Posterior reversible encephalopathy syndrome in the setting of IgA vasculitis.

IgA vasculitis (IgAV), formerly known as Henoch-Scholein purpura, is a small vessel vasculitis, most commonly seen in pediatric patients, that can affect numerous internal organs including the kidneys, lungs, gastrointestinal tract, and the central nervous system (CNS). CNS manifestations of this condition include hypertensive encephalopathy, thrombosis, optic neuropathy, seizures, CNS vasculitis, and a more recently described phenomenon known as posterior reversible encephalopathy syndrome (PRES). Symptoms of PRES include hypertension, altered mental status, and seizures caused by vasogenic disruption of the blood-brain barrier, and the condition is diagnosed by characteristic edema-related gray-white matter changes in the parieto-occipital lobes on magnetic resonance imaging. Herein, we present a rare case of PRES as a presenting sign of IgAV to increase awareness about this unusual association.

[Immunoglobulin A vasculitis (IgAV)]. / Immunglobulin-A-Vaskulitis (IgAV).

IgA vasculitis (IgAV) is an immune complex-mediated vasculitis characterized by IgA1-dominant immune deposits in small vessels. It is the most common systemic vasculitis in childhood with a mostly uncomplicated and self-limiting course. Adults are less affected but the course is frequently more complicated and more frequently accompanied by renal involvement. IgAV characteristically manifests itself on the skin with palpable purpura and in joints, the kidneys and the gastrointestinal tract. In cases of incomplete or atypical symptoms a differential diagnostic work-up is required. A number of triggers have been suggested, especially infections and drugs. Disease management is tailored to organ manifestations and the severity of the symptoms. For children, optimized supportive care and targeted symptom relief are usually sufficient. Management of renal and gastrointestinal manifestations follows recommendations for ANCA-associated vasculitis and IgA nephropathy. Treatment options include glucocorticoids and immunosuppressive agents with varying and mostly insufficient evidence.

Association between common laboratory indices and IgAV recurrence in children.

BACKGROUND: IgA vasculitis (IgAV) is a common type of vasculitis seen in children. IgAV recurrence can result in chronic kidney disease. We aimed to explore the association between common laboratory indices and IgAV recurrence in children, and to establish a prediction model. METHODS: This retrospective study included children with diagnosed with IgAV hospitalized in Bazhong Central Hospital, Sichuan, from January 2014 to December 2019. Children were assigned to two groups based on IgAV recurrence, and baseline clinical data were collected for comparison. A logistic regression model to predict IgAV recurrence was established. The receiver operating characteristic curve was plotted. The area under the curve (AUC) was used to detect performance of the predictive model. RESULTS: This study included 193 children (39 [20.2%], recurrence group; 154 [79.8%], non-recurrence group). Based on multivariate regression analysis, the duration of illness and joint involvement were independent predictors of IgAV recurrence in children (P < 0.05). No significant differences were observed in common laboratory indices (P > 0.05). The AUC of the prediction model was 0.766 (P < 0.001) with sensitivity of 74.4% and specificity of 68.8%. CONCLUSION: Common laboratory indices were not associated with recurrence of IgAV in children.

Increased Urinary IgA in Paediatric IgA Vasculitis Nephritis.

IgA vasculitis (IgAV) is the most common form of paediatric vasculitis, with up to 50% of patients experiencing kidney inflammation. Much remains unknown about IgAV, but it is believed to arise due to galactose-deficient IgA1 promoting an auto-inflammatory response. This study assesses whether urinary IgA can be detected in children with IgAV to allow further evaluation of IgA1 and whether it has any relationship with nephritis. Urinary and serum IgA concentrations were measured using commercially available ELISA kits. Patients were grouped into IgAV nephritis (IgAVN) or IgAV without nephritis (IgAVwoN). Fifty-nine children were included: IgAVN n = 12, IgAVwoN n = 35, and healthy controls (HC) n = 12, with a mean age of 8.2 ± 4.1 years. Urinary IgA concentrations were statistically significantly higher in patients with IgAV (107.1 ± 136.3 µg/mmol) compared to HC (50.6 ± 26.3 µg/mmol; p = 0.027) and IgAVN (229.8 ± 226.3 µg/mmol) compared to both IgAVwoN (65.0 ± 37.8 µg/mmol; p = 0.002) and HC (p < 0.001). Urinary IgA concentrations were able to distinguish between renal status (AUC 0.838, 95%CI [0.704−0.973], p < 0.001) and did not correlate with proteinuria (r = 0.124; p = 0.407). Urinary IgA concentrations are increased in children with IgAVN, and it has the potential to act as a non-invasive biofluid to further evaluate nephritis in this disease.

