This document provides an overview of disorders of skeletal muscles. It defines different types of myopathies including muscular dystrophies, myositis, myotonias, metabolic myopathies, and congenital myopathies. Key details are provided on Duchenne muscular dystrophy, Becker muscular dystrophy, and myotonic dystrophy. Duchenne dystrophy is an X-linked disorder causing progressive weakness. Becker dystrophy has a less severe course. Myotonic dystrophy involves muscle weakness, myotonia, and multi-system involvement. Diagnostic testing and clinical features are summarized for each condition.

1. Ds of the Skeletal Muscles
FOR CLI
NICAL I STUDENTS

2. Introduction
• Disorders of skeletal muscle encompass several illnesses that
cause weakness, pain, and fatigue in any combination.
– Myopathy refers to an abnormality of the muscle and has no
other connotation.
– Muscular dystrophies are genetic myopathies, usually caused by a
disturbance of a structural protein.
– Myositis implies an inflammatory disorder, and the term is usually
reserved for disorders in which muscle histological preparations
show an inflammatory response.

3. – The myotonias are diseases in which the normal contractile process is
distorted by the occurrence of involuntary, persistent muscle activity
accompanied by abnormal repetitive electrical discharges, which may
occur after percussion or voluntary contraction.
– Metabolic myopathics, in this context, refer mainly to abnormalities of
muscle biochemistry that impair energy production.
• In a general medical context, metabolic myopathy is often synonymous with
endocrine myopathy.
– Congenital myopathies are a group of genetic disorders with structural
disturbances of the muscle cell that usually present at birth or during
childhood

4. – Striated muscle is the tissue that converts chemical energy into
mechanical energy.
– The component processes include
(1) Excitation and contraction occurring in the muscle
membranes,
(2) The contractile mechanism,
(3) Structural supporting elements that allow muscle to
withstand mechanical stress, and
(4) The energy system that supports the activity and integrity of
the other three systems.

5. • Logically, myopathies should be categorized according to the
part of the system involved.
– This was previously impossible because the molecular basis of
muscle activity was unknown.
– Recent advances in knowledge allow an attempt to classification
along these lines.
– Examples - Channelopathies
Dystrophinopathies

6. Diagnosis
Muscle biopsy
– Microscopic study
– Histochemical study
– Immunocytochemistry

7. • Myopathies are classified according to the possible mechanism of
the normal contractile function of the muscle.
– DYSTROPHINOPATHIES CHANNELOPATHIES
– METABOLIC MYOPATHY CONGENITAL MOPATHY
– MITOCHONRIAL MYOPATHY DRUG INDUCED
– SYSTEMIC ILLNESS MYOPATHY INFLAMMATORY MYOPATHY
– INFECTIOUS MYOPATHY

8. Most myopathies present with proximal,
symmetric limb weakness (arms or legs) with
preserved reflexes and sensation.
– However, asymmetric and predominantly distal
weakness can be seen in some myopathies
– No associated sensory abnormalities, no reflex
abnormalities and muscle atrophy occurs very
late.
– No bladder or bowel dysfunction

9. – Symptoms of muscle weakness can be either intermittent
or persistent.
– Disorders causing intermittent weakness include
• Myasthenia gravis, Periodic paralyses
(hypokalemic, hyperkalemic, and
paramyotoniacongenita),
• Metabolic energy deficiencies of glycolysis
• Fatty acid utilization Mitochondrial
myopathies

10. Most muscle disorders cause persistent weakness.
– In the majority of these, including most types of muscular
dystrophy, polymyositis, and dermatomyositis, the
proximal muscles are weaker than the distal and are
symmetrically affected, and the facial muscles are spared,
a pattern referred to as limb-girdle.
– The differential diagnosis is more restricted for other
patterns of weakness.
– Facial weakness (difficulty with eye closure and impaired
smile) and scapular winging are characteristic of
facioscapulohumeral dystrophy (FSHD).

