Transcript Internal Medicine Clinical Pathological Conference

Internal Medicine
Clinical Pathological
Conference
July 18, 2008
Diagnostic Procedure

Right thigh skeletal muscle biopsy
Further Evaluation:
TEST
Anti- RNP ab
REFERENCE
RANGE
Negative
Negative
RF (U/mL)
<15
<10
CCP IgG ab
<20
24
Anti Jo-1 ab
0-1 negative
>6
Anti SS-A ab
Negative
Negative
Anti SS-B ab
Negative
Negative
Anti Smith ab
Negative
Negative
Anti Scl-70 ab
Negative
Negative
Further Evaluation:

Thoracentesis
• Transudative fluid
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AFB sputum negative x 3
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EMG
• Sensory and motor neuropathy, but cannot exclude
myopathy

Modified Barium Swallow Examination
• Moderate dyshphagia with unilateral left pharyngeal weakness
Key Features:

Clinical
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•
•
•
•
• Proximal muscle
weakness
• Arthralgia
• Dysphagia
• Absence of rash
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Radiology
• Bilateral interstitial
fibrosis
• Transudative effusion
Laboratory

Elevated creatine kinase
Elevated Anti-Jo1
Elevated ESR, CRP
Transaminitis
EMG
• Neuropathy
Idiopathic Inflammatory Myopathy

Subclassified
• Polymyositis
• Dermatomyositis
• Inclusion body myositis
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Histological: endomysial inflammation and
activation of the immune response
Idiopathic Inflammatory Myopathy

Epidemiology
• Annual incidence: 2-10 per million
• Polymyositis:

Disease of adult; rare in people younger than 20 years old
• Dermatomyositis:
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Two peaks: 5-10 years old and 50 years old
Female to male – 2:1
• Inclusion body myositis
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Older than 50 years of age
Polymyositis/Dermatomyositis

Diagnostic criteria, Bohan and
Peter, 1975
1.
Symmetrical, proximal muscle
weakness
2.
Elevation of serum skeletal muscle
enzymes

CK, LDH, AST, ALT, and Aldolase
3.
Muscle biopsy with evidence of
myositis
4.
EMG pattern of myopathy
5.
Typical rash of dermatomyositisphotosensitive rash, heliotrope
rash, and gottron papules
Gottron Papules
Heliotrope rash
Polymyositis/ Dermatomyositis

Esophageal involvement (8-30%), inflammation
of cardiac muscle
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Interstitial Lung disease (50%)
• Nonspecific interstitial pneumonia (NSIP)
• Usual interstitial pneumonia (UIP)

Anti-Jo 1 and Anti-Mi2
• Anti- Jo-1 commonly have Interstitial lung disease
• Anti-M1 have skin findings

Increase cancer risk
• 7-10% of polymyositis
• 15-20% of dermatomyositis
Polymyositis/ Dermatomyositis
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Cellular immunity
• Polymyositis- Class II HLA antigen DR3,
predominant CD8 T cells
• Dermatomyositis- Predominant B cells
and CD4 T cells in inflammatory
infiltrates
Inclusion Body Myositis
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May be asymmetric and involves
distal muscles
Dysphagia is prominent( 40-80%)
Muscle enzyme is only mildly
elevated
EMG- Myopathic and Neuropathic
Biopsy- mononuclear infiltrates and
red-rimmed vacuoles in muscle cells
with inclusion bodies
Mild response to conventional
steroid treatment
Inclusion Body Myositis:
Pathogenesis

Engel and Arahata 1984
• Endomysial infiltrates are composed of
primarily CD8+ T Cells

Engela and Engel 1988; Orimo 1994; Schmidt 2004
• CD8+ T Cells surrounds MHC class I
myofibers and express perforin

Cupler 1996; Saperstien 1999; Tsuruta 2001; Dalakas
2006
• Association with chronic viral infection
Inclusion Body Myositis:
Pathogenesis

Hypothesis- Dalakas 2006
Dalakas, 2006
Disease begins with viral infection
HIV, HTLV-1, Hepatitis C
1. Clonal expansion of CD 8+ T cells and T-cell mediated, MHC class I
cytotoxicity via perforin pathway leading to necrosis
2. Cytokines upregulate MHC class I molecules leading to MHC-peptide loading
complex and endoplasmic reticulum (ER) stress
3. ER stress leads to activation of transcription factor NFkB, further stimulating
MHC/CD 8 complex and induce a self-sustain inflammatory response
Treatment

Polymyositis/ Dermatomyositis
• High dose corticosteroids- respond within 6
weeks
• Methotrexate, cyclosporine, and IVIG

Inclusion body myositis
• Most immunotherapeutic agents are
ineffective

Age appropriate cancer screening
FINAL DIAGNOSIS:
Inclusion Body Myositis
Dermatomyositis sine
dermatitis
Pathogenesis of Patient’s disease
Viral Infection
Clonal expansion of CD 8+ T Cell
Complex with MHC class I
Cytotoxicity via perforin
pathway causing necorsis
B cells and CD4 T cells in
inflammatory infiltrates
Cytokine release
Endoplasmic reticulum
stress and
Intracellular
peptide loading complex
Skeletal muscle
inflammation
Epidermal and
dermal
destruction
Skeletal muscle inflammation
Inclusion Body Myositis
Dermatomyositis
Interstitial lung disease
Cough
Recurrent
Aspiration
Dysphagia
Proximal muscle
Weakness,
myalgia
Elevated serum
muscle enzymes
Rash
Case Follow-up

Patient was started on empiric antibiotics
for aspiration pneumonia

Started on prednisone 30mg bid

Pt transferred to subacute inpatient
rehabilitation

CPK=5675, AST=237, ALT=252 after one week
of prednisone therapy

Pt with improvement in deltoid strength and
proximal muscle strength
Case Follow-up
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Eventually discharged with outpatient
rheumatology follow up
Initially, clinical symptoms improved and patient
was maintained on daily steroid for about 1 year
Patient was found to have rising CK, and
Azathioprine was added to his regimen
Azathioprine did not improve his CK levels, and
was switched to Mycophenolate mofetil
Patient was electively admitted 2 weeks ago for
IVIG as CK levels continue to be elevated
THANK YOU!

Medical Student Discussants
Michael Goldman
Juan Lado
Megan Mcgill
Nekee Pandya
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Moderator: Martin Blaser, MD
Faculty Discussant: Peter Izmirly, MD
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Radiology Speaker: Dr. David Naidich , MD

Pathology Speaker: David Zagzag, MD
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SPECIAL THANKS: Christina Yoon , MD, Harry

Shen, MD and Jean Park, M.D.