A genetically heterogenous, fatal immunodeficiency
syndrome of childhood as a result of dysfunctional oxidative metabolism in
the phagocytic cells, leading to recurrent and life-threatening bacterial
and fungal infections.
Fatal Granulomatosis of Childhood; Chronic Granulomatous
Disease of Childhood; Progressive Septic Granulomatosis;
Cytochrome-b-Negative X-Linked Granulomatous Disease.
Approximately 1:200,000-500,000 live births.
In two thirds of cases, inheritance is
X-linked recessive, with the responsible gene located on Xp21.1. In the
remaining one third, transmission is autosomal recessive
(Cytochrome-b-positive granulomatous disease), with the defect mapped to
The production of antimicrobial reactive oxygen
intermediates is impaired by a defective NADPH enzyme. The neutrophil
phagocytic metabolic burst is impaired. Neutrophil chemotaxis and killing of
organisms are defective. The disease is characterized by granulomas and recurrent infections by catalase-positive organisms.
Typical organisms are Aspergillus (most
common), Candida, Staphylococcus, Pseudomonas, Salmonella, Nocardia,Serratia species, and Burkholderia cenocepacia. Chronic granulomatous disease is caused by a
defect of one of the subcomponents of the reduced nicotinamide adenine
dinucleotide phosphate oxidase of neutrophils, monocytes, macrophages, and
eosinophils. This situation results in a reduced ability to produce
superoxide ions and hydrogen peroxide and is responsible for the
significantly impaired ability to kill intracellular microorganisms.
The most frequent presentation (75% of patients) are
recurrent childhood infections. Granulocyte function can be assessed by the
nitroblue tetrazolium test.
The disease manifests as skin infections,
pneumonias, lung abscesses, lymphadenitis, diarrhea, perianal abscesses,
hepatic, splenic, pancreatic, perinephritic, and subdiaphragmatic abscesses,
osteomyelitis, and sepsis (15% of patients). An incidence of 3.7 severe
infections requiring hospitalization per 100 patients and month has been
reported. Granulomas in the skin, gastrointestinal tract, and genitourinary
tract are characteristic and can result in esophageal, gastric outlet,
intestinal, and ureteral obstruction. The most common indications for
surgery include gastric outlet obstruction, hepatic abscesses, and enteric
fistulas. Long-term antibiotic prophylaxis with
trimethoprim-sulfamethoxazole has been successful in significantly reducing
the incidence of severe bacterial infections, but fungal infections are
increased. Itraconazole has been used successfully to reduce fungal
infections. Therapy with γ-interferon reduces infections. Long-term
complications include chronic lymphadenopathy (>80% of all patients),
underweight and short stature (31% and 23%, respectively), chronic
inflammatory processes (e.g., ulcerative stomatitis in almost 30%),
chronic diarrhea (15%), and pulmonary fibrosis (10%). Approximately
20% of the patients die at a median age of 21 years from cardiopulmonary
failure secondary to chronic or recurrent chest infections, but
approximately 50% of patients survive the fourth decade of life, with a
plateau after the third decade of life.
Obtain a complete blood count. Check
serum levels of electrolytes in patients with diarrhea. A chest radiograph
is recommended in the presence of respiratory symptoms. For elective cases,
patients with chronic pulmonary fibrosis should undergo pulmonary function
tests (including arterial blood gas analysis).
Early aggressive antimicrobial and
surgical treatment of infections has been recommended. Patients may present
for surgery in septic states. Anesthesia care is determined ...