- Email: [email protected]
Unusual Electromyographic Findings Associated With Colchicine Neuromyopathy: A Case Report
PM R XXX (2016) 1-4
www.pmrjournal.org
Case Presentation
Unusual Electromyographic Findings Associated With Colchicine Neuromyopathy: A Case Report Christina Marciniak, MD, Ashwin Babu, MD, Leda Ghannad, MD, Richard Burnstine, MD, Susan Keeshin, MD
Abstract An 83-year-old man with multiple medical problems, including gout, pseudogout, and renal insufficiency, presented with more than a year of proximal weakness. He had an extensive previous medical workup, including a normal creatinine kinase. His weakness persisted despite endurance and strength training. Electrodiagnostic findings were consistent with a myopathy, although without abnormal spontaneous activity and a length-dependent neuropathy. On the basis of these findings, colchicine was discontinued. The patient experienced marked symptomatic improvement within a week. Myopathies with neuropathies may be found with the use of colchicine. This case was unusual because of the absence of abnormal spontaneous activity and increased creatinine kinase, as typically reported with colchicine myopathy.
Introduction Colchicine is a commonly used drug for the treatment of gout. Its gastrointestinal toxicity is well known; however, its effects on the neuromuscular system are recognized less frequently. Myopathy is a reported complication with its use and may present in conjunction with a mild length-dependent neuropathy [1]. Although the myopathy generally is associated with increased levels of creatinine kinase (CK) and abnormal spontaneous activity on electromyographic testing, we report a case of colchicine neuromyopathy with atypical laboratory and electrodiagnostic findings. Case Presentation An 83-year-old man with a complicated medical history, including gout, pseudogout, renal insufficiency, polymyalgia rheumatica, asthma, deep-vein thrombosis, nephrolithiasis, Waldenstrom macroglobulinemia, bacterial overgrowth syndrome, vitamin B-12 deficiency, and temporal arteritis, presented to our outpatient musculoskeletal clinic with complaints of fatigue and difficulty rising from a chair. He had a 4-year history of weakness, which initially was attributed to polymyalgia
rheumatica on the basis of symptoms and an increased sedimentation rate (ESR). He was treated with oral steroids and responded with an improvement in ESR. The following year, he developed weakness and severe hypotension, first thought to be attributable to adrenal insufficiency, then subsequently diagnosed as biopsyproven temporal arteritis, again requiring treatment with steroids. Two years before his electrodiagnostic study, he was diagnosed with gout and pseudogout and was started on colchicine 0.6 mg daily. Because of recurrent knee effusions, colchicine was increased to twice daily approximately 1 year before presentation. He then developed progressive weakness and was evaluated by a neurologist, who diagnosed him with probable steroid myopathy and discontinued his steroids. ESR was stable, CK was 65, and creatinine was 1.6 at that time. His weakness persisted despite steroid discontinuation, and he subsequently was referred for physical therapy. Although he participated in resistance and endurance training, he showed no improvement in strength or subjective symptoms. He required push off with his arms to transition from sit to stand and began ambulating with a cane. At presentation to our outpatient clinic, the patient reported that his movements were slow and he was
1934-1482/$ - see front matter ª 2016 by the American Academy of Physical Medicine and Rehabilitation http://dx.doi.org/10.1016/j.pmrj.2016.03.003
2
Unusual EMG Findings in Colchicine Neuromyopathy
