Inflammatory
Myopathies. 1
Definition. 1
Epidemiology. 1
Pathogenesis. 1
Clinical
manifestations. 2
Polymyositis. 2
Dermatomyositis. 2
Inclusion
Body Myositis. 2
Jo-1
associated myositis. 3
Diagnosis/Investigations. 3
Treatment 3
Prognosis. 4
- Three main
groups:
- Polymyositis,
- Dermatomyositis
- Inclusion body
myositis
- Others
- Auto-immune
necrotising myopathy
- Myositis
associated with CT disorders.
- Prevalence
1/100,000
- F:M 3:1
- PM – adults
(rarer)
- DM – adults and
children
- Peak age for DM
and PM ~40-50years
- IBM - >50years, more common in men
- Familial
aggregations can occur
- DM
- Humoral
mechanism
- Endomysial inflammation
with angiopathy (vasculopathy)
and muscle fibre destruction
- Perifascicular
atrophy
- B-cells, CD4
- Activation of
complement
- PM
- Cell-mediated
mechanism
- Muscle fibres
induced to express MHC-I which results in destruction by T-cells
- CD8+ t-cells
- No evidence of vasculitis
- Endomysial inflammation
- IBM
- Similar
appearance to PM
- B-amyloid
deposits in IBM - ? degenerative process as
well?
- Rimmed vacuoles
in IBM
- Some evidence
of association with HIV and HTLV-1
- CD8 T cells and
macrophages predominate
-
- Association with
malignancy
- 15% in DM, 9%
in PM
General features
- Progressive and
symmetrical muscle weakness (except IBM which can have a asymmetrical
pattern)
- Proximal muscles
first
- Early
involvement of quadriceps in IBM resulting in falls
- Muscle pain
- Ocular muscles
are spared (and another diagnosis considered if they are affected).
- Facial muscles
can be affected in IBM
- Pharyngeal and
neck flexors can be affected – dysphagia, head drop
- Respiratory
muscles affected in some cases
- Sensation normal
- Tendon reflexes
preserved generally
- Progression over
weeks and months with DM, PM
- IBM progresses
more slowly over years (similar appearance to MND)
Polymyositis
- Really a
diagnosis of exclusion (including ruling out IBM)
- Usually occurs
in association with a systemic autoimmune or connective tissue disease or with
a known viral or bacterial infection.
Dermatomyositis
- Characteristic
rash aids diagnosis
- Usually
precedes muscle weakness
- Blue-purple
discolouration of the upper eyelids with oedema (heliotrope rash)
- Flat red rash
on the face and upper trunk (no nasolabial aparing)
- Erythema of the
knuckles with raised violaceous scaly eruption (Gottron’s
sign)
- Can occur on
chest (v-sign) or back (shawl sign)
- May worsen
after sun exposure
- Mechanics hands
(assoc with Jo-1 AB)
- Peri-ungal changes
- Can occur as
overlap syndrome with scleroderma (with specific antibody anti-PM/Scl)
- Most common of
the 3 in patients >50years
- Weakness of some
more distal muscles can
help differentiate it
- Finger flexors
and wrist flexors affected early
- Foot extensors
(tibialis anterior), quads
- Small muscles
of hands,
- Facial weakness
can occur (1/3 of pts)
- Dysphagia common (60%)
- NO myalgia (or at least rare)
- Atrophy
- Flexor forearms
and quadriceps
- NO fasciculations
- Reflexes reduced
or absent
- Sensation
usually unaffected
- Can be asymmetric
- EMG shows neuropathy as well as myopathic
features
- Characteristic
muscle biopsy
- Absence of
response to immunosupression is also suggestive
- Sort of subset
of DM/PM
- Always
associated with nucleolar or speckled ANA
pattern
- Associated with inflammatory
lung disease – interstitial
- Associated with
fever, arthritis and raynauds
- Poorer prognosis
– 70% 5yr survival
Extra-muscular
Manifestations
- Systemic
symptoms
- Joint
contractures
- Dysphagia and
GI symptoms
- Cardiac
disturbances
- Pulmonary
disease (ILD ~10%)
- Subcutaneous
calcifications (DM)
- Arthralgia’s/synovitis
(in patients with Jo-1 antibodies)
Association with
cancer
- DM is associated
weakly with development of a number of cancers
- Screening for
malignancy should be considered in patients with DM
- Diagnosis made
by:
- Clinical
features
- CK (frequently
not raised especially in dermatomyositis)
- EMG findings
- Muscle biopsy
- Anti-bodies
- Antibodies in up
to 20%
- Wide variety of
ANA and cytoplasmic antibodies
- Not for primary
diagnosis but may be useful as adjunct
- Anti-PM/Scl in DM/Scleroderma overlap syndrome
- Anti-Jo-1
predicts ILD, raynaud’s and arthritis
- Anti-SRP
- Anti-Mi-2
associated with acute DM
- MRI
- T1 shows
atrophy
- Increased signal
on T2 shows affected muscle with oedema and inflammation.
- Can be a guide
to muscle biopsy
- EMG
- Increased insertional activity and spontaneous fibrillations
- Abnormal
myopathic low amplitude and polyphasic motor potentials
- Complex
repetitive discharges
·
Muscle
biopsy
1.
IBM
–
1.
Basophilic
rimmed vacuoles within muscle fiber sarcoplasm
2.
(Filamentous)
Eosinophilic inclusion bodies adjacent to vaculoes
·
Skin
biopsy
1.
Of
skin lesion in DM can aid diagnosis
2.
- CK usually drops
when weakness resolves but not consistent – therefore taper treatment to
clinical weakness.
- Glucocorticoids
- Mainstay of
treatment
- 1mg/kg daily –
wean over period of 3-4 months to minimal acceptable dose
- May take three
months for significant improvement
- Nearly all DM and
PM patients respond to steroids to some extent for some time.
- ~30% overall
respond poorly (more often in PM)
- Steroids can
cause myopathy which can confuse the situation
- IBM not
traditionally steroid responsive.
- Other
immunosuppressive drugs
- Azathioprine
- Methotrexate
- Mycophenolate
- Rituximab
- Cyclosporine
- Cyclophosphamide
- Tacrolimus
- DM and PM have
very good survival rate if treated (95% 5 year)
- DM responds
better to treatment and has better prognosis
- Most patients
make full functional recovery with time
- 30% are left
with some residual loss of function
- The following
clinical features have been associated with a worse outcome:
- Delay in the
initiation of treatment for more than six months after symptom onset
- Greater weakness
at presentation
- The presence of
dysphagia
- Respiratory
muscle weakness
- Interstitial
lung disease
- Associated
malignancy
- Cardiac
involvement
- IBM has the
least favourable prognosis
- Poor response
to therapy
- Slow gradual
decline
- Most will
require mobility assistance within 5-10 years.
-
-