Download Case 14-2015: A 58-Year-Old Woman with Shortness of Breath

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Sally H. Ebeling, Assistant Editor
Nancy Lee Harris, M.D., Editor
Alice M. Cort, M.D., Associate Editor
Emily K. McDonald, Assistant Editor
Case 14-2015: A 58-Year-Old Woman
with Shortness of Breath
Barry S. Shea, M.D., Amita Sharma, M.D., and Eugene J. Mark, M.D.
Pr e sen tat ion of C a se
Dr. Christopher J. Mutrie (Thoracic Surgery): A 58-year-old woman was seen in the outpatient pulmonary clinic of this hospital because of shortness of breath on exertion.
The patient had been well until approximately 8 months before this presentation,
when she noted shortness of breath while jogging her usual 4 miles daily. During
the next 7 months, her symptoms gradually worsened until she became winded
within 7 minutes after starting to jog or after climbing stairs, with associated leg
fatigue. Approximately 1 month before this evaluation, she was seen at an outpatient
clinic of another hospital. On examination, the vital signs and oxygen saturation
were normal. The oropharyngeal mucosa had a cobblestone appearance, and there
were scattered inspiratory wheezes throughout the lung fields. The peak expiratory
flow rate measured 400 liters per minute (predicted value, 470). A chest radiograph
showed reticular linear peripheral opacities predominantly involving the upper
lung zones, without pleural effusions or pneumothorax. Results of electrocardiography were normal. Fluticasone (two puffs at a strength of 110 μg per puff, by inhalation twice daily) and an albuterol inhaler with a spacer were prescribed for use
before exercise. Five days later, results of pulmonary-function tests and the blood level
of d-dimer were normal.
Dr. Amita Sharma: The initial chest radiograph showed mild volume loss, biapical
pleural thickening, and peripheral nodular opacities in the upper lung zones
(Fig. 1). One week later, computed tomography (CT) of the chest, performed without the administration of contrast material, confirmed the presence of bilateral
peripheral nodules, which were broad-based and associated with nodular pleural
thickening extending into the fissures. Linear bands in the parenchyma were seen
adjacent to many peripheral nodules. A few peripheral opacities were present in
the middle lung zone, but no abnormalities were seen in the lower lung zone.
There was no hilar or mediastinal lymphadenopathy.
Dr. Mutrie: The patient was referred to the outpatient pulmonary clinic of this
hospital. She reported no orthopnea, paroxysmal nocturnal dyspnea, wheezing,
pedal edema, cough, sputum production, rash, chills, chest pressure, palpitations,
change in bowel habits, or urinary symptoms. She had osteopenia, migraine headaches, hyperlipidemia, seasonal allergies, intermittent mildly elevated aminotrans-
From the Departments of Medicine
(B.S.S.), Radiology (A.S.), and Pathology
(E.J.M.), Massachusetts General Hospi‑
tal, and the Departments of Medicine
(B.S.S.), Radiology (A.S.), and Pathology
(E.J.M.), Harvard Medical School — both
in Boston.
N Engl J Med 2015;372:1749-58.
DOI: 10.1056/NEJMcpc1415200
Copyright © 2015 Massachusetts Medical Society.
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1749
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medications included alendronate, simvastatin,
and lorazepam (as needed for insomnia). She had
no known allergies. She worked in an office. She
drank wine occasionally, had stopped smoking
30 years earlier (after 3 years of smoking), and did
not use illicit drugs. She exercised daily, walking
and jogging 4 miles. Her father had cardiac arrhythmias, a sister had breast cancer, another sister possibly had systemic lupus erythematosus, a
brother had type 1 diabetes mellitus, one of her
children had diabetes mellitus, and another one of
her children had a supraventricular arrhythmia.
