IgA Vasculitis Research Articles

Endothelial Damage-dominant Nephritis Related to IgA Vasculitis after 11 Years' Use of Infliximab for Rheumatoid Arthritis.

A 43-year-old Japanese woman with rheumatoid arthritis treated by infliximab and methotrexate for 11 years was admitted for proteinuria and purpura. A kidney biopsy revealed endothelial damage-dominant nephritis with IgA deposition. Infliximab and methotrexate were discontinued, and tocilizumab was started; however, proteinuria persisted. Therefore, tocilizumab was discontinued, and oral prednisolone and methylprednisolone pulse therapy were administered. After 6 months, urinary protein was less than 0.1 g/day, and purpura subsided. To our knowledge, this is the first case of endothelial damage-dominant nephritis related to IgA vasculitis involving the skin and kidney after long-term use of infliximab and methotrexate.

Thalidomide-Induced IgA Vasculitis in a Post-Autologous Stem Cell Transplant Recipient.

Thalidomide-Induced IgA Vasculitis in a Post-Autologous Stem Cell Transplant Recipient.

IgA Vasculitis and C3 Glomerulonephritis: One Patient... Various Autoimmune Diseases

Leucocytoclastic vasculitis refers to a small vessel vasculitis caused by immune complexes, infections and medications. IgA or IgM/IgG immune complexes can be found in direct immunofluorescence studies suggesting specific forms of leucocytoclastic vasculitis. Some authors suggested that IgA vasculitis and IgA nephropathy were two clinical mani- festations of the same disease. From a histological point of view, it is not possible to distinguish a glomerulonephritis as part of an IgA vasculitis from an IgA nephropathy.The authors present a case of a 50-year-old woman diagnosed with vitiligo ad immune thrombocytopenic purpura (ITP). ITP was diagnosed 2 years before the present case. She presented to the autoimmune diseases’ appointment with a pruriginous rash of the lower extremities over the last 3 months. Skin biopsy was suggestive of leukocytoclastic vasculitis, revealing deposits of C3, IgG (less intensity) and IgA. IgA vasculitis was then assumed. After a few weeks, she kept peripheral edema, but an increasing decline in renal function was detected. Therefore, a renal biopsy was performed, which revealed endocapilar proliferative glomerulonephritis and predominantly C3 mesangial deposits, with IgA and vestigial IgM. These results were compatible with a C3 glomerulonephritis. The patient was started on systemic steroid treatment with prednisolone 1 mg/kg/day and ramipril 2.5 mg/day with progressive normalization of renal function.With this case, the authors emphasize the possibility that all these manifestations could be part of the same disease spectrum, but also, the importance of complement activation. So, this case may constitute additional evidence of the complement activation in pathogenesis of this vasculitis, however, further investigation is need, particularly to understand C3 glomerulonephritis, a rare kidney disease.

Spectrum of auto-inflammatory diseases in Morocco: a monocentric experience.

Auto-inflammatory diseases (AIDs) result from mutations in genes of the innate immune system leading to periodic multisystemic inflammation. We aimed to describe the clinical, biological and molecular features (when available) and outcomes of Moroccan patients with AIDs. Patient data were collected retrospectively and analysed over a 13-year period. Among 30 patients, 60% had FMF, 16% mevalonate kinase deficiency (MKD) and 24% other AIDs. The mean age at first consultation was 6.9 years, and the mean diagnostic delay was 3 years. Consanguinity was reported in 16 cases. IgA vasculitis was associated with 33% of FMF patients, in whom the main clinical features were fever (88.8%), abdominal pain (100%), arthralgias (88.8%) and arthritis (50%), and the most frequent mutation was M694V (66%). All FMF patients were treated with colchicine. Most MKD patients were confirmed by elevated urinary mevalonic acid levels, and four of five MKD patients received targeted therapy. Chronic recurrent osteomyelitis patients were confirmed by radiological and histological analysis. Two cases of Marshall syndrome were diagnosed according to validated criteria. A case of familial pustular psoriasis was diagnosed based on histological analysis and a patient with Muckle-Wells syndrome by clinical features. The outcome was favourable in 76%, partial in 13%, and three deaths were reported. FMF and MKD are the most reported diseases. AIDs are probably underestimated because they are unknown to clinicians. The aim of this work is to raise awareness among paediatricians about AIDs and create a network for best practice.

