Updated Oxford classification and the international study of kidney disease in children classification: application in predicting outcome of Henoch-Schönlein purpura nephritis.

BACKGROUND: Henoch-Schönlein purpura nephritis (HSPN) shares many similarities with IgA nephropathy. We aimed to analyze the predictive value of the International Study of Kidney Disease in Children (ISKDC) classification and the updated Oxford classification for IgA nephropathy in HSPN patients. METHODS: Data of 275 HSPN patients (aged≥14 years) were retrieved, and all of them underwent a renal biopsy. We re-classified the biopsies according to the ISKDC classification and the updated Oxford classification to analyze their correlations with clinical features and renal outcomes. The renal endpoints were defined as ≥30% reduction in baseline estimated glomerular filtration rate (eGFR) in 2 years, doubling of serum creatinine (Scr) or end stage renal disease. RESULTS: During follow-up period of 56(30,86) months, 30(10.9%) patients reached renal endpoints. Segmental sclerosis was the only pathological feature independently associated with renal endpoints (HR 4.086, 95%CI 1.111-15.026, P = 0.034). Tubular atrophy/ interstitial fibrosis was associated with eGFR and Scr levels, and its correlation with renal endpoints was found by univariate analysis. Endocapillary hypercellularity was associated with 24 h urine protein and is of prognostic value in univariate analysis. Mesangial hypercellularity was not associated with clinical features or renal endpoints. Crescents were associated with 24 h urine protein, Scr and eGFR levels, but both ISKDC and updated Oxford classifications of crescents were not associated with renal endpoints by multivariate analysis. CONCLUSIONS: The updated Oxford classification can help in disease management and renal outcome prediction of HSPN.

A retrospective analysis of children with Henoch-Schonlein purpura and re-evaluation of renal pathologies using Oxford classification.

BACKGROUND: Henoch-Schönlein purpura (HSP) is the most common vasculitis in childhood. The long-term prognosis is variable and depends on renal involvement. The aims of this study were to investigate the clinical and laboratory characteristics of our HSP patients, to identify the risk factors for the development of Henoch-Schönlein purpura nephritis (HSPN) and to assess the efficacy of the Oxford Classification system for predicting renal outcomes. METHODS: We performed a retrospective review of HSP patients who admitted to our center between 2001 and 2016, and were < 18 years on admission. RESULTS: A total of 1120 children with HSP were analyzed. Their mean age was 7.4 ± 3.4 years. At onset, purpura was present in all cases, arthritis/arthralgia in 42.4%, abdominal involvement in 39% and renal involvement in 37%. Risk factors for the development of nephritis were age ≥ 8 years, atypical distribution of purpura, ESR > 20 mm/h and abdominal pain. Renal biopsy was performed on 75 patients before immunosuppressive treatment. The mesangial score was strongly associated with proteinuria. Segmental glomerulosclerosis, tubular atrophy/interstitial fibrosis, and crescent formation of ≥ 50% were associated with reduced eGFR at the time of biopsy. A Kaplan-Meier plot showed that segmental glomerulosclerosis and tubular atrophy/interstitial fibrosis significantly predict poor renal outcome. CONCLUSION: The long-term morbidity of HSP is predominantly attributed to renal involvement. Patients with HSP, who have a high risk to develop nephritis, could be followed for longer periods of time. The Oxford classification is useful in predicting long-term outcomes of HSPN.

Clinical impact of endocapillary proliferation according to the Oxford classification among adults with Henoch-Schönlein purpura nephritis: a multicenter retrospective cohort study.

