Clinical manifestations of dermatomyositis and polymyositis in adults

Dermatomyositis (DM) and polymyositis (PM) are idiopathic inflammatory myopathies,

characterized by the shared features of proximal skeletal muscle weakness and by evidence of
muscle inflammation .DM, unlike PM, is associated with a variety of characteristic skin
manifestations. A form of DM termed amyopathic DM (ADM, historically termed "dermatomyositis
sine myositis") is a condition in which patients have characteristic skin findings of DM without
weakness or abnormal muscle enzymes.

The other major type of idiopathic inflammatory myopathy is inclusion body myositis.

There is a female to male predominance of about two to one. The peak incidence in adults occurs
between the ages of 40 and 50

Dermatomyositis (DM) and polymyositis (PM) are both multisystem disorders with a wide variety of
clinical manifestations. Most patients exhibit proximal skeletal muscle weakness. Several
characteristic skin eruptions are typical of DM . Interstitial pulmonary disease, dysphagia, and
polyarthritis are also common in DM and PM, along with constitutional symptoms; Raynaud
phenomenon is present in some patients. Features that overlap with other systemic rheumatic
diseases, such as systemic lupus erythematosus (SLE) and systemic sclerosis (SSc), may also be
present. The risk of malignancy may be increased, particularly in patients with DM.

Muscle weakness is the most common feature of DM and PM; over 90 percent of patients with PM
present with muscle weakness. However, cutaneous manifestations often precede or accompany
weakness, which is found at presentation in only 50 to 60 percent of patients with DM. Typically mild
myalgias and muscle tenderness occur in 25 to 50 percent of cases. The distribution of weakness is
characteristically symmetric and proximal in both PM and DM. Affected muscles typically include the
deltoids and the hip flexors. Weakness of the neck flexors is also common. Distal muscle weakness, if
present, tends to be mild and usually does not cause significant functional impairment. Rarely,
patients present with focal myositis that usually but not always progresses to the typical generalized
form over time Patients usually report a history of the insidious or subacute
development of the muscle weakness, with gradual worsening over a period of several months .
However, an acute onset of weakness is occasionally reported. Patients may describe increasing
difficulty climbing stairs, getting up from a chair, carrying heavy groceries, or picking up their
children due to the proximal muscle involvement. They may notice joint pain and swelling, if
present, and they occasionally mistakenly ascribe weakness to the joint involvement. Pain is mild, if
present, and stiffness is not a prominent complaint. Muscle atrophy is generally not seen in early
cases, even in patients with marked weakness, but it may occur in severe, longstanding disease.

Skin findings — Several distinct cutaneous eruptions, which are generally evident at the time of
clinical presentation, occur in DM but not in PM. Other skin changes may occur in patients with PM
and in patients with DM and are not specific to either disorder. Dermatologic manifestations may be
prominent but can be quite subtle in some patients.

Characteristic dermatomyositis findings — Gottron's papules and the heliotrope eruption are the
hallmark and likely pathognomonic features of DM. Gottron's sign, photodistributed erythema,
poikiloderma, nailfold changes, scalp involvement, and calcinosis cutis are also characteristic and
useful in distinguishing DM from PM.

●Gottron's papules – Gottron's papules are erythematous to violaceous papules that occur
symmetrically over the extensor (dorsal) aspects of the metacarpophalangeal (MCP) and
interphalangeal (IP) joints. In addition, these lesions may involve the skin between the MCP and IP
joints, particularly when the eruption is prominent. Gottron's papules often have associated scale
and may ulcerate. When scaling is present, the lesions may mimic psoriasis or lichen planus.

●Gottron's sign – presence of erythematous to violaceous macules, patches, or papules on the

extensor surfaces of joints in sites other than the hands, particularly the elbows, knees, or ankles.
●Heliotrope eruption –erythematous to violaceous eruption on the upper eyelids, sometimes
accompanied by eyelid edema, which, at times, may be quite marked
●Facial erythema –midfacial erythema that can mimic the malar erythema seen in SLE. In contrast to
those with SLE, patients with DM will often have involvement of the nasolabial fold, which can be
helpful in distinguishing these two photosensitive midfacial eruptions. ●Photodistributed
poikiloderma (including the shawl and V signs) – Poikiloderma refers to skin that demonstrates both
hyperpigmentation and hypopigmentation, as well as telangiectasias and epidermal atrophy. In DM,
patients may demonstrate poikiloderma in any photo-exposed site; however, classic areas of
involvement are the upper back (shawl sign) and the V of the neck and upper chest. The
poikiloderma in DM often presents with a violaceous hue. Early in the course of cutaneous disease,
these areas may demonstrate only erythema rather than well-developed poikiloderma. The
erythema may be macular (nonpalpable) or papular. In rare patients, these lesions become
thickened and resemble papular mucinosis. The cutaneous eruption of DM is often associated with
significant pruritus, which may assist in distinguishing its photo-exacerbated eruption from that of
lupus erythematosus (LE).

●Holster sign – Patients with DM may also have poikiloderma on the lateral aspects of the thighs,
referred to as the "Holster sign" . It is unclear why this cutaneous manifestation occurs on this
classically photo-protected site.

●Generalized erythroderma – In rare patients, erythroderma may occur, which involves extensive
cutaneous surface area, including areas that are less exposed to ultraviolet light.

●Periungual abnormalities – The capillary nail beds in DM may be erythematous and may show
vascular changes similar to those observed in other systemic rheumatic diseases (eg, scleroderma
and SLE). Abnormal capillary nail bed loops may be evident, with alternating areas of dilatation and
dropout and with periungual erythema. In addition, cuticular overgrowth, sometimes termed
"ragged cuticles," is characteristic and may be associated with hemorrhagic infarcts within the
hypertrophic area. The degree of cuticular involvement is thought to reflect ongoing cutaneous
disease activity, representing active vasculopathy.

●Psoriasiform changes in scalp – Changes in the scalp resembling seborrheic dermatitis or psoriasis
occur in a high percentage of patients with DM. The scalp involvement in DM is diffuse, often
associated with poikilodermatous changes and with prominent scaling. Scalp involvement may result
in severe burning, pruritus, and/or sleep disturbance. In addition, severe pruritus may occur in
patients without visible disease.

●Calcinosis cutis – The deposition of calcium within the skin, a finding known as calcinosis cutis,
occurs commonly in juvenile DM. It is infrequent in adult DM. In children, calcinosis has been
associated with a delay in treatment with glucocorticoids and/or immunosuppressive therapy.
Calcinosis cutis, which is known to be very challenging to treat, may be seen in a variety of
conditions, including SSc, particularly limited cutaneous SSc; SLE (rarely); and overlap connective
tissue disorders. It may be more common in patients with DM with the anti-p140/anti-MJ
autoantibody
Skin findings in antisynthetase syndrome — Patients with either DM or PM (classically those with the
antisynthetase syndrome) may have "mechanic's hands," which present with hyperkeratotic,
fissured skin on the palmar and lateral aspects of the fingers. Occasionally, these changes result in
irregular, dirty-appearing horizontal lines that resemble those of a manual laborer
Skin findings in MDA-5-associated dermatomyositis — Patients with melanoma differentiation-
associated gene 5 (MDA-5) antibodies are now known to have a characteristic phenotype with
classic findings that include cutaneous ulceration involving the Gottron's papules, elbows, digital
pulp, and nailfolds; erythematous, painful palmar macules and papules; alopecia; oral ulcers;
arthritis; and amyopathic disease. In addition, patients with MDA-5 antibodies are at a higher risk for
interstitial lung disease (ILD), including a rapidly progressive presentation with high mortality.
Recognizing the cutaneous features are thus imperative in order to allow the clinician to closely
monitor the patient's pulmonary status, particularly in the absence of widely available autoantibody
testing.