Lichen planus with IgA vasculitis: a rare association

<p>Lichen planus is an inflammatory skin disorder which has been shown to be associated with thyroid disorders, hepatitis B, hepatitis C. IgA vasculitis is a form of cutaneous small vessel vasculitis (CSVV) characterized by palpable purpura, abdominal pain and joint pain usually seen in children. We report a case of 45-year-old female patient came with violaceous itchy lesions which were distributed over trunk and extremities of 1 month duration. Complete blood count (CBC) and serum biochemistry tests were normal. Histopathology of violaceous lesions showed changes of lichen planus. Purpuric lesions showed mild perivascular and transmural inflammatory infiltrate, composed mainly of neutrophils and few lymphocytes in the superficial dermis. Direct immunofluorescence was positive for IgA (granular pattern along with vessel walls of small vessels). Based on clinical, histopathological findings, a diagnosis of lichen planus with IgA vasculitis was made. The patient was treated with 30 mg prednisolone, gradually tapered over 6 weeks and anti-histamines. Satisfactory response was observed at follow-up at 6 weeks. Our case highlights the rare association of lichen planus with IgA vasculitis. Thorough evaluation of the patient helped in reaching correct diagnosis. </p>

Landscape of intestinal microbiota in patients with IgA nephropathy, IgA vasculitis and Kawasaki disease.

To explore the common differential flora of IgAN, Kawasaki disease and IgA vasculitis by screening and analyzing the differential intestinal flora between the three disease groups of IgAN, Kawasaki disease and IgA vasculitis and their healthy controls. Papers on 16srRNA sequencing-related intestinal flora of IgAN, Kawasaki disease and IgA vasculitis were searched in databases, the literature was systematically collated and analysed, the original data was download from the relevant databases, and then the operational taxonomic unit and species classification analysis were performed. Besides, Alpha diversity analysis and Beta diversity analysis were performed to screen for IgAN, Kawasaki disease and I1gA vasculitis groups and finally compare the common intestinal differential flora among the three groups. Among the common differential flora screened, Lachnospiracea_incertae_sedis was lower in both the IgAN and Kawasaki disease groups than in the respective healthy controls; Coprococcus was low in the IgAN group but high in the IgA vasculitis group. Fusicatenibacter was lower in both the Kawasaki disease and IgA vasculitis groups than in their respective healthy controls, and Intestinibacter was low in the Kawasaki disease group, but its expression was high in the IgA vasculitis group. The dysbiosis of the intestinal flora in the three groups of patients with IgAN, Kawasaki disease and IgA vasculitis, its effect on the immunity of the organism and its role in the development of each disease group remain unclear, and the presence of their common differential flora may further provide new ideas for the association of the pathogenesis of the three diseases.

IgA vasculitis presenting as nephrotic syndrome following COVID-19 vaccination: a case report

BackgroundFollowing the strong recommendation for coronavirus disease 2019 (COVID‑19) vaccination, many patients with medical comorbidities are being immunized. However, the safety of vaccination in patients with autoimmune diseases has not been well established. We report a new case of biopsy-proven IgA vasculitis with nephritis presenting as a nephrotic syndrome after mRNA COVID-19 vaccination in a patient with a history of leukocytoclastic vasculitis.Case presentationA 76-year-old man with a history of cutaneous leukocytoclastic vasculitis presented with purpura in both lower limbs, followed by nephrotic syndrome after the second dose of BNT162b2 mRNA COVID-19 vaccination. Skin and renal biopsy revealed IgA vasculitis with nephritis. The patient’s past medical history of leukocytoclastic vasculitis and features of chronicity in renal pathology suggest an acute exacerbation of preexisting IgA vasculitis after COVID-19 vaccination. After the steroid and renin-angiotensin system inhibitor use, purpura and acute kidney injury recovered within a month. Subnephrotic proteinuria with microscopic hematuria remained upon follow-up.ConclusionPhysicians should keep in mind the potential (re)activation of IgA vasculitis following mRNA COVID-19 vaccines. It is important to closely monitor COVID-19 vaccinated patients, particularly those with autoimmune diseases.

