今日の臨床サポート

紫斑病性腎炎(小児科)

著者: 張田豊 東京大学 生殖・発達・加齢医学専攻 小児医学講座

監修: 五十嵐隆 国立成育医療研究センター

著者校正/監修レビュー済:2021/03/03
参考ガイドライン:
  1. 日本循環器学会、合同研究班参加学会:血管炎症候群の診療ガイドライン(2017年改訂版)
  1. 日本皮膚科学会:血管炎・血管障害診療ガイドライン2016年改訂版
  1. Interventions for preventing and treating kidney disease in Henoch-Schönlein Purpura (HSP). Cochrane Database Syst Rev. 2015 Aug 7;(8):CD005128. (https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD005128.pub3/full)
  1. KDIGO GN Guideline update: IgA nephropathy and IgA vasculitis-Henoch-Schonlein purpura (HSP) Nephritis. 2018(https://kdigo.org/wp-content/uploads/2018/08/Chap-11-HSP-nephritis-evidence-summary_Final_profiles.pdf)
  1. European consensus-based recommendations for diagnosis and treatment of immunoglobulin A vasculitis-the SHARE initiative. Rheumatology (Oxford). 2019 Sep 1;58(9):1607-1616.
患者向け説明資料

概要・推奨   

  1. IgA血管炎は小児で最も頻度の高い全身性血管炎であり、皮膚・関節・腹部症状(腹痛)の3つを主徴とする。
  1. 紫斑病性腎炎(Henoch-Schoenlein Purpura Nephritis、HSPN)は、IgA血管炎に合併する腎炎である。
  1. プレドニゾロンはIgA血管炎の腎炎発症予防としての効果はなく、IgA血管炎発症早期の投与は長期の腎機能を改善しない(エビデンスランクS/CS)。
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧に はご契約が必要となりま
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧に はご契約が必要となります。
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
張田豊 : 特に申告事項無し[2021年]
監修:五十嵐隆 : 特に申告事項無し[2021年]

改訂のポイント:
  1. ガイドライン、レビューに基づき、修正を行った。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. IgA血管炎(血管性紫斑病、アレルギー性紫斑病、ヘノッホ・シェーンライン紫斑病)は小児に多い全身の毛細・細小血管の血管炎(<図表>)であり、皮膚・関節・腹部症状(腹痛)の3つを主徴とする。
  1. 紫斑病性腎炎(Henoch-Schoenlein Purpura Nephritis: HSPN)とは、IgA血管炎 の1症状としてみられる腎炎である。
 
IgA血管炎の皮膚の病理

フィブリノイド壊死を伴う表皮の血管炎

 
  1. IgA血管炎では全例で下肢を中心に点状出血斑や紫斑を認める。そのほか関節痛(約40~70%)や腹部症状(50~90%)を合併する。関節痛や腹部症状は紫斑出現前に現れることがある。<図表>
 
IgA血管炎の発疹

皮膚の紫斑

 
  1. 紫斑の発症前に上気道感染が先行する症例が多い。
  1. 9割が小児であり、なかでも幼稚園から小学校低学年の小児に好発する。
IgA血管炎の3割程度(15~50%)に腎炎を合併する。75~90%は紫斑出現後1カ月以内(多くは2週間以内)で、3カ月以降に腎炎を発症することはまれであるが、6カ月頃までは腎炎が発症し得る。
  1. 微小血尿のみを来すものから、半月体を形成し急性進行性糸球体腎炎(RPGN)を呈するものまで幅広い。腎炎の重症度が長期予後を左右する。
  1. 発症年齢が高い(9歳以上)、腹痛、反復する血管炎がある場合、などが紫斑病性腎炎発症のリスクファクターである[1]
  1. 年長児および成人の紫斑病性腎炎は重症例が多い傾向がある。
問診・診察のポイント  
  1. 紫斑病性腎炎は小児の二次性糸球体腎炎のなかで最も頻度が高く重要な疾患である。

