Dongmei Shi, Han Chan, Xia Yang, Gaofu Zhang, Haiping Yang, Mo Wang, Qiu Li
Risk factors associated with IgA vasculitis with nephritis (Henoch-Schönlein purpura nephritis) progressing to unfavorable outcomes: A meta-analysis.
PLoS One. 2019;14(10):e0223218. doi: 10.1371/journal.pone.0223218. Epub 2019 Oct 1.
Abstract/Text
OBJECTIVE: To identify risk factors associated with unfavorable outcomes in children with IgA vasculitis with nephritis (Henoch-Schőnlein 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.
R Counahan, M H Winterborn, R H White, J M Heaton, S R Meadow, N H Bluett, H Swetschin, J S Cameron, C Chantler
Prognosis of Henoch-Schönlein nephritis in children.
Br Med J. 1977 Jul 2;2(6078):11-4.
Abstract/Text
All the survivors of a series of 88 patients with Henoch-Schönlein nephritis were examined after a follow-up of six and a half to 21 years (mean 9-9). Sixty-one patients had no demonstrable abnormality; six had minor urinary abnormalities; five had hypertension without urinary abnormally or renal dysfunction; four had heavy proteinuria; eight were in chronic renal failure, three of whom were on regular dialysis; and four patients had died within 25 months of onset. Neither corticosteroids nor immunosuppressive drugs alone or in combination appeared to influence the outcome. A clinical presentation with a combination of acute nephritis and a nephrotic syndrome and a high proportion of crescents in renal biopsy specimens was associated with a poor outcome. Neither the clinical presentation nor the renal morphology were, however, precise determinants of outcome. Outcome was not related to age, associated streptococcal infection, or recurrences of the rash. The clinical state two years after presentation was compared with the state six and a half years or more after presentation in 76 patients. The clinical state had changed in 32 patients, in 17 of whom it had deteriorated. It was not possible to identify with any certainty the patients who would deteriorate (or improve). Patients who have had Henoch-Schönlein nephritis should be followed up for at least five years.
Rosanna Coppo, Simeone Andrulli, Alessandro Amore, Bruno Gianoglio, Giovanni Conti, Licia Peruzzi, Francesco Locatelli, Leonardo Cagnoli
Predictors of outcome in Henoch-Schönlein nephritis in children and adults.
Am J Kidney Dis. 2006 Jun;47(6):993-1003. doi: 10.1053/j.ajkd.2006.02.178.
Abstract/Text
BACKGROUND: Factors predictive of renal outcome were investigated in 219 cases of biopsy-proven Henoch-Schönlein purpura nephritis (HSPN); 83 children and 136 adults enrolled in a national study were followed up for up to 27 years (median, 4.5 years).
METHODS: The criterion for defining disease progression was time elapsed until doubling of baseline creatinine level and until dialysis therapy. Age, sex, data at onset (renal function, proteinuria, hematuria, hypertension, and crescents), and data during follow-up (proteinuria and therapy) were tested as covariates.
RESULTS: Multivariate Cox regression analysis indicated the following parameters as independent prognostic predictors: age (adults versus children, relative risk, 3.57; 95% confidence interval, 1.18 to 10.79; P = 0.024 for creatinine level doubling; relative risk, 14.89; 95% confidence interval, 1.72 to 129.07; P = 0.014 for dialysis therapy), sex (females versus males, relative risk, 5.71; 95% confidence interval, 1.67 to 19.55; P = 0.006 for creatinine level doubling; relative risk, 26.03; 95% confidence interval, 2.64 to 256.73; P = 0.005 for dialysis therapy), and mean proteinuria during follow-up (for each 1 g/d of protein increase, relative risk, 1.77; 95% confidence interval, 1.35 to 2.32; P < 0.001 for creatinine level doubling; relative risk, 1.73; 95% confidence interval, 1.18 to 2.52; P = 0.005 for dialysis therapy). Information for mean proteinuria levels during follow-up increased the sensitivity at logistic regression to 62.5%, with dialysis therapy as the end point. No data detected at diagnosis, including renal function impairment, proteinuria, hypertension, and crescentic nephritis (involving > 50% of glomeruli in only 2.6%), were significantly related to functional decline at multivariate Cox.
CONCLUSION: This analysis indicates that, even more than when decreased renal function, severe proteinuria, hypertension, or crescents are present at onset, the risk for progression of HSPN (greater in adults and females) was associated with increasing mean proteinuria levels during follow-up.
Evangéline Pillebout, Eric Thervet, Gary Hill, Corinne Alberti, Philippe Vanhille, Dominique Nochy
Henoch-Schönlein Purpura in adults: outcome and prognostic factors.
J Am Soc Nephrol. 2002 May;13(5):1271-8.
Abstract/Text
Henoch-Schönlein Purpura nephritis (HSPN) has been extensively studied in children but, its natural history in adults is much less known. A cohort of 250 adults suffering HSP was retrospectively analyzed for a median follow-up period of 14.8 yr. All patients had biopsies consistent with HSP (predominant IgA mesangial deposits) associated with purpura, bowel angina, and/or abdominal pain. At presentation, palpable purpura was present in 96% of patients, and arthritis was reported in 61%, and gastrointestinal involvement in 48%. Thirty-two percent of the patients showed renal insufficiency (Creatinine clearance [CrCl] <50 ml/min), usually associated with proteinuria (99%) and/or hematuria (93%). Endocapillary glomerulonephritis was the most frequent lesion on renal biopsy (61%). At the end of follow-up, patient survival was only 74%. The first cause of death was carcinoma (most of them of respiratory or digestive tract). Regarding renal function, 11% of patients reached end-stage renal failure, 13% exhibited severe renal failure (CrCl <30 ml/min), and 14% moderate renal insufficiency (CrCl <50 ml/min). Clinical remission defined as the absence of proteinuria, hematuria, and a normal renal function was achieved in only 20%. This is a retrospective study; therefore, it is not possible to demonstrate any steroid and/or cyclophosphamide efficacy in diminishing the incidence of renal insufficiency. Multivariate analysis demonstrated that renal function impairment and proteinuria level at presentation and, on renal biopsy, the degree of interstitial fibrosis, percentage of sclerotic glomeruli, and presence of glomeruli with fibrinoid necrosis were associated with a poor renal prognosis. The data indicate that clinical presentation of HSPN in adults is severe and its outcome relatively poor, worse than in children. Identification of clinical and histologic prognostic factors may permit the design of appropriate therapeutic prospective studies.
