Transcript Myalgia, Neuralgia, and Arthralgia

Course: Myalgia, Neuralgia, and Arthralgia
“Myalgia: Muscle Disorders and Pain”
W. David Arnold, MD
AAPMR 2015
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Muscle Disorders and Pain
– Overview of the problem
– Examples of myopathies
associated with pain
– Non-muscle disorders
associated with myalgia
– Approach and diagnosis of the
patient with myalgia
Acknowledgements:
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I receive funding through the RMST program (NICHD 5K12HD001097-17)
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John T. Kissel’s expertise and input regarding content
Myalgia: the stats..
• Common reason for referral in NM clinics
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~50% of referrals (i.e. for muscle biopsy)
90% of myalgia patients have fatigue
– 95% of patients with chronic fatigue
syndrome have myalgia
Myalgia: the problem..
• Pain is often an isolated symptom
– No objective signs of disease (i.e. weakness)
• Myalgia may arise from many sources
– Orthopedic, rheum, endocrine, vascular,
psychological
– May not be related to muscle disease
• Many patients, despite extensive workup are
“not diagnosable”
Myalgia Terminology
Types of Pain
• May
be useful to classify into types:
 Contractures
 Stiffness
 Cramps
 Aching myalgia
(after Layzer, 1985)
Types of Muscle Pain
Contracture
• Least common myalgia, can be excruciating
• Forceful, sustained contraction
– Localized hard nodule in muscle
• Electrically silent by EMG!
• Sudden onset with exercise (may be mild)
– May persist for hours & result in rhabdo.
• Hallmark of glycolytic dx. (eg McArdle’s)
– FET useful screen for these disorders
• Others: Brody’s disease, hypothyroid
Types of “Muscle Pain”
Cramps
Idiopathic (normal cramps)
 Exertional, post-exertional, nocturnal
Neurogenic cramps
 MND, PN, radics, others.
Cramps due to altered neural environment
 Pregnancy
 Metabolic disorders (renal or liver failure)
 Hypothyroidism
 Adrenal insufficiency
 Electrolyte disturbances/volume depletion
Cramps are related to nerve hyperexcitability,
electrically active on EMG
Muscle Stiffness
Differential Diagnosis
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Myotonic disorders
– DM 1 & 2
– MC and PMC
Hypothyroidism
Hypo PP
Brody’s disease
PMR
Fibromyalgia
Myotonic Dystrophy
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Two characterized types
– DM1-more common and
usually more severe
– DM2
Multisystem disease
– Muscle
– Eyes (cataracts)
– GI
– Cardiac-mainly
arrhythmia (30%
mortality)
– CNS (cognitive and
personality)
– Pulmonary (restrictive
and hypoventilation)
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Autosomal Dominant
Triplet repeat disease
associated with anticipation
DM2 has been associated
with fibromyalgia in case
series and case reports
--Auvinen et al. 2008
Muscle Channelopathies
Disease/Phenotype
Gene
KCNJ2
Periodic Paralysis
Andersen-Tawil syndrome
Hypokalemic PP
CACNA1S
Hyperkalemic PP
Nondystrophic
myotonia
Sodium Channel myotonia
SCN4A
Paramyotonia congenita
Myotonic congenita
Stiffness, +/- pain
CLCN1
Treatment: medications and potential triggers
Medication
Paramyotonia
Congenita
Myotonia
Congenita
Sodium
Channel
Myotonia
HyperPP
HypoPP
ATS
Acetazolamide
Yes/No
No
Yes/No
Yes
Yes
Yes
Dichlorphenamide Yes/No
No
Yes/No
Yes
Yes
Yes
Thiazides
No
No
No
Yes
No
Yes
Mexiletine
Yes
Yes
Yes
Yes/No
No
No
Triggers
Cold,
exercise
Cold,
stress,
pregnancy
Cold,
exercise
Rest after
exertion, K
rich foods,
cold
Rest after
exertion,
carbs
Rest after
exertion
Meola et al 2008. Tawil et al 2000. Matthews et al 2011. Trip et al 2011.
Barohn et al. Clinical Investigation of Neurological Channelopathies (CINCH)
Study of Ranolazine in Myotonia Congenita and
Paramyotonia Congenita
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Sponsor:
Ohio State University and Gilead Sciences
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ClinicalTrials.gov Identifier:
NCT02251457
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This study is currently recruiting participants.
