-to-lymphocyte ratio (NLR) and mean platelet volume (MPV) with the severe gastrointestinal (GI) involvement in pediatric Henoch-Schonlein Purpura (HSP) has been reported in many studies. However, the conclusions from the previous studies were controversial. Therefore, for the first time, we performed a meta-analysis to systematically evaluate the relationship of NLR and MPV to the severe GI involvements. We retrieved PubMed, EMBASE, Web of Science, and Chinese National Knowledge Infrastructure (CNKI) (up to October 2020) thoroughly to acquire eligible studies. The pooled standard mean difference (SMD) with 95% confidence interval (CI) was used to describe the correlation of NLR and MPV with the severe GI involvement. A total of 12 studies comprising 2168 patients with HSP were included in this meta-analysis. Our combined analysis showed that NLR in HSP patients with the severe GI involvement was significantly higher than that in those without the severe GI involvement (SMD = 1.37; 95% CI: 0.70-2.05; p < 0.01). In addition, a lower MPV was observed in children with severe GI involvement (SMD = -0.29; 95% CI: -0.56 - -0.01, p = 0.042). Our sensitivity analysis and publication bias evaluation indicated that our combined results were reliable. Taken together, our study suggested NLR and MPV may be used as biomarkers for predicting or diagnosing the severe GI involvement in children with HSP. Nevertheless, more homogeneous studies with a larger sample size are required to validate these findings.

Serum levels of galactose-deficient IgA1 in Chinese children with IgA nephropathy, IgA vasculitis with nephritis, and IgA vasculitis.

OBJECTIVE: IgA nephropathy (IgAN) and IgA vasculitis with nephritis (IgAV-N) are related diseases. Galactose-deficient IgA1 (Gd-IgA1) plays an important role in the pathology of IgAV-N and IgAN, so we aim to compare the serum levels of Gd-IgA1 in Chinese pediatric patients with IgAN, IgAV-N, and IgAV. METHODS: We retrospectively enrolled 52 patients with IgAN, 57 patients with IgAV-N, 26 patients with IgAV, and 40 healthy children. The serum levels of Gd-IgA1 were measured at the time of biopsy using a lectin-based ELISA method. RESULTS: Gd-IgA1 levels in IgAV-N patients and IgAN patients were higher than in healthy controls (303.94 ± 39.37 U/ml, 314.91 ± 47.79 U/ml vs. 273.57 ± 48.29 U/ml, P < 0.001), and Gd-IgA1 levels in IgAV-N patients were higher than in IgAV patients (303.94 ± 39/ml vs. 286. 21 ± 38.81 U/ml, P = 0.059), but the latter result is not statistically significant. The Gd-IgA1 levels in IgAV patients were comparable with those in healthy controls (286.21 ± 38.81 U/ml vs. 273.57 ± 48.29 U/ml, P = 0.267). Among the four groups, we did not observe significant correlations of Gd-IgA1 levels with eGFR, proteinuria, or the MEST-C score. CONCLUSION: Serum Gd-IgA1 maybe involved in the pathogenesis of the IgAV-N and IgAN. However, we found no statistically significant correlation between Gd-IgA1 levels and clinical and pathological features.

The relevance of practical laboratory markers in predicting gastrointestinal and renal involvement in children with Henoch-Schönlein Purpura.

OBJECTIVES: Henoch-Schönlein Purpura (HSP) is the most common self-limiting vasculitis of childhood. Both serious gastrointestinal and renal complications may be observed during the disease course. The aim of this study was to evaluate the role of hematological markers in predicting the likely complications of the disease. METHODS: The demographic findings, clinical features, organ involvements and laboratory findings including white blood cell count (WBC), neutrophil, lymphocyte and platelet counts, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), mean platelet volumes (MPV), MPV/platelet count ratio (MPR) were evaluated retrospectively from the charts of the patients with HSP and all these parameters were compared with the same parameters of healthy children. RESULTS: A total of 376 patients with HSP and age- and sex-matched 233 healthy children were evaluated. Mean age at the diagnosis was 7.5 ± 3.5. All patients had palpable purpura, 46% had arthritis, 56.1% GIS involvement and 21.3% had renal involvement. While platelet counts, neutrophil counts, NLR, and PLR were higher, lymphocyte counts, MPV, and MPR were lower in patients with GIS involvement. NLR was the sole biomarker that was higher in patients with renal involvement. CONCLUSIONS: This study had shown that platelet counts, neutrophil counts, NLR, and PLR were increasing and lymphocyte counts, MPV, and MPR were decreasing when the patients had GIS involvement. However, these parameters were not relevant in distinguishing severe and mild GIS involvement. When patients had renal involvement NLR was the unique elevated parameter.

Onset age is a risk factor for refractory pediatric IgA vasculitis: a retrospective cohort study.