Lung disease — ILD is an important complication in at least 10 percent of cases of DM and PM. In
DM, it can be observed in patients with either classic or amyopathic disease. In addition, respiratory
insufficiency may result from diaphragmatic and chest wall muscle weakness. The occurrence of ILD
may be associated with rapidly progressive pulmonary failure and death. ILD in the inflammatory
myopathies often occurs in the context of antisynthetase antibodies and the antisynthetase
syndrome. Malignancy — An increased rate
of malignancy has been described, with a greater risk in patients with DM. The spectrum of
malignancies generally parallels the distribution in the general population with a few possible
exceptions. Esophageal disease — Weakness of the
striated muscle of the upper one-third of the esophagus (and/or the oropharyngeal muscles)
contributes to dysphagia, nasal regurgitation, and/or aspiration .Esophageal involvement is more
common in older patients and may underlie the increased incidence of bacterial pneumonia [28].

Cardiac disease — Cardiac involvement with histologic evidence of myocarditis is well-described in

DM and PM, and subclinical manifestations are frequent, including conduction abnormalities and
arrhythmia detected by electrocardiographic studies. Symptomatic cardiac disease, such as
congestive heart failure, is less common. However, patients with DM and PM are also at increased
risk for myocardial infarction .The use of serum creatine kinase (CK), the CK-MB/total CK ratio, and
cardiac troponin T in evaluating patients for cardiac involvement is problematic in patients with
inflammatory myositis, and additional testing may be required in patients in whom a myocardial
infarction is suspected clinically Antisynthetase syndrome — Up to 30
percent of patients with DM or PM have a constellation of clinical findings termed the
"antisynthetase syndrome" . These findings include relatively acute disease onset, constitutional
symptoms (eg, fever and weight loss), myositis, the Raynaud phenomenon, mechanic's hands,
arthritis that is generally nonerosive, and ILD [41]. Affected patients have antibodies to aminoacyl-
transfer ribonucleic acid (tRNA) synthetase enzymes; the presence of one of these antibodies is
highly specific for DM, PM, or ILD ●Not all patients with antisynthetase antibodies or even those
classified as having the antisynthetase syndrome have all manifestations of this syndrome. The
syndrome is generally considered present in patients with an antisynthetase antibody plus two of
the following features, which are elements of the syndrome: ILD, inflammatory myopathy, and
inflammatory polyarthritis.

●This group of clinical findings or this general clinical picture is not specific for antisynthetase
antibodies. Patients with other types of autoantibodies (eg, anti-PM-Scl or anti-U1 ribonucleoprotein
[RNP] antibodies) can also present with these types of features. However, patients with
antisynthetase antibodies generally have more prominent or severe myositis and ILD, and they
usually lack some of the other clinical features seen in patients with these other autoantibodies.
●Some patients with antisynthetase antibodies have relatively little or no myositis, while ILD or
other features are more prominent. The absence of myositis is seen more often with some
antisynthetase antibodies than with others.

Amyopathic dermatomyositis : classic cutaneous findings of DM without clinical evidence of muscle

weakness . There are two subsets within this group. One subset, referred to as "hypomyopathic
dermatomyositis" (HDM), has subclinical evidence of myositis upon investigation by laboratory,
electromyography, muscle biopsy, or imaging despite a lack of clinical muscle weakness; the other
subset, classified as "amyopathic dermatomyositis" (ADM), includes patients without clinical
weakness and without either laboratory or muscle study abnormalities.ADM is considered
"provisional" after six months and "confirmed" after two years [49,50]. A definite diagnosis of ADM
is further supported by such patients having neither received systemic immunosuppressive therapy
for more than two consecutive months within the first six months of skin disease onset nor taken
drugs known to induce DM-like skin changes .

CADM comprises 10 to 30 percent of DM cases. Patients with CADM also appear to be at increased
risk for internal malignancy, although this risk may be less than for patients with DM. In addition,
some evidence suggests that the presence of anti-MDA-5 antibodies, previously referred to as anti-
CADM-140 autoantibodies, suggests that the patient is likely to have amyopathic disease and
characteristic cutaneous findings [ Overlap
syndromes — DM and PM may overlap with features of other connective tissue diseases, particularly
scleroderma, SLE, and mixed connective tissue disease, as well as (less often) rheumatoid arthritis
and Sjögren's syndrome. The myopathy associated with the other connective tissue diseases varies
from clinically insignificant (with minimal muscle enzyme elevations and minimal inflammatory
changes on muscle biopsy) to typically severe DM or PM in which myopathy dominates the clinical
picture

LABORATORY FINDINGS — Several laboratory findings are characteristic of dermatomyositis (DM)

and polymyositis (PM). These include:

●Elevated levels of muscle enzymes ●Autoantibodies, including antinuclear antibodies, in up to 80

percent of patients with DM and PM . myositis-specific autoantibodies, in at least 30 to 40 percent of
patients; and myositis-associated autoantibodies, especially in patients with overlap syndromes

●Elevated levels of serum and urine myoglobin .The erythrocyte sedimentation rate (ESR) is often
normal or is only mildly elevated, even in patients with active muscle disease [5].

Muscle enzymes — Creatine kinase (CK), lactate dehydrogenase (LD), aldolase, aspartate
aminotransferase (AST), and alanine aminotransferase (ALT) are all muscle enzymes that may be
elevated in patients with inflammatory myopathy and other muscle disorders. At some point in the
course of the disease, almost all patients with DM and PM, except those with amyopathic DM
(ADM), have an elevation in at least one muscle enzyme; most have elevations in all enzymes. The
level of serum CK can vary widely. In untreated patients with active muscle disease, it is usually more
than 10-fold the upper limit of normal (ie, at least 2000 to 3000 international units/L). In severe
cases, the serum CK concentration may be elevated more than 50-fold or even 100-fold (ie, up to
10,000 to 20,000 international units/L), and higher levels are sometimes seen. A correlation between
the severity of the weakness and the height of elevation in serum muscle enzymes may be seen,
although the degree of muscle dysfunction may be much greater than the enzyme levels would
suggest. In some cases, there may be elevations in serum muscle enzymes without discernible
muscle weakness. This is particularly observed in patients with early disease. The occurrence of
muscle weakness with relatively normal enzyme levels is more likely to occur in DM than PM. Other
patients with no clinical muscle involvement, as in ADM, will also have normal enzyme levels.
Persistently low serum muscle enzyme levels in the setting of obvious muscle weakness may also
occur in patients with advanced disease and significant loss of muscle mass.

Measurement of cardiac troponin I may be helpful in patients in whom it may be difficult clinically to
determine whether elevations in CK or other muscle enzymes are due to cardiac rather than skeletal
muscle disease. Increased levels of cardiac troponin I appear relatively specific for myocardial injury,
unlike elevations of total CK, CK-MB, and other muscle enzymes or of cardiac troponin T, all of which
may be seen both in skeletal muscle inflammatory myopathy and in cardiac disease
Autoantibodies — Antinuclear antibodies may be present in up to 80 percent of patients with DM or
PM ●Myositis-specific autoantibodies, which are detected primarily in patients with inflammato ry
myositis and which may offer information regarding prognosis and potential patterns of organ
involvement ●Myositis-associated autoantibodies, which are found with other autoimmune
rheumatic diseases that may be associated with myositis

Myositis-specific autoantibodies — These autoantibodies occur in approximately 30 percent of

patients with DM and PM.There are several categories of myositis-specific autoantibodies,
including:●Antibodies to aminoacyl-transfer (t)RNA synthetases (antisynthetase antibodies),
including anti-Jo-1●Antibodies to signal recognition particle (SRP)●Antibodies to Mi-2, a nuclear
helicase

Antisynthetase antibodies — Anti-Jo-1 antibodies are the most common myositis-specific

autoantibody and the most frequently observed antisynthetase antibody. Anti-Jo-1 is seen in about
20 percent of patients with idiopathic inflammatory myopathy. These antibodies are strongly
associated with several clinical findings, including interstitial lung disease (ILD), the Raynaud
phenomenon, arthritis, and mechanic's hands

Anti-SRP antibodies — Anti-SRP antibodies are associated with severe myopathy and aggressive
disease that may be difficult to control, even with high-dose glucocorticoids and immunosuppressive
agents. These antibodies are not entirely specific for necrotizing myopathy or polymyositis, however,
as they have also been described in two patients each with limb girdle muscular dystrophy and SSc,
in a patient with the antisynthetase syndrome without myopathy, and in several patients with DM
Anti-Mi-2 antibodies — They are associated with the relatively acute onset of DM, are traditionally
associated with a classic shawl or V sign, and may respond well to therapy [

