Definition
• Group of hereditary diseases in which there is a decrease in oxidative burst when cells of the immune system are unable to form the superoxide radical that is used to kill certain ingested pathogens. This leads to the formation of granulomas in many organs.
Pathogenesis
• The inherited defect is in the gene encoding components of phagocyte oxidase
• In the X-linked variant the defect is in one of the membrane-bound components (gp91phox)
• In the autosomal recessive variant the defect is in the genes encoding two of the cytoplasmic components (p47phox and p67phox)
Clinical features
Epidemiology
• In the United States it affects 1 in 200,000 people with no race predilection
• Majority (two thirds) of cases X-linked and autosomal recessive; a few sporadic cases
Presentation
• Most patients given diagnosis of primarily gastrointestinal involvement in childhood
• Recurrent episodes of infections (diarrhea, pneumonia, skin abscesses, osteomyelitis, bacteremia, fungemia, cellulitis, and impetigo)
• Some present with atypical infections (catalase-positive bacteria, fungi)
• Lung involvement is rare and can occur at any time in the course of the disease in patients with an established diagnosis of CGD
Prognosis and treatment
• Without treatment children often die in the first decade of life
• Data indicates that X-linked CGD is more severe; most of these patients die in the third or fourth decade of life, even with treatment
• Prophylaxis with antibiotics and antifungal drugs
• Immunomodulation (e.g., interferon gamma-1b)
• Studies using gene therapy are currently under way
Pathology
Histology
• Lung involvement begins in the peribronchial or perivascular areas
• Suppurative inflammation with areas of massive necrosis and pigmented histiocytes
• Subsequently forms necrotizing granulomas
• Infrequently, foreign body and Langhans giant cells
Immunopathology/special stains
• Noncontributory for diagnosis but need to rule out infection (see Differential Diagnoses)
Main differential diagnoses
• Mycobacterial infections: need AFB stain to confirm
• Fungal infections: GMS stain demonstrates fungi
• Wegener granulomatosis: presents in young adults, classic triad (lung, nasal, and renal involvement)
• Aspiration: predominantly lower lobe involvement; foreign material identifiable
• Sarcoidosis: rare in children; usually nonnecrotizing granulomas
• Hypersensitivity pneumonitis: poorly formed granulomas, nonnecrotizing, with eosinophils
Fig 1 Chronic granulomatous disease of childhood. CGD involving the lung in a 10-year-old: A, Scanning view shows necrotizing granulomas involving perivascular area; B, high-power view shows necrotizing granulomas surrounded by mixed acute and chronic inflammatory cell infiltrate. Note multinucleated giant cells and necrotic debris within the granulomas.