Exogenous allergic alveolitis

Exogenous allergic alveolitis (hypersensitivity pneumonitis) is an allergic diffuse lesion of the alveoli and interstitial tissue of the lungs, developing under the influence of intensive and prolonged inhalation of antigens of organic and inorganic dust. Diagnosis is made by analyzing the anamnesis data, physical examination, results of radiological studies, bronchoalveolar lavage and histological examination of biopsy material. Short-term treatment with glucocorticoids is prescribed; subsequently, contact with the antigen must be stopped.

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Causes exogenous allergic alveolitis.

More than 300 antigens have been identified as causing hypersensitivity pneumonitis, although eight of these account for approximately 75% of cases. Antigens are usually classified by type and occupation; farmer's lung, caused by inhalation of hay dust containing thermophilic actinomycetes, is a classic example. There are significant similarities between hypersensitivity pneumonitis and chronic bronchitis in farmers, in which chronic bronchitis is much more common, is independent of smoking, and is associated with excretion of thermophilic actinomycetes. The clinical manifestations of the condition and the diagnostic findings are similar to those of hypersensitivity pneumonitis.

The disease exogenous allergic alveolitis probably represents a type IV hypersensitivity reaction in which repeated exposure to antigen in individuals with a hereditary predisposition leads to acute neutrophilic and mononuclear alveolitis accompanied by interstitial infiltration of lymphocytes and granulomatous reaction. With prolonged exposure, fibrosis with obliteration of the bronchioles develops.

Circulating precipitins (antibodies to the antigen) do not appear to play a primary etiologic role, and a history of allergic disease (asthma or seasonal allergies) is not a predisposing factor. Smoking probably delays or prevents the development of the disease, perhaps by reducing the lung's immune response to inhaled antigens. However, smoking may exacerbate disease that is already present.

Hypersensitivity pneumonitis (exogenous allergic alveolitis) must be differentiated from similar clinical conditions that have a different pathogenesis. Organic dust toxic syndrome (pulmonary mycotoxicosis, grain fever), for example, is a syndrome of fever, chills, myalgia, and dyspnea that does not require previous sensitization and is thought to be caused by inhalation of mycotoxins or other organic dust contaminants. Silo stacker's disease can lead to respiratory failure, acute respiratory distress syndrome (ARDS), and bronchiolitis obliterans or bronchitis, but is caused by inhalation of toxic nitrogen oxides released from newly fermented corn or ensiled alfalfa. Occupational asthma causes the development of dyspnea in individuals previously sensitized to an inhaled antigen, but other manifestations, in particular the presence of airway obstruction, their eosinophilic infiltration, and differences in trigger antigens, allow it to be differentiated from hypersensitivity pneumonitis.

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Symptoms exogenous allergic alveolitis.

Hypersensitivity pneumonitis (exogenous allergic alveolitis) is a syndrome caused by sensitization and subsequent hypersensitivity to an exogenous (often professional) antigen and manifested by cough, shortness of breath and malaise.

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

Acute onset of the disease occurs in previously sensitized individuals with acute, intense exposure to the antigen and is characterized by fever, chills, cough, chest tightness, and dyspnea, developing within 4 to 8 hours after exposure to the allergen. Anorexia, nausea, and vomiting may also be present. Physical examination reveals tachypnea, diffuse fine- to medium-bubble inspiratory rales, and, in almost all cases, absence of noisy breathing.

The chronic variant occurs in individuals with chronic exposure to low-level antigen (e.g., bird owners) and presents with dyspnea on exertion, productive cough, malaise, and weight loss that progresses over months to years. Physical examination reveals no significant changes; fingertip thickening is uncommon and fever is absent. In severe cases, pulmonary fibrosis leads to manifestations of right ventricular and/or respiratory failure.

The subacute variant of the disease is intermediate between the acute and chronic variants and is manifested either by cough, shortness of breath, malaise and anorexia, developing over several days to several weeks, or by an exacerbation of chronic symptoms.

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Forms

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

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Diagnostics exogenous allergic alveolitis.

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

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Diagnostic criteria for exogenous allergic alveolitis

Known antigen exposure:

• History of exposure.
• Confirmation of the presence of antigen in the environment by appropriate testing.
• The presence of an increased concentration of specific serum precipitating IgG.

Results of clinical examination, radiography and pulmonary function tests:

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

Lymphocytosis in bronchoalveolar lavage fluid:

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

Recurrence of clinical manifestations and changes in lung function during a provocative test with a detected antigen:

• In environmental conditions
• Controlled response to extracted antigen.

Histological changes:

• Noncaseating granulomas.
• Mononuclear cell infiltrate.

Of key importance in the anamnesis are atypical recurrent pneumonias developing at approximately equal time intervals; development of manifestations of the disease after a change in employment or a move to a new place of residence; prolonged contact with a hot bath, sauna, swimming pool, or other sources of stagnant water at home or elsewhere; the presence of birds as pets; as well as exacerbation and disappearance of symptoms with the creation and elimination of certain conditions, respectively.

