title: Severe and Rapid Progression in Very Early-Onset Chronic Granulomatous Disease-Associated Colitis.
abstract: OBJECTIVE
  Chronic granulomatous disease (CGD) is a primary immunodeficiency disease that leads to recurrent infection and hyper-inflammation, occasionally represented by CGD-associated colitis (CGD colitis). Although clinical symptoms of CGD colitis mimic those of ulcerative colitis (UC), there is no reliable standard measurement of disease activity or standard therapeutic strategy for CGD colitis. Here, we examined the clinical manifestation of CGD colitis based on severity using a noninvasive measure of disease activity, the Pediatric Ulcerative Colitis Activity Index (PUCAI), which has been validated and widely used for pediatric UC.
  
  
  METHODS
  Sixteen of 35 CGD patients, who were diagnosed with CGD colitis based on colonoscopic and histological findings, were examined using the PUCAI. Both the PUCAI and the physician global assessment (PGA) tool were retrospectively scored by reviewing medical records.
  
  
  RESULTS
  Disease activity defined by PUCAI was correlated with PGA, and increased at diagnosis of CGD colitis, especially in patients who were younger than 6 years of age (very early-onset CGD colitis: VEO-CGD colitis) when diagnosed with CGD colitis. All severe patients had a more progressive form of VEO-CGD colitis. Unlike mild and moderate patients, severe patients required multidrug therapy of corticosteroids and immunomodulator/immunosuppressants, and some were eventually treated with hematopoietic stem cell transplantation.
  
  
  CONCLUSIONS
  Although the validation of PUCAI in CGD colitis should be considered for future use, our results indicate that noninvasive measures could be effective to measure disease activity and help to determine suitable treatment for CGD colitis. In patients with VEO-CGD colitis, multidrug therapy would need to be considered at an early stage on the basis of disease activity.
authors.affiliation: Department of Human Genetics, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan. kawai-t@ncchd.go.jp.
authors.forename: Toshinao
authors.initials: T
authors.lastname: Kawai
authors.affiliation: Division of Gastroenterology, National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Arai
authors.affiliation: Department of Pediatrics, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Shizuko
authors.initials: S
authors.lastname: Harayama
authors.affiliation: Department of Human Genetics, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Nakazawa
authors.affiliation: Department of Human Genetics, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan.
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Goto
authors.affiliation: Department of Pediatrics, National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Takanobu
authors.initials: T
authors.lastname: Maekawa
authors.affiliation: Department of Pediatrics, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Tamura
authors.affiliation: Department of Human Genetics, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Uchiyama
authors.affiliation: Department of Human Genetics, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Onodera
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D003092:Colitis / Q000175:diagnosis* / Q000453:epidemiology / Q000209:etiology / Q000628:therapy; D003424:Crohn Disease / Q000150:complications / Q000175:diagnosis* / Q000453:epidemiology / Q000628:therapy; D018450:Disease Progression; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D007564:Japan; D008297:Male; D012189:Retrospective Studies
keywords: CGD colitis; Chronic granulomatous disease; granuloma; inflammation; pediatric ulcerative colitis activity index; very early-onset CGD colitis