Materiały źródłowe

• #1 Chronic granulomatous disease: Treatment and prognosis – UpToDate

  https://www.uptodate.com/contents/chronic-granulomatous-disease-treatment-and-prognosis

  Chronic granulomatous disease (CGD) is a genetically heterogeneous condition characterized by recurrent, life-threatening bacterial and fungal infections and granuloma formation. CGD is caused by defects in the phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (phox). The cornerstones of CGD management are antimicrobial and immunomodulatory prophylaxis, early diagnosis and aggressive management of infectious complications, careful management of inflammatory complications, and consideration for hematopoietic stem cell repair or replacement. […] The management of CGD focuses on aggressive diagnosis and treatment of infections. The reduction in mortality and morbidity seen over the past few decades is largely attributable to antimicrobial prophylaxis and rapid recognition and treatment of infections in these patients. […] The cornerstones of CGD management are: Antimicrobial prophylaxis, Immunomodulatory therapy with interferon-gamma, Hematopoietic cell transplantation, Gene therapy/gene repair.

• #2 Chronic granulomatous disease: Treatment and prognosis – UpToDate

  https://www.uptodate.com/contents/chronic-granulomatous-disease-treatment-and-prognosis/print

  Chronic granulomatous disease (CGD) is a genetically heterogeneous condition characterized by recurrent, life-threatening bacterial and fungal infections and granuloma formation. The cornerstones of CGD management are antimicrobial and immunomodulatory prophylaxis, early diagnosis and aggressive management of infectious complications, careful management of inflammatory complications, and consideration for hematopoietic stem cell repair or replacement. […] The management of CGD focuses on aggressive diagnosis and treatment of infections. The reduction in mortality and morbidity seen over the past few decades is largely attributable to antimicrobial prophylaxis and rapid recognition and treatment of infections in these patients. […] The cornerstones of CGD management are.

• #3 Chronic Granulomatous Disease Diagnosis and Overview | ACTIMMUNE® (Interferon gamma-1b) HCP

  https://www.actimmunehcp.com/chronic-granulomatous-disease/about-cgd/clinical-overview

  With the development of preventative therapies and early recognition of infectious complications, 90% of children with CGD now survive into adulthood. This remains, however, largely dependent on several factors, including time of diagnosis, access to care, expertise of caregiver, adherence to therapy, and lifestyle modifications. […] Early diagnosis and prophylactic treatment benefits patients with CGD because they have a higher incidence of serious infections relative to the normal population. Serious infections can be life-threatening and result in long hospital stays. […] To help protect patients with CGD against serious infections, triple prophylactic therapy consisting of antibiotics, antifungals, and Interferon gamma, such as ACTIMMUNE, is recommended by the American Academy of Allergy, Asthma Immunology (AAAAI) and American College of Allergy, Asthma Immunology (ACAAI). […] ACTIMMUNE is the only FDA-approved therapy indicated for reducing the frequency and severity of serious infections associated with CGD.

• #4 Chronic Granulomatous Disease | Children’s Hospital of Philadelphia

  https://www.chop.edu/conditions-diseases/chronic-granulomatous-disease

  Currently, there is no cure for CGD, and there is no treatment that helps all children with CGD. There are however, some effective treatments that may help your child avoid infections and better manage their condition. […] Treatments to prevent infection and CGD complications may include: […] Continuous antibiotic and antifungal medication to protect against bacterial and fungal infections. In some patients, interferon gamma-1b injections (Actimmune) may be used preventatively to boost cell production to help your child better fight infections and decrease the frequency of severe infections. In most cases, these medications can prevent infections before they occur or before they worsen. However, if your child experiences an infection while on continuous antibiotics or antifungals, additional medications may be necessary.

• #5 Chronic Granulomatous Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK493171/

  When this disorder was first identified, affected children were certain to die, but now CGD can be managed and has a high survival rate. Management of CGD is based on 3 principles: 1) lifelong antibacterial and antifungal prophylaxis, 2) early diagnosis of infection, and 3) aggressive management of infectious complications. Globally, therapy involves trimethoprim-sulfamethoxazole and itraconazole. Some countries also add interferon-gamma therapy. However, this therapy is not accepted universally. This combination of treatments can reduce severe infections from 1 per patient per year to almost 1 per patient per 10 years. Live bacterial vaccines are best avoided. […] Treatment of acute infections should start early, including determining the exact complicating infectious agent and selecting antibiotics or anti-fungal therapies. Early and aggressive therapy is essential in preventing the spread of infection. Additional diagnostic procedures should be used to identify the microorganism for infections that fail to respond to therapy within 24 to 48 hours. Antifungal therapy should be started before a diagnosis of fungal infections is confirmed. Surgical removal of refractory fungal infections may be necessary as well. Oral glucocorticoids are commonly prescribed for inflammatory manifestations of CGD. The use of tumor necrosis factor-alpha inhibitors in patients with CGD can be associated with high-risk infections and is not generally recommended.

• #6 Pediatric Chronic Granulomatous Disease Treatment & Management: Medical Care, Surgical Care, Complications

  https://emedicine.medscape.com/article/956936-treatment

  Antimicrobial prophylaxis, early and aggressive treatment of infections, and interferon-gamma are the cornerstones of current therapy for chronic granulomatous disease (CGD). Hematopoietic stem cell transplantation (HSCT) from a human leukocyte antigen (HLA) compatible donor can cure CGD. […] HSCT remains a controversial therapeutic modality in this disease, even when stem cells from a matched sibling donor are available. […] Daily prophylaxis of bacterial infections with trimethoprim-sulfamethoxazole (TMP-SMZ; Bactrim) is indicated in CGD. TMP-SMZ prophylaxis reduces the incidence of bacterial infections in CGD without increasing the incidence of fungal infections. […] Ketoconazole is ineffective in reducing fungal infections in patients with CGD. […] High-dose interferon-gamma during severe infectious episodes has been advocated.

• #7 Immunodeficiency Search

  https://www.immunodeficiencysearch.com/chronic-granulomatous-disease

  8. Bactrim and Itraconazole daily prophylaxis and prompt aggressive treatment of infections have been keys to prolonging the lives of patients. […] 9. Stem cell transplantation should be considered for patients with minimal ROI production and recurrent severe infections despite antimicrobial prophylaxis. […] CGD was initially termed fatal granulomatous disease of childhood with most patients not surviving past their first decade of life. Currently the majority of patients are expected to survive to adulthood. The two main principles that have resulted in increased patient survival are antibacterial/antifugal prophylaxis and aggressive management of infections. […] A. PROPHYLAXIS: The following lifelong prophylactic regimens should be started for all patients: 1. Trimethoprim-sulfamethoxazole (TMP-SMX) 5mg/kg/day (based on TMP component) up to a maximum of 320mg.

