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Immune System

Chronic granulomatous disease (CGD)

Chronic granulomatous disease (CGD), also known as Bridges–Good syndrome and Quie syndrome is a diverse group of hereditary primary immunodeficiency disorders characterized by recurrent, life-threatening bacterial and fungal infections of the skin, the airways, the lymph nodes, the liver, the brain and the bones.

Chronic granulomatous disease (CGD), also known as Bridges–Good syndrome and Quie syndrome is a diverse group of hereditary primary immunodeficiency disorders characterized by recurrent, life-threatening bacterial and fungal infections of the skin, the airways, the lymph nodes, the liver, the brain and the bones.

  • Leads to the formation of granulomata (collection of histiocytes/macrophages) in many organs
  • Type of primary immunodeficiency
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(2020) Inherited Innate Immunodeficiencies (Immunology) Flashcards | Memorang. Retrieved February 07, 2020, from https://www.memorangapp.com/flashcards/29949/Inherited+Innate+Immunodeficiencies/

History:

Chronic granulomatous disease (CGD) was first identified in the 1950s in a 12-month-old Minnesotan child who presented with a constellation of findings, including chronic suppurative lymphadenitis, hepatosplenomegaly, pulmonary infiltrates, and eczematoid dermatitis. In the classic 1959 description of “fatal granulomatous disease of childhood,” Bridges et al reported that “no satisfactory therapy has been found, however, and the disease has relentlessly progressed through severe debilitation to ultimate death over a period of several years.”


Etiopathogenesis

Inheritance patterns:

  • X-linked CGD
  • Autosomal recessive cytochrome b-negative CGD
  • Autosomal recessive cytochrome b-positive CGD type I
  • Autosomal recessive cytochrome b-positive CGD type II
  • Atypical granulomatous disease

Defective phagocyte NADPH oxidase:

Disruption in the formation of reactive oxygen compounds (most importantly superoxide radical due to defective phagocyte NADPH oxidase) used to kill certain ingested pathogens leding to a dysregulated inflammatory response resulting in granuloma formation and other inflammatory disorders such as colitis.
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The pathogenesis of chronic granulomatous disease (CGD). The manner in which the metabolic deficiency of the CGD neutrophil predisposes the host to infection is shown schematically. Normal neutrophils accumulate hydrogen peroxide in the phagosome containing ingested Escherichia coli (left). Myeloperoxidase is delivered to the phagosome by degranulation, as indicated by the closed circles, and in this setting, hydrogen peroxide acts as a substrate for myeloperoxidase to oxidize halide to hypochlorous acid and chloramines that kill the microbes. The quantity of hydrogen peroxide produced by the normal neutrophils is sufficient to exceed the capacity of catalase, a hydrogen peroxide-catabolizing enzyme produced by many aerobic microorganisms, including most gram-negative enteric bacteria, Staphylococcus aureus, Candida albicans, and Aspergillus sp. When organisms such a E coli gain entry into CGD neutrophils, they are not exposed to hydrogen peroxide because the neutrophils do not produce it, and the hydrogen peroxide generated by the microbes is destroyed by their own catalase. When CGD neutrophils ingest streptococci or pneumococci, these organisms, which lack catalase, generate sufficient hydrogen peroxide to result in a microbicidal effect (right). On the other hand, as indicated in the middle figure, catalase-positive microbes, such as E coli, can survive within the phagosome of the CGD neutrophil. | Boxer LA. Neutrophil disorders: qualitative abnormalities of the neutrophil. In: Beutler E, Lichtman MA, Coller BS, Kipps TJ, Seligsohn U, eds. Williams Hematology. 6th ed. New York, NY: McGraw-Hill; 2001:845.

Presentation

Specific recurrent infections:

  • In decreasing order of frequency:
    • Pneumonia
    • Abscesses of the skin, tissues, and organs
    • Suppurative arthritis
    • Osteomyelitis
    • Bacteremia/fungemia
    • Superficial skin infections such as cellulitis or impetigo

Diagnosis

Screening tests:

  • Nitroblue tetrazolium dye reduction test (NBT)
    • Negative in CGD, meaning that it does not turn blue.
    • The higher the blue score, the better the cell is at producing reactive oxygen species

Confirmatory tests:

  • Flow cytometry

Management

Supportive management:

  • Bacterial infections: Trimethoprim-sulfamethoxazole (TMP-SMX)
  • Fungal infections: Itraconazole or voriconazole
  • Interferon: Interferon gamma-1b (Actimmune)

Definitive treatment: Hematopoietic stem cell transplantation (HSCT)


Summary:

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(2020) Inherited Innate Immunodeficiencies (Immunology) Flashcards | Memorang. Retrieved February 07, 2020, from https://www.memorangapp.com/flashcards/29949/Inherited+Innate+Immunodeficiencies/

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