これより先の閲覧には個人契約のトライアルまたはお申込みが必要です。

最新のエビデンスに基づいた二次文献データベース「今日の臨床サポート」。
常時アップデートされており、最新のエビデンスを各分野のエキスパートが豊富な図表や処方・検査例を交えて分かりやすく解説。日常臨床で遭遇するほぼ全ての症状・疾患から薬剤・検査情報まで瞬時に検索可能です。

まずは15日間無料トライアル
本サイトの知的財産権は全てエルゼビアまたはコンテンツのライセンサーに帰属します。私的利用及び別途規定されている場合を除き、本サイトの利用はいかなる許諾を与えるものでもありません。 本サイト、そのコンテンツ、製品およびサービスのご利用は、お客様ご自身の責任において行ってください。本サイトの利用に基づくいかなる損害についても、エルゼビアは一切の責任及び賠償義務を負いません。 また、本サイトの利用を以て、本サイト利用者は、本サイトの利用に基づき第三者に生じるいかなる損害についても、エルゼビアを免責することに合意したことになります。  本サイトを利用される医学・医療提供者は、独自の臨床的判断を行使するべきです。本サイト利用者の判断においてリスクを正当なものとして受け入れる用意がない限り、コンテンツにおいて提案されている検査または処置がなされるべきではありません。 医学の急速な進歩に鑑み、エルゼビアは、本サイト利用者が診断方法および投与量について、独自に検証を行うことを推奨いたします。

文献 

著者: Seza Ozen, Stephen D Marks, Paul Brogan, Noortje Groot, Nienke de Graeff, Tadej Avcin, Brigitte Bader-Meunier, Pavla Dolezalova, Brian M Feldman, Isabelle Kone-Paut, Pekka Lahdenne, Liza McCann, Clarissa Pilkington, Angelo Ravelli, Annet van Royen, Yosef Uziel, Bas Vastert, Nico Wulffraat, Sylvia Kamphuis, Michael W Beresford
雑誌名: Rheumatology (Oxford). 2019 Sep 1;58(9):1607-1616. doi: 10.1093/rheumatology/kez041.
Abstract/Text OBJECTIVES: IgA vasculitis (IgAV, formerly known as Henoch-Schönlein purpura) is the most common cause of systemic vasculitis in childhood. To date, there are no internationally agreed, evidence-based guidelines concerning the appropriate diagnosis and treatment of IgAV in children. Accordingly, treatment regimens differ widely. The European initiative SHARE (Single Hub and Access point for paediatric Rheumatology in Europe) aims to optimize care for children with rheumatic diseases. The aim therefore was to provide internationally agreed consensus recommendations for diagnosis and treatment for children with IgAV.
METHODS: Recommendations were developed by a consensus process in accordance with the EULAR standard operating procedures. An extensive systematic literature review was performed, and evidence-based recommendations were extrapolated from the included papers. These were evaluated by a panel of 16 international experts via online surveys and subsequent consensus meeting, using nominal group technique. Recommendations were accepted when ⩾80% of experts agreed.
RESULTS: In total, 7 recommendations for diagnosis and 19 for treatment of paediatric IgAV were accepted. Diagnostic recommendations included: appropriate use of skin and renal biopsy, renal work-up and imaging. Treatment recommendations included: the importance of appropriate analgesia and angiotensin-converting enzyme inhibitor use and non-renal indications for CS use, as well as a structured approach to treating IgAV nephritis, including appropriate use of CS and second-line agents in mild, moderate and severe disease along with use of angiotensin-converting enzyme inhibitors and maintenance therapy.
CONCLUSION: The SHARE initiative provides international, evidence-based recommendations for the diagnosis and treatment of IgAV that will facilitate improvement and uniformity of care.

© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
PMID 30879080  Rheumatology (Oxford). 2019 Sep 1;58(9):1607-1616. doi:・・・
著者: Seza Ozen, Angela Pistorio, Silvia M Iusan, Aysin Bakkaloglu, Troels Herlin, Riva Brik, Antonella Buoncompagni, Calin Lazar, Ilmay Bilge, Yosef Uziel, Donato Rigante, Luca Cantarini, Maria Odete Hilario, Clovis A Silva, Mauricio Alegria, Ximena Norambuena, Alexandre Belot, Yackov Berkun, Amparo Ibanez Estrella, Alma Nunzia Olivieri, Maria Giannina Alpigiani, Ingrida Rumba, Flavio Sztajnbok, Lana Tambic-Bukovac, Luciana Breda, Sulaiman Al-Mayouf, Dimitrina Mihaylova, Vyacheslav Chasnyk, Claudia Sengler, Maria Klein-Gitelman, Djamal Djeddi, Laura Nuno, Chris Pruunsild, Jurgen Brunner, Anuela Kondi, Karaman Pagava, Silvia Pederzoli, Alberto Martini, Nicolino Ruperto, Paediatric Rheumatology International Trials Organisation (PRINTO)
雑誌名: Ann Rheum Dis. 2010 May;69(5):798-806. doi: 10.1136/ard.2009.116657.
Abstract/Text 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 RESULTS: 827 patients with HSP, 150 with c-PAN, 60 with c-WG, 87 with c-TA and 52 with c-other were compared with each other. A patient was classified as HSP in the presence of purpura or petechiae (mandatory) with lower limb predominance plus one of four criteria: (1) abdominal pain; (2) histopathology (IgA); (3) arthritis or arthralgia; (4) renal involvement. Classification of c-PAN required a systemic inflammatory disease with evidence of necrotising vasculitis OR angiographic abnormalities of medium-/small-sized arteries (mandatory criterion) plus one of five criteria: (1) skin involvement; (2) myalgia/muscle tenderness; (3) hypertension; (4) peripheral neuropathy; (5) renal involvement. Classification of c-WG required three of six criteria: (1) histopathological evidence of granulomatous inflammation; (2) upper airway involvement; (3) laryngo-tracheo-bronchial involvement; (4) pulmonary involvement (x-ray/CT); (5) antineutrophilic cytoplasmic antibody positivity; (6) renal involvement. Classification of c-TA required typical angiographic abnormalities of the aorta or its main branches and pulmonary arteries (mandatory criterion) plus one of five criteria: (1) pulse deficit or claudication; (2) blood pressure discrepancy in any limb; (3) bruits; (4) hypertension; (5) elevated acute phase reactant.
CONCLUSION: European League Against Rheumatism/Paediatric Rheumatology International Trials Organisation/Paediatric Rheumatology European Society propose validated classification criteria for HSP, c-PAN, c-WG and c-TA with high sensitivity/specificity.

PMID 20413568  Ann Rheum Dis. 2010 May;69(5):798-806. doi: 10.1136/ard・・・
著者: H Narchi
雑誌名: Arch Dis Child. 2005 Sep;90(9):916-20. doi: 10.1136/adc.2005.074641. Epub 2005 May 4.
Abstract/Text BACKGROUND: The duration of follow up to assess the risk of long term renal impairment in Henoch-Schönlein purpura (HSP) without nephritic or nephrotic syndrome or renal failure on diagnosis remains undetermined.
AIMS: To undertake a systematic review of the literature to assess whether the risk of long term renal impairment without renal involvement on diagnosis could be estimated and to determine the time period when renal involvement is very unlikely after the diagnosis of HSP.
METHODS: Search of studies of unselected children with HSP, and available information on urinary findings, renal involvement, and long term renal function follow up. Studies of selected children with HSP nephropathy at diagnosis were excluded.
RESULTS: Twelve studies of 1133 children were reviewed. The follow up period ranged from 6 weeks to 36 years. Proteinuria and/or haematuria, which occurred in 34.2%, of which only one fifth were in association with nephritic or nephrotic syndrome, developed in 85% of cases within 4 weeks of the diagnosis of HSP, in 91% within 6 weeks, and in 97% within 6 months. Permanent renal impairment never developed after normal urinalysis; it occurred in 1.6% of those with isolated urinary abnormalities, and in 19.5% of those who developed nephritic or nephrotic syndrome.
CONCLUSION: No long term renal impairment occurred after normal urinalysis. Even if urinalysis is normal at presentation, the testing should be continued for six months. There is no need to follow up after the first six months those whose urinalysis remains normal.