1850. Purpura Fulminans and Invasive Streptococcus pneumoniae in Immunocompetent individual

Abstract Background Purpura Fulminans (PF) associated with invasive Streptococcus pneumoniae (ISP) is extremely rare. We present a case of PF associated with ISP in an immunocompetent person. Methods 45-year-old male previously healthy, presented with fall, and dizziness for 1 day, preceded by bloody bowel movements and abdominal pain. On arrival to ED, he had shortness of breath, chest tightness and headache. He had a temperature of 101.7 F, HR 128 BPM, RR 37 BPM, and SpO2 94% RA. He had coarse breath sounds bilaterally, petechial and purpuric rash on chest, lips, bilateral upper and lower extremities. Laboratory findings were significant for WBC 39.3 10*3/uL, Hemoglobin 9.3 g/dL, platelets 33 10*3/uL, creatinine 2.8 mg/dl, AST 523, ALT 242, total bilirubin 3.2 with direct 1.5. INR was 2.86, PT 28.9, PTT 57.2, D dimer >20, and fibrinogen 175. CK was 16,295, ferritin 5294, and LDH 1749. Blood smear revealed schistocytes. Blood cultures grew Streptococcus pneumoniae. He was found to be in DIC, with multi organ failure. Over the course of stay he required O2 support with HFNC of 30 L/min. CT chest showed bilateral ground glass opacities. CT A/P was unremarkable. Autoimmune work up including ANA, ANCA, completement and immunoglobulin levels were unremarkable. HIV and hepatitis panel were negative. TTE negative for vegetations. LP could not be performed due to low platelets. He was started on ceftriaxone 2gm IV Q12. He was given 2 doses of IVIG and 3 days of methylprednisolone 1gm due to initial concerns IgA vasculitis. Results However, skin biopsy revealed small vessel neutrophilic vasculitis with thromboses consistent with purpura fulminan. Conclusion PF is an acute purpuric rash characterized by coagulation of the microvasculature, leading to purpuric lesions and skin necrosis. It is rapidly progressive and is often accompanied by disseminated intravascular coagulation and circulatory collapse. However, it is extremely rare in immunocompetent individuals. Upon our literature review there are only handful of case reports that has described the association of ISP with PF in immunocompetent individual. Our case highlights such rare association and stress on early recognition and treatment as it can cause significant morbidity and mortality. Disclosures All Authors: No reported disclosures.

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.

Variations in Urinary Renin-Angiotensin-Aldosterone Component Concentrations in Paediatric IgA Vasculitis Nephritis

IgA Vasculitis (IgAV) is the most common form of vasculitis in children, and 1–2% of patients develop chronic kidney disease. In other forms of glomerulonephritis, there is strong evidence to support the role of the renin-angiotensin-aldosterone system (RAAS); however, data are lacking in IgAV nephritis. This study evaluated urinary RAAS components in children with IgA vasculitis, both with nephritis (IgAVN) and without nephritis (IgAVwoN). Urinary concentrations of renin, angiotensinogen and aldosterone were quantified using ELISAs. In total, 40 patients were included: IgAVN n = 9, IgAVwoN n = 17, HC n = 14, with a mean age of 8.3 ± 3.3 years. Urinary renin demonstrated no trend with nephritis. Urinary angiotensinogen was statistically significantly elevated in IgAV (1.18 ± 1.16 ng/mmol) compared to HC (0.28 ± 0.27 ng/mmol, p = 0.0015), and IgAVN (2.00 ± 1.22 ng/mmol) was elevated compared to IgAVwoN (0.74 ± 0.89 ng/mmol, p = 0.0492) and HC (p = 0.0233). Urinary aldosterone levels were significantly elevated in IgAV (1236 ± 1438 pg/mmol) compared to HC (73.90 ± 65.22 pg/mmol, p < 0.0001); this was most increased in IgAVwoN patients (1793 ± 1507 pg/mmol; IgAVN 183.30 ± 111.30 pg/mmol, p = 0.0035, HC p < 0.0001). As expected, the RAAS system is activated in patients with IgAVN and, more surprisingly, even in those without active nephritis. Further studies are needed to fully understand the role of the RAAS system in IgA vasculitis.

