Intestinal dysbiosis featuring abundance of Streptococcus associates with Henoch-Schönlein purpura nephritis (IgA vasculitis with nephritis) in adult.

BACKGROUND: The pathogenesis of Henoch-Schönlein purpura nephritis (HSPN) is closely associated with mucosal infection. But whether intestinal microbiota dysbiosis plays a role in it is not clear. METHODS: A total of 52 participants including 26 HSPN patients and 26 healthy controls were included. By using 16S ribosomal RNA gene sequencing, the intestinal microbiota composition between HSPN and healthy controls was compared. The diagnostic potency was evaluated by Receiver operating characteristic (ROC) with area under curves (AUC). Meanwhile, correlation analysis was also performed. RESULTS: The lower community richness and diversity of fecal microbiota was displayed in HSPN patients and the structure of gut microbiota was remarkedly different. A genus-level comparison indicated a significant increase in the proportions of g-Bacteroides, g-Escherichia-Shigella and g-Streptococcus, and a marked reduction of g-Prevotella_9 in HSPN patients, suggesting that the overrepresentation of potential pathogens and reduction of profitable strains were the main feature of the dysbiosis. The differential taxonomic abundance might make sense for distinguishing HSPN from healthy controls, with AUC of 0.86. The relative abundance of the differential bacteria was also concerned with clinical indices. Among them, Streptococcus spp. was positively associated with the severity of HSPN (P < 0.050). It was found that HSPN patients with higher level of Streptococcus spp. were more likely to suffering from hematuria and hypoalbuminemia (P < 0.050). CONCLUSIONS: The dysbiosis of gut microbiota was obvious in HSPN patients, and the intestinal mucosal streptococcal infection was distinctive, which was closely related to its severity.

Streptococcal infection in childhood Henoch-Schönlein purpura: a 5-year retrospective study from a single tertiary medical center in China, 2015-2019.

BACKGROUND: The present study focuses on the associations of streptococcal infection with the clinical phenotypes, relapse/recurrence and renal involvement in Henoch-Schönlein purpura (HSP) children. METHODS: Two thousand seventy-four Chinese children with HSP were recruited from January 2015 to December 2019. Patients' histories associated with HSP onset were obtained by interviews and questionnaires. Laboratory data of urine tests, blood sample and infectious agents were collected. Renal biopsy was performed by the percutaneous technique. RESULTS: (1) Streptococcal infection was identified in 393 (18.9%) HSP patients, and served as the most frequent infectious trigger. (2) Among the 393 cases with streptococcal infection, 43.0% of them had arthritis/arthralgia, 32.1% had abdominal pain and 29.3% had renal involvement. (3) 26.1% of HSP patients relapsed or recurred more than 1 time within a 5-year observational period, and the relapse/recurrence rate in streptococcal infectious group was subjected to a 0.4-fold decrease as compared with the non-infectious group. (4) No significant differences in renal pathological damage were identified among the streptococcal infectious group, the other infectious group and the non-infectious group. CONCLUSIONS: Streptococcal infection is the most frequent trigger for childhood HSP and does not aggravate renal pathological damage; the possible elimination of streptococcal infection helps relieve the relapse/recurrence of HSP.

Vasculitis IgA en el adulto. Informe de caso / IgA vasculitis in adults. Case report

RESUMEN La vasculitis IgA, también conocida como púrpura de Schönlein-Henoch, es una vasculitis leucocitoclástica que involucra pequeños vasos con depósito de inmunocomplejos IgA. Puede abarcar piel, articulaciones, riñones y tracto gastrointestinal. Su presentación en adultos es rara, y las formas clínicas suelen ser más agresivas. Es objetivo del presente trabajo describir el curso y evolución de vasculitis IgA, en un paciente de 59 años, con púrpuras en miembros inferiores y tronco, hematuria macroscópica, y edema de miembros inferiores. Los complementarios mostraron creatininas elevadas, proteinuria de rango nefrótico, elevación de la IgA y anticuerpos contra el citoplasma de los neutrófilos negativos. Se descartaron causas neoplásicas. El estudio anatomo-patológico del riñón concluyó una vasculitis IgA.

