Idiopathic Inflammatory Myopathies - PowerPoint Presentation

Slide1

Idiopathic InflammatoryMyopathies

Slide2

The idiopathic inflammatory

myopathies

(IIM) are a heterogeneous group of disorders characterized by symmetric proximal muscle weakness and elevated serum levels of enzymes derived from skeletal muscle.

These include

creatine

phosphokinase

(CPK),

aldolase

,

aspartate

, and

alanine

aminotransferases

(AST and ALT), and lactate

dehydrogenase

(LDH).

In addition, electromyography (EMG), magnetic resonance imaging (MRI), and muscle histology show changes indicative of non-

supparative

inflammation.

Slide3

FEATUERS OF IIM

1-Symmetric proximal muscle weakness

2. Muscle biopsy evidence

myositis

3. Increase in serum skeletal muscle enzyme

4. Characteristic

electromyographic

pattern

5. Typical rash

dermatomyositis

Slide4

Classification of idiopathic inflammatory

myopathies

I-

Primary idiopathic

polymyositis

II-

Primary idiopathic

dermatomyositis

III-

Polymyositis

or

dermatomyositis

with malignancy

IV -

Juvenile

dermatomyositis

(or

polymyositis

)

V -

Overlap syndrome of

polymyositis

or

dermatomyositis

with another connective tissue disease

VI -

Inclusion body

myositis

VII -

Rare forms of idiopathic

myositis

(a)

Granulomatous

myositis

(b)

Eosinophilic

myositis

(c)

Focal

myositis

(d)

Orbital

myositis

Slide5

The findings of

polymyositis

or

dermatomyositis

can be seen in patients with another collagen vascular disease, such as systemic lupus

erythematosus

(SLE) or scleroderma, or associated with a malignancy. Inclusion body

myositis

(IBM) occurs in the elderly and is characterized by a

polymyositis

like presentation (although the specific muscles involved are more variable) and a characteristic histology which includes rimmed vacuoles.

the presentations of the different

myositis

syndromes vary considerably from patient to patient. The usual presentation is insidious, progressive painless symmetric proximal muscle weakness which develops over 3 to 6 months before the patient seeks medical attention.

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CLINICAL FEATURES

Constitutional

Fatigue, fever, and weight loss may occur with any IIM. Weight loss may result from poor caloric intake associated with pharyngeal striated muscle dysfunction or

esophageal

dysmotility

and

dysphagia

. If weight loss persists or is severe, an associated malignancy should be considered.

Skeletal Muscle

Typically, skeletal muscle involvement develops insidiously, is bilateral and symmetric in distribution, affects proximal muscles much more than distal muscles, and is painless.

Slide7

In polymyositis

and

dermatomyositis

, the lower extremity (pelvic girdle) is often affected causing difficulty walking up steps or arising from a seated position. Upper extremity (shoulder girdle) symptoms, which may lag behind those of the lower extremity, include difficulty raising their arms overhead or combing their hair. Neck flexor weakness may also occur. When

myalgias

are present, they are more common with exercise. Proximal

dysphagia

, with nasal regurgitation of liquids and pulmonary aspiration, is a poor prognostic sign and indicates pharyngeal striated muscle involvement.

Slide8

Pharyngeal weakness also results in hoarseness or

dysphonia

and a nasal quality voice. Ocular or facial muscle weakness is very uncommon in IIM, and their presence should prompt consideration of another diagnosis.

Physical examination using manual muscle testing confirms weakness of individual muscles or muscle groups. In JDM, the Childhood

Myositis

Assessment Scale has been shown to be reliable and valid for assessing physical function, muscle strength, and endurance. Muscle atrophy and joint contractures are

sequelae

of disease damage and are late findings in chronic muscle inflammation.

Slide9

Skin

The skin rash of

dermatomyositis

may precede, develop simultaneously with, or follow symptoms of

myopathy

Gottron’s

papules and the heliotrope rash on eyelids are considered

pathognomonic

features.

Gottron’s

papules are scaly,

erythematous

, or

violaceous

papules and plaques located over bony prominences, particularly over the small joints of the hands, elbows, knees, and ankles.

Gottron’s

sign is a macular

erythema

that occurs in the same distribution.

Slide10

Gottron's papules

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Heliotrope rash

Slide12

Gottron's sign on knee

Slide13

Gottron's sign on elbow

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Photosensitivity with rash on the face or anterior chest, termed the V sign, may also be seen.