IgA Vasculitis in Adults: a Rare yet Challenging Disease.

PURPOSE OF REVIEW: IgA vasculitis (IgAV) is a rare and poorly understood systemic vasculitis in adults. Its diagnosis and treatment remain a challenge. Herein, we review the clinical manifestations, diagnosis, management, and prognosis of IgAV in adults. RECENT FINDINGS: The clinical course of IgAV in adults appears to be different from pediatric IgAV, especially due to its higher risk of evolving into end-stage renal disease. Rising awareness and interest in adult-onset IgA vasculitis has resulted in recent increasing number of publications on different treatment experiences. However, there is still controversy over the role of glucocorticoid (GC) and different immunosuppressive therapies such as cyclophosphamide, rituximab, and mychophenolate mofetil for more severe IgAV. Data regarding potential benefits of targeting the mucosal immune system, toll-like receptors, complements, and tyrosine kinase inhibitors in the treatment of IgA nephropathy are emerging. High quality evidence or guidelines in the treatment of severe IgAV are lacking and there is still a great need for controlled trials.

CureGN Study Rationale, Design, and Methods: Establishing a Large Prospective Observational Study of Glomerular Disease.

RATIONALE & OBJECTIVES: Glomerular diseases, including minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, and immunoglobulin A (IgA) nephropathy, share clinical presentations, yet result from multiple biological mechanisms. Challenges to identifying underlying mechanisms, biomarkers, and new therapies include the rarity of each diagnosis and slow progression, often requiring decades to measure the effectiveness of interventions to prevent end-stage kidney disease (ESKD) or death. STUDY DESIGN: Multicenter prospective cohort study. SETTING & PARTICIPANTS: Cure Glomerulonephropathy (CureGN) will enroll 2,400 children and adults with minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, or IgA nephropathy (including IgA vasculitis) and a first diagnostic kidney biopsy within 5 years. Patients with ESKD and those with secondary causes of glomerular disease are excluded. EXPOSURES: Clinical data, including medical history, medications, family history, and patient-reported outcomes, are obtained, along with a digital archive of kidney biopsy images and blood and urine specimens at study visits aligned with clinical care 1 to 4 times per year. OUTCOMES: Patients are followed up for changes in estimated glomerular filtration rate, disease activity, ESKD, and death and for nonrenal complications of disease and treatment, including infection, malignancy, cardiovascular, and thromboembolic events. ANALYTICAL APPROACH: The study design supports multiple longitudinal analyses leveraging the diverse data domains of CureGN and its ancillary program. At 2,400 patients and an average of 2 years' initial follow-up, CureGN has 80% power to detect an HR of 1.4 to 1.9 for proteinuria remission and a mean difference of 2.1 to 3.0mL/min/1.73m2 in estimated glomerular filtration rate per year. LIMITATIONS: Current follow-up can only detect large differences in ESKD and death outcomes. CONCLUSIONS: Study infrastructure will support a broad range of scientific approaches to identify mechanistically distinct subgroups, identify accurate biomarkers of disease activity and progression, delineate disease-specific treatment targets, and inform future therapeutic trials. CureGN is expected to be among the largest prospective studies of children and adults with glomerular disease, with a broad goal to lessen disease burden and improve outcomes.

Analysis of neutrophil to lymphocyte ratio, platelet to lymphocyte ratio and mean platelet volume to platelet count ratio in children with acute stage of immunoglobulin A vasculitis and assessment of their suitability for predicting the course of the disease.

