Download SDL-INFLAMMATORY MYOPATHIES INTRODUCTION

SDL-INFLAMMATORY MYOPATHIES
INTRODUCTION & EPIDEMIOLOGY
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The term “myositis” can be used for any disorder associated with skeletal muscle inflammation.
Inflammatory myopathies may be subdivided into two major groups:
o infectious myopathies.
o idiopathic inflammatory myopathies - comprise three major diagnoses
 (1) dermatomyositis (DM)
 (2) polymyositis (PM)
 (3) inclusion-body myositis (IBM)
 Although these disorders share several common features including muscle weakness
and inflammatory infiltrates on muscle biopsy, they are a heterogeneous group in terms
of morphologic findings, clinical presentation and pathogenesis.
 DM is the most common and PM is the least common.
 IBM is the most common myopathy above the age of 50.
 DM is twice as common in women as in men. DM affects children and adults equally.
 In adults, the peak age of DM onset = 50 years, in children, the peak age is
between 5 and 10 years of age.
THE SKELETAL MUSCLE BIOPSY
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First, A portion of the tissue is quick frozen in liquid nitrogen because the tissue is subjected to frozen
sections for special histochemical staining.
Secondly, a portion of the skeletal muscle is submitted in formalin fixative for routine processing.
Lastly, fragments of skeletal muscle are sectioned into 1 cubic millimeter fragments of tissue and
submitted into glutaraldehyde fixative for electron microscopic evaluation.
Most importantly, before subjecting a patient to a biopsy, make sure that the surgeon knows that the
tissue must be submitted to the pathology laboratory fresh and placed onto a clamp.
DERMATOMYOSITIS
1. Definition and Clinical Manifestations
 inflammatory process of the skin and skeletal muscle.
 Cutaneous manifestations:
o characterized by a distinctive rash accompanying (or preceding) muscle weakness.
 heliotrope rash, named for the flower because of the blue-purple discoloration of the
skin, may involve the upper eyelids.
 A flat, red rash may involve the face and upper trunk.
 Gottron rash, or papules, are raised violaceous scaly eruptions on the skin.
 The skin rash may worsen upon sun exposure.
o Calcinosis cutis, or deposition of calcium within the skin can also be seen in DM.
 Calcinosis cutis manifests as firm, yellow, or flesh-colored nodules, commonly seen over
bony prominences.
o Skin biopsy is oftentimes helpful in establishing the diagnosis of DM.
o Erythematous cutaneous lesions may occur on exposed skin such as the face, neck, and
anterior chest.
 This is called the “V” sign of the neck and the shawl sign on the upper back.
o Periungal telangiectasias involve the skin of the hands.
 Telangiectasias are small dilated blood vessels near the surface of the skin
The heliotrope rash is named for the color of the heliotrope flowering plant (left). Prominent bluepurple cutaneous discoloration of the eyelids with accompanying edema may be seen in patients
with dermatomyositis.
Gottron’s papules are erythematous plaques
located on the dorsal aspects of the hands
especially located over the proximal and
distal joints of the hand.
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Skeletal Muscle Manifestations
o Muscle weakness is typically characterized by slow
onset, is bilaterally symmetrical, and sometimes
associated with myalgias.
o DM typically affects the proximal skeletal muscle groups first.
o When involves skeletal muscle of oropharynx and proximal esophagus, dysphagia may occur.
o Myalgia is relatively uncommon in patients with DM.
Other Clinical Findings: Extracutaneous and extramuscluar manifestations are also seen:
o Arthralgias and arthritis:
 Arthralgias are joint pains or aches without obvious gross signs of inflammation
 arthritis is applied to cases of joint pain with obvious gross signs of inflammation.
 The arthritis of DM is not erosive or deforming, in contrast to rheumatoid arthritis.
o Esophageal disease may be another manifestation of DM.
 Dysphagia, or difficulty swallowing, is estimated to be present in 15-50% of patients.
 Interstitial pneumonitis is more frequent in patients with esophageal involvement.
o Cardiac disease in DM is associated with a poor prognosis..
o DM patients are also more likely to develop visceral cancers.
 The most common include carcinoma of the lung, breast, ovaries and colon.
Juvenile DM
o causes a similar cutaneous rash and involves skeletal muscles, but is more commonly
associated with abdominal pain and gastrointestinal tract dysfunction.
o Vasculopathy w/in blood vessels of the GI tract can lead to mucosal ulceration and perforation.
2. Etiology and Pathogenesis
 The cause unknown. Possibly thought to be caused by immune-mediated insults.
o Injury to the skeletal muscle in DM is primarily mediated by immunological mechanisms.
o capillaries within muscle tissue appear to be the primary targets for immune-mediated injury.
o Myocyte necrosis ensues.
o Similar mechanisms of disease are associated with the cutaneous manifestations of DM.
3. Morphology
 Dermatomyositis is characterized by inflammatory infiltrate, primarily mononuclear (lymphocytic) in
nature, around small blood vessels and within the perimysial connective tissue.
 Groups of atrophic muscle fibers are noted particularly within at the periphery of fascicles (perifascicular
distribution of atrophic fibers).
 Perifascicular atrophy is sufficient for the diagnosis of dermatomyositis even in the absence of a
significant inflammatory infiltrate.
 Skin punch biopsies may show significant epidermal atrophy and a lymphocytic perivascular
inflammatory infiltrate
Sections of skeletal muscle obtained from the quadriceps muscle
demonstrate a significant inflammatory infiltrate with associated cellular
necrosis. The increased space noted between muscle fascicles is
indicative of the atrophy associated with dermatomyositis
4. Laboratory Studies
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Because of the presence of myocyte necrosis in
skeletal muscle tissue, enzymes normally housed within the myocytes are released into the
extracellular space and serum.
