Chronic Granulomatous Disease

Epidemiology and Etiology:

• Dysfunction of the phagocyte NADPH oxidase system
• Normally generates the respiratory burst of reactive oxygen species in organism killing
• M > F (X-linked is most common)

Common sites:

• Lymph nodes
• Skin
• Lungs
• Liver
• GI
• GU

Gross features:

• Abscesses
• Fibrosis
• fistulas

Histologic features:

• May only see non-specific acute and or chronic inflammation and fibrosis
• No pathognomonic features
• Granulomatous inflammation (40%)
• Palisading granulomas maybe
• Pigmented macrophages
• Finely granular golden brown pigment
• Pigmented material thought to represent inadequate digestion of intracellular debris
• Predominantly portal tracts, but also found in the lobules
• GI tract:
• Pigmented macrophages within the lamina propria
• Active chronic inflammation mimicking Crohn disease
• Lymph nodes:
• Granulomatous inflammation (necrotizing or non-necrotizing)
• Liver:
• Necrosis
• Portal tract inflammation
• Granulomas
• Pigmented macrophages in sinusoids

Immunophenotype:

Marker:

Sensitivity:

Specificity:

Molecular features:

• Mutations in any of the genes which encode the various subunits of the superoxide-generating phagocyte NADPH oxidase system
• >400 mutations have been described
• 4 major types
• X-linked (65-75%):
• Most common variant
• Defects in gp91(phox)
• Mostly males, but females can be affected
• Other major types are autosmal recessive

Other features:

• Life expectancy 25-30y
• Recurrent severe bacterial and fungal infections with granuloma formation
• Unusual organisms
• Nocardia
• Aspergillus
• Persistent suppurative lymphadenopathy
• Subcutaneous abscesses
• Diagnosis confirmed by Nitroblue Tetrazolium (NBT) reduction test
• Organisms:
• Staphylococcus
• Enteric bacteria
• Aspergillus
• Nocardia
• Aspergillus

References:

• Levine S et al. (2005) Histopathological features of chronic granulomatous disease in childhood. Histopathology 47: 508-16.