ABSTRACT IgA vasculitis, also known as Henoch-Schönlein purpura, is a leukocytoclastic vasculitis that involves small vessels with deposition of IgA immune complexes. It can include skin, joints, kidneys, and gastrointestinal tract. Its presentation in adults is rare, and the clinical forms are usually more aggressive. The objective of this study is to describe the course and evolution of IgA vasculitis, in a 59-years-old patient, with purples in the lower limbs and trunk, macroscopic hematuria, and lower limb edema. The complementary ones showed elevated creatinines, nephrotic range proteinuria, elevated IgA and negative antibodies against the cytoplasm of neutrophils. Neoplastic causes were dismissed. The anatomical-pathological study of the kidney concluded IgA vasculitis.

Gastrointestinal Henoch-Schönlein purpura successfully treated with Mycophenolate Mofetil: Description of 2 case reports.

RATIONALE: Henoch-Schönlein Purpura (HSP) is an acute small vessel vasculitis. It is the most common vasculitis in children. In majority of the cases, the disease is self-limited. Relapses can occur, in particular during the first year of the disease. There is no consensus on a specific treatment. The efficacy and safety of steroidal treatment in treating HSP is still controversial. Immunosuppressive treatment of HSP nephritis is used in patients with severe renal involvement (nephrotic range proteinuria and/or progressive renal impairment). The literature on immunosuppressive treatment of severe HSP without kidney involvement is scanty. PATIENTS CONCERNS: We report 2 case reports of 2 adolescents affected from Henoch-Schönlein Purpura and severe gastrointestinal involvement. Both patients presented a poor response to steroids treatment. DIAGNOSES: The diagnosis of HSP was made according to the diagnostic criteria published by European League against Rheumatism and Pediatric Rheumatology European Society in 2006. INTERVENTIONS: In consideration of the recurrence of the Henoch Schönlein Purpura and the gastrointestinal involvement, we decided to start Mycophenolate Mofetil treatment. OUTCOMES: In both patients all clinical manifestations resolved in few days. LESSONS: In our cases of HSP with gastrointestinal involvement Mycophenolate Mofetil treatment has been very effective. This experience teaches us that immunosuppressive agents may be very useful to induce and maintain remission not only in renal involvement, but in all cases of persistent, recurrent, or complicated Henoch Schönlein Purpura in children.

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.

Purpurona: A Novel Report of COVID-19-Related Henoch-Schonlein Purpura in a Child.

The coronavirus disease 2019 global pandemic is reshaping our understanding of medicine, including the diagnostic approach to common medical presentations. We describe a novel case of a 3-year-old male with a clinical diagnosis of Henoch-Schonlein Purpura vasculitis with concurrent SARS-CoV-2 infection. This case highlights a potentially newly described presentation of coronavirus disease 2019 infection.

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.

The characteristics of video capsule endoscopy in pediatric Henoch-Schönlein purpura with gastrointestinal symptoms.

BACKGROUND: Henoch-Schönlein purpura (HSP) is a systemic small-vessel vasculitis also named IgA vasculitis that commonly affects the gastrointestinal tract. The video capsule endoscopy (VCE) characteristics of pediatric HSP patients are rarely reported. METHODS: Patients diagnosed with HSP and analyzed by VCE examination at our hospital from February 2010 to January 2019 are enrolled. The clinical features, laboratory findings, and the characteristics of VCE findings are studied. RESULTS: There are 30 patients enrolled in this investigation from February 2010 to January 2020. The mean age of these patients is 96.9 ± 35.8 months, and the most frequent finding of VCE is mucosal erosion, which account for 79.3% of the patients, and followed by mucosal erythema or petechia accounted for 69% of the patients. Regarding the disease location detected by endoscopy, jejunum is the most common involved part of the gastrointestinal tract in pediatric HSP patients. All the patients had the jejunum involved except in one patient the VCE did not pass through the pylorus. One third of the patients involved the descending portion of duodenum. No side effect is observed in this study. CONCLUSIONS: VCE may be an excellent adjust tool for evaluation of the gastrointestinal tract in children with abdominal symptoms without typical purpura in suspected pediatric HSP patients. VCE appears to be superior to esophagogastroduodenoscopy in detecting small intestinal lesions of HSP and has an excellent safety profile.