BACKGROUND: Henoch-Schönlein purpura nephritis (HSPN) is a form of small vessel vasculitis associated with purpura and IgA deposition in the glomeruli. The International Study of Kidney Disease in Children (ISKDC) classification predicts renal prognosis in children with HSPN, but not in adults. Additionally, it is not well known whether the Oxford classification 2016 and/or the Japanese Histologic classification (JHC) are associated with renal outcome. Herein, we investigated the relationship between pathological characteristics and renal outcome among adult patients with HSPN. METHODS: A multicenter retrospective cohort study was conducted in adult patients with HSPN who underwent renal biopsy between 2004 and 2014. Two nephrologists classified each patient according to the Oxford classification 2016, JHC, and the ISKDC classification. Renal outcome was defined by a 30% decline in the eGFR and/or end-stage kidney disease. RESULTS: We enrolled 74 adult patients with HSPN (mean age, 47.8 ± 17.4 years; mean eGFR, 76.4 ± 25.8 ml/min/1.73 m2; median proteinuria, 1.40 [IQR: 0.70-2.38] g/day). During a mean follow-up period of 68.0 ± 33.0 months, fourteen patients (18.9%) reached the renal outcome, and all 14 had received immunosuppressive therapy. The log-rank test revealed that event-free renal survival was significantly shorter in patients with endocapillary proliferation (E1) according to the Oxford classification than in those with E0 (p = 0.0072). However, the JHC, ISKDC classification and other Oxford lesions could not demonstrate a significant difference in event-free renal survival. In a multivariate Cox model adjusted for clinical and pathological factors, age (HR, 1.57; 95% CI, 1.12-2.21) and E lesion (HR, 6.71; 95% CI, 1.06-42.7) were independent risk factors for renal outcome. CONCLUSIONS: Endocapillary proliferation is significantly associated with renal outcome in adult patients with HSPN, including those receiving immunosuppressive therapy. Other Oxford classification lesions, JHC, and ISKDC classification were not associated with renal outcome.

The ISKDC classification and a new semiquantitative classification for predicting outcomes of Henoch-Schönlein purpura nephritis.

BACKGROUND: Histological findings from primary kidney biopsies were correlated with patient outcomes in a national cohort of paediatric Henoch-Schönlein nephritis (HSN) patients. METHODS: Primary kidney biopsies from 53 HSN patients were re-evaluated using the ISKDC (International Study of Kidney Disease in Children) classification and a modified semiquantitative classification (SQC) that scores renal findings and also takes into account activity, chronicity and tubulointerstitial indices. The ISKDC and SQC classifications were evaluated comparatively in four outcome groups: no signs of renal disease (outcome A, n = 27), minor urinary abnormalities (outcome B, n = 18), active renal disease (outcome C, n = 3) and renal insufficiency, end-stage renal disease or succumbed due to HSN (outcome D, n = 5). For the receiver operating characteristic and logistic regression analyses, outcomes A and B were considered to be favourable and outcomes C and D to be unfavourable. The median follow-up time was 7.3 years. RESULTS: The patients with an unfavourable outcome (C and D), considered together due to low patient numbers, had significantly higher total biopsy SQC scores and activity indices than those who had a favourable one (groups A and B). The chronicity and tubulointerstitial indices differed significantly only between group C + D and group A. The difference in areas under the curve between the total biopsy SQC scores and ISKDC findings was 0.15 [p = 0.04, normal-based 95% confidence interval (CI) 0.007-0.29, bias-controlled 95% CI -0.004 to 0.28]. CONCLUSIONS: Our results suggest that the modified SQC is more sensitive than ISKDC classification for predicting the outcome in HSN cases.

Using the Oxford classification of IgA nephropathy to predict long-term outcomes of Henoch-Schönlein purpura nephritis in adults.

Recently, there has been emerging concern that crescents, the main histologic feature of Henoch-Schönlein purpura nephritis, merely reflect active inflammation, and may not be useful in predicting long-term outcomes. We therefore conducted a single-center retrospective study to evaluate whether the new Oxford classification of immunoglobulin A nephropathy can be used to predict long-term outcome in patients with Henoch-Schönlein purpura nephritis. We included 61 biopsy-proven patients with Henoch-Schönlein purpura nephritis between January 1991 and August 2010. In addition to the International Study of Kidney Disease in Children classification, pathologic findings were also evaluated by the Oxford classification. Primary outcomes were defined as either the onset of estimated glomerular filtration rate <60 ml/min per 1.73 m(2) with ≥30% decrease in estimated glomerular filtration rate from baseline or end-stage renal disease. During a median follow-up of 49.3 months, 13 (21%) patients reached the primary end point. A Kaplan-Meier plot showed that renal event-free survival was significantly longer in patients with <50% crescents than in those with crescents in ≥50% of glomeruli (P=0.003). Among the components of the Oxford classification, patients with endocapillary hypercellularity (E1; P=0.016) and tubular atrophy/interstitial fibrosis (T1/T2; P=0.018) had lower renal survival rates than those with E0 and T0. In a multivariate Cox model adjusted for clinical and pathologic factors, E1 (hazard ratio=8.91; 95% confidence interval=1.47-53.88; P=0.017) and T1/T2 (hazard ratio=8.74; 95% confidence interval=1.40-54.38; P=0.020) were independently associated with reaching a primary outcome, whereas the extent of crescentic lesions was not. Our findings suggest that the Oxford classification can be used in predicting long-term outcomes of Henoch-Schönlein purpura nephritis.

