Chronic Granulomatous Disease

Suspect CGD in a child or adult with recurrent, severe, persistent, or deep bacterial and fungal infections, particularly pneumonia, suppurative lymphadenitis, pyoderma, liver abscess, osteomyelitis, or recurrent deep-tissue abscesses. The most characteristic organisms include Staphylococcus aureus, Serratia marcescens, Burkholderia cepacia complex, Nocardia species, and Aspergillus species. BMJ+1BMJChronic granulomatous disease - Symptoms, diagnosis and treatment | BMJ Best Practice USScienceDirectChronic Granulomatous Disease - an overview

Escalate suspicion when infection is unusually destructive, multifocal, refractory to standard antibacterial therapy, or caused by uncommon organisms. CGD-associated osteomyelitis may involve small bones of the hands or feet and can affect multiple sites; obtain imaging of symptomatic sites and pursue aspiration or biopsy of purulent material for organism identification. ScienceDirectScienceDirectChronic Granulomatous Disease - an overview

Do not restrict testing to infectious presentations. CGD can present with inflammatory bowel disease-like colitis, noninfectious granulomas causing gastrointestinal or urinary tract obstruction, or other dysregulated inflammatory manifestations. In a patient with early-onset inflammatory disease plus a compatible infection history, assess for CGD rather than treating presumed idiopathic inflammatory bowel disease alone. ScienceDirect+2ScienceDirectRecent advances in chronic granulomatous diseaseScienceDirectClinical features and outcomes of patients with chronic ...publications aapChronic Granulomatous Disease Presenting as ...

Use a flow cytometry-based dihydrorhodamine 123 assay as the practical diagnostic test for suspected CGD. An abnormal DHR result is consistent with CGD because affected phagocytes fail to generate a normal oxidative burst; nitroblue tetrazolium testing is an alternative historical functional assay. JAMA+3JAMACutaneous Inflammatory Manifestations of Chronic ...publications aapCase 3: Persistent Fever in an 8-month-old BoyCDCEpidemiology studies in immunotoxicity evaluationspublications aapTreatment-Resistant Bacterial Lymphadenitis in an ...

After an abnormal oxidative-burst study, obtain molecular genetic testing to confirm the disease-causing defect and support inheritance assessment. CGD reflects defects in components of the NADPH oxidase complex, and clinical severity varies by genotype; p22phox and p67phox defects have been associated with more severe complications, whereas p47phox mutations may produce a milder phenotype. JAMA+2JAMACutaneous Inflammatory Manifestations of Chronic ...BMJChronic granulomatous disease - Symptoms, diagnosis and treatment | BMJ Best Practice USScienceDirectChronic Granulomatous Disease - an overview

Interpret an abnormal DHR assay in clinical context rather than as an isolated laboratory finding. A compatible phenotype includes recurrent serious bacterial or fungal infection and exaggerated granulomatous inflammation; genetic confirmation is particularly important for family counseling, identification of carrier status, and selection discussions for curative therapy. JAMA+2JAMACutaneous Inflammatory Manifestations of Chronic ...BMJChronic granulomatous disease - Symptoms, diagnosis and treatment | BMJ Best Practice USWolters KluwerFamily Clusters of Variant X-linked Chronic Granulomatous...

In CGD with fever or focal symptoms, localize infection early with site-directed imaging and obtain microbiologic material before narrowing therapy. For abscesses, lymph nodes, bone lesions, and other purulent collections, aspiration is important for pathogen identification; send bacterial and fungal cultures and use molecular identification when routine methods fail. ScienceDirect+1ScienceDirectChronic Granulomatous Disease - an overviewCDCMethylotroph Infections and Chronic Granulomatous Disease - Volume 22, Number 3—March 2016 - Emerging Infectious Diseases journal - CDC

For pulmonary disease, obtain chest CT rather than relying on nonspecific symptoms or plain radiography alone. Invasive aspergillosis may produce nodular lesions, halo sign, or cavitation, but these findings are not specific; blood and respiratory cultures are often negative. fdafdaClinical Review

Use fungal biomarkers as adjuncts rather than replacements for imaging and sampling. In high-risk hematologic malignancy or hematopoietic stem-cell transplant populations with compatible clinical and radiologic findings, serum galactomannan positivity has been defined as at least 0.5 on two separate samples or at least 1.0 on one sample; BAL fluid positivity has been defined as at least 1.0 on two aliquots from one BAL specimen. Extrapolate these thresholds cautiously in CGD, where diagnostic performance is not established by this qualification. fdafdaClinical Review

When a pathogen is not identified despite ongoing disease, maintain suspicion for unusual CGD-associated organisms. Methylotroph infections have occurred in CGD and required 16S rRNA gene sequencing for correct diagnosis; affected patients often required prolonged antimicrobial therapy and some required surgery. CDCCDCMethylotroph Infections and Chronic Granulomatous Disease - Volume 22, Number 3—March 2016 - Emerging Infectious Diseases journal - CDC

Conventional CGD management centers on preventing and promptly treating infection while controlling inflammatory complications. Long-term antibacterial prophylaxis, antifungal prophylaxis, and interferon-gamma therapy are established components of conventional management, although specific agent selection and dosing should be individualized with an immunology and infectious-diseases team. Wiley+1WileyPhenotypic Prenatal Diagnosis of Chronic Granulomatous ...WileyProgress in treating chronic granulomatous disease

Maintain a low threshold to reassess prophylaxis adherence, antimicrobial tolerance, breakthrough pathogen identity, and occult focal infection after any serious infectious event. Prophylaxis does not eliminate risk: patient testimony submitted to the FDA described life-threatening infections occurring approximately every 3.5 years despite prophylactic treatment, underscoring the need for urgent evaluation of new fever or focal symptoms. fdafdaChronic Granulomatous Disease

Refer patients early to a center experienced in allogeneic hematopoietic stem-cell transplantation. HSCT can cure CGD, but whether every conventionally managed patient should proceed remains debated; transplant decisions should weigh infection history, inflammatory burden, genotype-associated severity, donor options, transplant risk, and patient preference. Wiley+2WileyOutcome of chronic granulomatous disease ‐ Conventional ...WileyConventional treatment vs stem cell transplantationScienceDirectChronic Granulomatous Disease - an overview

Consider transplantation particularly when severe or recurrent infections, difficult-to-control inflammatory disease, or cumulative treatment burden outweigh the risks of allografting. Durable cure after bone marrow transplantation has been reported, whereas mixed chimerism may coexist with persistent inflammatory manifestations and ongoing treatment needs. fda+2fdaChronic Granulomatous DiseaseWileyOutcome of chronic granulomatous disease ‐ Conventional ...WileyConventional treatment vs stem cell transplantation