AJR 2000; 174:1061-1066
© American Roentgen Ray Society
Hypersensitivity Pneumonitis
Luke D. Matar1,
H. Page McAdams1 and
Thomas A. Sporn2
1
Department of Radiology, Duke University Medical Center, Box 3808, Durham, NC
27710.
2
Department of Pathology, Duke University Medical Center, Durham, NC
27710.
Received July 19, 1999;
accepted after revision September 10, 1999.
Address correspondence to H.P. McAdams.
Introduction
Hypersensitivity pneumonitis, also known as extrinsic allergic alveolitis,
is an inflammatory lung disease caused by inhalation of airborne organic
particulate matter. These particles, which are usually 1-5 µm in diameter,
deposit in distal air spaces and produce an immune-mediated inflammatory
response in sensitized individuals. Causative agents are numerous and include
bacteria, fungi, avian proteins, and wood dusts
[1]
(Table 1). Most exposures are
occupational, but hobbies such as bird breeding are also implicated. The most
common and well-studied forms of hypersensitivity pneumonitis are farmer's
lung and bird fancier's lung
[1].
The clinical features of hypersensitivity pneumonitis are classically
divided into three syndromes: acute, subacute, and chronic. However,
significant clinical overlap often exists between syndromes. Diagnosis is
frequently delayed because symptoms are nonspecific and a relevant exposure
history may be absent
[1,2].
Elevated antibody titers to inhaled antigens such as avian proteins can
suggest the diagnosis. However, patients with clinical disease may not have
elevated titers and exposed individuals may have elevated titers without
clinical disease. Thus, lung biopsy is often necessary for confident
diagnosis. This disease is uncommon in smokers
[3].
Characteristic histopathologic features of acute, subacute, or chronic
hypersensitivity pneumonitis include cellular bronchiolitis, diffuse
lymphocytic interstitial infiltration, and noncaseating granulomas
[2] (Fig.
1A,1B).
The granulomas are typically small, poorly formed, and loosely arranged,
unlike those of sarcoidosis. Bronchiolitis obliterans with organizing
pneumonia is also a common histopathologic feature. Interstitial fibrosis and
end-stage lung disease may result from chronic exposure.
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Fig. 1A. —Microscopic features of hypersensitivity pneumonitis. Low-power
photomicrograph of histopathologic specimen shows diffuse uniform expansion of
pulmonary interstitium by mononuclear inflammatory cells with accentuation of
distribution around small airways. (H and E, x52)
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Fig. 1B. —Microscopic features of hypersensitivity pneumonitis. High-power
photomicrograph of histopathologic specimen shows interstitial inflammation
accompanied by organizing pneumonia (thick arrow) and multinucleate
giant cell (thin arrow) typical of hypersensitivity pneumonitis. (H
and E, x130)
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Although radiologic findings in hypersensitivity pneumonitis can be
nonspecific, characteristic patterns are described in acute, subacute, and
chronic disease
[1,2,3,4,5].
We review the spectrum of abnormal radiologic findings in patients with
hypersensitivity pneumonitis to facilitate prompt diagnosis and treatment.
Acute Hypersensitivity Pneumonitis
Acute hypersensitivity pneumonitis occurs after intense exposure to
antigens that may occur during handling of moldy hay (farmer's lung) or
cleaning birdcages or lofts (bird fancier's lung). Symptoms of cough, dyspnea,
chest tightness, wheezing, chills, and fever typically develop 4-6 hr after
exposure. These symptoms usually resolve within hours or days but may recur on
reexposure. Unless a careful occupational and social history is obtained,
affected patients are frequently misdiagnosed as having acute viral or
bacterial illnesses [1,
3]. Although this phase is
called acute, the term is misleading because most affected patients have been
previously sensitized.
The radiographic manifestations of acute hypersensitivity pneumonitis are
little studied, perhaps because of inherent difficulties in diagnosis. Chest
radiographs are often normal in patients with mild symptoms and can remain
normal despite severe symptoms
[1,
3] (Fig.
2A,2B).
Thin-section CT can be useful in patients with suspected hypersensitivity
pneumonitis and normal chest radiographs. Half of patients with normal chest
radiographs have characteristic findings of centrilobular ground-glass and
nodular opacities on CT [5].
Abnormal chest radiographs usually show bilateral areas of increased opacity
that may be either heterogeneous or homogeneous, simulating pulmonary edema
[1,
4] (Fig.
3A,3B).
These findings are typically seen in mid to lower lung zones with sparing of
the costophrenic angles. Less common radiographic findings include focal areas
of homogeneous opacity mimicking infection (Fig.
4A,4B)
and small poorly defined nodules
[1,
3].
