02-27 Myositis Flashcards
OBJECTIVES 1. Appreciate the differences between inflammatory myositis, steroid myopathy, and polymyalgia rheumatica (PMR). 2. Appreciate the pathologic changes in PM/DM/IBM. 3. Know at least 5 causes of myopathy or myositis that are not PM/DM.
1
Q
OBJECTIVE #3: Know at least 5 causes of myopathy or myositis that are not PM/DM (i.e. list DDx/categories muscle problems)
A
- Other Myosites (a.k.a. idiopathic inflammatory myopathies)
- Inclusion body myositis
- Cancer related myositis
- Rhabdomyolysis
- Drug induced myopathy (especially steroid induced, ?statins–he didn’t mention)
- Metabolic myopathies
- PMR (polymyalgia rheumatica)
2
Q
S/Sx of Myositis (i.e. Idiopathic Inflammatory Myopathies)
A
SIGNS/SYMPTOMS
- Slowly progressive, fixed (i.e. all the time) proximal muscle WEAKNESS is dominant feature
- Muscle pain is probably NOT myositis
- even though we usu. think about
- Premature fatigue
- signif. decline in their level of activity
- Post-exertional aches, cramps and pains
- Chronic myalgias are not a primary feature
- Increased risk of malignancy
- We don’t know if myositis causes cancer or prediposition to cancer causes myositis
- May have arthritis, Raynaud’s, pitting edema of the extremities, pulmonary involvement
3
Q
- Enzyme tests to order?
- Reasons for false positives
A
- ENZYMES TESTS TO ORDER
CPK (most commonly measured)
Be worried when > 400
- Also checked in ?MI
- Can also be raised in:
- Racial differences
- Trauma: sharp or blunt (even just biopsy or EMG needle!)
- Post-exercise
- Really muscular person
- Drugs: ETOH, cocaine, statins, AZT
- Genetics
- Glycogen storage disease
- Muscular dystrophy
- Periodic paralysis
- Malignant hyperthermia
- Benign hyper-CK-emia
Other Enzymes
- Aldolase
- “Liver enzymes”
- AST – Aspartate aminotransferase
- ALT – Alanine aminotransferase
- LDH – Lactate dehydrogenase
4
Q
Causes for CPK false positives
A
CPK can also be raised in:
- Racial differences
- Trauma: sharp or blunt (even just biopsy or EMG needle!)
- Post-exercise
- Really muscular person
- Drugs: ETOH, cocaine, statins, AZT
- Genetics
- Glycogen storage disease
- Muscular dystrophy
- Periodic paralysis
- Malignant hyperthermia
- Benign hyper-CK-emia
5
Q
What antibodies should you order when considiering a Dx of PM/DM?
A
- ANA – broadly interacts with nuclear proteins, not specific (+ in ~90% cases)
- Ro, La, RNP – suggests that myositis is secondary to other autoimmune condition (lupus, Sjogren’s).
- Jo-1 – Most common myositis specific antibody (+ in ~20% cases)
- targets anti-histidyl tRNA synthetase (anti-synthetase syndrome)
- Anti-synthetase syn strongly assoc’d w/ ILD*, also: Raynaud’s, arthritis, mechanic’s hands.
- *keep an eye on their pulm status!
- targets anti-histidyl tRNA synthetase (anti-synthetase syndrome)
- SRP – Almost exclusively with PM (+ in ~5% cases)
- portends a severe myopathy, refractory to tx
- Mi-2 – More common in DM (+ in 5-10% cases)
6
Q
Dx Criteria for Myositis
A
From 1975 paper, still used, problem: doesn’t include imaging
- Symmetrical weakness of limb-girdle muscles and anterior neck flexors.
- Muscle biopsy evidence of necrosis of Type I and II fibers, phagocytosis, regeneration, variation in fiber type with inflammatory exudation.
- Elevation in serum or skeletal-muscle enzymes.
- Electromyographic triad of short, small, polyphasia motor units, fibrillations and sharp waves; and bizarre, repetitive discharges.
- Dermatologic features.
7
Q
EMGs
- Utility
- How sensitive/specific?
A
- Utility: differentiate between neuropathic and myopathic dz
- Sensitivity/Specificity
- About 40% will have all classic features
- EMGs are entirely normal in 10%
- Abnormalities may be limited to paraspinous muscles
- Mixed neuropathic-myopathic findings may also be seen in
- Inclusion body myositis
- Myositis with anti-SRP antibodies
- Myositis and malignancy
8
Q
Imaging for Myositis?
- What modality?
- What’s the utility?
A
See edema esp w/ T2-weight “STIR image”
- Helps you decide where to biopsy
9
Q
Weakness 2° Myopathic vs. Neuropathic vs. Pain
A
Myopathic
- Proximal and symmetric
- Remainder of neurologic exam normal
Neuropathic
- Proximal, distal and/or asymmetric
- Other abnormalities on neuro exam
Pain
- Sometimes pts describe inability to move b/c of pain as “weakness”
- Example: pt w/ severe polyarticular gout mis-dx as having GBS
10
Q
DZ: Polymyositis
- Presenting S/Sx
- Biopsy findings?