easily fatigued. Functional deficits at presentation included difficulty with opening a water bottle, buttoning shirts, and rising from a chair. He denied numbness or tingling in the limbs. Medications at that time included lansoprazole, levothyroxine, allopurinol, amiloride, furosemide, and colchicine at a dose of 0.6 mg twice daily for gout/pseudogout. Findings of the physical examination were notable for periscapular, biceps, triceps, and gluteal muscle atrophy and difficulty rising from a chair or low surfaces. Muscle stretch reflexes were 1þ at the bilateral biceps, triceps, and patellae. Sensory examination demonstrated no reported abnormalities with light touch or pinprick testing in dermatomes C5-T1 or L2-S1 bilaterally. The patient was referred for electrodiagnostic testing, with formal manual muscle testing performed by physical therapy shortly before electrodiagnostic examination demonstrating proximal weakness: left hip extension/abduction/external rotation was 3þ/5 whereas on the right, these muscle groups were 4/5. Left and right hip adduction/flexion/internal rotation, knee flexion/ extension, and ankle dorsiflexion and plantarflexion were 5/5. Shoulder abduction could only be performed to 90 . Electrodiagnostic studies showed evidence of a chronic length-dependent sensory-motor polyneuropathy with axonal greater than demyelinative features. The right sural and superficial peroneal sensory responses were absent, peroneal motor amplitudes were decreased, and tibial motor nerve distal latency was prolonged with slowed conduction through the leg. Right tibial nerve F wave minimal latencies were prolonged. Abnormal temporal dispersion was not noted. In the upper limb, recording of the radial nerve at the proximal thumb was present; however, no response was obtained with a more distal sensory recording at the digital nerves at the thumb. Median and ulnar sensory distal latencies were prolonged. Needle electromyography showed distal lower limb findings of largeamplitude, long-duration motor unit potentials with reduced recruitment, consistent with a neuropathic axonal process with reinnervation. Conversely, lowamplitude, polyphasic motor unit potentials with early recruitment were noted only in the proximal limb muscles. No resting positive waves or fibrillation potentials were noted (Figure 1 and Tables 1-3). On the basis of the findings of neuropathy with a myopathy, the diagnosis of colchicine neuromyopathy was considered. Colchicine was discontinued after electrodiagnostics, after discussion with the patient’s rheumatologist. The patient reported striking improvement in symptoms within week of medication discontinuation. By 2 weeks, he reported he was not using his cane continuously, and by 3 weeks he had discontinued using his cane indoors. Follow-up at 3 months revealed marked improvement in strength, endurance, and mobility.
A Tibialis Anterior Right
1 mV
Trig: 1 mV
Tibialis anterior
Amp 1: 20-10k,60Hz
-2uV
Spontaneous #12 Record 11:33:03 A
10 ms
9.8/10s 10 ms
* New Muscle Other Side EMG Vol.SFEMG Stim.SFEMG IPA
20.1
B Deltoid Muscle – minimal contracon Right
200 uV
Deltoid
Amp 1: 20-10k,60Hz
Trig: -2uV 200 uV
Spontaneous #22 Record 12:20:44 P
10 ms
9.8/10s 10 ms
* New Muscle Other Side EMG Vol.SFEMG Stim.SFEMG IPA
20.1
Figure 1. Voluntary motor unit potentials in the tibialis anterior (A) and deltoid (B) muscles. Demonstrated are large-duration voluntary motor unit potentials in the tibialis anterior muscle, and lower amplitude, polyphasic motor unit potentials in the deltoid, the latter recorded with minimal contraction. Note that recordings were captured with different sensitivity settings e 1 millivolt per division in the tibialis anterior, and 200 microvolts per division in the deltoid muscle.
C. Marciniak et al. / PM R XXX (2016) 1-4
3
Table 1 Motor nerve conduction studies Nerve and Site Motor nerve conduction Ulnar, R Wrist Below elbow Above elbow Peroneal (fibular), R Ankle Fibula (head) Popliteal fossa Tibial, R Ankle Popliteal fossa
Latency, ms
Amplitude, mV
Segment
Conduction Velocity, m/s
Distance, mm
3.7 8.3 10.6
6.6 4.2 4.0
Abductor digiti minimi (manus)-Wrist Wrist-below elbow Below elbow-above elbow
51 50
80 235 115
6.3 14.9 17.1
1.2* 1.0 0.9
Extensor digitorum brevis-ankle Ankle-fibula (head) Fibula (head)-popliteal fossa
38 41
80 330 90
7.9* 21.2
3.4 3.0
Abductor hallucis-ankle Ankle-popliteal fossa
32*
80 420
R ¼ right. * Abnormal finding.