• #8 Chronic Granulomatous Disease (CGD): Commonly Associated Pathogens, Diagnosis and Treatment

  https://www.mdpi.com/2076-2607/11/9/2233

  Additionally, HCT is associated with event-free survival rates of more than 80% in patients with CGD and improves the quality of life. […] Antimicrobial and antifungal prophylaxis are the most common management routes used to minimize the incidence of infections. […] Drugs such as trimethoprim-sulfamethoxazole reduce the occurrence of bacterial infections in patients with CGD but do not interfere considerably with the gut microbiome. […] Itraconazole considerably reduces invasive fungal infections, and newer azole drugs, such as voriconazole, posaconazole, and isavuconazole, are available, providing more options for treating these fungal infections. […] Treatment using TNF-alpha inhibitors in patients with CGD could help improve the outcome of severe inflammatory complications despite the associated risk factors. […] Gene therapy remains in the experimental stage. […] Current gene therapy trials, which remains experimental, have demonstrated that lentiviruses or gene editing can be used as curative therapy where HCT is inappropriate for a patient and removes the risk of graft-versus-host disease.

• #9 Immunodeficiency Search

  https://www.immunodeficiencysearch.com/chronic-granulomatous-disease

  2. Itraconazole 5mg/kg once daily (maximum 200mg) […] 3. Interferon gamma (50mcg/m2 subcutaneously 3 times weekly) has demonstrated a reduction in the number of infections in a number of studies. […] B. ACUTE TREATMENT: Identification of causative pathogens is essential for directing appropriate treatment. […] C. COLITIS TREATMENT: Colitis is usually responsive to oral prednisone therapy (1mg/kg/day). […] D. GI AND GU OBSTRUCTION FROM GRANULOMA: Obstructive granulomas tend to be exquisitely sensitive to prednisone therapy (1mg/kg/day) for 1 week followed by a slow 6 week taper. […] E. STEM CELL TRANSPLANTATION: Stem cell transplantation is a curative therapy for this disease in patients who have a fully matched donor. […] Recent data indicate that patients with chronic granulomatous disease and modest residual production of ROI have significantly less severe illness and a greater likelihood of long-term survival than patients with little residual ROI production. Thus, early HSCT may be a consideration for patients with no ROI production.

• #10 Pediatric Chronic Granulomatous Disease Treatment & Management: Medical Care, Surgical Care, Complications

  https://emedicine.medscape.com/article/956936-treatment

  Antimicrobial prophylaxis, early and aggressive treatment of infections, and interferon-gamma are the cornerstones of current therapy for chronic granulomatous disease (CGD). Hematopoietic stem cell transplantation (HSCT) from a human leukocyte antigen (HLA) compatible donor can cure CGD. […] HSCT remains a controversial therapeutic modality in this disease, even when stem cells from a matched sibling donor are available. […] Daily prophylaxis of bacterial infections with trimethoprim-sulfamethoxazole (TMP-SMZ; Bactrim) is indicated in CGD. TMP-SMZ prophylaxis reduces the incidence of bacterial infections in CGD without increasing the incidence of fungal infections. […] Ketoconazole is ineffective in reducing fungal infections in patients with CGD. […] High-dose interferon-gamma during severe infectious episodes has been advocated.

• #11 Chronic Granulomatous Disease Diagnosis and Overview | ACTIMMUNE® (Interferon gamma-1b) HCP

  https://www.actimmunehcp.com/chronic-granulomatous-disease/about-cgd/clinical-overview

  With the development of preventative therapies and early recognition of infectious complications, 90% of children with CGD now survive into adulthood. This remains, however, largely dependent on several factors, including time of diagnosis, access to care, expertise of caregiver, adherence to therapy, and lifestyle modifications. […] Early diagnosis and prophylactic treatment benefits patients with CGD because they have a higher incidence of serious infections relative to the normal population. Serious infections can be life-threatening and result in long hospital stays. […] To help protect patients with CGD against serious infections, triple prophylactic therapy consisting of antibiotics, antifungals, and Interferon gamma, such as ACTIMMUNE, is recommended by the American Academy of Allergy, Asthma Immunology (AAAAI) and American College of Allergy, Asthma Immunology (ACAAI). […] ACTIMMUNE is the only FDA-approved therapy indicated for reducing the frequency and severity of serious infections associated with CGD.

• #12 Chronic granulomatous disease – Wikipedia

  https://en.wikipedia.org/wiki/Chronic_granulomatous_disease

  Management of chronic granulomatous disease revolves around two goals: 1) diagnose the disease early so that antibiotic prophylaxis can be given to keep an infection from occurring, and 2) educate the patient about his or her condition so that prompt treatment can be given if an infection occurs. […] Physicians often prescribe the antibiotic trimethoprim-sulfamethoxazole to prevent bacterial infections. This drug also has the benefit of sparing the normal bacteria of the digestive tract. Fungal infection is commonly prevented with itraconazole, although a newer drug of the same type called voriconazole may be more effective. The use of this drug for this purpose is still under scientific investigation. […] Interferon, in the form of interferon gamma-1b (Actimmune) is approved by the Food and Drug Administration for the prevention of infection in CGD. It has been shown to reduce infections in CGD patients by 70% and to decrease their severity. Although its exact mechanism is still not entirely understood, it has the ability to give CGD patients more immune function and therefore, greater ability to fight off infections. This therapy has been the standard treatment for CGD for several years. […] Hematopoietic stem cell transplantation from a matched donor is curative although not without significant risk.

• #13

  https://www.healio.com/news/pediatrics/20190910/qa-raising-awareness-of-chronic-granulomatous-disease

  Active treatment for CGD has shown to significantly improve patient outcomes, and earlier diagnosis and intervention can lead to patients living longer and healthier lives. There is even a cure for CGD, but patients must be diagnosed early and treated aggressively to be suitable candidates. […] The treatment of infections in patients with CGD requires prompt and aggressive use of antibiotics, along with surgical drainage when needed. Empiric antibiotics are initially aimed at the most common organisms until a specific infectious cause is identified. […] The cornerstone of long-term management of CGD includes antibiotic and antifungal prophylaxis taken daily to prevent infections, usually with trimethoprim/sulfamethoxazole and itraconazole. The introduction of antimicrobial prophylaxis significantly reduced the rates of serious infections and mortality in CGD. Prophylaxis treatment including interferon gamma subcutaneous injections helps to boost macrophage activity and reduces the rates of serious infection about 70%. Additionally, infections that occur while taking interferon gamma may also be less serious. The cure for CGD is a bone marrow transplantation, but there are a lot of risks and this option currently is not widely available. Gene therapy is a promising new treatment for CGD that may avoid many of the risks of a bone marrow transplant and is currently available in research clinical trials only. […] Prophylactic antibiotics, antifungals and interferon gamma reduce infections and increase healthy periods for patients and are important for reducing hospitalizations for infections and the need for intravenous antibiotics.

