Immunology · Year 2 · from Immunology
Case 1: Chronic Granulomatous Disease
Patient Demographics
- Age: 4 years old
- Sex: Male
- Ethnicity: Caucasian
Chief Complaint
Recurrent skin abscesses and pneumonia
History of Present Illness
A 4-year-old boy is brought to the pediatric immunology clinic for evaluation of recurrent infections. Since infancy, he has had multiple skin abscesses requiring surgical drainage, three episodes of pneumonia requiring hospitalization, and one episode of liver abscess. His mother notes that the abscesses often lack significant redness and pus despite being large. He was recently hospitalized for Aspergillus pneumonia requiring antifungal therapy.
Past Medical History
- Multiple skin abscesses (Staphylococcus aureus cultured from several)
- Pneumonia at ages 1, 2, and 4 years
- Liver abscess at age 3 (Serratia marcescens cultured)
- Perianal abscess at age 2
Family History
- Maternal uncle died at age 12 from recurrent infections
- Mother has no history of significant infections
Physical Examination
- General: Alert, thin-appearing child, below 10th percentile for weight
- Vital Signs: T 37.8C, HR 110, RR 22, BP 95/60
- HEENT: Cervical lymphadenopathy
- Lungs: Decreased breath sounds at right base, scattered rhonchi
- Abdomen: Hepatomegaly palpable 3 cm below costal margin
- Skin: Multiple hyperpigmented scars from prior abscesses, one active draining lesion on right thigh
Laboratory Workup
| Test | Result | Reference Range |
|---|---|---|
| WBC | 18,500/uL | 5,500-15,500/uL |
| Neutrophils | 72% | 40-70% |
| Immunoglobulins | Normal IgG, IgA, IgM | -- |
| DHR Flow Cytometry | Absent oxidative burst | Normal burst expected |
| Genetic testing | CYBB mutation | -- |
Clinical Image
Image source: Wikimedia Commons (https://commons.wikimedia.org/wiki/File:Chronic_Granulomatous_Disease.jpg). Licensed under CC BY-SA 3.0.
Diagnosis
X-linked Chronic Granulomatous Disease (CGD) due to CYBB mutation affecting the gp91phox component of the NADPH oxidase complex.
Discussion
CGD results from defects in the phagocyte NADPH oxidase complex, which generates superoxide and other reactive oxygen species essential for intracellular killing. The X-linked form (affecting CYBB/gp91phox) accounts for approximately 65% of cases. Patients characteristically develop infections with catalase-positive organisms (Staphylococcus aureus, Aspergillus, Serratia, Burkholderia cepacia, Nocardia) because these organisms destroy their own hydrogen peroxide, preventing the phagocyte from using this pathogen-derived source for oxidative killing.
Treatment
- Prophylaxis: Trimethoprim-sulfamethoxazole (TMP-SMX) for bacterial prophylaxis, itraconazole for fungal prophylaxis
- Interferon-gamma: Reduces infection frequency by enhancing residual phagocyte function
- Aggressive treatment of infections: Prompt identification and treatment with appropriate antimicrobials
- Definitive therapy: Hematopoietic stem cell transplantation (curative); gene therapy under investigation