Clinical features and prognoses of 23 patients with chronic granulomatous disease followed for 21 years by a single hospital in Japan

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.

Advances in treatment for chronic granulomatous disease

“…The majority of these transplants have occurred from 2000 on and have a median follow-up of 25 months. (personal communication) An additional 50 patients outside of the US and Canada are reported in various publications including single case reports and a survey of the European experience [31][32][33][34][35][36][37][38][39][40][41][42][43][44] with an overall survival rate of 94% and a success rate of 43 out of the 50 achieving stable donor engraftment. The longest reported follow up to date from the Europeans is 5 years in a patient transplanted using a HLA-matched sibling and a Busulfan/Cytoxan-based conditioning regimen.…”

Invasive Fungal Infections in Patients with Chronic Granulomatous Disease

“…ranges from 26 % in Europe [18] up to 46 % in Japan [19]. More importantly, independent of the epidemiology of fungal infections in the published data, in the cases of pulmonary infection, brain abscesses and osteomyelitis, Aspergillus spp.…”

Monocyte/macrophage-Specific NADPH Oxidase Contributes to Antimicrobial Host Defense in X-CGD

“…Invasive fungal infections, principally aspergillosis, increase with age and account for one-third to half of all deaths [2,[16][17][18][19]. CGD patients also frequently experience a variety of inflammatory complications such as granulomatous enteritis resembling Crohn's disease, and some have autoimmune disorders [20][21][22][23].…”