A case report on drug induced pancreatitis due to levofloxacin and methylprednisolone

Introduction: Acute pancreatitis is the acute inflammation of the pancreatic gland, attributed to a wide range of etiological factors. It is a well-known fact that approximately 80% of the causes are associated with cholelithiasis and alcohol abuse. However, the exact incidence of drug induced pancreatitis is difficult to determine due to the rare presentation, it requires larger, case-controlled studies to determine its incidence and prevalence. Up to 2% cases may be caused by drug. Case Report: This is a case report focusing on a 26-year-old female patient who developed acute pancreatitis following administration of levofloxacin and methylprednisolone for treatment of pneumonitis in intensive care unit. Both the drugs appear to be responsible for pancreatitis because of temporal relationship between the administration of drug, onset of symptoms and improvement of clinical symptoms when drugs were stopped. Conclusion: Levofloxacin and methylprednisolone appears to be responsible for pancreatitis because of the temporal relationship between the administration of drug, onset and improvement of clinical symptoms when drugs were stopped. (This page in not part of the published article.) International Journal of Case Reports and Images, Vol. 8 No. 1, January 2017. ISSN – [0976-3198] Int J Case Rep Images 2017;8(1):62–65. www.ijcasereportsandimages.com Rekhi et al. 62 CASE REPORT PEER REVIEWED | OPEN ACCESS A case report on drug induced pancreatitis due to levofloxacin and methylprednisolone Balwinder Kaur Rekhi, Srinath Reddy Mannem, H. S. Rekhi, Sushil Kumar Mittal, Sahil Arora, Sathya P., Ravitej Singh, Kaushal Seth


INTRODUCTION
Acute pancreatitis is the acute inflammation of the pancreatic gland associated with varying involvement of the surrounding regional tissues or remote organ system. It is characterized by deep seated abdominal pain radiating to back, nausea and elevated pancreatic enzymes.
Acute pancreatitis has been attributed to a wide range of etiological factors. Approximately, 80% of the cases are associated with cholelithiasis or alcohol abuse [1]. Approximately, 1% develop pancreatitis following endoscopic retrograde cholangiopancreatography (ERCP). Several drugs are casually related to pancreatitis particularly corticosteroids, thiazide diuretics, estrogens, azathioprine, and furosemide. Furthermore, in about www.ijcasereportsandimages.com Rekhi et al. 63 10% of cases, no cause can be identified. Pancreatic toxicity of drugs is of relatively recent knowledge through the publication of isolated cases or small series. Up to 2% of cases may be caused by drugs [2].
We report a case of acute pancreatitis in a young female receiving levofloxacin and methylprednisolone.

CASE REPORT
A 26-year-old female was admitted in intensive care unit as a case of pneumonitis. She presented with history of respiratory distress, cough for seven days and with fever for three days. There is no family history of pancreatic diseases. There is neither any history of alcohol abuse nor drug abuse. On examination, respiratory rate was 30 per min, pulse 128 per min, blood pressure was 118/82 mmHg. Chest examination showed bilateral diffuse crepts and ronchi with the use of accessory muscles. SpO 2 of 92% with venturi fiO 2 40%. After routine hematological and radiological investigations, she was diagnosed as pneumonitis and put on • Injection ceftriaxone and sulbactum 1.
Nebulization with salbutamol and budesonide The patient's general condition did not improve and further deteriorated, saturation dropped to spO 2 of 82% with oxygen and there after patient was shifted to ICU put on volume controlled mechanical ventilation and was put on • Injection ceftriaxone and sulbactum 1.5 g i.v bd • Injection levofloxacin 500 mg i.v od, • Injection solumedrol 50 mg iv od. • Injection omeprazole i.v od • Nebulization with salbutamol and budesonide After two days of treatment, the patient started responding to treatment, was weaned off from ventilator and put on venture mask. On the third day patient developed acute abdominal pain which is radiating to back and loose stools, for which ultrasonography was done which showed free fluid in the upper peritoneal recess and in between gut loops with left sided pleural effusion. Surgery call was sent and patient was diagnosed as a case of acute pancreatitis clinically, we advised serum amylase and lipase apart from routine investigations. Serum amylase was 346 U/L and serum lipase was 1432 U/L. Patient was advised contrast CT scan of abdomen which showed acute pancreatitis with modified CTSI of 6/10. Total leucocyte count raised from 11,600/mm 3 to 20,400/mm 3 on same day, the next day it increased to 52,000/mm 3 and then to 70,300/mm 3 . The initial antibiotics were stopped and patient was put on • injection meropenem 1 g i.v tds, • injection metronidazole 100 ml iv tds After three days patient responded well, serum amylase and lipase levels came back to normal range with normal ultrasonographic findings. Patient was later discharged and advised for follow-up.

