Colchicine poisoning related rhabdomyolysis in a child

Öz

To the Editor Colchicine is a natural alkaloid obtained from the plant of Colchicum Autumnale which has anti inflammatory action It is a drug used in Behçet rsquo;s disease goute arthritis scleroderma and especially in prevention of acute attacks of Familial Mediteranean Fever FMF and development of amiloidosis 1 Frequent use of colchicine in relation with the high prevalence of FMF has caused to an increase in cases of intoxication Especially high doses lead to mortality In a study performed by Özdemir et al 2 in 23 pediatric patients who were diagnosed as colchicine intoxication between 1985 and 2011 no mortality was observed in 16 patients who received less than 0 5 mg kg colchicine while one of three patients who received a dose of 0 5 0 8 mg kg and one of four patients who received more than 0 8 mg kg were lost Rhabdomyolysis related to colchicine has been reported rarely and it is important in terms of mortality risk 3 We present a pediatric patient who developed rhabdomyolysis and bone marrow supression following ingestion of high dose colchicine accidentally A 3 year old female patient presented to a hospital one hour after ingesting 10 tablets each containing 0 5 mg colchicine 0 4 mg kg She was discharged after gastric lavage and administration of active carchoal She presented to our hospital becasue of vomiting and malaise which started 48 hours later On physical examination the body temperature was found to be 37 1 ordm;C axillary the pulse was found to be 95 min the respiratory rate was found to be 28 min the blood pressure was found to be 90 60 mmHg Other physical examination findings were found to be normal In the laboratory tests aspartate transaminase AST was found to be 826 U L and alanine aminotransferase ALT was found to be 146 U L 5 50 Thrombocytopenia was present 50 000 mm3 The patient was internalized for follow up On the following day diffuse muscle pain was found on examination and the laboratory tests were repeated: AST: 395 U L ALT: 132 U L lactate dehydrogenase LDH : 2094 U L 150 500 creatinine kinase CK : 6530 U L 35 235 myoglobin:117 ng mL 21 58 sodium 131 mEq L potassium 2 9 mEq L chloride 101 mEq L and phosphate 1 7 mg dL On the second day of hospitalization leukopenia 3600 mm3 was added to thrombocytopenia Blood urea nitrogen creatinine blood gases calicum fibrinogen prothrombin time and activated partial thromboplastin time were found to be normal Medical history did not reveal any infection trauma intramuscular injection or use of drugs other than colchicine which could cause rhabdomyolysis The picture was considered as rhabdomyolysis related with colchicine Fluid 2500 cc m2 gün and alkalinization treatment was administered No other pathology was found in the follow up and the patient was discharged four days later because her physical examination and laboratory findings improved Colchicine intoxication is a rare but life threatenting toxicological emergency High doses are fatal Toxicity may be observed even with therapeutic doses Colchicine intoxication is divided into three stages according to clinical findings: Stage 1: In this stage intestinal mucosal cells with high division rate are affected Accordingly the most common initial findings include nausea vomiting abdominal pain and diarrhea Stage 2: This stage starts 24 hours after colchicine ingestion Findings related with multiple organ failure start to be observed in relation with involvement of some systems Bone marrow supression hepatic damage renal failure respiratory distress syndrome arythmias disseminated intravascular coagulation metabolic acidosis hyponatremia and hypokalemia are observed in this stage Stage 3: The third stage is the recovery stage In this stage transient alopecia and ldquo;rebound rdquo; leukocytosis are observed typically 4 Death may occur in the early period the first 48 hours because of hypovolemic shock central nervous system damage or cardiopulmonary failure 5 It occurs frequently in the late period after 7 10 days because of cardiogenic collapse or bone marrow supression 6 