PMID 15871983  Arch Dis Child. 2005 Sep;90(9):916-20. doi: 10.1136/adc・・・
著者: Stella F Edström Halling, Magnus P Söderberg, Ulla B Berg
雑誌名: Pediatr Nephrol. 2005 Jan;20(1):46-51. doi: 10.1007/s00467-004-1650-6. Epub 2004 Oct 22.
Abstract/Text We evaluated the renal hemodynamics and the urine protein excretion rates of 73 children with Henoch-Schonlein nephritis (HSN). In 40 children we also performed a renal biopsy. The glomerular filtration rate (GFR) and effective renal plasma flow were determined by the clearances of inulin and para-aminohippurate during water diuresis. Urine albumin and IgG excretion were assessed in short-term timed samples. The mean GFR at the first examination was reduced in the HSN patients and most reduced in those with nephrotic proteinuria. There was an inverse correlation between the GFR at the first examination and the amount of albuminuria and urinary IgG excretion. Among the 40 patients with some degree of proteinuria who underwent a renal biopsy, 9 of 13 patients with mild to moderate proteinuria had severe morphological changes. GFR correlated inversely and fractional albumin and IgG excretion directly with the severity of the pathological findings on the biopsy, and with segmental and global sclerosis, the grade of mesangial proliferation, and interstitial inflammation. In conclusion, GFR is moderately reduced early in HSN and more reduced in patients with more proteinuria and in those with more advanced morphological changes. Moreover, even mild to moderate proteinuria may indicate severe morphological changes, which increase the indications for early renal biopsy in these patients.

PMID 15503170  Pediatr Nephrol. 2005 Jan;20(1):46-51. doi: 10.1007/s00・・・
著者: A R Goldstein, R H White, R Akuse, C Chantler
雑誌名: 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.

PMID 1346291  Lancet. 1992 Feb 1;339(8788):280-2.
著者: Hitoshi Wakaki, Kenji Ishikura, Hiroshi Hataya, Yuko Hamasaki, Tomoyuki Sakai, Nahoko Yata, Tetsuji Kaneko, Masataka Honda
雑誌名: Pediatr Nephrol. 2011 Jun;26(6):921-5. doi: 10.1007/s00467-011-1827-8. Epub 2011 Mar 4.
Abstract/Text Nephritis develops in 18-81% of Henoch-Schönlein purpura patients, and the long-term outcomes of this nephritis show great variation. A nephrotic state at disease onset has been proposed as a predictor of poor renal outcomes. We studied 42 children with Henoch-Schönlein purpura nephritis (HSPN) who presented with a nephrotic state during the early phase of the disease. The median age of the patients at the time of diagnosis was 7.4 years. The median follow-up period was 6.2 years. Twenty-five children (60%) made a complete recovery; nine (21%) progressed to end-stage renal disease. Multivariate logistic regression analyses revealed that the nephrotic state lasting for more than 3 months had a significant effect on renal outcomes (odds ratio 11.6; 95% confidential interval, 1.16-348.4; p = 0.03), whereas initial renal insufficiency, renal pathological findings, age at onset, and types of treatment did not. These findings indicate that clinical presentation, particularly duration of the nephrotic state, is related to long-term outcomes in HSPN patients with nephrosis. Our results also indicate that the therapeutic options for HSPN patients with a nephrotic state should be based on the clinical presentation rather than on the initial pathological findings alone.

