Miopatias Flashcards
Qual a divisão didatica das miopatias?
Intro: Can be inherited/congenital or acquired. Broad c ategories include: Infl ammatory myopathies [dermatomyositis (DM), polymyositis (PM), inclusion body myositis (IBM)], & Myopathies due to other causes (i.e., endocrine abnlities, infections, medications).
Como abordar fraqueza muscular? iar
Approach to muscle weakness:
History & exam: Establish whether true weakness versus subjective “weakness” 2/2 other causes, e.g., pain, joint dysfn, disabling systemic condition.
# Evaluate for respiratory weakness: Tachypnea, consider mechanical ventilation if FVC < 15 mL/kg, NIF < 20 or rapid decline, evaluate for ineffective cough. São outros métodos validos - contar até 20 segundos, sustentar a cabeça 30 segundos, teste do copo d'água para disfagia. Note: A normal ABG & oxygen saturation in a patient w/ tachypnea are not helpful in determining the need for mechanical ventilation.
Quais os exames complementares uteis em miopatias?
Muscle enzymes, EMG/NCS, & muscle biopsy.
Como diferenciar entre as tres pricipais miopatias inflamatórias?
São as tres: polimiosite, dermatopolisiote e miosite com corpusculos de inclusão.
- Pele: papulas de Gottron e heliotropo somente na DM. Nenhuma alteração da IBM. Mãos de mecanico tanto em PM quanto DM.
- Biopsia: inflamação perimiseo endomisio na polimiosite, inflamação do perimiseo na dermatomiosite e multiplos vacuolos é de vacuolos de inclusão.
- Outras manifestações: Neuropatia tambem ocorre na IBM. Nas outras, acometimento cardiaco e pulmonar.
IBM tem pouca resposta ao tratamento, diferente das outras.
Quais doenças sistemicas são associadas as miopatias inflamatórias?
Association w/ systemic diseases: (1) Cancer: Risk increased 5–7-fold w/ DM; dx usu w/i 2 yr, either side of DM dx; 70% of cancers are solid tumors (cervix, lung, ovaries, pancreas, bladder, stomach). (2) Interstitial lung dz in 10% DM/PM (esp if antisynthetase Ab+). (3) Dysphagia 2/2 striated muscle weakness in upper 1/3 esophagus. (4) Myocarditis: Usu mild; check troponin I (more cardio-specifi c than CK-MB). (5) Other connective tissue dzs.
Como é a investigação das miopatias inflamatórias?
1) History & full physical examination (including breast/rectal/pelvic exam).
(2) Exclude drug-induced myopathy.
(3) Labs: CBC, ESR, CRP, chem7, anti-Jo1, antisynthetase ab, CK, LDH, AST, ALT, PSA, UA, anti-Ro, Sm, RNP, HIV, TSH. CK may be increased up to 50×, but if long-standing dz, CK may be low despite active dz.
(4) Autoantibodies: 80% ANA positive. Connective tissue disorders a/w myositis: Anti-Ro/Sm/RNP suggestive of overlap w/ connective tissue dz. Myositis-specifi c
auto-Abs: In 30% of pts; likely pathophysiologic role, though not yet entirely clear (antisynthetase ab, anti-Jo-1 ab, anti-SRP ab, anti-Mi-2 ab). Anti-Jo-1 probably most important since a/w interstitial pulmonary fi brosis.
(5) EMG/NCS: Increased membrane e xcitability (fi brillation potential activity & positive sharp waves in the active stages prior to Rx) & myopathic motor unit potentials w/ early recruitment (may be nl in up to 10%) supports dx but is not diagnostic.
(6) Consider MRI muscle (can show muscle infl ammation, edema, myositis, fi brosis, calcifi cation; may even use MR spectroscopy to look at muscle metabolism).
(7) Biopsy of muscle (ideally open biopsy) or skin in DM. (8) CT chest/abdomen/pelvis for malignancy.
(9) Ensure cancer screening is up-to-date
(10) Maintain vigilance for underlying malignancy for 2–3 yr after DM/PM dx.
Quais os fatores preditores de má resposta das miosites inflamatórias?
