Diseases of Muscle 1

Question 1

Classification of myopathies

Answer 1

Question 2

Symptoms of myopathies

Answer 2

Question 3

Laboratory and diagnostic studies used in the evaluation of myopathy

Answer 3

Question 4

Which laboratory finding suggests muscle than liver disease

Answer 4

Normal γ-gt

Question 5

Patterns of muscle weakness in myopathies

Answer 5

Question 6

EMG findings in myopathy

Answer 6

Classic EMG findings in myopathy include:
- short-duration, polyphasic, small-amplitude motor
unit potentials (this is due to loss of muscle fibers per motor unit)
- Early recruitment pattern is seen because more motor units (each with less force due to loss of muscle fibers) must be enlisted to generate a given force.
- Spontaneous activity in the form of positive sharp waves and fibrillations (which represent muscle membrane irritability due to necrosis or inflammation) may be present in varying amounts depending on the etiology

Question 7

Gold standrard for establishing muscle disease

Answer 7

Muscle biopsy

Question 8

Muscle biopsy indication

Answer 8

Muscle biopsy should be performed in patients presenting with clinical and/or laboratory evidence of myopathy who do not have extramuscular manifestations such as a typical DM rash or a myositis-specific autoantibody.

Question 9

Idiopathic Inflammatory myopathies

Answer 9

Most common:
1) dermatomyositis (DM)
2) polymyositis (PM)
3) inclusion body myositis (IBM)
4) immune-mediated necrotizing myopathy (IMNM)

Others
5) overlap syndromes
6) antisynthetase syndrome
7) clinically amyopathic DM (CADM)

Question 10

What should be done in every newly diagnosed DM and PM

Answer 10

All patients newly diagnosed with PM or DM should be evaluated for the possibility of an underlying malignancy.

Question 11

cancers associated with inflammatory myopathies

Answer 11

• Adenocarcinomas of the cervix (τραχήλου της μήτρας)
• lung
• ovaries
• pancreas
• bladder and
• stomach

account for approximately 70 percent of the cancers associated with inflammatory myopathies

Question 12

Most common acquired inflammatory myopathy (myositis) in adults >50years

Answer 12

IBM

Question 13

Inflammatory myopathies epidemiology

Answer 13

Dermatomyositis affects both children and adults and females more than males (2:1)

Polymyositis mostly affects adults

IBM usually presents after age 50 and affects men much more often than women (3:1) and whites slightly more often than blacks

Question 14

Percentage of patients with dermatomyositis/ polymyositis who have also a connective tissue disorder

Answer 14

11-40%

Question 15

Diseases associated with inflammatory myopathy (overlap syndromes)

Answer 15

• systemic lupus erythematosus
• Sjögren syndrome
• primary biliary sclerosis
• Crohn disease
• celiac disease
• Behçet disease
• graft-versus-host disease
• vasculitis
• sarcoidosis
• Hashimoto thyroiditis
• psoriasis
• myasthenia gravis
• HIV infection

Question 16

Is childhood dermatomyositis associated with cancer?

Answer 16

No

Question 17

Part of immune system associated with polymyositis and dermatomyositis

Answer 17

PM: T-cell mediated cytotoxicity, macrophages, CD8

dermatomyositis: B cells, plasma cells, CD4, complement-mediated tissue destruction –> systemic microangiopathy in which the endothelial cells of blood vessels in the endomysium are target of immune attack

Question 18

Percentage of patients with inflammatory myopathy and positive autoantibodies (associated or specific)

Answer 18

80%!!

Question 19

Myositis-associated autoantibodies

Answer 19

The detection of:
- anti-Ro/SSA
- anti-La/SSB
- anti-Sm
- anti-ribonucleoprotein (RNP) antibodies
in a patient with myositis suggests association or overlap with another systemic rheumatic disease.

