Allergic Bronchopulmonary Aspergillosis (ABPA)

Allergic bronchopulmonary aspergillosis (ABPA) is an allergic reaction within airways occurring almost exclusively in patients with asthma or cystic fibrosis. Less commonly reported in patients with bronchiectasis, chronic granulomatous disease, hyperimmunoglobulinemia E, and lung transplant.

Aspergillus fumigatus colonization leads to IgE and IgG immune responses. The combination of the immune response and colonization by the fungus leads to recurrent symptoms. There is no mucosal invasion; but is characterized by mucoid impaction, eosinophilic pneumonia, granulomatosis.

Symptoms of ABPA

Recurrent episodes of increased airway hyper-responsiveness.
Severe cases include bronchial obstruction, fever, expectoration of brown plugs, hemoptysis, pulmonary consolidation.
Some may also have allergic aspergillus rhinosinusitis with recurrent nasal congestion/obstruction, sinus pressure, dark nasal discharge.

Testing

Absolute blood eosinophilia (typically >500 cells/microL)
Elevated total serum IgE
Precipitating IgG antibodies (precipitins) to Aspergillus, IgE & IgG specific antibodies to Aspergillus.
Galactomannan is not useful in ABPA. See Diagnosis Table.
Sputum testing may show eosinophilic plugs, Charcot-Leyden crystals, or Aspergillus fumigatus.

Imaging

Central bronchiectasis, mucus plugging, parenchymal opacities nodularity, mucus plugging, tree-in-bud, ground glass attenuation, air trapping, or high-attenuation mucus (mucus that is radiographically denser than skeletal muscle) on high resolution CT of chest.

Spirometry

Most have airflow obstruction, air trapping. In severe disease with bronchiectasis or fibrosis may have mixed restrictive and obstructive pattern. A minority also have decreased DLCO.

Diagnosis

See Table.

Differential diagnosis: asthma with fungal sensitization, other causes for bronchiectasis (CF, hypogammaglobulinemia, ciliary disease), chronic pulmonary aspergillosis (pulmonary cavitation with aspergillus), mucoid impaction or bronchocentric granulomatosis, allergic bronchopulmonary mycyosis (ABPA like syndrome due to a different fungi)

Diagnostic criteria for Allergic Bronchopulmonary Aspergillosis
Most commonly favored is proposed by the International Society for Human & Animal Mycology (ISHAM) Working Group
Predisposing Conditions (one must be present): Asthma Cystic Fibrosis
Obligatory Critera (both must be present): Detectable serum IgE to Aspergillus fumigatus (>0.35 kU/L) or Aspergillus skin test positivity, AND Elevated total serum IgE (typically >1000 IU/mL)*
Other criteria (at least 2 must be present): Precipitating serum antibodies to A. fumigatus Elevated A. fumigatus IgG > 27 mg/uL Radiographic opacities consistent with ABPA Absolute eosinophil > 500 cells/uL in glucocorticoid naive patients.**
Children's Mercy-specific laboratory testing: The order “ABPA Cascade” includes the following labs: Total IgE, Aspergillus fumigatus IgE, Aspergillus fumigatus IgG. If total IgE is >500 kU/L, then A. fumigatus IgE & IgG is done. Normal IgE level varies by age. Normal A. fumigatus IgE : <3.7 k/L. Normal Aspergillus IgG: <50 mg/dL. If all ABPA is suspected.
*In other working groups, lower cut off values have been used; if Aspergillus specific IgG >27 mg/L, consideration for total IgE <1000 IU/mL may be acceptable. IgE up to 25,000 IU/mL has been described; if there is a significantly elevated IgE referral should be made to Immunology subspecialist for further evaluation.
**There is no upper limit of definition for eosinophilia in ABPA. For those with absolute eosinophils >2000 cells/uL, consideration should be given to other diagnoses such as eosinophilic granulomatosis with polyangiitis and hyper-eosinophilic syndromes.

Treatment

Referral to a subspecialist. For acute ABPA, treatment includes systemic oral corticosteroids. Antifungal therapies and Th-2 targeting biologic injections are reserved for steroid refractory cases or those unable to taper off of oral steroids.