Elevated erythrocyte sedimentation rates (ESRs) are often seen in patients with dermatomyositis, as
well as other connective tissue diseases.
Elevated serum muscle enzymes including creatine kinase, aldolase, aspartate aminotransferase (AST)
and lactic dehydrogenase (LDH) are often demonstrated in patients as well.
Serologic studies may document the presence of Anti-Jo-1 antibodies, especially if the patient has lung
involvement.
Autoantibodies directed against transfer RNA synthetases seem to be rather specific for inflammatory
myopathies.
5. Other Diagnostic Studies
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Electromyography (EMG) is a technique for evaluating and recording the electrical activity produced by
skeletal muscles
Based on the presence of edema; MRI can distinguish between affected and unaffected muscles.
6. Treatment and Prognosis
 Patients with DM, as well as other inflammatory myopathies are often treated with high dose steroids to
manage the immunologic/inflammatory assault on skeletal muscle microvasculature
OTHER INFLAMMATORY MYOPATHIES
POLYMYOSITIS
1. Definition and Clinical Manifestations
 PM is an inflammatory myopathy characterized by symmetric proximal muscle involvement
 There is an overalap in the clinical findings of polymyositis and dermatomyositis.
 Importantly, polymyositis is different from dermatomyositis in that this disease lacks the cutaneous
involvement of dermatomyositis.
 Polymyositis primarily affects adults.
 Pt’s may also experience involvement of blood vessels (vasculitis) of the heart, and lungs.
2. Etiology and Pathogenesis
 polymyositis is caused by direct cytotoxic T-lymphocyte (cell-mediated) injury to the myocyte. (vs.
immune-mediated damage w/ DM)
 Increased serum cytokines, like tumor necrosis factor alpha, may also be seen in patients with PM.
 Immunosuppressive therapy in patients with polymyositis is generally useless, in contrast to
dermatomyositis.
3. Clinical Manifestations
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Unlike patients with DM, patients with PM usually have muscle specific symptoms that are not
associated with some of the clinical findings associated with DM.
For example, patients with PM have no associated increased risk of malignancy and the typical
dermatologic manifestations of DM are not seen in patients with PM.
Heliotrope rash, shawl sign, and generalized erythroderma, all signs which may be seen in DM patients
are not seen in PM.
Features and the distribution of muscular weakness is similar to that seen in DM patients.
4. Morphology
 Polymyositis demonstrates histologic features similar to that seen in dermatomyositis.
 Lymphocytes are often seen invading the myocyte. – predominantly within the muscle fascicle.
 There are no signs of vasculopathy in patients with polymyositis.
H&E stained section (left) of muscle biopsy documents myocytic infiltration by lymphocytes. Immunohistochemical analysis
would confirm that these T-lymphocytes are CD8+ cytotoxic lymphocytes. The image on the right is a lymphocyte penetrating
underneath the basement membrane of a myofiber.
5.Laboratory Studies - same as for dermatomyositis.
6.Treatment and prognosis - similar to that of dermatomyositis.
INCLUSION BODY MYOSITIS
1. IBM is uncommon and characterized by an insidious onset
 involvement of distal muscles, esp. extensors of the knee(quadriceps) and flexors of wrist and fingers.
 Also unlike DM and PM, patients with IBM can show asymmetric muscle involvement.
 The disease almost always affects individuals over the age of 50 years.
 Most cases of inclusion body myositis are sporadic, but familial cases have also been described.
2. Etiology and Pathogenesis
 Cytotoxic T lymphocytes are present but immunosuppressive treatments are not beneficial
 intracellular deposits of beta-amyloid and tau proteins - possibly related to the aging process.
 There are two forms of inclusion body myopathy – autosomal recessive and autosomal dominant
3. Clinical Manifestations
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Sporadic IBM is more common in the sixth and seventh decades than in younger patients.
most common skeletal muscle disease in elderly population.
causes progressive proximal and distal muscle weakness.
o More prominent distal muscle weakness tends to be a more common finding in IBM as
compared to PM which has a more prominent proximal distribution of muscle weakness.
4. Morphology – The pathological changes of IBM are highly characteristic.
 Light microscopic examination of skeletal muscle tissue shows myofibers with vacuoles or cracks some
of which are lined by basophilic granules.
o best seen in frozen section slides prep by cryostat and stained w/ a modified Gomori trichrome.
 By electron microscopy, the abnormal fibers contain paired helical filaments similar to those of
Alzheimer's disease, straight filaments, myelinoid membranous bodies, increased glycogen, and
abnormal mitochondria.
 The filamentous inclusions of IBM have the optical properties of amyloid and contain beta amyloid,
hyperphosphorylated tau protein, apolipoprotein E, presenillin 1, prion protein, and other proteins,
similar to protein accumulations seen in patients with Alzheimer’s disease.
 The inflammatory component consists of cytotoxic T cells and macrophages, similar to polymyositis.
 pathogenesis is not known but probably involves ageing of myofibers, oxidative damage, and an
unknown trigger that initiates inflammation.
Histologic sections of muscle biopsy show intracellular
vacuolization (white areas within the eosinophilc cytoplasm on
the right) and peripheral basophilic stippling.
5. Laboratory Studies
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Mild creatine kinase (CK) elevations are seen in patients with IBM.
CK and other skeletal muscle enzyme elevations are generally higher in patients with DM and PM
compared to the lower level in patients with IBM.
6. Treatment
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Patients with IBM are often refractory to treatment with corticosteroids and other
immunosuppressant agents such as azathioprine