J C Davin, I J Ten Berge, J J Weening
What is the difference between IgA nephropathy and Henoch-Schönlein purpura nephritis?
Kidney Int. 2001 Mar;59(3):823-34. doi: 10.1046/j.1523-1755.2001.059003823.x.
Abstract/Text
Henoch-Schönlein purpura nephritis (HSPN) and IgA nephropathy (IgAN) are considered to be related diseases since both can be encountered consecutively in the same patient, they have been described in twins, and bear identical pathological and biological abnormalities. Apart from the presence of extrarenal clinical signs found only in HSPN, other differences are noticed between the two diseases. The peak age ranges between 15 and 30 years for a diagnosis of IgAN, whereas HSPN is mainly seen in childhood. Nephritic and/or nephrotic syndromes are more often seen at presentation in HSPN. In contrast to IgAN, HSPN has been described in association with hypersensitivity. Endocapillary and extracapillary inflammations as well as fibrin deposits in the glomerulus are more frequent in HSPN. No major biological differences have been found between the two illnesses, except for a larger size of circulating IgA-containing complexes (IgA-CC) and a greater incidence of increased plasma IgE levels in HSPN. As tissue infiltration by leukocytes is a major feature of HSPN vasculitis, a possible role of a more potent activation of the latter cells by IgA-CC and/or circulating chemokines in HSPN should be considered. Further studies are required to elucidate this possible mechanism as well as the role of hypersensitivity in HSPN.
Hiroyuki Komatsu, Shouichi Fujimoto, Norishige Yoshikawa, Hiroshi Kitamura, Hitoshi Sugiyama, Hitoshi Yokoyama
Clinical manifestations of Henoch-Schönlein purpura nephritis and IgA nephropathy: comparative analysis of data from the Japan Renal Biopsy Registry (J-RBR).
Clin Exp Nephrol. 2016 Aug;20(4):552-60. doi: 10.1007/s10157-015-1177-0. Epub 2015 Oct 11.
Abstract/Text
BACKGROUND: The clinical presentation of Henoch-Schönlein purpura nephritis (HSPN) has not been thoroughly investigated among patients of different ages. We therefore compared the features of HSPN and IgA nephropathy (IgAN) based on data from the Japan Renal Biopsy Registry (J-RBR).
METHODS: This cross-sectional study analyzed data from patients who were registered in the J-RBR between 2007 and 2012. Clinico-pathological findings at diagnosis were compared among children (aged ≤18 years), adult (aged 19-64 years) and elderly (aged ≥65 years) patients with HSPN (n = 513) and IgAN (n = 5679).
RESULTS: The age at diagnosis considerably differed between HSPN and IgAN; HSPN peaked at 1-19 and at 60-69 years, whereas IgAN peaked at 30-39 years. The clinical features were significantly more severe for HSPN than IgAN, especially proteinuria (children, 1.28 vs. 0.57; adult, 1.95 vs. 1.05; elderly patients, 2.71 vs. 1.64 g/day), and low albumin levels (children, 3.72 vs. 4.13; adults, 3.62 vs. 3.99; elderly patients, 3.07 vs. 3.57 g/dL). The rate (%) of histologically classified endocapillary proliferative or crescentic glomerulonephritis was higher in patients with HSPN than with IgAN. Multiple regression analysis revealed that low albumin level and high BP were independent factors associated with decreased estimated glomerular filtration rates in adult and elderly patients with HSPN.
CONCLUSIONS: Age at HSPN diagnosis was bimodally distributed, and the clinical features of HSPN were more severe than those of IgAN across all age groups.
A R Goldstein, R H White, R Akuse, C Chantler
Long-term follow-up of childhood Henoch-Schönlein nephritis.
Lancet. 1992 Feb 1;339(8788):280-2.
Abstract/Text
A study of long-term outcome of 78 subjects who had had Henoch-Schönlein nephritis during childhood (at a mean of 23.4 years after onset) shows that severity of clinical presentation and initial findings on renal biopsy correlate well with outcome but have poor predictive value in individuals. 44% of patients who had nephritic, nephrotic, or nephritic/nephrotic syndromes at onset have hypertension or impaired renal function, whereas 82% of those who presented with haematuria (with or without proteinuria) are normal. 17 patients deteriorated clinically from an initial assessment in 1971; 7 of these had apparently completely recovered in 1976. 16 of 44 full-term pregnancies were complicated by proteinuria and/or hypertension, even in the absence of active renal disease. These findings indicate that childhood Henoch-Schönlein nephritis requires long-term follow-up, especially during pregnancy.
Habib, R, Niaudet, P, Levy, M. Schönlein-Henoch purpura nephritis and IgA nephropathy. In: Renal Pathology with Clinical and Functional Correlations, Tisher, CC, Brenner, BM (Eds), Lippincott, Philadelphia 1993. p. 472.
Pamela F Weiss, James A Feinstein, Xianqun Luan, Jon M Burnham, Chris Feudtner
Effects of corticosteroid on Henoch-Schönlein purpura: a systematic review.
Pediatrics. 2007 Nov;120(5):1079-87. doi: 10.1542/peds.2007-0667.
Abstract/Text
OBJECTIVE: No consensus exists among general pediatricians or pediatric rheumatologists regarding whether corticosteroid therapy ameliorates the acute manifestations of Henoch-Schönlein purpura or mitigates renal injury. Therefore, we sought to synthesize the reported experimental and observational data regarding corticosteroid use.