- Work-up/dx?
A
Presenting S/Sx
- Gradual onset of fixed weakness in proximal muscle groups.
- May be some component of myalgias, usually post-exertional.
Biopsy Findings
- [See image here] black dots = lymphocytes which would stain for:
- Cytotoxic CD8+ Ts invading muscle fibers (vs. dermatomyositis where you see what?)
- Invading lymphocytes express CD45RO (antigen primed memory cells)
- ICAM-1 expressed on muscle fibers
Work-Up/Dx
- Rule out confounders (neuro dz, muscular dystrophies, etc.)
- ↑ muscle enzymes.
- Supportive EMG and MRI
- Muscle biopsy confirms dx
11
Q
Name this here queen
A
Jinkx Monsoon, Season 5 Drag Super Star
“It’s Monsoon Season!”
12
Q
Name this queen, all-star Cher impersonator and Winner of RuPaul’s Drag Race All-Stars?
A
Chad Michaels
13
Q
DZ: Dermatomyositis
- Presenting S/Sx
- Biopsy findings?
- Work-up/dx?
- Subsets + Their Characteristics
A
Presenting S/Sx
- Polymyositis plus rash
- heliotrope rash (Lilac discoloration of eyelids)
- Periorbital edema
- Scaly, erythematous rash over MCP and PIP joints (Gottron’s sign)
- Rash over knees, elbows, medial malleoli
- Rash over face, neck, and upper torso
- shawl sign (back)
- V-sign (neck) [IMAGE HERE]
- Capillary nail fold changes and periungual erythema
- ?actually a separate dz
- ?more likely to be a paraneoplastic phenomenon
- though PM also definitely assoc’d w/ cancer
Biopsy Findings (See image here)
- Muscle histology is different
- B lymphocytes, plasmacytoid dendritic cells, and CD4+ T lymphocytes close to vessels
- Loss of capillaries and perifascicular atrophy
- Activated terminal components of complement deposited on vessels
- ICAM-1 on vessels
Work-Up/Dx
- .
Subsets + Their Characteristics
- Adult DM (as above)
- Juvenile DM = Adult + …
- …Vasculitis
- …Lipodystrophy (usu face)
- …Calcinosis
- Amyopathic DM
- Just the rash
- Nl strength, enzymes, histo
- May become typical
- Higher risk of malig
14
Q
- What other disease have this nail finding of increased erythema around the nail bed?
A
Diseases w/ nails like this include:
- Dermatomyositis
- Scleroderma
- ~Sometimes lupus
Nails Capillary Changes under magnifying glass:
- Normal capillaries, w/ fine uniform
- Early on: dilation of capillaries
- drop-out w/ incr dilation and minor hemorrhages
- more advanced
When you see these in the setting of weakness think: dermatomyositis!
- But again, also scleroderma and lupus
15
Q
Path differences between PM & DM
A
PM
- Inflammation centered in the muscle fascicles.
- Primarily CD8+ T cells, lack of B cells.
- No vasculopathy
DM
- Inflammation peri-fascicular (primarily near blood vessels)
- B cells predominate, also CD4+ T cells.
- Vasculopathy and complement deposition present
16
Q
Pulm manifestations of PM/DM?
A
- Interstitial lung disease – inflammation leads to fibrosis
- Muscle weakness contributes to impaired breathing.
- Pharyngeal weakness can lead to aspiration pneumonitis
17
Q
Tx of PM and DM?
A
- Start w/ 40mg prednisone and taper over months
- Goal is to get off steroids and onto maintenance therapy
- Maintenance: azathioprine or MTX
- Skin manifestations difficult to tx
- May or may not respond to above
18
Q
DZ: Inclusion Body Myositis
- Presenting S/Sx
- Tx?
- Biopsy findings?
- Natural Hx?
A
PRESENTING S/SX
- Typically elderly males – very rare
- Weakness
- Proximal and symmetric
- Distal
- Asymmetric
TREATMENT
- No Response to Therapy
NATURAL HX
- Slow, gradual decline in muscle strength, though it may plateau.
- Die of aspiration pneumonia b/c of weak bulbar muscles, e.g.
BIOPSY FINDINGS
- Cellular infiltrate
- like PM but disappears
- Rimmed vacuoles
- Inclusions (see photo here)
- Amyloid deposits
- Mitochondrial abnormalities
19
Q
DZ: Rhabdomyolysis
- Refers to?
- CPK level?
- Causes?
A
- Refers to muscle necrosis
- Typically has very high CPK levels (10,000-100,000 or more)
- Many causes:
- Most often traumatic (geri found down)
- Somtimes ischemic
- Other:
- Hyperthermia
- Drugs/toxins (both prescription and illicit drugs)
- Infection (bacterial/viral)
- Metabolic
20
Q
DZ: Statin-Induced Myopathies
A
- Suspect in any pt taking statin w/ sx of myalgias and/or weakness.