DISCUSSION
Drug induced pancreatitis is relatively a less known concept in acute pancreatitis, as it is a relatively rare occurrence considering the small number of patients who develop pancreatitis compared to the large number of patients who receive potentially toxic drugs. Its incidence varies among different studies between 0.1% and 5.3% of all acute pancreatitis cases [3]. The clinical presentation and mechanisms of injury to the pancreas are not well understood and are controversial. The diagnosis of drug induced pancreatitis remains possible or probable in many patients. The resolution of pancreatitis after discontinuation of drug, could improve the diagnosis of drug induced pancreatitis. However, it is difficult to establish the direct correlation between resolution of symptoms and drug withdrawal sometimes.
Pancreatic toxicity of drugs is of relatively recent knowledge through the publication of isolated cases. According to pancréatox file prepared by the Paris Regional Centre -Saint-Antoine, the number of offending drugs reached 261, representing potentially 1-2% of acute pancreatitis [4]. More than 500 different drugs are listed in the World Health Organization (WHO) database suspected to cause acute pancreatitis as a side effect. Many of them are widely used to treat highly prevalent diseases [5].
Levofloxacin belongs to the new fluoroquinolones group. The most commonly reported adverse reactions are minor digestive disorders and elevated liver transaminases [6].
Mennecier et al. [7] suggest a possible pancreatic toxicity of levofloxacin used alone or with steroids and therefore, encourages us to recommend pancreatic biological tests before the onset of abdominal pain during treatment with levofloxacin. They also stated that there is temporal relationship between the drug intake and development of acute pancreatitis as well as resolution of acute pancreatitis upon discontinuation of drugs in a short interval.
In our case, the time criteria are based on the evolving profile of acute pancreatitis according to the administration and medication discontinuation.
Re-administration of drug has not been made. The temporal relationship between drug intake and the occurrence of pancreatitis is suggestive because the time between the administration of treatment and the occurrence of acute pancreatitis is short. Upon discontinuation of treatment, resolution of acute pancreatitis is suggestive as the clinical and laboratory abnormalities decreased within hours. The problem here is, what is the offending drug? Several cases of acute pancreatitis have been reported with methylprednisolone is a well-established fact [8]. In acute pancreatitis secondary to taking methylprednisolone, the time frame is 3 days to 22 weeks with a dose-dependent mechanism assumed. The mechanism of corticosteroid-induced pancreatitis is complex and currently unknown [9]. In a case report of Seneviratne et al. [9], the pancreatitis started after eight days of high-dose (250 mg) steroid treatment. In our patient, we started 50 mg dose of methylprednisolone. In our observation, the speed of the onset of acute pancreatitis can argue more in favor of an immunological mechanism. This suggests that the already incriminated levofloxacin in elevated pancreatic enzymes can cause acute pancreatitis. However, further observations are needed to confirm this hypothesis.

CONCLUSION
In this case reported, levofloxacin and methylprednisolone appears to be responsible for pancreatitis because of temporal relationship between the administration of drug, onset of symptoms and improvement of clinical symptoms when drugs were stopped. *********

Author Contributions
Balwinder Kaur Rekhi -Substantial contributions to conception and design, Acquisition of data, Drafting the article, Revising it critically for important intellectual content, Final approval of the version to be published Srinath Reddy Mannem -Substantial contributions to conception and design, Acquisition of data, Drafting the article, Revising it critically for important intellectual content, Final approval of the version to be published H. S. Rekhi -Substantial contributions to conception and design, Acquisition of data, Drafting the article, Revising it critically for important intellectual content, Final approval of the version to be published Sushil Kumar Mittal -Substantial contributions to conception and design, Acquisition of data, Drafting the article, Revising it critically for important intellectual content, Final approval of the version to be published Sahil Arora -Substantial contributions to conception and design, Acquisition of data, Drafting the article, Revising it critically for important intellectual content, Final approval of the version to be published Sathya P. -Substantial contributions to conception and design, Acquisition of data, Drafting the article, Revising it critically for important intellectual content, Final approval of the version to be published Ravitej Singh -Substantial contributions to conception and design, Acquisition of data, Drafting the article, Revising it critically for important intellectual content, Final approval of the version to be published Kaushal Seth -Substantial contributions to conception and design, Acquisition of data, Drafting the article, Revising it critically for important intellectual content, Final approval of the version to be published

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