1 / 15

What can I teach in 15 min?

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!. 69 y RHD male. PMHx : Angioplasty – 1995 Meds : Simvastatin , ASA, atenolol, terazocin, vits B/C/E

takoda
Download Presentation

What can I teach in 15 min?

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. 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.

  2. Case # 1– Lumber Jack! • 69 y RHD male. • PMHx: • 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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).

  8. Case # 2- Molecular issues • Athena claims that they can detect 99 % of DYS caseswith 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.

  9. 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).

  10. Case # 3– Skinny Legs • Male 65 y. • Slowly progressive thigh weakness. • CK = 1,200 • EMG = mixed pattern

  11. IBM • 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.

  12. 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.

  13. Thanks • 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 • Warren Lammert and Family • CIHR – Institute of aging. • McMaster Children’s Hospital and Hamilton Health Sciences Foundation.

More Related