Epidemiology of immunoglobulin A vasculitis (Henoch-Schönlein): current state of knowledge.

PURPOSE OF REVIEW: To review the current knowledge of epidemiological features of immunoglobulin (Ig) A vasculitis (Henoch-Schönlein) and disease etiology. RECENT FINDINGS: The annual incidence of IgA vasculitis in the population is an estimated 3-26.7/100 000 for children and infants and 0.8-1.8/100 000 for adults. These may be conservative approximations of the true frequency because of skewed case-finding strategies. In children, the marked autumn-winter peak in incidence rates, the frequent occurrence after an upper respiratory tract infection and the short interval between disease onset in index cases and in other family members collectively point to a transmissible infectious process. A subset of adult IgA vasculitis could be related to preceding or concurrent malignancies. Despite several lines of evidence supporting the critical role of an exogenous factor in IgA vasculitis, recent progress has been made in understanding the genetic susceptibility to IgA vasculitis. Recent findings also lessened the suggestion that IgA vasculitis might be triggered by vaccination. SUMMARY: IgA vasculitis is two to 33 times more common in children than adults and appears to have a strong environmental component, with possibly different risk factors in childhood and adulthood. Support is strengthening for a role of genetics in IgA vasculitis.

EULAR/PRINTO/PRES criteria for Henoch-Schönlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part II: Final classification criteria.

OBJECTIVES: To validate the previously proposed classification criteria for Henoch-Schönlein purpura (HSP), childhood polyarteritis nodosa (c-PAN), c-Wegener granulomatosis (c-WG) and c-Takayasu arteritis (c-TA). METHODS: Step 1: retrospective/prospective web-data collection for children with HSP, c-PAN, c-WG and c-TA with age at diagnosis

EULAR/PRINTO/PRES criteria for Henoch-Schönlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part I: Overall methodology and clinical characterisation.

OBJECTIVES: To report methodology and overall clinical, laboratory and radiographic characteristics for Henoch-Schönlein purpura (HSP), childhood polyarteritis nodosa (c-PAN), c-Wegener granulomatosis (c-WG) and c-Takayasu arteritis (c-TA) classification criteria. METHODS: The preliminary Vienna 2005 consensus conference, which proposed preliminary criteria for paediatric vasculitides, was followed by a EULAR/PRINTO/PRES - supported validation project divided into three main steps. Step 1: retrospective/prospective web-data collection for HSP, c-PAN, c-WG and c-TA, with age at diagnosis

EULAR/PReS endorsed consensus criteria for the classification of childhood vasculitides.

BACKGROUND: There has been a lack of appropriate classification criteria for vasculitis in children. OBJECTIVE: To develop a widely accepted general classification for the vasculitides observed in children and specific and realistic classification criteria for common childhood vasculitides (Henoch-Schönlein purpura (HSP), Kawasaki disease (KD), childhood polyarteritis nodosa (PAN), Wegener's granulomatosis (WG), and Takayasu arteritis (TA)). METHODS: The project was divided into two phases: (1) the Delphi technique was used to gather opinions from a wide spectrum of paediatric rheumatologists and nephrologists; (2) a consensus conference using nominal group technique was held. Ten international experts, all paediatricians, met for the consensus conference. Agreement of at least 80% of the participants was defined as consensus. RESULTS: Consensus was reached to base the general working classification for childhood vasculitides on vessel size. The small vessel disease was further subcategorised into "granulomatous" and "non-granulomatous." Final criteria were developed to classify a child as HSP, KD, childhood PAN, WG, or TA, with changes introduced based on paediatric experience. Mandatory criteria were suggested for all diseases except WG. CONCLUSIONS: It is hoped that the suggested criteria will be widely accepted around the world because of the reliable techniques used and the international and multispecialist composition of the expert group involved.

