Exogenous allergic alveolitis

Exogenous allergic alveolitis (hypersensitivity pneumonitis) is an allergic diffuse lesion of the alveoli and interstitial lung tissue that develops under the influence of intense and prolonged inhalation of antigens of organic and inorganic dust. Diagnosis is carried out by analyzing the history, physical examination, the results of radiation studies, bronchoalveolar lavage and histological examination of the biopsy material. Short-term treatment with glucocorticoids is prescribed; then it is necessary to stop contact with the antigen.

[1], [2]

Causes of the exogenous allergic alveolitis

More than 300 antigens have been identified as capable of causing hypersensitivity pneumonitis, although eight of them account for approximately 75% of cases. Antigens are usually classified by type and occupational affiliation; a farmer's lung caused by the inhalation of hay dust containing thermophilic actinomycetes is a classic example of this pathology. A significant similarity is observed between pneumonitis of hypersensitivity and chronic bronchitis in farmers, in whom chronic bronchitis occurs much more often, develops independently from smoking and is associated with secretions of thermophilic actinomycetes. The clinical manifestations of this condition and the results of diagnostic studies are similar to those for pneumonitis of hypersensitivity.

Disease exogenous allergic alveolitis is probably a type IV hypersensitivity reaction in which repeated contact with an antigen in people with a hereditary predisposition leads to acute neutrophil and mononuclear alveolitis accompanied by interstitial infiltration of lymphocytes and a granulomatous response. With prolonged contact, fibrosis develops with bronchioles obliteration.

Circulating precipiticins (antibodies to the antigen) do not appear to play a primary aetiological role, and the presence of allergic diseases in the anamnesis (bronchial asthma or seasonal allergies) is not a predisposing factor. Smoking is likely to delay or prevent the development of the disease, possibly due to a decrease in the lung's immune response to inhaled antigens. However, smoking can exacerbate the disease, which is already present.

Pneumonitis of hypersensitivity (exogenous allergic alveolitis) should be differentiated with similar clinical conditions having a different pathogenesis. Toxic syndrome of organic dust (pulmonary mycotoxicosis, cereal fever), for example, is a syndrome manifested by fever, chills, myalgia and shortness of breath, which does not require previous sensitization and is believed to be caused by the inhalation of mycotoxins or other contaminants of organic dust. The disease of the silo stacker can lead to respiratory failure, acute respiratory distress syndrome (ARDS) and bronchiolitis obliterans, but is caused by the inhalation of toxic nitrogen oxides released from freshly-fructified corn or silous alfalfa. Occupational asthma causes the development of dyspnea in persons previously sensitized to the inhaled antigen, but other manifestations, in particular the presence of airway obstruction, their eosinophilic infiltration, and the difference in trigger antigens, make it possible to differentiate it from pneumonitis of hypersensitivity.

[3], [4], [5]

Symptoms of the exogenous allergic alveolitis

Pneumonitis of hypersensitivity (exogenous allergic alveolitis) is a syndrome caused by sensitization and subsequent hypersensitivity to exogenous (often professional) antigen and manifested by cough, dyspnea and malaise.

Symptoms of exogenous allergic alveolitis depend on whether the onset is acute, subacute or chronic. Only a small proportion of affected individuals develop characteristic symptoms of the disease, and in most cases this occurs only for several weeks to several months after the onset of exposure and sensitization.

An acute onset of the disease occurs in previously sensitized individuals with acute intense exposure to the antigen and is manifested by fever, chills, coughing, chest tightness and shortness of breath, developing for 4 to 8 hours after exposure to the allergen. Anorexia, nausea and vomiting may also be present. Physical examination reveals tachypnea, diffuse small- or medium bubbling inspiratory rales and, in almost all cases, the absence of noisy breathing.

Chronic variant occurs in individuals who have chronic contact with a low concentration antigen (for example, in bird owners) and manifests itself as a dyspnea progressing from months to years with exercise, productive cough, malaise and weight loss. During a physical examination, no significant changes are detected; thickening of the terminal phalanges of the fingers occurs infrequently, fever absent. In severe cases, pulmonary fibrosis leads to the development of manifestations of right ventricular and / or respiratory failure.