11. – Facial and distal limb weakness associated with hand grip myotonia
is virtually diagnostic of myotonic dystrophy type 1.
– When other cranial nerve muscles are weak, causing ptosis or
extraocular muscle weakness, the most important disorders to
consider include
Neuromuscular junction disorders,
Oculopharyngeal muscular dystrophy,
Mitochondrial myopathies,
Some of the congenital myopathies

12. INTERMITTENT WEAKNESS

13. PERSISTENCE WEAKNESS

14. Other symptoms of muscle diseases include
–MUSCLE CRAMP (MYALGIA) MUSCLE
STIFFNESS
–MUSCLE CONTRACTURE MYOTONIA
–MUSCLE SPASM MUSCLE
ENLARGEMENT OR
ATROPHY

15. LABORATORY MEASURMEN
SERUM ENZYMES
– CK is the preferred muscle enzyme to measure in the evaluation of
myopathies.
• Damage to muscle causes the CK to leak from the muscle fiber to the
serum.
• The MM isoenzyme predominates in skeletal muscle, while creatine
kinase-myocardial bound (CK-MB) is the marker for cardiac muscle.
• Serum CK can be elevated in normal individuals without provocation,
presumably on a genetic basis or after strenuous activity, minor trauma
(including the EMG needle), a prolonged muscle cramp, or a generalized
seizure.
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT),
aldolase, and lactic dehydrogenase (LDH) are enzymes sharing an origin
in both muscle and liver.
• Serum GGT is not found in muscles

16. ELECTRODIANOSTIC STUDIES
– EMG, repetitive nerve stimulation, and nerve conduction studies are
essential methods for evaluation of the patient with suspected muscle
disease.
– In combination, they provide the information necessary to differentiate
myopathies from neuropathies and neuromuscular junction diseases.
– Routine nerve conduction studies are typically normal in myopathies but
reduced amplitudes of compound muscle action potentials may be seen
in atrophied muscles.
– The needle EMG may reveal irritability on needle placement suggestive
of a necrotizing myopathy (inflammatory myopathies, dystrophies, toxic
myopathies, myotonic myopathies), whereas a lack of irritability is
characteristic of long-standing myopathic disorders (muscular
dystrophies, endocrine myopathies, disuse atrophy, and many of the
metabolic myopathies).
– In addition, the EMG may demonstrate myotonic discharges that will
narrow the differential diagnosis.
– Another important EMG finding is the presence of short-duration, small-
amplitude, polyphasic motor unit action potentials (MUAPs)

17. DNA ANALYSIS
• This serves as an important tool for the definitive diagnosis of many
muscle disorders.
• Nevertheless, there are a number of limitations in currently available
molecular diagnostics.
• For example, in Duchenne's and Becker's dystrophies, two-thirds of
patients have deletion or duplication mutations that are easy to detect,
while the remainder have point mutations that are much more difficult
to find.
• For patients without identifiable gene defects, the muscle biopsy
remains the main diagnostic tool.
– FOREARM EXERCISE TEST

18. MUSCLE BIOPSY
• Muscle biopsy is an important step in establishing the diagnosis of a suspected
myopathy.
• The biopsy is usually obtained from a quadriceps or biceps brachii muscle, less
commonly from a deltoid muscle.
• Evaluation includes a combination of techniques—
Light microscopy,
Histochemistry,
Immunocytochemistry with a battery of antibodies, and
Electron microscopy
MOLECULAR AND GENETIC STUDIES

19. HEREDITARY DYSTROPHINOPATHIES

20. DUCHENNE’S MUSCULAR DYSTROPHY
This X-linked recessive disorder,
sometimes also called
pseudohypertrophic muscular
dystrophy, has an incidence of 30
per 100,000 live-born males.

21. Clinical features
– Duchenne's dystrophy is present at birth, but the disorder
usually becomes apparent between ages 3 and 5 years.
– The boys fall frequently and have difficulty keeping up
with friends when playing. Running, jumping, and hopping are
invariably abnormal.By age 5 years, muscle weakness is
obvious by muscle testing.
• On getting up from the floor, the patient uses his hands to climb up
himself [Gowers' maneuver].
• Contractures of the heel cords and iliotibial bands become apparent by
age 6 years, when toe walking is associated with a lordotic posture.
• Loss of muscle strength is progressive, with predilection for proximal
limb muscles and the neck flexors; leg involvement is more severe than
arm involvement

22. – Between ages 8 and 10 years, walking may require the use of braces;
joint contractures and limitations of hip flexion, knee, elbow, and
wrist extension are made worse by prolonged sitting.
– By age 12 years, most patients are wheelchair dependent.
• Contractures become fixed, and a progressive scoliosis often develops that
may be associated with pain.
• The chest deformity with scoliosis impairs pulmonary function, which is
already diminished by muscle weakness.
– By age 16–18 years, patients are predisposed to serious, sometimes
fatal pulmonary infections.
• Other causes of death include aspiration of food and acute gastric dilation.

