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Aspergillosis

Description of Medical Condition

Disease caused by a ubiquitous mold that primarily involves the lungs. Disease frequently lethal in neutropenic and bone marrow transplant (BMT) patients. Syndromes include:

  • Allergic aspergillosis
    • Extrinsic allergic alveolitis — hypersensitivity pneumonitis in individuals repeatedly exposed to the fungus
    • Allergic bronchopulmonary aspergillosis (ABPA)
  • pulmonary infiltrates, mucous plugging; secondary to allergic reaction to fungus
  • Aspergillomas: “fungus ball” saprophytic colonization within pre-existing pulmonary cavities
  • Invasive aspergillosis: most common and severe in BMT and neutropenic patients. Also occurs with increased frequency in other immunocompromised persons, such as those with AIDS, solid organ transplant or high dose corticosteroids; commonly fatal.

System(s) affected: Pulmonary, Nervous, Gastrointestinal, Musculoskeletal, Cardiovascular

Genetics: No known genetic pattern

Incidence/Prevalence in USA: Rare

Predominant age: None

Predominant sex: Male = Female

Medical Symptoms and Signs of Disease

  • Allergic — cough, wheezing, constitutional symptoms, plug expectoration
  • Aspergillomas — hemoptysis; manifestations of underlying disease
  • Invasive — fever, cough, rales, rhonchi; toxicity; CNS signs; Gl bleeding

What Causes Disease?

Aspergillus species in decreasing order of frequency: A. fumigatus, A. flavus, A. niger

Risk Factors

  • Allergic — exposure, asthma
  • Aspergillomas — COPD, bronchiectasis, TB, malignancy
  • Invasive — neutropenia, corticosteroid therapy, graft vs. host disease in recipients of bone marrow transplant. AIDS

Aspergillosis

Diagnosis of Disease

Differential Diagnosis

  • Allergic — other causes of asthma and hypersensitivity pneumonitis.
  • Aspergillomas — neoplasm, TB
  • Invasive — bacterial pneumonia, pulmonary hemorrhage, drug toxicity, malignancy; mucor (sinuses).

Laboratory

  • ABPA — eosinophilia, immediate skin reactivity to aspergillus antigen, precipitating-serum antibodies to aspergillus, elevated serum IgE concentrations.
  • Invasive — sputum culture, cultures of bronchoalveolar lavage or bronchial washings; biopsy is definitive; blood cultures almost never positive

Drugs that may alter lab results: None

Disorders that may alter lab results: None

Pathological Findings

Necrotiz ing pneumonia, hemorrhagic infarcts, bloodvessel invasion; branching septate hyphae if organism seen microscopically

Special Tests

  • ABPA — immediate skin reactivity to aspergillus antigen, precipitating serum antibodies (precipitins) against aspergillus antigens, elevated serum IgE concentrations, elevated serum IgE and IgG antibodies specific to A. fumigatus.
  • Invasive — none

Imaging

Chest x-ray — fleeting infiltrates (ABPA), round intracavity mass (aspergillomas); nodular or patchy infiltrates progressing to diffuse consolidation and cavitation (invasive); nodular, cavitary or pleural-based wedge-shaped lesions

Diagnostic Procedures

Bronchos copy, bronchial washings, bronchoalveolar lavage or transthoracic needle aspiration may be helpful in isolating organism in invasive disease; open lung biopsy is diagnostic but often not possible in severely ill, ventilated patients.

Treatment (Medical Therapy)

Appropriate Health Care

  • Allergic — outpatient usually
  • Aspergillomas — outpatient usually
  • Invasive- inpatient

General Measures

  • Allergic
    • Extrinsic allergic alveolitis -drug therapy, exposure avoidance. OABPA-corticosteroids
  • Aspergillomas – individualized therapy ranging from no therapy to surgical resection of cavities in cases of severe hemoptysis; systemic antifungal therapy is seldom useful
  • Invasive – (prognosis tends to be poor) high dose intravenous antifungal therapy; treatment of underlying disease; adjunctive cytokine therapy to reverse neutropenia

Activity

As tolerated

Diet

No special diet

Patient Education

To specifics of individual circumstances.

Medications (Drugs, Medicines)

Drug(s) of Choice

  • Allergic
    • Extrinsic allergic alveolitis — bronchodilators, cromolyn, steroids
    • ABPA-steroids
  • Aspergillomas — none
  • Invasive — high dose amphotericin B — up to 1 mg/kg/ day. The lipid formulations of amphotericin B (Abelcet. Ambisome) are preferred over standard amphotericin because of the reduced nephrotoxicity in view of the high doses required.
  • Caspofungin is approved for patients with aspergillosis unresponsive to other therapy or who have unacceptable toxicity to other agents
  • Voriconazole was superior to conventional amphotericin in a large study and is well absorbed orally
  • Note: because of the frequent failure of single drug therapy, combination therapy is frequently proposed

Contraindications: Refer to manufacturer’s literature

Precautions: Amphotericin B can cause significant renal insufficiency and electrolyte abnormalities. Saline infusion at the time of amphotericin B administration may decrease the nephrotoxicity.

Significant possible interactions:

  • Amphotericin B — other nephrotoxic drugs (aminoglycosides, cyclosporine, etc): accelerate development of renal insufficiency
  • Amphotericin B — diuretics: accelerate electrolyte depletion
  • Voriconazole — hepatically metabolized drug; serum levels may be altered
  • Itraconazole-hepatically metabolized drugs: serum levels altered
  • Itraconazole — gastric pH: normal, low pH is necessary for absorption

Alternative Drugs

Itraconazole is occasionally useful as an alternative agent

Patient Monitoring

  • Allergic
    • Extrinsic allergic, alveolitis — spirometry
    • ABPA — chest x-ray, IgE levels
  • Aspergillomas — chest x-ray, symptoms
  • Invasive — chest x-ray, CBC

Prevention / Avoidance

  • Allergic — avoid exposure
  • Aspergillomas — treatment of underlying diseases, eg. COPD, etc.

Possible Complications

  • Allergic- bronchiectasis, pulmonaryfibrosis, obstructive lung disease
  • Aspergillomas — hemoptyses
  • Invasive — metastatic infection of CNS, Gl tract and other organs; death

Expected Course / Prognosis

  • Allergic — with treatment prognosis is good; untreated can progress to severe fibrosis, COPD
  • Aspergillomas — prognosis more related to underlying disease
  • Invasive — poor prognosis

Miscellaneous

Associated Conditions

  • Allergic — asthma
  • Aspergillomas — COPD, TB, pulmonary mycoses, silicosis, sarcoidosis, non-tuberculosis mycobacteria, ankylosing spondylitis, malignancy
  • Invasive- neutropenia

Aspergillosis

Age-Related Factors

Pediatric: N/A

Geriatric: N/A

Others:

  • Allergic — Tends to occur in younger patients <35.
  • Aspergillomas — older patients with chronic lung disease
  • Invasive-all ages

Pregnancy

N/A

Synonyms

  • Hypersensitivity pneumonitis
  • Fungus ball

International Classification of Diseases

117.3 Aspergillosis

Abbreviations

ABPA:

monary aspergillosis

allergic bronchopul

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