The physical examination was normal, without
wheezing, cyanosis, clubbing, or lymphadenopathy. Results of pulmonary-function tests were
normal; the forced vital capacity (FVC) was 3.45
liters (101% of the predicted value), the forced expiratory volume in 1 second (FEV1) 2.62 liters
(97%), the ratio of FEV1 to FVC 0.76, the total
lung capacity 5.30 liters (97%), and the carbon
monoxide diffusing capacity 22.4 (92%). The
blood level of aspartate aminotransferase was 56 U
per liter (reference range, 9 to 32), the level of
alanine aminotransferase was 60 U per liter (reference range, 7 to 30), and testing for antinuclear antibody (ANA) was positive at 1:40 dilution
in a homogeneous and speckled pattern (reference range, negative at 1:40 and 1:160 dilutions).
The complete blood count and white-cell differential count were normal, as were the anion gap
and blood levels of electrolytes, glucose, urea nitrogen, creatinine, calcium, total protein, albumin,
globulin, total bilirubin, alkaline phosphatase,
and angiotensin-converting enzyme; testing was
negative for rheumatoid factor, IgG antibodies to
anti–cyclic citrullinated peptide, antineutrophil
cytoplasmic antibody (ANCA), and IgE antibodies
to environmental allergens.
Dr. Sharma: At a follow-up examination 2.5
months later, CT of the chest, performed at this
hospital after the intravenous administration of
contrast material, was largely unchanged (Fig. 2).
An 8-mm nodule was seen in the left apex.
Dr. Mutrie: A diagnostic procedure was performed.
A
B
Figure 1. Radiographs of the Chest.
Chest radiographs obtained in posteroanterior (Pan‑
el A) and lateral (Panel B) views show pleuroparen‑
chymal opacities (Panel A, arrows) in the upper lung
zones.
Differ en t i a l Di agnosis
ferase levels, and breast calcifications; she had
undergone excision of an adenomatous colonic
polyp 2 years previously, as well as sinus surgery
and a tonsillectomy in the distant past. Additional
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n engl j med 372;18
Important Features of the Case
Dr. Barry S. Shea: This previously healthy, middleaged woman presented with insidious onset of
dyspnea on exertion and a notable decrease in ex-
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A
B
D
C
Figure 2. CT Scan of the Chest.
Approximately 2.5 months after the initial evaluation, CT was performed at the lung‑window setting after the ad‑
ministration of contrast material. Selected axial slices through the upper lung zones (Panels A, B, and C) and a cor‑
onal reformatted image (Panel D) show peripheral nodular opacities in the upper lung zones that are unchanged
from the initial evaluation (Panels A, C, and D, arrows). An 8‑mm nodule is seen in the left apex (Panel B, arrow).
Pleural thickening is best seen along the major fissures (Panel C, arrowheads).
ercise tolerance during an 8-month period. The
history does not include symptoms that are suggestive of some of the most common causes of
chronic dyspnea on exertion. The progressive,
nonepisodic nature of the symptoms and the absence of cough, wheezing, and chest discomfort
argue against asthma as the main diagnosis. The
minimal, remote history of smoking argues against
chronic obstructive pulmonary disease, and no additional symptoms are present that suggest ischemic heart disease or heart failure. The physical
examination that was performed in the outpatient pulmonary clinic was normal, although a
previous examination had indicated the presence
of inspiratory wheezes, suggesting a component
of airways disease. Results of extensive laboratory
testing were largely unremarkable, except for mild
elevations in the serum aminotransferase levels.
Results of pulmonary-function tests were normal,
n engl j med 372;18
which is surprising given the severity of the patient’s dyspnea and functional decline. I will return to this observation later, because it turns out
to be a key feature of the clinical scenario. I will
first discuss the radiographic abnormalities, which
help to narrow the differential diagnosis.
