Aspergillosis
Aspergillosis: Excerpt from The 5-Minute Pediatric Consult
Theoklis Zaoutis, MD
Aspergillosis - BASICS
Aspergillosis - description
- Applied to the wide variety of illnesses caused by fungi in the genus Aspergillus
- Most human disease is caused by Aspergillus fumigatus, Aspergillus flavus, or Aspergillus niger; other Aspergillus species may occasionally cause disease.
Aspergillosis - general prevention
Infection control:
- Hospitalized, immunosuppressed patients are at risk for invasive aspergillosis.
- Environmental measures to control airborne spread of conidiospores in hospitals during construction are indicated.
- Laminar-flow rooms with appropriate filters will significantly decrease contact with airborne conidiospores.
Aspergillosis - epidemiology
- Aspergillus species are saprophytic molds that are ubiquitous and worldwide, growing in soil, grain, dung, bird droppings, and decaying plant matter.
- Spores are resistant to desiccation, lightweight, and are easily dispersed in air currents.
- The main route of transmission is via inhalation of airborne spores; person-to-person spread does not occur.
- The incubation period has not been defined.
- Nosocomial outbreaks have occurred when ventilation or heating systems become contaminated, or when large numbers of spores become airborne during building construction or renovation.
Aspergillosis - incidence
The incidence of aspergillosis varies by the type of population. The overall incidence in immunocompromised children is ~0.4%. The incidence in bone marrow transplant patients is higher (4.5%).
Aspergillosis - risk factors
- Other than those with otomycosis or allergic bronchopulmonary disease, most patients infected with Aspergillus are immunocompromised in some way. Patients at risk include those with malignancy, solid-organ transplantation, bone marrow transplantation, HIV, and congenital immunodeficiencies.
- Transplantation, solid-organ transplantation
Aspergillosis - pathophysiology
- The most common portal of entry for Aspergillus is the respiratory tract; however, damaged skin or operative wounds, the cornea, and the ear can also serve as sites of entry.
- The development of disease depends on the interaction between the organism (virulence) and the host, specifically host defense mechanisms.
- Aspergillus produces toxic metabolites such as elastase, cytotoxins, endotoxins, phospholipases, and various inhibitors of immune function.
- Aspergillus is an unusual pathogen in immunocompetent patients. The first line of defense in the lungs is the macrophages. Neutrophils are also a key part of the host defense against Aspergillus.
- Conditions that alter the normal immunologic mechanisms predispose to invasive aspergillosis; leukemia (neutropenia), corticosteroids (decreased neutrophil mobilization and macrophage killing), chronic granulomatous disease (decreased oxidative-mediated killing)
Aspergillosis - etiology
Aspergillus sp., most commonly Aspergillus fumigatus
Aspergillosis - associated conditions
- Allergic bronchopulmonary aspergillosis (ABPA) is characterized by periodic episodes of wheezing, low-grade fever, eosinophilia on peripheral smear, transient infiltrates on chest radiographic film, and a cough productive of brown mucus plugs. Allergic bronchopulmonary aspergillosis is thought to represent a hypersensitivity response to Aspergillus colonization of the lungs. It occurs most commonly in patients with chronic respiratory disease (i.e., in children with cystic fibrosis).
- Otomycosis is a localized, noninvasive infection of the external ear seen in healthy hosts. It occurs more commonly in warm, wet climates.
- Sinusitis occurs in both healthy and immunocompromised patients. Healthy patients can present with signs and symptoms of chronic sinusitis or a mass (aspergilloma) in the maxillary or ethmoid sinuses. Immunocompromised patients present with invasive disease characterized by bony destruction, extension to contiguous sites such as the orbit or CNS.
- Noninvasive pulmonary aspergillosis (aspergillomas) are pulmonary fungus balls that grow in bronchogenic cysts or other lung cavities. They are the most frequent form of pulmonary aspergillosis.
- Invasive pulmonary aspergillosis occurs in the immunocompromised host, most commonly in patients with hematologic malignancy, solid-organ transplants, HIV infection, or other patients receiving long-term immunosuppressive therapy. Invasion of blood vessels by Aspergillus leads to infarction, necrosis, and hematogenous dissemination.
Aspergillosis - DIAGNOSIS
Aspergillosis - signs & symptoms
Aspergillosis - history
- Question: Is there a history of chronic otitis externa?
