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Chronic Granulomatous Disease: Differential Diagnoses & Workup

Author: Roman Janusz Nowicki, MD, PhD, Associate Professor, Department of Dermatology, Venereology and Allergology, Medical University of Gdansk, Poland
Contributor Information and Disclosures

Updated: May 29, 2009

Differential Diagnoses

Acne Conglobata
Eosinophilic Pustular Folliculitis
Acneiform Eruptions
Folliculitis
Aphthous Stomatitis
Gram-Negative Folliculitis
Cancers of the Oral Mucosa
Gram-Negative Toe Web Infection
Candidiasis, Chronic Mucocutaneous
Impetigo
Candidiasis, Cutaneous
Intertrigo
Candidiasis, Mucosal
Job Syndrome
Cheilitis Glandularis
Paronychia
Childhood HIV Disease
Perifolliculitis Capitis Abscedens Et Suffodiens
Coccidioidomycosis
Sarcoidosis
Common Variable Immunodeficiency
Seborrheic Dermatitis
Complement Receptor Deficiency
Wiskott-Aldrich Syndrome
Cutaneous Manifestations of HIV Disease

Other Problems to Be Considered

Bacterial diseases
Chronic mycoses 
Tuberculosis
Histoplasmosis

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

Imaging Studies

  • X-ray 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.

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
    • Polymerase chain reaction20
    • Sequencing
    • Allele-specific restriction enzyme analysis

Procedures

  • Skin biopsy is important in correctly diagnosing chronic granulomatous disease.

Histologic Findings

Chronic granulomatous disease 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.

More on Chronic Granulomatous Disease

Overview: Chronic Granulomatous Disease
Differential Diagnoses & Workup: Chronic Granulomatous Disease
Treatment & Medication: Chronic Granulomatous Disease
Follow-up: Chronic Granulomatous Disease
References
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Further Reading

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Keywords

chronic granulomatous disease, CGD, fatal granulomatosis of childhood, immunodeficiency disorders, X-linked recessive disorder, gp91phox, p22phox, p67phox, Xp21.1, Rac2, impaired phagocytic function, defective cytochrome b function, oxidase absence, oxidase malfunction

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Contributor Information and Disclosures

Author

Roman Janusz Nowicki, MD, PhD, Associate Professor, Department of Dermatology, Venereology and Allergology, Medical University of Gdansk, Poland
Roman Janusz Nowicki, MD, PhD is a member of the following medical societies: American Academy of Dermatology, European Academy of Dermatology and Venereology, and International Society for Human and Animal Mycology
Disclosure: Nothing to disclose.

Medical Editor

Jacek C Szepietowski, MD, PhD, Professor, Vice-Head, Department of Dermatology, Venereology and Allergology, Wroclaw Medical University; Director of the Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Poland
Disclosure: Stiefel Salary Employment; Orfagen Consulting fee Consulting; Maruho Consulting fee Consulting; Astellas Consulting fee Consulting

Pharmacy Editor

David F Butler, MD, Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic, Northside Clinic
David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Managing Editor

Robert A Schwartz, MD, MPH, Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi
Disclosure: Nothing to disclose.

CME Editor

Catherine Quirk, MD, Clinical Assistant Professor, Department of Dermatology, Brown University
Catherine Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology
Disclosure: Nothing to disclose.

Chief Editor

William D James, MD, Paul R Gross Professor of Dermatology, University of Pennsylvania School of Medicine; Vice-Chair, Program Director, Department of Dermatology, University of Pennsylvania Health System
William D James, MD is a member of the following medical societies: American Academy of Dermatology and Society for Investigative Dermatology
Disclosure: elsevier Royalty Other; american college of physicians Honoraria Other

 
 
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