Managing myocarditis in a patient with newly diagnosed dermatomyositis

Abstract

A woman in her 20s presented with chest pain, dyspnoea, arthralgia, muscle weakness and skin discolouration. She was diagnosed with dermatomyositis. During her admission, she developed pleuritic chest pain and shortness of breath accompanied by a significant troponin I rise. Her echocardiogram showed a hyperdynamic left ventricle with a trivial pericardial effusion; there were no regional wall motion abnormalities. Gadolinium-diethylenetriaminepantaacetic-enhanced cardiac MRI showed extensive myocarditis. She was started on corticosteroids and azathioprine which led to an improvement of symptoms and biochemical markers.

Background

Dermatomyositis is an idiopathic inflammatory myopathy (IIM) characterised by proximal skeletal muscle weakness, characteristic skin changes and elevated muscle enzymes. Cardiac involvement is a recognised complication of dermatomyositis and is recognised as a poor prognostic factor.¹ The incidence of cardiac involvement in IIM is between 9% and 72%.² The most frequent cardiac manifestations of IIM include left ventricular dysfunction due to myocarditis, arrhythmias and atherosclerotic coronary artery disease.² This case study outlines the presentation, diagnosis and subsequent management of a patient admitted with new-onset dermatomyositis with myocarditis, an important complication for dermatomyositis that may impact on prognosis.²

Case presentation

A woman in her 20s of Mediterranean origin with no significant medical history presented to the accident and emergency department with chest pain, dyspnoea, arthralgia, muscle weakness and skin discolouration. Her symptoms started 3 months before presentation as rapid-onset bilateral swelling, pain and early morning stiffness of the small joints of her hands. This evolved into symmetrical large-joint arthralgia (shoulders, elbows, knees and hips) and progressively diffuse muscle weakness manifesting as the inability to cough, shallow breathing, dysphagia, constipation and exercise tolerance of no more than 50 yards on the flat. Two weeks before admission she started experiencing pleuritic chest pain. Furthermore, she complained of lethargy and unintentional weight loss of 10 kg over the preceding 3 months in addition to patches of dark discolouration of her skin. Her mother was diagnosed with dermatomyositis 2 years previously.

On examination, there was marked widespread wasting of muscle bulk. There were symmetrical, hyperpigmented rashes over her knuckles, antecubital fossa, chest, upper back and torso, as well as around her eyes. There was no thickening of her skin. Her nails and nailbeds were normal. Neck flexion was graded 3/5 for power, and she required the assistance of one to sit upright. Upper limb power was reduced (4/5) for shoulder abduction, forearm flexion and extension, but preserved strength in her wrists and fingers. However, her wrists demonstrated bilaterally decreased extension at 70 degrees and flexion 80 degrees, and her elbows had fixed flexion of 20 degrees bilaterally with associated joint swelling, suggesting the presence of synovitis. Hip and knee flexion and extension were graded 4/5 for power symmetrically, but power in her feet was preserved. Lungs were clear throughout, heart sounds normal, oral mucosa moist, abdomen soft and non-tender and Glasgow Come Score (GCS) 15/15. She was clinically euvolemic. There were no signs of heart failure. Respiratory rate was 28 breaths per minute, oxygen saturations 97% on air, heart rate of 127 beats per minute and regularly regular, blood pressure of 121/86, and she was without fever.

Investigations

Significant findings at admission were a creatine kinase (CK) of 9646 units/L and an alanine transaminase of 263 units/L. Her full blood count, C reactive protein, erythrocyte sediment rate, remaining liver function tests, urea and electrolytes and blood gases were within normal ranges. Her troponin I was mildly elevated at 88 nanograms/L (ng/L) with no significant rise after 4 hours. Chest X-ray, serial ECG and a CT pulmonary angiogram demonstrated no abnormalities. Echocardiography showed a hyperdynamic left ventricle with an ejection fraction of 65%–70%, absence of regional wall motion abnormalities and a trivial pericardial effusion. She underwent MRI of both her thighs which demonstrated symmetrical myositis of all compartments of her thighs with some focal fatty atrophy. A subsequent muscle biopsy confirmed the presence of inflammatory myopathy. Skin biopsy was not performed as the clinical picture was entirely in keeping with dermatomyositis; the rash was relatively mild and there was an attendant risk of infection with the high dose steroid treatment that had been started. It was therefore thought that in view of the relatively limited information this would likely give, the risk would outweigh the benefit.

Tumour marker panels and ultrasound of her abdomen, pelvis, breasts and transvaginal ultrasound found no evidence to suggest that this was a paraneoplastic syndrome. Viral hepatitis, HIV and COVID-19 screening were all negative. Autoantibody testing was achieved using a standard extractable nuclear antigen panel: the only myositis specific antibody which this included was Jo-1, which was negative. However, she was positive for anti-centromere antibody (anti-CENP) and antinuclear antibody titre of 1:5120 (nucleolar pattern). Complement C3 and C4 were within normal ranges.

