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JOP. J Pancreas (Online) 2006; 7(3):311-314. A Case of Probable Ibuprofen-Induced Acute Pancreatitis
Paul Magill1, Paul French Ridgway1, Kevin Christopher Conlon2, Paul Neary1
1Department of General and Vascular Surgery; 2Professorial Surgery Unit, Department of Surgery, Trinity College Dublin. Adelaide Meath and National Childrens Hospital. Tallaght, Ireland ABSTRACT
CASE REPORT
Context The incidence of drug-induced
An eighteen-year-old man with no previous pancreatitis is rare. There have been no prior medical or surgical history presented to our definite cases reported of ibuprofen-induced history of severe epigastric pain. He reported that five hours prior to the onset of symptoms, Case report We present a case of a young
he had ingested seven tablets of ibuprofen 400 mg (equivalent to a 51.4 mg/kg bolus) in an attempt at deliberate self harm. He had been Immediately preceding the onset of the attack taking ibuprofen as prescribed for low back he took a 51 mg/kg dose of ibuprofen. He had pain for one week prior to this event. He other causes of acute pancreatitis excluded by denied ingestion of other drugs or alcohol in the preceding days. This was confirmed by collateral history. The diagnosis of acute pancreatitis was made as per the UK Working Discussion In the absence of re-challenge we
Party on Acute Pancreatitis update criteria [3]. believe it is probable that ibuprofen has a range: 0-90 IU/L) and urinary amylase was 4,786 IU/L (reference range: 0-460 IU/L). His INTRODUCTION
(reference range: 100-350 IU/L) and he had a leucocytosis of 11.6 x109/L (reference range: 4.0-11.0 x109/L). Liver function tests, calcium level and lipid profile were all normal. The associations with acute pancreatitis [1, 2]. It is imperative to identify specific drugs as course (score 0) of pancreatitis. The standard possible causative aetiologies early in the acute predicted mild pancreatitis treatment was commenced. Standard toxicology screen ongoing pancreatic injury. Non steroidal anti- at twenty-four hours was negative for alcohol, salicylates and paracetamol. The screening been identified as a definitive cause for acute pancreatitis. We present the most probable evidence of cholelithiasis. Although not case to date of ibuprofen-induced pancreatitis. standard practice, given the unusual clinical JOP. Journal of the Pancreas - http://www.joplink.net - Vol. 7, No. 3 - May 2006. [ISSN 1590-8577] JOP. J Pancreas (Online) 2006; 7(3):311-314. suggested in two previous publications. The tomography at 48 hours which was graded as first report [6] was in a patient with systemic Balthazar A, consistent with mild pancreatitis hyperamylasaemia along with parotiditis in notably no double duct sign [5]. We did not what was termed a general hypersensitivity feel that any further invasive investigation reaction to ibuprofen. There was no definite diagnosis here and lupus itself is considered a risk factor for the development of acute ingestion, to rule out a gastric cause of pancreatitis. The second was by Eland et al. epigastric pain a gastroscopy was performed, reaction reports in the Netherlands over a normalised by day three using conservative investigated links between acute pancreatitis management, without a need for antibiotics. and a number of agents. They were able to He commenced oral diet on day three and on pancreatitis in 34 out of 55 reported cases and seen for out-patient follow-up at the 6-week they then labelled the association as definite if there was a positive re-challenge. In one case avoid using ibuprofen and hence there has history of protracted use of ibuprofen. The diagnosis however was not clearly established and there was no positive re-challenge and so DISCUSSION
the case was defined as a probable association The UK guidelines for diagnosis of acute between acute pancreatitis and ibuprofen pancreatitis [3] include a rise of amylase (or ingestion. This relationship has only been lipase where available) within 48 hours of characteristic abdominal pain. A greater than four-fold rise, as seen in our case, is desirable Table 1. Class I and Class II drug associations with
acute pancreatitis. Derived from a literature review
but not always required. We eliminated the from 1966 to April 2004 by Trivedi et al. [13]. developing pancreatitis and are therefore left with either idiopathic or ibuprofen-induced pancreatitis. Given the temporal relationship between ingestion and onset and the general rarity of acute idiopathic pancreatitis in an 18- year-old, we believe it is reasonable to Eland et al. proposed the ibuprofen effect at a (dose/kg unknown). Our patient ingested a bolus of 2,800 mg which correlates to 51.4 recommended if ingestion of more than 400 mg/kg in the preceding hour has occurred [8]. Class I: more than 20 cases of acute pancreatitis Our patient had been taking 1,600 mg daily reported for said drug, at least one of these cases citing for one week prior to this event. It is not clear whether the cumulative effect is important but Class II: more than 10 cases of acute pancreatitis reported for said drug. with a plasma half-life of 1.9 to 2.2 hours [9], JOP. Journal of the Pancreas - http://www.joplink.net - Vol. 7, No. 3 - May 2006. [ISSN 1590-8577] JOP. J Pancreas (Online) 2006; 7(3):311-314. it would seem improbable unless a steady state had been maintained up to the overdose. There are a multitude of drugs which are also consensus guidelines [3]. We do not have data possible causes of acute pancreatitis (Tables 1 to recommend whether this index case should and 2) [1, 2, 7, 10, 11, 12, 13, 14, 15]. Other reports of NSAID-induced pancreatitis are future. However, it would seem appropriate to few. Sulindac seems to be the most reported follow up the case at regular intervals for [14, 15] and the mechanism by which this occurs is unknown. One hypothesis however In summary, we document a clinical case of links the possibility of NSAIDS reducing the acute mild pancreatitis. The patient had no amount of systemic glutathione and hence previous medical history and no risk factors inducing an oxidative stress reaction [16]. for the development of acute pancreatitis. Indeed there is no data to predict the clinical Immediately preceding the onset of the attack course in these cases. Clinical scoring systems he took a 51 mg/kg dose of ibuprofen. He had have not been validated in this population other causes of acute pancreatitis excluded by (owing to rarity) nor has it been determined whether they are likely to follow a more Table 2. Class III drug associations with acute pancreatitis. Derived from a literature review from 1966 to April 2004
by Trivedi et al. [13].