Discussion To our knowledge, this is the first reported case of colchicine myopathy producing motor unit potential changes consistent with a myopathy without elevated CK and without abnormal spontaneous activity in proximal muscles on electrodiagnostic testing [1]. In this case, colchicine toxicity was suspected after electrodiagnostic findings of both a neuropathy and a myopathy. In addition, this patient was at risk for neuromuscular complications with colchicine use because of his concurrent renal insufficiency, which has been demonstrated to impair drug clearance [2]. Our patient experienced persistent, longstanding symptoms that did not rebate over months even with discontinuation of other putative myotoxic medications and with interventions, including an appropriate physical therapy exercise regimen. His muscle weakness instead resolved very rapidly after stopping colchicine, consistent with other reports of this pathology. Colchicine acts to inhibit microtubule polymerization. It may have multiple-organ system effects, including gastroenteritis, blood dyscrasias, and dermatitis [1,3]. Its myotoxic effects are thought to be related to impaired autophagosome-lysosome fusion with accumulation of autophagic vacuoles resulting in myonecrosis [4]. Muscle biopsy may reveal sarcoplasmic vacuoles [5]. Generally, the myopathy associated with colchicine presents as a painless proximal subacute or acute lower limb weakness [1,5]. Fatigue has been reported to precede the weakness in cases of myopathy [6]. Table 2 F-wave studies Nerven Tibial, R Ankle stimulation-abductor hallucis R ¼ right. * Abnormal finding.
F-Latency Mean
F-Latency Minimum
72 ms*
70 ms*
Laboratory findings include mild-to-marked elevations of CK, typical myopathic electromyographic motor unit potential (polyphasic, short duration, with early recruitment) findings in proximal muscles on electromyography, as well as marked fibrillation potentials [1]. It is possible that our patient may not have shown abnormal spontaneous activity because of the length of symptoms; however, the lack of CK elevation suggests that that this finding may have been absent earlier as well. It is possible that his intermittent corticosteroid use may have blunted the expected elevations of CK; however, because the mechanism of this myopathy is not inflammatory, this hypothesis is purely speculative. The differential diagnosis for proximal muscle weakness and fatigue includes inflammatory myopathies. The finding of a coexistent neuropathy can be a distinguishing factor, indicative of a neuromyopathy. In cases with renal dysfunction, neuropathy findings that are characteristically axonal, in conjunction with an Table 3 Sensory nerve conduction Nerve and Site Median, R Wrist-index Ulnar, R Wrist-fifth digit Radial, R Wrist-anatomical snuffbox Wrist-first digit Sural, R Lower leg-lateral ankle Superficial peroneal (fibular), R Lower leg-anterior ankle
Peak Latency, ms
Amplitude, mV
Distance, mm
5.1*
10
140
4.3*
8
140
2.8
9
100
NR*
NR*
100
NR*
NR*
140
NR*
NR*
140
R ¼ right; NR ¼ no response. * Abnormal finding.
