{"paper_id":"564ad522-0a48-45ff-af6b-eb17489b468f","body_text":"Acute pancreatitis, responsible for about 230 000 hospitalizations in the United\nStates per year, is caused by the self-digestion of pancreatic tissue. 1 , 2  The Atlanta Criteria, used to\nmake a diagnosis of acute pancreatitis, states 2 of 3 following findings must be\nmet: abdominal pain suggestive of pancreatitis, elevated serum amylase/lipase at\nleast 3 times the normal level, and imaging characteristic of pancreatitis. \n 3 \n  The most common causes are cholelithiasis and alcohol use while other causes\ninclude hypertriglyceridemia, endoscopic retrograde cholangiopancreatography (ERCP),\nscorpion bites, and medications such as diuretics and antibiotics. 4 , 5  Drugs are responsible for about\n0.1% to 2% of all acute pancreatitis cases. \n 2 \n  According to the World Health Organization, 525 different drugs have been\ndescribed as having an adverse effect of acute pancreatitis, with mesalazine,\nazathioprine, and simvastatin shown to have the strongest correlation. \n 6 \n  Drug-induced acute pancreatitis (DIAP) is a diagnosis of exclusion, and\nmanagement usually requires removal of the offending agent as well as supportive\ncare.\nOne such drug that is rarely associated with pancreatitis is losartan, an angiotensin\nreceptor blocker (ARB) at the AT1 receptor site, resulting in compensatory elevation\nof renin and angiotensin I levels. \n 7 \n  Losartan is used primarily for stage I hypertension. Other uses of losartan\ninclude treating diabetic nephropathy and heart failure. Losartan is associated with\nadverse effects such as hyperkalemia, renal insufficiency, and cough/angioedema.\nAlthough many cases of DIAP have been reported in literature, very few reported cases\nare associated with losartan. To our understanding, only four cases of\nlosartan-induced pancreatitis have been noted. \n 8 \n  We report a case of losartan-induced pancreatitis in the setting of attempted\noverdose with an onset time of over a week.\n\nA 34-year-old female with a history of asthma, hypertension, and chronic respiratory\nfailure from obesity hypoventilation syndrome presented to the emergency room (ER)\ndue to a suicide attempt in which she attempted to swallow 30 tablets of 25 mg\nlosartan (reported by her mother) a few hours earlier . She presented to the ER\nsomnolent, with accompanying shortness of breath, and wheezing on auscultation.\nToxicology was consulted in the emergency department; however, no note could be\nfound in the electronic medical record. Vitals were positive for tachypnea but was\nfound to be hemodynamically stable otherwise. Her home medications included\namlodipine, losartan, and albuterol inhaler as needed, which was confirmed by her\npharmacy as her primary care provider (PCP) could not be reached. She had one\nprevious suicide attempt where she overdosed on acetaminophen an year prior to her\nvisit and was hospitalized at a neighboring hospital for 1 week. Her psychiatric\nmedical history included major depressive disorder, a learning disability, and\nadjustment disorder for which she was prescribed an antidepressant that could not be\nconfirmed on the Psychiatric Services and Clinical Knowledge Enhancement System\n(PSYCKES). Records showed no other inpatient psychiatric encounters. Her drug and\nalcohol use was significant for cannabis use once in a while, and her urine drug\nscreen did not reveal any substance use. In addition, the patient denied any smoking\nhistory. Her alcohol and smoking history were confirmed with her mother when\ngathering collateral information by the attending psychiatrist. The patient was\nadmitted with an impression of acute asthma exacerbation and intentional losartan\noverdose . Her vital signs and chest x-ray showed no significant abnormalities\nbesides tachypnea. In addition, the patient denied any trauma prior to\npresentation.\nDue to the patient’s self-inflicted poisoning and ongoing suicidal ideation, she was\nhospitalized by recommendation of the psychiatry team. During her hospitalization,\nthe patient developed acute kidney injury with her creatinine peaking at 2.9 mg/dL\nand potassium level of 6.0 mEq/L. The patient was not cleared by the psychiatry team\nand as a result, had an extended stay. On the ninth day of hospitalization, the\npatient began complaining of diffuse abdominal pain. Additional testing was\nobtained, which revealed an elevated lipase of 161 U/L (normal range: 22-51 U/L).\nComputerized tomography imaging of abdomen and pelvis revealed stranding of the\nperi-pancreatic head with thickening of the left para-renal space and lesser sac.\nEnlargement of the pancreatic body and tail were also noted with no evidence of\nintrahepatic or extrahepatic bile duct dilation, cholelithiasis, or a pancreatic\npseudocyst ( Figure 1 ). The\npatient was diagnosed with acute pancreatitis and managed with supportive care that\nincluded fluid resuscitation, analgesia, and regular monitoring of her labs. Over\nthe next 2 days, the patient’s abdominal pain improved.\nComputed tomographic image of the abdomen showing an inflammatory process in\nthe pancreas.