NEJM的一个病例，感觉不错，大家看看。
A 79-Year-Old Woman with Myalgias, Fatigue, and Shortness of Breath.Dr. Celine R. Gounder (Department of Medicine): A 79-year-old woman was admitted
to the hospital because of myalgias, fatigue, and shortness of breath.
Hyperlipidemia had been diagnosed six years earlier and had been controlled
with simvastatin. Three years before admission, treatment with simvastatin was
discontinued because of myalgias, and atorvastatin was started. Seven months before
admission, pain developed over the lateral aspect of the chest wall bilaterally,
extending from the axillas to the middle of her rib cage. The area was sore to the
touch, but the pain was not affected by activity or changes in position. It did not
awaken her from sleep. She also felt a lump in her throat when swallowing and
had pain that radiated to her right ear. She discontinued atorvastatin, and the
symptoms gradually resolved. One to two months later, she resumed atorvastatin,
and the symptoms recurred, along with fatigue and reduced tolerance for exercise.
Because of this, one month before admission, ezetimibe was added to her medications,
and the dose of atorvastatin was reduced from 20 mg to 10 mg per day. Two
days later, bilateral shoulder aches and neck and back pain developed. She stopped
taking both ezetimibe and atorvastatin, but the symptoms persisted.
Eleven days before admission, she saw her primary care physician. She had what
she described as “unbearable” pain in the morning and difficulty arising from her
bed and from chairs, a sore throat, and pain over the lateral aspect of the chest wall
bilaterally, extending from the axillas to the middle of her rib cage. On examination,
there was normal range of motion of all joints. There was tenderness with
abduction of the shoulders at about 45 degrees, worse on the left than the right.
Motor strength was 4+ out of 5+ in all muscle groups of the arms and legs. There
was no muscle tenderness. The results of liver- and renal-function tests and the
levels of serum electrolytes, creatine kinase, aldolase, and aminotransferase were
normal. Hematologic test results are shown in Table 1.
During the next week, the pain and fatigue persisted, and weakness worsened.
The patient reported continuing difficulty arising from a chair and difficulty combing
her hair. She did not have headaches, visual changes, jaw claudication, difficulty
chewing food, fevers, night sweats, or a change in weight. Four days before admission,
she again saw her primary care physician, who documented increased proximal
muscle weakness; the findings on physical examination were otherwise unchanged.
Prednisone was started at a dose of 20 mg per
day. The pain and weakness improved, but two
days before admission progressively worsening
shortness of breath developed with minimal exertion
and with prolonged speaking. She did not
have chest pain or palpitations. She was admitted
to this hospital.
The patient had had a myocardial infarction
six years before admission that had required
placement of a stent in the right coronary artery.
Ten years before admission, a diagnosis of breast
cancer had been made; the cancer had been treated
by lumpectomy and radiation therapy, with no
recurrence. The patient had had several admissions
to the hospital for management of pancreatitis
and pseudocyst formation. Eight months
before admission, an endoscopic ampullectomy
had been performed for treatment of an ampullary
adenoma. Six weeks before admission, an
episode of atrial fibrillation occurred, which was
controlled with metoprolol. A cardiac ultrasonographic
examination at that time showed trace
mitral regurgitation and an ejection fraction of
67 percent.
There was a history of anxiety, depression,
osteoarthritis, and gastroesophageal reflux. The
patient’s mother and an aunt had had breast cancer;
her father and two brothers had had coronary
artery disease, and a sister had died of lung
cancer. She was a retired widow who lived alone;
a son and daughter were well. She had never
smoked, and she drank alcohol rarely. Her medications
on admission were prednisone, aspirin,
venlafaxine, esomeprazole, lorazepam, ranitidine,
and metoprolol.