23. – A cardiac cause of death is uncommon despite the presence of a
cardiomyopathy in almost all patients.
• Congestive heart failure seldom occurs except with severe stress such as
pneumonia.
• Cardiac arrhythmias are rare.
• The typical electrocardiogram (ECG) shows an increased net RS in lead V1;
deep, narrow Q waves in the precordial leads; and tall right precordial R
waves in V1.
– Intellectual impairment in Duchenne's dystrophy is common; the
average intelligence quotient (IQ) is 1 SD below the mean.
• Impairment of intellectual function appears to be non progressive and
affects verbal ability more than performance tasks.

24. GOWER’S SIGN LORDOSIS

25. • Laboratory findings
– Serum CK levels are invariably elevated to between 20 and 100 times
normal.
• The levels are abnormal at birth but decline late in the disease because of
inactivity and loss of muscle mass.
– EMG demonstrates features typical of myopathy.
– The muscle biopsy shows muscle fibers of varying size as well as
small groups of necrotic and regenerating fibers.
• Connective tissue and fat replace lost muscle fibers.
– A definitive diagnosis of Duchenne's dystrophy can be established on
the basis of dystrophin deficiency in a biopsy of muscle tissue or
mutation analysis on peripheral blood leukocytes

26. – Duchenne's dystrophy is caused by a mutation of the gene that encodes
dystrophin, a 427-kDa protein localized to the inner surface of the
sarcolemma of the muscle fiber.
• The dystrophin gene is >2000 kb in size and thus is one of the largest identified
human genes. It is localized to the short arm of the X chromosome at Xp21.
• The most common gene mutation is a deletion.
– A diagnosis of Duchenne's dystrophy can also be made by Western blot
analysis of muscle biopsy specimens, revealing abnormalities on the
quantity and molecular weight of dystrophin protein.
– In addition, immunocytochemical staining of muscle with dystrophin
antibodies can be used to demonstrate absence or deficiency of
dystrophin localizing to the sarcolemmal membrane

27. • Pathogenesis
– The dystrophin-glycoprotein
complex appears to confer
stability to the sarcolemma,
although the function of each
individual component of the
complex is incompletely
understood.
– Deficiency of one member of
the complex may cause
abnormalities in other
components.

28. • Treatment
– Glucocorticoids, administered as prednisone in a dose of 0.75 mg/kg per
day, significantly slow progression of Duchenne's dystrophy for up to 3
years.
• Some patients cannot tolerate glucocorticoid therapy; weight gain and increased
risk of fractures in particular represent a significant deterrent for some boys.
– As in other recessively inherited dystrophies presumed to arise from loss
of function of a critical muscle gene, there is optimism that Duchenne's
disease may benefit from novel therapies that either replace the
defective gene or missing protein or implement downstream corrections
• E.g., skipping mutated exons or reading through mutations that introduce
stop codons

29. BECKER’S MUSCULAR DYSTROPHY
This less severe form of X-linked recessive
muscular dystrophy results from allelic
defects of the same gene responsible for
Duchenne's dystrophy.
• Becker's muscular dystrophy is 10 times less
frequent than Duchenne's, with an incidence
of about 3 per 100,000 live-born males.

30. Clinical features
The pattern of muscle wasting in Becker's muscular dystrophy
closely resembles that seen in Duchenne's.
– Proximal muscles, especially of the lower extremities, are
prominently involved.
• As the disease progresses, weakness becomes more generalized.
• Significant facial muscle weakness is not a feature.
– Hypertrophy of muscles, particularly in the calves, is an
early and prominent finding.