Anti-Ro and occasionally anti-La can be seen in up to one-fifth of those with IBM but often may not have any associated clinical features of Sjögren’s disease

Question 20

Myositis specific antibodies

Answer 20

• Antisynthetase antibodies
  Anti-Jo-1 is the most common - approximately 20 percent of IIM patients
• Anti-SRP antibody
  highly specific for immune-mediated necrotizing myopathy
• Anti-HMGCR antibody
  develop an IMNM with little inflammatory infiltrate similar to patients with anti-SRP antibody.
  Anti-HMGCR is also associated with statin use, although up to 50 percent of patients with this antibody are statin naïve
  Σχετίζεται με κακοήθεια!
• Anti-NXP-2 antibody
  associated with juvenile or young-onset DM with severe disease, edema, and calcinosis
  May be associated with malignancy in adults, particularly in males
  Can also be associated with prominent muscle disease, dysphagia, myalgia, and calcinosis in adults and has been found in 11 to 24 percent of DM patients
• Anti-TIF-1gamma antibody
  associated with a characteristic cutaneous phenotype including palmar hyperkeratotic papules, psoriasis-like lesions, and hypopigmented and telangiectatic “red-on-white” patches
  Strongly associated with an increased risk of cancer
  Another associated clinical feature is the ovoid palatal patch, which is strongly correlated with malignancy
• Anti-MDA5 antibody
  strongly associated with interstitial lung disease, including a rapidly progressive phenotype with high morbidity and mortality
  tend to lack muscle involvement but often have arthritis
  There is a characteristic cutaneous phenotype that includes ulcerations over the Gottron papules and sign, painful palmar papules and macules, oral ulcerations, and nonscarring alopecia
• Anti-Mi-2 antibody
  associated with the relatively acute onset of DM
  associated with a classic shawl or V-sign
  may respond well to therapy
• Anti-SAE antibody
  high prevalence of dysphagia and cutaneous manifestations that precede the development of myopathy

Question 21

Polymyositis clinical findings

Answer 21

Progressive limb-girdle pattern of symmetric weakness (usually over weeks to months)
May precede viral infection.

Additional symptoms and signs occur when PM is associated with systemic autoimmune diseases.

Shortness of breath may be the consequence of cardiac or pulmonary muscle involvement or interstitial lung disease (as with the antisynthetase syndrome).
Respiratory failure may result from weakness of the diaphragm and chest wall muscles.

Cardiac involvement occurs in up to 40% of patients with PM, causing conduction defects, tachyarrhythmias, dilated cardiomyopathy, congestive heart failure, and myocarditis.

Dysphagia is a result of weakness of the oropharynx and distal esophagus.
Facial muscle involvement is not rare.

Palpation of involved muscles may reveal tenderness, especially early on in the disease.
Weight loss, fatigue, and generalized malaise are common.

Question 22

Dermatomyositis clinical findings

Answer 22

Same as polymyositis plus:

1. Heliotrope rash with eyelid edema and a facial rash
2. Gottron sign (erythema of knuckles accompanied by a raised violaceous scaly eruption)
3. Erythematous rash over the knees, elbows, malleoli, at the base of the neck and upper chest (“V” sign), or over upper back and shoulders (“shawl” sign) that worsens with sun exposure
4. Dilated capillary loops at the base of the fingernails
5. Mechanic-like hands are present in the antisynthetase
   syndrome

Question 23

Antisynthetase syndrome

Answer 23

associated with antibodies to aminoacyl-tRNA synthetases (eg, anti–Jo-1 antibody)
inflammatory myopathy and extramuscular findings:
fevers, interstitial lung disease, Raynaud phenomenon, mechanic hand (hyperkeratosis and cracking of the skin over the palms and fingers) and arthralgias

There does not appear to be an increased risk of malignancy in this group

Question 24

Polymyositis and dermatomyositis laboratory findings and special tests

Answer 24

The serum CK level may be normal even in patients with
active disease, but is usually 50 times greater than the upper limit of normal.
Levels of other muscle enzymes (eg, aldolase, aminotransferases, and lactate dehydrogenase) may also be elevated.

The CRP and/or ESR are often normal or only mildly elevated, even in patients with active muscle disease.

Myositis (specific MSA and associate MAA!) antibodies are used to support diagnosis and to classify subtype of myositis.

A myopathic EMG with profuse spontaneous activity is usually seen, which signifies ongoing myonecrosis and inflammation.
NCSs show normal sensory nerve action potentials
and low-amplitude motor responses when recording from weak muscles.

Muscle biopsy is definitive and shows endomysial inflammatory infiltrates, necrosis of muscle fibers, and scattered atrophy and regeneration of muscle fibers.

