Abstract
Purpose
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.
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References
Marciano BE, Wesley R, De Carlo ES, Anderson VL, Barnhart LA, Darnell D, et al. Long-term interferon-gamma therapy for patients with chronic granulomatous disease. Clin Infect Dis. 2004;39(5):692–9.
Martire B, Rondelli R, Soresina A, Pignata C, Broccoletti T, Finocchi A, et al. Clinical features, long-term follow-up and outcome of a large cohort of patients with chronic granulomatous disease: an Italian multicenter study. Clin Immunol. 2008;126(2):155–64.
Alimchandani M, Lai JP, Aung PP, Khangura S, Kamal N, Gallin JI, et al. Gastrointestinal histopathology in chronic granulomatous disease: a study of 87 patients. Am J Surg Pathol. 2013;37(9):1365–72.
Marks DJ, Miyagi K, Rahman FZ, Novelli M, Bloom SL, Segal AW. Inflammatory bowel disease in CGD reproduces the clinicopathological features of Crohn’s disease. Am J Gastroenterol. 2009;104(1):117–24.
Marciano BE, Rosenzweig SD, Kleiner DE, Anderson VL, Darnell DN, Anaya-O’Brien S, et al. Gastrointestinal involvement in chronic granulomatous disease. Pediatrics. 2004;114(2):462–8.
Schappi MG, Klein NJ, Lindley KJ, Rampling D, Smith VV, Goldblatt D, et al. The nature of colitis in chronic granulomatous disease. J Pediatr Gastroenterol Nutr. 2003;36(5):623–31.
Turner D, Otley AR, Mack D, Hyams J, de Bruijne J, Uusoue K, et al. Development, validation, and evaluation of a pediatric ulcerative colitis activity index: a prospective multicenter study. Gastroenterology. 2007;133(2):423–32.
Hyams JS. Crohn’s disease in children. Pediatr Clin N Am. 1996;43(1):255–77.
Kuhns DB, Alvord WG, Heller T, Feld JJ, Pike KM, Marciano BE, et al. Residual NADPH oxidase and survival in chronic granulomatous disease. N Engl J Med. 2010;363(27):2600–10.
Kapur KC, Williams GT, Allison MC. Mesalazine induced exacerbation of ulcerative colitis. Gut. 1995;37(6):838–9.
Holland SM. Chronic granulomatous disease. Clin Rev Allergy Immunol. 2010;38(1):3–10.
Uzel G, Orange JS, Poliak N, Marciano BE, Heller T, Holland SM. Complications of tumor necrosis factor-alpha blockade in chronic granulomatous disease-related colitis. Clin Infect Dis. 2010;51(12):1429–34.
Kang EM, Marciano BE, DeRavin S, Zarember KA, Holland SM, Malech HL. Chronic granulomatous disease: overview and hematopoietic stem cell transplantation. J Allergy Clin Immunol. 2011;127(6):1319–26. quiz 27-8.
Seger RA. Modern management of chronic granulomatous disease. Br J Haematol. 2008;140(3):255–66.
Matts SG. The value of rectal biopsy in the diagnosis of ulcerative colitis. Q J Med. 1961;30:393–407.
Levine A, de Bie CI, Turner D, Cucchiara S, Sladek M, Murphy MS, et al. Atypical disease phenotypes in pediatric ulcerative colitis: 5-year analyses of the EUROKIDS registry. Inflamm Bowel Dis. 2013;19(2):370–7.
Ruel J, Ruane D, Mehandru S, Gower-Rousseau C, Colombel JF. IBD across the age spectrum: is it the same disease? Nat Rev Gastroenterol Hepatol. 2014;11(2):88–98.
Hasegawa M, Yada S, Liu MZ, Kamada N, Munoz-Planillo R, Do N, et al. Interleukin-22 regulates the complement system to promote resistance against pathobionts after pathogen-induced intestinal damage. Immunity. 2014;41(4):620–32.
Acknowledgments
We are grateful to all patients and families affected by CGD who participated in this study. The manuscript was proofread and edited by Ms. Emma Barber and Dr. Eisuke Inoue of the National Center for Child Health and Development, Tokyo, Japan. This study was supported by a Grant from the National Center for Child Health and Development.
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Highlights
• Disease activity defined by PUCAI increased at diagnosis of CGD colitis
• Patients with very early-onset CGD colitis had an aggravated and more progressive form of the condition
• Severe patients with very early-onset CGD colitis required multidrug therapy
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Kawai, T., Arai, K., Harayama, S. et al. Severe and Rapid Progression in Very Early-Onset Chronic Granulomatous Disease-Associated Colitis. J Clin Immunol 35, 583–588 (2015). https://doi.org/10.1007/s10875-015-0180-2
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DOI: https://doi.org/10.1007/s10875-015-0180-2