It's quite common to see a subject with raised CK in the Rheumatology clinic. Most of these subjects will not have one of the idiopathic inflammatory myopathies (IIM), the traditional forte of Rheumatologists, as these are quite rare disorders. While some of these cases will be undoubtedly, and correctly, passed to the Neurologists, it'd be helpful to formulate an approach to these subjects. No one individual can hope to have mastery of the hundreds of muscle disorders that can present in a tertiary clinic, and all too often one runs out of ideas when confronted by the patient with the raised CK. Failure to ask the right questions and to examine properly will result in an incorrect diagnosis. Here, therefore, is a brief approach, by no means comprehensive, but focusing on common muscle disorders seen in the clinic, with a suggested set of questions and helpful examination findings and investigations that might lead to a diagnosis. Certain obvious questions such as age and duration are deliberately ignored. Most experienced physicians will not miss out on such basics.
History
The three questions to ask to rule out metabolic myopathies
Is weakness or pain the main feature?
An overwhelming majority of subjects with IIM present with weakness. Pain in the absence of weakness often points to metabolic muscle diseases.
Are the symptoms related to exercise? How long does it take to appear?
Pain or cramps that is brought on by exercise, but is absent at rest, is typical of metabolic myopathies rather than IIM. In one series, the two commonest metabolic disorders that presented with exertional muscle pain were carnitine palmitoyl transferase II (CPT2) deficiency and myophosphorylase deficiency. While CPT2 deficiency typically causes pain after 30-60 minutes of exercise, myophosphorylase deficiency would be expected to cause pain within 5 minutes. (The next two commonest were phosphorylase kinase deficiency and myoadenylate aminase deficiency).
Does the patient pass dark urine during/after episodes of pain?
If so, this is due to myoglobinuria due to rhabdomyolysis, strongly associated with metabolic myopathies.
The four questions to rule out IIM
Raynaud?
Supports anti-synthetase syndromes.
Dysphagia?
IIM or overlap with scleroderma.
Joint pains?
Favours anti-synthetase syndromes
Weight loss?
Favours malignancy
Severe pain?
Makes IIM unlikely
Six questions to rule out toxin/drug induced myopathy
What is your alcohol intake?
Acute alcoholic myopathy often associated with low PO4, K.
Do you use any recreational drugs?
Cocaine, heroine, amphetamines, phencyclidine
Are you on statins or fibrates?
Are you on hydroxychloroquine?
Unpredictable myoneurotoxicity- not dose related. Can occur early or late. Can be associated with cardiomyopathy. Fully reversible with discontinuation. No pain. Reflexes diminished and loss of vibration in legs.
Are you on colchicine?
Usually dose related, prolonged use. Typically in subjects with renal impairment. No pain. Fully reversible with discontinuation.
Do you take nutritional supplements?
Creatine
Four questions to rule out adult onset muscular dystrophies/myopathies
Family history
Diabetes+ Hypogonadism+Cataracts
Myotonic dystrophy.
Diabetes+Deafness
Mitochondrial myopathy
Four questions to rule out MND (CK<1000)
Fasciculations?
Cramps?
Weight loss?
Nasal regurgitation?
One question to rule out parasitic muscle disease
Do you eat uncooked pork?
Trichinellosis
Examination
PM & DM causes symmetrical & proximal myopathy
IBM causes weakness of wrist and finger flexors- often asymmetrical
Expose the patient fully, so as not to miss shawl sign, V sign, Gottron's sign on knees, Holster sign and Flagellate erythema. Look for Gottron's papule and mechanics hands
Myotonia- handgrip and abductor pollicis
Myotonic Dystrophy 1 and 2.
Short stature? Ptosis and squint but no diplopia
Mitochondrial myopathy
Fasciculations, Babinski
MND
Typical DM rash?
Make sure patient is not on hydroxyurea.
Listen to chest.
Velcro crackles favours anti-synthetase and CADM
Synovitis?
Anti-synthetase or overlap
Periorbital oedema?
DM, PM or Trichinellosis,
Investigations
Metabolic myopathy
Plasma acylcarnitines raised in CPT-2 deficiency and other fatty acid disorders (but not in long chain acyl coA dehydrogenase deficiency)
Ask specifically for immunohistochemical staining for myophosphorylase, phosphorylase kinase and myoadenylate deaminase when you request muscle biopsy
If necessary, genetic testing for myophosphorylase, CPT2, myoadenylate deaminase
Serum amino acids (includes alanine)
24-hour urine for organic amino acids
Mitochondrial myopathy
Fasting lactate
Myotonic dystrophy
Immunoglobulins (Hypogammaglobulinemia)
Blood sugar, HbA1c
FSH, LH, Testosterone
ECG
Genetic tests- No. of CTG repeats in DMPK (MD1) or CCTG repeats in ZNF9 (MD2)
Trichinellosis
Eosinophilia
Serology- ELISA, followed by Western Blot
Drug/Toxin induced Myopathy
Screen for drugs of abuse
EMG , Muscle biopsy & MRI
Request EMG in one leg and Muscle biopsy in other leg to avoid artefact. Muscle biopsy ideally done in leg opposite to the one in which EMG abnormalities were demonstrated, but on the same side as abnormal MRI
Ask for staining for dystrophin, merosin and sarcoglycans when you request muscle biopsy
Avoid biopsy of calf- risk of artefact. Quads and deltoids best. Vastus lateralis safest.