PMID 21373776  Pediatr Nephrol. 2011 Jun;26(6):921-5. doi: 10.1007/s00・・・
著者: Jan Dudley, Graham Smith, Anne Llewelyn-Edwards, Kate Bayliss, Katie Pike, Jane Tizard
雑誌名: Arch Dis Child. 2013 Oct;98(10):756-63. doi: 10.1136/archdischild-2013-303642. Epub 2013 Jul 11.
Abstract/Text BACKGROUND: The long-term prognosis of Henoch-Schönlein Purpura (HSP) is predominantly determined by the extent of renal involvement. There is no consensus as to whether treatment with prednisolone at presentation can prevent or ameliorate the progression of nephropathy in HSP.
METHODS: Children under 18 years of age with new-onset HSP were randomly assigned to receive prednisolone or placebo for 14 days. The primary outcomes were (a) the presence of proteinuria at 12 months (defined as urine protein : creatinine ratio (UP : UC) >20 mg/mmol) and (b) the need for additional treatment (defined as the presence of hypertension requiring treatment or renal biopsy anomalies or the need for treatment of renal disease) during the 12 month study period.
RESULTS: 352 children were randomised. Of those patients with laboratory UP : UC results available at 12 months, 18/123 (15%) patients on prednisolone and 13/124 (10%) patients on placebo had UP : UC >20 mg/mmol. There was no significant difference in the proportion of patients with UP : UC >20 mg/mmol at 12 months between the treatment groups (OR (prednisolone/placebo)=1.46, 95% CI 0.68 to 3.14, n=247), even after adjusting for baseline proteinuria and medications known to affect proteinuria (adjusted OR=1.29, 95% CI 0.58 to 2.82, n=247). Similarly, there was no significant difference in the time needed for additional treatment between the two groups (hazard ratio (HR) (prednisolone/placebo)=0.53, 95% CI 0.18 to 1.59, n=323).
CONCLUSIONS: This is the largest trial of the role of steroids in children with HSP. We found no evidence to suggest that early treatment with prednisolone reduces the prevalence of proteinuria 12 months after disease onset in children with HSP.
TRIAL REGISTRATION NUMBER: ISRCTN71445600.

PMID 23845696  Arch Dis Child. 2013 Oct;98(10):756-63. doi: 10.1136/ar・・・
著者: Jaana Ronkainen, Olli Koskimies, Marja Ala-Houhala, Marjatta Antikainen, Jussi Merenmies, Jukka Rajantie, Timo Ormälä, Juha Turtinen, Matti Nuutinen
雑誌名: J Pediatr. 2006 Aug;149(2):241-7. doi: 10.1016/j.jpeds.2006.03.024.
Abstract/Text OBJECTIVE: To evaluate the efficacy of early prednisone therapy in preventing renal and treating extrarenal and renal symptoms in Henoch-Schönlein purpura (HSP) in a placebo-controlled trial.
STUDY DESIGN: A total of 171 patients (84 treated with prednisone and 87 receiving placebo) were included and followed up for 6 months. The endpoints were renal involvement at 1, 3, and 6 months and healing of extrarenal symptoms. The analyses were performed on an intent-to-treat basis.
RESULTS: Prednisone (1 mg/kg/day for 2 weeks, with weaning over the subsequent 2 weeks) was effective in reducing the intensity of abdominal pain (pain score, 2.5 vs 4.8; P = .029) and joint pain (4.6 vs 7.3; P = .030). Prednisone did not prevent the development of renal symptoms but was effective in treating them; renal symptoms resolved in 61% of the prednisone patients after treatment, compared with 34% of the placebo patients (difference = 27%; 95% confidence interval = 3% to 47%; P = .024).
CONCLUSIONS: The general use of prednisone in HSP is not supported, but patients with disturbing symptoms may benefit from early treatment, because prednisone reduces extrarenal symptoms and is effective in altering (but not preventing) the course of renal involvement.

