Chronic Granulomatous Disease Treatment & Management
- Author: Roman Janusz Nowicki, MD, PhD; Chief Editor: Dirk M Elston, MD more...
Early diagnosis and treatment can significantly improve the prognosis. Modern therapy for chronic granulomatous disease (CGD) includes aggressive and prolonged administration of antibiotics and prednisone. Treatment for inflammatory and autoimmune complications in patients with CGD is problematic because most agents are immune suppressive and immunity is already impaired in patients with CGD. Many patients respond well to corticosteroids, but they might require prolonged courses.
Sulfasalazine and azathioprine are useful steroid-sparing agents. Tumor necrosis factor-α (TNF-α) inhibitors such as infliximab are effective anti-inflammatory agents but might significantly increase the risk of severe and even fatal infections. The risk of infection needs to be weighed carefully against the risks of uncontrolled mucosal inflammation or surgery that might be further complicated by persistent inflammation, abscesses, and fistulae formation at surgical sites. If TNF-α inhibitors are used, augmented prophylaxis and enhanced vigilance regarding exposures are mandatory.
Methotrexate and hydroxychloroquine (Plaquenil) can be effective in those with arthritides or lupuslike problems.
Conventional treatment consists of lifelong anti-infectious prophylaxis with antibiotics such as trimethoprim-sulfamethoxazole (TMP-SMZ), antimycotics such as itraconazole, and/or interferon (INF)–gamma.
Long-term antibiotic therapy may be helpful. All infections should be treated with broad-spectrum systemic antibiotics. Aggressive treatment should be initiated at the first signs of infection. Antibiotics should be carefully chosen, and therapy should be vigorous. Currently, standard therapy is continuous antibiotic treatment with TMP-SMZ.
Continuous antifungal therapy with itraconazole is effective in preventing infection by Aspergillus species. Amphotericin B should be added to the therapeutic regimen of CGD patients with established invasive aspergillosis. Aspergillus and other fungal infections of the lung typically require prolonged treatment (3-6 mo).
INF-gamma therapy subcutaneously appears to be a promising way of improving neutrophil and monocyte function and may prove to be of particular value in the prevention or treatment of deep fungal infections. INF-gamma is now recommended as life-long therapy for infection prophylaxis in persons with CGD.[26, 27]
Granulocyte transfusions from granulocyte colony-stimulating factor– and dexamethasone-stimulated donors could be a choice of treatment in CGD patients, especially those with disseminated invasive aspergillosis.
Hematopoietic stem cell transplantation (HSCT) may be considered as an early treatment option for CGD. Equivalent outcomes can be obtained with stem cells from matched related donors and matched unrelated donors.
Bone marrow transplantation, as a last resort, can be undertaken. This treatment has been partially successful. Transplantations with other than perfectly matched donors are presently discouraged.[30, 31]
Recurrent impetigo, frequently in the perinasal area and caused by S aureus, usually requires prolonged courses of oral and topical antibiotics to clear.
Noninfectious granulomas may resolve spontaneously, and they rarely require systemic corticosteroid therapy unless vital organs are compromised.
Gene therapy for CGD, owing to the disease's monogenic character, may perhaps be possible in the future.[32, 33, 34, 35]
Surgical drainage of abscesses and resection (when possible) of granulomas.
Gastrointestinal manifestations include perineal abscesses; fistulae; and, characteristically, obstructive lesions associated with granulomatous infiltration; thus consultation with a surgeon may be necessary.
An internist consultation may be necessary because pyrexia should be carefully investigated to reveal the site of the causative infection and the responsible microorganism. Pulmonary disease (eg, recurrent pneumonia, empyema, lung abscess formation) should be treated.
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