++ περιδεσμιδική ατροφία υπάρχει μόνο στη δερματομυοσίτιδα γιατί είναι μια μικροαγγειοπάθεια και ισχαιμούν περισσότερο οι περιφερικές ζώνες του μυικού δεσμιδίου

Question 25

Percentage of dermatomyositis with normal CPK

Answer 25

5-15%

Question 26

DM, PM and CADM diagnosis

Answer 26

Dermatomyositis –
The diagnosis of classic DM can be made without a muscle or skin biopsy in patients with clinical and laboratory findings that are particularly characteristic of this disorder, which include symmetric proximal muscle weakness in the setting of marked elevation of muscle enzymes and characteristic cutaneous eruptions, in whom evidence suggesting an alternative diagnosis is lacking.

Clinically amyopathic dermatomyositis –
The diagnosis of CADM is based upon the presence of classic cutaneous manifestations of DM without clinical evidence of muscle weakness.
Skin biopsy may be performed to rule out other etiologies of rash that can mimic cutaneous DM.
EMG, MRI, or muscle biopsy may reveal occult muscle disease, but such studies are generally not needed in patients with classic clinical presentation.

Polymyositis –
The diagnosis of PM can be made in patients presenting with symmetric proximal muscle weakness and elevated muscle enzymes but typically requires a muscle biopsy to demonstrate typical histopathologic findings consistent with PM.
EMG or MRI may be required to help confirm the presence of myopathy and/or guide the location for the muscle biopsy.

In some cases, myositis-specific or myositis-associated autoantibodies are helpful in confirming the diagnosis and may provide management and prognostic information.

Question 27

Serum autoantibodies in DM and PM and cancer risk

Answer 27

Some serum autoantibodies in DM and PM confer a positive risk of malignancy, whereas others are associated with a negative risk.

“Cancer-associated myositis” in adults has been associated in several studies with antibodies to (TIF)-1gamma (anti-p155, anti-p155/140) and with antibodies to nuclear matrix protein (NXP)-2 (anti-MJ or anti-p140).

Anti HMGCR associated with cancer in over 40%

Conversely, the presence of myositis-specific (anti-synthetase antibodies, anti-Mi-2, anti-SRP) and myositis-associated antibodies (anti-RNP, anti-PM-Scl, anti-Ku) appears to be associated with a decreased risk of malignancy but an increased risk of interstitial lung disease in DM.

Question 28

clinically amyopathic DM

Answer 28

a condition in which patients have characteristic skin findings of DM without weakness, abnormal muscle enzymes, or other abnormal muscle studies

Question 29

Initial treatment of dermatomyositis and polymyositis in adults

Answer 29

We recommend glucocorticoids for inflammatory myopathy associated with significant muscle weakness

*We typically begin prednisone at a dose of 1 mg/kg per day and generally do not exceed 80 mg daily.

*For patients who are severely ill, we suggest initiating glucocorticoid therapy with an intravenous methylprednisolone pulse: 1000 mg/day for three days

*We suggest tapering prednisone to the lowest effective dose over a total of 9 to 12 months

Glucocorticoid-sparing agents –
We suggest initiating a glucocorticoid-sparing agent at the same time glucocorticoids are begun.
The first-line glucocorticoid-sparing agents are azathioprine and methotrexate.

*Selection between azathioprine and methotrexate is guided by a variety of factors including patient preference, underlying liver or lung disease, willingness to limit alcohol intake, and deficiencies in thiopurine methyltransferase (TPMT) alleles

*We suggest azathioprine in patients who have interstitial lung disease associated with their myositis, have underlying liver disease, or are unwilling to abstain from alcohol

*The usual starting dose for azathioprine is 50 mg/day. This can be increased gradually to up to 2.5 mg/kg/day. A complete blood count should be monitored within two weeks of starting azathioprine.

*The usual starting dose for methotrexate is 15 mg/week. If there is an inadequate response after two to three months, this can be increased to 25 mg/week.

Once treatment has begun, following muscle strength on serial physical examinations is a more important gauge of treatment response than are the serum concentrations of muscle enzymes!!!

