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Epidemiology and clinical features of childhood-onset anti-neutrophil cytoplasmic antibody–associated vasculitis: a clinicopathological analysis

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Abstract

Background

This study was performed to determine the clinical features and outcomes of childhood-onset anti-neutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV), particularly microscopic polyangiitis (MPA).

Methods

A retrospective Japanese multicenter study was performed in patients diagnosed with AAV before 16 years of age.

Results

Of 49 patients with AAV, 36 were female. The diagnoses were as follows: MPA (n = 38, 78%), granulomatosis with polyangiitis (GPA; n = 9, 18%), eosinophilic granulomatosis with polyangiitis (EGPA; n = 1, 2%), and other (n = 1, 2%). The median age at onset was 10.7 years, and median time to diagnosis was 2.0 months. Twenty-seven (55%) patients were identified through a school urinary screening program. Initial symptoms included fever and fatigue (45%), and renal (71%), pulmonary (29%), ocular (20%), and mucocutaneous involvement (22%). Although 27 (55%) patients achieved remission and none had died at the last follow-up, at least one recurrence occurred in 13 (48%) patients after a median of 48 months and was more common in patients with GPA (P < 0.01). After a median follow-up of 43 months, seven (14%) patients (all with MPA) progressed to end-stage renal disease (ESRD).

Conclusions

Childhood-onset AAV has an estimated prevalence of 3.41–4.28 per million children and is characterized by female predominance and high frequency of detection in school urinary screening programs. More than 10% of patients with childhood-onset AAV still progress to ESRD without achieving remission. Histological chronicity is a factor associated with ESRD.

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Acknowledgments

The authors would like to thank all the institutions that participated in the surveys and Takayuki Okamoto (Hokkaido University Graduate School of Medicine), Kazushi Tsuruga (Hirosaki University), Naonori Kumagai (Tohoku University School of Medicine), Shigeo Suzuki (Ohara General Hospital), Kazuhide Suyama (Fukushima Medical University Hospital), Yasuo Oyake (Hitachi General Hospital), Yoko Ohwada (Dokkyo Medical University), Isamu Kamimaki (National Hospital Organization Saitama National Hospital), Koji Sakuraya (Saitama Children’s Medical Center), Yoshihiro Aoki (Asahi Hospital), Shosuke Sunami (Japanese Red Cross Narita Hospital), Shinsuke Matsumoto (Matsudo City General Hospital), Takashi Sato (Funabashi Futawa Hospital), Mamiko Suehiro (Chiba Children’s Hospital), Yuji Tomii (Tokyo Women’s Medical University Hospital), Tae Omori (Tokyo Metropolitan Bokutoh Hospital), Shojiro Okamoto (Tokai University Hachioji Hospital), Riku Hamada (Tokyo Metropolitan Children’s Medical Center), Takeshi Yanagihara (Nippon Medical School Musashi Kosugi Hospital), Hisashi Kaneda (Toyama City Hospital), Shoko Iwata (Ogaki Municipal Hospital), Masayoshi Yamada (Shizuoka Children’s Hospital), Naoya Fujita (Aichi Children’s Health and Medical Center), Nami Okamoto (Osaka Medical College Hospital), Kosuke Shabana (Osaka Medical College Hospital), Rika Fujimaru (Osaka City General Hospital), Takahisa Kimata (Kansai Medical University Hospital), Takeshi Ninchoji (Kobe University Graduate School of Medicine), Shingo Ishimori (Kakogawa City Hospital), Toshiyuki Ohta (Hiroshima Prefectural Hospital), Masafumi Teramachi (Fukuoka University Hospital), Kei Nishiyama (Kyushu University Hospital), Toshihiko Shirakawa (Nagasaki University Hospital), Hitoshi Nakazato (Kumamoto University Hospital), Akio Furuse (Japanese Red Cross Kumamoto Hospital), Hideaki Imamura (Faculty of Medicine, University of Miyazaki Hospital), and Tomoo Kise (Nanbu Medical Center/Nanbu Child Medical Center) for their contributions to the study. The authors would also like to thank Mr. Masanori Nimura of Yamate Information Processing Center Ltd. (Tokyo, Japan) for his participation in data management.

Funding

This work was supported by a Health and Labour Sciences Research Grant for Research in Rare and Intractable Diseases from the Ministry of Health, Labour, and Welfare, Japan (H26-nanchitou(nan)-ippan-036).

Author information

Authors and Affiliations

  1. Department of Pediatrics, The Jikei University School of Medicine, Tokyo, Japan

    Daishi Hirano

  2. Department of Pediatrics, Nara Medical University, Nara, Japan

    Tomoaki Ishikawa

  3. Department of Pediatrics, Yokohama City University Medical Center, Yokohama, Japan

    Aya Inaba

  4. Division of Nephrology and Rheumatology, National Center for Child Health and Development, Tokyo, Japan

    Mai Sato

  5. Department of Biostatistics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

    Tomohiro Shinozaki

  6. Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan

    Kazumoto Iijima

  7. Department of Pediatrics, Graduate School of Medicine, Yokohama City University, 3-9 Fuku-ura, Kanazawa-ku, Yokohama, 236-0004, Japan

    Shuichi Ito

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  1. Daishi Hirano
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  2. Tomoaki Ishikawa
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  3. Aya Inaba
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Correspondence to Shuichi Ito.

Ethics declarations

This study was conducted in accordance with the ethical principles of the Declaration of Helsinki and with the ethical guidelines for epidemiological studies issued by the Ministry of Health, Labour and Welfare, Japan. The study was approved by the Ethics Review Committee of Graduate School of Medicine, Yokohama City University (institution of the principal investigator, SI, ID: B151201009) before commencement. Informed consent was not deemed necessary because the data were obtained retrospectively from the patient charts.

Conflict of interest

S.I. has received consulting fees from Novartis Pharma and Loche. S.I. has also received research grants from Asahi Kasei Pharma, Astellas Pharma, and Chugai Pharmaceutical. T.S. has received consulting fees from Takeda Pharmaceutical Company Limited. T.S. has also received lecture fees from Takeda Pharmaceutical Company Limited and Statcom Company Limited.

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The results presented in this paper have not been published previously in whole or part, except in abstract form.

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Hirano, D., Ishikawa, T., Inaba, A. et al. Epidemiology and clinical features of childhood-onset anti-neutrophil cytoplasmic antibody–associated vasculitis: a clinicopathological analysis. Pediatr Nephrol 34, 1425–1433 (2019). https://doi.org/10.1007/s00467-019-04228-4

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