Abstract
In this paper, we examined the details of severe infections, treatment efficacies, and the prognoses of 23 Japanese patients with chronic granulomatous disease (CGD). We described the mean ages at diagnosis and follow-up, which were 2.8 years (range, 0.7–10 years) and 14.9 years (range, 0.2–28.4 years), respectively. There were three deaths, two from Aspergillus pneumonia and one from liver abscess. Eighteen of the 23 patients (78%) had a complete loss of gp91phox, and three had p22-phox and one had p67phox deficiencies. Aspergillus species were found in 45% of 174 severe infections. The mean height and weight of the 20 surviving patients were −0.8 ± 1.3SD and −1.9 ± 1.9SD below the means for age, respectively. Short stature and underweight (below the 10th percentile of the means) for age were seen in 22% and 17% of the patients, respectively. This growth retardation reflects the severity of the disease. At 20 years of age, there was 87% survival. Ongoing prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMX) or antifungal drugs was given in 16 and 11 patients, respectively. Interferon-gamma (IFN-gamma) was given once a week to 14 patients. Four patients underwent hematopoietic stem cell transplantation (HSCT) and are currently well. There were infections observed in three of 21 identified related carriers of X-linked CGD. A carrier with a liver abscess had 5% normal neutrophils during the acute phase of infection, which returned to 40% normal neutrophils after recovery. The high survival rate in this hospital results from regular follow-up and prophylaxis with TMP-SMX and anti-fungal drugs beginning at the time of diagnosis, along with treatment with weekly IFN-gamma.
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Abbreviations
- CGD:
-
chronic granulomatous disease
- DHR:
-
dihydrorhodamine123
- TMP-SMX:
-
trimethoprim-sulfamethoxazole
- IFN-gamma:
-
interferon-gamma
- SD:
-
standard deviation
- HSCT:
-
hematopoietic stem cell transplantation
References
Aliabadi H, Gonzalez R, Quie PG (1989) Urinary tract disorders in patients with chronic granulomatous disease. N Engl J Med 321:706–708
Berendes H, Bridges RA, Good RA (1957) A fatal granulomatosus of childhood: the clinical study of a new syndrome. Minn Med 40:309–312
Bridges RA, Berendes H, Good RAA (1959) A fatal granulomatous disease of childhood: the clinical, pathological, and laboratory features of a new syndrome. Am J Dis Child 97:387–408
Curnutte JT (1993) Chronic granulomatous disease: the solving of a clinical riddle at the molecular level. Clin Immunol Immunopath 67:S2–S15
Dickerman JD, Colletti RB, Tampas JP (1986) Gastric outlet obstruction in chronic granulomatous disease of childhood. Am J Dis Child 140(6):567–570
Güngör T, Halter J, Klink A, Junge S, Stumpe KD, Seger R, Schanz U (2005) Successful low toxicity hematopoietic stem cell transplantation for high-risk adult chronic granulomatous disease patients. Transplantation 79:1596–1606
Hasui M; The Study Group of Phagocyte Disorders of Japan (1999) Chronic granulomatous disease in Japan: incidence and natural history. Pediatr Int 41:589–593
The International Chronic Granulomatous Disease Cooperative Study Group (1991) A controlled trial of interferon gamma to prevent infection in chronic granulomatous disease. N Engl J Med 324:509–516
Johnson FE, Humbert JR, Kuzela DC, Todd JK, Lilly JR (1975) Gastric outlet obstruction due to X-linked chronic granulomatous disease. Surgery 78(2):217–223
Kamani N, August CS, Douglas SD, Burkey E, Etzioni A, Lischner HW (1984) Bone marrow transplantation in chronic granulomatous disease. J Pediatr 105:42–46
Liese J, Kloos S, Jendrossek V, Petropoulou T, Wintergerst U, Notheis G, Gahr M, Belohradsky BH (2000) Long-term follow-up and outcome of 39 patients with chronic granulomatous disease. J Pediatr 137:687–693
Marciano BE, Wesley R, De Carlo ES, Anderson VL, Barnhart LA, Darnell D, Malech HL, Gallin JI, Holland SM (2004) Long-term interferon-gamma therapy for patients with chronic granulomatous disease. Clin Infect Dis 39:692–699
Margolis DM, Melnick DA, Alling DW, Gallin JI (1990) Trimethoprim-sulfamethoxazole prophylaxis in the management of chronic granulomatous disease. J Infect Dis 162:723–726
Mizukami T, Nunoi H (2004) Chronic granulomatous disease. Progress of basic science and clinical management (in Japanese). Nihon Shouniketueki Gakkaishi 18:69–78
Mouy R, Veber F, Blanche S, Donadieu J, Brauner R, Levron JC, Griscelli C, Fischer A (1994) Long-term itraconazole prophylaxis against Aspergillus infections in thirty-two patients with chronic granulomatous disease. J Pediatr 125:998–1003
Pasic S, Minic A, Minic P, Veljkovic D, Lilic D, Slavkovic B, Pejnovic N, Abinun M (2003) Long-term follow-up and prognosis of chronic granulomatous disease in Yugoslavia: is there a role for early bone marrow transplantation? J Clin Immunol 23(1):55–61
Rösen-Wolff A, Soldan W, Heyne K, Bickhardt J, Gahr M, Roestler J (2001) Increased susceptibility of a carrier of X-linked chronic granulomatous disease (CGD) to Aspergillus fumigatus infection associated with age-related skewing of lyonization. Ann Hematol 80:113–115
Segal BH, Leto TL, Gallin JI, Malech HL, Holland SM (2000) Genetic, biochemical, and clinical features of chronic granulomatous disease. Medicine (Baltimore) 79(3):170–200
Seger RA, Gungor T, Belohradsky BH, Blanche S, Bordigoni P, Di Bartolomeo P, Flood T, Landais P, Müller S, Ozsahin H, Passwell JH, Porta F, Slavin S, Wulffraat N, Zintl F, Nagler A, Cant A, Fischer A; European Group for Blood and Marrow Transplantation (2002) Treatment of chronic granulomatous disease with myeloablative conditioning and an unmodified hemopoietic allograft: a survey of the European experience, 1985–2000. Blood 100:4344–4350
Winkelstein JA, Marino MC, Johnston RB Jr, Boyle J, Curnutte J, Gallin JI, Malech HL, Holland SM, Ochs H, Quie P, Buckley RH, Foster CB, Chanock SJ, Dickler H (2000) Chronic granulomatous disease. Report on a national registry of 368 patients. Medicine 79:155–169
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Kobayashi, S., Murayama, S., Takanashi, S. et al. Clinical features and prognoses of 23 patients with chronic granulomatous disease followed for 21 years by a single hospital in Japan. Eur J Pediatr 167, 1389–1394 (2008). https://doi.org/10.1007/s00431-008-0680-7
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DOI: https://doi.org/10.1007/s00431-008-0680-7