• #14

  https://www.healio.com/news/pediatrics/20190910/qa-raising-awareness-of-chronic-granulomatous-disease

  Active treatment for CGD has shown to significantly improve patient outcomes, and earlier diagnosis and intervention can lead to patients living longer and healthier lives. There is even a cure for CGD, but patients must be diagnosed early and treated aggressively to be suitable candidates. […] The treatment of infections in patients with CGD requires prompt and aggressive use of antibiotics, along with surgical drainage when needed. Empiric antibiotics are initially aimed at the most common organisms until a specific infectious cause is identified. […] The cornerstone of long-term management of CGD includes antibiotic and antifungal prophylaxis taken daily to prevent infections, usually with trimethoprim/sulfamethoxazole and itraconazole. The introduction of antimicrobial prophylaxis significantly reduced the rates of serious infections and mortality in CGD. Prophylaxis treatment including interferon gamma subcutaneous injections helps to boost macrophage activity and reduces the rates of serious infection about 70%. Additionally, infections that occur while taking interferon gamma may also be less serious. The cure for CGD is a bone marrow transplantation, but there are a lot of risks and this option currently is not widely available. Gene therapy is a promising new treatment for CGD that may avoid many of the risks of a bone marrow transplant and is currently available in research clinical trials only. […] Prophylactic antibiotics, antifungals and interferon gamma reduce infections and increase healthy periods for patients and are important for reducing hospitalizations for infections and the need for intravenous antibiotics.

• #15 Immunodeficiency Search

  https://www.immunodeficiencysearch.com/chronic-granulomatous-disease

  2. Itraconazole 5mg/kg once daily (maximum 200mg) […] 3. Interferon gamma (50mcg/m2 subcutaneously 3 times weekly) has demonstrated a reduction in the number of infections in a number of studies. […] B. ACUTE TREATMENT: Identification of causative pathogens is essential for directing appropriate treatment. […] C. COLITIS TREATMENT: Colitis is usually responsive to oral prednisone therapy (1mg/kg/day). […] D. GI AND GU OBSTRUCTION FROM GRANULOMA: Obstructive granulomas tend to be exquisitely sensitive to prednisone therapy (1mg/kg/day) for 1 week followed by a slow 6 week taper. […] E. STEM CELL TRANSPLANTATION: Stem cell transplantation is a curative therapy for this disease in patients who have a fully matched donor. […] Recent data indicate that patients with chronic granulomatous disease and modest residual production of ROI have significantly less severe illness and a greater likelihood of long-term survival than patients with little residual ROI production. Thus, early HSCT may be a consideration for patients with no ROI production.

• #16 CGD Connections – Living with Chronic Granulomatous Disease

  https://www.cgdconnections.com/

  ACTIMMUNE is used to treat chronic granulomatous disease, or CGD. CGD is a genetic disorder, usually diagnosed in childhood, that affects some cells of the immune system and the body’s ability to fight infections effectively. […] The most common side effects with ACTIMMUNE are flu-like symptoms such as fever, headache, chills, muscle pain, or fatigue, which may decrease the longer you take ACTIMMUNE. Taking ACTIMMUNE at bedtime may help with these symptoms, and acetaminophen may help prevent fever and headache.

• #17 Chronic Granulomatous Disease Treatment | ACTIMMUNE® (Interferon gamma-1b) HCP

  https://www.actimmunehcp.com/chronic-granulomatous-disease/actimmune-for-cgd/why-actimmune

  ACTIMMUNE is thought to engage the adaptive immune response in chronic granulomatous disease (CGD) by aiding the innate immune system. […] ACTIMMUNE: An immunomodulatory therapy that helps reduce the frequency and severity of serious infections in patients with CGD. […] ACTIMMUNE is an immunomodulatory therapy, which helps reduce the frequency and severity of serious infections in patients with CGD and is proven to result in a 64 percent reduction in the total number and rate of serious infections. […] As part of a combination treatment regimen along with prophylaxis therapy that includes antibiotics and antifungals, interferon gamma therapy, such as ACTIMMUNE, is recommended by the American Academy of Allergy, Asthma Immunology (AAAAI) and The American College of Allergy, Asthma Immunology (ACAAI). […] ACTIMMUNE (Interferon gamma-1b) is indicated for reducing the frequency and severity of serious infections associated with chronic granulomatous disease.

• #18 Chronic granulomatous disease: Treatment and prognosis – UpToDate

  https://www.uptodate.com/contents/chronic-granulomatous-disease-treatment-and-prognosis

  Chronic granulomatous disease (CGD) is a genetically heterogeneous condition characterized by recurrent, life-threatening bacterial and fungal infections and granuloma formation. CGD is caused by defects in the phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (phox). The cornerstones of CGD management are antimicrobial and immunomodulatory prophylaxis, early diagnosis and aggressive management of infectious complications, careful management of inflammatory complications, and consideration for hematopoietic stem cell repair or replacement. […] The management of CGD focuses on aggressive diagnosis and treatment of infections. The reduction in mortality and morbidity seen over the past few decades is largely attributable to antimicrobial prophylaxis and rapid recognition and treatment of infections in these patients. […] The cornerstones of CGD management are: Antimicrobial prophylaxis, Immunomodulatory therapy with interferon-gamma, Hematopoietic cell transplantation, Gene therapy/gene repair.

• #19 Chronic Granulomatous Disease Treatment & Management: Medical Care, Surgical Care, Consultations

  https://emedicine.medscape.com/article/1116022-treatment

  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. […] If a fungal invasive infection is identified or strongly suspected, intravenous voriconazole is recommended as initial treatment. […] In case of multidrug refractoriness, life-threatening infections (eg, aspergillosis), hematopoietic stem cell transplantation (HSCT) with reduced-intensity conditioning represents a valid curative option. […] Gene editing is being studied. […] 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.

• #20

  https://www.healio.com/news/pediatrics/20190910/qa-raising-awareness-of-chronic-granulomatous-disease

  Active treatment for CGD has shown to significantly improve patient outcomes, and earlier diagnosis and intervention can lead to patients living longer and healthier lives. There is even a cure for CGD, but patients must be diagnosed early and treated aggressively to be suitable candidates. […] The treatment of infections in patients with CGD requires prompt and aggressive use of antibiotics, along with surgical drainage when needed. Empiric antibiotics are initially aimed at the most common organisms until a specific infectious cause is identified. […] The cornerstone of long-term management of CGD includes antibiotic and antifungal prophylaxis taken daily to prevent infections, usually with trimethoprim/sulfamethoxazole and itraconazole. The introduction of antimicrobial prophylaxis significantly reduced the rates of serious infections and mortality in CGD. Prophylaxis treatment including interferon gamma subcutaneous injections helps to boost macrophage activity and reduces the rates of serious infection about 70%. Additionally, infections that occur while taking interferon gamma may also be less serious. The cure for CGD is a bone marrow transplantation, but there are a lot of risks and this option currently is not widely available. Gene therapy is a promising new treatment for CGD that may avoid many of the risks of a bone marrow transplant and is currently available in research clinical trials only. […] Prophylactic antibiotics, antifungals and interferon gamma reduce infections and increase healthy periods for patients and are important for reducing hospitalizations for infections and the need for intravenous antibiotics.