Anti-MDA-5 has also been described in DM but little or no myositis, with increased risk of ILD, and
with vasculopathy affecting the skin. In addition to the typical cutaneous signs of dermatomyositis,
anti-MDA-5 patients characteristically develop cutaneous ulceration involving Gottron's papules and
Gottron's sign, digital pulp, and nailfolds, as well as erythematous, painful palmar papules and
macules, alopecia, and oral ulcers. These patients also frequently have arthritis and amyopathic
disease. Anti-MDA-5 antibodies are strongly associated with ILD with a rapidly progressive course
and poor overall survival related to pulmonary complications

Autoantibodies and overlap syndromes — The detection of anti-Ro, anti-La, anti-Sm, or anti-
ribonucleoprotein (RNP) antibodies in a patient with myositis suggests a diagnosis of myositis
associated or overlapping with another systemic rheumatic disease . Anti-Ro52 antibodies are
common in patients with antisynthetase antibodies, and anti-Ro60 and anti-La may be seen in a
smaller number of such patients and in those with other myositis-specific antibodies. The presence
of anti-Ro52 without anti-Ro60 is more common in myositis than in other conditions and is more
common in patients with the antisynthetase syndrome than in others with myositis. In general, anti-
Ro, anti-La, and anti-U1 RNP can be seen in some patients who also have myositis-specific
autoantibodies, but myositis-specific autoantibodies tend to be mutually exclusive with each other.
High titers of anti-RNP antibodies are associated with mixed connective tissue disease, the overlap
syndrome of myositis with features of scleroderma and SLE
Anti-PM-Scl and anti-Ku antibodies have been identified in patients with overlapping features of
myositis and scleroderma [58,65]. Many patients with these antibodies, however, do not have
myositis. The precise diagnosis of an underlying connective tissue disease is critical to patient
management because of the prognostic and treatment implications of specific diagnoses.

ELECTROMYOGRAPHY — Characteristic electrophysiologic abnormalities on EMG are often seen in

inflammatory myopathy. However, such changes are not specific for the diagnoses of (DM) or
polymyositis (PM), and the EMG is normal in approximately 10 percent of patients. Similar findings
may occur in various infectious, toxic, or metabolic myopathies.

MAGNETIC RESONANCE IMAGING — Magnetic resonance imaging (MRI) of skeletal muscles is a

noninvasive sensitive but nonspecific modality for detecting areas of muscle inflammation and
edema with active myositis, fibrosis, and calcification.

Diagnosis and differential diagnosis of dermatomyositis and polymyositis in adults

— Dermatomyositis (DM) and polymyositis (PM) are idiopathic inflammatory myopathies,

characterized by the shared features of proximal skeletal muscle weakness and evidence of muscle
inflammation [

n patients suspected of dermatomyositis (DM) or polymyositis (PM) (eg, patients who present with
progressive proximal muscle weakness and/or with a cutaneous eruption suggestive of DM), the
initial diagnostic evaluation helps to determine the nature and scope of testing that may be required
to confirm the diagnosis and to exclude other disorders that may cause similar weakness, cutaneous
eruptions, or multisystem disease.

●History –duration, mode of onset, location, and severity of weakness / ability to carry out various
activities that they commonly perform, such as climbing stairs, getting up from a chair, and carrying
heavy groceries or other objects/ severity and distribution of myalgia,/ presence or absence of
significant stiffness/ True muscle weakness should be distinguished from complaints of fatigue or
shortness of breath with exertion and from limitation due to joint disease/ history of dysphagia,
which may suggest esophageal involvement/ cough or shortness of breath, which may occur due to
pulmonary involvement/. Other symptoms of systemic rheumatic diseases, particularly systemic
lupus erythematosus (SLE) and systemic sclerosis (SSc), that may identify an overlap syndrome
cutaneous eruptions, photosensitivity, Raynaud phenomenon/ any symptoms suggesting malignancy
/ timing of the use of any drugs that may cause myopathy, particularly statins

● Examination of the skin, muscles, and joints is central/ particular attention to the scalp, face,
eyelids, hands, fingers, extensor aspects, and joints/ A detailed neurologic and neuromuscular
examination is critical to determine the severity and distribution of weakness and of muscle
tenderness, as well as the presence or absence of other abnormal neurologic findings
The laboratory evaluation should include testing for muscle enzymes, including creatine kinase and
aldolase, in addition to general laboratory testing. erythrocyte sedimentation rate (ESR), C-reactive
protein (CRP), liver function tests, and TSH

Testing should also be performed for antinuclear antibodies (ANA); anti-Ro/SSA, anti-La/SSB, anti-
ribonucleoprotein (RNP), and anti-Sm; and myositis-associated and myositis-specific antibodies
including anti-Jo-1 and other anti-synthetase antibodies, as well as antibodies directed against the
Mi2, SRP, PM/Scl, and Ku antigens.

●Imaging – Chest radiographs should be performed in all patients with findings suggesting DM or PM
to help detect the presence of pulmonary involvement, such as interstitial lung disease. This is of
particular importance in patients suspected of having an antisynthetase syndrome. Pulmonary
function tests and chest computed tomography (CT) scanning should be performed in patients with
pulmonary symptoms or with abnormal chest radiographs demonstrating interstitial lung disease.

FURTHER DIAGNOSTIC STUDIES ●Muscle biopsy ●Skin biopsy ●Magnetic resonance

Biopsy should be obtained from a muscle that is weak on physical examination but is not atrophied.
The usual muscle targets for biopsy are the quadriceps or the deltoid. Biopsying the muscle
contralateral to one shown to be abnormal by electromyography (EMG) increases the likelihood of a
diagnostic biopsy. We avoid muscles with severe weakness, marked atrophy, or recent EMG testing.
In addition, biopsy of the calf muscles is discouraged because of the frequency of artifactual findings
in biopsies from that region. If physical examination and EMG fail to identify an appropriate muscle
for biopsy, magnetic resonance imaging (MRI) may be useful. MRI may reveal areas of increased T2
signal in muscles that can then be selected for biopsy. Targeted study of the most accessible muscles
(eg, deltoid, biceps, quadriceps) by MRI is one approach, but whole-body imaging is another option
Important biochemical assays include:●Testing for metabolic myopathies due to defects in
carbohydrate, lipid, or purine metabolism●Immunohistologic assays for mutant proteins
including:•Dystrophin for Duchenne/Becker dystrophy•Merosin for congenital muscular
dystrophy•Sarcoglycan for limb-girdle muscular dystrophy

Skin biopsy — In patients with DM, characteristic findings may also be seen on skin biopsy, although
these findings are very similar on light microscopy to changes that can be seen in systemic lupus
erythematosus. Lesions of DM are difficult to distinguish histologically from those of systemic lupus
erythematosus (SLE), requiring careful clinical examination of the skin for confirmation of the
diagnosis [23]. This is particularly important in patients with amyopathic DM who often present after
being misdiagnosed as having LE;

Electromyography — Characteristic abnormalities on EMG can support a diagnosis of inflammatory

myopathy. However, such changes are not diagnostic of DM or PM, with similar findings occurring in
various infectious, toxic, or metabolic myopathies. EMG is most helpful in distinguishing myopathic
causes of weakness from neuropathic disorders, such as amyotrophic lateral sclerosis, peripheral
polyneuropathy, or myasthenia gravis. It also helps identify the muscle group that is likely to provide
useful information on biopsy. The biopsy is done on the side contralateral to that on which the EMG
is performed to avoid needle-related artifact, given the usually symmetrical muscle involvement. In
patients who are having blood drawn for muscle enzyme testing, it should be drawn prior to
performing the EMG, because samples obtained soon after (within 24 to 36 hours) may be elevated
due to the trauma associated with needle insertion into the muscle. Additionally, the
electromyographer should sample multiple sites, if initial sites are unremarkable, before concluding
that there are no myopathic changes, because muscle involvement may not be generalized
MRI — MRI of skeletal muscles is a non-invasive sensitive modality for evaluating patients with
myopathy. MRI can demonstrate areas of muscle inflammation, edema with active myositis, fibrosis,
and calcification. Unlike muscle biopsy, MRI can assess large areas of muscle, thereby avoiding
problems with sampling error. It is, however, nonspecific and may not distinguish the changes of
inflammatory myopathy from those that occur in rhabdomyolysis, muscular dystrophy, or metabolic
myopathy.

