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Introduction: Weakness is one of the
most common problems for which patients seek health care. But
sometimes a common problem can be a sign of an uncommon group
of diseases. What distinguishes myositis from other causes of
weakness is inflammation triggered by an over-active immune
system, resulting in muscle damage. The major forms of
myositis treated by a rheumatologist include polymyositis
(PM), dermatomyositis (DM), and inclusion body
myositis (IBM).
Only about 5 new myositis cases per 1 million
population in the United States are diagnosed every year. For
PM and DM, the most common ages of onset cluster around two
age groups: between 10 and 15 years of age and between 45 and
60 years of age. Childhood-onset myositis is more often DM,
while adults more often develop PM. Women outnumber men for
both conditions by about 2:1. IBM, on the other hand, tends
to develop in patients over the age of 50, and men outnumber
women 2:1. Because IBM is the rarest of the above conditions,
we will focus most of our discussion on PM and DM.
The outlook for patients with myositis has improved
with the discovery of effective therapies within the last
several decades. Overall, 5 year survival rates are 80% for
those with PM and DM, and these figures are more favorable for
those with childhood-onset disease. Involvement of other
organs (see below) or development of cancer (seen in DM
patients) are the top causes of death. While IBM is less
responsive to treatment and is associated with more long-term
disability than the other two forms of myositis, this
condition is associated with better survival rates due to its
slow progression.
Features of Myositis: The
weakness of PM and DM tends to occur mostly in the large
muscles of the shoulder, hip, and thigh region. Patients will
often report that it is difficult for them to keep their arms
above their head (to fix their hair, for example) or for them
to climb stairs or get out of chairs or back seats of cars.
These symptoms tend to progress gradually, and the weakness is
typically not associated with pain unless the patient is
experiencing an acute flare of muscle damage and
inflammation. Neck muscles, abdominal muscles, and muscles
further down the arms and legs tend to become affected less
commonly. By contrast, IBM is more slowly progressive but can
involve muscles of the forearms and hands more commonly early
in the course of the disease.
In patients with DM, a rash may occur in various
locations. Most typically, the skin above the eyelids
develops a red or purplish discoloration (known as a
heliotrope rash) or the skin over the knuckles of
the hands develops red raised or scaly patches (known as
Gottron�s papules). Other findings may include fissures
around the fingers known as mechanic�s hands, calcium
deposits under the skin known as calcinosis (also seen
in scleroderma), or small dilated blood vessels around the
cuticles of the fingernails. In up to 10 or 20% of
individuals, the rash may occur in the absence of any sign of
muscle involvement (called amyopathic DM).
Other organs may occasionally become inflamed in
patients with PM or DM. The esophagus may become weak,
impairing swallowing function and potentially resulting in
food or stomach contents being aspirated into the lungs. Lung
inflammation can occur as a direct result of inflammation and
cause difficulty breathing or scarring in the lungs. The
heart muscle may also become inflamed and cause rhythm
disturbances or heart failure. Both PM and DM may also be
accompanied by arthritis, cold-induced color changes in the
fingers (Raynaud�s phenomenon), or may overlap with
other rheumatic diseases such as rheumatoid arthritis (RA),
systemic lupus erythematosus (SLE) or systemic sclerosis (SScl)
(see related sections).
A final noteworthy feature of myositis is the
association with cancer, mainly observed with adult-onset DM.
On the average, about 25% of patients with DM are diagnosed
with cancer, about a 6-fold increase over individuals of the
same age in the general population. Solid tumors are most
often encountered rather than leukemia, with ovarian cancer
possibly being most strongly associated with DM. In about 80%
of cases, cancer and DM are diagnosed with one year of each
other. In spite of this association, the presence or absence
of cancer and the disease activity of DM do not always go hand
in hand, and removal of the tumor does not always result in
improvement in signs of DM.
Diagnosis: Criteria for diagnosing PM
and DM were devised in the 1970�s but are still in use today.
They include:
- History of and findings on physical
examination of muscle weakness of
hip and/or shoulder region
- Elevation of muscle enzymes on laboratory
testing
- Evidence for abnormal muscle activity on
electromyography (EMG) testing
- Findings of inflammation on muscle biopsy
- Typical rash of DM as described above
For a �probable� diagnosis of PM, 3 of the first 4
criteria are required, while for a �definite� diagnosis of PM,
all 4 are needed. For DM, #5 is included.