Infection, Cancer, and Vasculitis
Whenever multifocal nodular or consolidative
opacities are seen on chest imaging, the differential diagnosis should include infection, cancer,
and vasculitis. In this case, the duration of symptoms essentially rules out a typical viral or bacterial pneumonia. Chronic infections with predominant involvement of the upper lung zones, such
as histoplasmosis, blastomycosis, and tuberculosis, should be considered; however, the absence of
cough, fevers, and constitutional symptoms argues
strongly against a diagnosis of any of these chron-
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1751
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ic infections. Furthermore, nothing in the patient’s
history suggests exposure to tuberculosis or travel
to regions where the relevant fungi are endemic.
If this patient had cancer, the multifocal nature of her illness would indicate metastatic disease; however, patients with pulmonary metastases typically present with discrete nodules that
involve the lung bases rather than the apexes.1
Nodular pleural thickening can be seen in patients
with malignant mesothelioma, but multifocal disease is extremely rare, and the vast majority of
mesothelioma cases are associated with a history
of asbestos exposure.2
Patients with ANCA-associated vasculitides,
granulomatosis with polyangiitis, microscopic
polyangiitis, or the Churg–Strauss syndrome can
present with multifocal nodular opacities or areas
of dense consolidation on chest imaging. These
diseases can occur despite negative ANCA titers,
but in this case, the absence of fevers and constitutional symptoms argues against a diagnosis of
granulomatosis with polyangiitis or microscopic
polyangiitis, and the absence of peripheral eosinophilia and the absence of a history of asthma
make the Churg–Strauss syndrome unlikely.3 Because infection, cancer, and vasculitis are all unlikely in this case, the radiographic abnormalities
probably indicate the presence of an interstitial
lung disease.
Interstitial Lung Diseases with Predominant
Involvement of the Upper Zones
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nopathy is almost always present, and the most
commonly seen parenchymal abnormalities consist of reticular or nodular opacities along the
bronchovascular bundles.4,5 Sarcoidosis is often
difficult to rule out, but I think it is unlikely in
this case. Therefore, the pattern of radiographic
abnormalities does not suggest any of these classic
interstitial lung diseases with predominant involvement of the upper zones.
Idiopathic Interstitial Pneumonias
Many interstitial lung diseases are idiopathic in
origin. Idiopathic interstitial pneumonias are divided into the following seven distinct clinicopathological entities6: idiopathic pulmonary fibrosis,
nonspecific interstitial pneumonia, cryptogenic
organizing pneumonia, acute interstitial pneumonia, respiratory bronchiolitis–associated interstitial lung disease, desquamative interstitial pneumonia, and lymphoid interstitial pneumonia. Each
of these entities is associated with typical radiographic features, and this patient’s chest CT findings are not characteristic of any of these entities,
except possibly cryptogenic organizing pneumonia. Radiographs of patients with cryptogenic
organizing pneumonia typically reveal air-space
consolidation, which can be either unilateral or
bilateral and is often patchy in distribution. In a
minority of cases, the air-space consolidation can
be confined to the subpleural region.7 The clinical presentation of cryptogenic organizing pneumonia is typically characterized by a subacute
onset of cough and dyspnea, often with constitutional symptoms, although these can be absent.8
Cryptogenic organizing pneumonia should be
included in the differential diagnosis in this case.
However, it is important to note that the radiographic and histologic patterns associated with
cryptogenic organizing pneumonia (namely, patterns indicative of organizing pneumonia with
or without bronchiolitis obliterans) can be seen
with other conditions, most notably viral infections, connective-tissue disease–associated interstitial lung disease, and drug-induced interstitial
lung disease. Therefore, cryptogenic organizing
pneumonia is a diagnosis of exclusion that can
be made only when known causes of organizing
pneumonia have been ruled out.
When a pulmonologist is presented with a case of
interstitial lung disease with predominant involvement of the upper zones, a number of disease
entities should come to mind. These include two
fairly common interstitial lung diseases, sarcoidosis and hypersensitivity pneumonitis, as well as
rarer diseases, such as pulmonary Langerhans’-cell
histiocytosis and the pneumoconioses (berylliosis, silicosis, and coal worker’s pneumoconiosis).