●Duration of therapy – We suggest attempting to discontinue immunosuppressive therapy after the first round of treatment, with careful follow-up for the possibility of disease recurrence

We suggest tapering glucocorticoids off before beginning to taper the glucocorticoid-sparing agent

Question 30

Causes of glucocorticoid failure in inflammatory myopathy treatment

Answer 30

*The original diagnosis of DM or PM was incorrect

*The patient may have developed a glucocorticoid-induced myopathy

*An unrecognized malignancy associated with myositis may be the cause of the failure to respond to therapy

Question 31

General treatment measures in dermatomyositis and polymyositis

Answer 31

*Physical therapy and rehabilitation should begin early in the course of treatment, with regimens tailored to the severity of weakness.

*Aspiration precautions are advisable for patients with esophageal dysfunction. Speech therapy evaluations may be helpful for patients with esophageal disease.

*Patients with DM may be photosensitive and should, therefore, take measures to avoid ultraviolet light.

*Glucocorticoid-induced osteoporosis can be an important cause of long-term treatment-related morbidity.
We recommend that measures should be taken for the prevention of glucocorticoid-induced osteoporosis

*For patients treated with the combination of high-dose prednisone and any other immunosuppressive agent, we suggest prophylaxis against Pneumocystis jirovecii infections

*For Pneumocystis prophylaxis, one appropriate regimen is a single-strength tablet of trimethoprim-sulfamethoxazole (80 mg/400 mg) each day. Daily double-strength trimethoprim-sulfamethoxazole tablets should not be used in patients treated with methotrexate.

*If a female patient desires to become pregnant, disease manifestations should be as well-controlled as possible before the patient attempts to conceive.

Question 32

IBM clinical findings

Answer 32

IBM has an insidious, slowly progressive course that develops after age 50

Characteristic patterns include:
1. Early distal weakness (wrist and finger flexors, foot dorsiflexors)
2. Early quadriceps weakness with early loss of patellar reflexes
3. Asymmetric weakness

Extraocular muscles are usually spared, but mild facial weakness and significant dysphagia can occur in about one-third of patients.
Peripheral neuropathy is present in up to 30% of patients.

Signs of systemic autoimmune disease occur in up to 15% of patients.

Question 33

IBM laboratory findings

Answer 33

Laboratory studies reveal normal or moderately elevated CK
levels (up to 10 times the upper limit of normal).

++ cN1A antibody in 33-61% of patients (not specific - also detected in about 20 percent of patients with SLE and Sjögren’s disease in the absence of muscle disease)

EMG and NCSs may reveal mild axonal polyneuropathy and neurogenic-appearing motor units superimposed on predominantly “myopathic” features with abnormal spontaneous activity.

Βιοψία μυός: εκτός από τα φλεγμονώδη στοιχεία παρατηρούνται
- κενοχωριώδεις μυικές ίνες
- ενδοκυττάριες εναποθέσεις αμυλοειδούς
- ενδοκυττάρια σωληνοϊνιδιακά έγκλειστα μεγέθους 15-18nm

Question 34

Is IBM associated with cancer or connective tissue disorder?

Answer 34

Not associated with cancer
<15 % associated with connective tissue disorder

Question 35

IBM management and prognosis

Answer 35

The primary goal of therapy in inclusion body myositis is to optimize muscle strength and function.

● Nonpharmacologic therapy – Nonpharmacologic interventions such as physical therapy, occupational therapy, and/or speech therapy can be helpful in all patients

● Creatinine supplementation – Given negligible side effects and evidence for improved muscle strength in muscular dystrophy, we suggest supplementation with 3 g of creatine monohydrate per day.

● Limited role for immunosuppression – In contrast to other inflammatory myopathies such as dermatomyositis and polymyositis, IBM is relatively resistant to standard immunomodulatory therapies.
We only consider a trial of immunosuppressive medications (prednisone or methotrexate) in IBM patients with an atypical presentation or in patients with another systemic autoimmune disease

● Prognosis – Patients with IBM usually progress to disability over a period of years. The older the age at onset of the disease, the more rapid the loss of strength and function. By 15 years, most patients require assistance with basic daily activities, and some will need to use a wheelchair or need to stay in bed

Question 36

Immune-mediated necrotizing myopathy

Answer 36

Immune-mediated necrotizing myopathy (IMNM) is a distinct subgroup of IIM classically characterized by predominant myofiber necrosis with minimal inflammatory infiltrates on muscle biopsy

IMNM is also distinguished from other categories of IIM by highly elevated creatine kinase levels, paucity of extra-muscular involvement, and, occasionally, more severe disease that is difficult to fully control with immunosuppressive therapy

Most patients present with subacute proximal limb muscle weakness and a high serum creatine kinase level in the absence of characteristic skin findings for DM or overt connective tissue disease overlap features such as Raynaud phenomenon or an inflammatory arthritis.

