Chronic Granulomatous Disease Workup

Updated: Jul 29, 2019
  • Author: Roman J Nowicki, MD, PhD; Chief Editor: Dirk M Elston, MD  more...
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Workup

Laboratory Studies

The nitroblue tetrazolium (NBT) dye test

Laboratory diagnosis of chronic granulomatous disease (CGD) can be made using the NBT test, stimulated with substances such as phorbol myristate acetate or Escherichia coli lipopolysaccharide, which promote an oxidative response in 90-100% of normal neutrophils.

Neutrophils in patients with chronic granulomatous disease are unable to reduce oxidized NBT to insoluble blue formazan; this principle forms the basis of the standard diagnostic screening test for chronic granulomatous disease.

This test is best used to identify gene carriers, and it has been used for the prenatal diagnosis of chronic granulomatous disease.

Flow cytometric reduction of dihydrorhodamine

This test can also be used to diagnose chronic granulomatous disease. The principles are the same as for the NBT dye test, but a different dye is used. Additionally, X-linked carrier status can also be detected.

Complete blood cell counts

Peripheral blood leukocytosis (>8.5 X 103/µL) is a characteristic finding that reflects increased numbers of circulating neutrophils. Most patients are anemic (hemoglobin < 12.5 g%), usually with a microcytic hypochromic picture.

Microbiologic studies

Culture and sensitivity studies may be helpful. Bacteria isolated from lesions in patients with chronic granulomatous disease are usually catalase positive.

Quantitative immunoglobulin tests

Levels of the three major classes of immunoglobulins, immunoglobulin G, immunoglobulin M, and immunoglobulin A, are increased. Immunoglobulin E levels are increased or in the reference range.

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Imaging Studies

Radiography and CT imaging

Pulmonary disease is prominent, with recurrent pneumonia, empyema, and lung abscess formation.

Discrete areas of persistent consolidation may be observed on radiographs and are often called encapsulating pneumonia. This sign is highly distinctive of chronic granulomatous disease. Less specific reticulonodular shadowing and hilar lymphadenopathy are also commonly observed.

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Other Tests

Other diagnostic tests include the following:

  • Chemiluminescence testing to detect the degree of light generated by activated phagocytic cells

  • Direct measurements of oxygen consumption

  • Direct measurements of superoxide anion production

Molecular diagnostics may include the following:

  • Polymerase chain reaction [25]

  • Sequencing

  • Allele-specific restriction enzyme analysis [26]

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Procedures

Skin biopsy is important in correctly diagnosing chronic granulomatous disease.

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Histologic Findings

Chronic granulomatous disease (CGD) is histologically characterized by a mixed suppurative and granulomatous inflammation. A typical feature of visceral granulomas is the presence of golden-brown–pigmented histiocytes. Histochemical stains show that this material is composed of unsaturated fatty acids, phospholipids, and glycoproteins.

Periodic acid-Schiff (PAS) staining demonstrates the presence of carbohydrates, particularly polysaccharides such as mucoproteins. These substances stain reddish purple with the PAS reaction.

Electron microscopic findings suggest that the pigment represents lipofuscin bodies and appears to be derived from lysosomes. Granulomas consist of neutrophils and macrophages that contain yellow inclusions with areas of necrosis.

Aspergillus species is shown below.

Scanning electron micrograph of Aspergillus specie Scanning electron micrograph of Aspergillus species.
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