Subacute variant of the disease is intermediate between acute and chronic variants and manifests itself either as cough, dyspnea, malaise and anorexia, developing for several days to several weeks, or exacerbation of chronic symptoms.

[6], [7]

Forms

There are sharp, subacute and chronic forms; all are characterized by acute interstitial inflammation and development of granulomas and fibrosis with prolonged exposure.

[8], [9], [10]

Diagnostics of the exogenous allergic alveolitis

Diagnosis of exogenous allergic alveolitis is based on the analysis of the history, physical examination, the results of radiation studies, lung function tests, microscopy of bronchoalveolar lavage and biopsy material. The differential diagnosis spectrum includes lung diseases associated with environmental factors, sarcoidosis, bronchiolitis obliterans, lung lesions in connective tissue diseases and other IBLARB.

[11], [12], [13]

Diagnostic criteria for exogenous allergic alveolitis

Known antigen effect:

• Exposition in the anamnesis.
• Confirmation of the presence of antigen in the environment by appropriate research.
• The presence of an increased concentration of specific serum precipitating IgG.

Results of clinical examination, radiography and lung function tests:

• Characteristic clinical manifestations (especially after detection of antigen).
• Characteristic changes in the chest X-ray or HRCT.
• Pathological changes in lung function.

Lymphocytosis in washing waters of bronchoalveolar lavage:

• The ratio CD4 + / CDB + <1
• Positive result of the reaction of blast transformation of lymphocytes.

Recurrence of clinical manifestations and changes in lung function in a provocative sample with an antigen:

• In the environment
• Controlled reaction to the extracted antigen.

Histological changes:

• Noncaseating granulomas.
• Mononuclear cell infiltrate.

Of key importance in the history are atypical relapsing pneumonia, developing at approximately the same time intervals; the development of manifestations of the disease after moving to a new job or moving to a new place of residence; long-term contact with a hot bath, sauna, swimming pool or other sources of standing water at home or elsewhere; the presence of birds as pets; as well as exacerbation and disappearance of symptoms when creating and excluding certain conditions, respectively.

The examination often does not help in the diagnosis, although there may be pathological pulmonary noises and thickening of the terminal phalanges of the fingers.
Radiation studies are usually performed in patients who have a characteristic history and clinical manifestations. Radiography of chest organs is neither sensitive nor specific in the diagnosis of the disease, and its results are often normal in acute and subacute forms of the disease. There may be an increase in pulmonary pattern or focal shadows in the presence of clinical manifestations of the disease. In the chronic stage of the disease, it is more likely to detect an increase in the pulmonary pattern or focal dimming in the upper parts of the lungs, along with a decrease in their volume and the formation of a "cellular lung," similar to that found in idiopathic pulmonary fibrosis. Pathological changes are much more often detected when performing high resolution CT scans (CTWR), which is considered the standard for assessing parenchymal changes in pneumonitis of hypersensitivity. The most frequent change detected in HRCT is the presence of multiple centrilobular micro-nodes with a fuzzy contour. These micro-nodules can occur in patients with acute, subacute and chronic forms of the disease and, in the relevant clinical context, are highly likely to support pneumonitis of hypersensitivity. Occasionally, obscuring by the type of frosted glass is the predominant or only change. Darkening data are usually diffuse, but sometimes do not affect the peripheral parts of the secondary lobules of the lung. Local areas of increased intensity, similar to those detected with obliterating bronchiolitis, may be the main manifestation in some patients (for example, a mosaic increase in density with air retention in HRCT on exhalation). With chronic hypersensitivity pneumonitis, there are symptoms of lung fibrosis (eg, reduction in the volume of lobes, dimming of the linear form, enhancement of the pulmonary pattern or "honeycomb lung"). Some non-smoking patients with chronic hypersensitivity pneumonitis have signs of emphysema in the upper lobes of the lungs. The enlargement of the lymph nodes of the mediastinum is rare and helps to distinguish the pneumonitis of hypersensitivity from sarcoidosis.

