The patient presented in the question stem has recurrent infections by catalase-producing organisms. This presentation is consistent with chronic granulomatous disease, characterized by dysfunction of the respiratory burst.
Chronic granulomatous disease (CGD) is caused by a deficiency of neutrophil NADPH oxidase. Normally, NADPH oxidase generates reactive oxygen species in the neutrophil which are converted to hydrogen peroxide (a strong antibacterial chemical), in a series of reactions known as the respiratory burst. Patients with CGD are defenseless against those organisms that break down their own hydrogen peroxide, otherwise known as catalase-producing organisms. These include S. aureus, Pseudomonas, Serratia marescens, Nocardia, and Aspergillus - thus infections with these organisms are commonly seen in those with CGD. The nitroblue tetrazolium (NBT) test is the classic test for CGD. In patients with CGD, neutrophils FAIL to turn blue when exposed to nitroblue tetrazolium.
Cooper et al. discuss the primary immunodeficiencies including CGD. Though there may be as many as 500,000 persons with primary immunodeficiencies living in the US, the authors estimate that only 50,000 are diagnosed each year. The primary immunodeficiencies include: humoral immunodeficiencies (problems with B-cell differentiation or production of antibodies); T-cell disorders; phagocytic disorders; and complement deficiencies. Clinicians should suspect immunodeficiency given pattern of unusual, recurrent, or resistant infection, with family history.
Leiding et al. provide an overview of CGD in this excerpt. In addition to description of its common presenting illnesses, including pneumonias, abscesses, lymphadenitis, and osteomyelitis, they note that CGD may present any time between early childhood and late adulthood (so age is not a distinguishing factor). They discuss a newer diagnostic test, the dihydrorhodamine (DHR) test, which has in clinical practice surpassed the NBT test.
Illustration A shows the NBT test result. At left in Panel A, the neutrophils stain blue (negative for CGD). At right, the photo shows neutrophils that fail to turn blue (positive for CGD, negative NBT test).
Answer 1: CGD is a defect of phagocytes, not lymphocytes. Examples of lymphocyte disorders include Bruton's agammaglobulinemia and SCID among many others.
Answer 2: Defective immunoglobulin class switching may occur in other primary immunodeficiencies, such as hyper-IgM syndrome, but not in CGD.
Answer 3: Superoxide dismutase converts reactive oxygen species to hydrogen peroxide as described above. This enzyme is intact in CGD.
Answer 4: Myeloperoxidase is an enzyme that contributes to the respiratory burst. Myeloperoxidase deficiency presents similarly to CGD but with an NBT test in which the neutrophils turn blue due to the intact NADPH oxidase.
Cooper MA, Pommering TL, Korányi K. Primary immunodeficiencies. Am Fam Physician. 2003 Nov 15;68(10):2001-8. Review.
PMID:14655810 (Link to Abstract)
Leiding JW, Holland SM. Chronic Granulomatous Disease. 2012 Aug 09. In: Pagon RA, Bird TD, Dolan CR, Stephens K, Adam MP, editors. GeneReviews™ [Internet]. Seattle (WA): University of Washington, Seattle; 1993-. Available from http://www.ncbi.nlm.nih.gov/books/NBK99496/
PMID:22876374 (Link to Abstract)
USMLE World Step 1 QBank Question #571. Copyright © USMLEWorld, LLC 2012