Immunoglobulin A vasculitis (IgAV) is the most common systemic vasculitis in developmental age. The disease is most often characterized by a self-limiting course and good prognosis, but sometimes serious complications, like gastrointestinal bleeding or glomerulonephritis, may develop. The neutrophil to lymphocyte (NLR) and the platelet to lymphocyte (PLR) ratios are indicators related to clinical outcome in various inflammatory diseases. The mean platelet volume to platelet count ratio (MPR) has not been evaluated in patients with IgAV. The aim of this study was to analyze the values of the NLR, PLR and MPR in patients with an acute stage of IgAV compared to healthy children and to assess their suitability for predicting the severity of the disease. All children with IgAV hospitalized in our institution between 2012 and 2017 were reviewed retrospectively. The selected laboratory data were recorded before starting the treatment; these results allowed for NLR, PLR, and MPR calculation. The study involved 71 IgAV children. 57.7% of patients revealed signs of systemic involvement (including GT bleeding and/or glomerulonephritis) and 42.3% were nonsystemic (presenting skin and joint symptoms). 83% of patients were classified as mild and 17% as severe course of the disease. The NLR and the PLR were significantly higher in all IgAV children and in the systemic involvement group in comparison with non-systemic. The MPR was significantly lower in all IgAV group with the exception of children without systemic involvement. The NLR is a more valuable indicator than the PLR to identify patients at higher risk of systemic involvement in the course of IgAV. Clinical usefulness of the MPR requires further research.

Serum levels of selected cytokines [interleukin (IL)-17A, IL-18, IL-23] and chemokines (RANTES, IP10) in the acute phase of immunoglobulin A vasculitis in children.

The pathogenesis of the immunoglobulin A vasculitis (IgAV) is still unknown. The available data shows that interleukin (IL)-17, IL-18, IL-23, regulated on activation, normal T cell expressed and secreted (CCL 5, RANTES), and interferon (IFN)-γ-inducible protein 10 (IP10) participate in the pathogenesis of IgAV by influencing the recruitment of leukocytes to the site of inflammation. The aim of this study was to analyze the serum concentration of IL-17A, IL-18, IL-23, RANTES, and IP10 in patients with acute IgAV compared to healthy children. Moreover, we wanted to assess the suitability of the levels of tested cytokines to predict the severity of the disease. All children with IgAV hospitalized in our institution between 2012 and 2017 were included in the study. Cytokines levels were determined in a serum sample secured at admission to the hospital. Basic laboratory tests have also been analyzed. IL-17A, IL-18, and IL-23 were significantly higher in whole IgAV group (52.25 pg/ml; 164.1 pg/ml and 700 pg/ml, respectively) than in the control group (27.92 pg/ml; 140.1 pg/ml and 581.5 pg/ml, respectively). The receiver operating characteristic (ROC) curve analysis revealed the largest area under the curve (AUC 0.979, p < 0.001) for the IL-17A with 95.1% sensitivity and 91.7% specificity. There were no significant differences in cytokine levels depending on the severity of the IgAV. Although the serum levels of the IL-17A, IL-18, and IL-23 increase significantly in the acute phase of the IgAV, they cannot be used as indicators of predicting the course of the disease. IL-17A seems to be a good predictor of IgAV occurrences.

Significance of histological crescent formation in patients with IgA vasculitis (Henoch-Schönlein purpura)-related nephritis: a cohort in the adult Chinese population.

