Special Article: Chronic granulomatous disease in the United Kingdom and Ireland: a comprehensive national patient-based registry

Abstract

SummaryThere are no epidemiological studies from the British Isles of chronic granulomatous disease, characterized by recurrent, life-threatening bacterial and fungal infections and inflammatory sequelae. Patients were enrolled in a national registry and medical records were analysed. Of 94 subjects, 69 had X-linked disease, 16 had autosomal recessive disease and nine were unknown. Prevalence was 7·5/million for 1990-99 and 8·5/million for 1980-89. Suppurative adenitis, abscesses and pneumonia presented commonly. Twenty-three of 30 patients who underwent high resolution computerized tomography had chronic respiratory disease. Inflammatory sequelae included bowel stricture and urogenital tract granulomata. Growth failure was common; 75% of those measured were below the population mean. All patients received prophylactic antibiotics and 93% anti-fungal prophylaxis. Interferon gamma was used to treat infection, but rarely as prophylaxis. Despite prophylaxis, estimated survival was 88% at 10 years but 55% at age 30 years. Morbidity remains significant, severe infectious complications common. Curative treatments including stem cell transplantation should be considered for patients with frequent or serious complications.

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].…”

Chronic granulomatous disease with an initial presentation of arthritis and oral ulcers

“…The prevalence of CGD differs by country with estimated prevalence up to 1:111 000 to 1:1 330 000 in Israeli Arabs and the United Kingdom to as low as 1:1 000 000 in a recent Italian cohort (Jones et al 2008;Martire et al 2008;Wolach et al 2008). In North America, the reported disease prevalence is 1:200 000-250 000 with 70% of patients having the mutation in the X-linked CYBB gene encoding gp91 phox .…”

Stem Cell Transplantation for Primary Immunodeficiency

“…Severe combined immunodeficiencies are usually fatal within the first 18 months of life, patients with other primary immunodeficiencies live longer and can survive into adulthood, albeit with a deteriorating quality of life as they accumulate end organ damage secondary to infection and inflammatory complications of the underlying disease. Registry data has provided good quality information about long term prognosis for some of these disorders, even when appropriate antimicrobial prophylaxis is available, enabling parents, patients and physicians to make informed choices about timing of transplantation [6,11,57]. Most non-SCID PIDs are life limiting in the medium to long term, rather than fatal in the first few months of life.…”

“…Quality of life is poor with frequent hospital admissions and poor growth. Even with the best prophylactic treatment, only 50% of patients are alive at 30 years [6] ( Figure 1). HSCT can cure CGD with resolution of infection and colitis but was previously considered to be a high risk procedure.…”

“…Greater awareness of primary immunodeficiency (PID) amongst general paediatricians, highlighted by campaigns promoting warning signs has lead to earlier diagnosis and referral to specialist centres [5]. Indications for HSCT increase as advances in molecular immunology better define PIDs while parallel studies of the natural history of PIDs reveal which will benefit most from early HSCT before organ damage is present [6]. There are now nearly 200 molecularly defined PIDs.…”