The Merck Manual of Diagnosis and Therapy Section 6. Pulmonary

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The Merck Manual of Diagnosis and Therapy Section 6. Pulmonary

Disorders Chapter 76. Hypersensitivity Diseases Of The Lungs Topics

[General] Hypersensitivity Pneumonitis Eosinophilic Pneumonias

Allergic

Bronchopulmonary Aspergillosis

Hypersensitivity Pneumonitis

A diffuse interstitial granulomatous lung disease caused by an

allergic

response to inhaled organic dusts or, less commonly, to simple

chemicals.

Hypersensitivity pneumonitis (extrinsic allergic alveolitis) includes

numerous examples that are caused by specific antigens. Farmer's

lung,

associated

with repeated inhalation of dusts from hay containing thermophilic

actinomycetes, is the prototype.

Etiology and Pathogenesis

The number of specific substances known to be capable of causing

hypersensitivity pneumonitis is increasing. Most commonly, the agent

is a

microorganism

or a foreign animal or vegetable protein. However, simple chemicals,

when

inhaled in considerable amounts, may also cause the disease. _Table

76-2_

(http://www.merck.com/mrkshared/mmanual/tables/76tb2.jsp) lists

common

causative

antigens with examples of the associated diseases.

Hypersensitivity pneumonitis is thought to be immunologically

mediated,

although pathogenesis is not completely clear. Precipitating

antibodies to the

causative antigen are usually demonstrated, suggesting a type III

reaction,

although vasculitis is not common. Type IV hypersensitivity is

suggested by the

granulomatous primary tissue reaction and findings in animal models.

Only a small proportion of exposed persons develop symptoms, and

only after

weeks to months of exposure, which is required for induction of

sensitization. Chronic progressive parenchymal disease may result

from

continuous or

frequent low-level exposure to the antigen. A history of allergic

disease (eg,

asthma, hay fever) is uncommon and is not a predisposing factor.

Diffuse granulomatous interstitial pneumonitis is characteristic but

not

definitive or specific. Lymphocyte and plasma cell infiltrates occur

along

airways and in thickened alveolar septa; granulomas are single,

nonnecrotizing,

and randomly scattered in the parenchyma without mural vascular

involvement.

The degree of fibrosis is usually mild but depends on the stage of

the disease.

Bronchiolitis occurs to some degree in about 50% of patients with

farmer's

lung.

Symptoms and Signs

In the acute form, episodes of fever, chills, cough, and dyspnea

occur in a

previously sensitized person, typically 4 to 8 h after reexposure.

Anorexia,

nausea, and vomiting may also be present. Fine-to-medium inspiratory

rales

may be heard on auscultation. Wheezing is unusual. With avoidance of

the

antigen, symptoms usually lessen within hours, although complete

recovery may

take

weeks and pulmonary fibrosis may follow repeated episodes. A

subacute form

may develop insidiously with cough and dyspnea over days to weeks,

with

progression sometimes requiring urgent hospitalization. In the

chronic form,

progressive exertional dyspnea, productive cough, fatigue, and

weight loss may

develop over months to years; the disease may progress to

respiratory failure.

Chest x-ray findings range from normal to diffuse interstitial

fibrosis.

Bilateral patchy or nodular infiltrates, coarsening of

bronchovascular

markings,

or a fine acinar pattern suggestive of pulmonary edema may be seen.

Hilar

lymphadenopathy and pleural effusion are rare. CT, especially high-

resolution

CT, may be superior in assessing the type and extent of

abnormalities, but

there are no pathognomonic CT findings.

Pulmonary function tests show a restrictive pattern with decreased

lung

volumes, a decreased carbon monoxide diffusing capacity, abnormal

ventilation/perfusion ratios, and hypoxemia. Airway obstruction is

unusual in

acute disease

but may develop in chronic disease. Eosinophilia is not usual.

Diagnosis

Diagnosis depends on a history of environmental exposure and

compatible

clinical features, chest x-ray findings, and pulmonary function test

results.

