Thoracic Imaging 2003 - Society of Thoracic Radiology

SUNDAY
72
Hypersensitivity Pneumonitis (a.k.a. Extrinsic Allergic
Alveolitis
Aine M. Kelly, M.D.
University of Michigan Medical Center, Ann Arbor, Michigan
Overview:
The clinical settings associated with hypersensitivity pneumonitis,
its symptoms and the findings on physical examination
are initially discussed. Corresponding abnormalities on pulmonary
function testing and histologic examination are
described. The most common radiographic and HRCT findings
of acute, subacute and chronic hypersensitivity pneumonitis are
described with differential diagnoses.
Objectives:
To be familiar with the clinical, histological, radiographic
and HRCT features of hypersensitivity pneumonitis.
To be familiar with the differential diagnosis of the above findings
Pathophysiology:
Hypersensitivity pneumonitis (HP) or extrinsic allergic alveolitis
(EAA) represents the body’s immunological response to a
variety of inhalational particulate antigens. The offending agents
are many, with the resulting disorders having names such as
farmer’s lung, mushroom workers lung, pigeon fancier’s lung,
humidifier lung, hot tub lung etc. See Table 1 for details. The
antigens inhaled range in size from 1 to 5 micrometers and
include bacteria, fungi, amoebas, animal and plant proteins,
drugs and small molecular weight chemicals. For disease to be
induced there must be a high level of exposure. This can either
be heavy exposure of short duration or low-grade exposure of
long duration. Many exposures relate to particular occupations
or hobbies, with exceptions such as humidifier lung. Therefore,
an extensive social and occupational history should be sought.
The immune mechanism is thought to be mediated by the
alternate complement pathway and type III and IV hypersensitivity
reactions. Serum precipitins are evidence of exposure, and
may also be found in many asymptomatic individuals. Falsenegative
serum precipitins are common, particularly with
advanced chronic disease. HP has a higher incidence in nonsmokers.
Clinical presentation:
Acute disease occurs within hours of a heavy antigen exposure,
and manifests with fever, chills, dry cough, dyspnea,
wheeze, malaise, myalgia and malaise. This presentation may
simulate an acute viral or bacterial illness; however, repeated
exposures should arouse suspicion of HP. Physical examination
may yield lower lung crackles. Tachypnea and cyanosis occur in
severe cases. Spontaneous recovery in days usually follows
removal of the offending antigen from the individual's surroundings.
Acute disease is a common mode of presentation in pigeon
fancier's lung.
Subacute disease consists of repeated acute episodes on a
background of deteriorating lung function. Pulmonary function
tests may show an obstructive pattern.
Chronic disease occurs secondary to long-term low-grade
antigen exposure. Progressive shortness of breath, malaise, fever
and weight loss can occur. These symptoms mimic such diseases
as chronic granulomatous infections, idiopathic pulmonary
fibrosis and sarcoidosis. Pulmonary function tests show
a mixed obstructive and restrictive pattern.
Table 1: Spectrum of hypersensitivity pneumonitis
Syndrome Antigen Cause
Farmer`s lung Thermophilic actinomycetes Moldy hay
Bird fancier`s lung Avian proteins Pigeons, parakeets,
ducks,
(droppings, feathers) canaries, geese
Humidifier lung Mycobacterium Avium Air Conditioners, hottubs,
Intracellulare complex, fungi, humidifiers
Amebae, Klebsiella oxytoca
Mushroom worker`s Saccharopolyspora rectivirgula Mushroom culture
lung Micromonospora vulgaris compost
Pleurotus ostreatus
Pholiota nameko
Thermophilic actinomycetes
Malt worker`s lung Aspergillus clavatus Moldy malt / barley
Maple bark disease Cryptostroma corticale Tree bark
Japanese summer Trichosporum asahii House dust
type HP (formerly t.cutaneum)
Suberosis Penicillium frequentans Moldy cork
Bagassosis Thermoactinomyces sacchari Moldy sugar cane
Occupational Isocyanates Adhesives, paints,
Polyurethane foam
Histological Features: In the early or acute stage there is a
temporally uniform interstitial pneumonitis consisting of
mononuclear and lymphocytic infiltration of the inter- and
intralobular septa. Alveolar spaces may fill with cellular elements
and fluid. Bronchiolitis is common and bronchiolitis
obliterans has been described. These histological findings have a
patchy and peribronchiolar distribution. Acute changes predominate
in the lower lungs. In the subacute stage, non-caseating
granulomas occur surrounding the centrilobular structures.
Interstitial pneumonitis, alveolar filling and bronchiolitis also
occur at this stage in a peribronchiolar distribution. With the
chronic stage, granulomas resolve and fibrosis ensues. This
occurs more in the upper lungs. Scarring and honeycomb cysts
occur with compensatory emphysema, which may later be complicated
by pulmonary hypertension and cor pulmonale.
Radiographic Abnormalities: In the acute stage the chest
radiograph may be normal.
Small well-or ill-defined lung nodules, usually 1 to 3-mm in
size are most commonly found in the acute / subacute stage.
Superimposition leads to a generalized ground glass haze, usually
bilateral, in all lung zones, but most severe in the mid lungs,
sparing the extreme apices and bases. Occasionally, larger 4 to
8-mm nodules, patchy consolidation or a linear interstitial pattern
may be seen. In the chronic stage, lung volumes are
reduced with the development of fibrosis. This overlap of fibrosis
leads to combined reticular and nodular opacities, and usually
has an upper lung predominance. Linear parallel opacities
may occur due to traction bronchiectasis or bronchial wall
thickening. Nodules may persist into the chronic stage.
HRCT Findings
Acute/Subacute: HRCT is more sensitive than chest radiographs
in the detection and assessment of HP. Little published
data regarding the acute stage exists. Bilateral consolidation
with multiple small 1 to 3-mm nodules has been described. In
the subacute stage, in ground glass opacity (GGO) is found in
approximately 70% of cases, diffuse or patchy in distribution,