Predictors of poor outcome: Resp muscle weakness/interstitial lung dz; associated malignancy or cardiac involvement; dysphagia; delay in initiation of Rx for >6 mo after symptom onset; older age at onset (Am J Med 1993;94:379).
Qual o tratamento da miosite inflamatória?
In general, DM responds better to steroids than PM; goal is to increase muscle strength.
Treat w/ steroid taper ± steroid sparing agent until remission achieved, then attempt gradual taper, usu over 6–12 mo.
Recurrent dz or dz resistant to therapies may need other options, including rituximab or intravenous immune globulin.
# Steroids: Start at high doses, then taper to lowest effective maintenance dose. Initial dose: Prednisone at 1 mg/kg/day (but not >6 wk due to risk of steroid myopathy) ± steroid sparing agent (consult w/ neuromuscular specialist on preference/style). Assess response to Rx every few weeks by examining strength (more reliable than CK). If no response after 6 wk of high dose steroids, add steroid sparing agent (azathioprine or methotrexate) if not already added at beginning. If response, start tapering steroids as tolerated. # # Azathioprine: (1) Test for TPMT (thiopurine methyltransferase) defi ciency. Heterozygotes require lower doses & careful monitoring. Homozygotes (1/300) cannot metabolize drug leading to bone marrow toxicity (Ann Intern Med 1980;92:365). (2) Initial dose 25 mg/day; increase over weeks to 1.5–3 mg/kg/day; max dose 200 mg/day. (3) Side effects: Flu-like sx, fever, GI complaints; bone marrow suppression, liver toxicity, pancreatitis, possibly increased risk of malignancy. (4) Monitor CBC, LFTs initially every 2 wk, then monthly if stable. # Methotrexate: Only once weekly dosing; initial dose 15 mg/wk, ↑ by 5 mg/wk up to 25 mg/wk. Side effects: Stomatitis; GI symptoms, leukopenia, hepatotoxicity (don’t give to pts w/ liver dz or who drink alcohol), pulmonary toxicity. Can reduce risk of leukopenia w/ folic acid 1 mg/day.
Qual o padrão da miosite de corpusculo de inclusão? Qual a repercussão terapeutica?
Dx: (1) Labs: Nl or <10× elevated CK; usu nl ESR, ANA. (2) EMG/NCS: Myopathic pattern as in other myopathies. (3) MRI: Helps to distinguish IBM from PM (IBM in anterior muscle groups, more distally & more asymmetrical than PM). (4) Bx: Endomysial infl ammation; basophilic rimmed vacuoles w/in muscle fi ber sarcoplasm (on frozen bx only); eosinophilic inclusions, fi ber size variation. Electron microscopy: Filamentous inclusions & vacuoles in 90% of pts. Muscle fi ber inclusions w/ staining for β-amyloid deposits. Paired helical fi bers by EM or immunohistochemistry
Rx: Generally poor response to Rx, including steroids or immunosuppressants. IVIg w/ no real benefi t in small studies to date. PT/OT.
Quais outras causas de miopatia não inflamatórias adquiridas?
Que exames devemos solicitar?
- Associada ao HIV: Sorologia para HIV
- Endocrinopatias: TSH e T4L, cortisol e PTH
- Metabólicas: P e K, deficiencia de vitamina D e E
- Toxicas: corticoide, OH, estatinas, cocaina, antipsicoticos, colchicina e penicilamina.
Como monitorizar miopatia induzida por estatinas e qual a conduta frente a ela?
Monitorização: baseline CK prior to statin therapy; no need for routine CK monitoring while on statin. Dose CK in myalgias (10%): Proximal, symmetric muscle soreness & weakness; muscle enzymes can be nl. Most occur w/in 6 mo of starting statins but can occur at any time during Rx. ↑ risk w/: Cotreatment w/other drugs (esp Cyp3A4 inhibitors, such as cyclosporine, gemfi brozil, macrolides) & hypothyroidism
Conduta: Toxicity mgt: If CK elevation & myopathy thought to be caused by statin, rather than other factors, especially if CK increased 10-fold, stop statin; encourage oral fl uids, when CK back to nl, consider restarting statin a/w less muscle toxicity.
