Modern management of chronic granulomatous disease

Abstract

SummaryChronic granulomatous disease (CGD) is a rare primary immunodeficiency disorder of phagocytic cells resulting in failure to kill a characteristic spectrum of bacteria and fungi and in defective degradation of inflammatory mediators with concomitant granuloma formation. Current prophylaxis with trimethoprim-sulfamethoxazole, itraconazole and in selected cases additional interferon gamma is efficient, but imperfect. A significant recent progress towards new antibiotic (e.g. linezolid) and antifungal (e.g. voriconazole and posaconazole) therapy will allow survival of most patients into adulthood. Adolescent and adult CGD is increasingly characterized by inflammatory complications, such as granulomatous lung and inflammatory bowel disease, requiring immunosupressive therapy. Allogeneic haematopoietic stem cell transplantation from a human leucocyte antigen identical donor is currently the only proven curative treatment for CGD and can be offered to the selected patients. Gene-replacement therapy for patients lacking a suitable stem cell donor is still experimental and faces major obstacles and risks. However, it may offer some transitory benefits and has helped in a few cases to overcome life-threatening infections.

Humans with chronic granulomatous disease maintain humoral immunologic memory despite low frequencies of circulating memory B cells

“…2 The underlying causes and consequences of this deficiency remain uncertain, especially given that both hypergammaglobulinemia and hypogammaglobulinemia have been reported in CGD. [3][4][5] Humoral immunologic memory is maintained by antibodysecreting plasma cells in the bone marrow and by memory B cells that reside primarily in secondary lymphoid tissues. 6 CD27 is a convenient marker for identifying memory B cells in humans; however, a more accurate definition of a memory B cell is one that has undergone Ig somatic hypermutation (SHM) with/without class switching after encounter with antigen.…”

Femoral osteomyelitis due to Cladophialophora arxii in a patient with chronic granulomatous disease

“…Although guidelines for treatment of fungal osteomyelitis due to non-Aspergillus fungi are not well established, surgery generally plays an important role in the management of CGD patients [13]. In cases of Aspergillus osteomyelitis, surgical debridement appears to be very important for treatment, and extensive debridement is more effective than limited intralesional debridement [14].…”

Gentherapie der septischen Granulomatose: Chancen und Risiken. Der Weg zur erfolgreichen Therapie einer angeborenen Immundefizienz

“…Derzeit wird eine Prophylaxe mit Co-Trimoxazol und Itraconazol empfohlen [16]. Zudem kann Interferon-gamma zur Prophylaxe von Infektionen eingesetzt werden.…”