BACKGROUND: IgA vasculitis (IgAV, formerly Henoch-Schönlein purpura) is a type of systemic vasculitis. This study aimed to explore the clinicopathological features, treatment and renal outcomes of adult IgAV-related nephritis (Henoch-Schönlein purpura nephritis) patients with different degrees of crescent formation. METHODS: Adult patients with biopsy-proven IgAV-related nephritis in Nanjing Jinling Hospital were enrolled and divided into three groups as follows: control (no crescents, n = 257), group 1 (crescents < 25%, n = 381), and group 2 (crescents ≥25%, n = 60). The clinicopathological features, treatment and renal outcomes were compared among the three groups. RESULTS: There were no significant differences in gender and age at biopsy among the three groups. Groups with more crescents had shorter renal durations and higher prevalence of macroscopic hematuria, proteinuria and nephrotic syndrome than the control group. The presence of renal insufficiency at biopsy was similar, whereas laboratory findings indicated that patients with ≥25% crescents had higher levels of serum creatinine and blood urea nitrogen than the control and group 1. Histologically, the incidence of glomeruli-Bowman's capsule adhesion and capillary necrosis were proportional to the degree of crescent formation. Patients with more crescents received more positive immunosuppressive therapies. During follow-up, the levels of proteinuria and hematuria were in remission after treatment, and patients without crescents had lower levels of proteinuria. At the last follow-up, the renal function had deteriorated in the control and group 1, whereas the levels of serum creatinine at biopsy and last follow-up were similar in group 2. There was a significant difference in renal survival from end-stage renal disease (ESRD) or 50% decline in renal function among the three groups (log-rank, P = 0.030). However, no association between crescent formation and renal outcomes was found after adjusting potential confounders. CONCLUSIONS: Adult IgAV-related nephritis patients with more crescents had more-severe renal manifestations and worse treatment responses, whereas the proportions of crescents were not associated with higher risks for ESRD or 50% decline in renal function. A more suitable pathological classification standard is needed to predict renal prognosis.

A Rare Case of Immunoglobulin A Vasculitis in an Adult Male.

A 40-year-old Indian male presented with rash and abdominal pain, leading to a diagnosis of IgA vasculitis, a rare condition in adults. This systemic vasculitis involves IgA immune complex deposition, resulting in inflammation and tissue damage. Diagnosis relies on clinical features and biopsy findings, with management focused on symptom relief and addressing organ involvement. Long-term prognosis varies, emphasizing the importance of multidisciplinary care and patient education for optimal outcomes.

Navigating Adult-Onset IgA Vasculitis-Associated Nephritis.

PURPOSE OF REVIEW: IgA vasculitis (IgAV), formerly Henoch-Schonlein purpura, is the most common systemic vasculitis in childhood. In adults, however, this condition is poorly understood, yet associated with more severe disease and poorer outcomes. This necessitates the need for early diagnosis and management. SCOPE OF REVIEW: We describe the pathophysiology, clinical manifestations, and diagnosis of IgAV in adults. Poor outcomes are often due to the high frequency of glomerulonephritis in IgAV-IgA vasculitis-associated nephritis (IgAVN). We hence also aim to summarize the latest clinical data regarding treatment strategies in IgAVN. The diagnosis and differentiation in histology between IgAVN and IgA nephropathy (IgAN) remain a challenge. Review of treatment therapies: Pathological mechanisms between IgAVN and IgAN appear to be consistent between the two, and data from IgAN are often extrapolated to IgAVN. The role of various immunosuppression therapies remains controversial, and in this review, we will discuss immunosuppression use and highlight evidence surrounding emerging and promising novel therapies in IgAVN/IgAN. Our aim for this review is to guide future treatment strategies and direct future studies.

Successful rituximab therapy in adult-onset IgA vasculitis with diffuse alveolar hemorrhage and renal failure: a case report.

Background: Immunoglobulin A vasculitis (IgAV) is a rare condition that most commonly presents during childhood. Patients with adult-onset IgAV are more likely to exhibit severe symptoms at presentation with worse renal outcomes. Pulmonary manifestations of adult-onset IgAV have been described rarely in the literature and often indicate higher morbidity and mortality. Given the rarity of alveolar hemorrhage in IgAV, the literature describing the clinical entity and offering management recommendations is insufficient. Case Description: We describe a patient with known adult-onset IgAV who presented with one month of abdominal pain, bloody stools, new skin lesions, and progressive shortness of breath. She developed rapidly worsening hypoxic respiratory failure associated with a hemoglobin drop and diffuse pulmonary infiltrates on imaging. Bronchoscopy demonstrated progressively hemorrhagic effluent on bronchoalveolar lavage (BAL) consistent with a diagnosis of diffuse alveolar hemorrhage (DAH). She developed acute renal failure requiring the initiation of emergent renal replacement therapy. Given concomitant DAH and acute renal failure, methylprednisolone and rituximab (RTX) therapy were initiated. With this treatment regimen, she exhibited marked improvement in respiratory function and complete renal recovery. Conclusions: This case highlights the importance of considering DAH as a rare and life-threatening pulmonary manifestation of adult-onset IgAV. Our case demonstrates the novel and successful use of RTX in combination with steroids to treat a patient with adult-onset IgAV presenting with concomitant DAH and renal failure.

