The Combination of Mycophenolate Mofetil with Corticosteroids Induces Remission of Henoch-Schönlein Purpura Nephritis

Background: Henoch-Sch?nlein purpura (HSP) is a form of systemic vasculitis that can progress to Henoch-Sch?nlein purpura nephritis (HSPN), and the most effective treatment remains controversial. Our aim was to compare the effects of oral mycophenolate mofetil (MMF) with low-dose prednisone and the full-dose corticosteroids (CS; prednisone) for the induction therapy of HSPN with large proteinuria. Methods: Fifty-three patients with biopsy-proved HSPN with large proteinuria (>2.0 g/24 h) were divided into two groups: the MMF group (n = 27) who received oral MMF 1.0 g/day (1.5 g/day for patients with a body weight >70 kg) combined with low-dose prednisone (0.4-0.5 mg/kg/day), and the CS group (n = 26) who received the full-dose prednisone (0.8-1.0 mg/kg/day). We compared the effects of inducing remission at 6-month follow-up and the overall remission rate at the end of the follow-up between the two groups. Results: At 6 months, the estimated glomerular filtration rate level remained stable, while the urine protein decreased significantly in both groups, and the remission rate was 76.9% in the CS group and 55.5% in the MMF group (p = 0.101). With a median follow-up of 28.8 months in the CS group and 28.2 months in the MMF group, the overall remission rate was 80.8% in the CS group and 77.8% in the MMF group (p = 0.788). The MMF group had less side effects than the CS group (48.1 vs. 76.9%, p = 0.031). The relapse was 4/21 (19.0%) in the CS group and 0/21 in the MMF group (p = 0.115). Conclusion: MMF is useful for inducing remission and maintaining remission in Chinese HSPN, and may be used as a steroid-sparing agent in the treatment of HSPN.     

Henoch-Schönlein Purpura in adults: outcome and prognostic factors

Henoch-Sch?nlein 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.     

Glomerulonephritis without IgA deposits in a case of Henoch-Schönlein purpura

A boy aged 3 years 8 months with Henoch-Schönlein purpura (HSP) developed significant proteinuria with hematuria 2 days after the appearance of purpura rash. Although thought to be purpura nephritis, a percutaneous renal biopsy revealed diffuse mesangial proliferative glomerulonephritis (MesPGN) without deposition of immunoglobulin A or complement. Since his urine screening test during a health check at the age of 3.5 years had been unremarkable, HSP might have played a role in the pathogenesis of his non-IgA MesPGN. To our knowledge, non-IgA MesPGN is an uncommon renal manifestation of HSP.     

Treatment of Henoch-Schönlein Purpura glomerulonephritis in children with high-dose corticosteroids plus oral cyclophosphamide

BACKGROUND: Henoch-Sch?nlein Purpura (HSP) is a common childhood vasculitis with manifestations in numerous organ systems, including glomerulonephritis. Patients with more severe HSP-associated glomerulonephritis may develop chronic renal failure. Currently, no widely accepted treatment protocols exist for patients with significant renal involvement. METHODS: We retrospectively reviewed the clinical courses of 12 children (mean age 9 years) with HSP glomerulonephritis treated with high-dose corticosteroids plus oral cyclophosphamide. All patients had nephrotic-range proteinuria, and all had significant histopathologic changes on biopsy, including crescentic nephritis in 10 patients. Treatment consisted of either intravenous pulse methylprednisolone or oral prednisone followed by oral cyclophosphamide (2 mg/kg/day) for 12 weeks, along with either daily or alternate-day oral prednisone. Prednisone was tapered following completion of cyclophsophamide. RESULTS: Serum albumin rose significantly after treatment from 2.8 +/- (SD) 0.5 to 3.7 +/- 0.4 g/dl (p < 0.001), and there was a concurrent reduction in proteinuria, as reflected by decreasing serial protein-to-creatinine ratios: from 6.3 +/- 4.4 to 0.8 +/- 0.8 (p = 0.002). Renal function remained normal in all patients. Hypertension developed during treatment in 10 patients, all but 1 of whom were normotensive at last follow-up, 35 +/- 17 months following biopsy. CONCLUSIONS: We conclude that treatment of children with HSP nephritis with high-dose corticosteroids plus oral cyclophosphamide is safe and, as in nephrotic syndrome, appears to significantly reduce proteinuria which is a known risk factor for the development of renal insufficiency in HSP. Further studies with larger numbers of patients should be conducted to confirm this finding.     