METHODS: We performed a meta-analysis based on a comprehensive review of the literature in the Medline database (1956 to January 2007) and the Cochrane Controlled Trials Register. On the basis of reported outcomes among patients with Henoch-Schönlein purpura who were treated at diagnosis with corticosteroids compared with patients treated with supportive care only, we calculated odds ratios for the resolution of abdominal pain, the need for surgical intervention secondary to severe pain or intussusception, the likelihood of Henoch-Schönlein purpura recurrence, and the development of transient or persistent renal disease.
RESULTS: Of 201 articles retrieved from the initial literature search, 15 were eligible for inclusion. Corticosteroid treatment did not reduce the median time to resolution of abdominal pain but did significantly reduce the mean resolution time and increased the odds of resolution within 24 hours. Early corticosteroid treatment significantly reduced the odds of developing persistent renal disease. In addition, although the results were not statistically significant, the prospective data suggest reduced odds of both surgical intervention and recurrence.
CONCLUSIONS: Corticosteroids, given early in the course of illness, seem to produce consistent benefits for several major clinically relevant Henoch-Schönlein purpura outcomes.
W Chartapisak, S Opastiraku, N S Willis, J C Craig, E M Hodson
Prevention and treatment of renal disease in Henoch-Schönlein purpura: a systematic review.
Arch Dis Child. 2009 Feb;94(2):132-7. doi: 10.1136/adc.2008.141820. Epub 2008 Aug 13.
Abstract/Text
OBJECTIVE: To determine the benefits and harms of therapies used to prevent or treat renal involvement in Henoch-Schönlein purpura.
DESIGN: Systematic review of randomised controlled trials.
SETTING: Secondary and tertiary paediatric and paediatric nephrology services.
SUBJECTS: Ten trials involving 1230 children aged less than 18 years.
MAIN OUTCOME MEASURES: Persistent proteinuria and/or haematuria.
RESULTS: Meta-analyses of four trials showed no significant difference in the risk of persistent kidney disease at 6 months (379 children; relative risk (RR) 0.51, 95% CI 0.24 to 1.11) and 12 months (498 children; RR 1.02, 95% CI 0.40 to 2.62) in children given prednisone for 14-28 days at presentation of Henoch-Schönlein purpura compared with placebo or supportive treatment. In children with severe renal disease, there was no significant difference in the risk of persistent renal disease with cyclophosphamide compared with supportive treatment (one trial; 56 children; RR 1.07, 95% CI 0.65 to 1.78) and with cyclosporin compared with methylprednisolone (one trial; 19 children; RR 0.39; 95% CI 0.14 to 1.06).
CONCLUSIONS: Data from randomised trials for any intervention used to improve renal outcomes in children with Henoch-Schönlein purpura are very sparse except for short-term prednisone, which has not been shown to be effective.
Wattana Chartapisak, Sauwalak Opastirakul, Elisabeth M Hodson, Narelle S Willis, Jonathan C Craig
Interventions for preventing and treating kidney disease in Henoch-Schönlein Purpura (HSP).
Cochrane Database Syst Rev. 2009 Jul 8;(3):CD005128. doi: 10.1002/14651858.CD005128.pub2. Epub 2009 Jul 8.
Abstract/Text
BACKGROUND: To determine the benefits and harms of therapies used to prevent or treat kidney disease in Henoch-Schönlein Purpura (HSP).
OBJECTIVES: To evaluate the benefits and harms of different agents (used singularly or in combination) compared with placebo or no treatment or another agent for the prevention or treatment of kidney disease in patients with HSP.
SEARCH STRATEGY: Randomised controlled trials (RCTs) and quasi-RCTs were identified from the Cochrane Renal Group's specialised register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE using optimally sensitive search strategies combined with search terms for HSP.
SELECTION CRITERIA: RCTs comparing any intervention used to prevent or treat kidney disease in HSP compared with placebo, no treatment or other agents were included.
DATA COLLECTION AND ANALYSIS: Three authors independently assessed trial quality and extracted data from each study. Statistical analyses were performed using the random effects model and the results were expressed as risk ratio (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes with 95% confidence intervals (CI).
MAIN RESULTS: Ten studies (1230 children) were identified. There was no significant difference in the risk of persistent kidney disease at six months (3 studies, 379 children: RR 0.51, 95% CI 0.24 to 1.11) and 12 months (3 studies, 498 children: RR 1.02, 95% CI 0.40 to 2.62) in children given prednisone for 14 to 28 days at presentation of HSP compared with placebo or supportive treatment. In children with severe kidney disease, there was no significant difference in the risk of persistent kidney disease with cyclophosphamide compared with supportive treatment (1 study, 56 children: RR 1.07, 95% CI 0.65 to 1.78) and with cyclosporin compared with methylprednisolone (1 study, 19 children: RR 0.39, 95% CI 0.14 to 1.06).
AUTHORS' CONCLUSIONS: Data from RCTs for any intervention used in improve kidney outcomes in children with HSP are very sparse except for short-term prednisone. There was no evidence of benefit of prednisone in preventing serious long-term kidney disease in HSP.
Jean-Claude Davin
Henoch-Schonlein purpura nephritis: pathophysiology, treatment, and future strategy.
Clin J Am Soc Nephrol. 2011 Mar;6(3):679-89. doi: 10.2215/CJN.06710810. Epub 2011 Mar 10.
Abstract/Text
Henoch-Schönlein purpura nephritis is a rare kidney disease leading to chronic kidney disease in a non-negligible percentage of patients. Although retrospective studies suggest beneficial effects of some therapies, prospective randomized clinical trials proving treatment efficacy are still lacking. The dilemma of spontaneous recovery even in patients with severe clinical and histologic presentation and of late evolution to chronic kidney disease in patients with mild initial symptoms renders it difficult for clinicians to expose patients to treatment protocols that are not evidence-based. A better understanding of the pathophysiology of progression to chronic kidney disease in Henoch-Schönlein purpura patients could be achieved by designing prospective international multicenter studies looking at determinants of clinical and histopathological evolution as well as possible circulating and urinary markers of progression. Such studies should be supported by a database available on the web and a new histologic classification of kidney lesions. This paper reports clinical, pathologic, and experimental data to be used for this strategy and to assist clinicians and clinical trial designers to reach therapeutic decisions.