4
Unusual EMG Findings in Colchicine Neuromyopathy
unrecognized myopathy (particularly if muscle sampling is not performed sufficiently proximally), may instead be incorrectly ascribed to renal disease [2,5]. In addition to impaired renal function, coadministration of drugs that are CYP 3A4 and P-glycoprotein inhibitors may precipitate colchicine toxicity, including statins, tacrolimis, cyclosporine, ketoconazole, erythromycin, and clarithromycin [7-9]. Grapefruit juice may also increase concentrations of colchicine [8]. Cyclosporine in particular inhibits both hepatic and renal clearance of colchicine, resulting in elevated colchicine levels. Initiating treatment at lower dosages or use of an alternative treatment for gouty arthritis in posttransplantation patients should be considered. Toxic neuromyopathies have a limited differential diagnosis and can occur with alcohol, amiodarone, chloroquine, and vincristine. Other disease states that can produce myopathies with neuropathies include sarcoidosis, amyloidosis, paraneoplasic syndromes, infectious human immunodeficiency virus, thyroid disease, malabsorption with vitamin deficiencies, celiac sprue, critical illness, and inherited mitochondrial disorders [10]. This patient had several other concurrent diagnoses that could have contributed to the distal neuropathic changes noted on electrodiagnostic examination, in addition to the effect of colchicine. The rapid resolution of symptoms after drug withdrawal was confirmatory for this etiology. Conclusion Physiatrists frequently treat patients with medical comorbidities such as gout and renal dysfunction. It is important that we recognize that colchicine may produce weakness through myotoxicity, and, in particular, that myopathy may be found in conjunction with a
neuropathy. Prior to initiating colchicine therapy or escalating the dose, one should evaluate renal function, particularly in the presence of multiple comorbidities or in the elderly. Our finding that motor unit potential changes typically noted in a myopathy may be present without characteristic CK elevations or fibrillation potentials indicates that such a diagnosis may be more difficult to identify. Recognition of possible colchicine toxicity is imperative, as this iatrogenic disorder is rapidly reversible with drug cessation. References 1. Kuncl RW, Duncan G, Watson D, et al. Colchicine myopathy and neuropathy. N Engl J Med 1987;316:1562-1568. 2. Altiparmak MR, Pamuk ON, Pamuk GE, et al. Colchicine neuromyopathy: A report of six cases. Clin Exp Rheumatol 2002;20:S13S16. 3. Kuncl RW, Bilak MM, Craig SW, et al. Exocytotic “constipation” is a mechanism of tubulin/lysosomal interaction in colchicine myopathy. Exp Cell Res 2003;285:196-207. 4. Ching JK, Ju JS, Pittman SK, et al. Increased autophagy accelerates colchicine-induced muscle toxicity. Autophagy 2013;9:21152125. 5. Rana SS, Giuliani MJ, Oddis CV, et al. Acute onset of colchicine myoneuropathy in cardiac transplant recipients: Case studies of three patients. Clin Neurol Neurosurg 1997;99:266-270. 6. Lo YC, Lin KP, Lin CY, et al. Fatigue as the only clinical manifestation of colchicine induced myopathy. Acta Neurol Taiwan 2010; 19:184-188. 7. Justiniano M, Dold S, Espinoza LR. Rapid onset of muscle weakness (rhabdomyolysis) associated with the combined use of simvastatin and colchicine. J Clin Rheumatol 2007;13:266-268. 8. Finkelstein Y, Aks SE, Hutson JR, et al. Colchicine poisoning: The dark side of an ancient drug. Clin Toxicol (Phila) 2010;48:407-414. 9. Yousuf Bhat Z, Reddy S, Pillai U, et al. Colchicine-induced myopathy in a tacrolimus-treated renal transplant recipient: Case report and literature review. Am J Ther 2016;23:e614-e616. 10. Lacomis D. Electrodiagnostic approach to the patient with suspected myopathy. Neurol Clin 2012;30:641-660.
Disclosure C.M. Departments of Physical Medicine and Rehabilitation and Neurology, Northwestern University; and Rehabilitation Institute of Chicago, Room 1154, 345 E. Superior, Chicago, IL 60611. Address correspondence to C.M.; e-mail: [email protected] or [email protected] Disclosure: nothing to disclose A.B. Department of Physical Medicine and Rehabilitation, Harvard Medical School, and Spaulding Rehabilitation Hospital, Boston, MA Disclosure: nothing to disclose
R.B. North Shore Pediatrics, Evanston, IL Disclosure: nothing to disclose S.K. Departments of Physical Medicine and Rehabilitation and Neurology, Chicago, IL Disclosure: nothing to disclose Presented at the American Academy of Physical Medicine and Rehabilitation Annual Meeting, November 13-16, 2014, San Diego, CA. Submitted for publication November 16, 2015; accepted March 5, 2016.