Examination is often not diagnostic, although abnormal lung sounds and clubbing of the digital fingers may be present.
Imaging studies are usually reserved for patients with a characteristic history and clinical features. Chest radiography is neither sensitive nor specific for diagnosis and is often normal in the acute and subacute forms of the disease. Increased markings or focal opacities may be seen in the presence of clinical features. In the chronic stage of the disease, increased markings or focal opacities in the upper lungs are more likely to be seen, along with decreased lung volumes and honeycombing similar to that seen in idiopathic pulmonary fibrosis. Abnormalities are much more common on high-resolution CT (HRCT), which is considered the standard for evaluating parenchymal changes in hypersensitivity pneumonitis. The most common HRCT finding is the presence of multiple, ill-defined centrilobular micronodules. These micronodules may be present in patients with acute, subacute, and chronic disease and, in the appropriate clinical context, are highly suggestive of hypersensitivity pneumonitis. Occasionally, ground-glass opacities are the predominant or only finding. These opacities are usually diffuse but occasionally spare the peripheral portions of the secondary lobules. Focal areas of increased intensity, similar to those seen in bronchiolitis obliterans, may be the primary finding in some patients (eg, mosaic hyperdensity with air trapping on expiratory HRCT). Chronic hypersensitivity pneumonitis has features of pulmonary fibrosis (eg, decreased lobar volumes, linear opacities, increased lung markings, or honeycombing). Some nonsmoking patients with chronic hypersensitivity pneumonitis have evidence of upper lobe emphysema. Mediastinal lymph node enlargement is rare and helps differentiate hypersensitivity pneumonitis from sarcoidosis.

Pulmonary function tests should be performed in all cases of suspected hypersensitivity pneumonitis. Exogenous allergic alveolitis may cause obstructive, restrictive, or mixed changes. The terminal phase of the disease is usually accompanied by restrictive changes (reduced lung volumes), decreased diffusion capacity for carbon monoxide (DI_CO), and hypoxemia. Airway obstruction is unusual in acute disease, but may develop in its chronic variant.

Bronchoalveolar lavage findings are rarely specific for the diagnosis but are often part of the diagnostic workup in the presence of chronic respiratory manifestations and abnormal lung function. The presence of lymphocytosis in the lavage fluid (>60%) with a CD4+/CD8+ ratio <1.0 is characteristic of the disease; in contrast, lymphocytosis with a predominance of CD4+ (ratio >1.0) is more characteristic of sarcoidosis. Other changes may include the presence of mast cells in amounts greater than 1% of the total cell count (after an acute episode of the disease) and an increase in neutrophils and eosinophils.

Lung biopsy is performed when noninvasive studies are insufficient to provide information. Transbronchial biopsy performed during bronchoscopy is sufficient when multiple samples can be obtained from different areas of the lesion, which are then examined histologically. The changes detected may vary, but include lymphocytic alveolitis, noncaseating granulomas, and granulomatosis. Interstitial fibrosis may be detected, but is usually mild and there are no changes on radiography.

Additional tests are indicated when further information is needed to establish the diagnosis or to establish other causes of IBLAR. Circulating precipitins (specific precipitating antibodies to the suspected antigen) are presumably useful but are neither sensitive nor specific and thus are of no diagnostic value. Identification of the specific precipitating antigen may require detailed aerobiological and/or microbiological work-up by industrial hygienists but is usually guided by known sources of the offending antigen (eg, Bacillus subtilis in detergent manufacturing). Skin testing is of no value and eosinophilia is absent. Tests of diagnostic value in other diseases include serologic and microbiological tests (in ornithosis and other pneumonias) and autoantibody tests (in systemic diseases and vasculitides). 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 characteristic of sarcoidosis.

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Treatment exogenous allergic alveolitis.

Treatment of exogenous allergic alveolitis is with glucocorticoids, usually prednisolone (60 mg once daily for 1 to 2 weeks; then gradually reduced to 20 mg once daily for the next 2 to 4 weeks; then reduced by 2.5 mg per week until the drug is completely discontinued). This regimen can stop the initial manifestations of the disease, but probably does not affect long-term results.

The most important component of long-term treatment is avoidance of exposure to the antigen. However, complete lifestyle and work changes are rarely possible in the field, especially for farmers and other workers. In this case, dust control measures (eg, pre-wetting compost before handling), air filters, and face masks are used. Fungicides can be used to prevent the proliferation of antigen-producing organisms (eg, in hay or sugar beets), but the long-term safety of this approach has not been established. Thorough cleaning of humidifying ventilation systems, removal of damp carpets, and maintaining low humidity are also effective in some cases. Patients should be advised, however, that these measures may not be effective if exposure to the antigen continues.

Forecast

Pathological changes are completely reversible if the disease exogenous allergic alveolitis is detected early and the antigen is eliminated. Acute disease resolves spontaneously upon removal of the antigen; 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 it stabilizes upon cessation of contact with the damaging agent.

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