Demographics, clinical, laboratory findings and treatment results of pediatric patients with IgA Vasculitis: Single-center experience

Objective: Immunoglobulin A (IgA) vasculitis (IgAV), also known as Henoch-Schönlein purpura (HSP), is a vasculitis characterized by the accumulation of IgA in the vessel walls. In this study, we purposed to evaluate the demographics, clinical and laboratory findings, and treatment and treatment responses of patients diagnosed with IgAV/HSP in our center.
 Methods: The records of 201 IgAV/HSP patients who were followed up in the pediatric nephrology-rheumatology clinic were evaluated retrospectively.
 Results: It was seen with the equal frequency between girls and boys. While all patients had purpura, other findings were gastrointestinal, joint, renal, subcutaneous edema, and testicular involvement, in order of frequency. The rate of patients who developed intussusception was 2.5%, and none required surgical treatment. Biopsy was performed in patients with persistent proteinuria or hematuria. Histopathological diagnoses were mesangial proliferation, crescent, and minimal change, respectively. While the rate of renal involvement was high in cases with rash and relapse (p=0.046), there was no difference in gastrointestinal and joint involvement. In the histopathological findings of the boys, the crescent was higher than in the girls (p=0.017).
 Conclusion: IgAV/HSP generally has a good prognosis, but some patients suffer from renal involvement. In our study, renal histopathology in cases with renal involvement showed milder findings in girls than in boys, but there was no difference in other findings. Renal involvement was higher in relapsed patients.

Infective endocarditis misdiagnosed as IgA vasculitis

患者青年男性，因皮肤紫癜、血尿、大量蛋白尿、肌酐升高、高血压就诊，肾组织活检病理示系膜细胞和内皮细胞增生伴新月体形成，IgA、C3、C1q沿系膜区沉积，电镜示系膜区、内皮下电子致密物沉积。心脏彩色超声示先天性心脏病，室间隔缺损。最初诊断为IgA血管炎，予甲泼尼龙 80 mg 每日1次静脉输液，环磷酰胺0.6 g 静脉输液1次，利妥昔单抗600 mg 静脉输液1次，治疗18 d后出现脑出血，治疗1个月后出现发热伴肾功能恶化（肌酐 351 μmol/L）。心脏彩色超声见室间隔缺损，破口处和二尖瓣前叶赘生物形成；血培养示血孪生球菌，最终诊断感染性心内膜炎。予左氧氟沙星 0.25 g 每日1次静脉输液+头孢曲松2 g每12小时静脉输液共8周，转外科行二尖瓣、三尖瓣成形术+室间隔缺损修补术，甲泼尼龙减量为40 mg 每日1次静脉输液并逐渐减停。治疗后患者体温正常，血培养持续阴性，治疗后14个月肌酐降至86 μmol/L。感染性心内膜炎有时表现不典型，且与IgA血管炎在临床和病理有相似之处，可能误诊为IgA血管炎。对表现为紫癜和肾小球肾炎的患者，应注意除外感染性心内膜炎。.

Effects of Shengjiangsan, white silkworm and Periostracum cicadae on cytokines in Henoch-Schönlein purpura nephritis

Henoch-Schönlein purpura (HSP, also named IgA vasculitis) is a common childhood vascular disease, which is characterized by immunoglobulin A (IgA deposition) in small blood vessels; HSP causes kidney involvement to develop Henoch-Schönlein purpura nephritis (HSPN). However, the exact pathogenesis of HSPN is not fully understood, and it is still necessary to explorer new drugs for the treatment of HSPN. In this study, bovine serum albumin (BSA), lipopolysaccharide (LPS) and carbon tetrachloride (ClC4) were used to induce IgAN in rat, and the blood stasis and heat syndrome model was established concurrently, and was combined to establish the HSPN model. The therapeutic effects of different doses of Shengjiangsan (5, 10, 20 g/kg), white silkworm (1, 2, 4 g/kg), and Periostracum cicadae (0.5, 1, 2 g/kg) on HSPN model rats were studied, then 24 h urine was collected and blood from the abdominal aorta was taken to detect the protein changes in urine and blood. Immunofluorescence staining was used assess to IgA deposition in glomeruli. Tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin 6 (IL-6), and immunoglobulin A (IgA) levels were measured in serum by enzyme-linked immunosorbent assay. Hematoxylin and eosin (H&E) and periodic acid Schiff (PAS), immunohistochemical staining was performed to observe the histopathological changes in kidney tissues. In addition, Western blotting was used to detect the changes in the expression levels of IgA, TNF-α, and toll-like receptor 4 (TLR4). In the results, Shengjiangsan, white silkworm, and Periostracum cicadae could significantly reduce the levels of urine protein, blood urea nitrogen (BUN) and serum creatinine (CREA) in HSPN rats. Serum levels of IgA, TNF-α, IL-1β, and IL-6 were significantly reduced in the treatment groups. The treatment group can effectively improve renal tissue inflammation and mesangial hyperplasia. The accumulation of IgA protein in renal tissue was significantly reduced in the treatment group. The expression of monocyte chemoattractant protein (MCP)-1, TLR4, and IgA were significantly reduced and responded in a dose-dependent manner. Moreover, levels of transforming growth factor beta 1 (TGF-β1) decreased in kidney tissues in the treatment groups. In conclusion, Shengjiangsan, white silkworm, and Periostracum cicadae could improve HSPN in rats by reducing renal inflammation and fibrosis, and the therapeutic effects of white silkworm and Periostracum cicadae were slightly better than Shengjiangsan.