The

presence of specific precipitating antibodies to the suspected

antigen in

the serum helps confirm the diagnosis, although neither their

presence nor

absence is definitive. A history of exposure may provide clues (eg,

persons

exposed at work may become symptom-free every weekend, or symptoms

may reappear

4

to 8 h after reexposure). History of exposure to causative antigens

may not

be elicited easily, particularly for air-conditioner (humidifier)

lung, and an

assessment of the environment by experts may help in difficult

cases. In

puzzling cases or in those without a history of environmental

exposure, open

lung biopsy may be useful. Bronchoalveolar lavage is often used to

help

diagnose

interstitial lung diseases, but its value is not established. The

number of

lymphocytes, particularly T cells, may be increased in

hypersensitivity

pneumonitis (and in sarcoidosis). The CD8+ (suppressor/cytotoxic) T-

cell subset

may predominate in some stages of hypersensitivity pneumonitis,

whereas the

CD4+ (helper/inducer) subset may predominate in active sarcoidosis.

Transbronchial biopsy is of very limited value and may be misleading

because

the sample

size is small.

Atypical farmer's lung (pulmonary mycotoxicosis) refers to a

syndrome of

fever, chills, and cough occurring within hours of massive exposure

to moldy

silage (eg, when uncapping a silo); precipitins are not present,

suggesting a

nonimmunologic mechanism. Pulmonary infiltrates are usually present.

This

condition, associated with aspergillus-contaminated old silage, is

to be

distinguished from silo filler's disease, caused by toxic oxides of

nitrogen

given off

by fresh silage. Organic dust toxic syndrome is characterized by

transient

fever and muscle aches, with or without respiratory symptoms, and no

evidence

of sensitization after exposure to agricultural dusts (eg, grain

fever).

Humidifier fever refers to cases associated with contaminated

heating, cooling,

and humidifying systems (see under _Sick Building Syndrome_

(http://www.merck.com/mrkshared/mmanual/section6/chapter75/75e.jsp#A0

06-075-1020\

) in Ch. 75).

Endotoxin is thought to have an etiologic role in organic dust toxic

syndrome

and humidifier fever.

Hypersensitivity pneumonitis can be distinguished from psittacosis,

viral

pneumonia, and other infective pneumonias by cultures and serologic

tests.

Because of similar clinical features, x-ray findings, and pulmonary

function

test

results, idiopathic pulmonary fibrosis (Hamman-Rich syndrome,

cryptogenic

fibrosing alveolitis, usual interstitial pneumonia of Liebow) may be

difficult

to distinguish from hypersensitivity pneumonitis when the typical

history of

exposure followed by an acute episode is not elicited. Variants of

bronchiolitis in adults (eg, bronchiolitis obliterans with organizing

pneumonia) may

appear as restrictive (interstitial) disease and may be difficult to

differentiate in the absence of relevant history or typical findings

in open

lung

biopsy.

Evidence of autoimmunity, such as positive antinuclear antibody or

latex

fixation test or the presence of a collagen vascular disorder,

suggests an

idiopathic or a secondary type of usual interstitial pneumonia.

Chronic

eosinophilic pneumonias are often accompanied by peripheral blood

eosinophilia.

Sarcoidosis often results in hilar and paratracheal lymph node

enlargement and

may

affect other organs. Pulmonary angiitis-granulomatosis syndromes

(Wegener's,

lymphomatoid, and allergic granulomatosis [Churg-Strauss syndrome])

are

usually accompanied by upper respiratory tract or kidney disease.

Bronchial

asthma

and allergic bronchopulmonary aspergillosis produce eosinophilia and

airway

obstruction rather than restrictive abnormalities.

Prophylaxis and Treatment

The most effective treatment is cessation of further exposure to the

causative antigen. Acute disease is self-limiting if additional

exposure is

avoided.

Socioeconomic factors may preclude a complete change of environment.

Dust

control or the use of protective masks to filter the causative dust

particles

in contaminated areas may be effective. Sometimes, chemical means

can be used

to prevent the growth of antigenic microorganisms (eg, in hay).

Extensive

cleaning of wet ventilation systems and corresponding work areas is

also

effective in some settings.

Corticosteroids may be useful in severe acute or subacute cases but

have not

been shown to alter eventual outcome in chronic disease. Prednisone

60

mg/day is given po for 1 to 2 wk and then tapered over the next 2 wk

to 20

mg/day,

followed by weekly decrements of 2.5 mg until withdrawal is complete.

Recurrence or progression of symptoms requires modification of this

regimen.

Antibiotics are not indicated unless there is a superimposed

infection.