Chronic Granulomatous Disease (CGD) is no longer viewed solely as a phagocytic defect leading to infections – it is a systemic immune dysregulation disorder with life-threatening inflammatory complications. While NADPH oxidase deficiency predisposes to severe infections, real-world clinical data reveal that autoinflammation (colitis, granulomata, lupus-like disease) now drives significant morbidity and mortality in the era of effective antimicrobial prophylaxis. Despite advances in diagnostics and HSCT, critical gaps remain: Why do 40-60% of CGD patients develop inflammatory colitis? What explains the dramatic variability in clinical phenotypes? How should we balance immunosuppression with infection risks? This Research Topic will focus on clinical outcomes, treatment challenges, and phenotypic variability to guide evidence-based patient management.

The goals of this Research Topic collection include:

1) To define the real-world clinical spectrum of CGD beyond infections, leveraging large patient cohorts, registries, and long-term follow-up studies to:

o Characterize prevalence/predictors of inflammatory complications (colitis, granulomata, autoimmune disease).

o Identify clinical triggers (e.g., microbiome shifts, infections, or drug effects).

2) To evaluate treatment outcomes for immune dysregulation:

o Comparative effectiveness of steroids, anti-TNF, JAK inhibitors, or IL-1 blockade.

o HSCT outcomes in patients with pre-existing inflammation.

o Patient-reported outcomes (quality of life, treatment burdens).

3) To address unmet needs:

o Biomarkers to guide immunosuppression (who needs it? when to stop?).

o Paediatric-to-adult transition challenges in chronic CGD management.

To this Research Topic, we welcome the submission of Original Research, Meta-Analyses, and Case Series with direct clinical relevance, including:

• Real-world treatment data: Case series on refractory colitis, drug failure patterns, biologics (anti-TNF/IL-1/JAKi), and HSCT outcomes.
• Novel targets (e.g., IL-23/Th17 axis, inflammasome modulation).
• Phenotype-genotype correlations: Do specific CYBB/autosomal mutations predict inflammation?
• Comorbidity management: for example, Colitis surveillance, fertility issues, or cardiovascular risks in CGD patients.
• Case-based debates: How would you treat steroid-refractory CGD colitis?
• Gene editing: Clinical updates on CRISPR/Cas9 trials, lentiviral vectors, and safety considerations.
• Patient-centred research: Quality-of-life studies, adherence challenges, or transition care models.

Are you interested in contributing a manuscript to this Research Topic?

Chronic granulomatous disease in the real world: Clinical challenges, immune dysregulation, and patient-centered therapies