The CT findings in this case are not characteristic of Langerhans’-cell histiocytosis, hypersensitivity pneumonitis, or the pneumoconioses; furthermore, this patient has no history of current
smoking, which is almost universally present in
patients with Langerhans’-cell histiocytosis, and
no history of environmental exposures that suggest hypersensitivity pneumonitis or the pneumoconioses. Although patients with pulmonary Chronic Eosinophilic Pneumonia
sarcoidosis can present with myriad radiographic Chronic eosinophilic pneumonia is another idiopatterns, bilateral hilar or mediastinal lymphade- pathic interstitial lung disease that is associated
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Case Records of the Massachuset ts Gener al Hospital
with the presence of peripheral opacities on chest
imaging, a finding that is often referred to as the
photographic negative of pulmonary edema. Patients with chronic eosinophilic pneumonia often
present with cough, constitutional symptoms, and
peripheral eosinophilia, but these features can
be absent in 10 to 20% of patients. Approximately 50 to 60% of affected patients have a history
of atopic disease.9,10 In this case, there is an absence of clinical features that are characteristic of
chronic eosinophilic pneumonia, but because of
the appearance of multifocal, peripheral, plaquelike opacities on chest CT studies, this disease
should be considered high on the differential diagnosis. Chronic eosinophilic pneumonia shares
many clinical and radiographic features with cryptogenic organizing pneumonia, and thus, on examination of lung-biopsy specimens from patients with chronic eosinophilic pneumonia, it is
not uncommon to see both the histologic pattern
of bronchiolitis obliterans with organizing pneumonia and eosinophilic inflammation.11 Chronic
eosinophilic pneumonia is a diagnosis of exclusion that cannot be made definitively without first
ruling out known causes of pulmonary eosinophilia, including drug-induced lung disease.
Interstitial Lung Disease Associated
with Connective-Tissue Disease
Interstitial lung disease is a common manifestation of many connective-tissue diseases, including
systemic sclerosis, rheumatoid arthritis, dermatomyositis, polymyositis, Sjögren’s syndrome, mixed
connective-tissue disease, and systemic lupus erythematosus.12 The radiographic and histologic patterns of connective-tissue disease–associated interstitial lung disease often mimic those of the
idiopathic interstitial pneumonias.13 In this case,
there is no definitive clinical or laboratory evidence
of a connective-tissue disease, although interstitial lung disease can occasionally precede the onset
of systemic manifestations of a connective-tissue
disease.14 Patients with polymyositis or dermatomyositis can present with muscle fatigue, dyspnea
on exertion, and interstitial lung disease.15 This
patient has only a weakly positive ANA titer, but
ANA can be absent in up to 20% of patients with
polymyositis or dermatomyositis.16 The histologic
pattern of bronchiolitis obliterans with organizing pneumonia has been associated with these
conditions, but it is rare; most affected patients
have the histologic pattern of nonspecific intersti-
tial pneumonia.15 Polymyositis is also a diagnosis
of exclusion that can be made only when other
causes of inflammatory myositis, most notably
drug-induced myopathy, have been ruled out.
Statin-Induced Myopathy and Interstitial
Lung Disease
The differential diagnosis now includes three
entities — cryptogenic organizing pneumonia,
chronic eosinophilic pneumonia, and inflammatory myositis–associated interstitial lung disease
— none of which appear to fit this case perfectly.
However, all three of these diseases have at least
two things in common; they are all diagnoses of
exclusion, and they all share features associated
with a drug reaction.
At this point, I return to a key feature of the
case presentation — that the patient’s symptoms
are greatly out of proportion to the normal results
of pulmonary-function testing and the minimal
abnormalities seen on chest imaging. The patient’s
dyspnea could be attributed to her lung disease,
since dyspnea is a complicated sensation that is
difficult to quantify. However, what appears to
be a dramatic decrease in exercise tolerance cannot be explained by her lung disease, given the
minimal radiographic opacities and the completely
normal results of pulmonary-function tests. Therefore, this clinical scenario is highly suggestive of
a nonpulmonary cause of exercise limitation.