Worldwide Distribution and Extracutaneous Manifestations of Henoch-Schönlein Purpura in Adults: Narrative Review.

BACKGROUND: Henoch-Schönlein purpura (HSP), a leukocytoclastic small vessel vasculitis, exhibits both cutaneous and systemic manifestations. While predominantly observed in childhood, it may manifest in adults with more pronounced systemic involvement. Furthermore, HSP is a global phenomenon showcasing epidemiological and systemic variances. OBJECTIVE: This study aims to scrutinize extracutaneous manifestations in adults with HSP, discerning distinctions according to geographical regions on a worldwide scale. METHODS: A comprehensive search encompassing PubMed, Embase, Cochrane Library, and Web of Science was executed, covering papers published from January 1, 1970, to December 1, 2019. Keywords used included "Henoch-Schönlein purpura," "henoch schonlein purpura+adult," "IgA vasculitis+adult," "HSP+adult," and "IgAV." A total of 995 publications were identified, from which 42 studies encompassing 4064 patients were selected, with a predominant focus on cases reported in Asia, Europe, and the Americas. RESULTS: Among adults afflicted with HSP, European patients exhibited a higher propensity for male predominance (P<.001), gastrointestinal involvement (P<.001), and musculoskeletal complications (P<.001). Conversely, patients from the Americas were least likely to experience genitourinary involvement (P<.001). CONCLUSIONS: HSP demonstrates a variance in distribution and extracutaneous manifestations within distinct geographical boundaries. In the adult population, European patients exhibited a higher prevalence of male gender and gastrointestinal and musculoskeletal involvement. Asian patients were more predisposed to genitourinary involvement when compared to their American counterparts. The establishment of prospective studies using standardized reporting measures is imperative to validate the relationships unveiled in this investigation.

A case series on recurrent and persisting IgA vasculitis (Henoch Schonlein purpura) in children.

BACKGROUND: IgA vasculitis (IgAV) is a small vessel vasculitis that is more common in childhood. Very limited evidence exists on patients who experience an atypical disease course. The aim of this study was to describe a cohort of children diagnosed with recurrent or persisting IgAV to identify any themes associated with their disease course and areas of unmet needs. METHODS: A single centre retrospective study of children diagnosed with recurrent or persisting IgAV at Alder Hey Children's Hospital (Liverpool, UK). Clinical data, including features at presentation and during follow up, potential triggers, abnormal laboratory and histology results, treatment and outcome at last clinical review were retrospectively collected. Key themes were identified. RESULTS: A total of 13 children met the inclusion criteria (recurrent disease, n = 4; persisting disease, n = 9). Median age at first presentation was 10.2 years [2.6-15.5], female:male ratio 1.2:1. Children in the atypical cohort were significantly older than a larger cohort of children who followed a non-complicated disease course (median age 5.5 years (range [0.6-16.7], p = 0.003)). All children re-presented with a purpuric rash (either recurring or persisting), accompanied by joint involvement in 92% of patients (12/13). Disease-modifying anti-rheumatic drugs (DMARDs) were used in 8/13 (62%) children. The median time from first presentation to diagnosis of atypical disease was 18.4 months [5.3-150.8] and the time from first presentation to treatment was 24.1 months [1.8-95.4]. Use of corticosteroids was significantly higher in children with renal involvement (p = 0.026). During follow up, 8/13 (62%) children were admitted at least once, whilst 10/13 (77%) had re-presented at least once to the emergency department. Five (38%) children were referred to psychology services and 7 (54%) children reported feelings of frustration. CONCLUSIONS: This series describes some characteristics of a small cohort of children with atypical IgAV. It also identifies unmet needs in children with atypical IgAV, which includes delays in diagnosis and lengthy waits for treatment, lack of high-quality evidence regarding treatment choices and a high unrecognised disease burden. Further research is needed to study this subgroup of children as evidence is lacking.

