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Korean J Gastroenterol  <  Volume 83(5); 2024 <  Articles

Korean J Gastroenterol 2024; 83(5): 197-199  https://doi.org/10.4166/kjg.2024.024
Perimyocarditis in a Patient with Ulcerative Colitis Treated with 5-Aminosalicylic Acid
Hye Young Lee, Dong Hoon Baek
Department of Internal Medicine, Pusan National University School of Medicine and Biomedical Research Institute, Pusan National University Hospital, Busan, Korea
Correspondence to: Dong Hoon Baek, Department of Internal Medicine, Pusan National University College of Medicine, and Biomedical Research Institute, Pusan National University Hospital, 179 Gudeok-ro, Seo-gu, Busan 49241, Korea. Tel: +82-51-240-7869, Fax: +82-51-244-8180, E-mail: dhbeak@naver.com, ORCID: https://orcid.org/0000-0003-1512-9475

Financial support: This work was supported by a clinical research grant from the Pusan National University Hospital in 2024.
Received: March 11, 2024; Revised: April 15, 2024; Accepted: April 18, 2024; Published online: May 25, 2024.
© The Korean Journal of Gastroenterology. All rights reserved.

This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
5-Aminosalicylic acid (5-ASA) is recommended for managing ulcerative colitis. Common adverse effects associated with 5-ASA include gastrointestinal disorders, headaches, and skin rashes. Perimyocarditis induced by 5-ASA is a rare adverse effect, with only a limited number of cases reported. This paper presents a case of 5-ASA-induced perimyocarditis in a 29-year-old female who had been taking 5-ASA for three weeks. The patient was admitted to the emergency department with dyspnea, chest discomfort, and fever. She subsequently underwent laboratory investigations, including electrocardiography, transthoracic echocardiography, chest computed tomographic angiography, cardiac magnetic resonance imaging, and heart biopsy. Intravenous steroid was administered, and 5-ASA was discontinued. The patient’s signs and symptoms improved significantly within a few days of discontinuing 5-ASA, leading to her subsequent discharge. This case highlights the importance of considering perimyocarditis in patients exhibiting cardiac symptoms during 5-ASA therapy, despite it being a rare adverse effect. Drug withdrawal in such cases may lead to rapid clinical improvement.
Keywords: Perimyocarditis; 5-Aminosalicylic acid; Ulcerative colitis
INTRODUCTION

5-Aminosalicylic acid (5-ASA) is commonly recommended for the management of ulcerative colitis (UC), but it is frequently associated with adverse reactions such as nausea, vomiting, and abdominal pain. Rare side effects include pancreatitis, nephrotoxicity, and cardiotoxicity.1 In particular, perimyocarditis is an extremely rare complication.2

CASE REPORT

A 29-year-old female with active ulcerative colitis was diagnosed based on her medical history, colonoscopy, histopathological findings, and a fecal calprotectin level of 4,207 mg/kg. Two weeks after initiating therapy with 4,800 mg of 5-ASA per day, her symptoms of diarrhea and hematochezia improved, prompting the continuation of treatment.

On the 21st day of 5-ASA administration, the patient was hospitalized with chest discomfort, fever, and dyspnea that worsened while lying down. At the time of emergency admission, she had a blood pressure of 100/60 mmHg, a pulse rate of 120 beats per minute, respiration rate of 22 beats per minute, body temperature of 38℃, and oxygen saturation of 98%. The laboratory investigations revealed elevated white blood cell (WBC) counts (17,330 /mm3), erythrocyte sedimentation rate (120 mm/hr), C-reactive protein (CRP) (25.88 mg/dL), prohormone brain natriuretic peptide (proBNP) (4,750 pg/mL), and high-sensitivity troponin I (hsTroponin I) (184.02 pg/mL). Although she tested positive for antinuclear antibodies (1:160), the other autoimmune disorder-related tests showed no specific findings. She tested negative for tuberculosis interferon and other viral tests, including parvovirus, enterovirus, cytomegalovirus, Epstein-Barr virus, and COVID-19. Electrocardiography revealed a heart rate of 120 beats/min, ST depression, and an abnormal T wave. Transthoracic echocardiography showed regional wall motion abnormalities and pericardial effusion. Chest computed tomography and angiography revealed fluid collection with peripheral rim enhancement of the pericardial recess. Cardiac magnetic resonance imaging confirmed acute perimyocarditis with diffuse pericardial late gadolinium enhancement in the lateral wall of the left ventricle and pericardial effusion (Fig. 1). A heart biopsy indicated the infiltration of inflammatory cells, consistent with perimyocarditis (Fig. 2).

