Disorders of Phagocyte Function

Chapter 18 Disorders of Phagocyte Function

Clinical Approach to Patients With Disorders of Phagocyte Function

Index of Suspicion

Patients with disorders of phagocyte function usually present at a young age with recurrent, deep-seated bacterial and fungal infections. Unlike patients with severe neutropenia caused by bone marrow failure, these patients usually do not have sepsis. Blood cultures are often negative. The major diagnostic problem faced by the clinician is to determine if the history of infection is unusual enough to warrant consideration of an underlying neutrophil dysfunction defect. The first point to remember is that primary immunodeficiency disorders are rare and primary neutrophil dysfunction syndromes form only a small percentage of all primary immunodeficiency syndromes. The patient is more likely to have recurrent community-acquired Staphylococcus infection than chronic granulomatous disease.

Specific features that may suggest a phagocytic defect are shown in Figure 18-2. Excellent discussions of this problem have been published (see Kyono and Coates1 and Dinauer and Newburger2). Four aspects of each patient’s infection history should be considered: frequency, severity, location, and responsible pathogen. Patients with unusual features in at least one of these aspects should alert the clinician to a possible underlying phagocyte disorder. When considering frequency, the patient’s age and associated medical conditions must be taken into account. For example, recurrent otitis media in a 2-year-old patient is far less worrisome than a similar history in a 40-year-old patient. The more unusual or severe the infections, the less frequently these have to occur before a phagocyte evaluation is indicated. Infections in unexpected anatomic locations, such as hepatic, pulmonary, and rectal abscesses, may indicate an underlying phagocyte defect. Childhood periodontal disease or gingivitis is distinctly uncommon, and in the absence of neutropenic conditions, strongly suggests underlying neutrophil dysfunction. The identification of certain pathogens (e.g., Serratia marcescens, Klebsiella spp., Aspergillus spp., Nocardia spp., Burkholderia cepacia, invasive candidiasis) in children and young adults can provide the strongest indications for pursuing further studies. A history of delayed separation of the umbilical cord is often mentioned as a sign of phagocytic defect. This is fairly common as an isolated finding and is usually of no significance. However, this is in conjunction with omphalitis or other pyogenic infections raises the possibility of LAD or chemotactic defects. A child with nystagmus, fair skin, and recurrent staphylococcal infections should be evaluated for CHS.


Performing a good history and physical examination to eliminate common causes of recurrent infection is important before looking for rare syndromes. For example, is the recurrent pneumonia caused by an aspirated foreign body in the bronchus? In general, patients should first be evaluated for lymphocyte or complement defects. A useful algorithm is presented in Figure 18-2. Note that testing described in this algorithm is not exhaustive, and patients with truly striking histories of unusual kinds of infections should be referred for further evaluation by specialized research laboratories.

Diagnosis of Chronic Granulomatous Disease

The diagnosis of CGD is easily established by doing an NBT slide test or flow cytometry of DHR 123 fluorescence to detect neutrophil NADPH oxidase activity. The NBT slide test is very easy to set up, as is DHR flow cytometry. However, because the probability of getting an abnormal result is very low, there may be confusion in interpretation because of a lack of experience. In the authors’ experience, incorrect positive and negative results have been reported for both assays. Thus, if the index of suspicion is high, consultation should be obtained from a center with extensive experience with the test and with the disorder.

Neutrophil respiratory burst activity is preserved in anticoagulated blood maintained at room temperature for several days; thus, DHR testing can be done 1 to 2 days later after shipping to a commercial laboratory. A normal control should always be shipped with the patient specimen to eliminate problems in specimen handling during transport.

DHR Flow Cytometry

• This approach has replaced the NBT slide test in many laboratories. It has the advantage of assessing large numbers of cells and can give quantitation of the amount of oxidant production.

• The change in fluorescence channel number with stimulation is the critical number and not the percent positive cells.

• X-linked CGD patients will not respond at all and show no increase in fluorescence with stimulation (see Fig. 18-3, F).

• X-linked carriers will show about 50% of the cells that respond with a normal increase in fluorescence, and the other half will have no response. Degrees of unequal X inactivation are much more accurately quantified by this assay (see Fig. 18-3, G).

• AR patients, particularly those with absent p47phox, have some response to stimulation and show a small increase in fluorescence (see Fig. 18-3, H). This level of oxidant production is usually not visible on the NBT test.

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Jun 12, 2016 | Posted by in HEMATOLOGY | Comments Off on Disorders of Phagocyte Function

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