Allergic bronchopulmonary aspergillosis (ABPA) develops when airways of patients with asthma Asthma Asthma is a disease of diffuse airway inflammation caused by a variety of triggering stimuli resulting in partially or completely reversible bronchoconstriction. Symptoms and signs include dyspnea... read more or cystic fibrosis Cystic Fibrosis Cystic fibrosis is an inherited disease of the exocrine glands affecting primarily the gastrointestinal and respiratory systems. It leads to chronic lung disease, exocrine pancreatic insufficiency... read more become colonized with species of Aspergillus (ubiquitous fungi in the soil).
Pathophysiology of ABPA
For unclear reasons, colonization in these patients prompts vigorous antibody (IgE and IgG) and cell-mediated immune responses (type I, III, and IV hypersensitivity reactions Classification of Hypersensitivity Reactions Allergic (including atopic) and other hypersensitivity disorders are inappropriate or exaggerated immune reactions to foreign antigens. Inappropriate immune reactions include those that are... read more ) to Aspergillus antigens, leading to frequent, recurrent asthma exacerbations Evaluation of exacerbations Asthma is a disease of diffuse airway inflammation caused by a variety of triggering stimuli resulting in partially or completely reversible bronchoconstriction. Symptoms and signs include dyspnea... read more . Over time, the immune reactions, combined with direct toxic effects of the fungus, lead to airway damage with dilation and, ultimately, bronchiectasis Bronchiectasis Bronchiectasis is dilation and destruction of larger bronchi caused by chronic infection and inflammation. Common causes are cystic fibrosis, immune defects, and recurrent infections, though... read more and fibrosis. The disorder is characterized histologically by mucoid impaction of airways, eosinophilic pneumonia Overview of Eosinophilic Pulmonary Diseases Eosinophilic pulmonary diseases are a heterogeneous group of disorders characterized by the accumulation of eosinophils in alveolar spaces, the interstitium, or both. Peripheral blood eosinophilia... read more , infiltration of alveolar septa with plasma and mononuclear cells, and an increase in the number of bronchiolar mucous glands and goblet cells.
Rarely, other fungi, such as Penicillium, Candida, Curvularia, Helminthosporium, and Drechslera, cause an identical syndrome called allergic bronchopulmonary mycosis in the absence of underlying asthma or cystic fibrosis.
Aspergillus is present intraluminally but is not invasive. Thus, ABPA must be distinguished from
Aspergillomas, which are collections of Aspergillus in patients with established cavitary lesions or cystic airspaces
Aspergillus pneumonia, which is rare and occurs in patients who take low doses of prednisone long term (eg, patients with chronic obstructive pulmonary disease Chronic Obstructive Pulmonary Disease (COPD) Chronic obstructive pulmonary disease (COPD) is airflow limitation caused by an inflammatory response to inhaled toxins, often cigarette smoke. Alpha-1 antitrypsin deficiency and various occupational... read more )
Although the distinction can be clear, overlap syndromes have been reported.
Symptoms and Signs of ABPA
Symptoms are those of asthma Symptoms and Signs Asthma is a disease of diffuse airway inflammation caused by a variety of triggering stimuli resulting in partially or completely reversible bronchoconstriction. Symptoms and signs include dyspnea... read more or pulmonary cystic fibrosis Respiratory Cystic fibrosis is an inherited disease of the exocrine glands affecting primarily the gastrointestinal and respiratory systems. It leads to chronic lung disease, exocrine pancreatic insufficiency... read more exacerbation, with the addition of cough productive of dirty-green or brown plugs and, occasionally, hemoptysis. Fever, headache, and anorexia are common systemic symptoms in severe disease. Signs are those of airway obstruction, specifically, wheezing and prolonged expiration, which are indistinguishable from asthma exacerbation.
Diagnosis of ABPA
History of asthma
Chest x-ray or high-resolution CT
Skin prick test with Aspergillus antigen
Aspergillus precipitins in blood
Positive sputum culture for Aspergillus species (or, rarely, other fungi)
Blood eosinophil count
The diagnosis is suspected in patients with asthma with recurrent asthma exacerbations, migratory or nonresolving infiltrates on chest x-ray (often due to atelectasis resulting from mucoid plugging and bronchial obstruction), evidence of bronchiectasis Diagnosis Bronchiectasis is dilation and destruction of larger bronchi caused by chronic infection and inflammation. Common causes are cystic fibrosis, immune defects, and recurrent infections, though... read more on imaging studies, sputum cultures positive for A. fumigatus, or notable peripheral eosinophilia.