31. – By definition, patients with Becker's dystrophy walk beyond age 15,
while patients with Duchenne's dystrophy are typically in a
wheelchair by the age of 12.
• Patients with Becker's dystrophy have a reduced life expectancy, but most
survive into the fourth or fifth decade.
– Mental retardation may occur in Becker's dystrophy, but it is not as
common as in Duchenne's.
– Cardiac involvement occurs in Becker's dystrophy and may result in
heart failure; some patients manifest with only heart failure.
– Other less common presentations are asymptomatic hyper-CK-emia,
myalgias without weakness, and myoglobinuria.

32. Laboratory findingsSerum CK levels, results of EMG, and
muscle biopsy findings closely resemble those in Duchenne's
dystrophy.
– The diagnosis of Becker's muscular dystrophy requires
Western blot analysis of muscle biopsy samples,
demonstrating a reduced amount or abnormal size of
dystrophin or mutation analysis of DNA from peripheral
blood leukocytes.
– Genetic testing reveals deletions or duplications of the
dystrophin gene in 65% of patients with Becker's
dystrophy, approximately the same percentage as in
Duchenne's dystrophy

33. MYOTONIC DYSTROPHY
Myotonic dystrophy is also known as dystrophia
myotonica (DM).
• The condition is composed of at least two clinical
disorders with overlapping phenotypes and distinct
molecular genetic defects:
1.Myotonic dystrophy type 1 (DM1), the classic disease
originally described by Steinert
2. Myotonic dystrophy type 2 (DM2), also called
proximal myotonic myopathy

34. • Clinical feature
– The clinical expression of DM1 varies widely and involves
many systems other than muscle.
– Affected patients have a typical "hatchet-faced" appearance
due to temporalis, masseter, and facial muscle atrophy and
weakness.
– Frontal baldness is also characteristic of the disease.
– Neck muscles, including flexors and sternocleidomastoids, and
distal limb muscles are involved early.
– Weakness of wrist extensors, finger extensors, and intrinsic
hand muscles impairs function.
– Ankle dorsi-flexor weakness may cause footdrop.

35. – Proximal muscles remain stronger throughout the course, although
preferential atrophy and weakness of quadriceps muscles occur in
many patients.
– Palatal, pharyngeal, and tongue involvement produce a dysarthric
speech, nasal voice, and swallowing problems.
– Some patients have diaphragm and intercostal muscle weakness,
resulting in respiratory insufficiency.
– Myotonia, which usually appears by age 5 years, is demonstrable by
percussion of the thenar eminence, the tongue, and wrist extensor
muscles.
• Myotonia causes a slow relaxation of hand grip after a forced voluntary
closure.
• Advanced muscle wasting makes myotonia more difficult to detect.

36. – Cardiac disturbances occur commonly in patients with DM1.
• ECG abnormalities include first-degree heart block and more extensive
conduction system involvement.
• Complete heart block and sudden death can occur.
• Congestive heart failure occurs infrequently but may result from cor
pulmonale secondary to respiratory failure.
• Mitral valve prolapse also occurs commonly.
– Other associated features include intellectual impairment,
hypersomnia, posterior sub capsular cataracts, gonadal atrophy,
insulin resistance, and decreased esophageal and colonic motility.

37. – DM2, or PROMM, has a distinct pattern of muscle weakness affecting
mainly proximal muscles.
– Other features of the disease overlap with DM1, including cataracts,
testicular atrophy, insulin resistance, constipation, hypersomnia, and
cognitive defects.
– Cardiac conduction defects occur but are less common, and the
hatchet face and frontal baldness are less consistent features.

38. • Laboratory findings
– The diagnosis of myotonic dystrophy can usually be made on the basis
of clinical findings.
– Serum CK levels may be normal or mildly elevated.
– EMG evidence of myotonia is present in most cases of DM1 but may
be more patchy in DM2.
– Muscle biopsy shows muscle atrophy, which selectively involves type 1
fibers in 50% of cases,a and ringed fibers in DM1 but not in DM2.
• Typically, numerous internalized nuclei can be seen in individual muscle
fibers as well as atrophic fibers with pyknotic nuclear clumps in both DM1
and DM2.
• Necrosis of muscle fibers and increased connective tissue, common in other
muscular dystrophies, are less apparent in myotonic dystrophy.