L.G. Midwest Orthopedics at Rush University Medical Center, Chicago, IL Disclosure: nothing to disclose
www.pmrjournal.org
Case Presentation
Unusual Electromyographic Findings Associated With Colchicine Neuromyopathy: A Case Report Christina Marciniak, MD, Ashwin Babu, MD, Leda Ghannad, MD, Richard Burnstine, MD, Susan Keeshin, MD
Abstract An 83-year-old man with multiple medical problems, including gout, pseudogout, and renal insufficiency, presented with more than a year of proximal weakness. He had an extensive previous medical workup, including a normal creatinine kinase. His weakness persisted despite endurance and strength training. Electrodiagnostic findings were consistent with a myopathy, although without abnormal spontaneous activity and a length-dependent neuropathy. On the basis of these findings, colchicine was discontinued. The patient experienced marked symptomatic improvement within a week. Myopathies with neuropathies may be found with the use of colchicine. This case was unusual because of the absence of abnormal spontaneous activity and increased creatinine kinase, as typically reported with colchicine myopathy.
Introduction Colchicine is a commonly used drug for the treatment of gout. Its gastrointestinal toxicity is well known; however, its effects on the neuromuscular system are recognized less frequently. Myopathy is a reported complication with its use and may present in conjunction with a mild length-dependent neuropathy [1]. Although the myopathy generally is associated with increased levels of creatinine kinase (CK) and abnormal spontaneous activity on electromyographic testing, we report a case of colchicine neuromyopathy with atypical laboratory and electrodiagnostic findings. Case Presentation An 83-year-old man with a complicated medical history, including gout, pseudogout, renal insufficiency, polymyalgia rheumatica, asthma, deep-vein thrombosis, nephrolithiasis, Waldenstrom macroglobulinemia, bacterial overgrowth syndrome, vitamin B-12 deficiency, and temporal arteritis, presented to our outpatient musculoskeletal clinic with complaints of fatigue and difficulty rising from a chair. He had a 4-year history of weakness, which initially was attributed to polymyalgia
rheumatica on the basis of symptoms and an increased sedimentation rate (ESR). He was treated with oral steroids and responded with an improvement in ESR. The following year, he developed weakness and severe hypotension, first thought to be attributable to adrenal insufficiency, then subsequently diagnosed as biopsyproven temporal arteritis, again requiring treatment with steroids. Two years before his electrodiagnostic study, he was diagnosed with gout and pseudogout and was started on colchicine 0.6 mg daily. Because of recurrent knee effusions, colchicine was increased to twice daily approximately 1 year before presentation. He then developed progressive weakness and was evaluated by a neurologist, who diagnosed him with probable steroid myopathy and discontinued his steroids. ESR was stable, CK was 65, and creatinine was 1.6 at that time. His weakness persisted despite steroid discontinuation, and he subsequently was referred for physical therapy. Although he participated in resistance and endurance training, he showed no improvement in strength or subjective symptoms. He required push off with his arms to transition from sit to stand and began ambulating with a cane. At presentation to our outpatient clinic, the patient reported that his movements were slow and he was
1934-1482/$ - see front matter ª 2016 by the American Academy of Physical Medicine and Rehabilitation http://dx.doi.org/10.1016/j.pmrj.2016.03.003
2
Unusual EMG Findings in Colchicine Neuromyopathy