Henoch-Schoenlein nephritis in adults-clinical features and outcomes in Finnish patients.

BACKGROUND: Henoch-Schoenlein purpura (HSP) is a small vessel vasculitis that often involves the kidneys. It affects many more children than adults. Few studies on HSP nephritis (HSN) in adult patients have been reported. One aim of the study described here was to determine clinical features in adults diagnosed at a single center as suffering from HSN. Other aims were to record outcomes of the disease and factors associated with its progression. METHODS: Between 1980 and 1995, 42 adults attending our clinic were diagnosed consecutively, by means of renal biopsy, as suffering from HSN. Data on 38 patients with a follow-up period of at least a year were subsequently analyzed to determine whether any clinical, laboratory or histopathological variable was associated with the progression of HSN. RESULTS: The mean age of the patients on biopsy was 42.0 years (SD 16.5). Eighteen of the 38 patients were male. Eleven of the 38 patients had isolated hematuria as an indication for renal biopsy and 25 had Ccr > or = 85 ml/min on diagnosis. Eight patients exhibited progression of HSN, 3 to end-stage renal failure (ESRF), during a mean follow-up time of 6.1 years (SD 4.3). Renal survival 10 years after renal biopsy was 91%. No histopathological findings were associated with poor outcome. The only factor statistically significantly related to the progression of HSN was a level of proteinuria greater than 1.0 g/24 h (p < 0.05). Hypertension and level of renal function were not significant prognostic factors either, except in a subgroup of 25 patients with initially normal renal function on diagnosis (p < 0.05 in both). In this subgroup, lower serum albumin levels were also found to be predictive for the progression of HSN. CONCLUSIONS: HSN is rare in adults and outcomes are unpredictable. However, any adult with purpura and persistent urinary abnormalities should undergo renal biopsy to determine a diagnosis: all patients suffering from HSN should be carefully monitored to determine whether the condition progresses. Attention should be paid especially to the degree of proteinuria, and also to hypertension in early stages of the disease.

Problems of classification of Henoch Schonlein purpura: an Indian perspective.

A 2-year prospective study was carried out in which 71 patients with primary cutaneous vasculitis were classified using the American College of Rheumatology (ACR) classification and the Chapel Hill Consensus Conference (CHCC) recommendations for Henoch Schonlein purpura (HSP). The sensitivity of the ACR criteria was 64.8% and that of the CHCC definition 31%. When the ACR criteria were combined with results of direct immunofluorescence (DIF) the sensitivity was 78.9%. The concordance between the two systems was low as only 12 patients fulfilled criteria for both classifications. Although the ACR criteria were found to be more useful in the classification of HSP our data suggest that they need to be modified to include adults with disease. The age at onset of disease was higher than that in the west. Seventy per cent of patients identified by either classification were > 20 years of age. The prevalence of gut involvement, microhaematuria and proteinuria was < 25% in both groups. The sensitivity of histopathology on the other hand was 80.4% and was not influenced by the duration of the lesion. The DIF test was a useful adjunct to histopathology if it was done within 48 h as the yield of a positive test was significantly higher in this group as compared to the patients who had the test done later.

A prospective study of vasculitis patients collected in a five year period: evaluation of the Chapel Hill nomenclature.

