B6.015 Myositis - Big Case

Question 1

epimysium

Answer 1

ECM proteins including collagen

Question 2

perimysium

Answer 2

well defined layer of CT surrounding individual bundles of muscle fibers (fascicles)

Question 3

endomysium

Answer 3

network of fine collagen fibers and other ECM proteins, separates fibers from each other

Question 4

describe the size and orientation of adult male quadricep fibers

Answer 4

40-80 micrometers thick
may reach 10 cm in length
closely packed to each other and in transverse section are polygonal in shape

Question 5

structure of the myocardium

Answer 5

striated as a result of arrangement of actin and myosin filaments in sarcomeres
smaller than skeletal muscle fibers (15 micrometers) and shorter (85-100 micrometers)
1-2 nuclei per cell (rather than many like skeletal)

Question 6

intercalated disc

Answer 6

junction between two cardiac muscle cells, distinguishing feature
help transverse signal quickly

Question 7

internal components of myocardium

Answer 7

more vascularized than skeletal muscle
more abundant mitochondria (40% of volume)
glycogen granules between myofibrils

Question 8

what is myositis

Answer 8

inflammation of the muscles

Question 9

what are the 2 classes of muscular injury

Answer 9

myopathic - damage myofibers directly

neurogenic - disrupt muscle innervation

Question 10

discuss the pathological process of neurogenic muscular injury

Answer 10

nerve injury leads to denervation and atrophy of the nerve
surrounding nerves that are not damaged reinnervate myofibers and regenerate
what was previously a mixed pattern of muscle groups now becomes a dual population, one type right next to the other rather that the interspersed pattern or normal tissue

Question 11

3 main primary inflammatory myopathies

Answer 11

polymyositis
dermatomyositis
inclusion body myositis

Question 12

what types of features can polymyositis and dermatomyositis display

Answer 12

typical features of autoimmune inflammatory diseases, including associations with certain autoantibodies (HLA-DR)

Question 13

what is dermatomyositis

Answer 13

systemic autoimmune disease

damage to small blood vessels contributes to muscle injury

Question 14

general symptoms associated with dermatomyositis

Answer 14

vasculopathic changes seen as telangiectasias in nail folds, eyelids, and gums
dropout of capillary vessels in skeletal muscle
associated with aching pains in shoulders or hips
some weakness (proximal and symmetrical)

Question 15

additional findings that may be associated with dermatomyositis

Answer 15

heliotrope rash
erythema in nail beds, knees, elbows
skin tightness (shiny, red)
ulcers at pressure points

Question 16

what other pathology can be associated with dermatomyositis

Answer 16

malignancy
usually present within a short time of each other
occasionally, myopathy may precede diagnosis of tumor by months or years

Question 17

pathogenesis of dermatomyositis

Answer 17

• deposition of complement MAC within cap beds
• upregulation of MHC-1 in myofibers
• B lymphocytes and plasma cells part of inflammatory infiltrate

Question 18

genetic component of Caucasian juvenile dermatomyositis and polymyositis

Answer 18

HLA-B8
HLA-DR3
HLA-DQA1*** (most important)

Question 19

autoantibodies associated with dermatomyositis

Answer 19

anti-Mi2
anti-Jo1
anti-P155/P140
-can all be associated with specific clinical features

Question 20

what is polymyositis

Answer 20

adult onset inflammatory myopathy that shares myalgia and weakness w dermatomyositis, but lacks cutaneous features
DIAGNOSIS OF EXCLUSION

Question 21

symptoms/findings of polymyositis

Answer 21

symmetric proximal muscle involvement
inflammatory involvement of heart and lungs
similar autoantibodies to dermatomyositis

Question 22

immunologic basis of polymyositis

Answer 22

CD-8 positive cytotoxic T cells are prominent part of inflammatory infiltrate

Question 23

lab test/ imaging studies used in diagnosing myositis

Answer 23

CBC
CK
ESR
serology (autoantibodies)
biopsy
EMG
MRI

Question 24

why is MRI useful in myositis diagnosis

Answer 24

shows increased signal in relation to edema and inflammatory changes in subQ fat
helps determine a good place to take a biopsy
helps monitor therapy

Question 25

what type of muscle do you want to biopsy in myositis?