P Niaudet, R Habib
Methylprednisolone pulse therapy in the treatment of severe forms of Schönlein-Henoch purpura nephritis.
Pediatr Nephrol. 1998 Apr;12(3):238-43.
Abstract/Text
Between 1980 and 1994, 38 children with severe forms of Schönlein-Henoch purpura glomerulonephritis were entered into a prospective study to evaluate methylprednisolone pulse therapy on the outcome of nephropathy in terms of clinical symptoms and histopathological changes. The patients were considered at risk of developing chronic renal failure when they presented with a nephrotic syndrome and/or had 50% or more crescentic glomeruli. Initial renal biopsies were obtained from all patients and revealed diffuse proliferative endocapillary glomerulonephritis in 2, focal and segmental glomerulonephritis in 4, and endo- and extracapillary glomerulonephritis in 32, 21 of whom had 50% or more glomeruli with crescents. Patients were treated with intravenous pulse methylprednisolone (3 days) followed by oral prednisone (3.5 months). At the latest follow-up, 1-16 years after initiation of therapy, 27 children had clinically recovered, 3 showed minimal urinary abnormalities, 4 persistent nephropathy, and 4 had progressed to end-stage renal failure. Sequential renal biopsies were obtained from 30 patients, 7-25 months after initiation of therapy. The clinical outcome correlated well with of the activity (hypercellularity, cellular and fibrocellular crescents, and interstitial edema with mononuclear cell infiltrates) and the chronicity (fibrous crescents, glomerular sclerosis, tubular atrophy, and interstitial fibrosis) indexes of post-therapy biopsies. Of particular interest were the post-therapy biopsies of the 18 patients who clinically recovered. They showed a significant decrease of the activity index from 5.1+/-1.1 to 0.4+/-0.8 with a decrease or even a disappearance of IgA deposits, while the chronicity index remained low (0.4+/-0.8 compared with 1.4+/-1). Although uncontrolled, our study suggests that methylprednisolone pulse therapy is effective in those patients at risk of progression of their nephropathy, especially if started early during the course of the disease before the crescents become fibrous.
Penina Tarshish, Jay Bernstein, Chester M Edelmann
Henoch-Schönlein purpura nephritis: course of disease and efficacy of cyclophosphamide.
Pediatr Nephrol. 2004 Jan;19(1):51-6. doi: 10.1007/s00467-003-1315-x. Epub 2003 Nov 22.
Abstract/Text
Nephritis in Henoch-Schönlein purpura (HSP) is the primary cause of morbidity and mortality. Although many therapeutic regimens have been reported to be effective, no therapy has been shown in a controlled trial to be beneficial. Fifty-six patients with histopathologically severe HSP nephritis were randomized to receive supportive therapy with or without cyclophosphamide, 90 mg/m(2)/day for 42 days. Patients were classified according to status at final follow-up: Fully Recovered 48.2%, Persistent Abnormalities 39.3%, or ESRD/Death 12.5%. There were no differences in onset data or outcome between the two trial groups or in outcome between trial and 23 non-trial patients followed concurrently. Therefore, data from trial and non-trial patients were combined for further analysis. There was no correlation between outcome and age, blood pressure, serum total protein, or serum albumin. Although rates of proteinuria did not correlate with outcome, all those with progression to ESRD had nephrotic levels of proteinuria at onset. Only five of 28 patients with nephrotic levels of proteinuria and severe onset histopathology recovered fully. No patient with crescents in 50% or more of glomeruli went on to full recovery. Recurrence of non-renal symptoms did not correlate with outcome. Nephrotic syndrome, decreased GFR, and more severe histopathology at onset, as well as persistence of urinary abnormalities for several years, are ominous signs.
A Oner, K Tinaztepe, O Erdogan
The effect of triple therapy on rapidly progressive type of Henoch-Schönlein nephritis.
Pediatr Nephrol. 1995 Feb;9(1):6-10.
Abstract/Text
Twelve patients with Henoch-Schönlein purpura, aged 6-14 years (mean 10.3 years), presenting with rapidly progressive glomerulonephritis (RPGN) were investigated prospectively. Analysis of the initial clinical features revealed: oedema (8 patients), hypertension (7 patients), gross haematuria (11 patients), oliguria (5 patients) and a decreased glomerular filtration rate (GFR) (< 40 ml/min per 1.73 m2, 8 patients). Renal biopsies were available in 9 patients and revealed focal necrotising and a fibroepithelial type of crescentic glomerulonephritis (with 60%-90% crescent formation). The remaining 3 patients fulfilled the clinical criteria of RPGN. Two patients who were in the acute stage required peritoneal dialysis for a period of 2 weeks. The treatment protocol in all patients consisted of intravenous pulse methylprednisolone (3 days), oral cyclophosphamide (2 months), oral dipyridamole (6 months) and oral prednisolone (3 months). At the end of triple therapy, GFR returned to normal in all but 1 patient. During a follow-up period of 9-39 months, 7 patients achieved complete remission, while 4 patients showed partial remission, 3 of whom had persistent proteinuria and haematuria and 1 microscopic haematuria only. One patient had persistent nephropathy with decreased GFR and macroscopic haematuria and nephrotic-range proteinuria. His renal biopsy, performed 30 months after the onset of the disease, showed chronic diffuse sclerosing glomerulonephritis and intratubular severe IgA deposition. Although our patient group was small, this type of intensive treatment appears to be effective; further studies are needed.
K Iijima, S Ito-Kariya, H Nakamura, N Yoshikawa
Multiple combined therapy for severe Henoch-Schönlein nephritis in children.
Pediatr Nephrol. 1998 Apr;12(3):244-8.
