Extrinsic Allergic Alveolitis/ Hypersensitivity Pneumonitis:
View cases of extrinsic allergic alveolitis
Clinical:
Hypersensitivity pneumonitis (HP) comprises a group of diseases characterized by an inappropriate host response to inhaled organic or chemical allergens that is often occupationally related. A combination of immune complex disease (type III reaction) and type I (immediate hypersensitivity) and type IV (cellular mediated reaction) reaction occur as a result of exposure. Two of the most common forms of the disorder are farmers lung (due to thermophilic actinomycetes in moldy hay) and pigeon breeders lung (from avian protein in droppings and feathers). There are innumerable other causes of hypersensitivity pneumonitis including mushroom workers lung, bagassosis (from Thermoactinomyces sacchari in moldy sugar cane), byssinosis (cotton worker's lung), and humidifier or air conditioner lung (from T. vulgaris). Elevated antibodiy titers to inhaled antigens such as avian proteins can suggest the diagnosis. However, titers may be elevated in patients without clinical disease, and can be normal in patients with symptoms [7]. Improvement in clinical symptoms following removal of the offending antigen also supports the diagnosis [7]. Lung biopsy is often required for a definitive diagnosis [7]. Cigarette smokers are considerably LESS LIKELY to develop HP- possibly due to increased mucociliary clearance.
There are essentially three phases to hypersensitivity pneumonitis- acute, subacute, and chronic. The acute phase occurs after intense exposure to antigens. Patients may present with a clinical picture resembling pulmonary edema. Patients present with fever, chills, myalgia, dyspnea, and other respiratory symptoms usually 4 to 12 hours following exposure. The symptoms usually resolve within hours to days, but may recur on re-exposure.
Subacute disease develops over weeks to months of exposure and can lead to chronic or end-stage lung disease. Patients with subacute or chronic disease often present with the insidious onset of dyspnea and lack systemic symptoms. A classic temporal relationship to exposure may not be present at these stages. Clinical management of patients with hypersensitivity pneumonitis differs markedly from that of patients with idiopathic pulmonary fibrosis (desquamative interstitial pneumonitis [DIP]), however, the two may be indistinguishable on clinical examination. HP is usually best treated by removing the offending agent from the affected patients environment and a course of steroids, while the treatment of IPF requires the use of steroids and immunosuppressive agents. Following treatment, patients with acute HP demonstrate complete clearing of radiographic findings. Subacute or chronic HP may not reverse.
Histologic findings in HP include a combination of loosely formed granulomas and lymphcytic infiltrates centered on the bronchioles, however, sometimes the findings may be indistinguishable from DIP or cryptogenic organizing pneumonia (BOOP).
X-ray:
CXR: On plain film, acute hypersensitivity reactions typically produce a diffuse ground glass opacity or a fine micronodular pattern. The CXR is often normal in patients with mild symptoms [7]. About half of the patients with normal CXR's will have CT evidence of hypersensitivity pneumonitis [7]. In the chronic stages, fibrosis predominates and manifests as volume loss, reticular opacity, and honeycombing. Gallium exam may show increased pulmonary accumulation of the radiotracer prior to x-ray changes.
Computed tomography: On HRCT the findings in HP are related to the stage of disease. With very heavy acute exposure to the offending antigen, a diffuse air-space consolidation resembling pulmonary edema can be seen which will resolve over a few days. The sub-acute phase occurs from several days to months after exposure. The most typical finding in sub-acute HP is scattered, poorly defined, centrilobular 1-5mm nodules distributed diffusely throughout the lungs, but primarily involving the middle and lower lung zones. The ill-defined nodules can be found at all stages of the disorder. Associated areas of ground glass opacity are also commonly seen and often produce a mosaic pattern of attenuation (up to 86% of cases). Areas of ground glass attenuation correlate pathologically with mononuclear cell infiltration of the alveolar walls [3]. Less commonly, there is widespread ground glass attenuation which is indistinguishable from desquamative interstitial pneumonitis (DIP). The areas of ground glass attenuation are usually diffuse, but they may spare the periphery. About 20% of patients demonstrate perivascular interstitial thickening which is often irregular. A mixed appearance with both regions of air trapping (best seen on expiratory images) and ground-glass attenuation can be seen in patients with hypersensitivity pneumonitis [6,7,8]. Chronic inflammatory infiltrates along small airways (cellular bronchiolitis) produces bronchiolar narrowing which results in air trapping [8].
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 [7]. There is usually relative sparing of the lung apices and the costophrenic sulci which aids in distinguishing this disorder from idiopathic pulmonary fibrosis [2,4]. Honeycombing is found in about 75% of patients with end-stage lung disease as a result of HP.
The presence of ill-defined centrilobular micronodules is a finding which can be used to help distinguish HP from idiopathic pulmonary fibrosis (IPF), whereas honeycombing and a lower lung zone or peripheral involvement favor IPF. Micronodules may also be identified in respiratory bronchiolitis, but many of these patients have a smoking history which is generally not associated with HP (5). Nodules associated with sarcoidosis are usually larger, better defined, and more dense than those seen in HP. Although patients with BOOP may have a similar clinical presentation to HP, the areas of parenchymal opacification are typically denser and more patchy than that associated with HP. It is important to note that a normal HRCT scan does not exclude the diagnosis of hypersensitivity pneumonitis- the scan can be normal in up to 50% of patients.
REFERENCES:
(1) Radiol Clin North Am 1994. High-resolution computed tomography in acute diffuse lung disease in the immunocompromised patient. Jul 32(4):731-744
(2) Radiographics 2001; Kim KI, et al. Imaging of occupational lung disease. 21: 1371-1391
(3) AJR 1997. Ground-glass opacity at CT: the ABCs. 169(2), 355-367 (No abstract available)
(4) Applied Radiol, Oct 95, p.47
(5) AJR 1995 Oct;165(4):807-811
(6) Society of Thoracic Radiology Course Syllabus 1999; Webb WR. Inhomogeneous opacity on high resolution lung CT: Differential diagnosis. p. 239-250
(7) AJR 2000; Matar LD, et al. Hypersensitivity pneumonitis. 174: 1061-1066
(8) AJR 2000; Arakawa H, et al. Expiratory high-resolution CT: Diagnostic value in diffuse lung disease. 175: 1537-1543
(9) AJR 2005; Miller WT, Shah RM. Isolated diffuse ground-glass opacity in thoracic CT: causes and clinical presentations. 184: 613-622
Farmer's Lung:
Clinical:
Farmer's lung is the result of a type III hypersensitivity reaction to spores contained within moldy hay (thermophylic actinomyetes and microsporia faeni). Symptoms of shortness of breath, fever, malaise, and nonproductive cough begin 4-6 hours following exposure and are generally related to the amount of exposure. A subacute or chronic form of the disorder occurs with weeks to months of continued exposure. Bronchiolitis obliterrans is seen in up to 50% of cases.
X-ray:
On plain film, CXR's are normal in up to 70% of cases, but when abnormal, acutely the disorder is characterized by a pattern of diffuse air space disease or a ground glass pattern mimicking pulmonary edema. These changes are reversible and improve over several days. Over time 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. On HRCT ground glass opacifications with superimposed, ill-defined, centrilobular nodules can be seen during the acute or subacute period. These findings predominantly involve the midlung zones. Chronic disease produces a pattern of interstitial fibrosis.
