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ESSENTIALS OF DIAGNOSIS

  • Most common cause of non-candidal invasive fungal infection in transplant recipients and in patients with hematologic malignancies.

  • Predisposing factors: leukemia, bone marrow or organ transplant, late HIV infection.

  • Pulmonary, sinus, and CNS are most common disease sites.

  • Detection of galactomannan by ELISA or PCR in serum or other body fluids is useful for early diagnosis and treatment.

GENERAL CONSIDERATIONS

Aspergillus fumigatus is the usual cause of aspergillosis, though many species of Aspergillus may cause a wide spectrum of disease. The lungs, sinuses, and brain are the organs most often involved. Clinical illness results either from an aberrant immunologic response or tissue invasion.

CLINICAL FINDINGS

A. Symptoms and Signs

1. Allergic forms of aspergillosis

Allergic bronchopulmonary aspergillosis (ABPA) occurs in patients with preexisting asthma or cystic fibrosis who develop worsening bronchospasm and fleeting pulmonary infiltrates accompanied by eosinophilia, high levels of IgE, and IgG Aspergillus precipitins in the blood. Allergic aspergillus sinusitis produces a chronic sinus inflammation characterized by eosinophilic mucus and noninvasive hyphal elements.

2. Chronic aspergillosis

Chronic pulmonary aspergillosis produces a spectrum of disease that usually occurs when there is preexisting lung damage but not significant immunocompromise. Disease manifestations range from aspergillomas that develop in a lung cavity to chronic fibrosing pulmonary aspergillosis in which the majority of lung tissue is replaced with fibrosis. Long-standing (longer than 3 months) pulmonary and systemic symptoms such as cough, shortness of breath, weight loss, and malaise are common.

3. Invasive aspergillosis

Invasive aspergillosis most commonly occurs in profoundly immunodeficient patients, such as those who have undergone hematopoietic stem cell transplantation or have prolonged, severe neutropenia, but it can occur among critically ill immunocompetent patients as well. Specific risk factors in patients who have undergone a hematopoietic stem cell transplant include cytopenias, corticosteroid use, iron overload, cytomegalovirus disease, and graft-versus-host disease. Pulmonary disease is most common, with patchy infiltration leading to a severe necrotizing pneumonia. Invasive sinus disease also occurs. There is often tissue infarction as the organism grows into blood vessels; clues to this are the development of pleuritic chest pain and elevation of serum LD. At any time, there may be hematogenous dissemination to the CNS, skin, and other organs. Early diagnosis and reversal of any correctable immunosuppression are essential.

B. Laboratory Findings

There is eosinophilia, high levels of total IgE, and IgE and IgG specific for Aspergillus in the blood of patients with ABPA.

Blood cultures have very low yield in any form of aspergillosis. Detection of galactomannan by ELISA or Aspergillus DNA by PCR, or both, has been used for the early diagnosis of invasive disease, though multiple determinations should be done and usefulness is decreased in patients receiving anti-mold prophylaxis (ie, voriconazole or posaconazole). Galactomannan levels ...

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