Cyclosporin A therapy for severe Henoch-Schönlein nephritis with nephrotic syndrome

To evaluate the efficacy of cyclosporin A (CyA) for treating severe Henoch-Schönlein nephritis (HSN), seven patients with nephrotic syndrome, aged 3.9–13.8 years (mean 6.5 years), were analyzed retrospectively. Mean follow-up times were 5.5 years (range 2–9 years). All underwent renal biopsy before treatment, and follow-up renal biopsy was performed in six of the seven patients. All patients improved, with 24-h protein declining from a mean of 9.2 g/m²/day (range 1.5–16 g/m²/day) to 0.3 g/m²/day (range 0.03–1.2 g/m²/day) (p=0.016) and serum albumin increasing from a mean of 2.1 g/dl (range 1.5–2.4 g/dl) to 4.6 g/dl (range 3.5–5.3 g/dl) (p=0.016) after CyA therapy. The activity index decreased significantly at the second renal biopsies obtained at a mean interval of 11.7 months after the first (6.4±3.3 vs 3.5±1.2, p=0.042, respectively), while the chronicity index and the tubulointerstitial scores did not change. On the immunofluorescent findings at the second biopsies, the degree of deposits of immunoglobulins such as IgA, IgM, C3, and fibrinogen decreased in five of the six patients. Although this case series is without controls, our study suggests that CyA may be beneficial to a subset of HSN patients with nephrotic syndrome.     

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.     

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.     

Masked severe stenosing ureteritis: a rare complication of Henoch-Schönlein purpura

Henoch-Schönlein purpura (HSP)-associated stenosing ureteritis represents a rare complication of the disease, typically presenting with severe manifestations. This article reports on a 3.5-year-old boy with HSP and severe nephritis who developed a unilateral stenosing ureteritis with atypical manifestations, resulting in a nonfunctional kidney and consequent nephrectomy. The urinary tract ultrasound was normal in the first week of illness, and the diagnosis was made during follow-up 8 months after onset. The predominance of nephritic manifestations may have masked any signs of ureteritis, leading to the delay in diagnosis. To clarify the clinical spectrum of this complication, an extensive review of the literature was performed. We emphasize the necessity of repeated urinary tract ultrasound both early and later in the course of HSP, especially in cases with renal involvement, so that an early diagnosis of this complication can prevent a potentially serious renal outcome.     

Can azathioprine and steroids alter the progression of severe Henoch-Schönlein nephritis in children?

To evaluate the effect of azathioprine with steroids on the clinical course and histologic parameters of severe Henoch-Schönlein nephritis (HSN), 20 patients with a median age of 9.3 years (range 4.4–17 years) and a follow-up period of 4.8 years (range 1–14 years) were included in this study. The patients were divided into two groups. Ten patients received azathioprine with steroids for 8 months (group A), and the other ten received steroids alone (group B). All patients underwent renal biopsy at presentation, and ten of them who were treated with azathioprine underwent follow-up biopsy after therapy. Six patients in group A achieved clinical remission, and the remaining four showed minor urinary abnormalities at the latest observation. The histological grades of the International Study of Kidney Disease in Children (ISKDC) improved in four of the ten patients, and the activity index decreased significantly from 6.8±2.0 to 4.3±2.3 (p=0.016). In group B, however, four patients had normal urine and renal function; two had minor urinary abnormalities; one had active renal disease, and three had chronic renal insufficiency, at the latest observation. The combination treatment of azathioprine and steroids may be beneficial in ameliorating histopathological features and improving the clinical course of severe HSN.     

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.     

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.     

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.     

