Chronic granulomatous disease (CGD) is an inherited immunodeficiency syndrome caused by a defect in phagocytic function that results in recurrent infections with low-grade bacterial and fungal pathogens. We report a ten-month-old boy with an unusual presentation of CGD.
The patient was an infant with a history of latent tuberculosis infection, diagnosed at ten months of age who was being treated with isoniazid. He presented with a ten-day history of fever, non-productive cough and a decreased appetite. An initial chest radiograph was normal and cultures of the blood and urine were negative. A complete blood count showed 31,300 white blood cells/mm3 with 42% neutrophils, 43% lymphocytes, and 8% monocytes. Ebstein-Barr antibody titers were negative. He was started on daily intramuscular ceftriaxone but since the fever persisted and he developed rigors, he was admitted for evaluation. A full sepsis workup was done and cerebrospinal fluid (CSF) analysis revealed 14 leukocytes/mm3 with 74% lymphocytes and 24% monocytes, glucose and protein concentrations were normal for age. The Gram stain showed no cells or organisms and cultures of the blood, urine and CSF were negative. A computed tomography (CT) scan of the chest revealed multiple nodules bilaterally, enlarged mediastinal lymph nodes and a mass that extended from the hilum to mediastinum and the left lung apex (image 1). Three gastric aspirates were negative for tuberculosis and a bone marrow aspirate was normal. A left-sided thoracotomy with lung and lymph node biopsies was performed. There was no evidence of lymphoproliferative disease, acid-fast bacilli, fungi, or parasites. In the lung tissue were necrotizing granulomas, lipid-laden macrophages, and gram-negative rods. A lymph node culture grew Acinetobacter lwoffi. Intravenous amikacin and meropenem were started and because of the granulomas and the presence of a catalase positive gram-negative enteric organism, an oxidative burst test was done. Results revealed 0% oxidation (normal >75%) and a phagocytic index of 1.2 (normal >1.7) and the diagnosis of CGD was confirmed. The patient went home on hospital day 40 on itraconazole and interferon-gamma.
CGD is a primary immunodeficiency characterized by the inability of phagocytes to generate the required reactive oxygen species (ROS) resulting in a predisposition to severe infections with catalase-positive bacteria, Staphylococcus species and fungi, especially Aspergillus. The incidence of CGD in the United States is estimated to be about 1:250,000 in all ethnic groups. The most common form is an X-linked presentation, consisting of about 70% of the cases. Infections in many different organ systems can occur and since there is inadequate removal of the organisms, granulomas and abscesses are common, recurrent and difficult to treat. Pneumonias are the most common serious infection in all age groups and pneumonias due to Aspergillus infection are the most common cause of death.
Early diagnosis and aggressive and timely prevention and management of the frequent infections are the basis for a good outcome and improved prognosis in patients with CGD. Prophylactic administration of antibiotic and antifungal agents significantly decreases the incidence of serious infections. Both bone marrow transplantation and gene therapy have demonstrated preliminary successes toward curing the disease.
H.C. Opsimos, None.