• #21 Chronic Granulomatous Disease

  https://www.aaaai.org/conditions-treatments/primary-immunodeficiency-disease/chronic-granulomatous-disease

  Therapeutic options for CGD include prophylactic antibiotics and antifungal medications, interferon-gamma injections, and aggressive management of acute infections. […] Bone marrow transplantation can cure CGD, however this therapy is complex and transplant candidates and donors must be carefully selected, weighing the risks and benefits carefully. […] The best treatment plan for CGD is to prevent infections from occurring. Special preventative antibiotics are a mainstay of treatment for CGD. These greatly reduce the chances of infection. […] When an infection occurs, antibiotic treatment is prescribed but it generally requires a much longer amount of time to be effective. […] Bone marrow transplant is another treatment option for some people with severe symptoms of CGD.

• #22 Chronic Granulomatous Disease Treatment & Management: Medical Care, Surgical Care, Consultations

  https://emedicine.medscape.com/article/1116022-treatment

  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. […] If a fungal invasive infection is identified or strongly suspected, intravenous voriconazole is recommended as initial treatment. […] In case of multidrug refractoriness, life-threatening infections (eg, aspergillosis), hematopoietic stem cell transplantation (HSCT) with reduced-intensity conditioning represents a valid curative option. […] Gene editing is being studied. […] 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.

• #23 Chronic Granulomatous Disease Treatment & Management: Medical Care, Surgical Care, Consultations

  https://emedicine.medscape.com/article/1116022-treatment

  HSCT may be considered as an early treatment option for CGD. […] Bone marrow transplantation (BMT), as a last resort, can be undertaken. This treatment has been partially successful. […] Noninfectious granulomas may resolve spontaneously, and they rarely require systemic corticosteroid therapy unless vital organs are compromised. […] In addition to systemic antifungal treatment, surgical debridement or excision of consolidated infection is advised when possible, including surgical drainage of abscesses and resection (when possible) of granulomas.

• #24 Chronic Granulomatous Disease (CGD) – Immunology; Allergic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/immunology-allergic-disorders/immunodeficiency-disorders/chronic-granulomatous-disease-cgd

  Treatment of chronic granulomatous disease is continuous prophylactic antibiotics, particularly sulfamethoxazole/trimethoprim 800/160 mg orally twice a day. Oral antifungals are given as primary prophylaxis or are added if fungal infections occur even once; most useful are itraconazole, voriconazole, and posaconazole. […] Interferon gamma may reduce severity and frequency of infections and is usually included in the treatment regimen. […] Granulocyte transfusions can be lifesaving when infections are severe. […] Consider hematopoietic stem cell transplantation.

• #25 Chronic Granulomatous Disease: The European Experience | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0005234

  Granulocyte transfusions are increasingly given to CGD patients when traditional therapies fail to resolve life-threatening infections, especially with Aspergillus spp. Seven percent of the patients received a granulocyte transfusion at one point. […] A curative therapy for CGD is stem-cell transplantation. However, this treatment has a considerable risk of transplantation-related morbidity and mortality, especially in patients with severely compromised pulmonary function or other debilitating illnesses. In this cohort, 24 patients (6%) had been treated with stem-cell transplantation, of whom 5 had died at the time of inclusion. No patients in this cohort had at the time of inclusion been treated with gene therapy. This treatment had a promising, though transient, clinical effect in some selected patients, but insertional mutagenesis also bears new risks.

• #26 Chronic Granulomatous Disease Treatment & Management: Medical Care, Surgical Care, Consultations

  https://emedicine.medscape.com/article/1116022-treatment

  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- (TNF-) 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- inhibitors are used, augmented prophylaxis and enhanced vigilance regarding exposures are mandatory.

• #27 Chronic Granulomatous Disease Treatment & Management: Medical Care, Surgical Care, Consultations

  https://emedicine.medscape.com/article/1116022-treatment

  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- (TNF-) 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- inhibitors are used, augmented prophylaxis and enhanced vigilance regarding exposures are mandatory.

• #28 Chronic Granulomatous Disease Treatment & Management: Medical Care, Surgical Care, Consultations

  https://emedicine.medscape.com/article/1116022-treatment

  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- (TNF-) 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- inhibitors are used, augmented prophylaxis and enhanced vigilance regarding exposures are mandatory.

• #29 Chronic Granulomatous Disease Treatment & Management: Medical Care, Surgical Care, Consultations

  https://emedicine.medscape.com/article/1116022-treatment

  HSCT may be considered as an early treatment option for CGD. […] Bone marrow transplantation (BMT), as a last resort, can be undertaken. This treatment has been partially successful. […] Noninfectious granulomas may resolve spontaneously, and they rarely require systemic corticosteroid therapy unless vital organs are compromised. […] In addition to systemic antifungal treatment, surgical debridement or excision of consolidated infection is advised when possible, including surgical drainage of abscesses and resection (when possible) of granulomas.

• #30 Immunodeficiency Search

  https://www.immunodeficiencysearch.com/chronic-granulomatous-disease

  2. Itraconazole 5mg/kg once daily (maximum 200mg) […] 3. Interferon gamma (50mcg/m2 subcutaneously 3 times weekly) has demonstrated a reduction in the number of infections in a number of studies. […] B. ACUTE TREATMENT: Identification of causative pathogens is essential for directing appropriate treatment. […] C. COLITIS TREATMENT: Colitis is usually responsive to oral prednisone therapy (1mg/kg/day). […] D. GI AND GU OBSTRUCTION FROM GRANULOMA: Obstructive granulomas tend to be exquisitely sensitive to prednisone therapy (1mg/kg/day) for 1 week followed by a slow 6 week taper. […] E. STEM CELL TRANSPLANTATION: Stem cell transplantation is a curative therapy for this disease in patients who have a fully matched donor. […] Recent data indicate that patients with chronic granulomatous disease and modest residual production of ROI have significantly less severe illness and a greater likelihood of long-term survival than patients with little residual ROI production. Thus, early HSCT may be a consideration for patients with no ROI production.