Her chest pain and shortness of breath gradually worsened and 6 days postadmission blood tests revealed a troponin I rise to 924 ng/L, type 2 respiratory failure Pco₂ 9.4 kPa, PO₂ 6.0 kPa, pH 7.31, HCO₃⁻ 29.8 mmol/L and an FEV₁ of 0.55 L prompting a brief admission to the intensive care unit in anticipation of a requirement for respiratory support. However, she improved spontaneously and respiratory support was not required. Her troponin I increased to a maximum of 1861 ng/L. Her ECG demonstrated sinus tachycardia PR depression and T wave inversion in V1 and V2. CK remained elevated and a repeat echocardiogram did not note any changes in systolic or diastolic function. No significant valvular abnormalities were seen. A gadolinium-diethylenetriaminepantaacetic-enhanced cardiac MRI (Gd-DTPA-MRI) showed a non-dilated left ventricle with mildly impaired systolic function (left ventricular ejection fraction 53%) with non-ischaemic myocardial scarring with globally elevated T1 and T2 at areas of late gadolinium enhancement indicating an active inflammatory process suggestive of extensive active myocarditis (see figure 1). There was also noted to be a mild circumferential pericardial effusion.

Figure 1.

(A–D) Chamber and short-axis views (mid-left ventricle level) from gadolinium-diethylenetriaminepantaacetic-enhanced cardiac MRI. The figure shows bright subepicardial basal lateral and inferoseptal late gadolinium enhancement which becomes circumferential through mid to apical segments. There is also late gadolinium enhancement at the right ventricle wall.

Treatment

The diagnosis made was dermatomyositis (anti-CENP positive) with myocarditis. She was started on prednisolone 60 mg orally once daily alongside ibuprofen 400 mg three times a day and paracetamol 1 g four times a day; omeprazole 40 mg once daily was added for stomach protection. She required a single dose of immediate-release morphine 5 mg for her pain, with good analgesic effect. She required regular laxatives and an enema to assist with her bowel motions. She was given cotrimoxazole as pneumocystis pneumonia prophylaxis 960 mg oral three times a week. She required oral nystatin for the treatment of oral thrush. Bisoprolol and ramipril were given for cardioprotection. Episodes of objective deterioration, defined as increasing muscular weakness and worsening shortness of breath, were treated with 500 mg intravenous doses of methylprednisolone; this was required a total of three times over a 2-week admission. She was put on a soft diet due to an unsafe swallow as assessed by the speech and language therapists, largely attributed to breathlessness.

Outcome and follow-up

Overall, she required inpatient admission for 16 days. She made gradual improvements in her physical function (swallowing, bowel motions, breathing and mobilisation), her pains and rashes resolved, and down-trending of her CK and troponin I was observed (see figure 2). Thus, she was discharged on bisoprolol, prednisolone 60 mg, cotrimoxazole, ramipril and omeprazole. She was followed up in the rheumatology outpatient clinic reporting gradual improvement of all her symptoms. By 3 weeks postdischarge, she reported feeling much better. She was able to eat and drink comfortably, her breathing became less troublesome, with an exercise tolerance of approximately 15 min on a flat surface. She was able to stand up from sitting without using her hands (previously unable). Power remained at 4/5 for her shoulders bilaterally, but 5/5 throughout the rest of her limbs. There were no objective signs of heart failure and the rest of her clinical examination remained normal. ECG showed sinus rhythm, with a rate of 90 beats per minute, blood pressure (BP) 105/71 mm Hg and a respiratory rate of 14 breaths per minute. Her thiopurine methyltransferase levels were normal; she was started on azathioprine as a steroid-sparing agent; and her cotrimoxazole was discontinued. She was also started on Adcal-D3 and risedronate for bone protection. Follow-up blood tests correlated with clinical findings and demonstrated marked improvement in troponin I (23 ng/L), CK (659 units/L) and alanine aminotransferase (84 units/L).

Figure 2.

A trend of CK and troponin I levels from the beginning of admission, and subsequent measurements during outpatient visits. The maximum CK value was recorded as 9646 units/L, and troponin I of 1861.4 ng/L. CK, creatine kinase.

She did not attend her cardiology appointment and did not wish to do another cardiac MRI at this point.

At 5 months postdischarge, she had continued to improve and was able to engage in small amounts of running (however, this was limited to 2.5 min intervals). Blood tests were normal, CK 124 units/L and troponin I <3.2 ng/L. Her steroid dose had been weaned to 10 mg a day and her azathioprine up-titrated to 150 mg daily. Her tachycardia had resolved and her BP was 115/86 mm Hg, so her bisoprolol and ramipril were stopped.

Discussion

We have presented a case of dermatomyositis in a young woman complicated by myocarditis with elevated troponin I levels.