Abstract/Text
From 1980 through 1992, 14 children with Henoch-Schönlein nephritis (HSN) showing severe glomerular changes (grade IV or V) were given a multiple combined therapy with prednisolone, cyclophosphamide, heparin/warfarin, and dipyridamole, and were followed for 7.5+/-0.9 years. The period between the onset of nephritis and the start of therapy was 0.8+/-0.4 years. Ten patients underwent follow-up biopsy after therapy. The percentage of glomeruli having crescents/segmental lesions was significantly reduced after therapy (70%+/-5% vs. 42%+/-7%, P <0.01), due mainly to the resolution of crescents (51%+/-8% vs. 13%+/-5%, P <0.01). Thus, histological grade was significantly improved (5 grade IV and 5 grade V vs. 7 grade III and 3 grade IV, P <0.01). After an average follow-up period of 7.5 years, 9 patients showed normal urine and renal function, 4 showed minor urinary abnormalities, and 1 heavy proteinuria. No patient developed chronic renal insufficiency. These findings suggest that the multiple combined therapy could be effective. for histologically severe HSN, although a prospective controlled study should be performed.
Yukihiko Kawasaki, Junzo Suzuki, Hitoshi Suzuki
Efficacy of methylprednisolone and urokinase pulse therapy combined with or without cyclophosphamide in severe Henoch-Schoenlein nephritis: a clinical and histopathological study.
Nephrol Dial Transplant. 2004 Apr;19(4):858-64. doi: 10.1093/ndt/gfg617.
Abstract/Text
BACKGROUND: There have been few controlled studies of combined therapy with multiple drugs, including immunosuppressives, for severe Henoch-Schoenlein nephritis (HSPN). We evaluated the efficacy of methylprednisolone and urokinase pulse therapy combined with cyclophosphamide for patients with HSPN of at least grade IVb.
METHODS: We studied 37 patients who had been diagnosed with HSPN of at least grade IVb. Of them, 20 (Group A) were treated with methylprednisolone and urokinase pulse therapy, and 17 (Group B) were treated with methylprednisolone and urokinase pulse therapy combined with cyclophophamide. We analysed the clinical features, laboratory and pathological findings of the two groups retrospectively.
RESULTS: After 6 months of treatment, mean urinary protein excretion in Group B had significantly decreased compared with Group A, and the activity index of both groups at the second biopsy was lower than that at the first. Furthermore, at the second biopsy, the chronicity index of Group B was lower than that of Group A. Four patients of Group A but none of Group B had persistent nephropathy (P<0.05).
CONCLUSIONS: Our study suggests that methylprednisolone and urokinase pulse therapy combined with cyclophosphamide is useful for patients with severe HSPN.
R H Kauffmann, D A Houwert
Plasmapheresis in rapidly progressive Henoch-Schoenlein glomerulonephritis and the effect on circulating IgA immune complexes.
Clin Nephrol. 1981 Sep;16(3):155-60.
Abstract/Text
Two adult patients with Henoch-Schoenlein purpura and rapidly progressive glomerulonephritis were treated with plasmapheresis. One patient also received cyclophosphamide. Both patients recovered their renal function. Before plasmapheresis circulating IgA immune complexes were demonstrated in both patients by two assays with specificity for IgA. The level of IgA immune complexes decreased after each plasma exchange. IgA immune complexes disappeared in the patient who was treated with cyclophosphamide but remained present in the other patient. Plasma exchange may be a useful form of therapy for patients with Henoch-Schoenlein purpura and progressive renal failure. Measurement of circulating IgA immune complexes may provide insight into the in vivo effect of plasmapheresis.
M Hattori, K Ito, T Konomoto, H Kawaguchi, T Yoshioka, M Khono
Plasmapheresis as the sole therapy for rapidly progressive Henoch-Schönlein purpura nephritis in children.
Am J Kidney Dis. 1999 Mar;33(3):427-33.
Abstract/Text
To clarify the therapeutic role of plasmapheresis (PP) for patients with Henoch-Schönlein purpura (HSP) nephritis, the clinical courses of nine children with a rapidly progressive type of HSP nephritis, who were treated with PP as the sole therapy, were retrospectively evaluated. All patients had nephrotic-range proteinuria (4.9 +/- 2.5 g/m2/d, mean +/- SD) and decreased glomerular filtration rate (GFR) (46.5 +/- 9.5 mL/min/1.73 m2) at the time of the initiation of PP. Biopsy specimens taken before PP showed large crescents involving more than 50% of the glomerular circumference in 56.8 +/- 6.9% of the glomeruli examined. The mean interval between disease onset and initiation of PP was 39.1 +/- 22.1 days. The PP regimen consisted of thrice-weekly treatment for 2 weeks, then weekly treatment for 6 weeks. No patients received any steroids or cytotoxic drugs, except for the use of steroids to manage severe abdominal pain. All patients responded promptly to PP with improvement in renal function, reduction of proteinuria, and subsidence of purpuric rash and abdominal pain. Six of nine patients showed further improvements without any other treatments; four had complete recovery, and two had only microscopic hematuria at the latest observation (follow-up period, 9.6 +/- 4.3 years). The remaining three patients showed a rebound increase of proteinuria after completion of PP; two of whom progressed to end-stage renal failure at 14.1 years and 1.8 years after disease onset. Because all patients had the most severe forms of nephritis, reported to carry a grave prognosis, this study suggests that PP as the sole therapy is effective in improving the prognosis of patients with rapidly progressive HSP nephritis, particularly if instituted early in the course of the disease. The role of PP in treating HSP nephritis deserves to be assessed further in larger randomized controlled trials.
Evangéline Pillebout, Corinne Alberti, Loic Guillevin, Amel Ouslimani, Eric Thervet, CESAR study group
Addition of cyclophosphamide to steroids provides no benefit compared with steroids alone in treating adult patients with severe Henoch Schönlein Purpura.
Kidney Int. 2010 Sep;78(5):495-502. doi: 10.1038/ki.2010.150. Epub 2010 May 26.