Rhabdomyolysis is a picture characterized with diffuse muscle damage which develops in relation with different etiologies Myoglobin which may lead to acute tubular necrosis is a significant product of muscle destruction and is released into the plasma 7 8 Association of muscle pain muscle weakness and dark colored urine observed in adults is rare in children Muscle pain and diffuse muscle weakness are the most common complaints in children The diagnosis is made with increased CK levels accompanying muscle pains and presence of myoglobinuria Life threatening complications including renal failure and disseminated intravascular coagulation are observed more frequently in adults 9 10 Our patient had increased muscle tenderness and malaise Colchicine intoxication is a rare cause of rhabdomyolysis in children In the study performed by Melli et al 11 7 of the cases of rhabdomyolysis related to drug ingestion were found to be secondary to colchicine intoxication In most of these patients a second drug ingestion was present antipsychotic statin and serotonin reuptake inhibitors In the literature colchicine related rhabdomyolysis has been reported in four pediatric patients 12 13 14 The doses used by the patients ranged beween 07 and 1 3 mg kg The most common complaint at presentation included vomiting and diarrhea The most common clinical findings included sepsis septic shock disseminated intravascular coagulation and alopesia One child was lost In our patient the diagnosis of rhabdomyolysis was made because CK and myoglobulin values which were measured because of muscle pain which started 48 hours after ingestion of 0 4 mg kg colchicine were found to be high All patients with a suspicion of colchicine intoxication should be monitored closely since the outcome can not be predicted The clinical and laboratory findings should be followed up closely and rhabdomyolysis should be considered in patients with severe muscle pain Ad shy;dress for Cor shy;res shy;pon shy;den shy;ce: Fatih Demircioğlu MD Abant İzzet Baysal University Medical Faculty Department of Pediatrics Bolu Turkey E mail: fatih_demircioglu@yahoo com Re shy;cei shy;ved: 04 18 2012 Ac shy;cep shy;ted: 08 28 2012 References 1 Ben Chetrit E Bergmann S Sood R Mechanism of the anti inflammatory effect of colchicine in rheumatic diseases: a possible new outlook through microarray analysis Rheumatology Oxford 2006; 45 3 : 274 282 2 Ozdemir R Bayrakci B Teksam O Fatal poisoning in children: acute colchicine intoxication and new treatment approaches Clin Toxicol Phila 2011; 49 8 : 739 743 3 Bismuth C Gaultier M Conso F Aplastic médullaire aprés intoxication aigue á la colchicine Nouv Presse Med 1977; 6: 1625 1629 4 Milne ST Meek PD Fatal colchicine overdose: report of a case and review of the literature Am J Emerg Med 1998; 16 6 : 603 608 5 Stapczynski JS Rothstein RJ Gaye WA Niemann JT Colchicine overdose: report of two cases and review of the literature Ann Emerg Med 1981; 10 7 : 364 369 6 Ben Chetrit E Levy M Colchicine: 1998 update Semin Arthritis Rheum 1998; 28 1 : 48 59 7 Harris R Marx G Gillett M Kark A Arunanthy S Colchicine induced bone marrow suppression: treatment with granulocyte colony stimulating factor J Emerg Med 2000; 18 4 : 435 440 8 Criddle L Rhabdomyolysis Pathophysiology recognition and management Critical Care Nurse 2003; 23 6 : 14 32 9 Mannix R Tan ML Wright R Baskin M Acute pediatric rhabdomyolysis: causes and rates of renal failure Pediatrics 2006; 118 5 : 2119 2125 10 Watemberg N Leshner RL Armstrong BA Lerman Sagie T Acute pediatric rhabdomyolysis J Child Neurol 2000; 15 4 : 222 227 11 Vanholder R Sever MS Erek E Lameire N Rhabdomyolysis J Am Soc Nephrol 2000; 11 8 : 1553 1561 12 Melli G Chaudhry V Cornblath DR Rhabdomyolysis: an evaluation of 475 hospitalized patients Medicine Baltimore 2005; 84 6 : 377 385 13 Biçer S Soysal DD Ctak A Uçsel R Karaböcüoğlu M Uzel N Acute colchicine intoxication in a child: a case report Pediatr Emerg Care 2007; 23 5 : 314 317 14 Güven AG Bahat E Akman S Artan R Erol M Late diagnosis of severe colchicine intoxication Pediatrics 2002; 109 5 : 971 973

