INTRODUCTION: Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disorder. We report a case of a 31-year-old male with undiagnosed CGD who presents with pulmonary masses.
CASE PRESENTATION: A 31-year-old male was referred to our clinic for evaluation of pulmonary nodules. The patient had a recent history of fevers, productive cough and dyspnea. His history was significant for “recurrent pneumonias” and acne. He has 17 siblings. A sister died of Crohn's disease in her 40s; another brother had a history of severe lung infections and was also recently diagnosed with Crohn's disease. One sister died of a “neck cyst” in infancy and another sister died of a lung disease at age 32. Physical examination revealed a mildly ill-appearing thin young man. Severe cystic facial acne was present. His chest exam was clear to auscultation. Since his symptoms were slow to improve with treatment for community-acquired pneumonia, a CT of the chest was performed. This revealed a large mass in the left upper lobe measuring 3 x 5.4 cm. A 1.8 × 1.5 cm spiculated nodule was seen in the right upper lobe. Other smaller pulmonary nodules as well as enlarged mediastinal lymph nodes were also seen. WBC was normal; a PPD skin test, HIV, CF by DNA analysis, and ANCA were negative. A transthoracic needle biopsy under CT guidance was performed which revealed necrotizing granulomas. He subsequently underwent surgical resection of the right upper lobe lesion. Necrotizing granulomatous inflammation was again seen on pathological specimens. Cultures grew B. cepacia and the patient was treated with sulfamethoxazole-trimethoprim for two weeks, with improvement in his symptoms. Culture of B. cepacia is unusual in a patient without cystic fibrosis. In addition, his family history is suggestive of a primary immunodeficiency. Flow cytometry utilizing dihydrorhodamine 123 (DHR) led to the diagnosis of chronic granulomatous disease.
DISCUSSIONS: CGD was first described in 1959 by Bridges et al. The incidence of this disorder is approximately four per million. It is characterized by recurrent bacterial and fungal infections in patients with impaired neutrophil function. These patients have a defect in the NADPH oxidase (PHOX) gene, which impairs the generation of reactive oxygen species needed for effective microbial killing. The PHOX enzyme is comprised of five subunits which catalyze the production of superoxide from molecular oxygen. Seventy percent of cases are inherited in an X-linked fashion due to mutations in the gp91 gene. Mutations in one of three other subunits have been implicated in the autosomal recessive forms, which tend to have a milder phenotype. Patients with CGD are prone to catalase positive organisms such as S. aureus, Aspergillus sp., Serratia, E. coli, and B. cepacia. Clinical manifestations include recurrent pneumonias, abscess, osteomyelitis, superficial skin infections, bacteremia, and fungemia. The common noninfectious manifestations include granulomatous involvement of the genitourinary and gastrointestinal tracts (mimicking Crohn's disease).The nitroblue tetrazolium (NBT) is the oldest and most widely known screening test for CGD. Flow cytometry using DHR is rapidly becoming the test of choice at most centers.The mainstay of treatment for CGD is antimicrobial prophylaxis, mainly with sulfamethoxazole-trimethoprim and itraconazole. In addition, γ-interferon therapy as been shown to reduce the incidence of serious life-threatening infections in CGD patients. Survival has improved since the first description of “fatal granulomatosis of childhood”. In a recent description of patients in the US CGD registry, more than 25% of all living CGD patients and 42% of those with autosomal recessive CGD were 20 years or older.
CONCLUSION: Undiagnosed CGD should be in the differential diagnosis of any young patient with a strong personal and family history of recurrent infections, and who presents with pulmonary infiltates, nodules, or masses.
DISCLOSURE: Ronald Mudry, None.