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Fig. 2A. —Acute hypersensitivity pneumonitis in 25-year-old man with severe
dyspnea after attic renovation. Chest radiographs (not shown) were normal.
Thin-section CT (1.0-mm collimation), initially interpreted as normal, shows,
in retrospect, subtle centrilobular nodules (arrowhead).
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Fig. 2B. —Acute hypersensitivity pneumonitis in 25-year-old man with severe
dyspnea after attic renovation. Chest radiographs (not shown) were normal.
Cone-down view of chest CT shows centrilobular nodule in left lower lobe
(arrowhead) more clearly than A. Thoracoscopic lung biopsy
revealed hypersensitivity pneumonitis. Offending antigen was never
identified.
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Fig. 3B. —Acute hypersensitivity pneumonitis (bird fancier's lung) in
34-year-old man with severe dyspnea. CT scan (1.0-mm collimation) shows
scattered ground-glass opacities. Radiologic and clinical findings resolved
within 5 days of removal of antigen and institution of corticosteroid
therapy.
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Fig. 4A. —Acute hypersensitivity pneumonitis in 38-year-old woman with acute
dyspnea, hypoxemia, and chills. Chest radiograph shows focal area of
homogeneous opacity (arrows) in right lower lung. Note subtle
heterogeneous opacities in left lower lobe.
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Fig. 4B. —Acute hypersensitivity pneumonitis in 38-year-old woman with acute
dyspnea, hypoxemia, and chills. CT scan (1.0-mm collimation) shows scattered
areas of consolidation and ground-glass opacities in centrilobular and
bronchovascular distribution. Thoracoscopic lung biopsy revealed
hypersensitivity pneumonitis. Offending antigen was never identified. Clinical
and radiographic findings resolved after institution of corticosteroid
therapy.
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Subacute Hypersensitivity Pneumonitis
Symptoms in the subacute phase of hypersensitivity pneumonitis are similar
to, but less severe than, those in the acute phase and can be prolonged over
weeks to months. Affected patients may experience recurrent episodes of acute
symptoms superimposed on a background of deteriorating respiratory function.
Corticosteroid therapy is frequently used to treat acute exacerbations and for
prophylaxis against recurrence. However, early diagnosis and removal of the
offending antigen are most important for preventing recurrent disease and
progression to fibrosis [1,
3].
Although considerable overlap in the radiographic findings of acute and
subacute hypersensitivity pneumonitis can occur, diffuse homogeneous opacities
are usually not seen during the subacute phase of the disease. Heterogeneous
or small nodular opacities that predominate in mid to lower lung zones are
much more common. In transition from acute to subacute disease, poorly defined
air-space opacities may be replaced by well-defined reticular or nodular
opacities (Fig.
5A,5B,5C,5D).
The nodules may be so well defined that they mimic the findings of miliary
tuberculosis or pulmonary metastases (Fig.
6A,6B).
As with acute disease, chest radiographs may be normal in patients with
subacute disease. Characteristic thin-section CT findings of subacute
hypersensitivity pneumonitis are ground-glass and nodular opacities in a
centrilobular distribution [4,
5] (Figs.
7 and
8). These findings, in the
appropriate clinical setting, strongly suggest the diagnosis. Irregular linear
opacities are less common on CT images. Air trapping on expiratory
thin-section images is a helpful ancillary finding, reflecting associated
bronchiolitis [6].
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Fig. 5A. —Acute and subacute hypersensitivity pneumonitis in 36-year-old
woman. (Reprinted from [10])
Chest radiograph at patient's initial presentation with severe dyspnea and
hypoxemia shows bilateral scattered heterogeneous opacities with more focal
homogeneous opacity in lung bases. During patient's hospitalization, all
radiographic and clinical manifestations resolved in several days and patient
was discharged.
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Fig. 5B. —Acute and subacute hypersensitivity pneumonitis in 36-year-old
woman. (Reprinted from [10])
Full (B) and coned (C) chest radiographs obtained 9 months after
A show diffuse small nodules (arrows) and normal lung volumes.
Patient complained of mild dyspnea at this time.
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Fig. 5C. —Acute and subacute hypersensitivity pneumonitis in 36-year-old
woman. (Reprinted from [10])
Full (B) and coned (C) chest radiographs obtained 9 months after
A show diffuse small nodules (arrows) and normal lung volumes.
Patient complained of mild dyspnea at this time.
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Fig. 5D. —Acute and subacute hypersensitivity pneumonitis in 36-year-old
woman. (Reprinted from [10])
CT scan (1.5-mm collimation) obtained at same time as B and C
predominantly shows poorly defined centrilobular nodules (arrows).
Note peripheral well-defined nodule in right upper lobe (arrowhead).