On physical examination, the patient was alert
and in no distress. The temperature was 36.7°C,
the blood pressure 130/70 mm Hg, and the pulse
78 beats per minute with a regular rhythm; the
respiratory rate was 16 breaths per minute. The
head and neck appeared to be normal without
areas of tenderness; the temporal arteries were
not palpable or tender. There was no cervical or
axillary lymphadenopathy. Inspiratory crackles
were heard at both lung bases. The heart sounds
were normal without murmurs. The abdomen was
soft and nontender without masses or organomegaly.
There was pitting edema (+) of the legs
extending proximally to 3 cm below the knees.
The peripheral pulses were easily felt, and the
distal extremities were warm. The motor strength
was rated 5 out of 5 in all muscle groups. An
electrocardiogram demonstrated a normal sinus
rhythm with a rate of 90 beats per minute and
Q waves in leads II, III, and aVF. A chest radiograph
demonstrated patchy bibasilar atelectasis.
Hematologic laboratory results are listed in Table
1. Her symptoms improved over the next two
days while she was receiving the same dose of
prednisone, and she was discharged on the third
hospital day.
Shortly after discharge, the patient’s sore throat
and hoarseness recurred. A diagnostic procedure
was performed one week later.
DIFFERENTIAL DIAGNOSIS
Dr. Nancy Lee Harris (Pathology): Dr. Finn will give
us the general internist’s perspective on this case.
Dr. David S. Finn: This patient initially presented
to my office with generalized muscle aches. She
had a known history of coronary artery disease;
her low-density lipoprotein cholesterol level was
above 70 mg per deciliter (1.80 mmol per liter),
and she had not been able to tolerate doses of
atorvastatin greater than 10 to 20 mg in the past;
these doses caused myalgias with normal creatine
kinase levels. One week before her presentation at
my office, ezetimibe, at a dose of 10 mg per day,
had been added to her regimen in accordance with
the 2004 National Cholesterol Education Program
guidelines.1
The patient had stopped taking the ezetimibe
several days before the office visit after reading
the package insert, which listed all her symptoms
as possible side effects from the medication. An
examination revealed mild weakness of the upper
and lower extremities that was greater proximally
than distally. There was no synovitis on
examination, and she had full range of motion
of all her joints without pain. The initial intervention
was to continue to withhold her lipidlowering
medications, on the assumption that
these were responsible for her symptoms.
The incidence of statin-associated myalgias
ranges from 1 to 5 percent in the randomized,
controlled trials in which the symptom is reported.
2 This level did not differ markedly from that
of placebo in most trials. This small percentage,
however, is in vast contrast to the clinical experience;
25 percent or more of patients in surveillance
databases report myalgias, with the average
between 5 to 10 percent.2 The cause of this large
discrepancy between the clinical-trial experience
and the outpatient-practice experience is unclear,
but there is some evidence that patients can have
a statin-associated myopathy with normal levels
of creatine kinase.3 Ezetimibe has also been reported
to cause myalgias in up to 4 percent of
patients, and there have been additional case reports
of myositis associated with the combination
of atorvastatin and ezetimibe.4
My initial differential diagnosis also included
polymyalgia rheumatica, temporal arteritis, a viral
infection, subacute bacterial endocarditis, hypothyroidism,
inflammatory arthritis, and even a recurrence
of breast cancer in the form of a paraneoplastic
syndrome. A recent test showed a
normal level of thyroid-stimulating hormone. I
ordered routine laboratory tests, and the patient
was instructed to return to the office in one week.
At the time of her return, she had increased weakness,
much greater proximally than distally, as
well as fatigue. On examination, there was increased
proximal muscle weakness, but no other
abnormalities were evident, and no abnormality
was noted on palpation of the temporal arteries.
The laboratory-test results were normal except for
an elevated erythrocyte sedimentation rate and a
decrease in the hematocrit from her usual level
of 38 percent to 35 percent. The combination of
her symptoms, her elevated sedimentation rate,
and the general lack of an alternative cause led me
to a diagnosis of polymyalgia rheumatica.