PMID 16887443  J Pediatr. 2006 Aug;149(2):241-7. doi: 10.1016/j.jpeds.・・・
著者: F T Saulsbury
雑誌名: 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.

PMID 10575422  Medicine (Baltimore). 1999 Nov;78(6):395-409.
著者: Marco Zaffanello, Vassilios Fanos
雑誌名: Pediatr Nephrol. 2009 Oct;24(10):1901-11. doi: 10.1007/s00467-008-1066-9. Epub 2008 Dec 9.
Abstract/Text Considerable concern has been expressed on the importance of identifying an improved therapeutic protocol for use in the treatment of childhood Henoch-Schönlein purpura nephritis, primarily due to the unpredictable success shown to date in improving long-term renal outcome. This review focuses on published reports describing the outcomes of therapeutic approaches currently being used in the treatment of pediatric Henoch-Schönlein purpura nephritis, with the aim of providing information that will facilitate a treatment-based approach in children presenting with varying degrees of kidney disease. The conclusions of the authors of this review are that currently prescribed treatments of children affected by Henoch-Schönlein purpura nephritis are not adequately guided by evidence obtained in properly designed, randomized, placebo-controlled trials with outcome markers related to the progression to end stage renal disease (level I evidence). Moreover, firm evidence supporting the best practice to be applied with the aim of delaying the progression of kidney disease is still lacking.

PMID 19066976  Pediatr Nephrol. 2009 Oct;24(10):1901-11. doi: 10.1007/・・・
著者: Outi Jauhola, Jaana Ronkainen, Olli Koskimies, Marja Ala-Houhala, Pekka Arikoski, Tuula Hölttä, Timo Jahnukainen, Jukka Rajantie, Timo Örmälä, Matti Nuutinen
雑誌名: Pediatr Nephrol. 2012 Jun;27(6):933-9. doi: 10.1007/s00467-012-2106-z. Epub 2012 Feb 5.
Abstract/Text BACKGROUND: Corticosteroids have been shown not to prevent the development of Henoch-Schönlein nephritis. However, long-term follow-up data are scarce.
METHODS: The long-term outcome of patients in a randomized placebo-controlled prednisone study was evaluated 8 years later with a health questionnaire completed by 160/171 (94%) patients and by urine and blood pressure screening (138/171, 81%).
RESULTS: Twelve patients had hematuria and/or proteinuria and seven had hypertension. The patients with nephritis at onset of Henoch-Schönlein purpura (HSP) had an increased risk of hypertension and/or urine abnormalities (odds ratio 3.6, p = 0.022, 95% confidence interval 1.3-10.0). There were no differences between the prednisone and placebo groups. Recurrences of purpura were reported by 15 patients, with some recurrences continuing for 10 years. All five reported pregnancies were complicated by proteinuria. Four patients presented with hematuria and/or proteinuria at the control visit, and four had hypertension. Of these, two had a decreased estimated glomerular filtration rate.
CONCLUSIONS: HSP has a good long-term prognosis in unselected patients, although skin relapses with/without late-onset nephritis may occur, even a decade after the initial disease. Urine and blood pressure abnormalities 8 years after HSP are associated with nephritis at its onset. Early prednisone treatment does not affect the outcome and should not be routinely used.

PMID 22311342  Pediatr Nephrol. 2012 Jun;27(6):933-9. doi: 10.1007/s00・・・
著者: Yukihiko Kawasaki, Junzo Suzuki, Hitoshi Suzuki
雑誌名: 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.