Ask for staining for SDH and cytochrome oxidase- abnormal in mitochondrial myopathy
EMG will pick up myotonic dystrophy.
PM causes inflammation of fascial planes on MRI, IBM entire muscles.
History
The three questions to ask to rule out metabolic myopathies
Is weakness or pain the main feature?
An overwhelming majority of subjects with IIM present with weakness. Pain in the absence of weakness often points to metabolic muscle diseases.
Are the symptoms related to exercise? How long does it take to appear?
Pain or cramps that is brought on by exercise, but is absent at rest, is typical of metabolic myopathies rather than IIM. In one series, the two commonest metabolic disorders that presented with exertional muscle pain were carnitine palmitoyl transferase II (CPT2) deficiency and myophosphorylase deficiency. While CPT2 deficiency typically causes pain after 30-60 minutes of exercise, myophosphorylase deficiency would be expected to cause pain within 5 minutes. (The next two commonest were phosphorylase kinase deficiency and myoadenylate aminase deficiency).
Does the patient pass dark urine during/after episodes of pain?
If so, this is due to myoglobinuria due to rhabdomyolysis, strongly associated with metabolic myopathies.
The four questions to rule out IIM
Raynaud?
Supports anti-synthetase syndromes.
Dysphagia?
IIM or overlap with scleroderma.
Joint pains?
Favours anti-synthetase syndromes
Weight loss?
Favours malignancy
Severe pain?
Makes IIM unlikely
Six questions to rule out toxin/drug induced myopathy
What is your alcohol intake?
Acute alcoholic myopathy often associated with low PO4, K.
Do you use any recreational drugs?
Cocaine, heroine, amphetamines, phencyclidine
Are you on statins or fibrates?
Are you on hydroxychloroquine?
Unpredictable myoneurotoxicity- not dose related. Can occur early or late. Can be associated with cardiomyopathy. Fully reversible with discontinuation. No pain. Reflexes diminished and loss of vibration in legs.
Are you on colchicine?
Usually dose related, prolonged use. Typically in subjects with renal impairment. No pain. Fully reversible with discontinuation.
Do you take nutritional supplements?
Creatine
Four questions to rule out adult onset muscular dystrophies/myopathies
Family history
Diabetes+ Hypogonadism+Cataracts
Myotonic dystrophy.
Diabetes+Deafness
Mitochondrial myopathy
Four questions to rule out MND (CK<1000)
Fasciculations?
Cramps?
Weight loss?
Nasal regurgitation?
One question to rule out parasitic muscle disease
Do you eat uncooked pork?
Trichinellosis
Examination
PM & DM causes symmetrical & proximal myopathy
IBM causes weakness of wrist and finger flexors- often asymmetrical
Expose the patient fully, so as not to miss shawl sign, V sign, Gottron's sign on knees, Holster sign and Flagellate erythema. Look for Gottron's papule and mechanics hands
Myotonia- handgrip and abductor pollicis
Myotonic Dystrophy 1 and 2.
Short stature? Ptosis and squint but no diplopia
Mitochondrial myopathy
Fasciculations, Babinski
MND
Typical DM rash?
Make sure patient is not on hydroxyurea.
Listen to chest.
Velcro crackles favours anti-synthetase and CADM
Synovitis?
Anti-synthetase or overlap
Periorbital oedema?
DM, PM or Trichinellosis,
Investigations
Metabolic myopathy
Plasma acylcarnitines raised in CPT-2 deficiency and other fatty acid disorders (but not in long chain acyl coA dehydrogenase deficiency)
Ask specifically for immunohistochemical staining for myophosphorylase, phosphorylase kinase and myoadenylate deaminase when you request muscle biopsy
If necessary, genetic testing for myophosphorylase, CPT2, myoadenylate deaminase
Serum amino acids (includes alanine)
24-hour urine for organic amino acids
Mitochondrial myopathy
Fasting lactate
Myotonic dystrophy
Immunoglobulins (Hypogammaglobulinemia)
Blood sugar, HbA1c
FSH, LH, Testosterone
ECG
Genetic tests- No. of CTG repeats in DMPK (MD1) or CCTG repeats in ZNF9 (MD2)
Trichinellosis
Eosinophilia
Serology- ELISA, followed by Western Blot
Drug/Toxin induced Myopathy
Screen for drugs of abuse
EMG , Muscle biopsy & MRI
Request EMG in one leg and Muscle biopsy in other leg to avoid artefact. Muscle biopsy ideally done in leg opposite to the one in which EMG abnormalities were demonstrated, but on the same side as abnormal MRI
Ask for staining for dystrophin, merosin and sarcoglycans when you request muscle biopsy
Avoid biopsy of calf- risk of artefact. Quads and deltoids best. Vastus lateralis safest.
Ask for staining for SDH and cytochrome oxidase- abnormal in mitochondrial myopathy
EMG will pick up myotonic dystrophy.
PM causes inflammation of fascial planes on MRI, IBM entire muscles.
Great post.
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