Lung function tests should be performed in all cases with suspicion of hypersensitivity pneumonitis. Exogenous allergic alveolitis can cause an obstructive, restrictive or mixed type of change. The terminal phase of the disease is usually accompanied by restrictive changes (decrease in lung volumes), a decrease in diffusion capacity for carbon monoxide (DI_CО) and hypoxemia. Obstruction of the respiratory tract is unusual for an acute disease, but can develop with its chronic variant.

The results of bronchoalveolar lavage are rarely specific for this diagnosis, but are often a component of a diagnostic study in the presence of chronic manifestations of the respiratory system and lung function disorders. The presence of lymphocytosis in rinsing waters (> 60%) with a CD4 + / CD8 + ratio <1.0 is characteristic for this disease; on the contrary, lymphocytosis with predominance of CD4 + (ratio> 1.0) is more typical for sarcoidosis. Other changes may include the presence of mast cells in an amount of more than 1% of the total number of cells (after an acute episode of the disease) and an increase in the number of neutrophils and eosinophils.

Lung biopsy is performed with insufficient information content of non-invasive studies. Transbronchial biopsy performed with bronchoscopy is sufficient when it is possible to obtain several samples from different parts of the lesion, which are subsequently examined histologically. The revealed changes may vary, but include lymphocytic alveolitis, noncaseating granulomas and granulomatosis. Interstitial fibrosis may be detected, but is usually mild in the absence of changes in radiography.

Additional studies are assigned if necessary to obtain other information for diagnosis or to establish other causes of IBLARB. Circulating precipitipins (specific precipitating antibodies to a suspected antigen) are presumably significant, but are neither sensitive nor specific and thus useless in diagnosis. Identification of a specific precipitating antigen may require a detailed aerobiological and / or microbiological study of the workplace by industrial hygienists, but is usually guided by known sources of provoking antigens (for example, the presence of Bacillus subtilis in the manufacture of detergents). Skin tests do not matter, and eosinophilia is absent. Studies that have diagnostic value in detecting other diseases include serological and microbiological studies (for ornithosis and other pneumonia) and studies of autoantibodies (for systemic diseases and vasculitis). An increased number of eosinophils may indicate chronic eosinophilic pneumonia, and an increase in lymph nodes in the roots of the lungs and paratracheal lymph nodes is more common in sarcoidosis.

[14], [15], [16], [17]

Treatment of the exogenous allergic alveolitis

Treatment of exogenous allergic alveolitis is carried out using glucocorticoids, usually prednisolone (60 mg once a day for 1 to 2 weeks, then the dose gradually decreases to 20 mg once a day for the next 2 to 4 weeks, then reduce the dose 2.5 mg per week until complete withdrawal of the drug). This mode allows you to stop the initial manifestations of the disease, but probably does not affect the long-term results.

The most important component of long-term treatment is the prevention of contact with the antigen. However, a complete change in lifestyle and work is rarely possible in real conditions, especially among farmers and other workers. In this case, measures are taken to reduce dust (for example, pre-humidify the compost before working with it), use air filters and protective masks. Fungicides can be used to prevent the multiplication of antigen-producing microorganisms (for example, in hay or sugar beet), but the remote safety of this approach has not been proven. Thorough cleaning of moisturizing ventilation systems, removal of damp carpets and maintenance of low humidity are also effective in some cases. Patients need to be clarified, however, that these measures may not have the effect of continuing contact with the antigen.

Forecast

Pathological changes are completely reversible if the disease of exogenous allergic alveolitis is detected early and the effect of the antigen is eliminated. Acute disease is resolved spontaneously when antigen is removed; symptoms of exogenous allergic alveolitis usually decrease within a few hours. Chronic disease has a less favorable prognosis: the development of fibrosis makes exogenous allergic alveolitis irreversible, although the contact with the damaging agent stops its stabilization.

[18]