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!Case # 1– Lumber Jack! 69 y RHD male.69 y RHD male. PMHxPMHx::
Angioplasty – 1995Angioplasty – 1995 MedsMeds: : SimvastatinSimvastatin, ASA, , ASA,
atenolol, terazocin, vits atenolol, terazocin, vits B/C/EB/C/E
HPIHPI: tree cutting x 2 ++ : tree cutting x 2 ++ DOMS w/ CK to 4869 then DOMS w/ CK to 4869 then dropping to 341 over 2 d.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. 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.
Treatment: – Vitamin D = 30 nmol/L;testosterone = N.– Creatine monohydrate (0.1 g/kg/d).
Case # 2- Molecular issues
Athena 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.
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.
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 LegsCase # 3– Skinny Legs
Male 65 y. Slowly progressive thigh
weakness. CK = 1,200 EMG = mixed pattern
IBM More common in older men.More common in older men. Quadriceps and finger flexor Quadriceps and finger flexor
atrophy.atrophy. CK is elevated but mild/moderate.CK is elevated but mild/moderate. EMG is often distinct from others.EMG is often distinct from others. Swallowing affected in about 70 %.Swallowing affected in about 70 %. Biopsy shows rimmed vacuoles (+ Biopsy shows rimmed vacuoles (+
ααB crystallin, tau, APP) + COX –B crystallin, tau, APP) + COX –ve.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.
Thanks The clinic:
Ms. L. BrandtMs. Erin HatcherMs. L. BradyMs. D. JohnstonMs. H. VeyMs. K. Scott The lab:
Dr. M. NilssonDr. M. AkhtarDr. L. MacNeillMr. D. Ogborn Collaborators:
Dr. B. LachDr. J. ProviasDr. J. BourgeoisDr. T. HawkeDr. J. Schertzer
• Warren Lammert and Family
• CIHR – Institute of aging.
• McMaster Children’s Hospital and Hamilton Health Sciences Foundation.