Serum levels of galactose-deficient IgA in children with IgA nephropathy and Henoch-Schönlein purpura

IgA nephropathy and Henoch-Schönlein purpura nephritis (HSPN) are related diseases characterized by deposits of IgA1-containing immune complexes in the renal mesangium. Adult patients with IgA nephropathy have aberrantly glycosylated IgA1 (galactose-deficient O-linked glycans) in the circulation and renal deposits. However, IgA1 glycosylation has not been studied in pediatric patients with IgA nephropathy. Using our quantitative lectin enzyme-linked immunosorbent assay (ELISA) test, we measured serum levels of galactose-deficient IgA1 of children with IgA nephropathy and HSPN and controls. Children with IgA nephropathy and HSPN had serum levels higher than those of healthy children or renal-disease controls with C1q nephropathy. Furthermore, lectin ELISA identified patients with HSPN whose clinical course mimicked that of IgA nephropathy. In summary, pediatric patients with IgA nephropathy and HSPN have an aberrancy in the glycosylation in IgA1 O-linked glycans that is similar to that in adults with IgA nephropathy.     

Aberrant glycosylation of IgA1 is inherited in both pediatric IgA nephropathy and Henoch-Schönlein purpura nephritis

Serum galactose-deficient immunoglobulin A1 (Gd-IgA1) is an inherited risk factor for adult IgA nephropathy (IgAN). In this paper, we determined the heritability of serum Gd-IgA1 levels in children with IgAN and Henoch-Sch?nlein purpura nephritis (HSPN), two disorders with clinical phenotypes sharing common pathogenic mechanisms. Serum Gd-IgA1 concentrations were quantified using a Helix aspersa-lectin-based enzyme-linked immunosorbent assay. As a group, 34 children with either disorder (20 with HSPN and 14 with IgAN) had significantly higher Gd-IgA1 levels compared with 51 age- and ethnicity-matched pediatric controls. Serum levels of Gd-IgA1 were also elevated in a large fraction of 54 first-degree relatives of pediatric IgAN and HSPN patients compared with 141 unrelated healthy adult controls. A unilineal transmission of the trait was found in 17, bilineal transmission in 1, and sporadic occurrence in 5 of 23 families when both parents and the patient were analyzed. There was a significant age-, gender-, and household-adjusted heritability of serum galactose-deficient IgA1 estimated at 76% in pediatric IgAN and at 64% in HSPN patients. Thus, serum galactose-deficient IgA1 levels are highly inherited in pediatric patients with IgAN and HSPN, providing support for another shared pathogenic link between these disorders.     

Resolution of Henoch-Schönlein purpura nephritis after acquired IgA deficiency

We report a case of Henoch-Schönlein purpura nephritis (HSPN) with acquired IgA deficiency due to parvovirus B19 infection. The patient was diagnosed as having Henoch-Schönlein purpura (HSP) at 6 years old, and subsequently developed macrohematuria and massive proteinuria of 7.4 g/day with decreased creatinine clearance of 70.2 ml/min/1.73 m² and significantly elevated serum IgA level of 449 mg/dl. The first kidney biopsy yielded the diagnosis of severe HSPN. After the initiation of the immunosuppressive therapy, the patient was infected with parvovirus B19 and developed virus-associated hemophagocytic syndrome (VAHS). Thereafter, the serum level of IgA selectively decreased and remained undetectable until the present time. Repeated kidney biopsies performed over a period of 14 years revealed a remarkable histological improvement in association with stabilization of the patient's kidney function. Considering the severity of initial kidney injury, persistent acquired IgA deficiency was likely to add favorable effects to the immunosuppressive therapy in this patient with HSPN.     

Subcutaneous nodules in Henoch-Schönlein purpura

A 6.5-year-old boy with active Henoch-Schönlein purpura developed subcutaneous nodules (SCN), a vasculitic manifestation previously unreported in children with this disease. The authors suggest that pressure played a role in the pathogenesis of the SCN.     

Pathogenesis of Henoch-Schönlein purpura nephritis

The severity of renal involvement is the major factor determining the long-term outcome of children with Henoch-Schönlein purpura (HSP) nephritis (HSPN). Approximately 40% children with HSP develop nephritis, usually within 4 to 6 weeks after the initial onset of the typical purpuric rashes. Although the pathogenetic mechanisms are still not fully delineated, several studies suggest that galactose-deficient IgA1 (Gd-IgA1) is recognized by anti-glycan antibodies, leading to the formation of the circulating immune complexes and their mesangial deposition that induce renal injury in HSPN.     