Abstract/Text
Henoch Schönlein Purpura (HSP) is a common disease in children, usually associated with a good prognosis. In adults there are no prospective studies concerning its prognosis or treatment, especially in cases of severe visceral involvement. Here we compared steroid therapy without or with cyclophosphamide co-treatment in adults with severe HSP in a 12-month, multi-center, prospective, open-label trial that treated 54 adults with biopsy-proven HSP including proliferative glomerulonephritis and severe visceral manifestations. All received steroids; however, 25 were randomized to also receive cyclophosphamide. The primary endpoint that occurred in three patients in each group was complete disease remission defined as zero on the Birmingham Vasculitis Activity Score with no persistent or new clinical and/or biological vasculitis at 6 months. No patient had active visceral involvement. The secondary endpoints were renal outcome, deaths, and adverse events at 12 months. Renal function, proteinuria, safety data, incidence of diabetes, and severe infections were similar between the two groups. At the last follow-up, renal function remained stable. The small population size of our study does not permit definitive conclusions; however, we suggest that treatment of adults with severe HSP by adding cyclophosphamide provides no benefit compared with steroids alone.
Outi Jauhola, Jaana Ronkainen, Helena Autio-Harmainen, Olli Koskimies, Marja Ala-Houhala, Pekka Arikoski, Tuula Hölttä, Timo Jahnukainen, Jukka Rajantie, Timo Ormälä, Matti Nuutinen
Cyclosporine A vs. methylprednisolone for Henoch-Schönlein nephritis: a randomized trial.
Pediatr Nephrol. 2011 Dec;26(12):2159-66. doi: 10.1007/s00467-011-1919-5. Epub 2011 May 28.
Abstract/Text
Knowledge about how to treat severe Henoch-Schönlein nephritis (HSN) is scarce. The aim of our study is to compare cyclosporine A (CyA) and methylprednisolone pulses (MP) in the treatment of severe HSN. Out of 24 pediatric HSN patients with nephrotic-range proteinuria or crescentic HSN in kidney biopsy, seven were randomized to receive CyA for 12 months at an initial dose of 5 mg/kg and eight to receive 3 MP pulses of 30 mg/kg followed by prednisone for 4 months. The other nine patients received identical treatment without randomization. Kidney biopsies were performed at inclusion and after 2 years. The primary outcomes were the duration of proteinuria and hematuria, estimated glomerular filtration rate, and renal biopsy histology. All the 11 CyA-treated patients achieved resolution of nephrotic-range proteinuria within 3 months, while the MP-group response was slower, and in 6/13 was not achieved with the initial treatment. Additional immunosuppressive treatment was needed in none of the CyA-treated patients but in six patients treated with MP (difference in proportion 46%, p = 0.008). The 2-year control biopsies were similarly improved in both groups. After mean 6.1 years (2.2-10.4 years), 16 patients (eight CyA, eight MP) had no renal symptoms and six (three CyA, three MP) had persistent nephropathy but normal renal function. One MP-treated patient had reduced renal function and another had developed ESRD and received a renal transplant. CyA gave a 100% resolution of nephrotic-range proteinuria and a 100% renal survival rate without additional therapy after a mean follow-up of 6 years. Treatment of HSN with CyA is efficacious, safe and not inferior to MP.
Jee Min Park, Sung Chul Won, Jae Il Shin, Hyunee Yim, Ki Soo Pai
Cyclosporin A therapy for Henoch-Schönlein nephritis with nephrotic-range proteinuria.
Pediatr Nephrol. 2011 Mar;26(3):411-7. doi: 10.1007/s00467-010-1723-7. Epub 2010 Dec 24.
Abstract/Text
To evaluate the therapeutic role of cyclosporin A (CyA) for the treatment of Henoch-Schönlein nephritis (HSN), 29 patients (18 boys, 11 girls) with nephrotic-range proteinuria were analyzed retrospectively. Mean age was 8.6 years (range 2.0-15.5 years) at diagnosis of Henoch-Schönlein purpura (HSP). All patients had developed the nephrotic-range proteinuria at a mean interval of 4.4 months (range 0-50.7 months) after the diagnosis of HSP. Mean duration of CyA treatment was 12.3 months (range 2.6-55.0 months). Mean follow-up times were 3.7 years (range 1.2-12.9 years) from the beginning of the CyA treatment. Steroids were tapered off and stopped gradually after initiation of CyA. All patients responded to the CyA treatment within a mean of 1.8 months (range 1 week to 3.5 months). Twenty-three patients achieved stable remission with mean follow-up duration of 3.2 years and 6 patients seemed to become CyA-dependent, since they developed proteinuria when the treatment was stopped. Renal function was preserved in all patients but one who developed end-stage renal disease after poor compliance with CyA. We concluded that CyA treatment for HSN showing nephrotic-range proteinuria is very effective and a safe method, although some patients become CyA-dependent.
F T Saulsbury
Henoch-Schönlein purpura in children. Report of 100 patients and review of the literature.
Medicine (Baltimore). 1999 Nov;78(6):395-409.
Abstract/Text
Henoch-Schönlein purpura (HSP) is an acute leukocytoclastic vasculitis that primarily affects children. In the current report, the author presents the clinical features of 100 children with HSP and reviews the literature, placing particular emphasis on new information concerning the etiology, immunopathogenesis, and treatment of HSP. The dominant clinical features of HSP are cutaneous purpura (100%), arthritis (82%), abdominal pain (63%), gastrointestinal bleeding (33%), and nephritis (40%). The etiology of HSP remains unknown, but it is clear that IgA plays a critical role in the immunopathogenesis of HSP, as evidenced by increased serum IgA concentrations, IgA-containing circulating immune complexes, and IgA deposition in vessel walls and renal mesangium. There are 2 subclasses of IgA, but HSP is associated with abnormalities involving IgA1 exclusively, and not IgA2. This finding may be a consequence of abnormal glycosylation of O-linked oligosaccharides unique to the hinge region of IgA1 molecules. Although several lines of evidence suggest a genetic susceptibility to HSP, the fundamental basis for the abnormalities involving IgA remain unclear. In general, HSP is an acute, self-limited illness, but one-third of patients will have 1 or more recurrences of symptoms. Corticosteroid therapy may hasten the resolution of arthritis and abdominal pain, but does not prevent recurrences. To date, no form of therapy has been shown to shorten appreciably the duration of HSP. The long-term prognosis of HSP is directly dependent on the severity of renal involvement. Corticosteroids in usual doses have no effect on established nephritis. Evidence is emerging that treatment with high-dose intravenous pulse methylprednisolone coupled with azathioprine or cyclophosphamide may be beneficial in patients with severe nephritis.