• #31 Chronic Granulomatous Disease (CGD): Commonly Associated Pathogens, Diagnosis and Treatment

  https://www.mdpi.com/2076-2607/11/9/2233

  Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by a defect in the phagocytic function of the innate immune system owing to mutations in genes encoding the five subunits of the nicotinamide adenine dinucleotide phosphatase (NADPH) oxidase enzyme complex. […] Antibacterial prophylaxis with trimethoprim-sulfamethoxazole, antifungal prophylaxis usually with itraconazole, and interferon gamma immunotherapy have been successfully used in reducing infection in CGD. Haematopoietic stem cell transplantation (HCT) have been successfully proven to be the treatment of choice in patients with CGD. […] HCT is the principal treatment for managing CGD with favourable results regardless of symptoms, age, sex, or mutations. […] Transplantation therapy has an overall survival rate of over 90% in children under 14 years and has improved in the last decade, particularly with early diagnosis.

• #32

  https://link.springer.com/article/10.1007/s12325-017-0636-2

  Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by defects in any of the five subunits of the NADPH oxidase complex responsible for the respiratory burst in phagocytic leukocytes. […] The implementation of routine antimicrobial prophylaxis and the advent of azole antifungals has considerably improved overall survival. […] At present, hematopoietic stem cell transplantation (HCT) is the only curative treatment, and transplantation outcomes have improved over the last few decades with overall survival rates now 90% in children less than 14 years of age. […] The current evidence suggests that myeloablative conditioning results is more durable myeloid engraftment but with increased toxicity and high rates of graft-versus-host disease. […] In recent years, gene therapy has been proposed as an alternative to HCT for patients without an HLA-matched donor.

• #33 Management of Chronic Granulomatous Disease Treatment – For HCPs

  https://www.cgdpathways.com/chronic-granulomatous-disease-management

  Prevention of serious infections is vital for patients with CGD. Serious infections can be difficult to manage and may require lengthy hospitalizations. […] CGD treatment guidelines recommend combination immunomodulatory and prophylaxis therapy. […] For the treatment of active infections, using appropriate antimicrobials based on suspected pathogens or identification is recommended. […] Because of the risk of life-threatening infections, a hematopoietic stem cell transplant (HSCT) may be considered. HSCT provides the recipient with the donors immune system, which has neutrophils with functional nicotinamide adenine dinucleotide phosphate (NADPH) and superoxide anion production. […] It is a potentially curative treatment for patients with CGD but is a procedure associated with potential morbidity and mortality, usually related to graft-versus-host disease. As with any invasive procedure, the risks and benefits of HSCT in the appropriate patient should be carefully considered.

• #34

  https://link.springer.com/article/10.1007/s12325-017-0636-2

  Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by defects in any of the five subunits of the NADPH oxidase complex responsible for the respiratory burst in phagocytic leukocytes. […] The implementation of routine antimicrobial prophylaxis and the advent of azole antifungals has considerably improved overall survival. […] At present, hematopoietic stem cell transplantation (HCT) is the only curative treatment, and transplantation outcomes have improved over the last few decades with overall survival rates now 90% in children less than 14 years of age. […] The current evidence suggests that myeloablative conditioning results is more durable myeloid engraftment but with increased toxicity and high rates of graft-versus-host disease. […] In recent years, gene therapy has been proposed as an alternative to HCT for patients without an HLA-matched donor.

• #35

  https://link.springer.com/article/10.1007/s12325-017-0636-2

  Allogeneic HCT is the only curative treatment for CGD and may reverse both infectious and inflammatory complications. […] Importantly, several studies have demonstrated that outcomes with 10/10 matched unrelated donors (MUD) are comparable to those with matched sibling donors (MSD). […] Gene therapy is an attractive alternative to HCT and would provide an option for patients without an HLA-identical donor. […] Nevertheless, gene editing approaches remain limited by low efficiency and hematopoietic stem cell toxicity through the process of transfection, expansion, and selection. […] Ultimately, as HCT becomes more widely available and better tolerated, we expect overall life expectancy for patients with CGD to increase substantially over the next several years.

• #36 Chronic Granulomatous Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK493171/

  Hematopoietic cell transplantation (HCT) is the only established curative treatment for CGD. Making a rapid diagnosis is important to identify if HCT is possible. The success rate in patients who have undergone HCT is highest in young and disease-free individuals. Ultimately, the decision to undergo HCT depends on the prognosis, donor availability, access to transplantation, and patient preference. […] Patients without an HLA-compatible donor for HCT may be candidates for gene therapy. Gene therapy may also be suited for CGD patients since the disease often results from single genetic defects. This process includes the transfer of autologous hematopoietic stem and progenitor cells (HSPCs) by retroviral vectors and semi-random integration into the genome. Retroviral vectors provide normal genes to reconstruct the NADPH oxidase activity in deficient cells. Until now, gene therapy’s success has been limited. Some patients have experienced severe complications, including death, due to abnormal clonal hematopoiesis caused by vector integration. As gene repair technology advances, DNA editing using short palindromic repeat/CRISPR associated 9 (CRISPR/Cas9) may be used to repair defective genes in X-linked recessive CGD cases. This gene therapy method has been shown to restore NADPH oxidase in vitro.

• #37 Chronic Granulomatous Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK493171/

  Hematopoietic cell transplantation (HCT) is the only established curative treatment for CGD. Making a rapid diagnosis is important to identify if HCT is possible. The success rate in patients who have undergone HCT is highest in young and disease-free individuals. Ultimately, the decision to undergo HCT depends on the prognosis, donor availability, access to transplantation, and patient preference. […] Patients without an HLA-compatible donor for HCT may be candidates for gene therapy. Gene therapy may also be suited for CGD patients since the disease often results from single genetic defects. This process includes the transfer of autologous hematopoietic stem and progenitor cells (HSPCs) by retroviral vectors and semi-random integration into the genome. Retroviral vectors provide normal genes to reconstruct the NADPH oxidase activity in deficient cells. Until now, gene therapy’s success has been limited. Some patients have experienced severe complications, including death, due to abnormal clonal hematopoiesis caused by vector integration. As gene repair technology advances, DNA editing using short palindromic repeat/CRISPR associated 9 (CRISPR/Cas9) may be used to repair defective genes in X-linked recessive CGD cases. This gene therapy method has been shown to restore NADPH oxidase in vitro.

• #38 Management of Chronic Granulomatous Disease Treatment – For HCPs

  https://www.cgdpathways.com/chronic-granulomatous-disease-management

  Prevention of serious infections is vital for patients with CGD. Serious infections can be difficult to manage and may require lengthy hospitalizations. […] CGD treatment guidelines recommend combination immunomodulatory and prophylaxis therapy. […] For the treatment of active infections, using appropriate antimicrobials based on suspected pathogens or identification is recommended. […] Because of the risk of life-threatening infections, a hematopoietic stem cell transplant (HSCT) may be considered. HSCT provides the recipient with the donors immune system, which has neutrophils with functional nicotinamide adenine dinucleotide phosphate (NADPH) and superoxide anion production. […] It is a potentially curative treatment for patients with CGD but is a procedure associated with potential morbidity and mortality, usually related to graft-versus-host disease. As with any invasive procedure, the risks and benefits of HSCT in the appropriate patient should be carefully considered.