- Associated with otomycosis
- Question: Is there a history of sinusitis that does not clear?
- Indolent or noninvasive paranasal sinusitis presents with signs and symptoms of chronic sinusitis that are unresponsive to antibiotic therapy
- Question: Does an asthmatic patient cough up large, dark mucus plugs?
- Allergic bronchopulmonary aspergillosis should be considered in the asthmatic patient with a history of expectorating dark mucus plugs, or a history of fleeting pulmonary infiltrates on chest radiography (due to bronchial plugging).
- Question: Is the patient immunocompromised?
- Immunocompromised patients, especially those with prolonged neutropenia, are at highest risk for invasive aspergillosis. Patients with neutropenia, who are febrile for 1 week despite broad-spectrum antibiotics, are at increased risk of invasive fungal infection.
Aspergillosis - physical exam
- Otomycosis is characterized by a mass of black spores (Aspergillus niger) that start close to the eardrum and eventually fill the external canal, pain on tragal movement, and occasionally a purulent discharge. It is only rarely an invasive disease.
- Invasive sinus aspergillosis may present with severe pain, proptosis, monocular blindness, and bony destruction on radiographic films, with evidence of direct extension to the anterior fossa or orbit, or with widespread dissemination.
- Invasive pulmonary aspergillosis may be indistinguishable from other causes of pneumonia on physical examination. Findings may include fever, tachypnea, rales, hypoxemia, and hemoptysis (secondary to the angioinvasive potential of the organism).
Aspergillosis - tests
Aspergillosis - lab
- Isolation of Aspergillus species by culture is required for definitive diagnosis.
- Aspergillus can be recovered from samples of blood, cerebrospinal fluid, sputum, urine, broncho-alveolar lavage sample, or tissue biopsy. Types of specimens collected are guided by history and physical examination.
- Aspergillus species recovered from cultures of the respiratory tract (e.g., sputum and nasal cultures) are usually a result of colonization in the immunocompetent host but may indicate invasive disease in the immunocompromised host. The positive predictive value may be as high as 80–90% in patients with leukemia or bone marrow transplants.
- Microscopic examination of specially stained tissue samples, or of 10% potassium hydroxide wet-preparation samples, which are positive for branching, septate hyphae are suggestive of Aspergillus or other fungal invaders.
- Elevated serum IgE eosinophilia, serum antibody for Aspergillus, and an immediate-type skin test response to Aspergillus antigen are often present in patients with allergic aspergillosis and are helpful in establishing the diagnosis.
- Radiographic studies may include characteristic findings such as wedge-shaped pleural-based densities or cavities on plain x-rays. Findings on CT scans include the “halo sign” (an area of low attenuation surrounding a nodular lung lesion) initially (caused by edema or bleeding surrounding an ischemic area) and later the “crescent sign” (an air crescent near the periphery of a lung nodule, caused by contraction of infarcted tissue).
- Recent developments in early diagnosis include the use of high-resolution chest CT, new rapid stain techniques and monoclonal antibodies for broncho-alveolar lavage samples, and serum ELISA for Aspergillus galactomannan.
Aspergillosis - differencial diagnosis
- Other bacterial and fungal infections in immunocompromised hosts
- Allergic pneumonitis (other causes):
- Chronic bacterial sinusitis
- Neoplasm
Aspergillosis - TREATMENT
Aspergillosis - general measures
- Allergic bronchopulmonary aspergillosis is frequently managed with oral or inhaled corticosteroids. In patients with corticosteroid-dependent allergic bronchopulmonary aspergillosis, the addition of itraconazole has been shown to be an effective adjunctive agent.
- If paranasal sinusitis is noninvasive, surgical drainage or débridement usually results in clearance of the infection.
- Otomycosis (most commonly secondary to Aspergillus niger) is often found in association with a bacterial external otitis. Débridement of the external canal and treatment of underlying bacterial external otitis usually produces a good therapeutic response.
Aspergillosis - medication
Aspergillosis - first line
The newer azole antifungal agent voriconazole is considered primary therapy for invasive aspergillosis.
Aspergillosis - second line
- Amphotericin B and the lipid-based amphotericin preparations remain appropriate second-line therapeutic options for patients who do not tolerate voriconazole or who are not responding to therapy. For patients in whom amphotericin is being considered, the lipid-based formulations may be preferred as initial therapy in those with marginal renal function or in those receiving other nephrotoxic drugs.