The diagnosis of DM can generally be made without a tissue biopsy in patients with clinical and
laboratory findings that are particularly characteristic of this disorder, including symmetric proximal
muscle weakness and marked elevation of muscle enzymes, in whom evidence suggesting an
alternative diagnosis is lacking. Examples of such patients include the following:●Patients with a
cutaneous finding that is relatively specific for DM, such as Gottron's papules or a heliotrope
eruption, in the absence of another explanation ●Patients with the extramuscular manifestations of
the antisynthetase syndrome including rash, polyarthritis, Raynaud phenomenon, and interstitial
lung disease, particularly if an antisynthetase antibody (most often anti-Jo-1) is present / Some
experts also obtain an electromyogram (EMG) and/or magnetic resonance imaging (MRI) in this
setting to further document that findings characteristic of an inflammatory myopathy are present.

typical but nonspecific presentation of symmetric proximal muscle weakness and elevated muscle
enzymes, in the absence either of highly specific cutaneous manifestations or myositis-specific
antibodies (MSA) : obtain tissue confirmation of the diagnosis by muscle biopsy

In patients in whom the EMG and/or MRI suggest a myopathy and in those in whom another form of
myopathy is under consideration, a muscle biopsy should be performed to confirm the diagnosis of
DM or PM and to exclude alternative diagnoses, such as inclusion body myositis (IBM), metabolic or
mitochondrial myopathy, muscular dystrophy, necrotizing myositis, or drug-induced myopathy.

Atypical features that may suggest an alternative diagnosis include:●An asymmetric or distal
presentation of weakness●Intermittent symptoms●Painful muscles●Marked muscle atrophy●Family
history of muscle disease●A history of medication that could be associated with
myopathy●Neuropathic symptoms or findings

Cutaneous features without weakness — Patients who present with cutaneous signs of DM but with
normal strength and normal muscle enzymes require a skin biopsy to confirm the diagnosis. In such
patients, EMG and MRI may reveal occult muscle disease, but such studies are generally not needed
in patients with classic clinical presentations, if the clinician can be confident that there is no muscle
weakness present. These patients may develop myopathy over time, so close follow-up is needed.
In addition, these patients may have or develop pulmonary disease or a malignancy; thus, a
thorough evaluation should be performed including pulmonary function testing and an assessment
for malignancy.

DIFFERENTIAL DIAGNOSIS — Dermatomyositis (DM) DM and polymyositis (PM) must be

distinguished from other conditions that cause muscle weakness, with or without muscle enzyme
elevation. The differential diagnosis of DM and PM thus includes other inflammatory myopathies,
motor neuron disease, myasthenia gravis, and the muscular dystrophies, as well as a variety of
inherited, metabolic, drug–induced, endocrine, and infectious myopathies. Notably, none of these
disorders are associated with the skin lesions that are characteristic of DM. Additionally, in DM and
PM, myalgia tends to be mild, unlike the more prominent muscle pain that occurs in polymyalgia
rheumatica, fibromyalgia, and viral or bacterial myositis
●Inclusion body myositis – Inclusion body myositis (IBM) is the inflammatory myopathy most
commonly misdiagnosed as PM, and, in cases of "refractory PM," the correct diagnosis often proves
to be IBM. In contrast to PM, IBM generally has a more insidious onset and more prominent distal
muscle weakness . Unlike PM, the combination of muscle atrophy and weakness of the wrist and
finger flexors in the upper extremities with weakness of the quadriceps and anterior tibial muscles in
the legs is characteristic. Furthermore, in many patients with IBM, the muscle involvement is
asymmetric, particularly in early disease. Serum muscle enzyme levels are generally lower in IBM
than in PM, usually less than 10 times the upper limit of normal, although substantial elevations may
occur. The presence of typical inclusion bodies on muscle biopsy is diagnostic of this disorder, but a
single biopsy lacks the characteristic histopathologic features in 20 to 30 percent of patients.
Magnetic resonance imaging (MRI) findings may help to distinguish PM from IBM. Whereas MRI
changes suggestive of inflammation are noted along fascial planes in PM, such changes are observed
throughout the muscle in IBM. Fatty infiltration and muscle atrophy are more prominent in IBM than
in PM, perhaps owing to the longer preclinical phase and to the relative refractoriness to treatment
exhibited by IBM.

●Drug-induced myopathy – A number of drugs can produce a myopathy that can mimic the
inflammatory myopathies. These include glucocorticoids, statins, antimalarials, antipsychotics,
colchicine, penicillamine, alcohol, cocaine, and certain antiretrovirals. the distinction can usually be
made by electromyography (EMG) and muscle biopsy if needed. ●Necrotizing
myopathy – Autoimmune necrotizing myopathy is a rare disorder that clinically resembles PM but
that is histologically distinct from PM or DM . It is described most often following exposure to
statins, but, unlike typical statin-induced myopathy, it persists following withdrawal of drug therapy .
It may also be seen in association with an underlying autoimmune rheumatic disease, such as
scleroderma or mixed connective tissue disease, may be seen as a paraneoplastic syndrome, or may
be idiopathic . The autoimmune necrotizing myopathies, similar to PM and DM, are characterized
most often by proximal upper and lower extremity muscle weakness. Also, EMG findings are typical
of an inflammatory myopathy, and muscle enzymes are elevated. In contrast to PM and DM,
however, muscle biopsies show necrotic muscle fibers without significant inflammatory cell infiltrate
around non-necrotic fibers, as well as a lack of perifascicular atrophy. Some of these patients exhibit
antibodies to signal recognition peptide or to another antibody, anti-200/100. The latter antibody,
seen in patients with statin-induced necrotizing myopathy, recognizes the hydroxymethylglutaryl
(HMG)-coenzyme A reductase protein

●Hypothyroidism – subacute onset of proximal muscle weakness and elevated muscle enzymes.
●HIV infection – In addition to causing weakness through chronic disease and cachexia, human
immunodeficiency virus (HIV) infection is also associated with an inflammatory myopathy that is
indistinguishable from PM. The myopathy either can be a presenting manifestation of HIV infection
or can occur in the later stages of infection. With the widespread use of combination antiretroviral
therapy (ART), though, it is an uncommon occurrence . Patients with HIV myopathy present with
myalgias and muscle tenderness with elevated muscle enzymes. EMG findings in HIV myopathy are
generally the same as those in idiopathic polymyositis, and muscle biopsy demonstrates an
endomysial mononuclear cell infiltrate / HIV myopathy appears to have a better prognosis than
idiopathic PM, with some patients improving spontaneously. For those who do not, high-dose
steroids, as used in idiopathic PM, have been shown to be effective / Therapeutic options for steroid
non-responders are uncertain. Immunosuppressive agents such as methotrexate and azathioprine,
which are employed in this setting in idiopathic PM, should be approached with caution in HIV-
infected patients In HIV-infected patients with myopathy, other considerations include
rhabdomyolysis and opportunistic infections (eg, toxoplasmosis). Older-generation nucleoside
reverse transcriptase inhibitors, predominantly zidovudine, have also been associated with a
myopathy that improves with discontinuation of the drug. However, these antiretroviral agents are
uncommonly used, particularly in resource-rich settings.

●Myasthenia gravis – Myasthenia gravis is a disorder of the neuromuscular junction, caused by

antibodies to the acetylcholine receptor. Although the classic physical examination finding in
myasthenia gravis is muscle fatigability (the development of muscle weakness as exercise proceeds),
the disease can occasionally cause diffuse weakness without prominent fatigability symptoms.
Myasthenia gravis is distinguished from myositis by the frequent presence of facial muscle
weakness, normal muscle enzymes, characteristic EMG changes, and anti-acetylcholine receptor
antibodies. In contrast to myasthenia gravis, DM and PM rarely involve the oculobulbar muscles. A
condition related to myasthenia gravis, known as the Lambert-Eaton syndrome, can mimic DM and
PM more closely, because the oculobulbar muscles are usually spared.

