A Case Report of Colchicine-Induced Polyneuropathy Mimicking Guillain-Barre Syndrome

Abstract

A 55-year-old woman, with underlying diabetes mellitus, hypertension and gout on low dose colchicine, presented with acute flaccid quadriparesis, distal paresthesia without ocular, facial, bulbar and respiratory involvement, preceded by acute gastroenteritis. Admission investigations revealed bicytopenia (leukopenia and thrombocytopenia), uremia, hyponatremia and metabolic acidosis. Nerve conduction study was normal but electromyography showed diffuse spontaneous complex repetitive discharges (CRD) but normal motor unit potentials. She was diagnosed as Colchicine neurotoxicity rather than Guillain-Barre syndrome. Discontinuation of colchicine and generous hydration reverted her urea level to baseline with recovery of weakness dramatically back to normal. Here we report a case of colchicine-induced polyneuropathy triggered by acute renal failure due to dehydration after gastroenteritis to increase awareness by clinical practitioners.

Keywords: colchicine toxicity; neuropathy; renal failure

Introduction

Colchicine is used in the treatment of gout flares and less commonly in prevention of attacks of gout¹.In gout, it acts by preventing microtubule assembly and thereby disrupting inflammatory cascade². Impaired microtubule assembly also affects axonal transport. Although its side effects of diarrhoea and bone marrow suppression are well-known, colchicine-induced myopathy and neuropathy are less recognized.

Case Presentation

A 55-year-old woman, underlying diabetes mellitus, hypertension and gout, was admitted to our hospital with weakness of all four limbs associated with glove-and-stocking pattern tingling and numbness amounting to bedbound in a week. There was history of prior diarrhoea and vomiting for 3 days with reduced urine output. Apart from that, there was no history of pain, fever, headache or seizures. She could control urination and defaecation well. Her vision, swallowing and voice were also normal. She had been taking colchicine 0.5mg once a day for more than one month together with oral hypoglycemics and antihypertensives. On examination, she was afebrile, no pallor, well conscious with stable vitals. Neck power was 5/5. There was no meningism, no cranial neuropathy and no ataxia but she had symmetrical weakness of power 3/5 proximally and 4/5 distally in upper limbs and 2/5 proximally and 4/5 distally in lower limbs with hypotonia, areflexia and bilateral flexor plantar responses. Her numbness was up to elbows and knees bilaterally. Other systemic examinations were normal. ECG, chest X-ray and abdominal ultrasonogram were unremarkable. Baseline blood tests on admission showed random blood sugar 129 mg/dl, haemoglobin 13.3 g/dL, WBC 2.59 x 10⁹/L, platelet count 140x 10⁹/L, erythrocyte sedimentation rate 35 mm/1^st hour, C reactive protein 44.74 mg/L, creatinine 295 µmol/L (baseline 1 month ago was 95 µmol/L), urea 30.5 mmol/L, sodium 129 mmol/L, potassium 5mmol/L, chloride 97 mmol/L, bicarbonate18 mmol/L, HbA1c7% and uric acid 769µmol/L. Thyroid function, corrected calcium and phosphate were all normal. Serum creatinine kinase was also within the normal range of 142 U/L. HIV, HBV, HCV, and syphilitic screening were all negative. Motor and sensory nerve conduction studies were normal. Electromyography (EMG) revealed diffuse spontaneous complex repetitive discharges (CRD) in all the sampled muscles of both upper and lower limbs but motor unit potentials were of normal morphology and recruitment. Cerebrospinal fluid study was normal. At first point, our diagnosis on admission was Guillain-Barre syndrome. But after diagnostic findings of diffuse CRD in EMG and detailed clinical information, colchicine-induced polyneuropathy was diagnosed. Colchicine was immediately discontinued, and she was treated with generous hydration, correction of electrolyte imbalance and antibiotics to cover gastroenteritis. Physiotherapy and rehabilitation were also done. Her weakness obviously improved in a few days, and she could walk with one support on discharge on day 10after admission. Her weakness returned to normal completely with normal blood parameters including white cell count, platelet count, renal function and electrolytes at 4 weeks follow up. Repeat NCS and EMG at 3-month follow up was normal.