• #39

  https://link.springer.com/article/10.1007/s12325-017-0636-2

  Nevertheless, the median age of death remains around 30-40 years, and patients tend to become increasingly debilitated with poor quality of life with advancing age. […] This review aims to summarize the clinical phenotype of CGD, including infectious and inflammatory manifestations, and to update the current data on conventional management, HCT, and gene therapy. […] Conventional management is predominantly with lifelong antibiotic and antifungal prophylaxis. […] Lifelong prophylaxis with trimethroprim-sulfamethoxazole (5 mg/kg/d div BID up to 320 mg trimethoprim a day) and itraconazole (5 mg/kg/d up to 200 mg daily) is recommended. […] The prophylactic use of IFN- remains variable. […] Treatment of CGD colitis is often long-term and difficult. […] Hematopoietic stem cell transplantation is curative, and most patients have complete resolution of colitis following transplantation.

• #40 Pediatric Chronic Granulomatous Disease Treatment & Management: Medical Care, Surgical Care, Complications

  https://emedicine.medscape.com/article/956936-treatment

  Interferon-gamma is now recommended as life-long therapy for infection prophylaxis in CGD. […] HSCT is the only curative therapeutic modality currently available for CGD. […] Anecdotal experience suggests that engraftment of 10-20% normal donor phagocytes may be sufficient for a clinically significant benefit. […] Despite the increased risk of wound healing associated with surgical intervention, surgery is still an important tool for patients with CGD. […] Surgery may be required to relieve obstruction of ureters from large granulomas, drainage of abscesses, and aggressive removal of established infection, especially in the lung and liver.

• #41 Chronic Granulomatous Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK493171/

  Hematopoietic cell transplantation (HCT) is the only established curative treatment for CGD. Making a rapid diagnosis is important to identify if HCT is possible. The success rate in patients who have undergone HCT is highest in young and disease-free individuals. Ultimately, the decision to undergo HCT depends on the prognosis, donor availability, access to transplantation, and patient preference. […] Patients without an HLA-compatible donor for HCT may be candidates for gene therapy. Gene therapy may also be suited for CGD patients since the disease often results from single genetic defects. This process includes the transfer of autologous hematopoietic stem and progenitor cells (HSPCs) by retroviral vectors and semi-random integration into the genome. Retroviral vectors provide normal genes to reconstruct the NADPH oxidase activity in deficient cells. Until now, gene therapy’s success has been limited. Some patients have experienced severe complications, including death, due to abnormal clonal hematopoiesis caused by vector integration. As gene repair technology advances, DNA editing using short palindromic repeat/CRISPR associated 9 (CRISPR/Cas9) may be used to repair defective genes in X-linked recessive CGD cases. This gene therapy method has been shown to restore NADPH oxidase in vitro.

• #42

  https://link.springer.com/article/10.1007/s12325-017-0636-2

  Allogeneic HCT is the only curative treatment for CGD and may reverse both infectious and inflammatory complications. […] Importantly, several studies have demonstrated that outcomes with 10/10 matched unrelated donors (MUD) are comparable to those with matched sibling donors (MSD). […] Gene therapy is an attractive alternative to HCT and would provide an option for patients without an HLA-identical donor. […] Nevertheless, gene editing approaches remain limited by low efficiency and hematopoietic stem cell toxicity through the process of transfection, expansion, and selection. […] Ultimately, as HCT becomes more widely available and better tolerated, we expect overall life expectancy for patients with CGD to increase substantially over the next several years.

• #43 Chronic Granulomatous Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK493171/

  Hematopoietic cell transplantation (HCT) is the only established curative treatment for CGD. Making a rapid diagnosis is important to identify if HCT is possible. The success rate in patients who have undergone HCT is highest in young and disease-free individuals. Ultimately, the decision to undergo HCT depends on the prognosis, donor availability, access to transplantation, and patient preference. […] Patients without an HLA-compatible donor for HCT may be candidates for gene therapy. Gene therapy may also be suited for CGD patients since the disease often results from single genetic defects. This process includes the transfer of autologous hematopoietic stem and progenitor cells (HSPCs) by retroviral vectors and semi-random integration into the genome. Retroviral vectors provide normal genes to reconstruct the NADPH oxidase activity in deficient cells. Until now, gene therapy’s success has been limited. Some patients have experienced severe complications, including death, due to abnormal clonal hematopoiesis caused by vector integration. As gene repair technology advances, DNA editing using short palindromic repeat/CRISPR associated 9 (CRISPR/Cas9) may be used to repair defective genes in X-linked recessive CGD cases. This gene therapy method has been shown to restore NADPH oxidase in vitro.

• #44 Chronic Granulomatous Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK493171/

  Hematopoietic cell transplantation (HCT) is the only established curative treatment for CGD. Making a rapid diagnosis is important to identify if HCT is possible. The success rate in patients who have undergone HCT is highest in young and disease-free individuals. Ultimately, the decision to undergo HCT depends on the prognosis, donor availability, access to transplantation, and patient preference. […] Patients without an HLA-compatible donor for HCT may be candidates for gene therapy. Gene therapy may also be suited for CGD patients since the disease often results from single genetic defects. This process includes the transfer of autologous hematopoietic stem and progenitor cells (HSPCs) by retroviral vectors and semi-random integration into the genome. Retroviral vectors provide normal genes to reconstruct the NADPH oxidase activity in deficient cells. Until now, gene therapy’s success has been limited. Some patients have experienced severe complications, including death, due to abnormal clonal hematopoiesis caused by vector integration. As gene repair technology advances, DNA editing using short palindromic repeat/CRISPR associated 9 (CRISPR/Cas9) may be used to repair defective genes in X-linked recessive CGD cases. This gene therapy method has been shown to restore NADPH oxidase in vitro.

• #45 Lentiviral gene therapy for X-linked chronic granulomatous disease | Nature Medicine

  https://www.nature.com/articles/s41591-019-0735-5

  Chronic granulomatous disease (CGD) is a rare inherited disorder of phagocytic cells. We report the initial results of nine severely affected X-linked CGD (X-CGD) patients who received ex vivo autologous CD34+ hematopoietic stem and progenitor cell-based lentiviral gene therapy following myeloablative conditioning in first-in-human studies (trial registry nos. NCT02234934 and NCT01855685). The primary objectives were to assess the safety and evaluate the efficacy and stability of biochemical and functional reconstitution in the progeny of engrafted cells at 12 months. […] The primary objective was met in six of the nine patients at 12 months follow-up, suggesting that autologous gene therapy is a promising approach for CGD patients.

