Case 4 -
"Hot tub" lung
Jeffrey L. Myers
University of Michigan
Ann Arbor, MI
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A 46-year-old woman was referred for evaluation of diffuse lung disease. She developed symptoms of
cough in January 2006. Over the next several weeks these progressed to worsening dry cough with
dyspnea. Pulmonary function tests showed mild airflow limitation, and a CT scan was described as showing
mosaic attenuation. She improved within 48 hours of being started on prednisone, but her symptoms
returned within 1 week of being tapered from the drug. She was a non-smoker. She started working in a
new office environment that included a "large bird, something like a parakeet" around the time that her
symptoms began. She had worked previously as a daycare provider. She underwent surgical lung biopsy.
Case 4 - Slide 1
Case 4 - Figure 1 - Low magnification photomicrograph showing granulomatous inflammation exquisitely localized to small airways. Intervening lung tissue is relatively unaffected.
Case 4 - Figure 2 - Higher magnification photomicrograph showing well formed, non-necrotizing granuloma.
Case 4 - Figure 3 - Intermediate magnification photomicrograph showing chronic bronchiolitis with associated granuloma within the lumen of the affected airway.
Case 4 - Figure 4 - Higher magnification view of intralumenal granuloma illustrated in Figure 3.
Case 4 - Figure 5 - Intermediate magnification photomicrograph showing granuloma with central necrosis.
Case 4 - Figure 6 - Higher magnification view of granuloma depicted in Figure 5 illustrating focal central necrosis.
Case 4 - Figure 7 - Intermediate magnification photomicrograph showing chronic bronchiolitis with associated granuloma in peribronchiolar interstitium. This focus more closely resembles classical chronic hypersensitivity pneumonia.
Case 4 - Figure 8 - Higher magnification view showing interstitial granuloma illustrated in Figure 7.
At low magnification, sections prepared from the right lower lobe biopsy show a patchy,
airway-centered process characterized by a peribronchiolar and intralumenal inflammatory infiltrate with
minimal associated fibrosis. At higher magnification the inflammatory infiltrate comprises a combination
of lymphocytes and variably well formed granulomas. Many of the granulomas reside mainly within the
lumens of distal airways and show focal central necrosis. Special stains were negative for fungi,
pneumocystis, and acid-fast bacilli.
"Hot tub" lung
She initially improved with prednisone therapy and quitting her job, but her symptoms returned when
the drug was tapered. After re-review of her biopsy it was discovered that she had used a hot tub for 10
years. She had drained the tub because she thought that it was responsible for her cough. No cultures
of the hot tub were obtained. Three months after biopsy she was back to baseline without specific
therapy other than hot tub avoidance.
Hypersensitivity pneumonia (-itis), also called extrinsic allergic
alveolitis, is a diffuse interstitial lung disorder that results from sensitization to a variety of
inhaled organic dusts or aerosols. Offending agents are typically derived from thermophilic bacteria,
molds, and various plant or animal proteins. Criteria for diagnosis of chronic hypersensitivity
pneumonia are controversial but generally include an appropriate exposure history, subjective and
objective evidence of lung disease temporally linked to antigen exposure, and the presence of serum
antibodies directed against the suspected antigen.
Confirming the diagnosis is difficult,
in part because the presence of precipitating antibodies reflects exposure and not necessarily disease.
Hypersensitivity pneumonia is often divided into acute, subacute and chronic – or more simply acute and chronic – forms. The terms have been
inconsistently applied, reflecting significant overlap between these interrelated categories. In
general, acute hypersensitivity pneumonia is applied to patients suffering
from a first attack with symptom duration of less than one month. Subacute
hypersensitivity pneumonia refers to patients with periodic symptoms for less than one year, and chronic hypersensitivity pneumonia to patients with progressive respiratory
complaints for at least one year. Chronic hypersensitivity pneumonia need not be preceded by acute
disease, and only a small number of patients with acute disease develop chronic hypersensitivity
Acute hypersensitivity pneumonia follows exposure to relatively large doses of the responsible antigen
and is the most easily recognized variant. Symptoms occur within 4 to 6 hours of exposure and include
severe dyspnea and cough frequently associated with fever, chills, sweating, nausea, and
anorexia.  Symptoms subside 24 to 48 hours after cessation of exposure and, in most patients,
are followed by radiographic resolution over a period of days or weeks. Lung biopsy is rarely necessary
for diagnosis and management of patients with acute hypersensitivity pneumonia, and for that reason
pathologic findings in this form of the disease are incompletely understood.
Chronic hypersensitivity pneumonia results from intermittent exposure to the offending antigen and, in
some patients, represents the cumulative effect of multiple acute episodes. Patient are often unaware of
the environmental exposure responsible for their respiratory symptoms, further complicating diagnosis.
Chronic hypersensitivity pneumonia typically presents as a slowly progressive respiratory illness with an
insidious onset that may be indistinguishable from other diffuse lung diseases, most importantly usual
interstitial pneumonia.  Cough, often with associated dyspnea on exertion, is the most common
presenting complaint. Fever usually accompanies respiratory symptoms during periods of acute
exacerbation in patients with subacute disease.
Laboratory studies show nonspecific
abnormalities, including mild leukocytosis occasionally associated with mild peripheral eosinophilia.
Pulmonary function studies demonstrate restricted lung volumes and reduced DLco.
Radiologic findings in chronic hypersensitivity pneumonia are not specific. Conventional radiographs
are normal in some patients but in most show a nonspecific pattern of ground glass and reticular
opacities, often with an upper lobe distribution. Volume loss and honeycomb change are present in
patients with long standing disease. HRCT scans show a distinctive combination of ground glass
opacities, small centrilobular nodules and mosaic attenuation.
change is seen in about half of patients. In patients with honeycomb change the findings may be
indistinguishable from usual interstitial pneumonia.
