Mesalazine-induced myocarditis: a case report

A 49-year-old British man presented to our hospital with an acute flare of UC, describing a 2-week history of bloody diarrhea. He was initially prescribed both oral and topical 5-ASA therapy and responded well to therapy, reporting an improvement in his abdominal symptoms. However, 10 days after commencing 5-ASA therapy, he was readmitted with central chest pain, pleuritic in nature and associated with severe dyspnea. The patient’s cardiovascular and respiratory examinations were unremarkable, and he was normotensive and apyrexial. His electrocardiogram demonstrated sinus tachycardia, and his cardiac enzymes were elevated, with a troponin T level of 146 ng/ML. He was treated for an acute coronary syndrome with dual-antiplatelet therapy, and an urgent inpatient angiogram was scheduled.

The coronary angiogram revealed smooth, unobstructed coronary arteries, and no cause was identified to account for the patient’s chest pain and troponin rise. Subsequently, cardiac magnetic resonance imaging (CMR) was performed, which showed subepicardial delayed gadolinium enhancement in the basal to middle inferior and inferolateral segments of the heart (Fig. 1), with matching high signal intensity seen on T2-weighted images of the same area. The left ventricle was nondilated with preserved systolic function. On the basis of these CMR findings, the patient was diagnosed with acute myocarditis, and the etiology for this was considered, including viral myocarditis, extraintestinal manifestation of IBD, a vasculitic or autoimmune process, or a drug-induced myocarditis. The patient had no history of a prodromal illness to suggest an underlying infection, and he was systemically well, making a vasculitic or autoimmune process less likely. Extraintestinal symptoms of IBD usually occur years following diagnosis, whereas our patient’s symptoms developed soon after starting a new drug therapy, which suggested that 5-ASA was the culprit.

The patient was treated conservatively with analgesia, and 5-ASA was promptly stopped. A working diagnosis of 5-ASA-induced myocarditis was supported by the gradual improvement in the patient’s condition following cessation of the drug, and he was discharged to home 3 days later. Follow-up CMR was performed after 2 months, and this showed no myocardial edema as well as reduced gadolinium enhancement of the epicardium and myocardium. This scan was compatible with a resolving myocarditis episode, and the patient subsequently made a full recovery.

Cardiac disease can be associated with IBD or can be a consequence of drug side effects, with over 100 cases of pericarditis and perimyocarditis reported in the literature [7]. In fact, up to one-third of patients may develop myocarditis during the course of their disease, and this can be clinically indistinguishable from 5-ASA-induced myocarditis [8].

Myocarditis is a rare but potentially fatal adverse effect of 5-ASA therapy that usually occurs within 2–4 weeks of initiation of treatment [8]. Although the mechanism remains unclear, it is postulated that cell-mediated hypersensitivity causes myocarditis, and this is thought to be more plausible than a direct cardiotoxic effect of the drug [9]. Studies have shown that cardiac complications of 5-ASA respond well to simple discontinuation of this medication, further supporting a hypersensitivity reaction [10, 11]. However, establishing a diagnosis of myocarditis caused by 5-ASA is particularly difficult because there are no specific findings derived from laboratory or cardiac imaging that are pathognomonic of this condition [12]. The key features to recognize are the onset of chest pain, dyspnea, or fever shortly after commencing the drug, usually within 28 days. Noninvasive imaging techniques such as echocardiography and CMR have a good diagnostic yield and can offer an alternative to myocardial biopsy, which is the gold standard but is rarely performed, owing to safety reasons [13, 14]. Cessation of the drug should ensue, and other causes of myocarditis should also be excluded, including viral myocarditis, vasculitis, or an extraintestinal manifestations of IBD.

The case of our patient illustrates that clinicians should be aware of this very rare but potentially life-threatening adverse effect of 5-ASA because this drug is widely prescribed for patients with IBD. It is vital to consider myocarditis in the differential diagnosis for chest pain in a patient taking 5-ASA because treatment is simply to discontinue the medication, which should improve symptoms rapidly within 24 h without leading to any permanent sequelae.