• #46 Gene therapy for CGD shows promising early results – Boston Children’s Answers

  https://answers.childrenshospital.org/cgd-chronic-granulomatous-disease-gene-therapy/

  Brenden Whittaker, a college student in Ohio, has been caught off guard by his good health. […] At 22, he came to Boston Children’s Hospital and became the first person in the U.S. to receive a genetic therapy for CGD under a new international trial. And so far it has worked. […] The CGD gene therapy treatment is the product of a decades-long scientific journey, largely at Boston Children’s Hospital, that started with the development of a better diagnostic test for CGD and the cloning of the relevant gene. […] The gene therapy restores a healthy copy of gp91phox, part of a protein complex needed to kill the germs. […] The treatment required Brenden to stay at Boston Children’s for about six months. […] The engineered virus was designed to “turn on” gp91phox only in a few cell types, including neutrophils.

• #47 Gene therapy for CGD shows promising early results – Boston Children’s Answers

  https://answers.childrenshospital.org/cgd-chronic-granulomatous-disease-gene-therapy/

  It was a rigorous course of treatment, not without its own risks. […] Within a month, Brenden’s treatment team, led by David Williams, MD, chief scientific officer at Boston Children’s, saw early signs that the treatment was working. […] While only about 10 to 15 percent of Brenden’s cells neutrophils were genetically corrected, that appears to be enough to prevent the severe infections. […] Six, including Brenden, no longer need antibiotic prophylaxis, with tests showing that the healthy gene had remained at stable levels in their neutrophils. […] While it is still too early to talk about permanent cure, the data so far are quite encouraging that the effectiveness is stable over time. […] The gene therapy team will follow Brenden and the other patients to the 15-year mark to ensure that the treatment is safe and that its effects are lasting.

• #48 Chronic Granulomatous Disease (CGD): Commonly Associated Pathogens, Diagnosis and Treatment

  https://www.mdpi.com/2076-2607/11/9/2233

  Additionally, HCT is associated with event-free survival rates of more than 80% in patients with CGD and improves the quality of life. […] Antimicrobial and antifungal prophylaxis are the most common management routes used to minimize the incidence of infections. […] Drugs such as trimethoprim-sulfamethoxazole reduce the occurrence of bacterial infections in patients with CGD but do not interfere considerably with the gut microbiome. […] Itraconazole considerably reduces invasive fungal infections, and newer azole drugs, such as voriconazole, posaconazole, and isavuconazole, are available, providing more options for treating these fungal infections. […] Treatment using TNF-alpha inhibitors in patients with CGD could help improve the outcome of severe inflammatory complications despite the associated risk factors. […] Gene therapy remains in the experimental stage. […] Current gene therapy trials, which remains experimental, have demonstrated that lentiviruses or gene editing can be used as curative therapy where HCT is inappropriate for a patient and removes the risk of graft-versus-host disease.

• #49 Chronic Granulomatous Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK493171/

  Hematopoietic cell transplantation (HCT) is the only established curative treatment for CGD. Making a rapid diagnosis is important to identify if HCT is possible. The success rate in patients who have undergone HCT is highest in young and disease-free individuals. Ultimately, the decision to undergo HCT depends on the prognosis, donor availability, access to transplantation, and patient preference. […] Patients without an HLA-compatible donor for HCT may be candidates for gene therapy. Gene therapy may also be suited for CGD patients since the disease often results from single genetic defects. This process includes the transfer of autologous hematopoietic stem and progenitor cells (HSPCs) by retroviral vectors and semi-random integration into the genome. Retroviral vectors provide normal genes to reconstruct the NADPH oxidase activity in deficient cells. Until now, gene therapy’s success has been limited. Some patients have experienced severe complications, including death, due to abnormal clonal hematopoiesis caused by vector integration. As gene repair technology advances, DNA editing using short palindromic repeat/CRISPR associated 9 (CRISPR/Cas9) may be used to repair defective genes in X-linked recessive CGD cases. This gene therapy method has been shown to restore NADPH oxidase in vitro.

• #50 Chronic Granulomatous Disease: Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/21157-chronic-granulomatous-disease-cgd

  Reducing your risk of infection by taking the following precautions can also help: […] You can’t prevent CGD. People with a family history of the disease who want to have children should seek genetic counseling to learn about the risk of having a child with CGD. […] The outlook is generally very good. Healthcare providers can usually manage symptoms of CGD and prevent serious infections. Treatment may continue indefinitely to keep infections and inflammation from becoming severe. […] With ongoing treatment and support, many people with CGD live active and fulfilling lives. Prompt treatment is necessary so that your provider can treat infections before they become severe or life-threatening. […] Having a condition like CGD requires ongoing treatment to manage your symptoms. Work with your provider to find a regimen that gives you the freedom to enjoy your life and do things you love.

• #51 Chronic granulomatous disease: Symptoms and treatment

  https://www.medicalnewstoday.com/articles/chronic-granulomatous-disease

  Treatment options for CGD typically consist of continuous antibiotic therapy to help prevent bacterial and fungal infections. If a person with CGD acquires an infection, they generally require additional antibiotics and a longer time for the drugs to be effective. A doctor may also suggest corticosteroids and bone marrow transplants to help relieve symptoms. […] A doctor may also recommend using Actimmune, also known as interferon gamma-1b. This protein may improve the activity of phagocytes, which could help reduce the number of severe infections. Ongoing research is also investigating gene therapy approaches to address the underlying genetic alterations that cause CGD. Some people may also consider genetic counseling when planning for pregnancy. […] Management of the condition includes trying to avoid exposure to organisms that, while safe for the general population, may cause infections in those with CGD.

• #52

  https://step2.medbullets.com/pediatrics/120736/chronic-granulomatous-disease-of-childhood-cgd

  Chronic granulomatous disease (CGD) is a rare primary immunodeficiency of phagocytes. […] Treatment includes good skin hygiene, antifungals and antibiotics. […] Interferon- is also used. […] Antibacterial and antifungal prophylaxis is recommended. […] The only curative therapy is hematopoietic stem cell transplant. […] Improving with treatment. […] 50% survival rate to age 30-40.

