Transcript Document

‫‪Inflammatory Muscle Disease‬‬
‫ד"ר סוהיל אעמר‬
‫ראומטולוגיה – הדסה הר הצופים‬
Classification of IMD
Adult Polymyositis (PM)
Adult Dermatomyositis (DM)
Bohan & Peter
CRITERIA
1-MUSCLE WEAKNESS
2-ENZYMES
3-EDT=EMG
4-MUSCLE BIOPSY
all for PM
5-TYPICAL RASH
for DM
Classification of IMD
Adult Polymyositis
Adult Dermatomyositis
Childhood Dermatomyositis
Poly/Dermato-myositis associated with
malignancy
Poly/Dermato-myositis associated with
Connective Tissue Disease
Inclusion Body myositis
Amyopathic Dermatomyositis
EPIDEMIOLOGY
Annual Incidence: 2-10 case /million
Peak age : 10-15 and 45-55 years old
Female: Male ratio:
3:1 total
1:1 childhood DM
10:1 PM/DM assoc. CTD
Black: White (USA):
4:1
CLINICAL MANIFESTATIONS
Weakness of muscles
-shoulder girdle
- pelvic girdle
- neck flexors
Myalgia is minimal
Constitutional symptoms-fatigue, fever…
CLINICAL MANIFESTATIONS
Rheumatic: arthralgia/arthritis 20-70%
Pulmonary: interstitial lung disease 10%
GIT: esophageal dysmotility 10-30%
Cardiac: conduction blocks and arrhythmia
Vascular: Raynaud’s phenomenon 20-40%
Skin : Rash, livedo reticularis
RAYNAUD’S PHENOMENON
DERMATOLOGIC-SKIN RASH
DERMATOMYOSITIS:HELIOTROPE RASH: purple /erythematous
rash affecting eyelids,periorbital edema
+/- malar, forehead and nasolabial folds
LIVEDO RETICULARIS- cutis marmorata like
Heliotrope Rash
DERMATOLOGIC-SKIN RASH
GOTTRON’S PAPULES:
Purple /erythematous raised lesions over
knuckles and extensor regions
V-SIGN :
Erythematous rash over anterior chest and
neck. (photosensitivity)
DERMATOLOGIC-SKIN RASH
SHAWL-SIGN:
Erythematous rash over the shoulders,
upper back and proximal arms
HOSTLER SIGN:
Erythema over lateral thigh
NAILFOLD PATHOLOGY :
Cuticular overgrowth and dilated capillary
loops
PM/DM
DERMATOLOGIC-SKIN RASH
MECHANIC’S HANDS:
Cracking/fissuring the finger pads
CALCINOSIS:
Subcutaneous calcifications ( exclusive in
childhood dermatomyositis)
DM -childhood
DIFFERENTIAL DIAGNOSIS
-MYOPATHY- DRUG/TOXIN
-NEURO-MUSCULAR
-ENDOCRINE DISEASE
-INFECTIOUS MYOSITIS
-METABOLIC STORAGE MYOPATHIES
-MITOCHONDRIAL MYOPATHY
-OTHERS
CRITERIA
1-MUSCLE WEAKNESS
2-ENZYMES
3-EDT=EMG
4-MUSCLE BIOPSY
DIAGNOSTIC CRITERIA
1. PROXIMAL MOTOR WEAKNESS:
symmetric, proximal muscles
2. HIGH SERUM MUSCLE ENZYMES:
CPK, aldolase, myoglobin, AST,
ALT, LDH
DIAGNOSTIC CRITERIA
3. EDT= electro-diagnostic tests
PM/DM
NEUROPATHIC
DISORDER
EMG
-Poly-phasic action
-Poly-phasic action
NCV
normal
abnormal
potentials
-short duration
-low amplitude
potentials
-long duration
-large amplitude
DIAGNOSTIC CRITERIA
4. MUSCLE BIOPSY:
biopsy a clinically weak muscle,
contralateral to an abnormal muscle ( by
EDT), MRI directed.
a. Perivascular and endomysial inflammation
CD8+ T cells in PM,
CD8+, CD4+ T and B cells in DM
b. Muscle fiber necrosis and regeneration
.b
LABORATORY TESTS
HIGH MUSCLE ENZYMES:- CPK
ELEVATED ESR , CRP:- 50%
POSITIVE ANA:- 50-80%
AUTOANTIBODIES:anti- RNP (MCTD)
anti-PM/Scl (OVERLAP)
Myositis-specific AUTOANTIBODIES
ANTI Jo-1 part of ANTI SYNTHETASE Ab’s
Antibodies to the antigen- Aminoacyl-tRNA
synthetase, in 20-50% of PM>>DM
ANTI SRP = anti signal recognition particle
In 5% of PM
ANTI Mi-2 in 10% of DM.
ANTI-SYNTHETASE
SYNDROME
associated with anti-Jo1 antibodies
with acute onset of PM>> DM disease.