Pruritus

is common, particularly in the scalp. Other

cutaneous

changes include a rash located over the upper back and across both shoulders (the shawl sign), rash on the lateral surface of the thighs and hips (holster sign),

erythroderma

,

cuticular

hypertrophy,and

periungual

erythema

.

Capillary changes are often present proximal to the cuticles in patients with

Raynaud’s

phenomenon. Cracking, fissuring, or both, of the lateral and

palmar

digital skin pads is termed mechanic’s hands.

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Linear erythema

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Scalp rash

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V sign

Slide18

Shawl sign

Slide19

Note the changes on the knuckles and dorsum of the hand in dermatomyositis

(

Gottron's

sign). B, Rash is absent on the knuckles but present on the phalanges in lupus

Slide20

Capillary nail-fold changes in dermatomyositis.

Slide21

Mechanic's hands in a white (A) and a black (B) patient. Note the characteristic skin changes on the lateral side of the fingers

Slide22

Joints

Arthralgias

or arthritis, if they occur, usually develop early in the disease course. They tend to be rheumatoid like in distribution and are generally mild. Joint findings are more common with overlap syndromes and in childhood

dermatomyositis

.

Lung

Dyspnea

may result from interstitial lung disease as well as non-

parenchymal

problems, such as

ventilatory

(diaphragmatic and

intercostal

) muscle weakness or cardiac dysfunction. Pulmonary function testing reveals restrictive physiology, The presence of a “ground glass” appearance on high resolution computed tomography (CT) indicates

alveolitis

, a potentially treatment-responsive inflammatory condition with a more

favorable

prognosis. In contrast, the presence of “honeycombing” usually indicates fibrosis.

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Heart

Cardiac involvement is common in IIM but is seldom symptomatic The most common finding is a rhythm disturbance. More ominous complications, such as congestive heart failure and pericardial

tamponade

, are quite rare.

Gastrointestinal Tract

Swallowing problems (upper

dysphagia

) manifest as difficulty in the initiation of deglutition or nasal regurgitation of liquids. If severe, aspiration of oral contents leads to chemical

pneumonitis

.

Cricopharyngeal

muscle dysfunction is more common in inclusion body

myositis

, Gastrointestinal mucosal ulceration and

hemorrhage

are rare.

Slide24

INVESTIGATIONS

Serum Muscle Enzymes

Enzymes that leak into the serum from injured skeletal muscle include the CK,

aldolase

, AST, ALT, and LDH . Which enzymes are elevated and which one is the best to follow varies from patient to patient. Some feel that the CK is the most reliable enzyme to use in routine patient care and best reflects disease activity.

The CK is elevated at least at some time during the course of illness in patients with an IIM. Lower values are often seen late in the disease course, in IBM, and in cancer-related

myositis

. The myocardial fraction of CK (CK-MB) may be increased in

myositis

without any cardiac involvement because this

isoform

is also released from regenerating

myoblasts

.

Slide25

Electromyography

Electromyography is a sensitive but nonspecific method of evaluating muscle for evidence of inflammation. Of the 90% of patients with active

myositis

who have an abnormal EMG, about half show the classic findings of inflammation of fibrillation potentials, complex repetitive discharges, positive sharp waves, and complex motor unit potentials of low amplitude and short duration.

In addition to aiding in the diagnosis, EMG is helpful in the selection of a site for muscle biopsy. When this is the case, the study should be performed unilaterally and a

contralateral

muscle chosen for biopsy to avoid confusion with inflammation

artifact

that can result from injury caused by the needle.

Slide26

Muscle Biopsy

Muscle histology remains the gold standard for confirming the diagnosis of an IIM . Despite the characteristic features described below, some patients with active

myositis

have a normal biopsy.

Because the disease is patchy in distribution, sampling error precludes 100% sensitivity. Furthermore, the changes in some biopsies may be too

nonspecific.The

most characteristic changes in

polymyositis

include degeneration and regeneration of muscle

fibers

and CD8+ T lymphocytes invading non-necrotic

fibers

.

Slide27

In

dermatomyositis

, CD4+ T cells and B cells predominate in the

perivascular

areas and

perifascicular

atrophy, related to capillary depletion and dropout, is noted. The histology of IBM is characterized by the presence of lined or rimmed vacuoles.

Otherwise IBM may appear identical to that of

polymyositis

, be essentially normal, or show triangulated cells with

fiber

-type grouping, changes considered to be indicative of a neuropathic process. In chronic

myositis

, macrophages are seen

phagocytosing

necrotic

fibers

and muscle is replaced by fibrous connective tissue or fat .

