Chronic Granulomatous Disease: An Overview M . E L I Z A B E T H - - PowerPoint PPT Presentation

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Oct 30, 2023 340 likes •538 views

Chronic Granulomatous Disease: An Overview M . E L I Z A B E T H M . Y O U N G E R A S S I S T A N T P R O F E S S O R , P E D I A T R I C S J O H N S H O P K I N S U N I V E R S I T Y S C H O O L O F M E D I C I N E B A L T I M O R E

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M . E L I Z A B E T H M . Y O U N G E R A S S I S T A N T P R O F E S S O R , P E D I A T R I C S J O H N S H O P K I N S U N I V E R S I T Y S C H O O L O F M E D I C I N E B A L T I M O R E , M A R Y L A N D

Chronic Granulomatous Disease: An Overview

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C S L B E H R I N G : C O N S U L T A N T , R E S E A R C H S U P P O R T R M S : C L I N I C A L A D V I S O R Y P A N E L B I O P R O D U C T S L A B : A D V I S O R Y B O A R D H O R I Z O N P H A R M A : C O N S U L T A N T ; A D V I S O R Y B O A R D I M M U N E D E F I C I E N C Y F O U N D A T I O N : N U R S E A D V I S O R Y C O M M I T T E E

Disclosures

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History

AMA Journal of Diseases of Children, 1954 AMA Journal of Diseases of Children, 1959

First described in 1954: And defined in 1959:

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So What is CGD?

 A disorder of phagocytes (a type of white blood cell)  Phagocytes cannot kill some bacteria and fungi

because they cannot make an oxidative burst resulting in:

 Severe infections from “bugs” that would not necessarily cause

a bad infection in someone without CGD

 Inflammation

 It is important to know that the other parts of the

immune system (antibody production, complement activation, etc.) are NORMAL

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White Blood Cells

Types: Phagocytes are neutrophils and monocytes

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Phagocytosis

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Characteristics

 Inheirited disease

 X-linked inheritance  Autosomal recessive inheritance

 ~1:200,000 births (in the US:~20 babies annually)  Boys affected more than girls (~ 2:1)  Usually presents in early years of life (aged 1-3)  Presentation is usually acute or recurrent bacterial

infections

 Sometimes presents as early onset inflammatory

bowel disease

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Age of Age at Diagnosis variable

 CGD may present at any time from

infancy to adulthood1,2

Median age at diagnosis is

2.5 to 3 years1

Age at diagnosis is older for people with

autosomal recessive vs X-linked mode of inheritance3-5

Adapted from van den Berg JM, et al. PLoS One. 2009;4(4):e5234. References: 1. Leiding JW, et al. Chronic granulomatous disease. GeneReviews. 1993-2017. 2. Wolfe LC, et al. Medscape website. http://emedicine.medscape.com/article/956936-clinical. 3. van den Berg JM, et al. PLoS One. 2009;4(4):e5234. 4. Jones LB, et al. Clin Exp Immunol. 2008;152(2):211. 5. Martire B, et al. Clin Immunol. 2008;126(2):155. (Slide used with permission of HorizonPharma)

Age at Diagnosis of CGD

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X-linked inheritance

x x x xx xx y xy xy

xy-Male xx-female x-x chromosome carrying CGD

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Autosomal Recessive Inheritance

D d D DD Dd d Dd dd D D D DD DD d Dd Dd

D-normal gene d-CGD gene Both parents carriers of CGD One parent a carrier of CGD

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Autosomal Recessive Inheritance

D d D DD Dd d Dd dd d d d d

D-normal gene d-CGD gene Both parents are carriers of CGD Both parents have CGD

dd dd dd dd

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Diagnosis

 Assess the oxidative burst which is what kills the

bacteria or fungi after the phagocytes attach to the germ and surround it Tests:

 Nitroblue tetrazolium test (NBT):

 Qualitative test-person has CGD or does not

 Dihydrorhodamine neutrophil burst assay (DHR);

the “Gold Standard”

 Quantitative test that can distinguish between x-linked

disease, autosomal recessive disease, and carrier status

 Limitations

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Diagnosis: Nitroblue Tetrazolium Test

negative positive (normal)

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Presentation: Infections

 Especially in:

 Lymph nodes  Lungs  Liver  Skin

 Caused by “CGD” pathogens

(usually bacteria or fungi that produce an enzyme called catalase)

 Don’t get better or take a long time to treat with

appropriate treatment

 Recur

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Typical CGD Pathogens

 Staph aureus (50-60% of infections)  Burkholderia cepacia  Serratia marcesens  Nocardia  Candida  Aspergillis

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Presentation: Granuloma Formation

 Gastrointestinal system

 Granulomata found throughout the GI tract  Can cause abdominal pain, diarrhea, strictures and fistulae  Can mimic Crohn’s disease

 Genitourinary System

 In the bladder, urethra and ureters  Can cause pain and obstruction

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Co-morbidities (other illnesses)

 Autoimmune disease

 Eyes: inflammation of the cornea, retina and uvea  Kidneys: IgA nephropathy  Joints: Juvenile arthritis  Myasthenia gravis  Skin: Raynuad’s phenomena, light sensitivity, rash