Abacavir
Class III: less than 10 but at least one case of acute pancreatitis reported for said drug. JOP. Journal of the Pancreas - http://www.joplink.net - Vol. 7, No. 3 - May 2006. [ISSN 1590-8577] JOP. J Pancreas (Online) 2006; 7(3):311-314. challenge we believe it is probable that outcome. JOP. J Pancreas (Online) 2001; 2:373-81. ibuprofen has a causative link with acute 6. Ruppert GB, Barth WF. Ibuprofen hypersensitivity in systemic lupus erythematosus. South Med J 1981; 7. Eland IA, van Puijenbroek EP, Sturkenboom MJ, Wilson JH, Stricker BH. Drug-associated acute pancreatitis: twenty-one years of spontaneous reporting in the Netherlands. Am J Gastroenterol 1999; 94:2417- Keywords
8. Volans G, Monaghan J, Colbridge M. Ibuprofen overdose. Int J Clin Pract Suppl 2003; 135:54-60. Correspondence
9. Ibuprofen data sheets. November 2004. Available at http://www.medsafe.govt.nz/DatasheetPage.htm (search for ibuprofen). Accessed, 17th October 2005. 10. Singh S, Nautiyal A, Dolan JG. Recurrent acute pancreatitis possibly induced by atorvastatin and rosuvastatin. Is statin induced pancreatitis a class effect? JOP. J Pancreas (Online) 2004; 5:502-4. [PMID 11. Antonopoulos S, Mikros S, Kokkoris S, Protopsaltis J, Filioti K, Karamanolis D, Giannoulis G. A case of acute pancreatitis possibly associated with combined salicylate and simvastatin treatment. JOP. J References
Pancreas (Online) 2005; 6:264-8. [PMID 15883478] 1. Banerjee AK, Patel KJ, Grainger SL. Drug- 12. Nigwekar SU, Casey KJ. Metronidazole-induced induced acute pancreatitis. A critical review. Med pancreatitis. A case report and review of literature. Toxicol Adverse Drug Exp 1989; 4:186-98. [PMID JOP. J Pancreas (Online) 2004; 5:516-9. [PMID 2. Wilmink T, Frick TW. Drug-induced pancreatitis. 13. Trivedi CD, Pitchumoni CS. Drug-induced Drug Saf 1996; 14:406-23. [PMID 8828018] pancreatitis: an update. J Clin Gastroenterol 2005; 3. UK Working Party on Acute Pancreatitis. UK guidelines for the management of acute pancreatitis. 14. Goldstein J, Laskin DA, Ginsberg GH. Sulindac associated with pancreatitis. Ann Intern Med 1980; 4. Balthazar EJ, Robinson DL, Megibow AJ, Ranson JH. Acute pancreatitis: value of CT in establishing 15. Lilly EL. Pancreatitis after administration of prognosis. Radiology 1990; 174:331-6. [PMID sulindac. JAMA 1981; 246:2680. [PMID 7310962] 16. Memis D, Akalin E, Yucel T. Indomethacin- 5. Delhay M, Matos C, Deviere J. Acute relapsing induced pancreatitis: A case report. JOP. J Pancreas pancreatitis. Congenital variants: diagnosis, treatment, JOP. Journal of the Pancreas - http://www.joplink.net - Vol. 7, No. 3 - May 2006. [ISSN 1590-8577]

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