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Chronic Granulomatous Disease Clinical Presentation

  • Author: Roman Janusz Nowicki, MD, PhD; Chief Editor: Dirk M Elston, MD  more...
 
Updated: Aug 21, 2015
 

History

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

  • Pneumonias [16]
  • 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 CGD emphasize dermatitis as a characteristic and often presenting manifestation of the disease.[17, 18] 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 CGD.

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) [19]
  • Hepatic (and perihepatic) abscesses (Patients usually present with fever, malaise, and weight loss.)  
  • Perirectal abscesses (can persist for years despite aggressive antimicrobial therapy and fastidious local care)

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 (CGD) 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 CGD 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 CGD.

Fungal infections in CGD 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[20] :

  • Pneumonia -  Aspergillus species , Staphylococcus aureus, Nocardia, and Serratia species and Burkholderia cepacia (formerly Pseudomonas cepacia) [21]
  • 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 - Can arise from hematogenous spread of organisms ( S aureus, Salmonella species, S marcescens) or contiguous invasion of bone, seen typically with non– Aspergillus fumigatus pneumonia, such as Aspergillus nidulans spreading to the ribs or vertebral bodies [1]
  • Bacteremia and/or fungemia -Salmonella and Candida species and B cepacia 
  • Other frequently encountered catalase-positive microbial agents -  Escherichia coli species, Listeria species, Klebsiella species, and  Nocardia.
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Contributor Information and Disclosures
Author

Roman Janusz Nowicki, MD, PhD Professor and Chairman, 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, International Society for Human and Animal Mycology

Disclosure: Nothing to disclose.

Specialty Editor Board

David F Butler, MD Section Chief of Dermatology, Central Texas Veterans Healthcare System; Professor of Dermatology, Texas A&M University College of Medicine; Founding Chair, Department of Dermatology, Scott and White Clinic

David F Butler, MD is a member of the following medical societies: American Medical Association, Alpha Omega Alpha, Association of Military Dermatologists, American Academy of Dermatology, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Phi Beta Kappa

Disclosure: Nothing to disclose.

Robert A Schwartz, MD, MPH Professor and Head of Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, Rutgers New Jersey Medical School; Visiting Professor, Rutgers University School of Public Affairs and Administration

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, New York Academy of Medicine, American Academy of Dermatology, American College of Physicians, Sigma Xi

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

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

Disclosure: Nothing to disclose.

Additional Contributors

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: Received consulting fee from Orfagen for consulting; Received consulting fee from Maruho for consulting; Received consulting fee from Astellas for consulting; Received consulting fee from Abbott for consulting; Received consulting fee from Leo Pharma for consulting; Received consulting fee from Biogenoma for consulting; Received honoraria from Janssen for speaking and teaching; Received honoraria from Medac for speaking and teaching; Received consulting fee from Dignity Sciences for consulting; .

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Scanning electron micrograph of Aspergillus species.
 
 
 
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