\nAn ultrasound of the abdomen was performed, which revealed no abnormalities. The\npatient developed symptoms on day 9 and her Ranson score was 0, while on day 11, her\nRanson score was 1. This translated to a 1% predicted mortality rate.  Table 1  describes the\npatient’s pertinent complete metabolic panel on admission, day 7 (development of\nacute kidney injury), day 9, and day 11 of her hospitalization.\nComprehensive Metabolic Panel for the Patient on Days 1, 7, 9, and 11.\nAbbreviations: ALT/SGPT, alanine aminotransferase/serum glutamic-pyruvic\ntransaminase; AST/SGOT, aspartate aminotransferase / serum\nglutamic-oxaloacetic transaminase.\nUnfortunately, triglyceride levels were not obtained due to the patient’s refusal and\npsychiatric history, and IgG4 testing were not obtained as a result of hospital\nresources. The patient was offered a follow-up visit to the clinic; however, she did\nnot show for her visits and as a result, no follow-up imaging was done.\n\nDIAP is a rare etiology of acute pancreatitis occurring in 2% of the general population. \n 9 \n  In this case, the patient ingested an abnormally high dosage of losartan, a\nmedication that rarely leads to pancreatitis.\nDIAP has been divided into 4 categories. Class I medications are those that have at\nleast 1 reported case of DIAP and can further be divided into Class Ia and Ib. Class\n1a medications are medications the most likely to cause acute pancreatitis after the\nmost common etiologies of pancreatitis have been excluded. Medications that fall\nunder class 1b are those with a positive rechallenge, but fail to rule out other\ncommon causes of pancreatitis, and losartan falls under this class. 1 , 10  A rechallenge was not pursued\nin this case. \n 11 \n  Class II drugs demonstrate a latency period. Class III drugs include those\nthat had 2 or more reported cases published, but no rechallenge or latency period\npresent. Last, class IV drugs include medications similar to Class III, but have\nonly 1 case report published.\nThe selection of Losartan over other antihypertensive agents is curious. Since the\npatient had a history of asthma, beta-blockers were not a good choice as an\nantihypertensive agent as a result of its bronchoconstrictive properties. In\naddition, angiotensin-converting enzyme (ACE) inhibitors have been associated with\nan increased possibility of angioedema in the African American population, and since\nthe patient identified as African American, her PCP may not have wanted to prescribe\nACE inhibitors. It is difficult to assess why thiazide diuretics or other calcium\nchannel blockers were not considered in the management of this patient’s\nhypertension.\nTo our understanding, there are four documented case reports of losartan-induced\npancreatitis.\nAnwar et al, Birck et al, and Bosch all describe cases where DIAP occurred with\npositive rechallenge and varying lengths of latency: 0 days, 7 days, and 3 days,\nrespectively. 4 , 7 , 11  Tripathi et\nal describe a case with a latency period of 2 days. Similar to our case, the patient\nwas not rechallenged. \n 8 \n  The most striking difference between these previous case reports of\nlosartan-induced pancreatitis and ours is the latency period. Our patient developed\nacute pancreatitis 9 days after overdosing on losartan. However, compared with Anwar\net al and Birk et al, we did not pursue rechallenge. In addition, our patient\ndeveloped pancreatitis in the setting of overdose while the previous case reports\nwere in the setting of routine medication use. The Naranjo adverse reaction\nprobability score can help establish the link between losartan and acute pancreatitis. \n 12 \n  In this case, the probability score was 5, suggesting the drug may have\ncaused the side effect. Furthermore, an R factor for liver injury was done, which\nsuggested a score of 2.9. This score suggests the patient may have suffered from a\nmixed injury, suggesting physicians to perform acute viral hepatitis serologies, HCV\nRNA, and other imaging studies.\nWe were able to rule out alcohol use and cholelithiasis by retrieving the patient’s\nsocial drug use habits and imaging. The patient did not experience any trauma as\npreviously stated, had not used any steroids, and had no evidence of scorpion\nstings. She had not undergone ERCP. Unfortunately, there were several limitations\npresent in our case. Triglyceride levels and IgG4 autoimmune disorders are a\npotential cause of pancreatitis; however, due to the patient’s psychiatric history\nas previously stated, triglyceride levels were not obtained, though the patient had\nno history of hyperlipidemia. The patient did not have any history of autoimmune\ndisorders, and IgG4 was not obtained due to hospital resources.\n\nWhen a clear cause of acute pancreatitis cannot be identified, especially when its\npresentation is delayed, it is important for physicians to consider a holistic\napproach, which may include examining triglyceride levels, even if the patient has\nno history of hyperlipidemia, or sending out IgG4 levels. DIAP should be added to\nthe differential as an early diagnosis can facilitate prompt cessation of the drug,\nbetter treatment outcomes, and a shorter hospital stay.","source_license":"CC-BY-4.0","license_restricted":false}