Ulcerative colitis and acute perimyocarditis

Clinical record

A 32‐year‐old man with 15years of intermittent bloody diarrhoea was diagnosed with ulcerative proctosigmoiditis. He was commenced on mesalazine 4.8g four times per day with prednisone enemas. After 13days of treatment, he presented with ten bloody stools per day and sharp, pleuritic chest pain. The patient was febrile (38.1°C) and clinically hypovolemic, with blood pressure 110/70mmHg, heart rate 107 beats per minute, and peripheral oxygen saturation on room air 97%. A 12‐lead electrocardiogram (ECG) demonstrated sinus tachycardia with PR segment depression and concave ST segment elevation without dynamic changes (Box 1). High sensitivity troponin T (on admission, 122ng/L; serial [2h], 109ng/L; reference interval [RI], ≤14ng/L), erythrocyte sedimentation rate (22mm/h; RI, 0–10mm/h), C‐reactive protein (23mg/L; RI, ≤4.9mg/L) and faecal calprotectin (70μg/g; RI, ≤50μg/g) were elevated. Blood cultures and respiratory viral testing, including for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), were negative. Perimyocarditis was suspected and colchicine 500μg twice daily was commenced.

Transthoracic echocardiography on admission demonstrated normal left ventricular size with significant regional wall motion abnormality involving the apical segments and overall moderate left ventricular systolic dysfunction (left ventricular ejection fraction, 38%; RI, >50%; global longitudinal strain [GLS], ‐10.43%; RI, <‐18%), normal right ventricular size and function, atrial area, pericardial appearance and valvular function (Supporting Information, video). Mesalazine was ceased from admission, as it is known to induce perimyocarditis. Bisoprolol 5mg and valsartan 20mg daily were initiated. Cardiac catheterisation revealed angiographically normal coronary arteries.

Flexible sigmoidoscopy demonstrated continuous, circumferential inflammation with spontaneous bleeding and ulcerations consistent with acute ulcerative colitis (Box 2). Histology confirmed active chronic colitis with negative cytomegalovirus stain. The flare was treated with intravenous hydrocortisone 100mg four times per day, and intravenous cyclosporin (2mg/kg/day) was used instead of infliximab due to the left ventricular dysfunction. Bloody stools improved after 12days of hydrocortisone and 7days of cyclosporin. Due to ongoing diarrhoea, inpatient cardiac magnetic resonance imaging (MRI) was not performed. A repeat transthoracic echocardiography (15days after index scan) demonstrated significant improvement in left ventricular function (left ventricular ejection fraction, 74% [RI, >50%]; GLS, ‐24.66% [RI, <‐18%]). The patient was discharged on day 20 on azathioprine 100mg daily.

At 30‐day follow‐up, cardiac MRI demonstrated no evidence of late gadolinium enhancement and there was complete resolution of symptoms.

Discussion

Perimyocarditis can be an extraintestinal manifestation of ulcerative colitis or a hypersensitivity idiosyncratic reaction from mesalazine. Key differences exist and are important to identify the underlying cause (Box 3).

Extraintestinal myocardial inflammation from ulcerative colitis generally occurs during an acute exacerbation but can occur any time throughout the disease course.1 By contrast, hypersensitivity reaction from mesalazine is not dose‐dependent and occurs within weeks of commencing therapy. Mesalazine is also associated with other cardiac reactions, including myocardial infarction (<0.2% incidence) and atrioventricular conduction defects (<0.3% incidence).2

In patients treated with mesalazine, identifying the cause of perimyocarditis can be challenging. Typically, myocardial inflammation is associated with elevated serum biomarkers (creatinine kinase‐MB and troponin), ECG changes (concave ST segment elevation), impairment of left ventricular function and pericardial effusion. Despite being considered the gold standard, endomyocardial biopsy is invasive and rarely used. Histologically, mesalazine‐induced myocardial inflammation is associated with eosinophilic infiltration, whereas cases due to ulcerative colitis are characterised by lymphocytes.3,4 As an alternative, cardiac MRI is accurate and can identify myocardial fibrosis with late gadolinium enhancement often in subepicardial or mid‐wall regions. The subendocardium is typically spared, thus distinguishing this pattern from myocardial infarction (Box 4).5

Overall, the prognosis is excellent but both forms can be fatal.1 Generally, patients with mesalazine‐associated myocardial inflammation have rapid improvement in left ventricular function upon cessation of therapy but inflammation can recur if rechallenged with mesalazine.1 On the other hand, ulcerative colitis‐associated myocardial inflammation occurs irrespective of treatment and even though left ventricular function can improve, these patients are more likely to have late gadolinium enhancement on cardiac MRI.3

We present a case of perimyocarditis in a patient with acute severe ulcerative colitis treated with mesalazine. In these patients, we suggest immediate cessation of mesalazine followed by assessment of left ventricular function. In those with left ventricular dysfunction, treatment with guideline‐directed heart failure therapy is recommended. Coronary angiography should be performed if clinically indicated. Cardiac MRI should be used to further quantify left ventricular function and identify fibrosis. Alternative anti‐inflammatory therapy should be commenced to treat the ulcerative colitis flare keeping in mind the potential cardiotoxic effects of infliximab. Follow‐up imaging with transthoracic echocardiography or cardiac MRI is recommended to assess prognosis and direct further treatment.

Box 1 – The patient’s electrocardiogram demonstrating sinus rhythm with PR segment depression and concave ST segment elevation

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Box 2 – Flexible sigmoidoscopy demonstrating severe ulcerative proctosigmoiditis*

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* Note continuous and circumferential inflammation with spontaneous bleeding and ulcerations

Box 4 – Typical T2‐weighted late gadolinium enhancement cardiac magnetic resonance images of acute myocarditis*

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* (A) Four‐chamber image demonstrating late gadolinium enhancement in the septal wall in a mid‐wall pattern (yellow arrow). (B) Short axis mid‐left ventricular image demonstrating late gadolinium enhancement in the anteroseptal wall in a mid‐wall pattern (red arrow).