A case report of colchicine-induced myopathy in a patient with chronic kidney disease / 北京大学学报(医学版)

Colchicine plays an important role in the treatment of gout and some other diseases. Besides gastrointestinal symptoms, myopathy has been reported as a rare side effect of colchicine in some patients. We report a case of myopathy in a patient with chronic kidney disease caused by high-dose colchicine, and then review literature on colchicine-induced myopathy, so as to provide some experience for the clinical diagnosis, treatment and medication safety. A 51-year-old male patient with 10 years of gout and 5 years of chronic kidney disease history and irregular treatment was admitted to the hospital with complaint of recurrent left wrist arthralgia and emerging lower extremities myalgia after intake of 40-50 mg colchicine in total within 20 days. Laboratory examinations showed significantly increased creatine kinase (CK) and then colchicine-induced myopathy was diagnosed preliminarily. After withdrawl of colchicine and implementation of hydration, alkalization and intramuscular injection of compound betamethasone, the symptoms of arthralgia and myalgia were relieved within 3 days and CK decreased to normal range gradually. According to literature reports, colchicine related myopathy was mostly characterized by proximal myasthenia and myalgia, accompanied by elevated CK level, which usually occurred days to weeks after initial administration of colchicine at the usual dosage in patients with renal impairment or a change in the underlying disease state in those receiving long-term therapy, and the features might remit within three to four weeks after the drug was discontinued. Electromyography of proximal muscles showed myopathy marked by abnormal spontaneous activity and muscle pathology waa marked by accumulation of lysosomes and autophagic vacuoles. Chronic kidney disease, liver cirrhosis, higher colchicine dose and concomitant cytochrome P450 3A4 (CYP3A4) inhibitors were associated with increased risk of myo-pathy. Based on the similar efficacy and lower adverse reaction rate compared with larger dosage, small dose of colchicine was recommended by many important current guidelines and recommendations in the treatment of gout. In consideration of potential risks, colchicine should be used with caution in patients with kidney or liver impairment, and in those taking CYP3A4 or P-glycoprotein inhibitors. For those patients, the drug dose should be adjusted and the latent adverse reactions should be monitored carefully.

Assessment of effectiveness of anakinra and canakinumab in patients with colchicine-resistant/unresponsive familial Mediterranean fever

Abstract İntroduction: Familial Mediterranean fever (FMF) is a hereditary auto-inflammatory disease characterized by recurrent fever and serosal inflammation. Anti-interleukin-1 (Anti-IL-1) treatments are recommended in colchicine resistant and/or intolerant FMF patients. This study aims to evaluate the efficacy of anakinra and canakinumab in FMF patients that are resistant/intolareted to colchicine or complicated with amyloidosis. Methods: Between January 2014 and March 2019, 65 patients following-up at Sivas Cumhuriyet University (Medical Faculty Rheumatology-Internal Medicine Department) who were diagnosed with FMF according to the criteria of Tel-Hashomer were included in the study. The laboratory values and clinical features of patients and disease activities were recorded at least every 3 months, and these data were analyzed. Results: Forty-one (63.1%) patients used anakinra (100 mg/day) and 24 (36.9%) patients used canakinumab (150 mg/8 week). The median duration of anti-IL-1 agents use was 7 months (range, 3-30). Fifteen (23.1%) cases were complicated with amyloidosis. Seven (10.8%) patients had renal transplantation. Overall, the FMF 50 score response was 96.9%. In the group that had a glomerular filtration rate (GFR) ≥ 60 ml/min/m2, the median proteinuria decreased from 2390 mg/day (range, 1400-7200) to 890 mg/day (range, 120-2750) (p = 0.008). No serious infections were detected, except in one patient. Conclusions: Anti-IL-1 agents are effective and safe in the treatment of FMF patients. These agents are particularly effective at reducing proteinuria in patients with GFR ≥ 60 ml/min/m2, but less effective in cases with FMF associated with arthritis and sacroiliitis. Large and long follow-up studies are now needed to establish the long-term effects of these treatments.

Colchicine resistant FMF is not always true resistance

Crohn's disease and familial Mediterranean fever are both inflammatory diseases characterized by similar clinical manifestations. The concurrence of the two diseases may pose a challenge to diagnosis and treatment. In this report, we present a child with familial Mediterranean fever and undiagnosed Crohn's disease which made him apparently resistant to colchicine therapy. Symptoms of Crohn's disease were masked by the resistant fever of FMF. Amelioration of symptoms of both diseases was achieved when treatment of both diseases were gradually introduced. Searching of IBD in children with colchicines resistant FMF is mandatory, as both diseases have similar symptoms and responsible genes may modify one another

Role of oral colchicine in plaque type psoriasis. A randomized clinical trial comparing with oral methotrexate