Subgroups:
1) associated anti-HMGCR autoantibodies with or without a history of statin use.
2) associated autoantibodies to SRP

The incidence of cancer in patients with anti-HMGCR–IgG antibody positive immune-mediated necrotizing myopathy may exceed 40%, so routine screening for cancer in patients with these conditions is recommended.
The incidence of cancer in individuals with SRP–antibody immune-mediated necrotizing myopathy is low

https://www.uptodate.com/contents/image?imageKey=RHEUM%2F139886&topicKey=RHEUM%2F131941&search=necrotizing%20myopathy&rank=1~150&source=see_link

++ Continuum 2022

Question 37

Cholesterol-lowering agent myopathy: agents

Answer 37

Cholesterol-lowering agents, including statins, niacin, clofibrate, and gemfibrozil, has potential myotoxic effects.

Διάφορες στατίνες (ατορβαστατίνη, σιμβαστατίνη, λοβαστατίνη) μεταβολίζονται από το ένζυμο CYP3A4 του P450.
Φάρμακα που το αναστέλλουν αυξάνουν τον κίνδυνο μυοτοξικότητας.
(Προσοχή σε συγχορήγηση με μακρολίδες, βεραπαμίλη, κυκλοσπορίνη, διλτιαζέμη)
Εναλλακτικά χρησιμοποίηση στατινών που δεν χρησιμοποιούν το CYP3A4 όπως πραβαστατίνη, φλουβαστατίνη, ροσουβαστατίνη.

Όταν είναι απαραίτητη η συγχορήγηση στατίνης με φιβράτη προτιμάται η φενοφιβράτη

Σχετικά ασφαλής συνδυαμός στατίνη + εζετιμίμπη

Question 38

Which antibiotic increases the risk of myopathy in patients taking statins?

Answer 38

Macrolides

Question 39

Risk of myositis with statins according to agent

Answer 39

Atorvastatin poses the highest risk

simvastatin, lovastatin, and pravastatin are of intermediate risk

fluvastatin is of lowest risk

Question 40

Cholesterol-lowering agent myopathy: clinical findings and diagnosis

Answer 40

Statins can cause a variety of myopathic symptoms and signs:
1. Myalgias — with or without mild CK elevation
2. Asymptomatic hyperCKemia (elevated serum CK without weakness or pain)
3. Myopathy — mild proximal weakness, myalgias, elevated CK, rarely associated with rhabdomyolysis (usually in combination with other drugs)
4. IMNM—severe myopathy with weakness, elevated CK, anti-HMGCR antibodies

The first three conditions resolve with statin discontinuation,
and the fourth is a distinct (but rare) entity in which the myopathy progresses despite discontinuation of the statin and often requires long-term immunosuppression.

EMG may show abnormal spontaneous activity, including myotonic-like discharges, and myopathic features.

Muscle biopsy findings in statin-associated myotoxicity are generally nonspecific and include atrophy and necrosis

Question 41

Which factors increase risk of myopathy in statin use

Answer 41

1) taking a statin that is extensively metabolized by cytochrome P450 3A4 (CYP3A4; lovastatin, simvastatin, atorvastatin) together with a drug that interferes with CYP3A4

2) patients with impaired hepatic and renal function; hypothyroidism; diabetes mellitus; and the concomitant use of myotoxic agents, such as fibric acid derivatives (gemfibrozil), niacin, cyclosporine, azole antifungals, macrolide antibiotics, zidovudine, nefazodone, verapamil, diltiazem, amiodarone, and excessive daily consumption of grapefruit juice.

Question 42

Statin myopathy management

Answer 42

Patients with symptomatic or asymptomatic rhabdomyolysis or Immune-mediated necrotizing myopathy from a statin should discontinue therapy immediately.