Intravenous immunoglobulin therapy in immunoglobulin A vasculitis with gastrointestinal tract involvement.

The aim of this study is to evaluate the outcomes of patients who received intravenous immunoglobulin (IVIG) for immunoglobulin A vasculitis (IgAV) with gastrointestinal (GI) tract involvement, and to determine the differences between the groups that responded to IVIG and those that did not. This retrospective study comprised 152 patients with IgAV between 2018 and 2022. Sixty-five patients (43%) had GI tract involvement. Patients with IgAV-GI involvement who had been treated with IVIG were evaluated. Patients were classified with IgAV according to the 2008 Ankara-EULAR/PRINTO/PRES. Their demographics, presentation, and management are reported. Twelve (7boys/5girls) of these patients were treated with IVIG. The median age was 90.1 (31-177) months. The mean follow-up period was 30.6 ± 9.9months. All patients had skin involvement, joint involvement (arthralgia or arthritis), and abdominal pain. All 12 patients were given steroids (30mg/kg/day pulse methylprednisolone for 3-7days, followed by 2mg/kg/day steroids) before IVIG. Nine patients received cyclophosphamide treatment (four before IVIG and five after IVIG). Complete remission was achieved in 5 of the patients with IVIG. Four patients were diagnosed with IgAV concomitant familial Mediterranean fever, and colchicine treatment was initiated. IVIG may be used in steroids and/or immunosuppressive drug resistant IgAV. It can be considered as a treatment option, especially in patients with multi-organ/system involvement, comorbid inflammatory diseases such as familial Mediterranean fever, and in patients with IgAV-GI tract involvement resistant to standard treatment in the advanced pediatric age group.

Acalculous cholecystitis in the setting of immunoglobulin a vasculitis: a case report with literature review

Immunoglobulin A vasculitis (IgAV), also known as Henoch-Schönlein Purpura, is the most common childhood vasculitis which presents with a tetrad of symptoms: palpable purpura, abdominal pain, arthralgias, and renal involvement. Gastrointestinal involvement has been reported with findings including abdominal pain, pancreatitis, intussusception, ischemia, and gallbladder involvement. Our patient had the classical presentation of IgAV with additional gallbladder thickening found on imaging. He was managed conservatively for his symptoms and gallbladder thickening. This case adds to the six prior cases that we found in our literature search reported of gallbladder thickening alongside IgAV. However, this was the only case that was managed conservatively resulting in a complete resolution of symptoms.

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.

Obesity as a comorbidity in children and adolescents with autoimmune rheumatic diseases.

Childhood obesity is the public health issue with alarming rates recorded throughout developed world and an important modifiable health risk for developing various chronic diseases, with childhood-onset autoimmune rheumatic diseases among them also. The aim of this article was to summarize epidemiological, pathophysiological and clinical implication of obesity on juvenile idiopathic arthritis (JIA), childhood-onset systemic lupus erythematosus (cSLE), juvenile dermatomyositis (JDM), IgA vasculitis (IgAV) and Kawasaki disease (KD). We reviewed PubMed database and selected 74 relevant articles. Epidemiological data of obesity among children with autoimmune rheumatic diseases indicate an increased prevalence of it. Pathophysiological link between obesity, humoral adipokines and cytokines released from fat tissue and childhood-onset autoimmune rheumatic diseases is complex and still not entirely clear. From the clinical point of view, obesity was not associated with disease activity in JIA and cSLE, but proved to contribute on functional impairment in both diseases and affect poor treatment response in JIA patients. Early atherosclerosis and cardiovascular disease (CVD) development in obese children and adolescents with JIA, cSLE and JDM are certainly important obesity-related complications. Understanding how obesity affects children and adolescents with autoimmune rheumatic diseases may encourage clinicians to consider taking better preventive strategies in this population to improve their long-term outcome.