Patients with moderate to severe psoriasis generally require phototherapy, photochemotherapy or systemic agents to control their disease adequately. The potential toxic effects of long term use of the classic antipsoriatics, prolonged continuous therapy, higher cost and low socio-economic conditions of patients obligate us to consider some cheaper older alternatives like colchicine. A prospective, randomized controlled clinical trial was carried out on two groups of patient of psoriasis, group A [Case, n=30] was treated with 2.1 mg per day oral colchicine, in two divided doses and group B [Control, n= 30] was treated with 7.5 mg of oral methotrexate once weekly for 8 weeks. No topical agent except bland emollients was applied during the trial period. Psoriasis area severity index [PASI] was calculated as main outcome measure at entry level and follow up after one month and two months. The mean percentage reduction of PASI was statistically significant [p=0.001] at both first and second follow up with oral colchicine. PASI-50 was achieved in 23.3% of respondent in colchicine group and 53.3% in methotrexate group [p<0.05]. Oral colchicine is an effective therapy for chronic plaque psoriasis but it is less effective than methotrexate, the gold standard antipsoriatic therapy [p<0.05]

Common MEFV mutations in Egyptian patients with familial Mediterranean fever

Familial Mediterranean fever [FMF] which is an autosomal recessive condition that primarily affect population of the Mediterranean basin. If undiagnosed effectively and treated with coichicine for life it may lead to serious consequences in terms of renal amyloidosis and renal failure. We aim to check for the presence of FMF mutations in clinically suspected Egyptian patients, as an important step for family counseling and case management. The study is a pilot study to check for the presence of FMF mutations among suspected cases [24 cases] from Sharkia Govemorate. The control subjects [24] were selected from healthy volunteers. We examined FMF mutations by PCR technique for MEFV gene analysis in order to establish a diagnosis of FMF by examining two mutations, M694V and E148Q. We found 58.3%[14/24 cases] of cohort were positive for M694V mutation, and all cohort were negative for E148Q mutation. The normal controls were negative for previous two mutations. PCR technique provides a rapid, reliable, cost-effective, noninvasive, and sensitive test for establishing a diagnosis of FMF in symptomatic patients and also provides a rational basis for medical and genetic counseling of FMF patients and their families

Systemic treatment in severe cases of recurrent aphthous stomatitis: an open trial

PURPOSE: This study aimed to evaluate the efficacy of the systemic drugs thalidomide, dapsone, colchicine, and pentoxifylline in the treatment of severe manifestations of RAS. METHODS: An open, 4-year clinical trial was carried out for 21 consecutive patients with severe RAS. Initially, patients were given a 2-week course of prednisone to bring them to a baseline status. Simultaneously, one of the four test drugs was assigned to each patient to be taken for a period of 6 months. During the course of the trial, patients were switched to one of the other three drugs whenever side effects or a lack of satisfactory results occurred, and the 6-month limit of the treatment was then reset. RESULTS: The most efficient and best-tolerated drug was thalidomide, which was administered to a total of eight patients and resulted in complete remission in seven (87.5 percent). Dapsone was prescribed for a total of nine patients, of whom eight (89 percent) showed improvement in their symptoms, while five showed complete remission. Colchicine was administered to a total of ten patients, with benefits observed in nine (90 percent), of whom four showed complete remission. Pentoxyfilline was administered to a total of five patients, with benefits observed in three (60 percent), of whom one patient showed complete remission. CONCLUSION: The therapeutic methods used in this trial provided significant symptom relief. Patients experienced relapses of the lesions; however, this occurred after withdrawal of their medication during the follow-up period.

Two Cases of Acute Leukopenia Induced by Colchicine with Concurrent Immunosuppressants Use in Behcet's Disease

Colchicine-induced leukopenia usually occurrs in intentional or accidental overdoses or inappropriate use in combination with intravenous and oral colchine; however, there have been several reports of hematologic toxicity in short-term and small-dose colchicine medication courses. We present two cases of leukopenia induced by colchicine use concurrent with immunosuppressants in Behcet's disease. We postulate that the mechanism of colchicine-induced leukopenia might be the destruction of circulating leukocytes and an inhibition of leukocyte production by the immediate and direct toxic effect of colchicine on idiosyncrasies unique to each patient. The concurrently administered immunosuppressant might decrease the threshold for hematologic toxicity of colchicine in the leukocytes and their precursor cells.

Colchicine in the treatment of the inflammatory phase of Graves' ophthalmopathy: a prospective and randomized trial with prednisone

PURPOSE: To investigate if colchicine is valuable in the treatment of Graves' ophthalmopathy (GO), we compared its effect with prednisone in 22 patients during the inflammatory phase of GO. METHODS: All patients, similar in age, sex and smoking habits, were euthyroid for at least 3 months and randomly divided into two groups, one treated with colchicine (1.5 mg/day) and the other treated with prednisone (0.75 mg/kg/day). They were monitored with ophthalmologic assessment (clinical activity score-CAS) and magnetic resonance imaging, using a signal intensity ratio (SIR) of the recti muscles in comparison to the cerebral substantia alba. RESULTS: Amelioration of CAS was seen in 68 percent of the orbits in both groups. SIR also had a significant reduction after treatment: the initial median of 1.14 in G1 and 1.27 in G2, evolved, after treatment, to 1.07 in G1 and 0.69 in G2. The variation between both groups after treatment was not significant (p=0.22). None of the patients treated with colchicine had side effects; on the other hand, side effects in G2 were weight gain, edema, gastric complaints, hirsutism, weakness, depression, and alterations in blood pressure. CONCLUSION: Colchicine had a beneficial effect on the inflammatory phase of GO without the side effects of prednisone.