If we were to ignore the parenchymal abnormalities in the lung for a moment, we would see
a middle-aged woman with progressive dyspnea,
decreased exercise tolerance, leg fatigue, and mildly elevated aminotransferase levels who is taking a 3-hydroxy-3-methylglutaryl coenzyme A
(HMG-CoA) reductase inhibitor, also known as
a statin. This clinical picture is highly suggestive
of statin-induced myopathy, which could be the
primary cause of the patient’s symptoms. Statins
can cause a wide spectrum of myopathic injuries,
ranging from asymptomatic elevations in serum
creatine kinase levels to frank rhabdomyolysis.
Myalgias have been reported in up to 10% of patients who are taking statins, although the incidence of myositis among such patients is probably less than 1%.17 Hepatic dysfunction can also
be seen with statin use,18 and the elevated serum
aminotransferase levels in this patient could be
an important clue.
Statin-induced interstitial lung disease has been
described, although it is very rare. As of June 2007,
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only 162 cases of statin-induced interstitial lung
disease had been reported to the Food and Drug
Administration, with calculated rates of less than
1 reported case per 5 million prescriptions for
the most commonly used statins.19 A review of
statin-induced interstitial lung disease summarizes the existing literature on this topic, which
consists entirely of case reports and series.19 The
spectrum of associated radiographic features was
broad and included diffuse ground-glass abnormalities, multifocal opacities, and fibrosis; pleural
involvement was also described. In some cases,
elevated eosinophil levels were present in the peripheral blood, bronchoalveolar-lavage fluid, or
both; this finding is suggestive of a hypersensitivity reaction. Furthermore, in some cases, statininduced interstitial lung disease was associated
with the development of suspected statin-induced
systemic lupus erythematosus or dermatomyositis.20,21 A recent report also showed statin use to
be associated with an increased incidence of interstitial lung abnormalities in smokers.22
m e dic i n e
First, several years before the development of
dyspnea, the patient had back pain radiating to
the leg that impaired her exercise tolerance. Second, she has a child who had had a head injury
7 years earlier (as a teenager), with resulting functional impairment, and this situation continues to
be stressful for the patient. Perhaps as a result of
her child’s experience, this patient might have a
tendency to react to any symptom she has with
alarm. I explored the left chest by means of thoracoscopy. There were no pleural adhesions; there
were pleural plaques, predominantly in the apex,
and I could not feel the apical nodule that was
seen on imaging. I performed an apical wedge
resection, and the resection specimen contained
the nodule.
Cl inic a l Di agnosis
Interstitial lung disease, possibly cryptogenic organizing pneumonia.
Dr . B a r r y S . She a’s Di agnosis
Summary
On the basis of the clinical scenario provided,
my unifying diagnosis for this patient is myopathy
and interstitial lung disease due to statin use. The
key to this diagnosis is the discordance between
the patient’s dramatic functional limitation and
the normal results of pulmonary-function testing
and extent of radiographic abnormalities. Supporting information includes the presence of leg
fatigue, elevated serum aminotransferase levels,
and statin use. I would have obtained measurements of serum muscle enzymes (creatine kinase,
aldolase, and lactate dehydrogenase) to assess for
myositis, considered a trial of statin discontinuation, and evaluated the patient for other nonpulmonary causes of dyspnea and exercise limitation.
Dr. Eugene J. Mark: The patient was seen by Drs.
David Kanarek (Pulmonary and Critical Care) and
Henning Gaissert (Thoracic Surgery). We have
asked Dr. Gaissert for his impressions.
