Transcript post-surgery recovery - Ontario Rheumatology Association

What can I teach in 15 min?
 Update
on statin myopathies.
 What to consider when a diagnosis of
“inflammatory myopathy” is not responding.
 Do not miss IBM.
Case # 1– Lumber Jack!
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69 y RHD male.
PMHx:
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Angioplasty – 1995
Meds: Simvastatin, ASA,
atenolol, terazocin, vits
B/C/E
HPI: tree cutting x 2 ++
DOMS w/ CK to 4869 then
dropping to 341 over 2 d.
Statins and myopathy.
3
- 5 % of patients develop myalgias.
 0.1 % = rhabdomyolysis (10 X ULN).
 ? direct toxicity (phrenylation, COQ10).
 Recently there is evidence of delayed onset
necrotic myopathy responsive to
immunomodulation (Amato, M and N; Mammen,
AL, Arthritis and Rheum, 63:713-, 2011) =
induce expression of anti-HMGCR
autoanitbodies.
Statin myositis.
 100
% of patients had myonecrosis.
 20 % showed “inflammation”.
 MOST of the patients in both studies responded
to MTX and prednisone.
 27/28 of our patient IDed in past 4 years
responded to MTX and prednisone - one needed
pulse solu-medrol and IgG.
 50 % of our patients had inflammation in biopsy.
Case # 2- Calf atrophy
 26
y old male with difficulty getting up from
squat age 19 y > progressive.
 Family history - parents are consanguinous
(paternal great grandmother is sister to his
maternal great grandmother), one sister with
similar phenotype and brother sister no weakness.
 Examination: MS/CN = N; MOTOR = minimal
proximal UE weakness, profound calf > anterior
lower leg atrophy and weakness with hip flexors
= 2/5 and hamstrings 3/5.
Case #2- Calf atrophy.
 Muscle
biopsy = inflammation, N - dysferlin.
 CK > 3,000 iU.
 EMG: fibrillations, PSW, myopathic.
 Dx: inflammatory myopathy - no response to
corticosteroids.
 Rheumatologist wanted a second opinion.
 Patient wanted to know about Rx options.
Case # 2= New mutation
 Calf
atrophy - whole DYS gene sequenced.
 Mutation analysis = c.4747 T>G transversion
(homo); p.Tyr1583Asp.
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Athena = “Since these types of sequence variants are similar to
those observed in both disease-associated mutations and benign
polymorphisms, the nature of this variation precluded clear
interpretation.”
 in
silico evaluation:
– SIFT = “not tolerated”
– PolyPhen = “probably damaging”, score = 3.024.
– Tyr = tyrosine is highly conserved 46/46 vertebrata.
Case # 2- Molecular issues
claims that they can detect 99 % of DYS
cases with a blood lyphocyte Western blot.
 We found that the immunohistochemistry was
normal in this case and many others.
 We ran Western blotting and found none,
reduced, normal and overexpression in 9 cases.
 Athena
Muscle Nerve. 2013 May;47(5):740-7. Dysferlin aggregation
in limb-girdle muscular dystrophy type 2B/myoshi myopathy
necessitates mutational screen for diagnosis.
Nilsson MI, Laureano ML, Saeed M, Tarnopolsky MA.
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Physical Exam - Clues to a genetic
myopathy.
 Complete
Neurological Exam.
– Cataracts, myotonia (DM1).
– Ptosis (MG, OPMD, mito).
– PEO (MG, mito, RSS).
– Calf atrophy (DYS, hIBM).
– Calf hypertrophy (BMD,
LGMD)
 MSK exam:
– FSHD may get rotator cuff
issues.
– Contractures (Bethlem).
Case # 3– Skinny Legs
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Male 65 y.
Slowly progressive thigh
weakness.
CK = 1,200
EMG = mixed pattern
IBM
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More common in older men.
Quadriceps and finger flexor
atrophy.
CK is elevated but mild/moderate.
EMG is often distinct from others.
Swallowing affected in about 70 %.
Biopsy shows rimmed vacuoles (+
αB crystallin, tau, APP) + COX –
ve.
When to send for further testing.
 No
cause for the high CK.
 Neurological exam is abnormal (beyond radiculopathy
or diabetic neuropathy).
 Any CK over 1,000 iU/L.
 Positive family history of high CK or NMD or
arrhythmia/pacer or non-hypertensive cardiomyopathy
(lamin A/C, BMD)(HOCM screen @ CHEO).
 SOBOE + weakness (Pompe, MG, LGMD, mito.).
– Sitting/supine FVC - > 20 % drop = diaphragm weak.
The clinic:
Ms. L. Brandt
Ms. Erin Hatcher
Ms. L. Brady
Ms. D. Johnston
Ms. H. Vey
Ms. K. Scott
 The lab:
Dr. M. Nilsson
Dr. M. Akhtar
Dr. L. MacNeill
Mr. D. Ogborn
 Collaborators:
Dr. B. Lach
Dr. J. Provias
Dr. J. Bourgeois
Dr. T. Hawke
Dr. J. Schertzer

Thanks
• Warren Lammert and Family
• CIHR – Institute of aging.
• McMaster Children’s Hospital and
Hamilton Health Sciences Foundation.