OBJETIVO: Investigar se a colchicina é eficaz no tratamento da oftalmopatia de Graves, nós comparamos o seu efeito com a prednisona em 22 pacientes tratados na fase inflamatória da doença. MÉTODOS: Todos os pacientes, similares quanto à idade, sexo e hábitos de tabagismo, estavam em eutiroidismo por pelo menos três meses e foram randomizados em dois grupos. O grupo 1 (G1) recebeu colchicina (1,5 mg/dia) e o grupo 2 (G2) foi tratado com prednisona (0,75 mg/kg/dia). Os pacientes foram acompanhados com avaliação oftalmológica (escore de atividade clínica - CAS) e de imagem por meio da ressonância magnética, usando a relação da intensidade de sinal (SIR) dos músculos reto em comparação com a substância alba cerebral. RESULTADOS: Diminuição no CAS de 68 por cento foi notada em ambos os grupos. A SIR também apresentou redução significante após o tratamento: A mediana inicial do G1 de 1,14 e 1,27 do G2 diminui após o tratamento para 1,07 no G1 e 0,69 no G2. A variação entre os grupos após o tratamento não foi significante (p=0,22). Nenhum paciente tratado com colchicina apresentou efeito colateral; ao passo que os efeitos colaterais no G2 foram ganho de peso, edema, queixas gástricas, fraqueza, depressão e alteração na pressão arterial. CONCLUSÕES: A colchicina apresenta efeitos benéficos na fase inflamatória da oftalmopatia de Graves sem os efeitos colaterais da prednisona.

Quebra de normas de segurança na formulação de medicamentos e mortes por intoxicação pela colchicina em adultos / Non-compliance to safety rules regarding medication prescription, leads to two adults' death due to colchicine intoxication

São apresentados dados de dois casos de uma mesma família atendidos em pronto-socorro, com intervalo de uma semana, que evoluíram para morte com diagnósticos de septicemia e de enterite aguda hemorrágica. A investigação realizada pela vigilância epidemiológica e sanitária concluiu que a causa dos óbitos foi intoxicação acidental por colchicina, preparada em farmácia de manipulação e propiciada por quebra de duas normas de segurança que levaram à ingestão de doses 100 vezes maiores que a dose habitual. O relato tem por objetivo alertar os médicos que prestam assistência em serviços de pronto atendimento sobre a necessidade de se incluir na anamnese, com o paciente ou acompanhante, a questão específica a respeito da utilização ou não de medicamentos manipulados, uma vez que o uso de substâncias preparadas em farmácias vem aumentando e acidentes como o relatado poderão ocorrer com maior freqüência, inclusive com outros medicamentos.

We present data from two cases seen at an emergency facility, occurring within a one-week period with two members of the same family, who died of septicemia and acute hemorrhagic enteritis. The investigation, conducted by the sanitary and epidemiological surveillance department, concluded that these deaths were due to accidental intoxication with colchicines. The drug was prepared in a compounding pharmacy, and there were breaches of safety norms leading to the ingestion of doses 100 times higher than the recommended dosage. The present report intends to alert physicians who provide emergency care as to the need to include, during the anamnesis of patients, specific questions to them or to their companion regarding the use of compounded drugs, given that the use of medication prepared in compounding pharmacies is increasing and accidents, as the one reported, may become more frequent and may occur with other drugs as well.

Colchicine-induced myopathy in renal failure.

A 60 year-old woman with chronic renal failure developed acute proximal muscle weakness after receiving a regular dosage of colchicine. Elevation of muscle enzymes and electromyography were compatible with myopathy. Muscle biopsy revealed variation in muscle fiber size and few vacuolated fibers which were features of colchicine-induced myopathy. The clinical improvement and decreasing in muscle enzyme level occurred after colchicine withdrawal. Other potential causes of myopathy such as chronic renal failure and other drugs were ruled out. We suggested that colchicine should be used with caution in the presence of renal failure especially when other drugs which affect the metabolism of colchicine are also prescribed.

Histopathological changes of the optic nerve after intravitreal injection of colchicine

Colchicine is a drug commonly used in the prophylaxis and treatment of gout. Also, it is of good role in the therapy of Behcet's disease. The optic nerve effects after eight weeks durations of 10 and 100 micro .g of intravitreal injection of colchicine were studied on pigmented rabbits. The present histopathological electron microscopic studies on the optic nerve showed all forms of optic neuritis. These forms included decreased content of neurotubules in the axoplasm of myelinated fibers and oligodendrocytes. In addition, thinned out myelin sheath, reaching up to disrupted myelin in high doses were observed, indicating the myelinolyic effect of colchicine. Contracted axolemma, was also seen. Clumping of nuclear chromatin and intended nucleus of oligodendrocytes were prominent observations