Thoracoscopic lung biopsy revealed hypersensitivity pneumonitis. Offending
antigen was never identified.
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Fig. 6A. —Subacute hypersensitivity pneumonitis in 22-year-old woman with
progressive dyspnea. Full (A) and coned (B) chest radiographs
show bilateral, diffusely distributed, well-defined small lung nodules. No
adenopathy or pleural fluid is seen. Thoracoscopic lung biopsy found
hypersensitivity pneumonitis. Offending antigen was never identified.
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Fig. 6B. —Subacute hypersensitivity pneumonitis in 22-year-old woman with
progressive dyspnea. Full (A) and coned (B) chest radiographs
show bilateral, diffusely distributed, well-defined small lung nodules. No
adenopathy or pleural fluid is seen. Thoracoscopic lung biopsy found
hypersensitivity pneumonitis. Offending antigen was never identified.
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Fig. 7. —Subacute hypersensitivity pneumonitis in 30-year-old woman with
dyspnea. Chest radiographs (not shown) were normal. CT scan (1.5-mm
collimation) shows scattered ground-glass opacities. Note centrilobular
distribution peripherally (arrows). Thoracoscopic lung biopsy
revealed hypersensitivity pneumonitis. Offending antigen was never
identified.
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Fig. 8. —Subacute hypersensitivity pneumonitis (bird fancier's lung) in
40-year-old woman with dyspnea. Patient kept more than 200 parakeets. Chest
radiographs (not shown) were normal. CT scan (1.5-mm collimation) shows
scattered ground-glass opacities. Note more well-defined centrilobular nodules
in dependent right lung (arrowhead). These findings suggest diagnosis
of hypersensitivity pneumonitis, which was confirmed at thoracoscopic lung
biopsy.
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Chronic Hypersensitivity Pneumonitis
Long-standing exposure to the offending antigen can result in chronic
pulmonary fibrosis. Affected patients typically present with symptoms of
dyspnea, anorexia, weight loss, fatigue, and general malaise. Patients with
chronic hypersensitivity pneumonitis can experience progressive clinical
deterioration despite removal of the offending antigen and may ultimately
require lung transplantation.
Chronic hypersensitivity pneumonitis typically manifests on chest
radiographs as mid to upper lung zone fibrosis (Figs.
9 and
10A,10B,10C).
CT findings include small nodules, irregular linear opacities, traction
bronchiectasis, architectural distortion, and honeycombing
[7,
8]. The characteristic mid to
upper lobe distribution and the finding of small nodules on CT images help
distinguish chronic hypersensitivity pneumonitis from idiopathic pulmonary
fibrosis. Occasionally, however, mid to lower lung zone fibrosis without
nodularity is seen; such cases are radiologically indistinguishable from
idiopathic pulmonary fibrosis
[4,
8] (Fig.
11A,11B).
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Fig. 9. —Chronic hypersensitivity pneumonitis (bird fancier's lung) in
29-year-old woman with progressive dyspnea. Chest radiograph shows coarse
reticulonodular opacities and volume loss in both upper lobes. Thoracoscopic
lung biopsy revealed hypersensitivity pneumonitis and fibrosis.
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Fig. 10A. —Chronic hypersensitivity pneumonitis in 61-year-old woman with
progressive dyspnea. Chest radiograph shows bilateral reticulonodular
opacities in mid lung zones and mild loss of lung volume.
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Fig. 10B. —Chronic hypersensitivity pneumonitis in 61-year-old woman with
progressive dyspnea. CT scan (10-mm collimation) shows irregular linear
opacities, architectural distortion, and traction bronchiectasis. Note
centrilobular nodules in right mid lung (arrows).
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Fig. 10C. —Chronic hypersensitivity pneumonitis in 61-year-old woman with
progressive dyspnea. CT scan (1-mm collimation) better shows traction
bronchiectasis (solid arrow) and architectural distortion,
particularly in left lung. Note subpleural honeycomb cyst formation (open
arrows). Thoracoscopic lung biopsy revealed hypersensitivity pneumonitis
and fibrosis. Offending antigen was never identified.
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Fig. 11A. —Chronic hypersensitivity pneumonitis (bird fancier's lung) in
70-year-old man with progressive dyspnea. Patient kept three cockatiels. Serum
antibodies to avian proteins were positive at greater than 1:20,000 dilution.
Chest radiograph shows bilateral coarse reticulonodular opacities,
honeycombing, and volume loss. Note small right pneumothorax after
transbronchial lung biopsy (arrows).
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Fig. 11B. —Chronic hypersensitivity pneumonitis (bird fancier's lung) in
70-year-old man with progressive dyspnea. Patient kept three cockatiels. Serum
antibodies to avian proteins were positive at greater than 1:20,000 dilution.
