Updated: 8/6/2018

Chronic Granulomatous Disease

Topic
Review Topic
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Questions
5
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Evidence
2
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Snapshot
  • A 2-month-old boy presents with a 2-day history of fever and a painful bump on his rear-end. On exam, there is a fluctuant, erythematous bump with purulent material draining. The abscess is drained and cultured, and the patient is started on antibiotics. The cultures come back positive for S. aureus. This is his second episode of a S. aureus-induced abscess. A nitroblue tetrazolium test is negative.
Introduction
  • Chronic granulomatous disease (CGD) is a rare primary immunodeficiency of phagocytes
  • Genetics
    • X-linked recessive
      • results in deficiency in NADPH oxidase 
  • Epidemiology
    • males > females due to inheritance pattern
  • 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
      • ↑ risk of catalase-positive species (S. aureus, E. coli, Aspergillus, Candida, etc.) 
  • Leads to granulomas
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
    • failure to thrive
  • Physical exam
    • short stature
    • eczematoid dermatitis
    • hepatomegaly
Evaluation
  • 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
Differential Diagnosis
  • IgA deficiency
  • HIV/AIDs
  • Other primary immunodeficiencies
Treatment
  • INF-γ
  • Antibacterial and antifungal prophylaxis
  • Only curative therapy
    • hematopoietic stem cell transplant
Prognosis, Prevention, and Complications
  • Prognosis
    • improving with treatment
    • 50% survival rate to age 30-40
  • Prevention
    • antifungals and antibiotics
  • Complications
    • severe fungal infections are often determinant of survival
 

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Questions (5)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Volume  
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Urine  
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2
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(M1.IM.74) A father brings his 3-year-old son to the pediatrician because he is concerned about his health. He states that throughout his son's life he has had recurrent infections despite proper treatment and hygiene. Upon reviewing the patient's chart, the pediatrician notices that the child has been infected multiple times with S. aureus, Aspergillus, and E. coli. Which of the following would confirm the most likely cause of this patient's symptoms? Review Topic

QID: 106679
1

Negative nitroblue-tetrazolium test

58%

(94/162)

2

Normal dihydrorhodamine (DHR) flow cytometry test

3%

(5/162)

3

Positive nitroblue-tetrazolium test

21%

(34/162)

4

Increased IgM, Decreased IgG, IgA, and IgE

13%

(21/162)

5

Increased IgE and IgA, Decreased IgM

3%

(5/162)

M1

Select Answer to see Preferred Response

PREFERRED RESPONSE 1

(M1.IM.68) A 5-year-old female suffers from recurrent infections by Aspergillus species, Pseudomonas species, and Staphylococcus aureus. The patient's neutrophils are examined in the laboratory and they fail to react during the nitroblue tetrazolium test. Which of the following is most likely dysfunctional in this patient? Review Topic

QID: 100489
1

Lymphocytes

2%

(1/45)

2

Immunoglobulin class switching

11%

(5/45)

3

Superoxide dismutase

11%

(5/45)

4

Myeloperoxidase

36%

(16/45)

5

Respiratory burst

38%

(17/45)

M1

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PREFERRED RESPONSE 5

(M1.IM.53) A 3-year-old female is found to have unusual susceptibility to infections by catalase-producing organisms. This patient likely has a problem with the function of which of the following cell types? Review Topic

QID: 100474
1

B cells

7%

(2/29)

2

T cells

10%

(3/29)

3

Natural killer cells

3%

(1/29)

4

Neutrophils

79%

(23/29)

5

Eosinophils

0%

(0/29)

M1

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PREFERRED RESPONSE 4
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