Obesity is associated with severe clinical course in children with Henoch-Schonlein purpura.

BACKGROUND: We aimed to evaluate the role of obesity on the clinical course and response to treatment in patients with Henoch-Schonlein purpura (HSP). METHODS: Data charts of children with HSP followed in a tertiary hospital between 2000 and 2018 were reviewed retrospectively. Persistent purpura was defined as skin involvement persisting for ≥ 30 days. Mild nephropathy was defined as the presence of microscopical hematuria and/or non-nephrotic proteinuria, while severe nephropathy as nephrotic proteinuria, nephritic syndrome, and/or kidney insufficiency. Obese and non-obese patients were compared for demographic, clinical, and laboratory parameters. RESULTS: There were 199 patients (M/F, 104/95; median (IQR) presenting age 7.1 (5.0-9.2) years; follow-up period 17.5 (6-50) months). Obese patients (n = 35 (17.6%)) had significantly higher rate of persistent purpura (46% vs 21%), severe renal involvement (58% vs 31%), high-grade renal histopathological lesions (83% vs 39%), hypertension (29% vs 9%), and increased erythrocyte sedimentation rate (79% vs 56%). Obese patients also showed delayed improvement of cutaneous (25 vs 14 days), articular (12.5 vs 10.0 days), and kidney (280 vs 57 days) symptoms. Obese children used steroids for significantly longer period of time (236 vs 40 days). Furthermore, need for immunosuppressive medications were higher in obese patients (40% vs 9%). CONCLUSIONS: Obese children with HSP had higher erythrocyte sedimentation rate, hypertension, and severe renal involvement; showed delayed improvement of skin, joint, and kidney findings; and need more immunosuppressive medications and a longer period of steroid treatment. These findings may be associated with the effect of adipose tissue on inflammation.

Hypertension in the absence of urinary abnormalities - An unusual presentation of anaphylactoid purpura.

Henoch-Schonlein Purpura (HSP) or anaphylactoid purpura, currently named IgA vasculitis is the most common form of systemic vasculitis in children. In adults and young infants, HSP tends to have atypical presentations with higher rates of severe gastrointestinal problems and delayed renal complications. While hypertension is a known complication of HSP nephritis, it is rarely seen in individuals with normal renal function and urinary findings. We report a case of a 7-year-old boy with HSP, who presented with abdominal pain and severe hypertension without other features of glomerulonephritis.

Recurrent Henoch-Schönlein Purpura with bullous rash and pulmonary nodules.

BACKGROUND: Henoch-Schönlein purpura (HSP) is the most common vasculitis of childhood. It has a characteristic rash described as palpable purpura that most frequently affects the distal lower extremities and buttocks. HSP rarely presents with bullous rash nor pulmonary nodules. CASE PRESENTATION: We present a novel case of a 12-years-old female with recurrent pediatric HSP with a combination of the rare manifestations of bullous rash and pulmonary nodules. She initially presented with the bullous rash, chest pain, cough, and abdominal pain. Patient was successfully treated with intravenous pulse corticosteroids followed by a high dose oral corticosteroid taper, with resolution of the bullous rash and pulmonary nodules. CONCLUSION: The rare manifestations of scarring bullous rash and pulmonary nodules can be presenting features of pediatric HSP, the combination of which has not been previously reported. The treatment of intravenous corticosteroid resolved patient's abdominal symptoms, rash and pulmonary nodules.

Severe Attack of Henoch-Schönlein Purpura With Neurological Involvement During Adalimumab Treatment for Crohn's Disease.

Tumour necrosis factor-α [TNF-α] inhibitors have revolutionised the management of chronic inflammatory conditions. A number of cutaneous adverse events have been reported with TNF inhibition, including vasculitis. Most reactions are mild and rarely warrant treatment withdrawal. Here we describe a patient with Crohn's disease treated with adalimumab in whom severe multivisceral Henoch-Schönlein purpura developed, including neurological involvement, requiring definitive TNF blocker withdrawal.

Prognostic implications of normal or minimal urinary findings on long-term renal impairment in adults with Henoch-Schönlein purpura.

