You are in: eMedicine Specialties > Radiology > CHEST Extrinsic Allergic AlveolitisArticle Last Updated: May 2, 2008AUTHOR AND EDITOR INFORMATIONSection 1 of 8
  Author: Ali Nawaz Khan, MBBS, FRCS, FRCP, FRCR, LRCP, Chairman of Medical Imaging, Professor of Radiology, NGHA, King Fahad National Guard Hospital, King Abdulaziz Medical City, Riyadh, Saudi Arabia Ali Nawaz Khan is a member of the following medical societies: American Institute of Ultrasound in Medicine, Radiological Society of North America, Royal College of Physicians, Royal College of Physicians and Surgeons of the United States, Royal College of Radiologists, and Royal College of Surgeons of England Coauthor(s): 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 Editors: Satinder P Singh, MD, Associate Professor of Radiology, Chief of Cardiopulmonary Radiology, Director of Cardiac CT, Director of Combined Cardiopulmonary and Abdominal Radiology, Department of Radiology, University of Alabama at Birmingham; Bernard D Coombs, MB, ChB, PhD, Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand; John D Newell, Jr, MD, FACR, FCCP, FASER, Co-Director of Thoracic Imaging, UCDHSC; Director of Lung Imaging Center, Professor of Radiology and Professor of Medicine, Department of Radiology, University of Colorado Health Sciences Center, National Jewish Medical and Research Center; Univ. Colorado Hospital; Robert M Krasny, MD, Consulting Staff, Department of Radiology, The Angeles Clinic and Research Institute; Kavita Garg, MD, Professor, Department of Radiology, University of Colorado Health Sciences Center Author and Editor Disclosure Synonyms and related keywords: hypersensitivity pneumonitis, HP, heykatarr, hypersensitivity reaction, farmer's lung, bagassosis, mushroom worker's lung, malt worker's lung, humidifier lung, air-conditioner lung, grain handler's lung, bird breeder's lung, cheese worker's lung, paprika splitter's lung, compost lung, peat moss worker's lung, wheat weevil, mollusk-shell hypersensitivity, chemical worker's lung, suberosis, maple bark stripper's lung, wood pulp worker's lung, wood trimmer's disease, sequoiosis, Japanese summer-type hypersensitivity pneumonitis, hot-tub lung INTRODUCTIONSection 2 of 8
  BackgroundExtrinsic 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. PathophysiologyExtrinsic 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. Table 1: Selected etiologic agents for hypersensitivity pneumonitis
FrequencyUnited StatesResistance 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. InternationalThe 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/MorbidityThe 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.
SexThe sex prevalence varies in accordance with the subtype and the trend of sex distribution in the high-risk occupations (see Table 1 above).
AgeExtrinsic allergic alveolitis and hypersensitivity pneumonitis are predominantly seen in adults—and uncommonly seen in children—exposed to the causative allergens. Clinical DetailsPatients 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 1).10, 11, 12, 13, 14, 15, 16 Preferred ExaminationConventional 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 2 through 4). Limitations of TechniquesConventional 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. DIFFERENTIALSSection 3 of 8
Asbestosis Pneumonia, Viral Other Problems To Be ConsideredChemical worker's lung RADIOGRAPHSection 4 of 8
FindingsThe most common abnormality in acute or subacute disease is small bilateral pulmonary nodules, which are usually 1-5 mm in size (see Images 5, 6, 11, 12, 14, 15). The nodules may be well defined or indistinct. In 1 published series, only 2% of the nodules were unilateral.19 The nodules have a predilection for the mid or lower zones, with comparative sparing of the upper zones. The nodules may appear within a few hours after exposure and take weeks or months to resolve. The nodules/opacities may be so small that they give a ground-glass appearance. Focal consolidation is found in 10-25% of patients.20 Interstitial type change is occasionally seen with accentuated bronchovascular markings and Kerley B lines. Generally, there are no pleural changes, but occasional thickening of minor fissures is noted. Hilar lymphadenopathy is rare but has been reported in mushroom worker's lung,21 farmer's lung,22 and bird fancier's lung.23 In farmer's lung, plain chest radiographs are normal in up to 70% of cases. When the images are abnormal, acute disease is characterized by a pattern of diffuse airspace disease or a ground-glass pattern mimicking that of pulmonary edema. These changes are reversible and improve over several days. Over time, the disease progresses to a granulomatous reaction that may eventually lead to a small nodular pattern, followed by interstitial fibrosis and end-stage honeycomb lung. Pleural effusion is rare, and the disorder is not associated with hilar adenopathy. Chronic changes reflect healing by fibrosis and may occur after 1 or more attacks. Alternatively, they may develop insidiously in relation to chronic low-grade antigen exposure, eg, with bird fancier's lung related to budgerigars. The characteristic radiologic changes in the chronic stage are scarring process with loss of lung volume, which has a marked (85%) upper lobe preponderance. The principal opacities are reticular, sometimes with a definite honeycomb pattern. Larger ring shadows 1-4 mm in diameter are due to