The first criterion listed above is simply evaluated
during physical examination by an experienced physician.
Testing muscle strength is both a useful way to evaluate a
patient with possible myositis and a useful way to follow a
patient�s progress after the diagnosis is made. A doctor may
test a patient�s strength directly or time them on performing
an activity (arising from a chair, for example) to determine
the function of the muscles.
Laboratory tests are often useful in evaluating
myositis. Muscle enzyme elevations are seen in at least
90-95% of patients with PM and DM but are often less elevated
in patients with IBM. The creatinine phospho-kinase (CPK)
is the most widely used and most accurate muscle enzyme that
is elevated in these conditions, but the CPK may be elevated
in other diseases as well or may be abnormal in some
individuals with no apparent muscle disease. The aldolase
is another enzyme that is often elevated in myositis, as well
as the LDH, SGOT, and SGPT, tests that
can also be elevated when liver damage is present. These
enzyme levels should return to normal or near normal levels as
the patient is treated, but the CPK level usually improves
before a return in strength is observed, and some will remain
weak even when the muscle enzyme levels improve.
Antibody testing is often abnormal in PM and DM but
frequently unhelpful in patients with IBM. The antinuclear
antibody (ANA), also seen in SLE, is elevated in
60-75% of PM or DM patients. Other more specific studies
known as myositis-specific antibodies may be ordered if
needed to clarify the diagnosis, and many of these antibodies
may predict more aggressive forms of the disease.
The EMG is a test involving needles that are applied to
the muscles and which measure electrical currents in the
muscles. Certain abnormal patterns are observed in 85-90%
patients with myositis and can provide valuable evidence to
support the diagnosis. This test is often painful but may be
helpful both in diagnosing and monitoring the progress of
myositis patients.
The muscle biopsy is perhaps the most useful test in
diagnosing various forms of myositis and distinguishing these
conditions from other causes of muscle weakness. Typically,
the muscle that is most weak or that is abnormal on EMG study
is chosen, and the biopsy is most commonly performed on the
thigh muscles. A small incision is made under local
anesthetic, and a small piece of muscle is removed and
examined under a microscope. Depending on the pattern of
inflammation present or the type of muscle damage that is
seen, PM, DM, or IBM may be diagnosed. For IBM, abnormal
proteins are found to be deposited in the muscle, which are
the �inclusion bodies� for which this disease is named. While
the biopsy may be nonspecific or falsely negative in a small
percentage of patients, this study usually is diagnostic and
allows the physician to confidently treat the patient
appropriately.
While not included in the criteria, magnetic
resonance imaging (MRI) is a tool that has gained
popularity recently in the evaluation of myositis. This study
is usually performed on thigh muscles and demonstrates changes
suggesting inflammation that can strongly suggest the
diagnosis and may help guide the muscle biopsy to increase the
yield of this procedure. Moreover, the MRI can be used to
assess the progress of a patient with myositis after
treatment.
Because of the association of DM with cancer, all adult
patients diagnosed with this form of myositis should be
evaluated for cancer. Most authorities in the field simply
recommend that types of cancer most common for the patient�s
age group and gender be screened. While not all cancers can
be detected, some patients can receive an early diagnosis and
possibly better outcomes if an alert physician performs an
appropriate search for the most likely malignancies expected
in each individual patient.
Even with all of these studies at our disposal, many
other conditions can mimic myositis. Weakness and/or
elevation of muscle enzymes can be seen in other nerve or
muscle disorders such as muscular dystrophy, various hormonal
diseases such as thyroid dysfunction, genetic or metabolic
diseases, infections, or exposure to certain medications such
as cholesterol-lowering drugs, to name a few. The rash of DM
may occur in sun-exposed areas and mimic SLE, and patients
with SScl often demonstrate Raynaud�s and calcinosis that are
seen with DM. A skin biopsy or certain laboratory tests may
help distinguish between these conditions. Also, as mentioned
above, other rheumatic diseases may overlap with myositis,
adding to the confusion between these diseases.
As painstaking as the diagnostic workup for myositis
may seem, it is necessary to go through these steps to assure
it has been adequately diagnosed and differentiated from other
conditions. This process helps guide therapy and avoids side
effects of inappropriate medical treatment.