Dr. Henning A. Gaissert: Dr. Kanarek thought
that the features seen on the imaging studies
were probably not indicative of sarcoidosis and
favored a diagnosis of interstitial lung disease,
possibly cryptogenic organizing pneumonia. I
was asked to perform a lung biopsy.
Two additional features of this patient’s history may have played a role in the presentation.
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of
Statin-induced myopathy and interstitial lung
disease.
Pathol o gic a l Discussion
Dr. Mark: The principal pathological feature was
marked pleural thickening by dense fibroelastotic
tissue (Fig. 3A). The process was relatively confined
to the pleura, although there was extension into
the lung parenchyma along lobular septa (Fig. 3B)
and deformation of normal pulmonary architecture in the subpleural region (Fig. 3C). A few active fibroblastic foci were present in the areas of
fibrosis extending into the subjacent lung (Fig. 3D).
These findings are commonly associated with
usual interstitial pneumonia, but they can be
seen in patients with other conditions. An elastic-tissue stain revealed a prominent component
of elastic tissue (Fig. 3E). These pathological features are distinctive and characteristic of idiopathic pleuroparenchymal fibroelastosis (PPFE).
The histopathological findings associated with
idiopathic PPFE include a particularly dense elastotic subpleural band, with more elastic tissue than
collagen in the scar.23-28 There may be extension
of fibrosis into the interstitium in the underlying
lung. A few active fibroblastic foci may be present
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A
B
P
P
P
D
C
P
P
A
A
P
A
L
P
E
Figure 3. Lung-Biopsy Specimen.
Panels A through D show hematoxylin and eosin staining of a lung‑biopsy specimen. Panel A shows marked fibrous
thickening of the pleura (P), with sharp demarcation from the underlying lung (dashed line). Panel B shows that fi‑
brous tissue extends from the pleura (P) into the subjacent lung along a lobular septum (between dashed lines).
Panel C shows alveolar simplification, with deformation and ectatic air spaces (A) beneath the pleura (P). Panel D
shows an isolated active fibroblastic focus (oval) at the interface between the pleural fibrosis (P) and subjacent nor‑
mal lung (L). Panel E shows a Verhoeff–van Gieson elastic stain of the thickened pleura, revealing numerous thick
elastic fibers in the collagenous tissue.
at the interface of the elastotic scar in the sub- monia, and the absence of temporal heterogenepleural lung parenchyma. The absence of a dif- ity serves to differentiate this condition from usual
fuse lymphocytic infiltrate serves to differentiate interstitial pneumonia.
this condition from nonspecific interstitial pneuThe clinical features may be less distinctive
n engl j med 372;18
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1755
The
n e w e ng l a n d j o u r na l
than the pathological features.29-32 Predominant
involvement of the upper lung zones and a chronic progressive course are common. Pneumothorax is relatively common. There is a small number
of reported cases; these consist principally of
case reports in previous decades and small case
series in recent decades. There is variation in the
taxonomy at this time and no complete agreement
about whether idiopathic PPFE should be viewed
as a specific type of interstitial lung disease.
The histopathological differential diagnosis
of PPFE includes a particularly extensive pleural
apical cap, asbestos-related pleural fibrosis, collagen vascular disease resulting in interstitial
fibrosis with predominant pleural involvement, a
drug reaction, and diffuse pleural scarring with
myriad causes. The pathogenetic mechanisms of
idiopathic PPFE are unclear. It is possible that
the disease is a variant of usual interstitial pneumonia or nonspecific interstitial pneumonia, that
the disease is some form of pneumoconiosis, that
some cases in patients who have undergone lung
transplantation represent chronic allograft rejection, or that the disease is an exaggerated form
of a pleural apical cap. A few familial cases have
been reported.
