Abstract
Acute pancreatitis is defined as inflammation of the pancreas and is most commonly caused by gallstones and alcohol use. Less commonly, acute pancreatitis can be drug induced from medications that are divided into 5 subgroups (classes Ia-V). The subgroups are determined based on the cases reported, reaction with rechallenge and a consistent period of latency. We describe a case of a 34-year-old female who overdosed on losartan pills in a suicide attempt but developed symptoms of drug-induced acute pancreatitis nearly a week later without gallstones, alcohol involvement, or other drug toxicity.
Introduction
Acute pancreatitis, responsible for about 230 000 hospitalizations in the United States per year, is caused by the self-digestion of pancreatic tissue.1,2 The Atlanta Criteria, used to make a diagnosis of acute pancreatitis, states 2 of 3 following findings must be met: abdominal pain suggestive of pancreatitis, elevated serum amylase/lipase at least 3 times the normal level, and imaging characteristic of pancreatitis. 3 The most common causes are cholelithiasis and alcohol use while other causes include hypertriglyceridemia, endoscopic retrograde cholangiopancreatography (ERCP), scorpion bites, and medications such as diuretics and antibiotics.4,5 Drugs are responsible for about 0.1% to 2% of all acute pancreatitis cases. 2 According to the World Health Organization, 525 different drugs have been described as having an adverse effect of acute pancreatitis, with mesalazine, azathioprine, and simvastatin shown to have the strongest correlation. 6 Drug-induced acute pancreatitis (DIAP) is a diagnosis of exclusion, and management usually requires removal of the offending agent as well as supportive care.
One such drug that is rarely associated with pancreatitis is losartan, an angiotensin receptor blocker (ARB) at the AT1 receptor site, resulting in compensatory elevation of renin and angiotensin I levels. 7 Losartan is used primarily for stage I hypertension. Other uses of losartan include treating diabetic nephropathy and heart failure. Losartan is associated with adverse effects such as hyperkalemia, renal insufficiency, and cough/angioedema.
Although many cases of DIAP have been reported in literature, very few reported cases are associated with losartan. To our understanding, only four cases of losartan-induced pancreatitis have been noted. 8 We report a case of losartan-induced pancreatitis in the setting of attempted overdose with an onset time of over a week.
Case Presentation
A 34-year-old female with a history of asthma, hypertension, and chronic respiratory failure from obesity hypoventilation syndrome presented to the emergency room (ER) due to a suicide attempt in which she attempted to swallow 30 tablets of 25 mg losartan (reported by her mother) a few hours earlier . She presented to the ER somnolent, with accompanying shortness of breath, and wheezing on auscultation. Toxicology was consulted in the emergency department; however, no note could be found in the electronic medical record. Vitals were positive for tachypnea but was found to be hemodynamically stable otherwise. Her home medications included amlodipine, losartan, and albuterol inhaler as needed, which was confirmed by her pharmacy as her primary care provider (PCP) could not be reached. She had one previous suicide attempt where she overdosed on acetaminophen an year prior to her visit and was hospitalized at a neighboring hospital for 1 week. Her psychiatric medical history included major depressive disorder, a learning disability, and adjustment disorder for which she was prescribed an antidepressant that could not be confirmed on the Psychiatric Services and Clinical Knowledge Enhancement System (PSYCKES). Records showed no other inpatient psychiatric encounters. Her drug and alcohol use was significant for cannabis use once in a while, and her urine drug screen did not reveal any substance use. In addition, the patient denied any smoking history. Her alcohol and smoking history were confirmed with her mother when gathering collateral information by the attending psychiatrist. The patient was admitted with an impression of acute asthma exacerbation and intentional losartan overdose . Her vital signs and chest x-ray showed no significant abnormalities besides tachypnea. In addition, the patient denied any trauma prior to presentation.
Due to the patient’s self-inflicted poisoning and ongoing suicidal ideation, she was hospitalized by recommendation of the psychiatry team. During her hospitalization, the patient developed acute kidney injury with her creatinine peaking at 2.9 mg/dL and potassium level of 6.0 mEq/L. The patient was not cleared by the psychiatry team and as a result, had an extended stay. On the ninth day of hospitalization, the patient began complaining of diffuse abdominal pain. Additional testing was obtained, which revealed an elevated lipase of 161 U/L (normal range: 22-51 U/L). Computerized tomography imaging of abdomen and pelvis revealed stranding of the peri-pancreatic head with thickening of the left para-renal space and lesser sac. Enlargement of the pancreatic body and tail were also noted with no evidence of intrahepatic or extrahepatic bile duct dilation, cholelithiasis, or a pancreatic pseudocyst (Figure 1). The patient was diagnosed with acute pancreatitis and managed with supportive care that included fluid resuscitation, analgesia, and regular monitoring of her labs. Over the next 2 days, the patient’s abdominal pain improved.