easily fatigued. Functional deficits at presentation included difficulty with opening a water bottle, buttoning shirts, and rising from a chair. He denied numbness or tingling in the limbs. Medications at that time included lansoprazole, levothyroxine, allopurinol, amiloride, furosemide, and colchicine at a dose of 0.6 mg twice daily for gout/pseudogout. Findings of the physical examination were notable for periscapular, biceps, triceps, and gluteal muscle atrophy and difficulty rising from a chair or low surfaces. Muscle stretch reflexes were 1þ at the bilateral biceps, triceps, and patellae. Sensory examination demonstrated no reported abnormalities with light touch or pinprick testing in dermatomes C5-T1 or L2-S1 bilaterally. The patient was referred for electrodiagnostic testing, with formal manual muscle testing performed by physical therapy shortly before electrodiagnostic examination demonstrating proximal weakness: left hip extension/abduction/external rotation was 3þ/5 whereas on the right, these muscle groups were 4/5. Left and right hip adduction/flexion/internal rotation, knee flexion/ extension, and ankle dorsiflexion and plantarflexion were 5/5. Shoulder abduction could only be performed to 90 . Electrodiagnostic studies showed evidence of a chronic length-dependent sensory-motor polyneuropathy with axonal greater than demyelinative features. The right sural and superficial peroneal sensory responses were absent, peroneal motor amplitudes were decreased, and tibial motor nerve distal latency was prolonged with slowed conduction through the leg. Right tibial nerve F wave minimal latencies were prolonged. Abnormal temporal dispersion was not noted. In the upper limb, recording of the radial nerve at the proximal thumb was present; however, no response was obtained with a more distal sensory recording at the digital nerves at the thumb. Median and ulnar sensory distal latencies were prolonged. Needle electromyography showed distal lower limb findings of largeamplitude, long-duration motor unit potentials with reduced recruitment, consistent with a neuropathic axonal process with reinnervation. Conversely, lowamplitude, polyphasic motor unit potentials with early recruitment were noted only in the proximal limb muscles. No resting positive waves or fibrillation potentials were noted (Figure 1 and Tables 1-3). On the basis of the findings of neuropathy with a myopathy, the diagnosis of colchicine neuromyopathy was considered. Colchicine was discontinued after electrodiagnostics, after discussion with the patient’s rheumatologist. The patient reported striking improvement in symptoms within week of medication discontinuation. By 2 weeks, he reported he was not using his cane continuously, and by 3 weeks he had discontinued using his cane indoors. Follow-up at 3 months revealed marked improvement in strength, endurance, and mobility.
A Tibialis Anterior Right
1 mV
Trig: 1 mV
Tibialis anterior
Amp 1: 20-10k,60Hz
-2uV
Spontaneous #12 Record 11:33:03 A
10 ms
9.8/10s 10 ms
* New Muscle Other Side EMG Vol.SFEMG Stim.SFEMG IPA
20.1
B Deltoid Muscle – minimal contracon Right
200 uV
Deltoid
Amp 1: 20-10k,60Hz
Trig: -2uV 200 uV
Spontaneous #22 Record 12:20:44 P
10 ms
9.8/10s 10 ms
* New Muscle Other Side EMG Vol.SFEMG Stim.SFEMG IPA
20.1
Figure 1. Voluntary motor unit potentials in the tibialis anterior (A) and deltoid (B) muscles. Demonstrated are large-duration voluntary motor unit potentials in the tibialis anterior muscle, and lower amplitude, polyphasic motor unit potentials in the deltoid, the latter recorded with minimal contraction. Note that recordings were captured with different sensitivity settings e 1 millivolt per division in the tibialis anterior, and 200 microvolts per division in the deltoid muscle.
C. Marciniak et al. / PM R XXX (2016) 1-4
3
Table 1 Motor nerve conduction studies Nerve and Site Motor nerve conduction Ulnar, R Wrist Below elbow Above elbow Peroneal (fibular), R Ankle Fibula (head) Popliteal fossa Tibial, R Ankle Popliteal fossa
Latency, ms
Amplitude, mV
Segment
Conduction Velocity, m/s
Distance, mm
3.7 8.3 10.6
6.6 4.2 4.0
Abductor digiti minimi (manus)-Wrist Wrist-below elbow Below elbow-above elbow
51 50
80 235 115
6.3 14.9 17.1
1.2* 1.0 0.9
Extensor digitorum brevis-ankle Ankle-fibula (head) Fibula (head)-popliteal fossa
38 41
80 330 90
7.9* 21.2
3.4 3.0
Abductor hallucis-ankle Ankle-popliteal fossa
32*
80 420
R ¼ right. * Abnormal finding.