Discussion

Colchicine at toxic levels can induce myopathy, neuropathy or neuromyopathy in combination in addition to possible other organs involvement. In our case, neuropathy was diagnosed because weakness was associated with peripheral sensory symptoms, areflexia and normal creatinine kinase level together with EMG evidence of generalized CRD³ and EMG not showing myopathic units. In literature, colchicine-induced myopathic cases are more common than neuropathy but most were concluded as combined neuromyopathy cases.^4,5

Vacuolar changes can be seen in muscle biopsy of colchicine-induced myopathy cases⁶. In our case, muscle biopsy was not performed because of clinical and neurophysiological diagnosis of neuropathy and rapid improvement. So combined subtle myopathy might not be ruled out. Since colchicine is metabolized in the liver as well as excreted by the kidney, colchicine-induced neuropathy and myopathy are more frequent in liver failure and kidney failure. These serious side effects can even occur with usual or low dose colchicine in case of renal and liver failure. Our case suffered polyneuropathy while on low dose because of acute kidney disease which was triggered by dehydration. Patients should be advised to discontinue colchicine if diarrhea occurs and doctors must also be aware of and do dose adjustment and discontinuation as necessary, and instant hydration. Wallace et al concluded that the most practical predictor of the risk of colchicine toxicity was creatinine clearance⁷. Robinson et al also suggested that dosing interval of even low dose therapy should be adjusted since low dose can lead to toxic levels when used in patients without advanced renal or liver disease or when used concomitantly with most medications that are CYP3A4 inhibitors such as clarithromycin, fluconazole, ritonavir, cyclosporine, ciprofloxacin, atorvastatin, grapefruit, etc. and P-glycoprotein inhibitors such as verapamil, amiodarone, carvedilol8. Our patient was also taking atorvastatin and carvedilol, which had worsened the condition. The same study also concluded that because of possibility of drug-drug interactions especially with polypharmacy in elderly, colchicine dose should not exceed 0.5-0.6 mg daily in the elderly even in the absence of advanced renal or liver disease8. In conclusion, clinical practitioners need to have a high index of clinical suspicion of colchicine-neuropathy and/or myopathy even with low dose colchicine in case of renal and liver dysfunction since correct diagnosis will save patients with simple effective measures and can avoid expensive inappropriate treatment.

Conflict Of Interest

None

Consent

Written informed consent was obtained from the patient’s family.

References

1. Robinson PC, Terkeltaub R, Pillinger MH, Shah B, Karalis V, Karatza E, Liew D, Imazio M, Cornel JH, Thompson PL, Nidorf M. 2022 “Consensus Statement Regarding the Efficacy and Safety of Long-Term Low-Dose Colchicine in Gout and Cardiovascular Disease”. Am J Med. 135(1):32-38.
2. Dalbeth N, Lauterio TJ, Wolfe HR. 2014 “Mechanism of action of colchicine in the treatment of gout”. Clin Ther.36(10):1465-79.
3. Kuncl RW, Cornblath DR, Avila O, Duncan G. 1989 “Electrodiagnosis of human colchicine myoneuropathy”. Muscle Nerve. 12(5):360-4.
4. DağErsel, TürkelYakup, GökçeBurcu. 2013 “Colchicine-Related Polyneuropathy and Multiple Organ Failure”. Turkish Journal of Neurology. 19:69-71.
5. Altiparmak MR, Pamuk ON, Pamuk GE, Hamuryudan V, Ataman R, Serdengecti K. 2002 “Colchicine neuromyopathy: a report of six cases”. Clin Exp Rheumatol.20(suppl 4):13-16
6. Kuncl RW, Duncan G, Watson D, Alderson K, Rogawski MA, Peper M. 1987 “Colchicine myopathy and neuropathy”. N Engl J Med.316:1562-8
7. Wallace SL, Singer JZ, Duncan GJ, Wigley FM, Kuncl RW. 1991 “Renal function predicts colchicine toxicity: guidelines for the prophylactic use of colchicine in gout”. J Rheumatol. 18(2):264-9.
8. Robinson PC, Terkeltaub R, Pillinger MH, Shah B, Karalis V, Karatza E, Liew D, Imazio M, Cornel JH, Thompson PL, Nidorf M. 2022 “Consensus Statement Regarding the Efficacy and Safety of Long-Term Low-Dose Colchicine in Gout and Cardiovascular Disease”. Am J Med. 135(1):32-38.

Author Information

Ohnmar¹, Zin Nwe Win², Win Min Thit³

1. MBBS (Ygn), MMedSc (Int Med), MRCP (UK), FRCP (Edin), DrMedSc(Neurology), Fellowship in Neuromuscular (NNI), Associate Professor/Consultant Neurologist,Asia Royal Hospital and Yangon General Hospital
2. MBBS (Ygn), MMedSc (Int Med), MRCP (UK), FRCP (Glasg), DrMedSc (Neurology), Consultant Neurologist, Yangon General Hospital
3. MBBS (Ygn), MMedSc (Int Med), MRCP (UK), FRCP (Edin,Glasg,London), DipMed Ed. Professor/Consultant Neurologist, Asia Royal Hospital