Associated with ILD -40-60%,
deforming and non-erosive arthritis,
Mechanic’s hands and Raynaud’s
phenomenon
Myositis-specific
AUTOANTIBODIES
Ab’s
prevalence
Clinical
HLA
prognosis
Steroid
response
DR3
moderate
moderate
association
Anti- 20-50%
Jo-1 (PM)
Antisynthetase
syndrome
Anti- 5%
SRP (PM)
Severe PM DR5
bad
(cardiac)
poor
Anti- 5-10%
Mi-2 (DM)
Classical
DM
good
good
DR7
INFLAMMATORY MUSCLE
DISEASE
1.Adult Polymyositis
2.Adult Dermatomyositis
3.Childhood Dermatomyositis
4.Poly/Dermato-myositis associated with
Connective Tissue Disease
5.Poly/Dermato-myositis associated with
malignancy
6.Inclusion Body myositis
7.Amyopathic Dermatomyositis
Poly/Dermato-myositis associated
with malignancy
Associated neoplasms present within the
first 2 years of PM/DM followup
In PM- 10 %
In DM- 15 %
Reports of: carcinoma-lung, stomach, ovary
lymphoma
Routine screening in DM
Inclusion Body myositis
(IBM)
POLYMYOSITIS
Demography
F>M all ages
Muscle involved proximal
IBM
M>>F age >50
Prox. And distal
Extramuscular
Symmetric
Legs=arms
Cardiac, lung,
joints
Asymmetric
Lower >upper
Neuropathy
EMG
myopathic
Myopathic/
neuropathic
Inclusion Body myositis
(IBM)
POLYMYOSITIS
IBM
Muscle Biopsy
CD8+ T cells
infiltrate
CD8+ T cells,
red-rimmed
vacuoles with
beta amyloid
Auto-antibodies
ANA=frequent
ANA= rare
Myositis-specific
antibodies
yes
no
Response to
therapy
frequent
no
IMD-PROGNOSIS
5-YEAR SURVIVAL IS AROUND 85% IN PM,
DM, PM/DM ASSOC. CTD.
MUCH LOWER IN PM/DM ASSOC.
MALIGNANCY.
Anti-Mi2 Ab’s in DM – better 5-Y-S ,>90%
Anti-Jo1 positive decrease 5-Y-S to 65%
Anti-SRP Ab’s worsens 5-Y-S to 30%
‫גורמי הרעת פרוגנוזה ב‪IMD -‬‬
‫‪ ‬גיל מבוגר‬
‫‪ ‬עיכוב באיבחון‬
‫‪ ‬עיכוב במתן טיפול סטרואידלי ואימונוספרסיבי‬
‫‪ ‬ממאירות‬
‫‪ ‬מעורבות אברים פנימיים‬
‫‪IBM ‬‬
‫‪ ‬חוסר תגובה ראשונית לטיפול‬
‫‪ ‬נוכחות נוגדנים מריעים פרוגנוזה‬
INFLAMMATORY MUSCLE
DISEASE
TREATMENT:
1. STEROIDS
2. IMMUNOSUPPRESSIVE AGENTS:
methotrexate, azathioprine, cytoxan,
cellcept
3. IMMUNOMODULATORY AGENTS:
IVIG, Plasmapheresis
4. REHABILITATION
‫מחלות שריר דלקתיות‪ -‬טיפול‬
‫טיפולים ביולוגים ?‬
‫נוגדי ‪TNF‬‬
‫‪Anti CD 20‬‬
‫‪IL-6 antagonist‬‬
Cytokines in Inflammation
sTNFR
TNFa
IL-10
IL-1Ra
IL-1b
Pro-inflammatory
Anti-inflammatory
Synthesis and Function of TNFa
Soluble TNFa
Macrophage or
Activated T Cell
Receptor-Bound TNFa
Transmembrane
TNFa
Signal Induction
TNFa
Receptor
Target Cell
Inhibition of Cytokines
Normal interaction
Neutralization of cytokines
Inflammatory
cytokine
Monoclonal
antibody
Cytokine
receptor
Soluble
receptor
Inflammatory
signal
No signal
Activation of
Receptor blockade anti-inflammatory pathways
Monoclonal
antibody
Receptor
antagonist
No signal
Adapted with permission from Choy EHS, Panayi GS. N Engl J Med. 2001;344:907-916.
Copyright © 2001 Massachusetts Medical Society. All rights reserved.
Anti-inflammatory
cytokine
Suppression of
inflammatory
cytokines
Humira- The first fully human
antiTNFa
Chimeric
Humanized
Chimeric
Antibody
70% Human
Humanized
Antibody
95% Human
Mouse
Human
49
Fully Human
Fully Human
Antibody
100% Human
‫מחלות שריר דלקתיות‬
TNF ‫אנטי‬
ETANERCEPT= Enbrel
REMICADE= Infliximab
HUMIRA= Adalimumab
Research & treatment
IMD