●Muscular dystrophy – The muscular dystrophies are an inherited group of progressive myopathic
disorders resulting from defects in a number of genes required for normal muscle function. Patients
with muscular dystrophy occasionally have a prominent endomysial inflammatory cell infiltrate,
which may cause diagnostic confusion with PM, particularly in dystrophic disorders such as limb-
girdle and facioscapulohumeral muscular dystrophies. ●Myotonic dystrophy – Proximal myotonic
myopathy (PROMM), also known as myotonic dystrophy type 2, must also be considered in the
differential diagnosis. It presents in adults, but, unlike in PM, the majority of patients exhibit
myotonia, a slowed relaxation following a normal muscle contraction, and a family history of the
disorder. There is often early involvement of the finger flexors in addition to proximal muscle
groups, and other findings may be present, such as cataracts, mild cognitive impairment, and
glucose intolerance. Genetic testing can confirm the diagnosis.

●Inherited metabolic myopathies – Inherited metabolic myopathies include disorders of

carbohydrate and lipid metabolism, such as carnitine deficiency and myoadenylate deaminase
deficiency. These diseases are characterized by intermittent episodes of acute muscle pain and
tenderness, usually induced by exertion. The episodes are often accompanied by myoglobinuria with
red or brown urine. Occasional patients develop chronic weakness after years of repeated acute
episodes

●Other muscle disease •Acute myopathy – Acute viral or bacterial infections (pyomyositis),
immobilization, and trauma can be characterized by acute, fulminant presentations that are often
complicated by rhabdomyolysis •Amyotrophic lateral sclerosis – Amyotrophic lateral sclerosis (ALS,
also called motor neuron disease) can present with muscle weakness, but ALS has a number of
clinical features that differ from DM and PM, including presentation with distal rather than proximal
weakness, most often with asymmetric onset; presence of long-tract signs, such as hyperreflexia and
muscle spasticity; absence of myopathic changes on EMG; and normal or only mildly elevated
muscle enzymes (creatine kinase [CK] up to about 1000 units/L). •Familial idiopathic myositis –
Muscle weakness occurring in multiple family members is not always due to inherited metabolic
defects or dystrophies but may rarely result from the development of idiopathic myositis in several
members of the same family. •Chronic GVHD – Muscle disease that is clinically and
histopathologically similar to PM has been well-documented in patients with chronic graft-versus-
host disease (GVHD) . The onset of myositis is typically more than one year after transplantation
•Focal myositis – Rare patients present with focal myositis that usually but not always progresses to
the typical generalized form over time •Amyloid myopathy – Amyloid myopathy can occur in
immunoglobulin-related or familial amyloidosis . Other manifestations of the particular form of
amyloidosis are typically present, unlike in DM or PM. The diagnosis may be confirmed by biopsy, if
needed. •Sarcoid myopathy – Myopathy may occur in one of several patterns, including an
inflammatory myopathy, in a majority of patients with sarcoidosis, but it is usually asymptomatic. It
is distinguished from DM or PM by the presence of other clinical and histologic manifestations of
sarcoid. •Trichinellosis – Parasitic infections, particularly trichinellosis, may cause severe muscle pain
and enzyme elevations, but it is distinguished by the history of ingesting inadequately cooked meat
and by the presence of eosinophilia. Muscle biopsy can confirm the diagnosis •Diabetic
amyotrophy and diabetic muscle infarction – Diabetic amyotrophy is characterized typically by acute,
asymmetric, focal onset of pain followed by weakness involving the proximal leg, with associated
autonomic failure and weight loss. Some patients present with distal involvement. The clinical
findings in the setting of type 2 diabetes and the electrodiagnostic findings help to distinguish it from
DM or PM. The diagnosis of diabetic muscle infarction is suggested clinically by the acute or
subacute onset of muscle pain, swelling, and associated tenderness, often in the muscles of the
thigh and calf, and may be confirmed by biopsy of the affected area.

●Other skin disease – Patients with systemic lupus erythematosus (SLE) may also develop facial
erythema and other photosensitive eruptions, resembling some of the facial changes seen in DM.
However, unlike in patients with SLE, the midfacial erythematous eruption that may be seen in DM
often does not spare the nasolabial folds. These disorders are generally distinguished by the severity
of muscle involvement in DM or PM compared with SLE Scalp involvement in psoriasis or
seborrheic dermatitis may resemble scalp DM. Unlike in DM, a thicker, silvery or micaceous scaling
may be present in psoriasis, and a more yellow, greasy scaling may be evident in seborrheic
dermatitis. Unlike in DM, both scalp psoriasis and seborrheic dermatitis lack any evidence of
poikiloderma. Finally, scalp DM may be distinguished from both of these disorders on skin biopsy.
Drug-induced cutaneous DM should be suspected particularly in patients who have been treated
with hydroxyurea, the most commonly reported cause, but it may also occur with statins and other
agents.

Additional studies may be important in the evaluation of a given patient once the diagnosis of
dermatomyositis (DM) or polymyositis (PM) has been made. All patients with DM or PM should
undergo a thorough medical history; physical examination with breast, rectal, and pelvic
examinations; laboratory testing; and age-appropriate cancer screening tests (eg, mammography
and colonoscopy). ●Cardiac involvement :obtain an echocardiogram and electrocardiogram.
●Pulmonary disease –plain radiography of the chest, additional studies may include pulmonary
function testing and computed tomography (CT) of the chest. ● esophageal motility studies should
be performed.

Initial treatment of dermatomyositis and polymyositis in adults

The severity of disease in dermatomyositis (DM) and polymyositis (PM) is highly variable, ranging
from mild weakness that responds readily to treatment to muscle dysfunction associated with a
relentless downhill course that is unresponsive to all treatment modalities. The following clinical
features have been associated with a worse outcome ●Delay in the initiation of treatment for more
than six months after symptom onset [●Greater weakness at presentation●The presence of
dysphagia ●Respiratory muscle weakness ●Interstitial lung disease●Associated malignancy●Cardiac
involvement

Sex, race, the presence or absence of rash, and the height of the serum creatine kinase (CK)
elevation do not predict the course of disease or the response to treatment reliably
Inflammatory myopathies are associated with an increase in mortality .The most common causes of
death in patients with inflammatory myopathies are malignancies, infection, respiratory failure, and
cardiovascular disease. Important predictors of mortality are age, cardiovascular involvement, and
respiratory compromise.

Type of myositis — A new approach to classification of inflammatory myopathy suggests that

patients with PM have a lower likelihood of responding to glucocorticoids alone than do patients
with DM or myositis associated with a connective tissue disease (so-called "overlap" myositis).

Certain myositis-specific autoantibodies may define clinically discrete subgroups that have some
predictive value for the response to treatment ●The most common myositis-specific autoantibody in
DM and PM is the anti-Jo-1 antibody, directed against histidyl-tRNA synthase. Patients with anti-Jo-1
antibodies tend to have an incomplete response to treatment and a worse long-term prognosis. The
worse outcome may be related to the interstitial lung disease often seen in association with this
antibody ●Some patients with anti-signal recognition particle (SRP) antibodies have a more
fulminant onset of proximal muscle weakness, very high serum CK levels, and muscle biopsies that
show muscle fiber necrosis and regeneration but little to no inflammation . Early treatment with
glucocorticoids is beneficial in some of these patients ●Patients with anti-Mi-2 antibodies, which
only occur in DM, often have a fulminant onset and florid cutaneous findings. However, they also
respond well to treatment and have a good long-term prognosis ●In overlap myositis, the
autoantibody profile may also predict disease course. In a review that included 67 patients with
overlap myositis, anti-RNP, anti-PM-Scl, and anti-Ku antibodies (present in 16 patients) were markers
for monophasic episodes of myositis in 100 percent of cases [4]. In contrast, the presence of anti-
synthetase, anti-SRP, or nucleoporin autoantibodies (present in 25 patients) was a marker for
chronic disease in 95 percent of the evaluable patients.

.INITIAL THERAPY — The goals of treatment are to improve muscle strength and to avoid the
development of extramuscular complications. In patients with dermatomyositis (DM), resolution of
cutaneous disease manifestations is an additional goal.

Despite the absence of placebo-controlled trials demonstrating their effectiveness, glucocorticoids

are the cornerstone of initial therapy for DM and polymyositis (PM). Some clinicians also begin
treatment immediately with a glucocorticoid-sparing agent, generally azathioprine or methotrexate,
particularly in patients who are severely ill.