bullae, blebs, cysts, or bronchiectasis. Line shadows secondary to scarring are common, particularly in the upper zones. Parallel line shadows are caused by bronchiectasis or simple bronchial wall thickening; in the latter case, they are often transient. Other changes sometimes seen in chronic stage include persisting small nodules, massive opacities, and evidence of pulmonary heart disease. Pneumothorax is recorded in the fibrotic stage, but this is uncommon (see Images 7 through 10, 13, 16 through 25). Degree of ConfidenceThe chest radiograph is often normal in patients with hypersensitivity pneumonitis. For this reason, HRCT is recommended in the proper clinical setting if the radiograph is normal. False Positives/NegativesThere is some evidence that the radiographic changes are the same whatever the extrinsic provocative agent, but the evidence is incomplete.24 In the acute phase of the disease, the radiographic changes may be subtle, or the radiograph may appear normal. The radiograph may also appear normal in the chronic stage of the disease despite abnormal diffusing capacity25, 26 and biopsy-proved allergic granulomatous disease.27, 28 CT SCANSection 5 of 8
FindingsIn hypersensitivity pneumonitis, HRCT findings are related to the stage of disease. With heavy acute antigen exposure, diffuse airspace shadowing may mimic that of pulmonary edema; if present, this finding generally resolves over a few days. The subacute phase occurs from several days to months after exposure. In this phase, diffuse ground-glass opacities and small (1-5 mm) centrilobular and poorly defined nodules often affect all zones, though a middle and upper lobe predominance is often seen. The ill-defined nodules can be found at all 3 stages of the disorder. Associated areas of ground-glass opacification are common (86%) and often produce a mosaic pattern of attenuation. Less commonly, there is widespread ground-glass attenuation, which is indistinguishable from that of desquamative interstitial pneumonitis. The areas of ground-glass attenuation are usually diffuse, but they may spare the periphery. A mixed appearance with both regions of airtrapping (best seen on expiratory images) and ground-glass attenuation can be seen in patients with hypersensitivity pneumonitis. About 20% of patients have perivascular interstitial thickening, which is often irregular. Chronic inflammatory infiltrates along small airways produces bronchiolar narrowing that results in airtrapping. Chronic hypersensitivity pneumonitis develops as a result of continuous or intermittent antigenic exposure over several months or years and commonly demonstrates intralobular interstitial thickening (evidence of fibrosis) predominantly involving the mid and upper lung zones. Usually present is relative sparing of the lung apices and the costophrenic sulci, which aids in distinguishing this disorder from idiopathic pulmonary fibrosis (IPF). Honeycombing is found in about 75% of patients with end-stage lung disease resulting from hypersensitivity pneumonitis. Degree of ConfidenceThe finding of poorly defined centrilobular nodules on HRCT scans in an appropriate clinical setting should prompt consideration of this disease. The sensitivity of HRCT for the detection of hypersensitivity pneumonitis reported in a population-based study is greater than that of chest radiography. False Positives/NegativesThere are several causes of nodular and ground-glass attenuation on HRCT. Causes of a nodular pattern include sarcoidosis, silicosis, coal worker's pneumoconiosis, and pulmonary histiocytosis X. Causes of a ground-glass pattern include IPF, desquamative interstitial pneumonia, and alveolar proteinosis. Micronodules may also be identified in respiratory bronchiolitis, but many patients with micronodules have a smoking history, which is generally not associated with hypersensitivity pneumonitis. Nodules associated with sarcoidosis are usually larger, better defined, and denser than those seen in hypersensitivity pneumonitis. Ill-defined centrilobular micronodules can help distinguish hypersensitivity pneumonitis from IPF, whereas honeycombing and a lower lung zone or peripheral involvement suggest IPF. Although patients with bronchiolitis obliterans with organizing pneumonia (BOOP) may have a clinical presentation similar to that of hypersensitivity pneumonitis, the areas of parenchymal opacification are typically denser and more patchy than those associated with hypersensitivity pneumonitis. A normal HRCT scan does not exclude hypersensitivity pneumonitis, as HRCT scans can be normal in up to 50% of patients. INTERVENTIONSection 6 of 8
In many cases, lung biopsy is required for histologic confirmation of the diagnosis. Transbronchial biopsy should be attempted in the first instance. Results of a transbronchial biopsy are diagnostic in two thirds of cases, though surgical lung biopsy is sometimes necessary. The biopsy material may reveal small, poorly formed noncaseating granulomas near respiratory or terminal bronchioles, which are associated with multinucleated giant cells. Patchy mononuclear cell infiltration (lymphocytes and plasma cells) of alveolar walls may be present. Large histiocytes with foamy cytoplasm may be present in the interstitium. Medical/Legal Pitfalls
See also the Medscape Resource Center Medical Malpractice and Legal Issues. MULTIMEDIASection 7 of 8
REFERENCESSection 8 of 8
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