Adult Henoch-Schönlein purpura

Henoch-Sch?nlein purpura (HSP) is a systemic IgA vasculitis affecting small vessels. HSP usually affect children whereas it is rare in adults (150 to 200 for 1) in which the disease is often more serious with more frequent and severe nephritis. Prevalence of adult PR is unknown and its annual incidence is 1 in 1 million. The dominant clinical features include cutaneous purpura, arthritis and gastrointestinal symptoms. Some times nephritis can add, typically as glomerulonephritis with IgA mesangial deposits. Pulmonary, cardiac, genital and neurological symptoms have also been observed. Although the cause is unknown, it is clear that IgA plays a pivotal role in the immunopathogenesis of HSP. Only symptomatic treatment is advised in case of self limited disease. Treatment of severe HSP, nephritis or gastrointestinal manifestations, is not established but some studies, which need to be confirmed, reported the benefit of corticosteroids combined with immunosuppressive drugs. Short term outcome depends on the severity of the gastro-intestinal manifestations. The long term prognosis is heavily dependent on the presence and severity of nephritis. Studies with prolonged follow-up show up to one third of adult patients reaching end stage renal failure.     

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.     

Plasmapheresis therapy for rapidly progressive Henoch-Schönlein nephritis

Six Japanese children with rapidly progressive Henoch-Schönlein purpura nephritis (HSPN) received multiple drug therapy combined with plasmapheresis (PP). After five courses of PP, multiple drug therapy, including methylprednisolone and urokinase pulse therapy, oral prednisolone, cyclophophamide, dipyridamole, and warfarin was given. At presentation, urine protein excretion and histological indices of the mean activity and chronicity were 245±101 mg/m² per hour, 6.6±1.2, and 1.5±1.3, respectively. After 6 months of therapy, urinary protein excretion had decreased significantly (P<0.001). The activity index decreased significantly at the second renal biopsy performed at a mean interval of 4.3 months after the first (2.8±1.4, P<0.05), while the chronicity index did not change. At the most recent observation, all showed clinical improvement. Two patients had normal urine, three had proteinuria of <20 mg/m² per hour, one had proteinuria of >20 mg/m² per hour, and none had renal insufficiency. Although this case series is without controls, our treatment protocol may be of benefit to children with rapidly progressive HSPN.     

A case of pediatric Henoch-Schönlein purpura and thrombosis of spermatic veins

The authors report a case of thrombosis of the spermatic veins associated with Henoch-Sch?nlein purpura mimicking an acute scrotum, which responded to a low-molecular-weight heparin treatment.     

A case of Henoch-Schönlein purpura in a patient on hemodialysis

Henoch-Sch?nlein purpura(HSP) is a systemic vasculitis and characterized by the tissue deposition of IgA-containing immune complexes. A 50-year-old man with end stage renal failure due to diabetic nephropathy on maintenance hemodialysis, presented purpura, hematuria, abdominal pain, and joint pain. He also presented a high fever with neutrophilia. Biopsy of skin lesions revealed inflammation of the small vessel accompanied by vascular IgA deposition. Based on the clinical symptoms and skin biopsy, we made the diagnosis of HSP. Oral prednisolone was administered resulting in an improvement of the clinical symptoms. A skin biopsy should be performed for histological and immunofluorescence studies in the case of clinical suspicion of HSP with end stage renal disease on hemodialysis.     

Cyclosporin A in adult patients with Henoch-Schönlein purpura nephritis and nephrotic syndrome; 5 case reports

Henoch-Sch?nlein purpura (HSP) is usually followed by mild renal involvement, but heavy proteinuria may also occur. Limited experience with cyclosporin A in children shows reduction of proteinuria. In this report, the use of cyclosporin A in 5 adult HSP patients with nephrotic-range proteinuria is described. Cyclosporin A in combination with prednisolone was given in 3 patients with HSP nephritis and nephrotic syndrome after a course of other immunosuppressive drugs and in 2 patients as initial treatment. All patients showed complete or partial remission of nephrotic syndrome with cyclosporin A and preserved stable renal function over a follow-up period of 5 years. We conclude that the combination of cyclosporin A with corticosteroids is effective in inducing remission of nephrotic syndrome in adult patients with HSP nephritis.     

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.