Atypical Immunoglobulin A Vasculitis in a Pediatric Patient With Ulcerative Colitis.

Rates of pediatric inflammatory bowel disease and biologic therapy use continue to rise. Consequently, specialists and generalists should recognize potential complications and side effects. We report the unique case of an adolescent with ulcerative colitis (UC) on vedolizumab presenting with severe abdominal pain, hematochezia, and subsequent purpura. After extensive investigation and a complex clinical course, diagnosis of atypical immunoglobulin A vasculitis was made. This is the first pediatric case of vasculitis in a patient with UC on vedolizumab and only the second reported case overall in UC. This case illustrates the emerging diagnostic challenge of distinguishing inflammatory bowel disease treatment complications from other common pediatric conditions.

SARS-CoV-2 Infection as a Possible Trigger for IgA-Associated Vasculitis: A Case Report.

BACKGROUND: IgA-associated vasculitis (IgAV), formerly known as Henoch-Schönlein purpura (HSP) disease, is the most common type of systemic vasculitis observed during developmental age. Available published studies associate the outbreak of the disease with streptococci, adenovirus, parvovirus, mycoplasma, respiratory syncytial virus (RSV), and influenza infection in approximately 50% of patients with HSP, while some emerging reports have described a few cases of COVID-19 infection being associated with HSP in both adults and children. CASE PRESENTATION: a 7-year-old girl was diagnosed with HSP, fulfilling the four required clinical criteria (palpable purpura and abdominal pain, arthralgia and edema, and periodic renal involvement). Infection with SARS-CoV-2 was confirmed via the presence of IgM and IgG antibodies. The disclosure of the Henoch-Schönlein purpura (HSP) disease was preceded by a mild, symptomatically treated infection of the upper respiratory tract. High levels of inflammatory markers were observed during hospitalization, including leukocytosis, an increased neutrophil count and a high neutrophil-to-lymphocyte ratio (NLR). All of these markers are associated with IgAV gastrointestinal bleeding, which was also associated with rotavirus diarrhea observed in the patient. CONCLUSIONS: This case presented by us and similar cases presented by other authors indicate the possible role of SARS-CoV-2 in the development of HSP, but this assumption requires further research and evidence-based verification.

Adding Methylprednisolone and Cyclophosphamide Pulse Therapy Provides No Benefit in Pediatric IgAV Nephritis Grade III.

Although immunoglobulin (Ig) A vasculitis (IgAV) nephritis is a common form of secondary pediatric glomerulonephritis, there is no consensus on an appropriate therapeutic regimen for moderate-to-severe pediatric IgAV nephritis grade III or the effectiveness of aggressive immunosuppressive therapy. The objective is to evaluate the efficacy and renal outcomes of methylprednisolone pulse therapy with or without cyclophosphamide pulse therapy for grade III IgAV nephritis in children. This retrospective, single-center study included 115 children with IgAV nephritis grade III. The primary endpoint was proteinuria reduction from moderate or severe levels to a normal level. The secondary endpoint was stable renal function, that is, an increase of less than 25% from the baseline creatinine level over the 4-month follow-up period. Among 115 children with IgAV nephritis grade III, 59 received methylprednisolone and cyclophosphamide double-pulse treatment; methylprednisolone and cyclophosphamide double-pulses did not significantly improve proteinuria remission. Proteinuria improvement did not show any difference with or without cyclophosphamide treatment. Furthermore, methylprednisolone pulse therapy showed no benefit over steroid therapy alone. The demographic and baseline disease characteristics among the treatment groups were well-balanced. The rates of complete remission in 24-hour proteinuria excretion over the 4-month follow-up period in the methylprednisolone and cyclophosphamide double-pulse, methylprednisolone plus oral prednisolone, and oral prednisolone-only groups were 91.52%, 92.31%, and 100%, respectively. Renal function remained stable in all the patients. Most patients with IgAV nephritis grade III showed a good prognosis. However, the addition of methylprednisolone and/or cyclophosphamide pulses did not offer benefits over steroid-only therapy.