OBJECTIVE: To test the usefulness of the Chapel Hill nomenclature, supplemented with surrogate parameters, as diagnostic criteria for primary vasculitides. METHODS: To prospectively evaluate vasculitis patients according to a standardised clinical and para-clinical programme. In accordance with the Chapel Hill publication surrogate parameters were used: proteinuria, haematuria and red blood cell casts (glomerulonephritis), angiographic or ultrasonic demonstration of aneurysms or stenoses (arteritis), radiological lung infiltrates or cavitations of more than one month's duration (granuloma in the lungs), bloody nasal discharge or crusts, chronic sinusitis, otitis and/or mastoiditis, bone and/or cartilage destruction, and acute hearing loss (granuloma in upper airways). RESULTS: The following entities were diagnosed: giant cell arteritis (n=14), Takayasu arteritis (n=1), polyarteritis nodosa (n=2), Wegener's granulomatosis (n=27), Churg-Strauss syndrome (n=2), microscopic polyangiitis (n=12), Henoch-Schönlein purpura (n=2), cutaneous leucocytoclastic angiitis (n=37), and secondary vasculitis (n=21). Giant cell arteritis and cutaneous leucocytoclastic angiitis were in all cases diagnosed by biopsy. Using the Chapel Hill nomenclature supplemented with surrogate parameters, only 8 of 27 patients were diagnosed with Wegener's granulomatosis, and 3 of 12 cases with microscopic polyangiitis. The number of patients in the remaining diagnostic entities were considered to few to evaluate. CONCLUSIONS: The Chapel Hill nomenclature, supplemented with surrogate parameters, failed to act as diagnostic criteria in Wegener's granulomatosis and microscopic polyangiitis. The following diagnostic criteria are proposed for Wegener's granulomatosis: (1) Biopsy or surrogate parameter for granulomatous inflammation in the respiratory system and (2) Biopsy verified necrotising vasculitis in small to medium sized vessels or biopsy/surrogate parameter for glomerulonephritis or positive PR3-ANCA test and (3) Lack of eosinophilia in blood and biopsy samples. The following diagnostic criteria are proposed for microscopic polyangiitis: (1) Biopsy verified necrotising vasculitis in small vessels and/or glomerulonephritis with few or no immune deposits and (2) Involvement of more than one organ system as indicated by biopsy verified vasculitis in small to medium sized vessels or surrogate parameter for glomerulonephritis and (3) Lack of biopsy and surrogate parameter for granulomatous inflammation in the respiratory system. Using these criteria all Wegener's patients and 9 of 12 patients with microscopic polyangiitis could be diagnosed.

Púrpura de Scholein-Henoch: evaluación de once pacientes pediátricos / Schoenlein-Henöch purpura: evaluation of eleven pediatric cases

Se presentan once pacientes afectados de síndrome de Schonlein-Henoch, lo que motivó a su internación en el Servicio de Pediatría de nuestro hospital. Las edades oscilaron entre 4 y 15 años, el período de estudio fue de 3 años (1994-1996). Se evalúan los factores etiológicos involucrados, las características clínicas, la evolución y el tratamiento

Henoch-Schönlein nephritis in children and adults. Morphological features and clinicopathological correlations.

Rheumatoid purpura or Henoch-Schönlein syndrome is an IgA vasculitis affecting small vessels. The acute disease progresses by successive flare-ups of limited duration. Long-term prognosis depends mainly on the degree of initial renal damage. A review of the literature shows that renal involvement occurs in about 33% of children and 63% of adults with rheumatoid purpura. The most typical manifestation is segmentary focal glomerulonephritis, always associated with granulous IgA deposits in the mesangium. When renal signs are severe enough to warrant renal biopsy (generally at urine protein > 1 g/d and/or organic renal failure) the risk of developing chronic renal failure is 18% in children and 28% in adults. The best prognostic features are histological. The percentage of crescents, the presence of interstitial fibrosis and the presence of dense sub-epithelial deposits are correlated with risk of chronic renal failure. This risk is high (47%) in children with crescents in more than half the glomeruli. In adults, the percentage of crescents associated with unfavorable course appears to be lower than 50%. Predictions are only valid if no further renal flare-up occurs. In addition, histology cannot precisely predict the course of persistent renal sequelae. The severity of sequelae determines the risk and the rapidity of developing chronic renal failure. It is thus recommended to follow patients with Henoch-Schönlein nephritis for long periods.

Henoch-Schönlein purpura in adulthood and childhood: two different expressions of the same syndrome.