Mycophenolate mofetil treatment of crescentic Henoch-Schönlein nephritis with IgA depositions

Mycophenolate mofetil (MMF) is considered to be a promising therapeutic agent in primary glomerulonephritis but there are no data on the use of MMF in Henoch-Sch?nlein nephritis (HSN). Herein we report the first adult crescentic HSN patient in whom long-term complete remission was achieved after MMF therapy.     

Tonsillectomy in the treatment of pediatric Henoch-Schönlein nephritis

The exact pathophysiology of HSN remains to be elucidated. Hence, a therapeutic strategy that enables curative treatments for all the various grades of HSN patients has yet to be established. We report our experience performing tonsillectomy combined with steroid therapy for 16 pediatric proteinuric Henoch-Sch?nlein nephritis (HSN) patients. All patients exhibited hematuria and proteinuria in their first HSN attack with the mean age of onset 7.7 years (range 4.75 - 13.9 years). Nine patients were diagnosed with clinically severe HSN presenting with massive proteinuria (> 1 g/m(2)/day). Renal biopsy findings performed in 6 patients were Grade II (3), Grade III (2) and Grade IV (1) according to the International Study of Kidney Diseases in childhood classification. Tonsillectomy was performed after 1-4 cycles of methylprednisolone pulses during oral prednisolone (0.5 - 1.5 mg/kg/day) therapy. In 2 patients, oral cyclophosphamide therapy was added before the tonsillectomy. The interval between the onset of HSN and tonsillectomy was 97.4 +/- 24.5 days (range 27 424 days). In all patients, proteinuria had disappeared by 6 months after the tonsillectomy and the urine findings had normalized. The interval between therapy initiation and complete remission was 9.6 +/- 2.0 months (range 2 - 26 months). Over follow-up periods of 4.9 +/- 0.6 years (range 2.2 - 9.3 years), no recurrences of Henoch-Schonlein purpura or HSN were observed. There was a significant correlation between early tonsillectomy performance and decreased time until normalization of the urine findings, indicating that the tonsils may have pivotal roles in the initiation and progression of HSN. Their elimination might promote the reversal of nephritis. Although this study is retrospective, we suggested that tonsillectomy at an early stage of HSN may be beneficial by shortening the period of illness and contributing to clinical recovery. Randomized controlled trials will be needed to confirm this supposition.     

Polymorphism of the ACE gene in Henoch-Schönlein purpura nephritis

Individuals with IgA nephropathy (IgAN) who are homozygous for the deletion (D) polymorphism of the gene for angiotensin converting enzyme (ACE) are reported to be at increased risk of progressive renal damage. Since IgAN and Henoch-Schönlein purpura with associated nephritis (HSPN) share a common aetiology, we have investigated this influence in 31 children with HSPN. The distribution of genotypes was as follows: II: 4, ID: 17 and DD: 10 patients. Median length of follow-up was 4.5 years (range 0.5–15.75 years). Severe onset with nephrotic oedema and crescent formation on renal biopsy was seen in 10 of 17 patients with ID genotype and 5 of 10 patients with DD genotype. In the ID group, 2 patients have undergone renal transplantation and 4 have persistent proteinuria 4, 7, 9 and 10 years after presentation. One patient in the DD group has been transplanted and 1 patient has proteinuria and a reduced glomerular filtration rate 5 years after initial presentation. All other patients have either made a complete recovery or have microscopic haematuria alone. These results do not support an association between disease severity and DD genotype in children with HSPN; however larger studies are required to confirm this.     

