Therapeutic strategy in p47-phox deficient chronic granulomatous disease presenting as inflammatory bowel disease

Gastrointestinal Abnormalities among Patients with Chronic Granulomatous Disease

“…In contrast to a recent Swedish report [38], yet similar to the UK and Ireland CGD Registry [26], we did not find significant difference in mortality between patients that did or did not receive BMT, while morbidity was reduced following transplantation. Among our patients, colitis that was present prior to transplantation resolved and none of the patients without colitis pre-BMT developed colitis during 3.2-4.6 years of follow-up, which is similar to previous reports (Table 5) of the overwhelming beneficial effects of hematopoietic stem cell transplantation on colitis [15,16,[19][20][21][22][23][24][25][26]38]. Indeed, a recent multicenter study reported that transplantation cured colitis in 22 of 24 patients with CGD, with 1 patient dying after refusing immune suppressive treatment for acute graft versus host disease [27].…”

“…Because of the frequent GI manifestations, patients are often initially evaluated and managed by care providers, who may not be aware to the possibility of an underlying primary immune deficiency. Moreover, several reports identified patients with abnormal neutrophil superoxide generation as suffering from inflammatory bowel disease [2,7,14,15,34,35]. Clues to the correct diagnosis include the very early age of presentation, which is uncommon among patients with inflammatory bowel disease, the presence of extra-intestinal infections typical of CGD and histological features such as pigmented macrophages and granuloma [7,36,37].…”

“…Some have added interferon-gamma for treatment of infections or prophylaxis [12,13], although the long-term benefits are still not clear [14]. Allogeneic bone marrow transplantations (BMT) from HLA matched family donors with myeloablative or non-myeloablative preparation can cure the increased susceptibility to infections of CGD patients [15,16]. Autologous gene therapy has also been explored in limited number of patients with X-linked CGD using higher (10 mg/kg) but still not ablative dose of busulfan [17].…”

“…For CGD patients suffering also from inflammatory GI manifestations, conservative local and systemic immune modulating medications such as low or high doses of steroids, azathioprine [18] or monoclonal antibodies to TNFalpha have been used with varying degree of success [8]. Several studies have also shown resolution of the GI manifestations after BMT [15,16,[19][20][21][22][23][24][25][26][27]. However direct comparison of the outcome of the GI manifestations in CGD patients following the different treatment options are scarce.…”

Clinical immunology Primary Immunodeficiency Diseases in two neighboring pediatric centers: registry data bring out a wide spectrum of diseases with complex clinical presentations

“…Nowadays, it is a well accepted concept that the clinical spectrum of PID includes inflammatory, autoimmune and lymphoproliferation symptoms as well as recurrent or severe infections. Indeed, even disorders classically characterized by infections may present at first with non-infectious symptoms [4]. DOI: 10.5114/ceji.2012.32727 As a consequence, warning signs developed many years ago to improve the recognition of PIDs -such as the 10 signs promoted by the Jeffrey Modell Foundation -may be insufficient today, in particular in pediatric practice [5].…”