Anahtar Kelimeler

• -

Çocuk hastada kolşisin zehirlenmesine bağlı rabdomiyoliz

Öz

Kolşisin, Colchicum Autumnale bitkisinden ele edilmiş enflamasyon karşıtı etkisi olan doğal bir alkaloiddir. Behçet hastalığı, gut artriti, skleroderma ve özellikle Ailevi Akdeniz Ateşi’nin (AAA) akut ataklarını ve amiloidoz gelişimini önlemede kullanılan bir ilaçtır (1). Ailevi Akdeniz Ateşi hastalığının yaygınlığına bağlı olarak kolşisinin sık kullanımı, zehirlenme olgularının sayısının artışını da beraberinde getirmiştir. Özellikle yüksek dozlarda alındığında ölüme neden olmaktadır. Özdemir ve ark. (2) 1985-2011 yılları arasında kolşisin zehirlenmesi saptanan 23 çocuk hasta üzerinde yaptıkları çalışmada, kolşisini 0,5 mg/kg’dan düşük dozda alan 16 hastadan hiçbirinde ölüm görülmezken, 0,5-0,8 mg/kg dozunda ilaç alan üç hastadan birinde ve 0,8 mg/kg’dan fazla dozda ilaç alan dört hastadan ikisinde ölüm gelişmiştir. Kolşisine bağlı ortaya çıkan rabdomiyoliz nadir olarak bildirilmiş olup hastalık riski nedeniyle önemlidir (3). Biz yanlışlıkla yüksek doz kolşisin alımı sonrası rabdomiyoliz ve kemik iliği baskılanması gelişen bir çocuk olguyu sunuyoruz.

Anahtar Kelimeler

• Çocuk
• hastada
• kolşisin
• zehirlenmesi

Kaynakça

1. Ben-Chetrit E, Bergmann S, Sood R. Mechanism of the anti-inflammatory effect of colchicine in rheumatic diseases: a possible new outlook through microarray analysis. Rheumatology (Oxford) 2006; 45(3): 274-82.
2. Ozdemir R, Bayrakci B, Teksam O. Fatal poisoning in children: acute colchicine intoxication and new treatment approaches. Clin Toxicol (Phila) 2011; 49(8): 739-43.
3. Bismuth C, Gaultier M, Conso F. Aplastic me ́dullaire aprés intoxication aigue a ́ la colchicine. Nouv Presse Med 1977; 6: 1625-29.
4. Milne ST, Meek PD. Fatal colchicine overdose: report of a case and review of the literature. Am J Emerg Med 1998; 16(6): 603-8.
5. Stapczynski JS, Rothstein RJ, Gaye WA, Niemann JT. Colchicine overdose: report of two cases and review of the literature. Ann Emerg Med 1981; 10(7): 364-9.
6. Ben-Chetrit E, Levy M. Colchicine: 1998 update. Semin Arthritis Rheum 1998; 28(1): 48-59.
7. Harris R, Marx G, Gillett M, Kark A, Arunanthy S. Colchicine-induced bone marrow suppression: treatment with granulocyte colony-stimulating factor. J Emerg Med 2000; 18(4): 435-40.
8. Criddle L. Rhabdomyolysis. Pathophysiology, recognition, and management. Critical Care Nurse 2003; 23(6): 14-32.

9. Mannix R, Tan ML, Wright R, Baskin M. Acute pediatric rhabdomyolysis: causes and rates of renal failure. Pediatrics 2006; 118(5): 2119-25. Watemberg N, Leshner RL, Armstrong BA, Lerman-Sagie T. Acute pediatric rhabdomyolysis. J Child Neurol 2000; 15(4): 222-7.
10. Vanholder R, Sever MS, Erek E, Lameire N. Rhabdomyolysis. J Am Soc Nephrol 2000; 11(8): 1553-61.
11. Melli G, Chaudhry V, Cornblath DR. Rhabdomyolysis: an evaluation of 475 hospitalized patients. Medicine (Baltimore) 2005; 84(6): 377-85.
12. Biçer S, Soysal DD, Ctak A, Uçsel R, Karaböcüoğlu M, Uzel N. Acute colchicine intoxication in a child: a case report. Pediatr Emerg Care 2007; 23(5): 314-7.
13. Güven AG, Bahat E, Akman S, Artan R, Erol M. Late diagnosis of severe colchicine intoxication. Pediatrics 2002; 109(5): 971-3. 75 Türk Ped Arfl 2013; 48: 74-5 Turk Arch Ped 2013; 48: 74-5 Demircioğlu ve ark.
14. Çocuk hastada kolşisin zehirlenmesine bağlı rabdomiyoliz / Colchicine poisoning related rhabdomyolysis in a child