https://orcid.org/0009-0008-4865-2522
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Abstract
Mesalazine represents a key treatment for intestinal bowel diseases and only in rare cases produces cardiac toxicity, with a not completely known mechanism. We report a case of a 25-year-old man with a first episode of myocarditis after 2 weeks from the first mesalazine intake, documented also by a characteristic cardiac magnetic resonance pattern. Then, after less than 1 month, he suffered myocarditis recurrence and so, guided by a multidisciplinary team evaluation, in the suspicion of mesalazine-induced myocarditis, the drug was promptly stopped, with consequent recovery of cardiac damage. In our patient, the recurrence of myocarditis because of the non-interruption of the drug is very peculiar (only three cases described in literature) and definitively confirms the diagnosis.
Plain language summary
This paper reports an exemplary case of cardiac toxicity induced by mesalazine, a key treatment for inflammatory bowel diseases such as Crohn's disease and ulcerative colitis. In rare cases, this drug can lead to cardiac impairment, with a mechanism not yet clarified. The young patient described experiencing a first episode of myocarditis (inflammation of the heart muscle cells) after 2 weeks of starting mesalazine. The diagnosis was possible thanks to cardiac magnetic resonance, a noninvasive exam providing high-definition images associated with tissue characterization. Mesalazine was not discontinued because drug-induced etiology was not suspected, due to its rarity. Consequently, the patient suffered a second episode of myocarditis, diagnosed by endomyocardial biopsy, an invasive technique that can accurately assess the etiology of myocardial damage, leading to prompt cessation of treatment. Since myocarditis can have various causes, diagnosis was also facilitated through a multidisciplinary team, which ruled out other possible causes for this condition. This case report is highly educational and underscores the importance of clinicians being vigilant about this side effect and considering it in patients taking mesalazine who present with myocarditis, to promptly discontinue the treatment. Mesalazine interruption is otherwise the only effective therapy for this condition, in addition to anti-inflammatory and analgesic drugs. Furthermore, this paper highlights the increasing importance of multidisciplinary teams, comprising various specialists, for accurate diagnosis and therapeutic decisions. The authors also propose an algorithm for diagnosing mesalazine-induced myocarditis, with certainty derived from recurrence after drug rechallenge, either voluntarily or accidentally, as demonstrated in this case.
5-aminosalicylic acid (5-ASA) is an important treatment for inflammatory bowel diseases, and its cardiac toxicity is reported in 0.3% of cases. The mechanism of mesalazine-induced myocarditis is not completely understood.
The clinical, instrumental, and laboratory presentation is similar to common forms of myocarditis (e.g., chest pain, troponin increase, electrocardiogram abnormalities). The use of imaging techniques is useful, particularly cardiac magnetic resonance, which has acquired increasing importance because of its potential for tissue characterization.
The gold standard for confirming the diagnosis of myocarditis is endomyocardial biopsy, although a certain etiological definition is not always possible.
The diagnosis of 5-ASA-induced myocarditis must be made first by ruling out other causes of myocarditis. Two main findings support the suspicion: clinical manifestation within 2–4 weeks after the first drug intake and improvement of the patient's condition immediately after discontinuation of therapy, which represents the only effective treatment for this condition.
We report the case of a 25-year-old patient who experienced a first episode of myocarditis 2 weeks after the first mesalazine intake, with a characteristic cardiac magnetic resonance pattern. Then, after less than one month, he experienced myocarditis recurrence due to the non-interruption of 5-ASA. Endomyocardial biopsy, associated with laboratory tests, excluded other possible causes (e.g., infectious, autoimmune). Through multidisciplinary team evaluation, in suspicion of mesalazine-induced myocarditis, the drug was promptly stopped, leading to the recovery of cardiac damage.
This case raises awareness about myocardial inflammation as a side effect of 5-ASA, and clinicians should always suspect this condition in patients taking this drug who present with cardiac impairment.
In our patient, the recurrence of myocarditis due to the non-interruption of the drug is very peculiar (only 3 cases described in the literature) and definitively confirms the diagnosis, associated with the ex juvantibus criterion.
In the end, we propose a diagnostic algorithm for 5-ASA-induced myocarditis; it starts from myocarditis diagnosis and exclusion of other possible causes, reaching progressive levels of likelihood by considering symptoms onset within 2–4 weeks of first drug intake (diagnosis possible), recovery after 5-ASA interruption (diagnosis likely) and myocarditis recurrence after rechallenging/non-stopping 5-ASA (diagnosis certain).
Author contributions
MM Dicorato: Investigation (lead), conceptualization (lead); writing – original draft (lead); writing – review and editing (equal); data curation (supporting); supervision (supporting). P Caretto: Investigation (supporting); writing – original draft (supporting) – review and editing (equal). C Colucci: Investigation (supporting); writing – original draft (supporting) – review and editing (equal). M Ciaccia: Software (equal); review and editing (equal). M Rella: Software (equal); review and editing (equal). E Muscogiuri: Software (equal); review and editing (equal). P Colonna: Software (equal); conceptualization (supporting); investigation (supporting); data curation (lead); supervision (lead); review and editing (equal).
Financial disclosure
The authors have no financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Competing interests disclosure
The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Writing disclosure
No writing assistance was utilized in the production of this manuscript.
Ethical conduct of research
Written informed consent has been obtained from the patient for the inclusion of their medical and treatment history within this case report.