Answer 25

one that is weakened and affected, but not "end stage" so that it is completely destroyed by fat and fibrosis

Question 26

pattern of EMG findings in neuropathic disorders

Answer 26

fewer voluntary motor units available to respond to central drive reduced recruitment surviving motor units are larger than normal with increased fiber density near the electrode BIGGER AMPLITUDE RANDOM FIRINGS

Question 27

pattern of EMG findings in myopathic disorders

Answer 27

total number of units is normal force generated by units is reduced amplitude is reduced, but overall pattern is normal

Question 28

histo findings in generalized myositis

Answer 28

fiber irregularity | interstitial area contains inflammatory cells

Question 29

specific histo findings of dermatomyositis

Answer 29

ischemic changes, especially on edges of bundles (edges have least vasculature and are most at risk) "peri vesicular atrophy"

Question 30

epidemiology of sporadic inclusion body myositis

Answer 30

most commonly acquired in patients over 50 more common in males more insidious onset

Question 31

what helps alert a clinician to the possibility of IBM

Answer 31

unresponsive to corticosteroid therapy | different pattern of weakness than other myositis types

Question 32

pattern of weakness in IBM

Answer 32

``` proximal and distal prominent weakness in quadriceps weakness at wrists, fingers, and ankles asymmetrical (non dominant more severe) dysphagia ```

Question 33

CK in IBM

Answer 33

normal or <10x normal

Question 34

CK in polymyositis

Answer 34

>10x normal

Question 35

epidemiology of polymyositis

Answer 35

female > male common before age 50 acute or subacute onset w more rapid course

Question 36

histo findings in IBM

Answer 36

inflammation, rimmed vacuoles, inclusions | seen well with trichrome

Question 37

what is CK

Answer 37

creatine kinase, most widely used enzyme to diagnose and follow muscle disease presents in highest concentration in serum w muscle injury most sensitive indicator of muscle injury best measure of course of muscle injury

Question 38

what type of CK is in skeletal muscle

Answer 38

99% MM subtype, small amounts of MB

Question 39

how can CK distinguish between myopathic and neurogenic muscular injuries

Answer 39

CK >1000 in myopathic | do not see high CK with neurogenic, cells get smaller but are not destroyed releasing CK

Question 40

what is immune mediated necrotizing myopathy (IMNM)/ necrotizing autoimmune myopathy (NAM)

Answer 40

novel entity among inflammatory myopathies necrotic muscle fibers associated with macrophage infiltration and numerous regenerating fibers (without lymphocytic infiltrates)

Question 41

autoantibodies associated with IMNM

Answer 41

anti-SRP

Question 42

other associations with IMNM

Answer 42

malignancy statin treatment active viral infection

Question 43

weakness pattern of IMNM

Answer 43

proximal and severe

Question 44

labs and treatment of IMNM

Answer 44

CK levels high (>3000) | poor response to steroids (like IBM)

Question 45

what is granulomatous myositis

Answer 45

rare condition that may be a manifestation of sarcoidosis or isolated

Question 46

presentation of granulomatous myositis

Answer 46

chronic proximal muscle weakness rarely: acute myositis or palpable nodular type may mimic IBM

Question 47

treatment of granulomatous myositis

Answer 47

steroid treatment usually effective in isolated type | less effective in sarcoid

Question 48

histology of granulomatous myositis

Answer 48

inflammation | multinucleated giant cells w peripheral nuclei

Question 49

goals of treatment of myositis

Answer 49

improve muscle strength avoid development of extra muscular complications resolution of cutaneous manifestations in DM

Question 50

1st line myositis treatment

Answer 50

glucocorticoids improves strength and preserves muscle function prednisone tapering for 9-12 months no standard regimen

Question 51

what are glucocorticoid sparing agents

Answer 51

steroid sparing immunosuppressive agents generally initiated along with glucocorticoids reduce cumulative dose of steroids and diminish glucocorticoid induced morbidity

Question 52

example glucocorticoid sparing agent

Answer 52

azathioprine

Question 53

mechanism of azathioprine

Answer 53

purine analog and antimetabolite family of medication disrupts RNA and DNA synthesis response takes 4-6 months

Question 54

adverse effects of azathioprine

Answer 54

systemic flue like reactions with fever and GI complaints (discontinue drug) BM suppression, pancreatitis, liver toxicity long term increased risk of malignancy

Question 55

advantage of methotrexate

Answer 55

once a week administration

Question 56

mechanism of methotrexate

Answer 56

inhibits DHFR to stop purine and pyrimidine synthesis

Question 57

adverse effects of methotrexate

Answer 57

``` stomatitis, GI symptoms, leukopenia (minimized by giving folic acid) potential hepatotoxicity (DO NOT DRINK) ```

Question 58

IVIg use in myositis

Answer 58

for patients with life threatening weakness (Severe dysphagia with risk for aspiration) rapid onset prolonged treatment is limited by difficulty of admin, cost, and potential toxicity

Question 59

use of antimalarial in myositis

Answer 59

hydroxychloroquine effective in up to 75% of patients in controlling skin disease no benefit for muscles

Question 60

use of rituximab in myositis

Answer 60

targets CD20+, depletion of B cells within several weeks of admin promising for treatment of recurrent/resistant DM and PM