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.