PMID 15031341  Nephrol Dial Transplant. 2004 Apr;19(4):858-64. doi: 10・・・
著者: Yukihiko Kawasaki, Junzo Suzuki, Ruriko Nozawa, Shigeo Suzuki, Hitoshi Suzuki
雑誌名: Pediatrics. 2003 Apr;111(4 Pt 1):785-9.
Abstract/Text OBJECTIVE: To evaluate the efficacy of methylprednisolone and urokinase pulse therapy (MUPT) for severe Henoch-Schönlein nephritis, we examined the clinical manifestation and prognosis of patients with MUPT on long-term observation.
METHODS: We enrolled 56 patients with Henoch-schönlein nephritis who had been diagnosed with at least type IIIb from 1980 to 1998 on long-term observation and had been treated with MUPT. The clinical features, laboratory data, and pathologic findings between "pre-MUPT" and "post-MUPT," and the prognosis of these patients on long-term observation were retrospectively investigated.
RESULTS: The mean urinary protein excretion after 6 months of treatment had decreased significantly compared with "pre-MUPT." Hypercoagulant state in "after the completion of urokinase pulse therapy" improved compared with "pre-MUPT." First renal biopsies were performed in all patients and second biopsies were performed in 27 patients. The activity index decreased significantly from 4.1 +/- 1.9 at first biopsy to 2.5 +/- 1.7 at second biopsy, while the chronicity index did not differ between first and second biopsy. None had renal insufficiency and renal survival rate was 100% for the decade.
CONCLUSIONS: Although uncontrolled, our study suggested that MUPT is effective for those patients with the risk of progression of their nephropathy, especially if started early during the course of the disease before the crescents become fibrous.

PMID 12671112  Pediatrics. 2003 Apr;111(4 Pt 1):785-9.
著者: A Oner, K Tinaztepe, O Erdogan
雑誌名: 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.

PMID 7742225  Pediatr Nephrol. 1995 Feb;9(1):6-10.
著者: K Iijima, S Ito-Kariya, H Nakamura, N Yoshikawa
雑誌名: 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.

PMID 9630047  Pediatr Nephrol. 1998 Apr;12(3):244-8.
著者: Yukihiko Kawasaki, Kazuhide Suyama, Koichi Hashimoto, Mitsuaki Hosoya
雑誌名: Clin Rheumatol. 2011 Apr;30(4):529-35. doi: 10.1007/s10067-010-1572-6. Epub 2010 Sep 16.
Abstract/Text We evaluated whether methylprednisolone and urokinase pulse therapy combined with mizoribine (MUPM) was effective in children with severe Henoch-Schoenlein purpura nephritis (HSPN). We studied 12 patients who had been diagnosed with HSPN of at least ISKDC type III. All patients were treated with MUPM. Clinical features, pathological findings, and prognosis were prospectively investigated. Ten patients (responders; nine with ISKDC grade IIIb and one with grade IVb) were treated with MUPM, whereas MUPM was discontinued due to the lack of response in two patients (non-responders; two with grade IVb). Among responders, urinary protein excretion had decreased significantly from 99.7 ± 37.8 to 25.9 ± 33.4 mg/m(2) per hour after 3 months of therapy. The acute index and tubulointerstitial scores decreased significantly from 5.8 ± 1.5 and 3.8 ± 0.6 at the first biopsy to 2.3 ± 1.3 and 1.0 ± 0.8 at the second biopsy, respectively. At the most recent follow-up, eight of the responders had normal urine, and two had minor urinary abnormalities. Non-responders demonstrated continued high levels of urinary protein excretion after 3 months of therapy, and MUPM was discontinued. Our study suggests that MUPM is effective in ameliorating the proteinuria and the histological severity of HSPN in patients with <50% crescents but is not so effective for HSPN in patients with >50% crescents.

PMID 20844911  Clin Rheumatol. 2011 Apr;30(4):529-35. doi: 10.1007/s10・・・
著者: Outi Jauhola, Jaana Ronkainen, Helena Autio-Harmainen, Olli Koskimies, Marja Ala-Houhala, Pekka Arikoski, Tuula Hölttä, Timo Jahnukainen, Jukka Rajantie, Timo Ormälä, Matti Nuutinen
雑誌名: 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.