OBJECTIVE: To assess the possible differences between children (< or = 20 years) and adults (> 20 years) with Henoch-Schönlein purpura (HSP). METHODS: A retrospective study of an unselected population of patients with HSP who presented to our teaching hospital between 1975 and 1994. Patients were classified as having HSP according to the criteria proposed by Michel et al. RESULTS: Following the above-mentioned criteria, 162 white patients (113 male and 49 female) were classified as having HSP; 46 of the patients were adults (mean +/- SD age 53.2 +/- 16.9 years) and 116 were children (6.9 +/- 3.1 years). We were unable to identify any precipitating event in 72% of the adults and 66% of the children. The frequency of previous drug treatment, primarily antibiotics or analgesics, was similar in both groups, whereas previous upper respiratory tract infection was more frequent among the children (P < 0.02). At symptom onset, cutaneous lesions were the main clinical manifestation in both groups. However, adults had a lower frequency of abdominal pain (P < 0.008) and fever (P < 0.01), and a higher frequency of joint symptoms (P < 0.001). During the clinical course, adults had more frequent (P < 0.001) and severe renal involvement. An increased erythrocyte sedimentation rate was also more frequent in the adults (P < 0.001). Adults required more aggressive therapy, consisting of steroids (P < 0.002) and/or cytotoxic agents (P < 0.001). The outcome was relatively good in both age groups, with complete recovery in 107 children (93.9%) and in 33 adults (89.2%) after a mean +/- SD followup of 19.4 +/- 27.7 (median 12) and 21.8 +/- 33.5 (median 15) months, respectively. CONCLUSION: In adulthood, HSP, as defined by the criteria proposed by Michel et al, represents a more severe clinical syndrome, with a higher frequency of renal involvement. However, the final outcome of HSP is equally good in patients of both age groups.

Classification of vasculitis.

Usually classifications of vasculitic syndromes are based on clinical and histopathologic findings because pathogenetic mechanisms are poorly understood. A subcommittee of the Diagnostic and Therapeutic Criteria Committee of the American College of Rheumatology recently developed classification criteria for seven major vasculitic disorders through the analysis of prospectively collected patient data from 48 centers. Using two classification methods, the subcommittee derived criteria for polyareritis nodosa, Churg-Strauss syndrome, Wegner's granulomatosis, hypersensitivity vasculitis, Henoch-Schönlein purpura, giant cell (temporal) arteritis, and Takayasu's arteritis. Although such criteria may identify typical patients with a distinct form of vasculitis, they are not intended to establish a diagnosis in an individual patient; rather, they should aid comparability of different patient groups in various research endeavors.

The American College of Rheumatology 1990 criteria for the classification of Henoch-Schönlein purpura.

Criteria for identifying Henoch-Schönlein Purpura (HSP) and distinguishing HSP from other forms of systemic arteritis were developed by comparing the manifestations in 85 patients who had HSP with those of 722 control patients with other forms of vasculitis. By the traditional format of choosing different combinations of candidate criteria and comparing the combinations for their ability to separate HSP cases from controls, 4 criteria were identified: age less than or equal to 20 years at disease onset, palpable purpura, acute abdominal pain, and biopsy showing granulocytes in the walls of small arterioles or venules. The presence of any 2 or more of these criteria distinguish HSP from other forms of vasculitis with a sensitivity of 87.1% and a specificity of 87.7%. The criteria selected by a classification tree method were similar: palpable purpura, age less than or equal to 20 years at disease onset, biopsy showing granulocytes around arterioles or venules, and gastrointestinal bleeding. These were able to distinguish HSP from other forms of vasculitis with a sensitivity of 89.4% and a specificity of 88.1%.

Berger disease: Henoch-Schönlein syndrome without the rash.

Identical 7-year-old twin boys each had a proved adenovirus infection at the same time. A few days later one developed florid Henoch-Schönlein purpura, severe alimentary tract symptoms, and transient joint symptoms. He had an acute nephritic syndrome, which progressed to nephrotic syndrome and renal insufficiency. Biopsy showed severe proliferative glomerulonephritis with crescents and marked deposition of IgA, IgG, C3, and fibrin. The second twin had hematuria and abdominal pain but no rash. Biopsy showed mesangial proliferative glomerulonephritis with mesangial deposits of IgA and, to a lesser extent, IgG and C3. The appearance was characteristic of Berger disease, and the subsequent clinical course has been that of symptomless microscopic hematuria and recurrent macroscopic hematuria with normal renal function. Immunologic studies have not revealed why these identical twins responded differently to the same provocation. Perhaps Berger disease may be considered a variant of Henoch-Schönlein nephritis.