Discussion To our knowledge, this is the first reported case of colchicine myopathy producing motor unit potential changes consistent with a myopathy without elevated CK and without abnormal spontaneous activity in proximal muscles on electrodiagnostic testing [1]. In this case, colchicine toxicity was suspected after electrodiagnostic findings of both a neuropathy and a myopathy. In addition, this patient was at risk for neuromuscular complications with colchicine use because of his concurrent renal insufficiency, which has been demonstrated to impair drug clearance [2]. Our patient experienced persistent, longstanding symptoms that did not rebate over months even with discontinuation of other putative myotoxic medications and with interventions, including an appropriate physical therapy exercise regimen. His muscle weakness instead resolved very rapidly after stopping colchicine, consistent with other reports of this pathology. Colchicine acts to inhibit microtubule polymerization. It may have multiple-organ system effects, including gastroenteritis, blood dyscrasias, and dermatitis [1,3]. Its myotoxic effects are thought to be related to impaired autophagosome-lysosome fusion with accumulation of autophagic vacuoles resulting in myonecrosis [4]. Muscle biopsy may reveal sarcoplasmic vacuoles [5]. Generally, the myopathy associated with colchicine presents as a painless proximal subacute or acute lower limb weakness [1,5]. Fatigue has been reported to precede the weakness in cases of myopathy [6]. Table 2 F-wave studies Nerven Tibial, R Ankle stimulation-abductor hallucis R ¼ right. * Abnormal finding.
F-Latency Mean
F-Latency Minimum
72 ms*
70 ms*
Laboratory findings include mild-to-marked elevations of CK, typical myopathic electromyographic motor unit potential (polyphasic, short duration, with early recruitment) findings in proximal muscles on electromyography, as well as marked fibrillation potentials [1]. It is possible that our patient may not have shown abnormal spontaneous activity because of the length of symptoms; however, the lack of CK elevation suggests that that this finding may have been absent earlier as well. It is possible that his intermittent corticosteroid use may have blunted the expected elevations of CK; however, because the mechanism of this myopathy is not inflammatory, this hypothesis is purely speculative. The differential diagnosis for proximal muscle weakness and fatigue includes inflammatory myopathies. The finding of a coexistent neuropathy can be a distinguishing factor, indicative of a neuromyopathy. In cases with renal dysfunction, neuropathy findings that are characteristically axonal, in conjunction with an Table 3 Sensory nerve conduction Nerve and Site Median, R Wrist-index Ulnar, R Wrist-fifth digit Radial, R Wrist-anatomical snuffbox Wrist-first digit Sural, R Lower leg-lateral ankle Superficial peroneal (fibular), R Lower leg-anterior ankle
Peak Latency, ms
Amplitude, mV
Distance, mm
5.1*
10
140
4.3*
8
140
2.8
9
100
NR*
NR*
100
NR*
NR*
140
NR*
NR*
140
R ¼ right; NR ¼ no response. * Abnormal finding.