Systemic glucocorticoids : there is a general consensus that glucocorticoid therapy improves

strength and preserves muscle function .Patients will be on prednisone in tapering doses for
approximately one year, depending upon their response to therapy and achievement of disease
control. There is no standard glucocorticoid regimen for treating the inflammatory myopathies, but
two general principles apply: ●Initiation of treatment with high doses for the first several months to
establish disease control ●Slow taper to the lowest effective dose for a total duration of therapy
between 9 and 12 months

Initial glucocorticoid therapy — Glucocorticoid therapy in DM or PM is typically initiated with

prednisone at a dose of 1 mg/kg per day, to a maximum daily dose of 80 mg. Pulse
methylprednisolone (1000 mg per day for three days) may be used at the start of therapy for
patients who are severely ill. For the first four to six weeks of therapy, prednisone is continued at 1
mg/kg per day with ongoing assessment of the clinical response. Maintenance of the prednisone
dose at 1 mg/kg per day beyond six weeks may increase the risk of developing glucocorticoid
myopathy.

Assessing treatment response — The response to glucocorticoids should be assessed every few
weeks after the start of therapy. Muscle enzymes begin to decline within a few weeks of treatment
and generally normalize by about six weeks. Muscle strength recovery, however, lags behind the
decline in muscle enzymes, and maximal recovery of strength may not occur until three months,
although this is variable. In DM, the time courses of cutaneous responses to therapy are similar:
some patients respond promptly, and, in others, improvement is more delayed.

Once treatment has begun, the clinician should select several muscle groups to test on a regular
basis as the primary gauge of clinical progress. It is useful to determine which muscles are the
weakest for a given patient and to test these muscles sequentially over time. Since proximal muscles
are typically most involved, the following muscle groups are often tested:

●Lower extremity: •Quadriceps – asking the patient to extend the lower leg against resistance with
the limb flexed at the hip and knee •Hip flexors – asking the patient to flex the thigh against
resistance with the leg flexed at the knee and hip

Proximal lower extremity strength, including the quadriceps and other muscles, may also be
evaluated by asking the patient to cross his or her arms and to rise from a chair, using only the
proximal leg muscles.

●Upper extremity and neck: •Deltoids – asking the patient to abduct the arms to 90 degrees and
resist the examiner pushing down on the arms •Neck flexors – asking the patient to push his or her
head forward while the examiner applies reverse pressure against the forehead

Patients with respiratory muscle weakness or interstitial lung disease can be assessed with serial
pulmonary function testing. It is reasonable to test at two to three months after initiating treatment.

Glucocorticoid tapering — The decision to begin tapering glucocorticoids should be based on a

combination of the improvement in muscle enzymes and recovery of muscle strength. Ideally,
normalization of enzymes and complete recovery of muscle strength should occur before
glucocorticoids are tapered, although continuation of high-dose glucocorticoids for more than six
weeks may cause steroid myopathy and decline in strength. Assuming that a patient begins
prednisone treatment at 60 mg/day and remains on this dose for six weeks, the following taper will
require a total of 26 weeks to reach a daily dose of 5 mg:

●The prednisone dose should be tapered by 10 mg each week until a dose of 40 mg/day is
reached.●After one week on 40 mg/day, the prednisone dose should be tapered by 5 mg each week
until the patient reaches 20 mg/day.●After one week on 20 mg/day, the prednisone dose should be
tapered by 2.5 mg each week until the patient reaches 10 mg/day.●After one week on 10 mg/day,
the prednisone dose should be tapered by 1 mg every two weeks until the patient reaches 5 mg/day.

Deviations from this regimen may be necessary if patients develop glucocorticoid myopathy or
experience disease flares. Continuation of the prednisone taper can be considered if the patient has
achieved and maintained good disease control. Tapering off prednisone completely should not
proceed faster than 1 mg decreases every two weeks.

The patient should be monitored carefully during the tapering period and should be watched for
signs of recurrent weakness, extramuscular complications of DM or PM, and signs of glucocorticoid
toxicity. The recurrence of proximal muscle weakness in a patient treated for a prolonged period
with glucocorticoids poses a significant clinical conundrum, as steroid myopathy also affects the
proximal musculature.
Alternate-day glucocorticoid tapers — Although some clinicians use alternate-day glucocorticoid
tapers for the treatment of inflammatory myopathies, there is little indication that such regimens
are associated with less toxicity compared with the conventional regimen outlined above.

Glucocorticoid responses — Overall, more than 80 percent of patients with inflammatory

myopathies improve with glucocorticoids alone. However, as noted above, as many as 50 percent of
patients with PM do not respond to glucocorticoid therapy alone . Furthermore, among patients
who do respond, the majority do not return to normal muscle strength

Apparent glucocorticoid failures — In the setting of apparent failure to respond to glucocorticoids,

three possibilities should be reviewed before intensifying immunosuppression:

●Alternative diagnoses such as inclusion body myositis, muscular dystrophy, or hypothyroidism

should be considered. Repeat muscle biopsies may need to be performed.
●If the diagnosis of DM or PM is confirmed, glucocorticoid-induced myopathy should be considered
if the patient remains weak or has developed recurrent weakness in the setting of normal muscle
enzyme levels. Continued evidence of fibrillation potentials and positive sharp waves on
electromyography suggests active myositis . Because of the patchy nature of inflammation and the
fact that inactivity may cause type 2 muscle fiber atrophy, muscle biopsy may not always help in
distinguishing glucocorticoid-induced myopathy from poorly controlled myositis. The potential utility
of magnetic resonance imaging to distinguish between glucocorticoid-induced myopathy and active
myositis remains undefined.An empiric trial of lowering the prednisone dose and observing the
muscle strength response is a practical approach to this dilemma.
●An unrecognized malignancy associated with myositis may be a cause of failed response to
glucocorticoids. Most myositis-associated malignancies are diagnosed within the two-year period
before and after the development of myositis

Once alternative underlying diagnoses, glucocorticoid myopathy, and occult malignancy have been
excluded satisfactorily, the next step is the addition of a glucocorticoid-sparing agent.

GLUCOCORTICOID-SPARING AGENTS — A steroid-sparing immunosuppressive agent is generally

initiated with glucocorticoid treatment because of the potential for these medications to reduce the
cumulative dose of prednisone and thereby diminish glucocorticoid-induced morbidity. For patients
in whom glucocorticoids are contraindicated, these steroid-sparing agents are occasionally used as a
first-line drug.

The current first-line glucocorticoid-sparing agent is usually either azathioprine or methotrexate.

Because of hepatotoxicity and pulmonary toxicity associated with methotrexate, azathioprine is
preferred in patients who have interstitial lung disease associated with their myositis, have
underlying liver disease, or are unwilling to abstain from alcohol.

Starting a glucocorticoid-sparing agent simultaneously with prednisone may prevent intermediate

and long-term side effects, particularly in patients with concomitant medical problems such as
diabetes. In addition, those patients with profound weakness or significant extramuscular
complications warrant treatment with two drugs from the outset. As examples, patients with
interstitial lung disease or severe esophageal dysfunction are candidates for a glucocorticoid-sparing
agent from the start of therapy.

Azathioprine — compared prednisone plus azathioprine with prednisone alone [1]. At three months,
there was no difference between the treatment groups in muscle strength or creatine kinase (CK)
levels. However, at three years, patients treated with combination therapy had better functional
outcomes and required less prednisone as maintenance therapy . The response to azathioprine may
take as long as four to six months [26,27].

Thiopurine methyltransferase testing — There is uncertainty regarding the benefits of routine

testing for thiopurine s-methyltransferase deficiency before beginning azathioprine. The authors do
not routinely perform such testing but initiate therapy at a low dose with close monitoring as the
dose is gradually increased. TPMT is responsible for the metabolism of thiopurines, including
azathioprine and mercaptopurine. Variation in the TPMT gene can result in functional inactivation of
the enzyme and a markedly increased risk of life-threatening myelosuppression. For this reason,
TPMT testing is recommended by the US Food and Drug Administration prior to treatment with a
thiopurine. However, TPMT genotyping has not been universally adopted, and the cost-effectiveness
and optimal clinical circumstances in which to perform routine testing are not well-defined.