Types of Muscle Pain
Deep Aching - Generalized
Differential Diagnosis
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With weakness
PM, DM
Hypothyroidism
Mitochondrial dx.
Myotonic dystrophy 2
Infectious myopathies
Other rare myopathies
Without weakness
• Infectious myalgia
(esp. viral)
• Toxic myopathies
(eg statin)
• PMR
• Fibromyalgia
Polymyalgia Rheumatica
Epidemiology
• Technically not muscle disease per se
• Common causes of myalgia
– 600-1000/100,000 in patients >age 50
– Incidence of ~50/100,000 per year
• Mean age of onset 70 (90% > age 60)
• Female predominance of 3:1
Polymyalgia Rheumatica
Treatment
• Prednisone (10-40 mg/day) causes
immediate and dramatic improvement
– Diagnostic and therapeutic
• Treat symptoms and ESR
– Taper slowly when sxs. under control
– Usually requires 1-2 years treatment
• 10% require treatment for over 10 years!
Diffuse Myalgia
Inflammatory Muscle Disease*
*Myth: ALL PM/DM pts. have sig. myalgias (only ~25% do!)
Examples of Focal Myalgia
Sarcoid Myopathy
Diabetic Thigh Infarct
Yield of workup:
Diagnoses in Myalgia Patients
Mills and Edwards, 1983
Diagnosis
# Pts.
Enzyme defects
16
Inflammatory myopathy 8
Neurogenic disorders
7
Endocrine & metabolic
6
No diagnosis
72
%
15%
7%
6%
6%
66%
Total
100%
109
Filosto et al, Neurology 2007
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240 patients presenting with myalgias
– Excluded statin patients; only 2 FM patients
Battery of tests done on each biopsy
– Histochem, biochem, immunohistochemistry
– No genetic testing
Correlated findings with CK, EMG, clinical picture
Filosto et al, 2007
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Five groups of biopsies
– 19% normal
– 81% abnormal
BUT
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Only 20% had diagnosis
Only 6% had muscle
diagnosis (metabolic)
Only 2% with normal
strength had diagnosis!
Myo
Mit Nl
Neu
Met
Filosto et al, Neurology 2007
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Many myalgia patients DO have biopsy abnormalities,
but they are usually non-specific
– They usually do NOT lead to a diagnosis
Routine biopsy NOT indicated in patients with isolated
myalgia; careful patient selection is needed
Important info for referring doctors AND patients!
The Patient with Muscle Pain
General Approach
• Careful history attending to type of pain
– Consideration of localization/pathogenesis
– Analysis of disease possibilities
• Exam. with attention to strength testing!
– Most common mistake we see (& make)!!
• Judicious lab tests
– Routine (e.g. CK and EMG)
– Specialized (biopsy, genetic testing)
Evaluation of Muscle Pain
MSK & neuro exam with particular
attention to strength
Labs. CK, CBC, ESR, TFTs, lytes,
Edx studies
Normal
Tender
points
present?
FM/sfn?
CK elevated
Weak, abn EMG, CK
Tender
points
absent?
<5x nl
No other
abn
FET,
>5x normal,
Genetic
other abn
testing
pmr,statins
Repeat
Biopsy
Biopsy
Myalgia in non-muscle related
disorders
Decreased nerve fiber density
noted in large percentage of
patients with FM
Objective evidence that small-fiber polyneuropathy underlies
some illnesses currently labeled as fibromyalgia.
Oaklander et al. Pain. 154(11):2310-2316, November 2013.
Other testing in myalgia: skin biopsy?
Normal skin biopsy
Normal innervation with arrows
indicating small nerve fibers in
epidermis.
Small fiber neuropathy
No small nerve fibers are seen in the
epidermis
TAVEE J , ZHOU L 2009
Testing in myalgiaQuantitative sudomotor axon reflex testing
Normal sweat response at forearm
QSART: assesses the integrity of
postganglionic sympathetic
sudomotor efferents, which are
activated via an axon reflex by
controlled iontophoretic stimulation
with acetylcholine
Abnormal: reduced sweat response at foot
Conclusions
• Pain is a frequent reason for referral to
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the neuromuscular specialist
Patients with myalgia infrequently have a
primary muscle disorder
Muscle biopsy is a low-yield evaluation in
the absence of weakness or a CK >1000
Non-muscle disorders are more often the
cause of myalgia-like symptoms