Allergic bronchopulmonary aspergillosis: causes, symptoms, diagnosis, treatment

Allergic bronchopulmonary aspergillosis is a hypersensitivity reaction to Aspergillus fumigatus, which occurs almost exclusively in patients with bronchial asthma or, more rarely, cystic fibrosis. Immune responses to aspergillus antigens cause airway obstruction and, if there is no treatment, bronchiectasis and pulmonary fibrosis.

Symptoms of allergic bronchopulmonary aspergillosis correspond to those in bronchial asthma, with the addition in the form of productive cough and, sometimes, fever and anorexia. The diagnosis is suspected on the basis of anamnesis and the results of instrumental examinations and is confirmed by an aspergillus skin test and determination of IgE level, circulating precipitinins and antibodies to A. Fumigatus. Treatment of allergic bronchopulmonary aspergillosis is carried out by glucocorticoids and itraconazole in the refractory course of the disease.

[1], [2], [3]

What causes allergic bronchopulmonary aspergillosis?

Allergic bronchopulmonary aspergillosis develops when the airways of patients with bronchial asthma or cystic fibrosis are colonized by aspergillus (an ubiquitous soil fungus). For unclear reasons, colonization in these patients causes the production of antibodies (IgE and IgG) and cellular immunity reactions (hypersensitivity reactions of types I, III and IV) on aspergillus antigens, leading to frequent, repeated exacerbations of bronchial asthma. Over time, immune reactions, together with direct toxic effects of the fungus, lead to damage to the respiratory tract with the development of dilations and, ultimately, bronchiectasis and fibrosis. Histologically, the disease is characterized by obstruction of the mucus of the respiratory tract, eosinophilic pneumonia, infiltration of the alveolar septa by plasma and mononuclear cells and an increase in the number of bronchiolar mucous glands and cubic cells. In rare cases, an identical syndrome called allergic bronchopulmonary mycosis, in the absence of bronchial asthma or cystic fibrosis, causes other fungi, for example Penicillum, Candida, Curvularia, Helminthosporium and / or Drechslera spp.

Aspergillus is intraluminarno, but not invasive. Thus, allergic bronchopulmonary aspergillosis should be distinguished from invasive aspergillosis, which occurs only in patients with weakened immunity; from aspergillus, which are aspergillus accumulations in patients with known cavernous lesions or cystic lesions in the lungs; and from a rare aspergillus pneumonia, which occurs in patients receiving long-term low doses of prednisolone (eg, patients with COPD ).

What are the symptoms of allergic bronchopulmonary aspergillosis?

Symptoms of allergic bronchopulmonary aspergillosis are similar to those in bronchial asthma or exacerbation of pulmonary cystic fibrosis, with an additional cough, discharge of dirty green or brown sputum and, occasionally, hemoptysis. Fever, headache and anorexia are frequent systemic symptoms of a severe illness. Symptoms are manifestations of airway obstruction, specific wheezing and elongated exhalation, which are indistinguishable from exacerbation of bronchial asthma, are specific.

Stages of allergic bronchopulmonary aspergillosis

• I - Acute - All diagnostic criteria are present
• II - Remission - No symptoms for more than 6 months
• III - Relapse - Appearance of one or more diagnostic signs
• IV - Refractory - Dependence on glucocorticoids or refractory to treatment
• V - Fibrosis - Diffuse fibrosis and bronchiectasis

Stages do not progress consistently.

How is allergic bronchopulmonary aspergillosis diagnosed?

The diagnosis is suspected in patients with bronchial asthma at any frequency of exacerbations, with migratory or unresolvable infiltrates on chest radiography (often due to atelectasis from mucous plug and bronchial obstruction), detection of signs of bronchiectasis using imaging techniques, detection of A. Fumigatus in bacteriological research and / or severe peripheral eosinophilia. Other radiographic findings include darkening in the form of tape or finger gloves due to the presence of mucous inclusions and linear shadows indicating swelling of the bronchial walls. These signs may also be present in bronchiectasis caused by other causes, but the sign of the seal ring due to the enlarged airways adjacent to the vascular network of the lungs distinguishes bronchiectasis from allergic bronchopulmonary aspergillosis in high-resolution CT.

Diagnostic criteria for allergic bronchopulmonary aspergillosis

• Bronchial asthma or cystic fibrosis
• Increased level of aspergillus-specific IgE and IgG
• Elevated serum IgE (> 1000ng / ml)
• Proximal bronchiectasis
• Papular-hyperergic skin reaction to aspergillus antigens
• Eosinophilia of the blood (> 1 x 109)
• Serum Precipitins to Aspergillus Antigens
• Migratory or fixed pulmonary infiltrate
• Minimal essential criteria are noted.
• The inclusion of proximal bronchiectasis is controversial and may not be required for diagnosis.

Several diagnostic criteria have been proposed, but in practice, four important criteria are usually evaluated. With a positive test with aspergillus antigen (immediate reaction in the form of blister and reddening of the face), serum IgE and aspergillus precipitin should be determined , although a positive skin test may be in 25% of patients with bronchial asthma without allergic bronchopulmonary aspergillosis. With an IgE level greater than 1000 ng / ml and a positive test for precipitin, the content of specific antiaspergillous immunoglobulins should be determined, although up to 10% of healthy patients have circulating precipitin. Analysis for aspergillosis: antibodies to the causative agent of aspergillosis in the blood can detect fungal-specific antibodies IgG and IgE in concentrations at least twice as high as in patients without allergic bronchopulmonary aspergillosis, confirms the diagnosis. Whenever the results diverge, for example, IgE is more than 1000 ng / ml, but tests for specific immunoglobulins are negative, the study must be repeated and / or the patient should be observed for a long time to definitively establish or exclude the diagnosis of "allergic bronchopulmonary aspergillosis."

The results of suspicion, but not specific for the disease, include the presence of mycelium, eosinophilia and / or Charcot-Leiden crystals (elongated eosinophilic bodies formed from eosinophilic granules) in the sputum and delayed-type skin reaction (erythema, edema and soreness through 6- 8 h) on aspergillous antigens.

[4], [5], [6], [7], [8]

Treatment of allergic bronchopulmonary aspergillosis

Treatment of allergic bronchopulmonary aspergillosis is based on the stage of the disease. Stage I is treated with prednisolone 0.5-0.75 mg / kg once a day for 2-4 weeks, then the dose decreases for more than 4-6 months. Chest X-ray, blood eosinophils and IgE levels should be examined quarterly. Recovery is noted when resolving the infiltrate, reducing eosinophils by more than 50% and reducing IgE by 33%. Patients who reach stage II of the disease require only annual monitoring. Patients of stage II with relapses (stage III) receive another course of treatment with prednisolone. Patients in stage I or III who are not amenable to treatment with prednisolone (stage IV) are candidates for antifungal treatment. Itraconazole 200 mg orally 2 times a day, fluconazole 200-400 mg per day for 4-6 months followed by a six-month maintenance therapy with low doses is recommended instead of prednisolone and as a drug that reduces the need for glucocorticoids. Therapy with itraconazole or fluconazole requires control of drug concentrations in the body, liver enzymes, triglycerides and K.

All patients need optimal treatment for the underlying disease - bronchial asthma or cystic fibrosis. In addition, patients taking long-term glucocorticoids should be screened to avoid complications such as cataracts, hyperglycemia and osteoporosis, and possibly receive drugs to prevent demineralization of bone tissue and infection with Pneumocystis jiroveci (formerly known as P. Carinii).