BACKGROUND: Though outcome differences between children and adults with immunoglobulin A vasculitis (IgAV) has been well documented, it remains unclear if disease features in pediatric IgAV patients vary with onset age. We aimed to explore clinical features and prognosis of pediatric IgAV stratified by onset age. METHODS: We retrospectively reviewed records of patients under 18 years old diagnosed with IgAV from January 1999 to December 2018 in one tertiary medical center in Taiwan. Patients were grouped by onset age: ≤ 6 years old, 6-12 years old (> 6, ≤ 12), and 12-18 years old (> 12, < 18). Demographics, laboratory data, incidence of gastrointestinal, renal, and joint involvement, corticosteroid dependence, recurrence, and refractory disease were analyzed. Recurrence was defined as disease flare-up after complete remission and discontinuation of all medications for at least 3 months. Corticosteroid dependence was defined by more than 6 weeks of daily oral corticosteroid intake. Refractory disease was defined as not achieving complete remission 6 months after disease onset. Statistical analysis was performed using R software (v3.6.0). RESULTS: There were 484 IgAV patients, with an onset age of 6.10 (4.72-8.58) (median (IQR)) years old. There were 234 (48.3%) patients ≤6 years old, 210 (43.4%) 6-12 years old, and 40 (8.3%) 12-18 years old. One hundred and thirty (26.9%) patients had renal involvement, which was more frequent in older children (≤ 6 years old, 18.4%; 6-12 years old, 31.0%; 12-18 years old, 55.0%; p <  0.001). There were 361 patients (74.6%) with joint involvement; younger children were affected more frequently (≤ 6 years old, 82.1%; 6-12 years old, 71.9%; 12-18 years old, 45.0%; p <  0.001). Gastrointestinal involvement was present in 311 (64.3%) patients, showing no difference among age groups. There were 46 patients (9.5%) with recurrent IgA vasculitis, 136 (28.1%) with corticosteroid dependent and 76 (15.7%) with refractory disease. Corticosteroid dependence and refractory disease occurred more frequently as onset age increased (p <  0.001). CONCLUSION: Pediatric IgAV with different onset ages are associated with distinct clinical manifestations and outcomes. The risk of developing corticosteroid dependence, refractory disease and renal involvement increased with onset age.

Is adiponectin in children with immunoglobulin A vasculitis a suitable biomarker of nephritis in the course of the disease?

INTRODUCTION: Immunoglobulin A vasculitis (IgAV) is the most common form of vasculitis in children. Nephritis in the course of this disease (IgAVN) is observed in 30-50% of patients and might lead to chronic kidney disease (CKD) and end-stage renal disease (ESRD). Finding a non-invasive biomarker to distinguish initially between patients with and without nephritis and to facilitate a therapeutic decision to reduce the risk of long-term renal impairment is currently the target of much research. The aim of this study was to evaluate the adiponectin concentration in children with IgAV and estimate whether it might be used as a marker of IgAVN. MATERIAL AND METHODS: The study involved 29 IgAV children and 34 healthy controls. Eleven (38%) patients had renal involvement (IgAV-N) and 18 (62%) did not exhibit nephritis (IgAV-noN). The serum adiponectin level was estimated in children in an acute phase of IgAV and after 2-6 months during a follow-up visit. The relationship between the concentration of adiponectin and anthropometric measurements, epidemiological data and laboratory parameters were evaluated. RESULTS: The concentration of adiponectin in serum was significantly higher in children with acute phase of IgAV as compared to the control group (p < 0.001), and in patients without renal involvement in comparison with IgAV-N children (p < 0.049). In analysis of correlation we found a negative relationship between adiponectin level and serum creatinine concentration (r = -0.437, p = 0.02). The logistic regression evaluation demonstrated that a low adiponectin level increased the risk of nephritis in the course of IgAV. CONCLUSIONS: Our study revealed that the serum adiponectin level increased markedly in patients with IgAV. We also documented that higher risk of nephritis in the course of the disease was associated with lower concentration of this hormone.

Analysis of the association between kidney injury biomarkers concentration and nephritis in immunoglobulin A vasculitis: A pediatric cohort study.

OBJECTIVE: The aim of this study was to investigate the clinical course, selected biochemical parameters and concentrations of renal injury biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1) and liver-fatty acid binding protein (L-FABP) in patients with immunoglobulin A vasculitis (IgAV) to identify the markers associated with nephritis in the course of the disease (IgAVN). METHODS: The study involved 29 children with IgAV and 34 healthy controls. Eleven (38%) patients had renal involvement (IgAV-N) and 18 (62%) did not exhibit nephritis (IgAV-noN). Initial laboratory tests, determining the concentrations of NGAL, KIM-1 and L-FABP in serum and urine, were conducted on children from the study group in an acute phase of IgAV as well as after an average of 6 months, during a follow-up visit. The interconnection between renal involvement, anthropometric measurements, epidemiological data, laboratory parameters and levels of examined biomarkers have been thoroughly evaluated. RESULTS: The serum and urine levels of NGAL, KIM-1 and L-FABP were significantly higher in children with an acute phase of IgAV as compared to the control group (P < .001) and markedly lower during follow-up retesting in comparison with the values obtained at inclusion (P < .001). However, the concentration of none of the evaluated biomarkers correlated with nephrological indices. Among all examined parameters, only male subjects were associated with nephritis (P = .017). CONCLUSIONS: We have established no evident association between the concentrations of NGAL, KIM-1 and L-FABP and nephritis in the course of IgAV in children. Additionally, we confirmed a significant male predominance in patients with nephritis.