Figure 1. Cardiac magnetic resonance imaging showed diffuse pericardial late gadolinium enhancement (LGE) in the lateral wall of the left ventricle (arrow) and pericardial effusion (arrow). (A) Axial LGE. (B) Sagittal LGE.

Figure 2. Histological examination of heart biopsy specimens revealed mixed inflammatory cell infiltrate comprising lymphocytes, histiocytes, and eosinophils, which is consistent with perimyocarditis. (A) H&E, ×40. (B) H&E, ×200.

The patient was treated with an intravenous steroid (methylprednisolone) and antibiotics (tazobactam/piperacillin), and the 5-ASA therapy was discontinued. Her clinical signs and symptoms improved significantly within a few days following the withdrawal of 5-ASA. On hospital day 5, the patient's leukocyte and neutrophil counts normalized, and significant reductions were noted in her CRP (1.81 mg/dL), hsTroponin I (39.69 pg/mL), and proBNP (86 pg/mL) levels. She was discharged with a regimen of tapering steroid therapy. During subsequent follow-up appointments, her WBC, CRP, proBNP, and hsTroponin I levels were all within the normal ranges. She is currently being followed up as an outpatient, and any UC aggravation will be addressed by treatment with biologics.

DISCUSSION

5-ASA is the first-line treatment for UC. The drug prevents prostaglandin formation by inhibiting cyclooxygenase. This leads to the downregulation of signaling via the peroxisome proliferator-activated receptor gamma pathway, a decrease in nuclear factor ĸB activity, and colon inflammation.3 5-ASA administration is associated with nausea, vomiting, abdominal pain, headaches, and skin rashes. Rarer adverse effects include interstitial nephritis, renal failure, pancreatitis, male infertility, atrioventricular block, and perimyocarditis.1

Cardiotoxicity is a severe adverse effect of 5-ASA, albeit extremely rare, and should be considered in patients who present with fever, chest pain, dyspnea, and similar symptoms, especially within the first two to four weeks of treatment initiation.2 Immediate discontinuation of 5-ASA is essential in such cases, coupled with investigations to exclude other potential causes of cardiotoxicity such as viral infections, vasculitis, or extra-intestinal manifestations of inflammatory bowel disease. The precise mechanisms underlying 5-ASA-induced cardiotoxicity remain elusive but may involve direct toxic effects, IgE-mediated allergic reactions, cell-mediated hypersensitivity, or humoral antibody responses.4

In the present case, the patient developed dyspnea, chest discomfort, and fever after three weeks of 5-ASA therapy. In addition, she had leukocytosis and elevated ESR, CRP, hsTroponin I, and proBNP levels. Electrocardiography, diagnostic imaging, and heart biopsy revealed findings consistent with perimyocarditis, with no evidence of viral perimyocarditis or vasculitis identified. The immediate cessation of 5-ASA constitutes the cornerstone of 5-ASA-induced perimyocarditis management, which typically results in rapid clinical improvement. The adjunctive administration of corticosteroids is aimed at attenuating inflammation, but the efficacy of such therapies in accelerating resolution is unclear. Furthermore, re-challenging the patient with 5-ASA compounds poses a high risk of recurrent inflammation.5

In conclusion, this case report describes perimyocarditis in a patient with UC receiving 5-ASA therapy. Although 5-ASA is generally well-tolerated and considered safe for patients with inflammatory bowel disease, it is vital to recognize the potential for life-threatening cardiotoxicity. While the underlying mechanism is unclear, the known association between 5-ASA therapy and cardiac complications aids reliable diagnosis of 5-ASA-induced perimyocarditis. A careful clinical evaluation and differentiation from other potential causes are crucial for patients who develop dyspnea and chest pain within two to four weeks of starting 5-ASA therapy. Prompt discontinuation of the drug in these cases typically results in rapid clinical improvement.6-8

Financial support

This work was supported by a clinical research grant from the Pusan National University Hospital in 2024.

Conflict of interest

None.

References
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