In patients with immune-mediated necrotizing myopathy treatment with oral steroid, methotrexate, intravenous immunoglobulin (IVIG), and/or rituximab appears to be reasonable and safe, and these agents are commonly used

• Switching statins – Pravastatin, pitavastatin, and fluvastatin appear to have much less associated muscle toxicity than other statins.
  Thus, in patients who have developed statin myopathy (other than rhabdomyolysis) on a statin other than pravastatin, pitavastatin, or fluvastatin, we suggest switching to one of these medications once symptoms have resolved off statin therapy
• Alternate-day dosing – In patients who are unable to tolerate daily dosing of pravastatin, fluvastatin, or pitavastatin, we suggest a trial of alternate-day or less frequent dosing (one to two times weekly) of statin therapy

Question 43

What could be the cause of not improving despite discontinuing statin?

Answer 43

1) Presence of autoimmune necrotic myopathy (antibodies against HMGCR should be sent and if positive immunomodulatory treatment may be needed)

2) Statin therapy may have revealed an underlying hereditary myopathy

Question 44

Sarcoid myopathy clinical findings and diagnosis

Answer 44

Three types of clinical muscle disease are recognized:
- insidious proximal muscle weakness
- acute myopathy with weakness and elevated muscle enzymes
- nodular myopathy (the least commonly seen)

Muscle involvement is commonly subclinical

● In a patient with sarcoidosis, the presence of muscle weakness, muscle pain, or muscle nodules is suggestive of sarcoid myopathy.
MRI may help to identify and distinguish between the different types of myopathy, but is normal in some patients with mild or acute disease.
EMG may reveal a myopathic pattern, but EMGs are normal in patients with nodular involvement.
Biopsy of affected muscle typically shows multiple characteristic noncaseating granulomas in perimysial connective tissue.

A diagnosis of sarcoid myopathy can generally be made in patients with
- sarcoid in another site
- elevated muscle enzymes
- myopathic EMG studies
- characteristic findings on MRI in patients with nodular myopathy
- diffuse inflammatory myopathic MRI findings in acute or chronic myopathy
- biopsy evidence of noncaseating granulomas, usually with a high CD4:CD8 T-lymphocyte ratio.

Question 45

Sarcoid myopathy management

Answer 45

● Early institution of therapy is critical, as glucocorticoids and other immunosuppressive agents cannot reverse muscle atrophy.
Asymptomatic muscle disease does not require specific pharmacotherapy.
All patients with sarcoidosis and muscle weakness should receive a physical therapy evaluation and instruction in a regular exercise program.

● In most patients with symptomatic acute or chronic myopathy , we suggest initiating glucocorticoids rather than other immunosuppressive agents.
For acute or nodular myositis we use prednisone 0.5 to 1 mg/kg daily with a goal of gradually tapering over no more than three months.
For chronic myopathy we use prednisone 1 mg/kg daily (to a maximum of 80 mg daily), then taper gradually over 6 to 12 months.
Patients at increased risk of adverse effects from glucocorticoids or with severe disease may benefit from starting methotrexate together with initiating glucocorticoids.
For patients with only one or few painful nodular lesions, we suggest intralesional injection of triamcinolone, bed rest, and a nonsteroidal antiinflammatory drug (NSAID) rather than oral glucocorticoids.

● In patients with an inadequate response to glucocorticoids either due to inefficacy after two to three months of therapy, an inability to taper prednisone below 10 mg after six months of therapy, or intolerance of the glucocorticoids, we suggest adding an additional immunosuppressive agent rather than higher doses of glucocorticoids.
We prefer either azathioprine or MTX

● In patients with an inadequate response to a three-month trial of glucocorticoids combined with MTX or AZA, we suggest adding a tumor necrosis factor (TNF) inhibitor rather than another immunosuppressive or biologic agent
We prefer infliximab or adalimumab, but not etanercept, which has failed to show benefit in patients with progressive pulmonary sarcoidosis or chronic ocular disease.

Question 46

Myopathy in HIV patients: causes

Answer 46

These myopathies include:
* mitochondrial myopathies related to antiretroviral therapy (nucleoside reverse transcriptase inhibitors [NRTIs], especially zidovudine)
* PM
* IBM
* microvasculitis
* secondary infections causing myositis (pyomyositis, fungal myositis),
* rhabdomyolysis
* HIV-wasting syndrome

Question 47

Most common viruses associated with myopathy

Answer 47

influenza
enteroviruses
retroviruses
hepatitis viruses

*Influenza and coxsackie viruses are the most common

Question 48

Risk factors for pyomyositis and most common organism

Answer 48

• HIV
• diabetes mellitus
• intravenous drug abuse
• skin infections
• malignancy
• rheumatologic conditions
• muscle trauma

Staphylococcus aureus

Question 49

Corticosteroid myopathy: clinical and laboratory findings

Answer 49

Two forms of corticosteroid myopathy have been clinically defined.