Therapy: Major goals of therapy for
myositis are reducing muscle inflammation, limiting muscle
damage, and restoring muscle function. Additionally, skin
involvement for DM patients and other organs affected by the
disease process must be addressed, which typically can be
accomplished with the same medications used to treat the
muscle disease. As mentioned above, IBM patients tend to
respond less dramatically to treatment but should at least be
given a trial of therapy to determine the reversibility of
their disease before abandoning these efforts altogether.
Corticosteroids are the treatment of choice for the
majority of patients with myositis. The most commonly used
medication in this class is oral prednisone, but intravenous
forms of corticosteroids can be given to rapidly control the
disease during an acute flare. Steroids work to suppress
inflammation in the muscle and other parts of the body but
must be given in high doses initially to control the disease.
When properly administered, corticosteroids improve disease
activity in 90% of patients and may be the only form of
therapy required in over 1/2 of all patients with myositis.
When a response is observed, the dose can be gradually reduced
to minimize side effects.
Adverse effects of corticosteroids include weight gain,
weakening of the bones, elevation of blood sugar or blood
pressure, cataracts, and increased susceptibility to
infection. Ironically, these medications that are being used
to improve muscle strength and function can actually cause
muscle weakness when given at high doses for long
periods of time. Sorting out whether a patient�s weakness is
due to the disease or the medications given requires a careful
evaluation by an experienced physician.
While few well-designed studies are available to
document which medications are most effective in treating
myositis, immunosuppressive drugs such as
methotrexate (MTX), azathioprine (AZA),
cyclosporine, cyclophosphamide, or
chlorambucil have been reported to demonstrate efficacy in
patients with myositis resistant to prednisone alone or in
those unable to taper off prednisone without experiencing a
relapse. Because of more favorable side effect profiles, most
physicians prefer MTX or AZA as the next therapy after
corticosteroids for such patients.
All of these medications work more slowly than
corticosteroids but have a powerful effect on suppressing
inflammation. They also suppress the immune system and may
make patients more prone to developing infections. Some of
these medications may also reduce the bone marrow�s ability to
produce white or red blood cells, cause liver enzyme
elevations, or other less common side effects (see Medications
section). Routine monitoring is needed to achieve the balance
between safety and effectiveness of each of these drugs.
In patients with myositis resistant to these standard
therapies, particularly those with DM, intravenous
immunoglobulin G (IVIgG) has been shown in
well-designed studies to have a beneficial effect on treating
the muscle disease and occasionally other manifestations.
IVIgG consists of antibodies taken from normal donors at the
blood bank and appears to work by blocking abnormal antibodies
produced by myositis patients. This therapy is expensive and
must be given in high doses once per month for at least 3
months but is relatively safe, associated only with infusion
reactions and volume overload in some patients.
For patients with DM in whom rashes remain active and
who do not require other therapies for the muscle disease,
hydroxychloroquine (HCQ) is a safe and often
effective alternative. HCQ, under the trade name Plaquenil,
suppresses inflammation in the skin without significantly
suppressing the immune system and has little adverse effects
on other parts of the body. Because 1 in 1,000 patients may
develop changes in the eye that can impair color vision,
monitoring with an eye doctor every 6 to 12 months is
recommended to pick up these problems before they progress.
Biologic response modifiers such as the tumor
necrosis factor (TNF) blocking drugs etanercept,
infliximab, adalimumab, and rituximab, a
medication inhibiting certain types of white blood cells, have
not been well-studied but have been reported in small series
of patients to produce impressive benefits. These drugs work
specifically on parts of the immune system believed to be
involved in myositis. The TNF blockers have been widely used
in the treatment of RA and other rheumatic diseases, but all
of these medications must still be considered experimental for
treating myositis until better evidence surfaces that would
establish their role in treating such patients.
The above therapies serve to reduce muscle inflammation
and damage, but to provide optimal function, physical
therapy for muscle strengthening has been shown to be
well-tolerated and effective in myositis patients. In a way,
the medications can be seen as ways to limit muscle damage,
and exercise can be seen as a way to strengthen what muscle
tissue is left. Even in patients with early active disease,
muscle strengthening produces desirable effects if performed
under the supervision of a skilled therapist.
Myositis is a challenging group of illnesses, both to
treat and to experience as a patient. A coordinated team of
health care practitioners is necessary to provide the proper
diagnosis and treatment to maximize muscle function and
improve outcomes.
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