Since the cause of PPFE is unknown, we were
intrigued by Dr. Shea’s diagnosis, which was submitted shortly before the conference, and wondered if in fact the disease in this case might be
related to statin use. However, on further review
of the patient’s record, we found that the statin
had been introduced only a few weeks before the
visit to the pulmonary clinic and thus could not
account for her symptoms or lung disease. We
also belatedly noticed that the discrepancy between the patient’s symptoms of breathlessness
and exercise tolerance had not been sufficiently
highlighted; the patient had described dyspnea
with exercise but was still able to complete her
daily routine of walking and jogging 4 miles.
Dr. Shea, we apologize for these oversights
and appreciate your willingness to discuss the
case further.
Dr. Shea: PPFE is an interesting pathological
diagnosis that has been identified as a distinct
clinicopathological entity in recent decades. The
original report of PPFE in the English literature
described a series of patients with disease predominantly involving the upper lung zones that
was characterized by dense fibroelastosis of the
1756
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visceral pleura and adjacent lung parenchyma.30
In this initial report and several subsequent reports, many persons with this disease had had
previous exposure to chemotherapeutic agents,
had undergone bone marrow transplantation, or
both.24,25,29,30 In one case series, one patient had
been receiving a statin, and in another series,
about half the patients had serologic features suggestive of an underlying autoimmune process.
Therefore, although PPFE may be idiopathic in many
cases, it may also occur as a secondary process
in response to an underlying condition. The vast
majority of patients with PPFE appear to have
clinically significant impaired lung function, and
most have disease progression over time, even
when they are treated aggressively with glucocorticoids and immunosuppressive therapy.28
The pathological diagnosis of PPFE fits with
the radiographic abnormalities seen in this case.
However, it would not explain the apparently
dramatic decrease in exercise tolerance described
in the case history, given the minimal extent of
disease and the normal results of pulmonaryfunction tests. If the patient’s functional decline
was as substantial as she indicated, then alternative explanations would need to be explored. However, it appears that her functional impairment
was not as substantial as had been implied in the
case history.
Dr. Mark: Would you comment on the findings
on imaging studies in the context of this diagnosis, Dr. Sharma?
Dr. Sharma: The CT findings correlate with the
pathological findings. Dr. Shea’s differential diagnosis describes how we assess the distribution
of disease, which is both predominant in the upper lung zones and peripheral. The combination
of pleural thickening, linear densities, and pleuroparenchymal opacities is difficult to explain by
any of the conditions that we considered, except
for this new entity of PPFE. Although it is very
rare, we may see it more in the future.
Dr. Shea: An important question is whether
autoimmune disease could play a role in this disease. Ankylosing spondylitis can be associated
with pleuroparenchymal fibrosis with predominant involvement of the upper lung zones.
Dr. Mark: How many people in the audience have
thought of or made the diagnosis of idiopathic
PPFE? Four out of 75. Even among a group of
specialists, this diagnosis is not well recognized.
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Case Records of the Massachuset ts Gener al Hospital
Dr. Martin P. Solomon (Internal Medicine, Brigham
and Women’s Hospital): I’m the patient’s primary
care doctor, and I’d like to make a couple of points.
One is that her presenting symptom was breathlessness. We treated her for asthma but went ahead
with the chest radiograph and further evaluation.
Although fatigue has been mentioned, her primary symptom is still breathlessness. The social
aspect of the history that was brought up by Dr.
Gaissert is very important. This woman is surrounded by illness and tragedy; her child was
struck by a car in front of her and is now dependent on her for care.
The final point is that this woman, who is
anxious and frightened, was first told she might
have cancer and was then told that she had a
rare disease that might require lung transplantation, which kept her in a state of panic. Although
her dyspnea has not worsened and she is able to
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A nat omic a l Di agnosis
Idiopathic pleuroparenchymal fibroelastosis.
This case was presented at “Thoracic Pathology: Fifth Annual
Course,” directed by Eugene J. Mark, M.D., and William D. Travis, M.D., and sponsored by the Harvard Medical School Department of Continuing Education.
No potential conflict of interest relevant to this article was
reported.
Disclosure forms provided by the authors are available with
the full text of this article at NEJM.org.
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