39. • Treatment
– The myotonia in DM1 rarely warrants treatment, though some patients
with DM2 are significantly bothered by the discomfort related to the
associated muscle stiffness.
• Phenytoin and mexiletine are the preferred agents for the occasional patient who
requires an antimyotonia drug; other agents, particularly quinine and
procainamide, may worsen cardiac conduction.
– A cardiac pacemaker should be considered for patients with unexplained
syncope, advanced conduction system abnormalities with evidence of
second-degree heart block, or trifascicular conduction disturbances with
marked prolongation of the PR interval.
– Molded ankle-foot orthoses help stabilize gait in patients with foot drop.
– Excessive daytime somnolence with or without sleep apnea is not
uncommon; treat it with Modafinil

40. INFLAMMATORY MYOPATHIES

41. Introduction
The inflammatory myopathies represent the
largest group of acquired and potentially
treatable causes of skeletal muscle weakness.
• They are classified into three major groups:
Polymyositis (PM),
Dermatomyositis (DM), and
Inclusion body myositis (IBM

42. Clinical Features
The prevalence of the inflammatory myopathies is estimated at
1 in 100,000.
– PM as a stand-alone entity is a rare disease.
– DM affects both children and adults and women
more often than men.
– IBM is three times more frequent in men than in
women, more common in whites than blacks,
and is most likely to affect persons aged >50
years.

43. – These disorders present as progressive and symmetric muscle weakness
except for IBM, which can have an asymmetric pattern.
• Patients usuaally report increasing difficulty with everyday tasks requiring the
use of proximal musclesa, such as getting up from a chair, climbing steps,
stepping onto a curb, lifting objects, or combing hair.
• Fine-motor movements that depend on the strength of distal muscles, such as
buttoning a shirt, sewing, knitting, or writing, are affected only late in the course
of PM and DM, but fairly early in IBM.
• Falling is common in IBM because of early involvement of the quadriceps muscle,
with buckling of the knees.
– Ocular muscles are spared, even in advanced, untreated cases; if these
muscles are affected, the diagnosis of inflammatory myopathy should be
questioned.
– Facial muscles are unaffected in PM and DM, but mild facial muscle
weakness is common in patients with IBM

44. – In all forms of inflammatory myopathy, pharyngeal and neck-flexor
muscles are often involved, causing dysphagia or difficulty in holding
up the head (head drop).
– In advanced and rarely in acute cases, respiratory muscles may also
be affected. Severe weakness, if untreated, is almost always
associated with muscle wasting
– Weakness in PM and DM progresses subacutely over a period of
weeks or months and rarely acutely;
– By contrast, IBM progresses very slowly, over years, simulating a late-
life muscular dystrophy or slowly progressive motor neuron disorder.

45. Features associated with inflammatory myopathy

46. • POLYMYOSITIS
– The actual onset of PM is often not easily determined, and patients
typically delay seeking medical advice for several weeks or even months.
– PM mimics many other myopathies and is a diagnosis of exclusion.
– It is a subacute inflammatory myopathy affecting adults, and rarely
children, who do not have any of the following:
• Rash,
• Involvement of the extraocular and facial muscles,
• Family history of a neuromuscular disease,
• History of exposure to myotoxic drugs or toxins,
• Endocrinopathy and Neurogenic disease,
• Muscular dystrophy, Biochemical muscle disorder
• IBM as excluded by muscle biopsy analysis

47. – As an isolated entity, PM is a rare (and over diagnosed) disorder;
– More commonly, PM occurs in association with
Systemic autoimmune or connective tissue disease,
A known viral or bacterial infection.
Drugs, especially d-penicillamine, statins, or zidovudine (AZT), may
also trigger an inflammatory myopathy similar to PM.

48. • DERMATOYOSITIS
– DM is a distinctive entity identified by a characteristic rash
accompanying, or more often preceding, muscle weakness.
– The rash may consist of a blue-purple discoloration on the upper
eyelids with edema (heliotrope rash)
– A flat red rash on the face and upper trunk, and erythema of the
knuckles with a raised violaceous scaly eruption (Gottron's sign)
– The erythematous rash can also occur on other body surfaces,
including the knees, elbows, malleoli, neck and anterior chest (often
in a V sign), or back and shoulders (shawl sign), and may worsen
after sun exposure.