I prescribed 20 mg per day of prednisone, with
the expectation that the patient would have a
dramatic improvement in her symptoms over the
next 48 to 72 hours. When I spoke with her on
the telephone four days later, she reported that the
myalgias had improved, but increasing dyspnea
had developed, to the extent that she was unable
to perform her activities of daily living.
At this point, she clearly had a systemic inflammatory
condition with fatigue, weakness, dyspnea,
pharyngitis, elevated inflammatory markers, and
a new anemia. Although she did not have many
of the typical symptoms of giant-cell arteritis
(headache, jaw claudication, and visual changes),
many patients do not present with typical symptoms,
and 4 percent of patients pre sent with
chiefly respiratory symptoms. Although the patient
had some improvement while taking lowdose
corticosteroids, it was not the dramatic improvement
I had expected to see in a patient with
polymyalgia rheumatica. The alternative diagnoses
(subacute bacterial endocarditis, cancer, and
other infections) all seemed unlikely. I began to
suspect the diagnosis of giant-cell arteritis and
admitted her to the hospital for further evaluation.
I asked for consultation from the rheumatology
service.
Dr. Jonathan Kay: This 79-year-old woman presented
with fatigue and the relatively sudden onset
of bilateral shoulder, neck, and back pain,
which were most pronounced on awakening and
did not improve with discontinuation of ezetimibe
and atorvastatin. She experienced difficulty arising
from chairs but had normal levels of muscle
enzymes, suggesting that her symptoms were not
due to a primary myopathic process. However, she
had a mild anemia, and her erythrocyte sedimentation
rate was markedly elevated at 90 mm per
hour. Four days before admission, she had been
started on oral prednisone (20 mg daily).
Her clinical presentation is typical of polymyalgia
rheumatica, for which two sets of diagnostic
criteria have been formulated empirically — by
Chuang et al.5 and Healey.6 Both sets of criteria
require the presence of pain and stiffness persisting
for at least one month and involving two of
the following areas: neck, shoulders, and pelvic
girdle. Patients must be 50 years of age or older
and have an erythrocyte sedimentation rate elevated
to more than 40 mm per hour. All other
diseases that might cause these musculoskeletal
symptoms, other than giant-cell arteritis (which
can be associated with polymyalgia rheumatica),
must be ruled out. In addition, Healey’s diagnostic
criteria require a rapid response to prednisone
therapy at a daily dose no higher than
20 mg; despite some initial improvement, this patient’s
symptoms worsened while she received
this therapy.
What other conditions might cause this woman’s
musculoskeletal symptoms? As Dr. Finn has
mentioned, statin drugs may cause a painful myopathy,
but there was no elevation of the level of
muscle enzymes and her symptoms did not improve
with the discontinuation of her lipid-lowering
medications. Idiopathic inflammatory myopathies,
such as polymyositis, dermatomyositis,
and inclusion body myositis, also would be accompanied
by elevated levels of muscle enzymes
and usually by painless muscle weakness. About
15 percent of patients with rheumatoid arthritis
present with polymyalgia rheumatica, with neck,
shoulder, and pelvic-girdle pain and stiffness.
However, this patient had no joint swelling or
tenderness. Patients with degenerative arthritis
may perceive pain above or below involved joints,
but the morning stiffness that this woman had is
more characteristic of an inflammatory process.
A patient with hypothyroidism may present
with fatigue and muscle pain. However, these
clinical manifestations usually are accompanied
by elevated levels of muscle enzymes and other
features of hypothyroidism, such as abnormal reflexes,
low levels of thyroid hormone, and elevated
levels of thyroid-stimulating hormone. Patients
with fibromyalgia and other diffuse pain syndromes
— which often accompany sleep disorders,
7 depression,8 and past physical or sexual
abuse9 — may present with fatigue and neck,
shoulder, and pelvic-girdle pain and stiffness that
are more pronounced on awakening. However,
patients with hypothyroidism or diffuse pain syndromes
also perceive pain in other areas and usually
do not have anemia or a marked elevation of
the erythrocyte sedimentation rate.