- Can be at anytime while on statin
- most commonly on higher doses
- usu. w/in first several months of starting
- CPK usually elev to ~1000 mg/dl.
- Stopping statin usually results in improvement.
- Rarey: inflammatory-mediated statin-induced myositis
- very aggressive,
- requires high dose immunosuppression
21
Q
DZ: Steroid Myopathy
A
- Primary manifestation is weakness.
-
Not an inflam process
- due to atrophy of type II fibers
- Can occur with any dose of steroid
- more common w/ higher doses and prolonged tx periods.
- Best dx test: dramatically ↓ the steroid → considerable improvement in 24-48 hrs?
22
Q
DZ: Metabolic Myopathies
- Refers to?
- Clinical Manifestations?
- Primary Causes?
A
Refers to
- abnormalities in muscle energy metabolism, resulting in altered skeletal muscle function.
- Many are genetic, yet still don’t present until adulthood (though several do present as children).
Clinical Manifestations
- NOT FIXED as w/ myositis: they feel good at rest
- feel shitty/fatigued w/ exercise (muscle cramps, pain, or weakness)
- Myoglobinuria (muscle breakdown)
- May have cardiac involvement, neurologic deficits, etc.
Don’t memorize these 1° and 2° causes, be familiar with presentation of metab myopathies and then look up a ddx in textbook
Primary Causes
- Defects of glycogen metabolism
- Acid maltase deficiency
- Phosphorylase b kinase deficiency
- Myophosphorylase deficiency (McArdle’s disease)
- Defects in lipid metabolism
- Carnitine deficiency
- Fatty acid transport defects
- Mitochondrial myopathies
- Disorders of purine metabolism
Secondary Causes
- Endocrine disorders
- Hyper- and hypothyroidism
- Acromegaly
- Cushing’s and Addison’s disease
- Hyperparathyroidism
- Electrolyte disorders
- High or Low levels of: sodium, potassium, calcium, phosphate, magnesium
- Uremia
- Liver failure
- Vitamin D or E deficiency
23
Q
DZ: PMR
- Presentation
- Labs
- Tx
A
Polymyalgia Rheumatica
Presentation
- NOT a myositis (inflam condition, but not of muscles)
- Not weakness, but PAIN
- Usu. > 50 y/o
- relatively rapid onset (a day to few days
- onset of hip pain (w/ mov’t) and shoulder pain (w/ tenderness to palp)
- Patients often describe an inability to walk or even to get up from a sitting position due to weakness.
- With careful questioning, it becomes evident that pain is primary cause, not weakness.
LABS
- Marked by elevated inflammatory markers, ESR and/or CRP (sometimes markedly elevated).
- CPK is normal, no autoantibodies present, no decrease in strength.
Treatment
- Responds remarkably well to 20mg prednisone
- Often better overnight!
- Slow taper
24
Q
Bx Dx here?
A
Polymyositis
- black dots = lymphocytes
- would stain for Cytotoxic CD8+ Ts
- are invading muscle fibers (vs. dermatomyositis?)
25
Q
Malignancy and myositis?
A
- There is an increased risk of malignancy in patients with PM and DM (~10-15%)
- Malignancies usu the ones normally common in pt’s demographic.
- so just make sure they’re up to date on their recommended screening
- unless of course they have sx
- Strongest associations are with ovarian, lung, pancreatic, stomach, and colorectal cancer.
- If their going to get a cancer, it’ll usu. be in first 2-3 years
26
Q
What is this sign?
A
Facial lipodystrophy in child w/ Juvenile Dermatomyositis
27
Q
Name this sign
A
calcinosis; can be seen in juvenile dermatomyositis
28
Q
Other drugs that can cause myopathy? (Besides steroids/statins)
A
- Illicit drug use
- Esp cocaine
- amphetamines
- marijuana
- heroin
- PCPToluene
- Alcohol
- Antimalarials
- AZT
29
Q
Pearls from this lecture
A
- AST and ALT may not always be elevated due to liver disease.
- Tease out: Is this pt weak from weakness or weak from pain?
- Common things are common:
- Hypothyroidism
- hypokalemia
- alcohol abuse leading to weakness.
- Minor elevations in CPK may not be pathologic
- (racial differences, body habitus, level of exercise, etc.).
30
Q
General Approach to the pt w/ weakness
A
- Is it truly weakness or is it pain?
- What is the chronicity (acute vs. chronic, fixed vs. waxing and waning)?
- What is the distribution?
- Proximal and symmetric, more likely myopathic
- Distal, asymmetric, more likely neuropathic
- Other symptoms (neurologic symptoms, arthritis, rash)?
- Muscle enzymes elevated?
- Are there electrolyte abnormalities, evidence of endocrine abnormalities, or use of offending substances?
- EMG, MRI imaging, muscle biopsy.
