Snapshot A 1-year-old boy presents with a persistent cough for the past 3 days. He has had multiple episodes of pneumonias and upper respiratory infections since being born. He has also had multiple skin infections. Finally, his medical chart reveals that his growth curve is in the 10th percentile for weight and 5th percentile for height, which is drastically different from his birth numbers, which were in the 50th percentile. A dihydrorhodamine test returns abnormal. Introduction Chronic granulomatous disease (CGD) is a rare primary immunodeficiency of phagocytes Epidemiology Males > females due to inheritance pattern etiology Pathogenesis recall normal physiology NADPH oxidase is important in respiratory or oxidative burst results in rapid release of reactive oxygen species such as superoxide CGD patients lack the oxidative burst can only use peroxide from microorganisms to make reactive oxygen species catalase-positive species (S. aureus, E. coli, Aspergillus, and Candida) can neutralize own peroxide with catalase CGD patients are susceptible especially to catalase-positive species can ingest bacteria, but can’t kill it persistent survival of bacteria leads to granulomas in body Genetics X-linked recessive (mainly) autosomal recessive disease is milder both result in deficiency in NADPH oxidase Presentation Symptoms often appear in first year of life with recurrent pyogenic infections recurrent infection with catalase-positive organisms pneumonias aspergillosis skin abscesses pulmonary abscesses chronic diarrhea ear infections osteomyelitis failure to thrive Physical exam short stature eczematoid dermatitis hepatomegaly lymphadenopathy studies Flow cytometry reduction of dihydrorhodamine abnormal can detect X-linked carrier status cannot differentiate oxidase-positive from oxidase-negative phagocyte subpopulations in CGD carriers Nitroblue tetrazolium dye reduction test negative finding = incubated leukocytes do not turn the plate blue Cytochrome C reduction assay measures production of reactive oxygen species CBC most show anemia ↑ IgG, IgM, and IGA Differential Diagnosis IgA deficiency HIV/AIDs Other primary immunodeficiencies Treatment Prevention good skin hygiene antifungals and antibiotics Interferon-γ Antibacterial and antifungal prophylaxis Only curative therapy hematopoietic stem cell transplant Complications Severe fungal infections are often determinant of survival Prognosis Improving with treatment 50% survival rate to age 30-40