A Rare Complication of Henoch-Schönlein Purpura/IgA Vasculitis in an Adult Woman After COVID-19 Infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can affect multiple organs due to activation of an inflammatory response. One of the key components of this response is the activation of immunoglobulin A (IgA), thus causing endothelial injury and inflammation. Henoch-Schönlein purpura (HSP) has been rarely reported in adult patients as a complication of the coronavirus disease 2019 (COVID-19) infection. In this report, we present a case of HSP occurring one week after the diagnosis of COVID-19 in a 23-year-old woman. Her symptoms included nausea, vomiting, diffused abdominal pain, joint pain, hematuria, and palpable purpura of the lower extremities. She was treated with intravenous methylprednisolone sodium succinate, followed by oral prednisone therapy, which resulted in clinical improvement, including resolution of abdominal and joint pain as well as skin rashes, without remaining renal complication.

Development of IgA vasculitis with severe glomerulonephritis after COVID-19 vaccination: a case report and literature review.

With the worldwide spread of the COVID-19 vaccine program during the COVID-19 pandemic, the numbers of reported cases with new-onset or relapsed kidney disease/vasculitis such as minimal change nephrotic syndrome, immunoglobulinA (IgA) nephropathy, and IgA vasculitis (IgAV) that developed after COVID-19 vaccination are increasing. We present the case of a 67-year-old Japanese woman who developed IgAV with purpura on her extremities and trunk in the evening of the day that she received the second dose of the Pfizer-BioNTech COVID-19 vaccine. She subsequently presented with acute kidney injury and nephrotic syndrome, and a kidney biopsy performed 14 days after the second vaccination showed diffuse mesangial and endocapillary glomerulonephritis with necrotizing crescent formation, accompanied by IgA deposition. One steroid pulse plus four administrations of a monthly intravenous cyclophosphamide injection were applied, followed by oral azathioprine during oral steroid tapering. Her response to this treatment was unsatisfactory and intractable for some time. Eventually, her renal function improved and nephrotic syndrome was resolved, while microscopic hematuria and proteinuria at ~ 1 g/gCr remained at 6 months post-vaccination. Unlike the previous milder renal-involved IgAV cases following COVID-19 vaccination, our patient's case presented severe glomerulonephritis and took a long time to recover despite intensive initial immunosuppressive treatment.

Urinary Protein Array Analysis to Identify Key Inflammatory Markers in Children with IgA Vasculitis Nephritis.

Chronic kidney disease is a recognised complication of immunoglobulin A vasculitis, (IgAV; formerly Henoch-Schonlein purpura-HSP). The pathophysiology of IgAV and why some patients develop significant renal involvement remains largely unknown. Identifying urinary inflammatory markers could direct targets for earlier intervention. The aim of this cross-sectional exploratory study was to perform a large protein array analysis to identify urinary markers to provide insight into the mechanisms of kidney inflammation in children with established IgAV nephritis (IgAVN). Determination of the relative levels of 124 key proteins was performed using commercially available proteome profiler array kits. Twelve children were recruited: IgAVN, n = 4; IgAV without nephritis (IgAVwoN), n = 4; healthy controls (HCs), n = 4. The urinary concentrations of twenty proteins were significantly different in IgAVN compared to IgAVwoN. The largest fold changes were reported for B-cell activating factor (BAFF), Cripto-1, sex-hormone-binding globulin and angiotensinogen. The urinary levels of complement components C5/C5a and factor D were also significantly elevated in patients with IgAVN. A total of 69 urinary proteins significantly raised levels in comparisons made between IgAVN vs. HCs and nine proteins in IgAVwoN vs. HCs, respectively. This study identified key urinary proteins potentially involved in IgAVN providing new insight into the pathophysiology. Further longitudinal studies with larger cohorts are needed to quantitatively analyse these biomarkers.