Slide28

Magnetic Resonance Imaging techniques add an important dimension to our approach to patients with

myopathy

. MRI is non-invasive and can be used to visualize large areas of muscle.

T1-weighted images provide excellent anatomic detail, with clear delineation of various muscle groups and are useful in assessing changes resulting from damage and

chronicity

. T2- weighted images with fat suppression or STIR (short tau inversion recovery) sequences can identify

edema

, which is indicative of active inflammation.

Accordingly, MRI can be used to document

myositis

or a disease flare, distinguish chronic active from chronic inactive

myositis

, and noninvasively direct the site of biopsy.

Slide29

Serum Autoantibodies

In addition, some antibodies are termed

myositis

-specific auto-antibodies (MSAs) because they are found exclusively in patients with features of an inflammatory

myopathy

.

Although a few patients have more than one serum autoantibody, several MSAs are rarely detected in the same patient.

A negative antinuclear antibody (ANA) test does exclude an MSA, as the latter antigens are

cytoplasmic

in location and the

immuno

-fluorescence staining pattern may be subtle. Testing for serum auto-antibodies can both solidify the diagnosis of

myositis

in patients with atypical clinical features and provide prognostic information regarding the likelihood of future clinical complications.

Slide30

Antisynthetase(anti JO)

autoantibodies

;More common in

polymyositis

than

dermatomyositis

; interstitial lung disease, arthritis,

Raynaud's

phenomenon, fevers, mechanic's hands

Signal recognition particle (SRP)

:

Polymyositis

; possible severe disease and cardiac involvement .

Slide31

PATHOLOGY ANDIMMUNOPATHOLOGY

The characteristic skeletal muscle pathology in the idiopathic inflammatory

myopathies

(IIM) consists of chronic inflammation with infiltration by mononuclear cells, including lymphocytes, plasma cells, macrophages and

dendritic

cells, in the

endo-mysium

(between

myocytes

),

perimysium

(within fascicles), or

perivascular

(vessels in

interstitium

surrounding muscle

fibers

) areas .

The muscle

fibers

(

myocytes

), which may be necrotic or non-necrotic, show evidence of degeneration and regeneration,

fiber

hypertrophy or atrophy, and replacement by fibrosis or fat, and are often accompanied by increased connective tissue or fibrosis in the interstitial areas around the muscle cells .

Slide32

PATHOGENESIS

While the

etiology

and pathogenesis of the IIM remain unclear, a number of lines of investigation have suggested possible ways in which selected environmental exposures in genetically susceptible individuals may lead to chronic immune activation and the ultimate immunologic attack on muscle and other involved tissues.

Genetic Factors

The finding of families in which two or more blood relatives have

myositis

and associations of

myositis

with particular genes support the hypothesis that

myositis

is at least in part inherited. Polymorphic alleles in the major

histocompatibility

locus (MHC) are the major

immunogenetic

risk and protective factors identified for the IIM.

Slide33

Environmental Factors

The temporal association of exposure to a number of infectious and non-infectious agents prior to the onset of the IIM in certain individuals, as well as reports documenting temporal, seasonal, or geographic clustering of IIM cases suggest a role for environmental factors in initiation of disease Epidemiologic investigations have also suggested a number of environmental factors which may be important in the development of IIM.

Most are not proven environmental risk factors, but for some exposures, case-controlled epidemiologic studies, cases of

dechallenge

and re-challenge, and biomarker assays strengthen the association with illness onset. Of the infectious agents, Group A streptococcus and influenza have the strongest evidence of association with onset of juvenile IIM and toxoplasmosis with adult DM from case-controlled epidemiologic studies.

Slide34

CLASSIFICATION AND DIAGNOSTIC CRITERIA

First exclude all other

myopathies

Symmetric proximal muscle weakness

Increase in serum muscle enzymes, such as CK, AST, ALT,

aldolase

, and LDH Abnormal

electromyographic

findings, such as short, small,

polyphasic

motor units; fibrillations; positive sharp waves;

insertional

irritability; and bizarre high-frequency repetitive discharges

Abnormal muscle biopsy findings, such as mononuclear infiltration, regeneration, degeneration, and necrosis

Skin rashes, such as the heliotrope rash,

Gottron's

sign, and

Gottron's

papules

Slide35

MANAGEMENT AND PROGNOSIS

PHARMACOLOGIC TREATMENT

The initial pharmacologic treatment in

polymyositis

and

dermatomyositis

is high-dose

glucocorticoids

: 0.75 to 1 (up to 2) mg/kg body weight per day for 4 to 12 weeks.

