Approach

Treatment involves prevention of infection with antimicrobial prophylaxis. Vigilant monitoring for infection is required, as patients may have few symptoms despite active serious infection. Because of the heterogeneity and the seriousness of infection, prompt therapeutic measures are indicated. Early consultation with physicians experienced in the care of Chronic granulomatous disease (CGD) is recommended.

Active infections

Procedures to aid in identification of the infecting organism, such as surgical biopsy of infected sites or bronchoalveolar lavage, are recommended before treatment if available. Immediate treatment of any infection should be undertaken in consultation with specialists in immunology and infectious diseases, as infections require aggressive and prolonged therapy. Initial treatment includes broad intravenous coverage of Staphylococcus aureus and gram-negative pathogens, such as Serratia marcescens and Burkholderia cepacia. Early broad antifungal coverage is often needed as well, specifically for Aspergillus species; voriconazole, posaconazole, or liposomal amphotericin are the agents of choice; itraconazole is an alternative option.[58][59][60] Once the organism is identified, directed therapy may be initiated.

Granulocyte transfusions may be administered as a "last resort" for life-threatening infections.[61][62][63][64][65][50] The short-term benefits of providing functional granulocytes should be weighed against the risk from exposure to foreign antigens (e.g., HLA antigens). Alloimmunization is associated with risk of transfusion reactions and may compromise future hematopoietic stem cell transplantation.[65]

The use of interferon gamma in the treatment of infections in CGD patients remains poorly studied and controversial, although some experts support its use in severely ill patients in the hope of providing benefit.[41]

Surgical or radiologic drainage of infected tissue may be required for life-threatening infections.

Hepatic abscesses

Hepatic abscesses are treated with antibiotics in conjunction with corticosteroids, although they may require surgical drainage or excision and are frequently associated with complications.[66][67] Definitive surgical excision and drainage should be considered in patients not responding to antibiotic and corticosteroid therapy.[50]S aureus is typically the etiology.[12] Percutaneous drainage may be helpful.

The use of normal donor granulocytes injected into lesions has been reported, as well as systemic granulocyte infusions and interferon gamma administration.[68] Systemic antibiotic and antifungal treatment is recommended postoperatively in those undergoing surgery.

Gastrointestinal or genitourinary sequelae

Enterocolitis, gastrointestinal obstruction, or genitourinary obstruction secondary to granuloma formation are possible complications. If enterocolitis is infectious in nature, then antibiotics are warranted. However, in CGD, patients often suffer from Crohn-like bowel disease, and the mainstay of therapy is immune suppression, most often with sulfasalazine (or an alternative aminosalicylate) for mild disease or corticosteroids for severe disease and flares. Other more potent immunosuppressive agents may also be used, although caution should be exercised with anti-TNF therapy due to a high rate of complications.[69] Most obstructions of hollow viscera can be managed with corticosteroids, although surgery is indicated for nonresolving obstruction or severe fistulae.[6][8][11]

Prophylactic treatment

Prophylactic treatment is an essential component of CGD management and consists of antimicrobial prophylaxis with or without interferon gamma. Trimethoprim/sulfamethoxazole decreases the incidence of bacterial infection in patients with CGD, with varying effects on the incidence of fungal infection.[15][16][70] Patients who have an allergy to trimethoprim/sulfamethoxazole may be treated with alternative antibiotics. An additional agent may be required to cover methicillin-resistant S aureus if prevalent.

Antifungal prophylaxis with itraconazole has become the standard of care for patients with CGD, and is shown to decrease the incidence of fungal infection.[71] Aspergillus infections have been the most common cause of death in patients with CGD, although this is changing with widespread use of antifungal prophylaxis.[3][16][13]

If itraconazole is not tolerated, choose an alternative antifungal prophylactic medication that is effective against Aspergillus species. Voriconazole is an oral alternative, but it carries the risk of reversible liver damage, photosensitivity, and cutaneous malignancy.[58][59][72] Posaconazole has been used for salvage therapy in patients, although this restricts treatment options for breakthrough infection.[73] Serum drug levels may be required in patients on azole antifungals.

Interferon gamma decreases the incidence of infection, although study results are conflicting.[30][74][75][76][77] Additionally, adverse effects limit usage. The routine use of interferon gamma is highly variable even among specialists. Fever is a common adverse effect associated with interferon treatment. However, the occurrence of fever in a patient with CGD always warrants medical evaluation.

Allogeneic stem cell transplantation

Allogeneic stem cell transplantation is a curative procedure, although it carries its own risks of mortality and morbidity particularly if undertaken later in life. Overall survival is greater than 80%, with the majority of surviving patients achieving cure, particularly if an HLA-matched donor is available.[78][79][80][81][82][83][84] Recent advances in critical care support and in carefully applied conditioning regimens are improving the mortality and morbidity for transplant patients. 

Transplantation should be considered as soon as diagnosis is made if a matched sibling donor is available.[50] Additionally, matched unrelated (including cord blood) donors should be considered appropriate sources for stem cells in children. In adults, very careful consideration must be given to the potential risks and benefits of stem cell transplantation.

Stem cell transplantation should be undertaken in medical centers experienced in transplantation for primary immunodeficiency disorders. Stem cell transplantation has been successfully used to rescue patients with refractory infection, although risks are increased.

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