With this woman’s history of breast cancer,
one must take into consideration that her neck,
shoulder, chest-wall, and low-back pain might herald
metastatic breast cancer. Furthermore, some
cancers may be accompanied by a paraneoplastic
syndrome that resembles polymyalgia rheumatica,
with an elevation of the erythrocyte sedimentation
rate that is associated with the pres ence of
the cancer.10 However, the onset of polymyalgia
rheumatica is often so sudden that the patient may
recall the exact date when symptoms first began,
whereas that of a paraneoplastic syndrome mimicking
polymyalgia rheumatica is much more
gradual. The most reliable feature that differentiates
polymyalgia rheumatica from a paraneoplastic
syndrome is the response to therapy: patients
with polymyalgia rheumatica usually experience
marked and rapid improvement of their pain
within four to five days of beginning treatment
with daily oral prednisone at doses of 20 mg or
less, whereas those with underlying malignant
tumors do not have improvement until the cancer
is treated successfully.
Giant-cell arteritis and polymyalgia rheumatica
are part of a single disease spectrum. Patients with
giant-cell arteritis and polymyalgia rheumatica
have a low frequency of the HLA-DRB1*01 allele.
As with rheumatoid arthritis, there is an association
with the HLA-DRB1*04 allele.11 A sequence
polymorphism in the second hypervariable region
of the HLA-DR molecule antigen-binding site has
been identified.12 The disease occurs more commonly
in people of northern European ancestry
than in other ethnic groups and may aggregate
in families.13
This woman reported no constitutional symptoms,
such as fever, night sweats, or weight loss.
She reported no headache, visual changes, or jaw
claudication, which might be symptoms of giantcell
arteritis, a large-vessel vasculitis that occurs
in some patients with polymyalgia rheumatica.
We are told that she had no areas of tenderness
on her head or neck, nor did she have thickening
of her temporal arteries, which is a typical physical
sign of giant-cell arteritis. The true prevalence
of giant-cell arteritis among patients with polymyalgia
rheumatica is not defined, because patients
presenting with polymyalgia rheumatica do
not routinely undergo temporal-artery biopsy. In
one report,14 giant-cell arteritis was demonstrated
in temporal-artery–biopsy samples from 41 percent
of patients with a clinical diagnosis of polymyalgia
rheumatica. Of these, 47 percent presented
without cranial symptoms. Thus, in the setting of
polymyalgia rheumatica and an elevated erythrocyte
sedimentation rate, one cannot rely on the
absence of cranial symptoms to rule out a diagnosis
of giant-cell arteritis.
Up to 10 percent of patients with giant-cell
arteritis have pulmonary symptoms.15 This patient
noted a sore throat; subsequently, progressively
worsening shortness of breath developed with
minimal exertion and with prolonged speaking.
Inspiratory crackles were heard at both lung
bases and patchy bibasilar atelectasis was evident
on a chest radiograph. Cough is the most common
presenting pulmonary symptom of giant-cell
arteritis. Sore throat, presumed to be a symptom
of ischemia involving the arteries that supply the
laryngeal and pharyngeal tissues, occurs almost
as frequently as cough. Peribronchial and interstitial
granulomas that have been found in tissue
obtained by transbronchial lung biopsy from a
patient with giant-cell arteritis have been interpreted
as being consistent with pulmonary involvement
by giant-cell arteritis.16
The diagnostic procedure in this case should
have been a temporal-artery biopsy to look for evidence
of giant-cell arteritis. Although all attempts
should be made to perform the temporal-artery
biopsy before or soon after the initiation of prednisone
therapy, findings diagnostic of giant-cell
arteritis still may be observed even after more than
14 days of prednisone therapy.17
Dr. Finn: The patient was seen in consultation
by the surgical service; a temporal-artery biopsy
was performed. 太长了，有可能请翻译过来？
呵呵 。。。。。。没看就头晕了 考我到的外文了。怕怕。
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