Most experts recommend that

glucocorticoid

treatment be combined with another immunosuppressive drug to reduce the side effects of the

glucocorticoids

and to boost the immunosuppressive effect.

The most frequently used immunosuppressive agents are

azathioprine

and

methotrexate

. In the extension phase of one of the few double-blind, placebo-controlled trials that have been reported, the combination of

azathioprine

and

glucocorticoids

, as compared with prednisone alone, was associated with better functional ability and a lower requirement for prednisone after 1 and 3 years.

The recommended

azathioprine

dosage is 2 mg/kg per day. The dosing regimen for

methotrexate

is similar to that for rheumatoid arthritis—up to 25 mg weekly, although there have been reports of higher doses. Pulmonary involvement related to

myositis

does not seem to be a contraindication for

methotrexate

.

Slide36

tapering of the corticosteroid dose, should be guided by clinical outcome measures.

the most appropriate outcome measures are muscle endurance and muscle strength.

Side effects of

glucocorticoids

in these high doses are frequent. Prophylaxis against osteoporosis is recommended with vitamin D and calcium and, when clinically indicated,

bisphosphonates

.

Steroid

myopathy

is another possible consequence of

glucocorticoid

treatment that is particularly problematic in patients with inflammatory

myopathies

. There is no specific test to verify steroid

myopathy

, but in the absence of active clinical disease, steroid

myopathy

could contribute to muscle weakness.

If steroid

myopathy

is suspected, tapering of the

glucocorticoid

dose with careful evaluation of the clinical response is recommended.

Glucocorticoids

may also cause

hypokalemia

, and if this is not corrected, it may be associated with muscle weakness and incorrectly interpreted as

myositis

activity.

Slide37

In patients with interstitial lung disease,

cyclophosphamide

could be of value.

There are also a few reports that cyclosporine A or

tacrolimus

can be beneficial in these cases.

In treatment-resistant

dermatomyositis

, a high dose of IVIG was found to have a beneficial effect on muscle strength when compared with placebo; however, the therapeutic effect was temporary, and repeated infusions were required.

In patients with severe, rapidly progressive disease that might be life threatening, high-dose pulses of intravenous

methylprednisolone

have been reported to be beneficial.

Slide38

DOSAGE REDUCTION

The dose is tapered slowly to a maintenance level over about 6 months, which can be achieved by 25 per cent reduction per month to a maintenance level (such as prednisone 5–10 mg/day or 10–20 mg every other day), sometimes continued for a year, or tapered slowly over 1–2 years. Some recommend routine conversion to an alternate-day regimen after the initial high-dose regimen.

Exacerbations of disease are common. If CK elevation occurs after initial response, causes other than disease flare should be considered, particularly when no other signs are present. Exacerbation without CK elevation may occur, even if the CK was elevated originally, but steroid

myopathy

should be considered. Other tests, such as MRI, EMG, or repeat needle biopsy, can help assess disease activity in these cases. Exacerbation is usually treated with an increase in steroid dosage and/or addition of an immunosuppressive agent.

Slide39

The side-effects of corticosteroids in PM/DM are similar to those in other situations. Steroid

myopathy

poses a special problem, as noted. Steroid-induced

hypokalaemia

may also lead to further weakness and should be avoided. The usually prolonged course increases risks of osteoporosis and preventive measures should be instituted. Aseptic necrosis is a risk. Gastric protection is commonly used. Diabetes, hypertension, cataracts, and opportunistic infections may be seen.

Slide40

NONPHARMACOLOGIC TREATMENT

Combining exercise and immunosuppressive therapy is a safe approach and has clear beneficial effects on muscle function.

The exercise regimen should be individualized and supervised by a physiotherapist to avoid the overuse of muscles.

Physical exercise is now recommended as combination therapy with immunosuppressive treatment.

Slide41

Recovery of strength

Prognosis for recovery of full strength is worse if treatment is delayed , or if the course is chronic and progressive. Patients whose treatment begins more than 6–12 months after onset may not recover full strength even with complete suppression of disease activity.

Older patients may respond less well and may require longer treatment. In general, those with adult DM do better than those with pure PM, and those with overlap syndromes do best .

Steroid side-effects of compression fracture and

avascular

necrosis add significantly to disability .

Antisynthetase

patients usually respond initially, but both

antisynthetase

(anti-Jo)

and anti-SRP patients have a higher frequency of incomplete response and flare with taper.