eMedicine Specialties > Radiology > Chest

Extrinsic Allergic Alveolitis

Author: Ali Nawaz Khan, MBBS, FRCS, FRCP, FRCR, Consultant Radiologist, North Manchester General Hospital, The Pennine Acute NHS Trust, Manchester UK
Coauthor(s): Sarah Al Ghanem, MBBS, Consulting Staff, Department of Medical Imaging, King Fahad National Guard Hospital, Saudi Arabia; Klaus L Irion, MD, PhD, Consulting Staff, The Cardiothoracic Centre Liverpool NHS Trust, The Royal Liverpool University Hospital, UK; Ram Sundar Kasthuri, MBBS, Specialist Registrar, Department of Radiology, North Manchester General Hospital; Sumaira MacDonald, MBChB, PhD, MRCP, FRCR, Lecturer, Sheffield University Medical School; Endovascular Fellow, Sheffield Vascular Institute
Contributor Information and Disclosures

Updated: May 2, 2008

Introduction

Background

Extrinsic allergic alveolitis, or hypersensitivity pneumonitis, was first described in Iceland in 1874.

The term heykatarr has been defined as "a group of related inflammatory interstitial lung diseases that result from hypersensitivity immune reactions to the repeated inhalation or ingestion of various antigens derived from fungal, bacterial, animal protein, or reactive chemical sources."¹ These antigens are often related to the patient's occupation. The most common antigens are thermophilic actinomycetes and avian proteins, and the most common diseases are farmer's lung and bird fancier's lung. The disease complex is characterized by diffuse inflammation of lung parenchyma and airways in previously sensitized patients.

Hypersensitivity pneumonitis has been traditionally classified into acute, subacute, and chronic phases. However, there are only 2 clinical phases or syndromes: acute and subacute/chronic. Most affected patients present acutely with flulike illness with cough. Patients can also present subacutely with recurrent pneumonia or chronically with exertional dyspnea, productive cough, and weight loss. Most patients recover completely after exposure to the inciting antigen ceases.^2,3

For excellent patient education resources, visit eMedicine's Allergy Center. Also, see eMedicine's patient education articles Allergic Reaction and Indoor Allergies.

Pathophysiology

Extrinsic allergic alveolitis is the result of hypersensitivity immune reactions to the repeated inhalation or ingestion of various antigens (see Table 1, below). These reactions were initially thought to be immunocomplex-mediated processes; however, studies have revealed that cell-mediated immunity is more important.

Most patients have circulating immunoglobulin G antibodies that are antigen specific. The antibody reacts with a specific antigen to form a precipitation. These antibodies can be detected in approximately 50% of asymptomatic people exposed to the sensitizing antigen. The first response to the antigen exposure is an increase in neutrophils in the alveoli and small airways. This is followed by an influx of mononuclear cells. These cells release proteolytic enzymes, prostaglandins, and leukotrienes. The production and release of interleukins, cytokines, growth factors, and various other mediators from T lymphocytes and macrophages play important roles in the pathogenesis of hypersensitivity pneumonitis.

Pathologically, acute hypersensitivity pneumonitis is characterized by poorly formed noncaseating interstitial granulomas and mononuclear cell infiltration in a peribronchial distribution with prominent giant cells.⁴ Subacute or intermittent disease is characterized by the formation of better-formed noncaseating granulomas, bronchiolitis with or without organizing pneumonia, and interstitial fibrosis. The chronic form is associated with these changes, as well as with chronic interstitial inflammation and alveolar destruction (honeycombing) associated with dense fibrosis. Cholesterol clefts or asteroid bodies are present inside or outside granulomas.^5,6,7,8,9

The most common antigens causing hypersensitivity pneumonitis are tabulated below.

Open table in new window

Frequency

United States

Resistance or susceptibility to infection following exposure varies. The incidence also varies considerably.

The prevalence varies by region, climate, and farming practices. Hypersensitivity pneumonitis affects 0.4-7% of the farming population. The reported prevalence among bird fanciers is estimated to be 20-20,000 cases per 100,000 persons at risk. Studies document 8-540 cases per 100,000 farmers per year and 6000-21,000 cases per 100,000 pigeon breeders per year.

High rates are also documented in sporadic outbreaks. In one report, approximately 52% of office workers exposed to an infected humidifier were infected, and 27% of workers at a molding plant for manufacturing polyurethane foam parts were infected.

International

The prevalence of farmer's lung in the United Kingdom is reported to be 420-3000 cases per 100,000 persons at risk. In France, the rate is 4370 cases per 100,000 persons at risk, and in Finland, the risk is 1400-1700 cases per 100,000 persons at risk.

Mortality/Morbidity

The mortality and morbidity of hypersensitivity pneumonitis is variable and depends on the type and length of antigen exposure. Most patients recover completely after removal of the offending antigen.