Dosing and monitoring — We use an initial dose of azathioprine of 50 mg/day and obtain a complete
blood count (CBC) after two weeks of therapy to assure that the counts are stable. We then increase
the daily dose by 50 mg each week to 1.5 mg/kg/day. In patients with an inadequate response after
three months of therapy, we increase the dose as tolerated up to as high as 2.5 mg/kg/day. We
obtain CBCs, a platelet count, and liver function tests monthly initially, and once a stable dose is
achieved we perform testing every three months.

Alternative approaches, including more gradual dose escalation and more frequent monitoring, are
recommended by some experts. Guidelines for dosing of azathioprine, which are based upon TPMT
genotype, have been developed for use in those patients in whom TPMT testing has been performed
Adverse effects — Systemic flu-like reactions associated with fever and gastrointestinal complaints
develop in up to 12 percent of patients treated with azathioprine. These reactions are independent
of TPMT status and require discontinuation of the drug .Other side effects include bone marrow
suppression, pancreatitis, and liver toxicity. Long-term side effects may include increased risk of
malignancy.

Methotrexate — response rates ranging from 71 to 82 percent, even in patients who initially failed
glucocorticoids Dosing — Methotrexate has an advantage over azathioprine in convenience,
requiring only once-a-week administration either orally or parenterally. Methotrexate is
administered with the same dosing regimen as that used for rheumatoid arthritis, generally starting
with an initial dose of 15 mg/week and increasing slowly by 2.5 mg increments to 25 mg/week if
there is inadequate response to the lower dose after two to three months.

Prior to the availability of alternative therapies, higher doses of methotrexate (up to 50 mg/week)
had been used for refractory or resistant disease. When used in doses above 25 mg/week, oral
administration of methotrexate is usually replaced by the subcutaneous, intramuscular, or
intravenous route, depending upon the clinical setting. In such circumstances, higher doses of folic
acid (eg, 2 or 3 mg/day) or leucovorin (folinic acid) may also be required depending on symptoms
associated with methotrexate use. For leucovorin, 5 mg of leucovorin is given once weekly, 8 to 12
hours after methotrexate administration.

Adverse effects — Methotrexate toxicity, including stomatitis, gastrointestinal symptoms, and

leukopenia, can be seen with low-dose therapy. This risk can be minimized by the concurrent
administration of folic acid (1 to 2 mg/day) or, in patients who do not respond completely to folic
acid, by the use of leucovorin (5 mg per week, 8 to 12 hours after the methotrexate dose). Because
of potential hepatotoxicity, the use of methotrexate may be problematic in patients with a history of
liver disease or in those who drink alcohol, even in modest quantities. Azathioprine is preferred in
patients with liver disease and in those unwilling to abstain from alcohol, although it also can cause
abnormalities in liver function. There is no evidence that methotrexate pulmonary toxicity is more
common in patients with myositis-associated interstitial lung disease. However, the development of
methotrexate pneumonitis in a myositis patient presents diagnostic difficulties. In addition, the
patient's already compromised pulmonary function increases the risk for a bad outcome.

Intravenous immune globulin — Selected patients with severe life-threatening weakness or patients
with severe dysphagia at risk for aspiration may benefit from the addition of intravenous immune
globulin (IVIG) to initial treatment with glucocorticoids. IVIg may have a more rapid onset of action
than glucocorticoids, but prolonged treatment is limited by difficulty of administration, cost, and
potential toxicity. IVIg also has a role in the treatment of resistant and recurrent cases.

Antimalarials — Hydroxychloroquine (200 to 400 mg/day) is effective in up to 75 percent of patients

in controlling skin disease but without any benefit to muscle disease

DURATION OF THERAPY — Most patients wish to discontinue immunosuppressive therapy at some

point if the disease is well-controlled. We attempt to discontinue all immunosuppressive
medications after the first round of therapy, with careful monitoring by the patient and clinician for
early signs of relapse.Most patients and clinicians prefer to discontinue glucocorticoids before
stopping azathioprine or methotrexate. Attempts to taper azathioprine or methotrexate gradually
are reasonable in patients who have achieved remission and have discontinued glucocorticoids.The
glucocorticoid tapering regimen is described above. If there are no disease flares during the course
of the taper, most patients discontinue glucocorticoids at 9 to 12 months. Tapering of azathioprine
or methotrexate should be conducted at monthly intervals after the patient is in clinical remission,
with planned cessation of therapy over approximately six months. The patient's clinical status must
be closely monitored to permit early detection of disease flares, at a severity that does not require
the resumption of high-dose glucocorticoids.

LONG-TERM FOLLOW-UP Sixty percent of the patients had courses characterized as chronic, 20
percent had polycyclic disease courses, and 20 percent had monophasic courses.

Side effects of therapy included:●Cushingoid appearance (71 percent)●Psychological or psychiatric

symptoms (35 percent)●Osteoporosis (29 percent)●Infections (29 percent). At 5 years, 24 %
considerable disability, 25% significant muscle weakness, and 84 %abnormal quality of life.

RECURRENT AND RESISTANT DISEASE — Some patients either relapse after an initial response or fail
to respond to the above regimens.

GENERAL MEASURES AND EXTRAMUSCULAR MANIFESTATIONS — In addition to drug therapy, there

are a variety of other important considerations in the treatment of patients with inflammatory
myopathy. These include the initiation of an exercise program under the supervision of a physical
therapist, steps to prevent aspiration in patients with esophageal dysfunction, counseling about the
need for patients with dermatomyositis (DM) to avoid ultraviolet light, and prophylaxis against
osteoporosis and opportunistic infections.

Exercise — While strength and aerobic exercise training programs do not appear to cause harm,
there is limited evidence to conclude that they offer benefit . However, observational studies
support the concept that physical therapy and rehabilitation should begin early in the course of
treatment, with regimens tailored to the severity of weakness:

●Bedridden or chair-bound patients with severe weakness should receive passive range of motion
exercises to prevent joint contractures. Careful attention to positioning reduces the risk of pressure
sores. ●Isometric and resistive exercises should begin as soon as the patient has recovered enough
strength to be able to participate.

Aspiration risk — Patients with dysphagia due to cricopharyngeal muscle dysfunction are at risk for
aspiration. Several interventions can reduce this risk:●Speech therapy consultation for advice about
aspiration risk and precautions.●Elevation of the head of the bed.●Semi-thick diets.●A
nasopharyngeal or gastric feeding tube may be necessary to provide adequate nutrition and to help
protect the airway in patients with severe dysphagia.

●Patients with myositis and overlap with scleroderma may develop reflux esophagitis due to
incompetence of the lower esophageal sphincter. Treatment with proton pump inhibitors decreases
both the risk of stricture formation and reflux symptoms, but some patients have persistent
symptoms.

Skin disease and avoidance of sunlight — The cutaneous manifestations of dermatomyositis

frequently respond to the agents used to treat the associated myositis, including glucocorticoids,
methotrexate, and azathioprine. However, skin manifestations can persist despite effective
treatment of myositis. Therapy for cutaneous disease is usually indicated due to the presence of
severe pruritus and patient distress over the appearance of skin lesions.Scrupulous protection from
the sun, including liberal use of sunscreens and sun-protective clothing, is important because the
rashes are often related to photosensitivity. Patients can also benefit from use of topical
corticosteroids. Antimalarial drugs can be used to treat the skin disease in patients with prominent
rash or dermatomyositis sine myositis (amyopathic dermatomyositis). In such patients,
hydroxychloroquine (HCQ) used in combination with quinacrine may be effective if HCQ alone is
inadequate. In addition, topical tacrolimus can be effective for skin lesions refractory to other
therapies.

Pruritus — Pruritus is often a significant complaint. Various topical remedies used include menthol,
camphor, antihistamines, pramoxine, and lidocaine. Systemic agents used include hydroxyzine,
doxepin, and amitriptyline.