Prognosis for hypersensitivity pneumonia is variable.  Antigen avoidance is the
cornerstone of therapy and is often curative in patients for whom a specific antigen source is
identified, assuming the absence of established fibrotic lung disease at the time of diagnosis.
Corticosteroids are useful in accelerating the rate of recovery but do not affect long term outcome
independent of eliminating antigenic exposure.
Lung function improves over a period of
months and years, but abnormalities may persist in as many as twenty to forty percent of
Disease-specific mortality rates in chronic hypersensitivity pneumonia range
from ten to nearly thirty percent.
Repeated symptomatic attacks, older age,
cigarette smoking, and the presence of established fibrosis and honeycomb change at the time of diagnosis
are associated with a more aggressive course.
Chronic interstitial pneumonia is the lesion most frequently described in subacute and chronic
hypersensitivity pneumonia and is present in nearly all cases.
magnification, alveolar septa are expanded by an infiltrate of mononuclear inflammatory cells accentuated
around bronchioles. The inflammatory infiltrate is composed mainly of lymphocytes, plasma cells, and
histiocytes which are occasionally admixed with eosinophils and neutrophils. Epithelioid histiocytes
predominate only focally, usually around the airways, and impart a subtle and vaguely granulomatous
appearance to the inflammatory infiltrate. Well formed granulomas are rare. Isolated multinucleated
giant cells occur frequently in hypersensitivity pneumonia and in a minority of cases may represent a
striking feature. Giant cells often contain various nonspecific cytoplasmic inclusions identical to
those seen in sarcoidosis such as Schaumann bodies, asteroid bodies, cholesterol clefts, and birefringent
calcium salts. Granulomatous features, although seen in the majority of patients with hypersensitivity
pneumonia, may be absent in as many as thirty percent of surgical lung biopsies.  In
advanced cases the changes are less characteristic and consist mainly of bland interstitial fibrosis and
honeycomb change. 
Chronic bronchiolitis is a consistent finding in hypersensitivity pneumonia and is usually present in
the form of a cellular peribronchiolar infiltrate, often accompanied by lymphoid aggregates.
The degree of airway inflammation is proportional to the associated interstitial
pneumonia.  Organizing pneumonia ("bronchiolitis obliterans") is present about half the time
and is characterized by polypoid plugs of intralumenal fibroblastic tissue indistinguishable from
organizing pneumonia in other contexts.
Clusters of finely vacuolated, foamy
alveolar macrophages within peribronchiolar interstitium and air spaces is a conspicuous feature in some
cases and is attributable to small airway dysfunction, reflecting microscopic obstructive ("endogenous
Hot Tub Lung
Hot tub lung is a syndrome that combines elements of hypersensitivity
pneumonia and atypical mycobacterial infection and results from exposure to contaminated hot tubs, spas,
jacuzzis or whirlpools.
Patients present with cough and dyspnea frequently
associated with fever. Weight loss is seen in about a fourth of patients. Symptoms show a temporal link
to hot tub exposure, a key finding for establishing the diagnosis. HRCT shows findings virtually
indistinguishable from the previous description of classical chronic hypersensitivity pneumonia.
Lung biopsy findings overlap with those seen in other examples of hypersensitivity
pneumonia except that the interstitial pneumonia is less conspicuous and the granulomas are well formed
and distributed within airway lumens rather than peribronchiolar interstitium.  Granulomas
are primarily non-necrotizing, but focal central necrosis may occur. Acid-fast stains are positive in
about 25% of surgical lung biopsies.
The differential diagnosis for hypersensitivity pneumonia includes other chronic interstitial
pneumonias. Peribronchiolar accentuation of the interstitial inflammatory infiltrate, granulomatous
inflammation, and BOOP-like changes are perhaps the most helpful features in separating hypersensitivity
pneumonia from the idiopathic interstitial pneumonias. Some cases may be indistinguishable from cellular
variants of NSIP, indicating that hypersensitivity pneumonia should always be considered a potential
etiology in patients with otherwise idiopathic NSIP.
Associated honeycomb change may
cause confusion with UIP
.  The changes in UIP tend to be more
peripherally distributed without the bronchiolocentric distribution characteristic of hypersensitivity
pneumonia. Peribronchiolar inflammation without fibrosis and isolated multinucleated giant cells are
additional features helpful in separating hypersensitivity pneumonia from UIP.
Well formed granulomas are rare in hypersensitivity pneumonia other than hot tub lung, and if present
should raise a suspicion of other entities. Sarcoidosis differs in that
well formed granulomas are distributed in a "lymphangitic" pattern, and lack the associated interstitial
pneumonia and bronchiolitis typical of hypersensitivity pneumonia. Chronic
aspiration may result in airway-centered granulomas,
thus resembling hot tub lung. 
Discovery of foreign material within the granulomas coupled with appropriate history should allow
confident distinction of the two conditions. Finally, lymphoid interstitial
pneumonia (LIP) is associated with granulomatous inflammation in as many as forty to fifty percent
of patients and can closely mimic the histology of hypersensitivity pneumonia.
septa are usually more extensively expanded by lymphocytes, plasma cells and lymphoid follicles in LIP.
Correlation with clinical and radiologic findings may be helpful in difficult cases. Patients with LIP
are more likely to have an underlying connective tissue disease or immunodeficiency syndrome, lack an
exposure history suggestive of hypersensitivity pneumonia, and have findings on imaging studies that
typically differ from those described in patients with hypersensitivity pneumonia.
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