Sandra Trapani, Annalisa Micheli, Francesca Grisolia, Massimo Resti, Elena Chiappini, Fernanda Falcini, Maurizio De Martino
Henoch Schonlein purpura in childhood: epidemiological and clinical analysis of 150 cases over a 5-year period and review of literature.
Semin Arthritis Rheum. 2005 Dec;35(3):143-53. doi: 10.1016/j.semarthrit.2005.08.007.
Abstract/Text
OBJECTIVE: To examine epidemiological, clinical, and outcome in Italian children affected with Henoch Schönlein purpura (HSP).
METHODS: Retrospective study of children discharged with a diagnosis of HSP from the Meyer Children's Hospital, between 1998 and 2002. Epidemiological, clinical, laboratory data, treatment, and outcome were collected by reviewing medical charts. One year after data collection, the children's parents were interviewed by telephone about the outcome.
RESULTS: 150 children entered the study: M:F=1.8:1; mean age 6.1+/-2.7 years. At onset, purpura was present in all cases, arthritis/arthralgias in 74%, abdominal involvement in 51%, scrotal edema in 13%, renal involvement in 54%, severe nephropathy in 7%, acute renal insufficiency in 2%, and intussusception in 0.6%. Purpura was the presenting symptom in 74%, arthritis in 15%, and abdominal pain in 12%. The most frequent laboratory abnormalities were high-erythrocyte sedimentation rate (ESR) (57%), hyper-IgA (37%), and proteinuria (42%). All patients recovered within 2 months. Recurrences, verified in 35%, were correlated with high ESR values and corticosteroid (CS) treatment, independently from other variables. After a mean 2.5-years follow-up, 2 patients had hematuria with normal renal function.
CONCLUSION: Epidemiological and clinical findings in our cohort are similar to those in the literature, even though the mean disease duration was shorter than previously reported. Relapses occurred significantly more frequently in children treated with CS. This finding supports the recommendation to limit the use of steroids to a carefully selected group of HSP children. The prognosis was excellent; although severe nephropathy was found in a small percentage of the children, at follow-up all had normal renal function. Thus, our study confirms the benignity of HSP in Italian children, especially regarding renal outcome.
M Levy, M Broyer, A Arsan, D Levy-Bentolila, R Habib
Anaphylactoid purpura nephritis in childhood: natural history and immunopathology.
Adv Nephrol Necker Hosp. 1976;6:183-228.
Abstract/Text
H A Austin, J E Balow
Henoch-Schönlein nephritis: prognostic features and the challenge of therapy.
Am J Kidney Dis. 1983 Mar;2(5):512-20.
Abstract/Text
Henoch-Schönlein purpura is an intriguing entity of uncertain etiology associated with circulating IaA immune complexes, enhanced spontaneous immunoglobulin production, and an apparent imbalance in T cell regulatory functions. The associated glomerulonephritis is highly variable in nature and may profoundly influence clinical outcome. Prognostic features are reviewed in an effort to identify high-risk patients. Age, non-renal manifestations, non-selectivity of proteinuria, and evidence of preceding streptococcal infection are relatively weak predictors of end-stage renal disease. The presenting clinical and histologic expressions of nephritis are more useful prognosticators, but neither are completely reliable. Patients with greater than 50% crescents, and those with nephrotic syndrome complicated by various combinations of hypertension, azotemia, oliguria, and/or hypoproteinemia, are at increased risk of renal failure and might benefit from therapeutic interventions. Experience with various modalities is reviewed. Faced with uncontrolled clinical data, it is unclear whether immunosuppressive agents or plasmapheresis offer a therapeutic advantage over oral corticosteroids alone.
S Shrestha, N Sumingan, J Tan, H Alhous, H Althous, L McWilliam, F Ballardie
Henoch Schönlein purpura with nephritis in adults: adverse prognostic indicators in a UK population.
QJM. 2006 Apr;99(4):253-65. doi: 10.1093/qjmed/hcl034.
Abstract/Text
BACKGROUND: Henoch Schönlein purpura with nephritis (HSN) in adults may cause severe organ injury, but its rarity has contributed to a lack of data.
AIM: To evaluate clinical outcomes and risk factors in adult HSN patients.
DESIGN: Retrospective analysis.
METHODS: Thirty-seven patients with adult HSN attending the Regional Vasculitis Clinic between 1974 and 2004 were assessed. For inclusion, a renal biopsy showing predominant mesangial IgA immune deposits was required, plus at least two of: purpuric rash, arthralgia, abdominal pain.
RESULTS: Ten patients (27%) progressed to end-stage renal failure (ESRF). Renal failure rates were highest in the first decade, with survival rate 72% at 5 years, 68% at 10 years and 46% at final review. Risk factors for ESRF were: proteinuria > or =1 g/day during follow-up (RR 83.8, p = 0.0006); hypertension at presentation (RR = 53.3, p = 0.0045) and during follow-up (RR = 5.9, p = 0.05); renal impairment at presentation (RR 8.0, p = 0.0015); age <30 years (RR 7.6, p = 0.02); and male sex (RR = 6.0, p = 0.05). Biopsies frequently showed crescents, mostly affecting <50% of glomeruli; their presence predicted ESRF, as did interstitial fibrosis and tubular atrophy. Renal remission, in contrast, was also high (43%). Cytotoxics were used in 32%, with no clear effect on outcome. Relapses affecting the classical extra-renal systems were common, but were not associated with declines in renal function. A high proportion of patients (41%) also suffered vasculitic organ injuries outside the classical systems.