Osteoporosis prevention — All patients treated with high-dose glucocorticoids are at risk for
glucocorticoid-induced osteoporosis. Thus, all patients embarking upon treatment courses for
inflammatory myopathy are potential candidates for antiresorptive therapy

Opportunistic infections — Because of the high-dose glucocorticoid therapy and other

immunosuppressive medications used to treat inflammatory myopathy, patients with DM and
polymyositis (PM) are at an increased risk for opportunistic infection. Pneumocystis jirovecii, a
common pathogen in immunosuppressed hosts, may cause lethal infections, particularly in patients
with interstitial lung disease. Fungal and mycobacterial infections of the lung and gastrointestinal
tract and herpesvirus infections may also occur Prophylaxis against pneumocystic jirovecii is thus
often indicated for patients treated with high-dose glucocorticoids and/or other immunosuppressive
agents. A common prophylactic strategy for Pneumocystis involves the use of one double-strength
tablet daily of trimethoprim-sulfamethoxazole (TMP/SMZ), which contains 160 mg of trimethoprim
and 800 mg of sulfamethoxazole. Because both trimethoprim and methotrexate are folate
antagonists, some have raised concerns that the use of double-strength TMP/SMZ tablets on a daily
basis combined with weekly methotrexate may lead to bone marrow suppression. For myositis
patients treated with methotrexate, daily single-strength TMP/SMZ (80 mg of trimethoprim and 400
mg of sulfamethoxazole) is likely to be safe.
Immunizations — We advise that patients receive appropriate immunizations prior to the institution
of immunosuppressive therapies (table 1).

●Chronic use of glucocorticoids may result in suppression of the hypothalamic-pituitary-adrenal axis.

Stress-dose glucocorticoids may be needed during childbirth.

Treatment of recurrent and resistant dermatomyositis and polymyositis in adults

— Dermatomyositis (DM) and polymyositis (PM) are two classic forms of inflammatory myopathy.
Most patients respond to initial therapy, and some achieve sustained disease control either off all
therapy or with low-dose maintenance therapy. There are two additional patterns of response:

●Recurrent disease – After achieving disease control with treatment, some patients experience
disease recurrences (flares) during or after the period of medication tapering.

●Resistant disease – In other patients, the disease does not respond entirely to conventional initial
approaches to remission induction, and other therapies must be considered after excluding
alternative diagnoses.

RECURRENT DISEASE — Complete discontinuation of treatment is unsuccessful in the majority of

patients. For patients who experience disease flares after the achievement of disease control, a
variety of clinical scenarios may occur.

●Flare at more than 10 mg/day of prednisone – Disease flares at such doses of prednisone require
one of two actions:•Addition of a glucocorticoid-sparing drug if neither azathioprine nor
methotrexate has been used •Treatment of the flare as a case of resistant disease if the patient is
already taking either azathioprine or methotrexate . With either action, a higher dose of prednisone,
generally in the range of 1 mg/kg per day, will be required to reestablish disease control.

●Flare at 10 mg/day of prednisone or less – If a disease flare occurs at a prednisone dose of 10

mg/day or less, there are two options that are not mutually exclusive:•Increase in prednisone to the
lowest dose required to reestablish disease control. This dose is based upon the severity of the
patient's clinical findings. If the disease flare is detected early, the dose required may be significantly
lower than 1 mg/kg per day. The usual minimum dose is 20 mg/day.•Increase in azathioprine or
methotrexate to a higher dose, if the dose of the patient's glucocorticoid-sparing drug has not
already been maximized. Once disease control is restored, we suggest slower tapering than that
which was used during the initial course. Some patients are maintained on low-dose prednisone (eg,
5 mg/day) for one year or more.

●Flare off prednisone but on a glucocorticoid-sparing drug – There are two options in such patients
that are not mutually exclusive:•Prednisone is reinstituted at the lowest dose required to reestablish
disease control. The dose selected is based upon the severity of the patient's clinical findings and
may be significantly lower than 1 mg/kg if the disease flare is detected early. The usual minimum
dose is 20 mg/day. •The glucocorticoid-sparing drug can be changed from azathioprine to
methotrexate or vice versa. If the patient has been treated previously with both azathioprine and
methotrexate, the flare should be regarded as a manifestation of resistant disease.

●Flare off all immunosuppressive medications – Prednisone should be reinstituted with the daily
dose varying with the severity of the relapse. The minimum starting dose of prednisone is 20
mg/day. In addition, a glucocorticoid-sparing drug should be resumed or started.

RESISTANT DISEASE — Before initiating alternative therapies in patients with resistant disease,
consideration should be given to an alternative diagnosis, particularly inclusion body myositis (IBM).
The picture of weakness and atrophy of the quadriceps in addition to wrist and finger flexion
involvement raises the suspicion of IBM. A repeat biopsy may be necessary to confirm the diagnosis.
In addition, the initial response to glucocorticoids in the patient with dermatomyositis and
polymyositis typically takes four to six weeks for normalization of creatine kinase (CK) levels, or three
to four months to regain muscle strength; thus, a patient should not be classified as having resistant
disease without considering these time factors.

Multiple options exist for treating patients who do not respond adequately to glucocorticoids plus
azathioprine or methotrexate. Evidence of clinically significant benefit is greatest with rituximab and
intravenous immune globulin (IVIG). We suggest using rituximab first in this setting, and then trying
IVIG if rituximab fails. Additional considerations that may influence the choice of therapies include
the presence of interstitial lung disease (ILD), particularly if it has not responded to initial treatment
measures. The reasons for favoring rituximab over IVIG include the following:

●Treatment with rituximab has been associated with substantial improvement in dermatomyositis
(DM) and polymyositis (PM) in patients with previously refractory disease.●Rituximab appears to be
effective in connective tissue disorders resembling DM and PM, such as systemic lupus
erythematosus and rheumatoid arthritis (RA). ●If effective, rituximab may be more likely to lead to a
prolonged period of disease control. Many patients who respond to IVIG require continued
treatments on a monthly basis.

Other agents that may be of benefit include mycophenolate mofetil; calcineurin inhibitors, such as
cyclosporine or tacrolimus; and cyclophosphamide.

. In rheumatic disease (particularly RA), the trend with the use of rituximab is to employ two 1 gram
doses two weeks apart.

Intravenous immune globulin — For DM, immunoglobulin (IVIG) is a reasonable second-line therapy
for patients with refractory disease. The 2012 American Academy of Neurology guidelines support
the use of IVIG for refractory DM, but found evidence insufficient to support or refute its use in PM
IVIG is an effective short-term therapy for resistant myositis. The mechanism of action is not known.

Each patient was treated with IVIG (1 g/kg per day for two days per month for four to six months).

An alternative subcutaneous approach to the administration of IVIG in patients with DM and PM has
also been associated with clinical improvement in strength and quality of life measures [13]. In this
small case series of seven patients, the usual monthly dose was divided into weekly doses given
subcutaneously through a programmable pump, and the treatment appeared to be safe and well-
tolerated.

Mycophenolate mofetil — Mycophenolate mofetil has been used with some success in retrospective
series of patients with inflammatory myopathy . These case series suggest a role for mycophenolate
mofetil in the treatment of resistant myositis. Mycophenolate mofetil may be used in patients who
have failed methotrexate or azathioprine, or in patients with interstitial lung disease (ILD).

Calcineurin inhibitors — The calcineurin inhibitors, which include cyclosporine and tacrolimus,
achieve their effects by interfering with T cell function.

Cyclophosphamide — Cyclophosphamide and chlorambucil (which is infrequently used because of

greater toxicity than cyclophosphamide) may be effective in treating myositis [26,27], but their
utility is limited by their potential for toxicity, particularly the induction of malignancy
In the absence of aggressive ILD or systemic vasculitis, cyclophosphamide should be considered only
in patients who fail to respond to multiple other second-line agents.Given the efficacy of alkylating
agents in the treatment of vasculitides, cyclophosphamide may also be useful in patients with
inflammatory myopathy who develop the complication of systemic vasculitis.

Combination methotrexate and azathioprine — Combination therapy may be effective among those
with resistant disease. This combination might be considered in the patient for whom
mycophenolate mofetil or other options were unaffordable or ineffective

EXTRAMUSCULAR DISEASE

Interstitial lung disease — The presence of ILD may influence the choice of therapeutic agents.
Refractory rash — In some cases of DM, the cutaneous manifestations are more refractory to
treatment than the muscle disease.