49. Heliotrope rash Gottron’s sign

50. – In some patients, the rash is pruritic, especially on the scalp, chest, and
back.
– Dilated capillary loops at the base of the fingernails are also
characteristic.
– The cuticles may be irregular, thickened, and distorted, and the lateral
and palmar areas of the fingers may become rough and cracked, with
irregular, "dirty" horizontal lines, resembling mechanic's hands.
– The weakness can be mild, moderate, or severe enough to lead to
quadriparesis.
– At times, the muscle strength appears normal, hence the term
dermatomyositis sine myositis.
– When muscle biopsy is performed in such cases, however, significant
perivascular and perimysial inflammation is often seen.

51. INCLUSION BODY MYOSITIS
– In patients 50 years of age, IBM is the most common of the
inflammatory myopathies.
• It is often misdiagnosed as PM and is suspected only later when a patient
with presumed PM does not respond to therapy.
– Weakness and atrophy of the distal muscles, especially foot
extensors and deep finger flexors, occur in almost all cases of IBM
and may be a clue to early diagnosis.
• Some patients present with falls because their knees collapse due to early
quadriceps weakness.
• Others present with weakness in the small muscles of the hands, especially
finger flexors, and complain of inability to hold objects such as golf clubs or
perform tasks such as turning keys or tying knots

52. On occasion, the weakness and accompanying atrophy can
be asymmetric and selectively involve the quadriceps,
iliopsoas, triceps, biceps, and finger flexors, resembling a
lower motor neuron disease.
– Dysphagia is common, occurring in up to 60% of IBM
patients, and may lead to episodes of choking.
Sensory examination is generally normal; some patients
have mildly diminished vibratory sensation at the ankles
that presumably is age-related.
Disease progression is slow but steady, and most patients
require an assistive device such as cane, walker, or
wheelchair within several years of onset.

53. • Extra-muscular features of IMs
– Systemic symptoms, such as fever, malaise, weight loss, arthralgia, and
Raynaud's phenomenon, especially when inflammatory myopathy is
associated with a connective tissue disorder.
– Joint contractures, mostly in DM and especially in children.
– Dysphagia and gastrointestinal symptoms, due to involvement of
oropharyngeal striated muscles and upper esophagus, especially in DM
and IBM.
– Cardiac disturbances, including atrioventricular conduction defects,
tachyarrhythmias, dilated cardiomyopathy, a low ejection fraction, and
congestive heart failure, may rarely occur, either from the disease itself
or from hypertension associated with long-term use of glucocorticoids.

54. – Pulmonary dysfunction, due to weakness of the thoracic muscles,
interstitial lung disease, or drug-induced pneumonitis (e.g., from
methotrexate), which may cause dyspnea, nonproductive cough, and
aspiration pneumonia. Interstitial lung disease may precede
myopathy or occur early in the disease and develops in up to 10% of
patients with PM or DM, most of whom have antibodies to t-RNA
synthetases, as described below.
– Subcutaneous calcifications, in DM, sometimes extruding on the skin
and causing ulcerations and infections.
– Arthralgias, synovitis, or deforming arthropathy with subluxation in
the interphalangeal joints can occur in some patients with DM and
PM who have Jo-1 antibodies

55. Association with malignanc
– Although all the inflammatory myopathies can have a chance
association with malignant lesions, especially in older age groups,
the incidence of malignant conditions appears to be specifically
increased only in patients with DM and not in those with PM or IBM.
– The most common tumors associated with DM are
Ovarian cancer, Breast cancer,
Melanoma, Colonic cancer, and
Non-Hodgkin lymphoma.

56. Overlap syndromes
– These describe the association of inflammatory
myopathies with connective tissue diseases.
– A well-characterized overlap syndrome occurs in patients
with DM who also have manifestations of systemic
sclerosis or mixed connective tissue disease, such as
sclerotic thickening of the dermis, contractures,
esophageal hypomotility, microangiopathy, and calcium
deposits

57. • Pathogenesis
– An autoimmune etiology of the
inflammatory myopathies is
indirectly supported by
1.an association with other
autoimmune or connective tissue
diseases;
2.the presence of various
autoantibodies;
3.an association with specific
major histocompatibility complex
(MHC) genes;
4.demonstration of T cell–
mediated myocytotoxicity or
complement-mediated
microangiopathy;
5. a response to immunotherapy.