DISCUSSION: HSN in adults is a serious relapsing disease, causing renal failure as frequently as in small-vessel ANCA-positive vasculitides. Prognosis and risks differed in this series from those in other countries, including a higher risk of ESRF than in previous series. Distinct groups developed either ESRF, or remitted. The absence of clear benefit suggests that corticosteroids should be reserved for patients with serious disease, and that cytotoxics may not be merited for those at high risk of renal failure.
Q Meulders, Y Pirson, J P Cosyns, J P Squifflet, C van Ypersele de Strihou
Course of Henoch-Schönlein nephritis after renal transplantation. Report on ten patients and review of the literature.
Transplantation. 1994 Dec 15;58(11):1179-86.
Abstract/Text
The frequency and the risk factors for clinical recurrence of Henoch-Schönlein nephritis following renal transplantation (TP) remain largely unknown. We report on 14 transplants performed at our center in 10 patients, detail the evolution of 2 of them with clinical recurrence, and review 64 other transplants reported in the literature. In our series, all patients are currently alive. Seven grafts are well-functioning 22-295 (mean, 97) months after TP without any sign of clinical recurrence. Five grafts were lost from rejection. Clinical recurrence occurred in 2 patients who were on cyclosporine/azathioprine/prednisone therapy. Pooling our series with that of Hasegawa et al., the actuarial risk for renal recurrence and for graft loss due to recurrence was 35 and 11% at 5 years after TP, respectively. In our series, duration of original disease was 2 and 28 months in the 2 patients with recurrence versus 31-144 months in the others without recurrence. In the literature, this duration was < or = 36 months in all 7 patients with recurrence. Recurrence occurred despite a > 12-month delay between disappearance of purpura and TP in our 2 patients and in 3 of 6 previously reported recurrences. We conclude that Henoch-Schönlein purpura nephritis frequently recurs after TP. Recurrence (1) seems to be associated with a shorter duration of the original disease, (2) can occur despite a delay of more than 1 year (as commonly advised) between disappearance of purpura and TP, and (3) is not prevented by a triple immunosuppressive regimen that includes cyclosporine.
Nada Kanaan, Georges Mourad, Eric Thervet, Patrick Peeters, Maryvonne Hourmant, Yves Vanrenterghem, Martine De Meyer, Michel Mourad, Céline Maréchal, Eric Goffin, Yves Pirson
Recurrence and graft loss after kidney transplantation for henoch-schonlein purpura nephritis: a multicenter analysis.
Clin J Am Soc Nephrol. 2011 Jul;6(7):1768-72. doi: 10.2215/CJN.00520111.
Abstract/Text
BACKGROUND AND OBJECTIVES: The actuarial risk at 5 years for clinical recurrence of Henoch-Schönlein purpura nephritis (HSPN) and graft loss caused by recurrence of -HSPN after renal transplantation was reported in 1994 to be as high as 35% and 11%, respectively. The aim of this study is to re-evaluate, in a large cohort of patients with a long-term follow-up, whether these rates have changed.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Patients from six transplant centers in Belgium and France with strict diagnostic criteria of HSPN and a potential post transplant follow-up of ≥3 years were included.
RESULTS: Forty-three patients were included. Patient survival is excellent: 98%, 95%, and 95% at 5, 10, and 15 years, respectively. Overall graft survival rates were 84%, 66%, and 56% at 5, 10, and 15 years, respectively. Clinical recurrence in a first kidney transplant occurred in five patients. Three patients lost their first graft due to HSPN recurrence 19 to 96 months after transplantation, two of whom had systemic signs of the illness. Actuarial risk for clinical recurrence in a first graft is 2.5% and 11.5% at 5 and 10 years, respectively. Actuarial risk for graft loss caused by recurrence in a first graft is 2.5% and 7.5% at 5 and 10 years, respectively. Severity of the disease at presentation and type of immunosuppression after transplantation did not affect recurrence.
CONCLUSIONS: We found that recurrence rates of HSPN after transplantation are lower than previously reported. The actuarial risk of graft loss from recurrence in a first graft is 7.5% at 10 years.
Joyce P Samuel, Cynthia S Bell, Donald A Molony, Michael C Braun
Long-term outcome of renal transplantation patients with Henoch-Schonlein purpura.
Clin J Am Soc Nephrol. 2011 Aug;6(8):2034-40. doi: 10.2215/CJN.01410211. Epub 2011 Jun 23.
Abstract/Text
BACKGROUND AND OBJECTIVES: Although Henoch-Schönlein purpura (HSP) is the most common form of renal vasculitis in childhood, progression to ESRD is rare, and there are few data on outcomes of renal transplantation in patients with HSP.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This is a matched retrospective cohort study of renal allografts using the United Network of Organ Sharing database (1987 to 2005). Of the 189,211 primary renal allografts, there were 339 with a diagnosis of HSP. The primary end point was allograft survival.
RESULTS: Compared with the remainder of the database, the HSP population was younger (25 years versus 46 years), and had a higher proportion of women (47% versus 40%), live donors (50% versus 35%), and Caucasians (77% versus 60%). Controlling for age, gender, donor source, ethnicity, and year of transplantation, death-censored graft survival for patients with HSP was 80.0% at 5 years and 58.8% at 10 years compared with 79.0% at 5 years and 55.4% at 10 years in the non-HSP population. Among patients with reported causes of graft loss, failure from recurrent disease occurred in 13.6% of patients with HSP, compared with 6.6% in the non-HSP population. When analyzing allograft survival in recipients with HSP compared with those with IgA nephropathy, there was no difference in 10-year allograft survival (58.4% and 59.3%, respectively).
CONCLUSIONS: These data indicate that although there is an increased risk of graft failure attributable to recurrent disease in patients with HSP, a diagnosis of HSP has little effect on overall renal allograft survival.