Treating severe Henoch-Schönlein and IgA nephritis with plasmapheresis alone

The aim of our study was to determine the outcome of children with severe Henoch-Schönlein nephritis (HSN) and immunoglobulin A (IgA) nephritis (IgAN) treated with early plasmapheresis alone. Children with acute renal impairment, heavy proteinuria or both and histology greater than grade 3 were treated with early plasmapheresis alone. Glomerular filtration rate (GFR) estimated from plasma creatinine (eGFR), urine albumin:creatinine ratio (UA/UC) and blood pressure 2 weeks after treatment and were measured at the last follow-up. Sixteen children (14 HSN, 2 IgAN) had a mean eGFR of 56 (17–136) ml/min per 1.73 m² and UA/UC of 590 (12–1,379) mg/mmol. Fifteen were referred at presentation and one after 2 months, and all commenced plasmapheresis within 6 (2–13) days. All had at least nine exchanges of 90 ml/kg over 2 weeks. At 2 weeks, the eGFR had increased by 51 (95% CI 34–68; P?=?0.002), and the UA/UC fell by 457 (95% CI 241–673; P?=?0.0001). At last review after 4 (1–7.5) years, the late-referred child had required a renal transplant but the other 15 had normal eGFRs (98–142), did not require hypotensive medication, and had normal or minimally elevated UA/UC (maximum 42). Children with severe HSN and IgAN recover well if treated with plasmapheresis alone without the need for immunosuppressive therapy. A randomised trial is needed.     

Therapeutic strategy in children with Henoch-Schönlein purpura

Henoch-Sch?nlein Purpura (HSP) is the most frequent childhood primary immune vasculitis which affected skin, joints, gastro-intestinal tract and kidney. Renal involvement signs the future disease prognosis. The HSP don't have etiologic treatment but its immuno-histological aspects, leukocytoclastic vasculitis with immune complexes, imposed the including in the therapeutic equation, immunosuppressive and/or cytotoxic drugs, plasmapheresis, kidney transplant (severe renal deficiency resistant to medical treatment) and surgical treatment (in severe gastro-intestinal complications). Identifications of serum and/or urinary markers for the therapeutic answer contribute to appreciate long prognosis disease and precocious and individualized treatment.     

Impaired vascular endothelium-dependent relaxation in Henoch-Schönlein purpura

Few reports have focused on vascular endothelial function in children with Henoch-Schönlein purpura (HSP). The purpose of the present study was to assess endothelial function and to follow serial changes from the acute to convalescent phases in children with HSP. Forearm flow-mediated vasodilation was evaluated in 21 patients with HSP, aged 4.0–10.3 years (median 6.2 years), and in 14 control subjects. Vascular dimension, mean velocity, and flow volume were measured by ultrasonography in brachial artery before and after hyperemia, and during incremental infusions of nitroglycerin (0.5, 1.0 g/kg per min). In the controls, significant increases in dimension, mean velocity, and flow volume were observed in reactive hyperemia (P<0.01). In contrast, patients in the acute phase of HSP showed a flow velocity profile indicating a highly resistant forearm circulation, and significantly attenuated responses after hyperemia (P<0.01 vs. control), whereas the responses to nitroglycerin were well preserved. In addition, the impaired hyperemic responses recovered in the convalescent phase, with no significant differences compared with controls. These results clearly suggest that forearm vascular endothelium-dependent relaxation was attenuated in patients with acute HSP.     

Contrast enema in children with Henoch-Schönlein purpura

Background/Purpose

There are references in the medical literature that Henoch-Schönle purpura (HSP) and abdominal pain are contraindictions to performing contrast enemas (CEs) for diagnosis and possible reduction of intussusceptions. We investigated the safety of performing CEs in patients with abdominal pain and HSP.

Methods

A retrospective chart review and literature search were conducted.

Results

CEs were not associated with complications in patients with HSP and abdominal pain and intussusceptions.

Conclusions

CEs are safe to perform in patients with HSP and suspected intussusceptions and may be useful for diagnosis and treatment.     

Clinical outcome in children with Henoch-Schönlein nephritis

Henoch-Schönlein purpura (HSP) is the most common vasculitis in childhood. The long-term prognosis is variable and depends on renal involvement. The aim of this study was to evaluate both clinical features of the children with HSP and the prognoses of short- and long-term outcome of patients diagnosed as HSP nephritis (HSN). This is a retrospective data study of all children with HSP hospitalized from January 1991 to December 2005. The patients with HSN were classified according to their initial presentation, histologic findings, type of treatment and clinical outcome. All patients have been evaluated once every 2 months. Fifty-three of the patients had kidney biopsies. The patient population consisted of 141 children included 78 boys (55.3%) and 63 girls (44.7%) ranging in age at disease onset from 2 to 17 (8.9±3.29) years. Renal involvement was determined in 58.1%. Nephrotic and/or nephritic syndrome were found to be an unfavorable predictor both for short and long-term outcome (P<0.05). However, 35% of these patients and 62% of them showed complete remission after 6 months and long-term course. Overall prognosis of HSN is relatively good and long-term morbidity is predominantly associated with initial presentation and renal involvement.