4
Unusual EMG Findings in Colchicine Neuromyopathy
unrecognized myopathy (particularly if muscle sampling is not performed sufficiently proximally), may instead be incorrectly ascribed to renal disease [2,5]. In addition to impaired renal function, coadministration of drugs that are CYP 3A4 and P-glycoprotein inhibitors may precipitate colchicine toxicity, including statins, tacrolimis, cyclosporine, ketoconazole, erythromycin, and clarithromycin [7-9]. Grapefruit juice may also increase concentrations of colchicine [8]. Cyclosporine in particular inhibits both hepatic and renal clearance of colchicine, resulting in elevated colchicine levels. Initiating treatment at lower dosages or use of an alternative treatment for gouty arthritis in posttransplantation patients should be considered. Toxic neuromyopathies have a limited differential diagnosis and can occur with alcohol, amiodarone, chloroquine, and vincristine. Other disease states that can produce myopathies with neuropathies include sarcoidosis, amyloidosis, paraneoplasic syndromes, infectious human immunodeficiency virus, thyroid disease, malabsorption with vitamin deficiencies, celiac sprue, critical illness, and inherited mitochondrial disorders [10]. This patient had several other concurrent diagnoses that could have contributed to the distal neuropathic changes noted on electrodiagnostic examination, in addition to the effect of colchicine. The rapid resolution of symptoms after drug withdrawal was confirmatory for this etiology. Conclusion Physiatrists frequently treat patients with medical comorbidities such as gout and renal dysfunction. It is important that we recognize that colchicine may produce weakness through myotoxicity, and, in particular, that myopathy may be found in conjunction with a
neuropathy. Prior to initiating colchicine therapy or escalating the dose, one should evaluate renal function, particularly in the presence of multiple comorbidities or in the elderly. Our finding that motor unit potential changes typically noted in a myopathy may be present without characteristic CK elevations or fibrillation potentials indicates that such a diagnosis may be more difficult to identify. Recognition of possible colchicine toxicity is imperative, as this iatrogenic disorder is rapidly reversible with drug cessation. References 1. Kuncl RW, Duncan G, Watson D, et al. Colchicine myopathy and neuropathy. N Engl J Med 1987;316:1562-1568. 2. Altiparmak MR, Pamuk ON, Pamuk GE, et al. Colchicine neuromyopathy: A report of six cases. Clin Exp Rheumatol 2002;20:S13S16. 3. Kuncl RW, Bilak MM, Craig SW, et al. Exocytotic “constipation” is a mechanism of tubulin/lysosomal interaction in colchicine myopathy. Exp Cell Res 2003;285:196-207. 4. Ching JK, Ju JS, Pittman SK, et al. Increased autophagy accelerates colchicine-induced muscle toxicity. Autophagy 2013;9:21152125. 5. Rana SS, Giuliani MJ, Oddis CV, et al. Acute onset of colchicine myoneuropathy in cardiac transplant recipients: Case studies of three patients. Clin Neurol Neurosurg 1997;99:266-270. 6. Lo YC, Lin KP, Lin CY, et al. Fatigue as the only clinical manifestation of colchicine induced myopathy. Acta Neurol Taiwan 2010; 19:184-188. 7. Justiniano M, Dold S, Espinoza LR. Rapid onset of muscle weakness (rhabdomyolysis) associated with the combined use of simvastatin and colchicine. J Clin Rheumatol 2007;13:266-268. 8. Finkelstein Y, Aks SE, Hutson JR, et al. Colchicine poisoning: The dark side of an ancient drug. Clin Toxicol (Phila) 2010;48:407-414. 9. Yousuf Bhat Z, Reddy S, Pillai U, et al. Colchicine-induced myopathy in a tacrolimus-treated renal transplant recipient: Case report and literature review. Am J Ther 2016;23:e614-e616. 10. Lacomis D. Electrodiagnostic approach to the patient with suspected myopathy. Neurol Clin 2012;30:641-660.
Disclosure C.M. Departments of Physical Medicine and Rehabilitation and Neurology, Northwestern University; and Rehabilitation Institute of Chicago, Room 1154, 345 E. Superior, Chicago, IL 60611. Address correspondence to C.M.; e-mail: [email protected] or [email protected] Disclosure: nothing to disclose A.B. Department of Physical Medicine and Rehabilitation, Harvard Medical School, and Spaulding Rehabilitation Hospital, Boston, MA Disclosure: nothing to disclose
R.B. North Shore Pediatrics, Evanston, IL Disclosure: nothing to disclose S.K. Departments of Physical Medicine and Rehabilitation and Neurology, Chicago, IL Disclosure: nothing to disclose Presented at the American Academy of Physical Medicine and Rehabilitation Annual Meeting, November 13-16, 2014, San Diego, CA. Submitted for publication November 16, 2015; accepted March 5, 2016.
L.G. Midwest Orthopedics at Rush University Medical Center, Chicago, IL Disclosure: nothing to disclose