Sensitization to Aspergillus species in the congenital neutrophil disorders chronic granulomatous disease and hyper-IgE syndrome,☆☆,

Presented as an abstract at the AAAAI annual meeting, Washington, DC, 1997.
https://doi.org/10.1016/S0091-6749(99)70023-0Get rights and content

Abstract

Background: Hyper-IgE syndrome (HIE) and chronic granulomatous disease (CGD) are congenital immunodeficiency diseases with increased susceptibility to bacterial and fungal infections. Both carry significant morbidity and mortality rates because of invasive infections by Aspergillus species. We encountered 2 patients, one with HIE and one with CGD, in whom detection of sensitization to Aspergillus species preceded the diagnosis of immunodeficiency. With high-dose systemic corticosteroids for allergic bronchopulmonary aspergillosis (ABPA), an inflammatory disorder caused by sensitization to Aspergillus species, pulmonary abscesses developed in the patient with HIE, and the patient with CGD succumbed to an overwhelming Aspergillus species–induced pneumonia. Objective: We sought to assess the prevalence of sensitization to Aspergillus fumigatus and the presence of diagnostic criteria for ABPA in patients with CGD and HIE. Methods: We measured A fumigatus –specific serum IgE, IgG, and precipitating antibodies as indicators for A fumigatus sensitization in the sera of 18 patients with neutrophil disorders (7 with HIE and 11 with CGD). Hospital records were reviewed for the presence of other diagnostic criteria for ABPA (asthma, elevated total serum IgE concentration, and radiographic abnormalities). Results: Twelve (67%) of 18 patients were sensitized to A fumigatus , as evidenced by precipitating A fumigatus –specific antibodies. Six (33%) of 18 patients had serologic evidence of ABPA. Five of those 6 patients had radiologic abnormalities consistent with a diagnosis of ABPA. One patient with HIE also had asthma, thus fulfilling minimal essential criteria for concurrent ABPA. Conclusions: Patients with HIE syndrome and CGD have a high incidence of sensitization to Aspergillus species. A clinical picture indistinguishable from ABPA may coexist or emerge in patients with CGD or HIE and create a major management dilemma because systemic corticosteroids may accelerate tissue damage and invasive fungal infections. It is important to distinguish individuals with congenital neutrophil disorders from uncomplicated classic ABPA. (J Allergy Clin Immunol 1999;1265-72.)

Section snippets

Case report 1

The patient is a 35-year-old bank accountant who was referred for immunologic evaluation in 1997 by an infectious disease specialist. In 1992, the patient was found to have a lung abscess of the left upper lobe caused by S aureus , which was surgically excised in 1993. Over the following years, the patient had recurrent right upper lobe infiltrates and hilar adenopathy and required repeated therapeutic bronchoscopic removal of impacted mucoid material from the right upper lobe bronchus. Fungal

RESULTS

Eighteen patients with either CGD or HIE were studied, 11 with CGD (mean age, 16 ± 11.7 years; 9 male and 2 female subjects) and 7 with HIE (mean age, 35 ± 14 years; 4 male and 3 female subjects). All male patients with CGD had the X-linked form of the disease, as determined by family history, molecular analysis, or both. A compilation of the clinical courses and outcomes of the patients is shown in Table I, Table II.

From the 18 patients studied, 12 (67%, 10 of 11 with CGD and 2 of 7 with HIE)

DISCUSSION

In CGD and HIE, invasive pulmonary Aspergillus infections are one of the more common disease manifestations.5, 6, 7, 8, 10 Aspergillus infections can cause pneumonia, disseminated interstitial disease, and granulomata in CGD and carry a significant mortality rate.9, 28 In HIE syndrome Aspergillus infections may produce lung abscesses and erosion of pulmonary vasculature, leading to hemoptysis.11 In contrast, in ABPA Aspergillus species serve as an immune stimulant, but tissue invasion does not

References (34)

  • M Dinauer et al.

    The glycoprotein encoded by the X-linked chronic granulomatous disease locus is a component of the neutrophil cytochrome b complex

    Nature

    (1987)
  • E Mills et al.

    Chemiluminescence, a rapid sensitive method for detection of patients with chronic granulomatous disease [abstract]

    Pediatr Res

    (1978)
  • J Curnutte

    Chronic granulomatous disease: the solving of a clinical riddle at the molecular level

    Clin Immunol Immunopathol

    (1993)
  • R Buckley

    Disorders of the IgE system

  • B Grimbacher et al.

    Hyper-IgE syndrome with recurrent infections—an autosomal dominant multisystem disorder

    N Engl J Med

    (1999)
  • D Chudwin et al.

    Aspergillus pneumonia in chronic granulomatous disease: recurrence and long-term outcome

    Acta Paediatr Scand

    (1982)
  • D Conrad et al.

    Microgranulomatous aspergillosis after shoveling wood chips: report of a fatal outcome in a patient with chronic granulomatous disease

    Am J Ind Med

    (1992)
  • Cited by (0)

    Supported in part by grant USPHS AI 42349 and the Ernest S. Bazley Grant to Northwestern Memorial Hospital and Northwestern University. Thomas Eppinger, MD, was a fellow of the Jeffrey Modell Foundation.

    ☆☆

    Reprint requests: Charlotte Cunningham-Rundles, MD, PhD, Mount Sinai Medical Center, Division of Clinical Immunology, Box 1089, 1425 Madison Ave, New York, NY 10029.

    0091-6749/99 $8.00 + 0  1/1/102871

    View full text