1) chronic, slowly progressive myopathy
* mild-to-moderate proximal muscle weakness, a cushingoid appearance, and chronic corticosteroid intake, usually at prednisone doses greater than 30 mg/d.
* serum CK level may be normal
* EMG findings are normal or show myopathic features without spontaneous activity, distinguishing this disorder from polymyositis.

2) myopathy in critically ill patients in intensive care units
* other myotoxic agents, especially neuromuscular blocking drugs, are often used concomitantly, and patients are septic with multiorgan failure.
Acute proximal and distal muscle weakness occurs, and facial and cardiopulmonary muscles are often affected.
Extraocular muscles are usually spared.
* The serum CK level is commonly elevated
* EMG findings are often myopathic, with abnormal spontaneous activity, although in critically ill patients coexisting polyneuropathy may be seen

Muscle biopsy specimens show atrophy of type 2b fibers.

Question 50

Corticosteroid myopathy management

Answer 50

Minimizing the dose and duration of glucocorticoid exposure is the most important intervention.
Muscle strength begins to improve within three to four weeks after sufficient dose reduction and eventually resolves in virtually all patients if glucocorticoid therapy can be discontinued.

Question 51

Alcoholic myopathy clinical findings and diagnosis

Answer 51

Acute alcoholic myopathy
* characterized by rapid (hours to days) onset of symptoms after a recent increase in alcohol consumption or binge drinking episode.
Proximal weakness and pain usually predominate, but regional or focal involvement can occur.
* Serum CK level is elevated in most patients and in severe cases may lead to rhabdomyolysis.
* EMG typically shows abnormal spontaneous activity with myopathic features.
* Muscle biopsy shows muscle necrosis with regenerating fibers. (not indicated in the acute setting)

Chronic alcoholic myopathy
* occurring in patients with chronic heavy alcohol consumption causes insidious, painless, proximal weakness, and, over time, atrophy.
* serum CK level may be normal or mildly elevated.
* EMG and nerve conduction studies may reveal both myopathic and neuropathic changes.
* Muscle biopsy shows atrophy of type 2 muscle fibers without necrosis.

Question 52

Acute generalized weakness syndromes in critically ill patients

Answer 52

https://www.uptodate.com/contents/image?imageKey=NEURO%2F114822&topicKey=NEURO%2F5144&search=critical%20illness%20myopathy&rank=1~25&source=see_link

Question 53

Secondary metabolic myopathies

Answer 53

• Hypokalemic
• Hypophosphatemic
• Chronic renal failure (uremic)
• Diabetic muscle infarction
• Hypothyroid
• Hyperthyroid
• Hyperparathyroid
• Vitamin D related
• Cushing disease

Question 54

Most common endocrinopathy that causes myopathy

Answer 54

Hypothyroidism

Question 55

Hypothyroid myopathy clinical findings

Answer 55

muscle weakness and cramping are often present

Prolonged or delayed relaxation of deep tendon reflexes is a characteristic finding, and myotonoid features (slow relaxation of a group of muscles following contraction) are seen in one fourth of patients.

Proximal weakness develops insidiously and may be associated with pain and tenderness.

rare: muscular enlargement or pseudohypertrophy, in adults
(Hoffman syndrome).

Question 56

Hyperthyroid myopathy clnical findings

Answer 56

Patients usually present insidiously with proximal weakness,
prominent atrophy, and, often, hyperactive deep tendon reflexes.

Scapular winging and bulbar and ocular muscle weakness are sometimes present.
Weakness may be painless, although occasional patients have myalgias.

Question 57

Hyperparathyroid myopathy

Answer 57

Patients may have proximal muscle weakness, atrophy, hyperactive deep tendon reflexes, and fasciculations, and in severe cases, this combination may resemble amyotrophic lateral sclerosis.
Muscle cramps are occasionally present, and respiratory failure, presumably due to severe hypercalcemia, has been reported