Procalcitonin and C-reactive Protein Levels as Biomarkers to Determine Gastrointestinal Involvement in Adult Henoch-Schönlein Purpura Patients.

OBJECTIVE: To investigate the association of procalcitonin (PCT) and C-reactive protein (CRP) levels with gastrointestinal (GI) involvement in adult HSP patients. METHOD: A retrospective study using clinical data and serum PCT and CRP levels from 121 adult HSP patients was performed. RESULTS: The proportion of male HSP patients with GI involvement was significantly higher compared to patients without GI involvement. PCT and CRP levels in adult HSP patients with GI involvement were higher compared to patients without GI involvement (P < 0.05); Among the patients with GI involvement, those with GI hemorrhage had significant higher PCT and CRP levels (P < 0.05); the median PCT value was lower compared to the threshold value for systemic infection. There was a positive correlation between PCT and CRP levels in HSP patients with GI involvement and GI bleeding (P < 0.05). ROC curve analysis demonstrated that the PCT and CRP cutoff levels of 0.07 ng/ml and 29.35 mg/L respectively had optimal diagnostic efficacy for GI bleeding in adult HSP patients. CONCLUSION: Elevated serum PCT and CRP levels were significantly associated with GI involvement in adult HSP patients, especially for GI bleeding. PCT levels correlated well with CRP levels.

A cross-sectional analysis of clinicopathologic similarities and differences between Henoch-Schönlein purpura nephritis and IgA nephropathy.

INTRODUCTION: Recent studies noted that Henoch-Schönlein purpura nephritis (HSPN) and IgA nephropathy (IgAN) share the feature of galactose-deficient IgA1 (Gd-IgA1)-oriented pathogenesis, although there are distinct clinical differences. We aimed to clarify the clinicopathologic differences between these 2 diseases. METHODS: We cross-sectionally analyzed adult patients with HSPN (n = 24) or IgAN (n = 56) who underwent renal biopsy (RB) between 2008 and 2018 at Showa University Hospital. Serum Gd-IgA1 (s-Gd-IgA1) levels at the time of RB were compared among study groups using enzyme-linked immunosorbent assay (ELISA) with anti-human Gd-IgA1-specific monoclonal antibody (KM55). We also immunohistochemically stained paraffin-embedded sections for glomerular Gd-IgA1 (g-Gd-IgA1)-deposition using KM55. Serum inflammatory cytokines were measured using ELISA. RESULTS: Glomerular endothelial injury with subendothelial IgA deposition was significant in patients with HSPN. Serum IL-8, MCP-1, TNF-α, and IL-6 levels were significantly higher in patients with HSPN than IgAN. Levels of s-Gd-IgA1 were comparable among patients with HSPN and IgAN, and a similar degree of g-Gd-IgA1-deposition was detected in both diseases. Furthermore, g-Gd-IgA1-deposition was evident in patients with histopathologically advanced HSPN or IgAN. In HSPN, significant positive correlations between s-Gd-IgA1 levels and crescent formation or IL-6 elevation were confirmed, and g-Gd-IgA1 intensity showed a significant positive correlation with MCP-1 and a tendency to positively correlate with IL-8. Meanwhile, patients with IgAN showed no correlation between inflammatory cytokines and both-Gd-IgA1. Moreover, most g-Gd-IgA1-positive areas were not double stained with CD31 in HSPN. CONCLUSIONS: Although assessing both-Gd-IgA1 alone was insufficient to distinguish between HSPN and IgAN, patients with HSPN showed considerable glomerular capillaritis with subendothelial IgA deposition and significant elevation of serum inflammatory cytokines. Furthermore, such glomerular subendothelial IgA deposition might not contain Gd-IgA1, and factors associated with Gd-IgA1 were inconsistent among these 2 diseases. Thus, developmental mechanisms for IgAN might not apply to HSPN completely, and these 2 diseases still have different aspects.

Intramuscular Hematoma as a Manifestation of IgA Vasculitis.

We describe an atypical pediatric case of immunoglobulin A vasculitis (IgAV), also referred to as Henoch-Schönlein purpura, in which formation of spontaneous hematoma of the paraspinal muscles developed. Spontaneous or unprovoked hematomas rarely occur in IgAV. These manifestations have not been described specifically in the pediatric literature as coinciding with IgAV. These findings are alarming for nonaccidental trauma, particularly in a patient without underlying blood dyscrasia. Our objective for this report is to highlight the possible association of muscular hematoma formation with IgAV and to help providers consider this association when trauma and hemophilia has been ruled out.