BACKGROUND: Renal involvement in adult Henoch-Schönlein purpura is a major cause of morbidity and can lead to significant long-term renal impairment. The prognostic significance of normal or minimal urinary abnormalities at diagnosis is unknown. OBJECTIVE: To assess the risk of long-term renal impairment in patients with Henoch-Schönlein purpura who present with normal or minimal urinary abnormalities. METHODS: Retrospective cohort study of adult Henoch-Schönlein purpura patients presenting with normal urinalysis results, microscopic hematuria, or low-grade proteinuria. Patients were followed for development of long-term renal impairment, with adjusting for comorbidities. RESULTS: Forty-seven patients were included, with median follow-up 73.9 months (interquartile range 35 to 98 months). Thirty-nine patients (83.0%) had abnormal urinalysis results, of whom 15 (38.5%) progressed to long-term renal impairment. In contrast, 8 patients (17%) had normal urinalysis results, of whom only 1 (12.5%) developed long-term renal impairment (adjusted hazard ratio 10.58; 95% confidence interval 1.18-94.73). Renal events occurred at a median 36.1 months (interquartile range 17.1 to 61 months) from diagnosis, earlier in patients with comorbidities compared with those with none, and in a constant event rate over time. LIMITATIONS: Small sample size. CONCLUSIONS: Microscopic hematuria and low-grade proteinuria at Henoch-Schönlein purpura diagnosis is a poor prognostic sign for the development of long-term renal impairment. This population should be targeted for prolonged surveillance.

Risk factors associated with IgA vasculitis with nephritis (Henoch-Schönlein purpura nephritis) progressing to unfavorable outcomes: A meta-analysis.

OBJECTIVE: To identify risk factors associated with unfavorable outcomes in children with IgA vasculitis with nephritis (Henoch-Schonlein purpura nephritis)(IgA-VN). METHODS: PubMed, Embase, and Web of Science databases were searched for studies, published in English through February 2019. The data were extracted to perform pooled analysis, heterogeneity testing, subgroup analysis, sensitivity analysis, and publication bias analysis. RESULTS: This meta-analysis showed that, older age at onset (WMD 1.77, 95% CI 0.35-3.18, p = 0.014), lower glomerular filtration rate (GFR; WMD -23.93, 95% CI -33.78- -14.09, p<0.0001), initial renal manifestations with nephrotic syndrome (OR 1.74, 95% CI 1.12-2.70, p = 0.013), with nephritic-nephrotic syndrome (OR 4.55, 95% CI 2.89-7.15, p<0.0001) and renal biopsy with crescentic nephritis (International Study of Kidney Disease in Children [ISKDC] grades III-V) (OR 3.85, 95% CI 2.37-6.28, p<0.0001) were significant risk factors associated with poor outcomes in IgA-VN, whereas initial clinical features with hematuria (OR 0.33, 95% CI 0.16-0.69, p = 0.003) and mild proteinuria±hematuria (OR 0.46, 95% CI 0.28-0.75, p<0.0001) were associated with progression to good outcomes. By contrast, gender, hypertension and initial renal manifestations of acute nephritic syndrome were not significantly associated with poor outcomes in IgA-VN. CONCLUSION: This meta-analysis showed that older age at onset, lower GFR, initial renal features of nephrotic syndrome and nephritic-nephrotic syndrome and renal biopsy with crescentic nephritis (ISKDC grades III-V) were predictive of poor prognosis in children with IgA-VN.

Early recognition and treatment of Henoch-Schönlein purpura in children.

Henoch-Schönlein purpura (HSP) is characterised by a non-blanching rash, which commonly affects the lower limbs of children aged 3-15 years. It is the most common vasculitis in children. HSP often develops after an upper respiratory tract infection and is more likely to present in autumn, winter and spring. The majority of cases resolve with symptomatic treatment although some cases may progress to serious complications, including renal involvement. A case study is presented and differential diagnoses are explored. The pathophysiology of HSP is discussed. Nurses are often the first to assess patients so they are in an ideal position to recognise and treat HSP early on. Admission of a child into hospital is a stressful event for the parents and child; the nurse can help by ensuring prompt admission to hospital and offering support and reassurance to the family.

