Hypersensitivity pneumonitis: causes, symptoms, diagnosis and treatment

By Cristiano Antonino On Apr 18, 2023

Hypersensitivity pneumonitis is a group of diffuse interstitial granulomatous diseases of the lung, caused by an allergic reaction to inhaled organic dust or, less frequently, simple chemicals, which often occurs in the workplace

Hypersensitivity pneumonitis (also called extrinsic allergic alveolitis) includes numerous forms caused by specific antigens.

The farmer’s lung, associated with repeated inhalation of hay dust containing thermophilic actinomycetes, represents its prototype.

Causes and pathogenesis of hypersensitivity pneumonitis

The number of specific substances capable of causing hypersensitivity pneumonitis is constantly increasing.

Most frequently, the agent is a microorganism or a foreign protein of animal or plant origin.

However, simple chemicals, when inhaled in large quantities, can also cause disease.

Hypersensitivity pneumonitis is considered to be immunologically mediated, although the pathogenesis is not fully understood

Precipitating antibodies against the causative antigens are usually demonstrated, suggesting a type III allergic reaction, although vasculitis is not a frequent finding.

The primary granulomatous tissue response and findings in animal models indicate a type IV hypersensitivity reaction.

Only a small fraction of exposed people develop symptoms and only after weeks or months of exposure, the time necessary to induce sensitization.

Continuous or frequent exposure to low doses of antigen can lead to chronic and progressive disease of the lung parenchyma.

Pre-existing allergic diseases (eg asthma and hay fever) are rare and are not a predisposing factor.

Diffuse granulomatous interstitial pneumonia is characteristic but not diagnostic or specific.

Lymphocytic and plasma cell infiltrates appear in the airways and thickened alveolar septa; granulomas are single, nonnecrotizing, and randomly spread throughout the parenchyma without involvement of the vascular walls.

The degree of fibrosis is usually mild but depends on the stage of the disease.

Bronchiolitis of variable severity is found in about 50% of patients with farmer’s lung.

Symptoms and signs

In the acute form, episodes of fever, chills, cough, and dyspnea occur in an already sensitized person, typically 4 to 8 hours after reexposure to the antigen.

Anorexia, nausea, and vomiting may also be present.

On auscultation, inspiratory rales with small or medium bubbles can be detected.

Hisses are rare. When the antigen is removed, symptoms usually ease within hours, although complete remission may take weeks. and pulmonary fibrosis may follow repeated episodes.

The subacute form can develop insidiously with cough and shortness of breath over a period of days to weeks, with progression sometimes requiring emergency hospitalisation.

In the chronic form, progressive dyspnea, productive cough, fatigue, and weight loss may develop over months to years; the disease can progress to respiratory failure.

Rx findings range from normal to diffuse interstitial fibrosis.

There may be irregular or nodular infiltrates, reinforcement of the bronchovascular network, or slight acinar involvement suggestive of pulmonary edema.

Hilar adenopathy and pleural effusion are rare.

CT, especially high-resolution CT, may be superior in determining the type and extent of the abnormality, but pathognomonic CT features are lacking.

Pulmonary function tests show a restrictive picture with reduced lung volumes, decreased CO diffusing capacity, hypoxemia, and abnormal ventilation/perfusion ratios.

Airway obstruction is uncommon in acute disease but can develop in the chronic form.

Eosinophilia is not common.

Diagnosis of hypersensitivity pneumonitis

Diagnosis is based on a history of environmental exposure and compatible clinical, x-ray, and pulmonary function findings.

The presence in the serum of specific precipitating antibodies against the suspected antigen helps confirm the diagnosis, although neither their presence nor their absence is considered decisive.

A history of exposure may provide suggestive clues (eg, a person exposed in the workplace may become asymptomatic every weekend or symptoms may reappear 4 to 8 hours after reexposure).

History of exposure to the causative antigens may not be easily gathered, particularly for air conditioner (humidifier) lung, and an expert site survey may be helpful in difficult cases.

In intricate cases or those with no history of environmental exposure, open lung biopsy may be required.

Bronchoalveolar lavage is often used as an aid in the diagnosis of interstitial lung disease, but its value is not yet established.

The number of lymphocytes, especially T cells, may be increased in hypersensitivity pneumonitis (and sarcoidosis).

The CD8+ T-cell subpopulation (suppressor/cytotoxic) may predominate in some stages of hypersensitivity pneumonitis, while the CD4+ T-cell subpopulation (helper/inducer) may predominate in active sarcoidosis.

Transbronchial biopsy is of very limited value and may be confounding due to small sample sizes.

Atypical farmer’s lung (pulmonary mycotoxicosis) refers to a syndrome consisting of fever, chills, and cough that occurs within hours after intense exposure to moldy forage (eg, when opening a silo); no precipitins are found, suggesting a nonimmunological mechanism.

Pulmonary infiltrates are usually present. This condition, associated with old silage contaminated with Aspergillus, must be distinguished from silo filler disease, caused by toxic nitrogen oxides produced by fresh silage.

Toxic organic dust syndrome is characterized by transient fever and body aches, with or without respiratory symptoms and without demonstrable sensitization after exposure to agricultural dust (eg, hay fever).

Humidifier fever refers to cases associated with contaminated heating, cooling, and humidification systems.

Endotoxin is thought to play an etiologic role in organic toxic dust syndrome and humidifier fever.

Hypersensitivity pneumonitis can be differentiated from psittacosis, viral pneumonia, and other infectious pneumonias based on culture and serological investigations

Because of the similarity of clinical findings, x-rays, and pulmonary function tests, it can be difficult to differentiate idiopathic pulmonary fibrosis (Hamman-Rich syndrome, cryptogenic fibrosing alveolitis, Liebow’s common interstitial pneumonia) from hypersensitivity pneumonitis when not obtain the typical story of an exposure followed by an acute episode.

Some variants of adult bronchiolitis (e.g., bronchiolitis obliterans with organizing pneumonia [BOOP]) may manifest as restrictive (interstitial) disease and may be difficult to distinguish without a significant history or typical findings obtained from an open biopsy.