CT scan (1.5-mm collimation) with patient prone shows basal honeycombing,
traction bronchiectasis, and architectural distortion. CT findings are
indistinguishable from those of idiopathic pulmonary fibrosis.
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Diagnosis and the Role of Imaging
Diagnosis of hypersensitivity pneumonitis is often challenging and rests on
documenting a close temporal relationship between occupational or
environmental exposure and onset of symptoms
[1]. The diagnosis is supported
by clinical improvement on removal or avoidance of the presumed antigen and
can be confirmed, with some risk, by the induction of symptoms after antigenic
challenge [9].
Often, particularly at initial presentation, a clear exposure history is
lacking and symptoms are typically nonspecific. A high index of suspicion is
key to making the diagnosis in such patients
[9]. As with all forms of
pulmonary disease, radiographs are usually obtained as part of the initial
workup, and high-resolution CT may also be performed when chest radiographs
are normal or show minimal abnormalities
[3]. Although radiologic
findings in patients with hypersensitivity pneumonitis are frequently
nonspecific, characteristic patterns (as previously described) may allow the
radiologist to suggest the correct diagnosis. By suggesting the diagnosis, the
clinician can be guided to exclusion of other diseases and to gathering a
relevant exposure history, supportive serologic data, and in some instances, a
biopsy specimen to confirm the diagnosis. When a typical history can be
elicited, diagnosis is often made clinically without resort to biopsy,
particularly with supportive radiographic findings
[4]. Lung biopsy is performed
when insufficient clinical certainty exists to establish a confident diagnosis
and is useful in excluding other treatable diseases. Histopathology is
characteristic but not pathognomonic, and correlation with clinical and
radiographic findings is often required to exclude sarcoidosis and
granulomatous infection
[9].
Summary
Hypersensitivity pneumonitis manifests with a broad spectrum of clinical
and radiologic findings. As the name implies, patients with acute disease are
typically acutely ill. Chest radiographs in affected patients may be normal;
thin-section CT can be helpful in these patients for showing characteristic
centrilobular ground-glass or nodular opacities. When abnormal, chest
radiographs typically show focal or diffuse heterogeneous or homogeneous
opacities. Patients with subacute disease usually have a more indolent
clinical presentation. Nodular opacities are a characteristic feature on chest
radiographs and CT. Centrilobular ground-glass or nodular opacities on CT
suggest the diagnosis. Chronic disease typically manifests with upper lung
zone fibrosis. Characteristic distribution and presence of centrilobular
nodules on CT help distinguish chronic hypersensitivity pneumonitis from
idiopathic pulmonary fibrosis.
References
-
Unger GF, Scanlon GT, Fink JN, Unger J de B. A radiologic approach
to hypersensitivity pneumonias. Radiol Clin North Am
1973;11: 339
-356[Medline]
-
Soleman A, Colby TV. Histologic diagnosis of extrinsic allergic
alveolitis. Am J Surg Pathol
1988;12: 514
-518[Medline]
-
Gurney JW. Hypersensitivity pneumonitis. Radiol Clin
North Am 1992;30: 1219
-1230[Medline]
-
Silver SF, Muller NL, Miller RR, Lefcoe MS. Hypersensitivity
pneumonitis: evaluation with CT. Radiology
1989;173: 441
-445[Abstract/Free Full Text]
-
Lynch DA, Rose CS, Way D, King TE Jr. Hypersensitivity pneumonitis:
sensitivity of high-resolution CT in a population-based study.
AJR
1992;159: 469
-472[Abstract/Free Full Text]
-
Nansell DM, Wells AU, Padley SP, Muller NL. Hypersensitivity
pneumonitis: correlation of individual CT patterns with functional
abnormalities. Radiology
1996;199: 123
-128[Abstract/Free Full Text]
-
Adler BD, Padley SP, Muller NL, Remy-Jardin M, Remy J. Chronic
hypersensitivity pneumonitis: high-resolution CT and radiographic features in
16 patients. Radiology
1992;185: 91
-95[Abstract/Free Full Text]
-
Lynch DA, Newell JD, Logan PM, King TE Jr, Muller NL. Can CT
distinguish hypersensitivity pneumonitis from idiopathic pulmonary fibrosis?
AJR
1995;165: 807
-811[Abstract/Free Full Text]
-
Sharma OP. Hypersensitivity pneumonitis. Dis
Mon 1991;37: 409
-471[Medline]
-
McAdams HP. Chest case of the day: hypersensitivity pneumonitis.
AJR
1995;165: 187
-189[Medline]
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Introduction
Acute Hypersensitivity...