• Individuals with farmer's lung recover with only minor functional abnormalities, and few go on to develop a disability. A significant number of farmers develop mild chronic lung impairment, which is predominantly obstructive airflow disease associated with mild emphysematous changes. Most patients experience total recovery of lung function, but this may take several years.
• Bird fancier's lung carries a prognosis worse than that of farmer's lung. The poorer prognosis has been linked to higher antigenic exposure and the persistence of avian antigens in the home environment, even after birds are removed. These factors may account for the substantial 5-year mortality rate of 30%.
• The outcome of other varieties of hypersensitivity pneumonitis is more variable than that of the varieties mentioned above.

Sex

The sex prevalence varies in accordance with the subtype and the trend of sex distribution in the high-risk occupations (see Table 1 above).

• Studies have shown that farmer's lung and the other occupational hypersensitivity conditions are more prevalent in men than women.
• Bird fancier's lung shows equal prevalence in males and females.

Age

Extrinsic allergic alveolitis and hypersensitivity pneumonitis are predominantly seen in adults—and uncommonly seen in children—exposed to the causative allergens.

Presentation

Patients with hypersensitivity pneumonitis may present acutely with a flulike illness with cough. They can also present subacutely with recurrent pneumonia or chronically with exertional dyspnea, productive cough, and weight loss.

Crepitant rales can be elicited in some patients. Pulmonary function tests generally reveal a restrictive defect in early disease and a restrictive, obstructive, or mixed defect in late disease. Specific precipitating antibodies are detectable in some cases.

The latent period between exposure to antigen and presentation varies from a few weeks to years. The onset of symptoms after acute exposure is usually between 4 and 12 hours. Some antigens provoke symptoms after repeated exposure; these include bioaerosols of microbial or animal antigens and a few reactive chemicals.

Resolution occurs with improvement or complete recovery if exposure is terminated early. Chronic exposure may cause the disease to progress to interstitial fibrosis (see Image below and Image 1 in Multimedia).^{10,11,12,13,14,15,16}

Preferred Examination

Conventional chest radiography is the examination of choice. Chest radiography is readily and universally available and has the added advantage of portability. In conjunction with the patient's clinical presentation, radiographic findings are generally sufficient to diagnose hypersensitivity pneumonitis, though high-resolution CT (HRCT) is commonly performed to confirm the diagnosis and to rule out other possibilities. HRCT is often performed in the setting of chronic parenchymal lung disease.^17,18

The chest radiograph is abnormal in most patients with hypersensitivity pneumonitis. It is also useful for differential diagnosis in patients presenting with respiratory symptoms.

In many cases, lung biopsy is required for histologic confirmation of the diagnosis (see Images below and Images 2 through 4 in Multimedia).

Limitations of Techniques

Conventional radiographs are nonspecific; without clinical input, a firm diagnosis of hypersensitivity pneumonitis cannot be made. The chest radiograph may be normal in established acute disease as well as chronic hypersensitivity pneumonitis. Chest radiography should be performed with caution in young or pregnant patients.

HRCT is comparatively expensive and exposes the patient to a radiation dose higher than that of other studies; it is indicated in patients in whom disease or poorly controlled airway disease is clinically suspected when a firm diagnosis has not been determined.

Ill-defined nonbranching centrilobular nodules with an upper lobe predominance or a diffuse distribution with or without ground-glass opacities are characteristic for acute or subacute hypersensitivity pneumonitis. These findings are diagnostic in an appropriate clinical setting, obviating biopsy. However, a normal HRCT scan does not exclude hypersensitivity pneumonitis, as HRCT scans can be normal in up to 50% of patients.

Biopsy has a small morbidity rate and also a small mortality rate. Therefore, biopsy should be performed only if it is absolutely essential. Results of a transbronchial biopsy are diagnostic in only two thirds of cases, and surgical biopsy may be required.

Differential Diagnoses

Asbestosis
Pneumonia, Viral

Other Problems to Be Considered

Chemical worker's lung
Chlamydia pneumonia
Coal worker's pneumoconiosis
Farmer's lung
Goodpasture syndrome
Metastatic cancer with an unknown primary site
Microscopic polyangiitis
Miliary tuberculosis
Mixed connective-tissue disease
Mycoplasma infections
Pneumonia, bacterial
Pneumonia, community acquired
Polymyositis
Pulmonary eosinophilia
Pulmonary fibrosis, idiopathic
Pulmonary fibrosis, interstitial (non-idiopathic)
Restrictive lung disease
Rheumatoid arthritis
Sarcoidosis
Systemic lupus erythematosus
Wegener granulomatosis
Inhalation fever
Organic dust toxic syndrome
Chronic bronchitis

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