PMID 21626222  Pediatr Nephrol. 2011 Dec;26(12):2159-66. doi: 10.1007/・・・
著者: Jee Min Park, Sung Chul Won, Jae Il Shin, Hyunee Yim, Ki Soo Pai
雑誌名: 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.

PMID 21184240  Pediatr Nephrol. 2011 Mar;26(3):411-7. doi: 10.1007/s00・・・
著者: Jae Il Shin, Jee Min Park, Youn Ho Shin, Ji Hong Kim, Pyung Kil Kim, Jae Seung Lee, Hyeon Joo Jeong
雑誌名: Pediatr Nephrol. 2005 Aug;20(8):1093-7. doi: 10.1007/s00467-005-1864-2. Epub 2005 Jun 10.
Abstract/Text 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/m(2)/day (range 1.5-16 g/m(2)/day) to 0.3 g/m(2)/day (range 0.03-1.2 g/m(2)/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.

PMID 15947993  Pediatr Nephrol. 2005 Aug;20(8):1093-7. doi: 10.1007/s0・・・
著者: M Hattori, K Ito, T Konomoto, H Kawaguchi, T Yoshioka, M Khono
雑誌名: 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.

PMID 10070905  Am J Kidney Dis. 1999 Mar;33(3):427-33.
著者: Chisato Umeda, Shuichiro Fujinaga, Amane Endo, Koji Sakuraya, Satoshi Asanuma, Daishi Hirano
雑誌名: Tohoku J Exp Med. 2020 Jan;250(1):61-69. doi: 10.1620/tjem.250.61.
Abstract/Text Henoch-Schönlein purpura (HSP) is regarded as a benign and self-limiting vasculitis characterized by purpura, arthritis, and gastrointestinal symptoms; however, about one third of the patients develop HSP nephritis (HSPN), the most serious long-term complication. Since 2013, we have proposed that tonsillectomy in addition to intravenous methylprednisolone pulse therapy (IVMP) be performed in all patients with HSPN, similar to immunoglobulin A nephropathy (IgAN) patients because both diseases are considered to a share common pathogenesis. Herein, we retrospectively reviewed the clinical courses of 71 Japanese children with HSPN (34 boys; median age at diagnosis, 6.7 years; median follow-up period, 5.6 years) who had received initial treatment with IVMP (15-20 mg/kg; on 3 consecutive days/week for 3 weeks) followed by oral prednisolone (initially 1 mg/kg; tapered off within 12 months) and achieved clinical remission (i.e., disappearance of both proteinuria and hematuria). The patients were divided into two groups: 31 patients receiving tonsillectomy after IVMP between 2013 and 2017 (tonsillectomy group) and 40 patients receiving IVMP monotherapy between 2003 and 2012 (IVMP group). For the 2 years after IVMP therapy, the rate of HSPN recurrence (i.e., persistent proteinuria combined with hematuria requiring additional treatments) after clinical remission was significantly lower in the tonsillectomy group than the IVMP group (0% vs. 19%, P < 0.05). Despite the short follow-up period in the tonsillectomy group, this study provides the evidence that tonsillectomy may be beneficial for preventing recurrence of HSPN from clinical remission with IVMP therapy in Japanese children.

PMID 31996498  Tohoku J Exp Med. 2020 Jan;250(1):61-69. doi: 10.1620/t・・・

ページ上部に戻る

戻る

さらなるご利用にはご登録が必要です。

こちらよりご契約または優待日間無料トライアルお申込みをお願いします。

(※トライアルご登録は1名様につき、一度となります)


ご契約の場合はご招待された方だけのご優待特典があります。

以下の優待コードを入力いただくと、

契約期間が通常12ヵ月のところ、14ヵ月ご利用いただけます。

優待コード: (利用期限:まで)

ご契約はこちらから