Computed tomographic image of the abdomen showing an inflammatory process in the pancreas.
An ultrasound of the abdomen was performed, which revealed no abnormalities. The patient developed symptoms on day 9 and her Ranson score was 0, while on day 11, her Ranson score was 1. This translated to a 1% predicted mortality rate. Table 1 describes the patient’s pertinent complete metabolic panel on admission, day 7 (development of acute kidney injury), day 9, and day 11 of her hospitalization.
Comprehensive Metabolic Panel for the Patient on Days 1, 7, 9, and 11.
Abbreviations: ALT/SGPT, alanine aminotransferase/serum glutamic-pyruvic transaminase; AST/SGOT, aspartate aminotransferase
Unfortunately, triglyceride levels were not obtained due to the patient’s refusal and psychiatric history, and IgG4 testing were not obtained as a result of hospital resources. The patient was offered a follow-up visit to the clinic; however, she did not show for her visits and as a result, no follow-up imaging was done.
Discussion
DIAP is a rare etiology of acute pancreatitis occurring in 2% of the general population. 9 In this case, the patient ingested an abnormally high dosage of losartan, a medication that rarely leads to pancreatitis.
DIAP has been divided into 4 categories. Class I medications are those that have at least 1 reported case of DIAP and can further be divided into Class Ia and Ib. Class 1a medications are medications the most likely to cause acute pancreatitis after the most common etiologies of pancreatitis have been excluded. Medications that fall under class 1b are those with a positive rechallenge, but fail to rule out other common causes of pancreatitis, and losartan falls under this class.1,10 A rechallenge was not pursued in this case. 11 Class II drugs demonstrate a latency period. Class III drugs include those that had 2 or more reported cases published, but no rechallenge or latency period present. Last, class IV drugs include medications similar to Class III, but have only 1 case report published.
The selection of Losartan over other antihypertensive agents is curious. Since the patient had a history of asthma, beta-blockers were not a good choice as an antihypertensive agent as a result of its bronchoconstrictive properties. In addition, angiotensin-converting enzyme (ACE) inhibitors have been associated with an increased possibility of angioedema in the African American population, and since the patient identified as African American, her PCP may not have wanted to prescribe ACE inhibitors. It is difficult to assess why thiazide diuretics or other calcium channel blockers were not considered in the management of this patient’s hypertension.
To our understanding, there are four documented case reports of losartan-induced pancreatitis.
Anwar et al, Birck et al, and Bosch all describe cases where DIAP occurred with positive rechallenge and varying lengths of latency: 0 days, 7 days, and 3 days, respectively.4,7,11 Tripathi et al describe a case with a latency period of 2 days. Similar to our case, the patient was not rechallenged. 8 The most striking difference between these previous case reports of losartan-induced pancreatitis and ours is the latency period. Our patient developed acute pancreatitis 9 days after overdosing on losartan. However, compared with Anwar et al and Birk et al, we did not pursue rechallenge. In addition, our patient developed pancreatitis in the setting of overdose while the previous case reports were in the setting of routine medication use. The Naranjo adverse reaction probability score can help establish the link between losartan and acute pancreatitis. 12 In this case, the probability score was 5, suggesting the drug may have caused the side effect. Furthermore, an R factor for liver injury was done, which suggested a score of 2.9. This score suggests the patient may have suffered from a mixed injury, suggesting physicians to perform acute viral hepatitis serologies, HCV RNA, and other imaging studies.
We were able to rule out alcohol use and cholelithiasis by retrieving the patient’s social drug use habits and imaging. The patient did not experience any trauma as previously stated, had not used any steroids, and had no evidence of scorpion stings. She had not undergone ERCP. Unfortunately, there were several limitations present in our case. Triglyceride levels and IgG4 autoimmune disorders are a potential cause of pancreatitis; however, due to the patient’s psychiatric history as previously stated, triglyceride levels were not obtained, though the patient had no history of hyperlipidemia. The patient did not have any history of autoimmune disorders, and IgG4 was not obtained due to hospital resources.
Conclusion
When a clear cause of acute pancreatitis cannot be identified, especially when its presentation is delayed, it is important for physicians to consider a holistic approach, which may include examining triglyceride levels, even if the patient has no history of hyperlipidemia, or sending out IgG4 levels. DIAP should be added to the differential as an early diagnosis can facilitate prompt cessation of the drug, better treatment outcomes, and a shorter hospital stay.
Footnotes
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.
Ethics Approval
Our institution does not require ethical approval for reporting individual cases or case series.
Informed Consent
Written informed consent was obtained from the patient(s) for their anonymized information to be published in this article.