COVID-19 Vaccination as a Trigger of IgA Vasculitis: A Global Pharmacovigilance Study.

IgA vasculitis (IgAV) can occur after vaccination. We aimed to assess a potential safety signal on the association between coronavirus disease 2019 (COVID-19) vaccines and IgAV. Cases of IgAV involving COVID-19 vaccines were retrieved in VigiBase. Disproportionate reporting was assessed using the Bayesian information component (IC) with all other drugs and vaccines as control groups. Three hundred thirty patients with de novo IgAV from 24 countries were included, mostly from the United States (193/330, 58%). Fifty percent (163/328) were female and median age was 32 years (IQR 15-59), of which 33% (84/254) were young (1-17 yrs). Median time to onset of IgAV was 7 days (IQR 2-16; n = 256) and 85% (280/330) of patients were vaccinated with mRNA vaccines. Seriousness was reported in 188/324 (58%) cases. Sixty-five percent (95/147) recovered and 1% (2/147) died. A positive rechallenge was reported for 3 of 4 patients (75%). A total of 996 cases of IgAV were identified with other vaccines. There was a small significant increase in IgAV reporting with COVID-19 vaccines compared with all other drugs (IC 0.22, 95% credible interval [CrI] 0.04 to 0.35). No disproportionality signal was found between COVID-19 vaccines and other vaccines (IC -1.42, 95% CrI -1.60 to -1.28). There was no significant difference between mRNA vaccines and viral vector COVID-19 vaccines. Men and children had a significant overreporting of IgAV compared with women and adults, respectively. This study provides reassuring results regarding the safety of COVID-19 vaccines in the occurrence of IgAV compared to other vaccines.

Cardiac involvement and cardiovascular risk factors in pediatric primary systemic vasculitides.

Pediatric primary systemic vasculitides are a complex group of diseases. Vasculitis subgroups are mainly determined according to the size of the predominantly affected vessels. In patients with primary systemic vasculitis, the location of vascular involvement, the size of the vessels, the extent of vascular damage, and the underlying pathology determine the disease phenotype and severity. Cardiac involvement is rare in some pediatric vasculitis, such as IgA vasculitis and polyarteritis nodosa, while it is more common in some others like Kawasaki disease and Takayasu arteritis. On the other hand, chronic inflammation in the setting of systemic vasculitis forms a major cardiovascular risk factor. Accelerated atherosclerosis and the tendency to thrombosis are the main issues determining the cardiovascular risks in pediatric systemic vasculitis. Early diagnosis and treatment are essential in these patients to minimize morbidity and mortality. In this review, we aimed to raise physicians' awareness of cardiac involvement and cardiovascular risks in pediatric patients with primary systemic vasculitis.

Renal manifestations in vasculitides of small and medium-sized vessels

Small-vessel vasculitides, in particular, are frequently manifested in the kidneys. A distinction is made between antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) and immune complex vasculitides. Even within the AAVs there are differences with respect to renal involvement, which manifest as necrotizing glomerulonephritis (GN) but renal involvement is much rarer in eosinophilic granulomatosis with polyangiitis than in microscopic polyangiitis and granulomatosis with polyangiitis. Disease progression, organ manifestation and prognosis vary according to the ANCA status. In immune complex vasculitides (cryoglobulinemic vasculitis, IgA vasculitis, hypocomplementemic urticarial vasculitis and antiglomerular basement membrane, GBM, disease), endothelial-adjacent activation of neutrophilic granulocytes leads to local vessel wall damage with subsequent ischemic tissue damage, similar to AAV. The sparse evidence of immune complexes is different in pauci-immune AAV. Polyarteritis nodosa is adisease with variable clinical presentations with necrotizing vasculitis of small and medium-sized arteries. Intrarenal aneurysms and hemorrhages but not GN lead to renal damage. Diagnostically, the detection of specific autoantibodies (e.g. anti-GBM), cryoglobulins or increased complement turnover can be decisive. Renal biopsy with qualified immunohistopathology is particularly important in cases of initial manifestation and unclear constellation of findings. The treatment of renal vasculitis is adapted to the severity, stage of disease, extrarenal organ manifestation and pathogenesis. It ranges from glucocorticoid monotherapy to moderate immunosuppression, up to targeted biologic therapy, chemotherapy and plasmapheresis.