Several criteria have been proposed for the diagnosis (see table Diagnostic Criteria for Allergic Bronchopulmonary Aspergillosis Diagnostic Criteria for Allergic Bronchopulmonary Aspergillosis Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction to Aspergillus species (generally A. fumigatus) that occurs almost exclusively in patients with asthma or, less... read more ), but in practice not all criteria are assessed in every case.
When the diagnosis is suspected, a skin prick test with Aspergillus antigen is the best first step, but serologic testing for Aspergillus precipitins may be a more practical initial test. An immediate wheal-and-flare reaction should prompt measurement of serum IgE and Aspergillus precipitins because up to 25% of patients with asthma without ABPA may have a positive skin test. An IgE level > 1000 ng/mL (> 417 IU/mL) and positive precipitins suggest the diagnosis, which should be confirmed by measurement of specific anti-Aspergillus immunoglobulins (up to 10% of healthy patients have circulating precipitins). When ABPA is suspected, a finding of A. fumigatus–specific IgG and IgE antibodies in concentrations at least twice those found in patients without ABPA establishes the diagnosis.
Sputum and bronchoscopic cultures for Aspergillus have a low sensitivity and specificity for the diagnosis of ABPA and are not included as diagnostic criteria.
Whenever test results diverge, such as when serum IgE is elevated but no A. fumigatus–specific immunoglobulins are found, testing should be repeated and the patient should be monitored over time to definitively establish or exclude the diagnosis.
Treatment of ABPA
Sometimes antifungal drugs
Treatment is based on disease stage (see table Stages of Allergic Bronchopulmonary Aspergillosis Stages of Allergic Bronchopulmonary Aspergillosis* Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction to Aspergillus species (generally A. fumigatus) that occurs almost exclusively in patients with asthma or, less... read more ).
Stage I is treated with prednisone 0.5 to 0.75 mg/kg orally once a day for 2 to 4 weeks, then tapered over 4 to 6 months. Chest x-ray, blood eosinophil count, and IgE levels should be checked quarterly for improvement, defined as resolution of infiltrates, ≥ 50% decline in eosinophils, and 33% decline in IgE. Patients who achieve stage II disease require annual monitoring only.
Stage II patients who relapse (stage III) are given another trial of prednisone. Stage I or III patients who do not improve with prednisone (Stage IV) are candidates for antifungal treatment. Itraconazole 200 mg orally twice a day for 16 weeks is recommended as a substitute for prednisone and as a corticosteroid-sparing drug.
Itraconazole therapy requires checking drug levels and monitoring liver enzymes and triglyceride and potassium levels.
All patients should be optimally treated for their underlying asthma or cystic fibrosis. In addition, patients taking long-term corticosteroids should be monitored for complications, such as cataracts Cataract A cataract is a congenital or degenerative opacity of the lens. The main symptom is gradual, painless vision blurring. Diagnosis is by ophthalmoscopy and slit-lamp examination. Treatment is... read more , diabetes mellitus Diabetes Mellitus (DM) Diabetes mellitus is impaired insulin secretion and variable degrees of peripheral insulin resistance leading to hyperglycemia. Early symptoms are related to hyperglycemia and include polydipsia... read more , and osteoporosis Osteoporosis Osteoporosis is a progressive metabolic bone disease that decreases bone mineral density (bone mass per unit volume), with deterioration of bone structure. Skeletal weakness leads to fractures... read more , and possibly prescribed treatments to prevent bone demineralization and Pneumocystis jirovecii lung infection.
Consider allergic bronchopulmonary aspergillosis (ABPA) if a patient with asthma or cystic fibrosis develops frequent exacerbations for unclear reasons, has migratory or nonresolving infiltrates on chest x-ray, evidence of bronchiectasis on imaging studies, persistent blood eosinophilia, or if a sputum culture reveals Aspergillus.
Begin testing with a skin prick using Aspergillus antigen, followed usually by serologic testing.
Treat initially with prednisone.
If ABPA persists despite prednisone, treat with an antifungal such as itraconazole.