Anaphylactoid Syndrome of Pregnancy.

Anaphylactoid syndrome of pregnancy (ASP) is a widespread, proinflammatory, anaphylactic-like reaction that can occur when amniotic fluid enters the maternal blood circulation. ASP is characterized by four cardinal findings: respiratory distress, altered mental status, hypotension, and disseminated intravascular coagulation. ASP is commonly associated with maternal and neonatal mortality. Early recognition followed by prompt and aggressive treatment can improve survival rates and are among the most critical activities for nurses and other clinicians caring for women with ASP.

Sex Differences in Pediatric Rheumatology.

Autoimmune diseases affect up to 10% of the world's population and, as a whole, they are far more common in females, although differences exist according to the single disease and also in different age groups. In childhood-onset autoimmune diseases, the sex bias is generally less evident than in adults, probably for the different hormonal milieau, being estrogens strongly implicated in the development of autoimmunity. Still, some rheumatic conditions, such as juvenile idiopathic arthritis (JIA), show a strong predilection for girls (F:M = 3-6.6:1), and differences may coexist between males and females regarding disease outcome. For example, chronic anterior uveitis associated with JIA affects more commonly girls but boys tend to have a more severe course. Systemic lupus erythematosus predominantly affects girls and women (F:M = 3-5:1 in children, F:M = 10-15:1 in adults). Behςet's disease has been reported to be more prevalent in adult males (F:M = 1:1-4); in children, there are no differences. The sex ratio is equal in children and adults for Henoch-Schönlein purpura (F:M = 1:1). A higher male-to-female ratio exists for Kawasaki disease (F:M = 1:1.1-1.6 in children, F:M = 1:1,5 in adults). Juvenile dermatomyositis (F:M = 2-5:1), systemic sclerosis (F:M = 4:1 in children, F:M = 6:1 in adults), and Takayasu arteritis (F:M = 2:1 in children, F:M = 7-9:1 in adults) are more common in girls and women then in boys and men. There is no gender bias for acute rheumatic fever in children, while in adults, the F:M ratio is 2:1. Given that estrogen levels are not different between genders during childhood, pediatric rheumatic diseases could represent good models to study other mechanisms related to the development of autoimmunity. Recently, the levels of miRNA expression, and their variation according to sex chromosomes, have been linked to the development of autoimmune diseases, with different impact among sexes. This review will focus not only on the sex bias reported in the more common rheumatic conditions of childhood, focusing on differences in incidence, but also on outcome and trying to depict the mechanisms underlying those differences.

Circulating suPAR as a biomarker of disease severity in children with proteinuric glomerulonephritis.

BACKGROUND: The increase of circulating urokinase plasminogen activator receptor (suPAR) was demonstrated in various diseases showing its prognostic value as well as the link to the inflammatory reaction. In glomerular diseases, suPAR was considered a causative factor of proteinuria. In the present study we aimed to evaluate serum concentration of suPAR in children with primary and secondary glomerulonephritis (GN) and its association with disease severity. METHODS: The study involved 22 children with minimal change disease (MCD), nine with primary focal segmental glomerulosclerosis (FSGS), seven with Henoch-Schönlein nephritis, seven with lupus nephritis (LN) and 16 controls. RESULTS: Serum suPAR was significantly higher in children with FSGS and LN than controls (4.47±1.39 ng/mL vs. 3.23±0.76 ng/mL; P=0.011 and 6.17±1.12 ng/mL vs. 3.23±0.76 ng/mL, respectively; P<0.0001). Further, suPAR was increased in LN when compared to FSGS (P=0.031). In the total group suPAR showed negative correlation with eGFR, serum complement C3 and positive with left ventricular mass index. In children with MCD and FSGS the inverse association of suPAR with eGFR was also shown. CONCLUSIONS: In children with primary and secondary glomerulonephritis suPAR levels are not associated with proteinuria. In primary GN elevated suPAR levels may result from reduced eGFR reflecting renal damage. In LN circulating suPAR can be increased further indicating both multi-organ involvement and systemic inflammation reflecting disease severity.