58. • Diagnosis
• The clinically suspected diagnosis
of PM, DM, or IBM is confirmed
by analysis of
Serum muscle enzymes,
EMG findings, and
Muscle biopsy

59. – The most sensitive enzyme is CK, which in active disease can be
elevated as much as fiftyfold.
– Although the CK level usually parallels disease activity, it can be
normal in some patients with active IBM or DM, especially when
associated with a connective tissue disease.
– The CK is always elevated in patients with active PM.
– Along with the CK, the serum glutamic-oxaloacetic and glutamate
pyruvate transaminases, lactate dehydrogenase, and aldolase may
be elevated.

60. – Needle EMG shows myopathic potentials characterized by short-
duration, low-amplitude polyphasic units on voluntary activation and
increased spontaneous activity with fibrillations, complex repetitive
discharges, and positive sharp waves.
– Mixed potentials (polyphasic units of short and long duration)
indicating a chronic process and muscle fiber regeneration are often
present in IBM.
– These EMG findings are not diagnostic of an inflammatory myopathy
but are useful to identify the presence of active or chronic myopathy
and to exclude neurogenic disorders.
– MRI

61. – Muscle biopsy—in spite of occasional variability in demonstrating all
of the typical pathologic findings—is the most sensitive and specific
test for establishing the diagnosis of inflammatory myopathy and for
excluding other neuromuscular diseases.
– Inflammation is the histologic hallmark for these diseases
– Additional features are characteristic of each subtype

62. • Polymyositis
– Demonstrates scattered
inflammatory foci with
lymphocytes invading or
surrounding muscle fibers.
– Note lack of chronic
myopathic features
(increased connective tissue,
atrophic or hypertrophic
fibers) as seen in inclusion
body myositis.

63. • Dermatomyositis
– Demonstrates atrophy of the
fibers at the periphery of the
fascicle (perifascicular
atrophy).

64. • Inclusion body myositis
– Demonstrate the typical
features of vacuoles with
lymphocytic infiltrates
surrounding non vacuolated
or necrotic fibers
– Tiny endomysial deposits of
amyloid visualized with
crystal violet

65. • Treatment
– The goal of therapy is to improve muscle strength, thereby improving
function in activities of daily living, and ameliorate the extra-
muscular manifestations (rash, dysphagia, dyspnea, fever).
– When strength improves, the serum CK falls concurrently; however,
the reverse is not always true.
– Unfortunately, there is a common tendency to "chase" or treat the
CK level instead of the muscle weakness, a practice that has led to
prolonged and unnecessary use of immunosuppressive drugs and
erroneous assessment of their efficacy

66. • Glucocorticoids
– Oral prednisone is the initial treatment of choice; the effectiveness
and side effects of this therapy determine the future need for
stronger immunosuppressive drugs.
• High-dose prednisone, at least 1 mg/kg per day, is initiated as early in the
disease as possible.
• After 3–4 weeks, prednisone is tapered slowly over a period of 10 weeks to 1
mg/kg every other day.
• If there is evidence of efficacy and no serious side effects, the dosage is then
further reduced by 5 or 10 mg every 3–4 weeks until the lowest possible dose
that controls the disease is reached.
– The efficacy of prednisone is determined by an objective increase in
muscle strength and activities of daily living, which almost always
occurs by the third month of therapy.

67. • Other immuno-suppressive drugs
– Azithropine Cyclophosphamide
– Cyclosporine Mycophenolate mofetil
– Methotrixate
• Immuno modulation

68. • Prognosis
– The 5-year survival rate for treated patients with PM and DM is 95% and
the 10-year survival rate is 84%; death is usually due to pulmonary,
cardiac, or other systemic complications.
– The prognosis is worse for patients who are severely affected at
presentation, when initial treatment is delayed, and in cases with severe
dysphagia or respiratory difficulties.
– Older patients, and those with associated cancer also have a worse
prognosis.
– Treatment response DM >> PM >> IBM