- Itraconazole has been shown to be efficacious in the treatment of invasive aspergillosis. The oral form of itraconazole may be considered as an alternative to amphotericin for prolonged treatment once disease progression has been halted with IV amphotericin therapy.
Aspergillosis - surgery
Surgical excision, in addition to amphotericin B, is sometimes required for localized débridement in invasive disease.
Aspergillosis - FOLLOW UP
Aspergillosis - prognosis
- Good in noninvasive disease, such as simple otomycosis or paranasal sinusitis
- Immunosuppressed or severely neutropenic patients may have rapid extension or dissemination of disease; prognosis is often very poor. Early recognition and aggressive treatment and débridement are necessary.
Aspergillosis - complications
- Disseminated infection, defined as infection of two or more organs, can involve any of the previously discussed sites, as well as the CNS, heart, bones, or skin. Invasiveness depends on the immune state of the host, as well as the period of time and number of spores in the exposure.
- Patients with underlying diseases that predispose them to pulmonary cavitations, blebs, or cysts (such as asthma, chronic bronchitis, tuberculosis, sarcoid, histoplasmosis, and bronchiectasis) may develop an aspergilloma (fungus ball) after seeding their pulmonary secretions with Aspergillus. When the mass is large enough to be demonstrated on chest x-ray study, serum levels of IgG antibody to Aspergillus are characteristically high. Patients may present with hemoptysis, exacerbation of their underlying disease, or, rarely, invasion or dissemination.
Aspergillosis - patient monitoring
The course of illness is variable, depending on host immune function and the location and invasiveness of disease.
- Any immunocompromised patient with persistent fevers or signs of invasive infection who does not improve on treatment with broad-spectrum antibiotics must be evaluated for fungal infection and the empiric use of antifungal medications should be considered.
- The rare finding of diffuse nodular pneumonia in children may be indicative of an underlying diagnosis of chronic granulomatous disease and aspergillosis.
Aspergillosis - bibliography
American Academy of Pediatrics. Aspergillosis. In: Pickering L, ed. 2006 Red Book: Report of the Committee on Infectious Diseases. 26th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2006:219–222.- Denning DW. Invasive aspergillosis. Clin Infect Dis. 1998;26:781–805.
- Marr KA, Patterson T, Denning D. Aspergillosis: Pathogenesis, clinical manifestations, and therapy. Infect Dis Clin North Amer. 2002;16(4):875–894, vi.
- Patterson TF. Combination antifungal therapy. Pediatr Infect Dis J. 2003;22(6):555–556.
- Steinbach WJ, Stevens DA. Review of newer antifungal and immunomodulatory strategies for invasive aspergillosis. Clin Infect Dis. 2003;37(suppl 3):S157–S224.
- Steinbach WJ. Pediatric Aspergillosis: Disease and treatment differences. Pediatric Infectious Diseases Journal. 2005;24(4):358–64.
- Stevens DA, Kan VL, Judson MA, et al. Practice guidelines for diseases caused by Aspergillus. Clin Infect Dis. 2000;30:696–709.
- Zaoutis TE, Heydon K, Chu JH, et al. Epidemiology, outcomes, and costs of invasive aspergillosis in immunocompromised children in the US, 2000. Pediatrics. 2006:711(4):711–716.
Aspergillosis - CODES
Aspergillosis - icd9
117.3 Aspergillosis
Aspergillosis - FAQ
- Q: What are rare complications of aspergillosis?
- A: Endocarditis, osteomyelitis, and cutaneous disease
- Q: Does person-to-person spread occur?
- A: No. The principal route of transmission is inhalation of airborne spores.
Book Source Details
- Book Title: The 5-Minute Pediatric Consult
- Author(s): M. William Schwartz MD; et al.
- Year of Publication: 2008
- Copyright Details: The 5-Minute Pediatric Consult, Copyright © 2008 Lippincott Williams & Wilkins.
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Copyright notice for book excerpts: Copyright © 2008 Lippincott Williams & Wilkins. All rights reserved.
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More About This Book:
Title: The 5-Minute Pediatric Consult
Authors: M. William Schwartz MD; et al.
Publisher: Lippincott Williams & Wilkins
Copyright: 2008
ISBN: 0-7817-7577-9
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