• #53 Chronic Granulomatous Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK493171/

  When this disorder was first identified, affected children were certain to die, but now CGD can be managed and has a high survival rate. Management of CGD is based on 3 principles: 1) lifelong antibacterial and antifungal prophylaxis, 2) early diagnosis of infection, and 3) aggressive management of infectious complications. Globally, therapy involves trimethoprim-sulfamethoxazole and itraconazole. Some countries also add interferon-gamma therapy. However, this therapy is not accepted universally. This combination of treatments can reduce severe infections from 1 per patient per year to almost 1 per patient per 10 years. Live bacterial vaccines are best avoided. […] Treatment of acute infections should start early, including determining the exact complicating infectious agent and selecting antibiotics or anti-fungal therapies. Early and aggressive therapy is essential in preventing the spread of infection. Additional diagnostic procedures should be used to identify the microorganism for infections that fail to respond to therapy within 24 to 48 hours. Antifungal therapy should be started before a diagnosis of fungal infections is confirmed. Surgical removal of refractory fungal infections may be necessary as well. Oral glucocorticoids are commonly prescribed for inflammatory manifestations of CGD. The use of tumor necrosis factor-alpha inhibitors in patients with CGD can be associated with high-risk infections and is not generally recommended.

• #54 Chronic Granulomatous Disease: Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/21157-chronic-granulomatous-disease-cgd

  Reducing your risk of infection by taking the following precautions can also help: […] You can’t prevent CGD. People with a family history of the disease who want to have children should seek genetic counseling to learn about the risk of having a child with CGD. […] The outlook is generally very good. Healthcare providers can usually manage symptoms of CGD and prevent serious infections. Treatment may continue indefinitely to keep infections and inflammation from becoming severe. […] With ongoing treatment and support, many people with CGD live active and fulfilling lives. Prompt treatment is necessary so that your provider can treat infections before they become severe or life-threatening. […] Having a condition like CGD requires ongoing treatment to manage your symptoms. Work with your provider to find a regimen that gives you the freedom to enjoy your life and do things you love.

• #55 Definitive Treatments for Chronic Granulomatous Disease with a Focus on Gene Therapy | SpringerLink

  https://link.springer.com/chapter/10.1007/978-3-031-23752-2_33

  The past 20 years have witnessed massive progress in the early diagnosis of Chronic Granulomatous Disease (CGD), leading to prompt initiation of prophylactic and immunosuppressive treatments with a substantial improvement in life expectancy. […] Allogeneic hematopoietic stem cell transplantation as definitive therapy has shown excellent results when offered to pediatric patients free from active infections. The outcome is worse if patients suffer from inflammatory complications and fungal infections at the time of transplant. […] Ex vivo correction of autologous hematopoietic stem and progenitor cells through gene therapy holds great promise, but it is more complex than anticipated. […] This chapter will cover definitive treatments for CGD and discuss the problems encountered in early gene therapy trials focusing on new platforms to overcome pitfalls and maintain the promise of an alternative and safe lifelong treatment for this disease.

• #56 Chronic Granulomatous Disease (CGD) | NIAID: National Institute of Allergy and Infectious Diseases

  https://www.niaid.nih.gov/diseases-conditions/chronic-granulomatous-disease-cgd

  People with CGD take lifelong regimens of antibiotics and antifungals to prevent infections. Injections with interferon gamma, a protein that improves the activity of phagocytes, also may help reduce the number of severe infections. Abscesses need aggressive care that may include surgery. Granulomas may require steroid therapy. Some people with CGD have been treated successfully with bone marrow transplantation. […] NIAID scientists are exploring gene therapy approaches to address the underlying genetic defects that cause CGD. In early 2017, they described using the CRISPR-Cas9 gene-editing strategy to correct the defective gene in cells taken from patients with the X-linked form of CGD. […] NIAID also supports the development of antifungal drugs and other therapies to curb infections and improve outcomes for people with CGD.

• #57 Chronic Granulomatous Disease | UPMC Children’s – Pittsburgh

  https://www.chp.edu/our-services/rare-disease-therapy/conditions-we-treat/chronic-granulomatous-disease

  The goal of treating CGD is to control the symptoms. […] Children with CGD may need aggressive treatment for their infections. Sometimes, doctors prescribe antibiotics to prevent infections even when a child doesn’t have any. […] Children whose disease is more severe may need a bone marrow or cord blood transplant to replace their immune system. […] If CGD causes severe health problems such as lung disease or lung failure a transplant may benefit your child. […] Hillman Center for Pediatric Transplant has the only program in the world that offers tandem lung and bone marrow transplants. […] We also pioneered a reduced-intensity bone marrow transplant program. It helps reduce the negative effects a bone marrow or stem cell transplant has on the body’s organs. […] Because transplants are high-risk treatments, your child may need to remain on lifelong medication.

• #58

  https://link.springer.com/article/10.1007/s12325-017-0636-2

  Allogeneic HCT is the only curative treatment for CGD and may reverse both infectious and inflammatory complications. […] Importantly, several studies have demonstrated that outcomes with 10/10 matched unrelated donors (MUD) are comparable to those with matched sibling donors (MSD). […] Gene therapy is an attractive alternative to HCT and would provide an option for patients without an HLA-identical donor. […] Nevertheless, gene editing approaches remain limited by low efficiency and hematopoietic stem cell toxicity through the process of transfection, expansion, and selection. […] Ultimately, as HCT becomes more widely available and better tolerated, we expect overall life expectancy for patients with CGD to increase substantially over the next several years.

• #59 Chronic Granulomatous Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK493171/

  When this disorder was first identified, affected children were certain to die, but now CGD can be managed and has a high survival rate. Management of CGD is based on 3 principles: 1) lifelong antibacterial and antifungal prophylaxis, 2) early diagnosis of infection, and 3) aggressive management of infectious complications. Globally, therapy involves trimethoprim-sulfamethoxazole and itraconazole. Some countries also add interferon-gamma therapy. However, this therapy is not accepted universally. This combination of treatments can reduce severe infections from 1 per patient per year to almost 1 per patient per 10 years. Live bacterial vaccines are best avoided. […] Treatment of acute infections should start early, including determining the exact complicating infectious agent and selecting antibiotics or anti-fungal therapies. Early and aggressive therapy is essential in preventing the spread of infection. Additional diagnostic procedures should be used to identify the microorganism for infections that fail to respond to therapy within 24 to 48 hours. Antifungal therapy should be started before a diagnosis of fungal infections is confirmed. Surgical removal of refractory fungal infections may be necessary as well. Oral glucocorticoids are commonly prescribed for inflammatory manifestations of CGD. The use of tumor necrosis factor-alpha inhibitors in patients with CGD can be associated with high-risk infections and is not generally recommended.

• #60 Chronic granulomatous disease – Overview of Information and Clinical Research

  https://clinicaltrials.eu/disease/chronic-granulomatous-disease/

  Treatment options include prophylactic antibiotics and antifungals, interferon-gamma therapy, and in some cases, hematopoietic stem cell transplantation or gene therapy. […] While there is no definitive cure for CGD, hematopoietic stem cell transplantation offers a potential cure for some patients. Gene therapy is also being explored as a future treatment option.

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