Chronic Granulomatous Disease Clinical Presentation

  • Author: Roman Janusz Nowicki, MD, PhD; Chief Editor: Dirk M Elston, MD   more...
 
Updated: Jan 4, 2012
 

History

The disease becomes apparent during the first 2 years of life in most patients, but the onset is occasionally delayed into the second decade of life.

  • The earliest manifestations often involve the skin. Recurrent pyodermas are common, and they often appear as perianal, axillary, or scalp abscesses.
  • Systemic findings include osteomyelitis, pulmonary abscesses and granulomas, spleen and/or liver abscesses, and hepatosplenomegaly.
  • Pyrexia may be noted.
  • Diarrhea may occur.
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Physical

Short stature is a prominent clinical feature in children and adults with chronic granulomatous disease.

Patients with chronic granulomatous disease usually present with recurrent bacterial and fungal infections in early childhood. The most common initial manifestations are as follows[15] :

  • Pneumonias
  • Otitis
  • Adenitis
  • Skin infections
  • Septicemia
  • Diarrhea
  • Spleen and/or liver abscesses
  • Gingival abscesses
  • Suppurative lymphadenitis

Patients may have inflammatory and presumably noninfectious conditions such as granulomatous colitis and obstructive granulomas.

The earliest reports of chronic granulomatous disease emphasize dermatitis as a characteristic and often presenting manifestation of the disease.[16, 17] The dermatitis was described as an eczematoid, seborrheic, or infectious eczematoid dermatitis that predominantly involved the eyelids and periorbital skin, nares, perioral skin, and ears. The skin lesions frequently became pustular. Similar eruptions were described on the scalp, neck, axillae, inguinal folds, retroauricular folds, and interdigital web spaces. Generalized maculopapular, pustular, and papulopustular eruptions of the newborn were also reported.

Cutaneous manifestations other than dermatitis can be present. Neonatal pustulosis is commonly the first sign of the disease. Recurrent pyodermas are common, and they appear as perianal or axillary abscesses. Eczema of the scalp and lesions of the periorbital, nasal, and postauricular regions are typical, and it is often complicated by infection with staphylococci or other bacteria. Minor abrasions frequently lead to furunculosis and subcutaneous abscesses. Abscesses characteristically heal slowly and leave prominent scars. Skin manifestations in older patients include healed scars of old lesions in the cervical or inguinal areas or scars secondary to multiple surgical procedures performed to drain abscesses.

Associated chronic blepharoconjunctivitis and serosanguineous nasal discharge is often described.

Intraoral ulcerations are described in many patients. These ulcerations resemble aphthous stomatitis, chronic gingivitis, perioral ulcers, scalp folliculitis, chronic suppurative paronychia, or seborrheic dermatitis. Recurrent ulcerative stomatitis is present at some time in almost all patients with chronic granulomatous disease.

Systemic findings are pronounced and include the following:

  • Hepatosplenomegaly
  • Osteomyelitis (particularly that caused by Aspergillus species)
  • Recurrent pneumonia with lung abscesses and granulomas (Pneumonia occurs in almost all affected children and may lead to abscess formation, cavitation, and empyema.)
  • Gastrointestinal manifestations (eg, malabsorption, perianal abscesses and fistulae, oral ulceration, characteristic obstructive lesions associated with granulomatous infiltration)[18]

Mothers of affected boys with the most commonly involved gene often have Jessner lymphocytic infiltrate or discoid lupus erythematosus. In rare instances, systemic lupus erythematosus is reported.

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Causes

The main defect in chronic granulomatous disease is a failure of neutrophils, monocytes, macrophages, and eosinophils to mount a respiratory burst and, therefore, to generate superoxide anions and other reactive oxygen species derived from superoxide, such as hydrogen peroxide. This renders the patients susceptible to severe, recurrent bacterial and fungal infections. The intracellular survival of ingested bacteria leads to the development of granulomata in the lymph nodes, skin, lungs, liver, gastrointestinal tract, and/or bones.

  • Leukocytes ingest bacteria but do not kill them because of a defect in the production of the superoxide anion.
  • Most infections in chronic granulomatous disease are caused by Staphylococcus aureus.
  • Infections are also caused by unusual opportunistic organisms such as Chromobacterium violaceum; Serratia marcescens; and Nocardia, Legionella, and atypical Mycobacteria species.
  • BCG vaccination may cause chronic granulomatous disease.
  • Fungal infections in chronic granulomatous disease patients have been reported to account for approximately 20% of infections. The most common fungal infections in these patients are caused by Aspergillus species. The spectrum of infection caused by Aspergillus species varies from flulike pneumonia to life-threatening invasive aspergillosis. The most common form of aspergillosis in chronic granulomatous disease patients is Aspergillus pneumonia, which can be accompanied by dissemination to the ribs, chest wall, and soft tissues. Infections with Aspergillus species, particularly of the lungs or bones, are difficult to eradicate.
  • The most common infecting organisms, on the basis of the type and site of infection, include the following[19] :
    • Pneumonia -Aspergillus, Staphylococcus, Nocardia, and Serratia species and Burkholderia cepacia (formerly Pseudomonas cepacia)[20]
    • Subcutaneous, liver, or perirectal abscess -Staphylococcus, Serratia, and Aspergillus species
    • Lung abscess -Aspergillus species
    • Brain abscess -Aspergillus species
    • Suppurative adenitis -Staphylococcus and Serratia species
    • Osteomyelitis -Serratia and Aspergillus species
    • Bacteremia and/or fungemia -Salmonella and Candida species and B cepacia
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Contributor Information and Disclosures
Author

Roman Janusz Nowicki, MD, PhD  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.

Specialty Editor Board

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 GSK Company Salary Employment; Orfagen Consulting fee Consulting; Maruho Consulting fee Consulting; Astellas Consulting fee Consulting; Abbott Consulting fee Consulting; Leo Pharma Consulting fee Consulting

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.

Robert A Schwartz, MD, MPH  Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, University of Medicine and Dentistry of New Jersey-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.

Catherine M Quirk, MD  Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania

Catherine M Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD  Director, Ackerman Academy of Dermatopathology, New York

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

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