Dermatomyositis in combination with myocarditis has only rarely been reported. A literature review of cardiac involvement in IIM by Gupta et al in 2011 found myocarditis as the most common feature (38%) in reported pathology literature.³ In a case report from 2018, a young man was described with a history of myocarditis who presented with symptoms of myocarditis and where further history and investigation demonstrated active myositis.⁴ Immunomodulatory therapy improved both his skeletal myositis and myocarditis. The use of newer, non-invasive cardiac imaging such as Gd-DTPA-MRI suggests a higher frequency of cardiac disease in IIM than what is found on clinical examination. A 2015 study of uncontrolled data of 53 patients with IIM showed a high proportion (62%–75%) had myocardial inflammation on Gd-DTPA-MRI.⁵

Dermatomyositis-induced myocarditis can lead to subsequent development of myocardial fibrosis, cardiac conductive system disease and cardiomyopathy resulting in both systolic and diastolic heart failure.⁶ The myocarditis is thought to be caused by inflammation of the heart muscle similar to that seen in the skeletal muscle leading to focal fibrosis, vasculitis, intimal proliferation and medial sclerosis of vessels.⁷

Most cardiac abnormalities associated with dermatomyositis are subclinical; however, if they are clinically detectable the most commonly reported clinical presentation of cardiac involvement is heart failure.⁸

Multiple studies have looked at biomarkers suggestive of cardiac involvement in patients with dermatomyositis. There is mixed evidence regarding the use of CK, with some studies showing a correlation between elevated CK and cardiac involvement, whereas others show normal CK levels in the presence of cardiac involvement.⁷ Use of troponin T also showed mixed results, as troponin T proteins are also expressed in adult skeletal muscle.⁸ In this case troponin I was used as per trust policy. Troponin I is more specific to myocardial damage and therefore is the most reliable serum marker to detect myocardial damage in patients with IIM.⁹ There is also mixed evidence for the use of B-type natriuretic peptide prohormone (NT-proBNP) in the prognostication of myocarditis (we did not use NT-proBNP in this case). NT-proBNP is commonly elevated at the time of presentation of myocarditis and is associated with cardiac dysfunction. However, NT-proBNP is not specifically related to myocarditis and is more associated with ventricular dysfunction.¹⁰ There have also been studies suggesting a relationship between raised NT-proBNP and inflammation.¹¹ There are no studies detailing its use in IIM associated myocarditis, which may complicate analysis as in these cases there is systemic inflammation which may falsely elevate it and impede its use as a marker of disease.

Both Gd-DTPA-MRI and technetium-99m pyrophosphate scintigraphy can detect subtle cardiac abnormalities.⁹ A 2012 systematic review proposed that Gd-DTPA-MRI could be used to diagnose and monitor myocarditis in dermatomyositis, due to their high sensitivity, these methods often suggest a higher proportion of cardiac involvement than clinically evident.^{7 8} These subtle changes found on imaging may represent early stages in cardiac remodelling that will later manifest as clinical heart disease; therefore, detecting these changes early offers clinicians the opportunity to intervene to prevent the subsequent development of cardiac disease.⁹

The frequency of echocardiographic abnormalities in patients with IIM varies between 14% and 62%.² Changes seen included left/right ventricular dysfunction, pericardial effusions, pulmonary hypertension, valvular disease and sometimes ventricular enlargement.¹² Echocardiography is a useful method to detect early cardiac abnormalities in myocarditis; however, changes are not specific to myocarditis. Gd-DTPA-MRI has a higher sensitivity to detect myocardial inflammation than echocardiography.²

At present, there are no specific guidelines available for the treatment of dermatomyositis-induced myocarditis. However, it is reasonable to assume that an early and sustained reduction in inflammation might reduce the risk of developing diffuse interstitial myocardial fibrosis, which is important since inflammation is treatable while fibrosis is irreversible. Case reports have demonstrated that in patients with untreated dermatomyositis presenting with myocarditis, treatment with corticosteroids and immunosuppressive agents helped improve both myocarditis and myositis and reduced the size of myocardial damage and improved wall hypokinesia.⁸

In addition to immunosuppressive therapy, management of cardiac involvement with reduced ejection fraction may require beta-blockers, angiotensin-converting enzyme inhibitors and further heart failure treatments, depending on the ejection fraction.⁷

Patient’s perspective.

As a young person experiencing dermatomyositis this early, it changed my whole life. Developing this disease over a period of months, without having a clear answer at the beginning, really made the whole experience more difficult. I felt confused and worried all the time about my future.

Being in hospital and having an amazing team taking care of my health and helping me with following the treatment made a huge difference.

Now I have a normal life, which at some point I really believed I could never have again. Having an ‘invisible’ disease at this age it is hard sometimes, having to explain your physical limits to not be confused with laziness is really tiring, especially when people have never heard about this illness.

I still take care of myself and follow the treatment adjusted to my needs and I hope some day we find the answer to this condition and maybe a cure.

Learning points.

• The occurrence of cardiac involvement is a poor prognostic factor for survival and is the most common cause of death among patients with dermatomyositis.

• Heart failure is the most common clinical syndrome.

• The use of corticosteroids and immunosuppressive agents reduced the size of myocardial damage and improved wall hypokinesia in the treatment of myocarditis.

• We suggest using gadolinium-diethylenetriaminepantaacetic-enhanced cardiac MRI as part of the clinical evaluation of patients with dermatomyositis if myocarditis is suspected.

Ethics statements

Patient consent for publication

Consent obtained directly from patient(s).