Successful treatment using corticosteroids in early phase of eosinophilic myocarditis with eosinophilic granulomatosis with polyangiitis

Abstract

We report the case of a 50-year-old man with eosinophilic myocarditis and bronchial asthma treated successfully with prednisolone. He was initially diagnosed with eosinophilia, and complained of acute chest pain with electrocardiographic changes and elevation of cardiac enzymes. Coronary angiography showed no atherosclerotic changes; therefore, we performed endomyocardial biopsy and started oral prednisolone therapy immediately. His general condition improved with the disappearance of eosinophilia upon treatment. He was finally diagnosed with eosinophilic granulomatosis with polyangiitis complicated by eosinophilic myocarditis. This case report highlights that eosinophilic myocarditis may occur in association with systemic disease, and early steroid therapy is essential.

<Learning objective: We report the case of a 50-year-old man diagnosed with eosinophilic granulomatosis with polyangiitis complicated by eosinophilic myocarditis. This was a rare case of eosinophilic granulomatosis with polyangiitis with eosinophilic infiltration that was observed pathologically in multiple organs, including the myocardium. This case report highlights that eosinophilic myocarditis may occur in association with systemic disease, and early steroid therapy is essential.>

Introduction

Eosinophilic myocarditis is a rare clinical entity characterized by eosinophilia and myocardial inflammation with infiltrating eosinophils [1]. Eosinophilic myocarditis has varied causes, and it occurs in 27–47% of patients with eosinophilic granulomatosis with polyangiitis (EGPA) [2]. Furthermore, it is the major cause of early death and poor long-term prognosis among patients with EGPA [2]. We report a patient with EGPA complicated by eosinophilic myocarditis treated successfully with oral prednisolone without any delay.

Case report

A 50-year-old male patient was referred to our hospital with edema in the lower extremities, arthralgia, myalgia, and linear erythema (Fig. 1a and b). He had a history of bronchial asthma and allergic rhinitis. He arrived at our hospital unmedicated. Physical examination on admission revealed that his body temperature was 37.3 °C, blood pressure was 124/87 mmHg, and pulse rate was 99 beats/min. Edema and linear erythema were observed on the front of the lower legs (Fig. 1a and b). Muscle pain was experienced on both upper and lower extremities. There was no heart murmur, crackle, or other abnormal findings. Hematology showed a white blood cell count of 20,900/μL (eosinophils, 54.7%; neutrophils, 38.4%; lymphocytes, 4.3%; monocytes, 2.4%; and basophils, 0.2%); red blood cell count of 5.2 × 10⁶/μL; hemoglobin level of 15.2 g/dL; and platelet count of 31.1 × 10⁴/μL. Serum samples showed C-reactive protein of 2.09 mg/dL, creatine kinase (CK) of 353 U/L, and IgE of 1410 IU/mL. Antinuclear antibodies, C-antineutrophil cytoplasmic antibody, and P-antineutrophil cytoplasmic antibody were negative. Chest X-ray revealed a reticular shadow on the left lower lung field (Fig. 1c). Chest computed tomography revealed an infiltrative shadow on both posterior basal segments (Fig. 1d). Electrocardiography revealed poor R progression and no ST segment changes on admission (Fig. 2a). He was admitted to our hospital with a diagnosis of eosinophilia for detailed examination.

Fig. 1.

Abnormal findings on admission. (a and b) Edema and linear erythema on the front of the lower extremities were observed. (c) Chest X-ray revealed a reticular shadow on the left lower lung field (blue arrows). (d) Chest computed tomography revealed an infiltrative shadow on both posterior basal segments (red arrows).

Fig. 2.

Electrocardiography and left ventriculography. (a) Electrocardiography revealed poor R progression and no ST segment changes on admission. (b) Horizontal ST depression in leads V_4–6 was observed at the time of acute chest pain. (c and d) Left ventricular end-diastolic volume was 281.9 mL, left ventricular end-systolic volume was 196.1 mL, and left ventricular ejection fraction was estimated as 30.4%.

On the night of the day of admission, he complained of acute chest pain. Electrocardiography showed sinus rhythm, poor R progression, and horizontal ST depression in leads V_4–6 (Fig. 2b). Bedside transthoracic echocardiography revealed impaired contractility of the left ventricle, including the anterior and septal walls left ventricular ejection fraction (LVEF) was visually estimated as approximately 30–40%. Blood examination showed elevation of cardiac enzymes including troponin-T (2.7 ng/mL), CK (1190 U/L) and CK-MB (110 U/L). We performed coronary angiography, with suspicion of acute coronary syndrome, after intravenous administration of methylprednisolone (80 mg) to avoid allergic reaction to the contrast media, because of history of bronchial asthma. Coronary angiography revealed no atherosclerotic change in coronary arteries, and left ventriculography showed dilated left ventricle with diffusely impaired contractility (LVEF, 30.4%; left ventricular end-diastolic volume, 281.9 mL; left ventricular end-systolic volume, 196.1 mL) (Fig. 2c and d). Right heart catheterization showed elevation of mean pulmonary capillary wedge pressure (19 mmHg), mean pulmonary arterial pressure (25 mmHg), right ventricular pressure (44/9 mmHg), and mean right atrial pressure (13 mmHg). We also performed endomyocardial biopsy from the septal wall of the right ventricle with suspicion of eosinophilic myocarditis. His condition was considered unstable because of uncontrollable chest pain and signs of heart failure with myocardial injury. Thus, we started treatment with oral prednisolone 0.5 mg/kg/day (30 mg) immediately after myocardial biopsy without pathological findings. A few days later, pathological examination showed significant infiltration with eosinophils in the myocardium, with no evidence of vasculitis or granuloma (Fig. 3a and b). On day 4, we performed skin biopsy from the linear erythema. Pathological examination of the skin biopsy also revealed infiltration with eosinophils and no evidence of vasculitis and granuloma (Fig. 3c and d). On day 5, we performed cardiac magnetic resonance imaging (MRI). Although cardiac MRI sometimes shows prominent delayed contrast enhancement in the endocardium in patients with eosinophilic myocarditis, there was no delayed enhancement in this case. Repeated transthoracic echocardiography revealed that estimated LVEF was 41%, by the modified Simpson method, 2 days after initiation of steroid therapy. At 2 weeks after therapy, LVEF was 42%.

Fig. 3.

Pathological findings. (a and b) Pathological findings of endomyocardial biopsy revealed that infiltration with many eosinophils in the myocardium. (c and d) Pathological findings of skin biopsy revealed no significant findings of vasculitis (black arrow), but infiltration with many eosinophils was observed.

His general condition and blood examination findings improved immediately after initiation of treatment with oral prednisolone. However, 4 days after initiation of corticosteroids, eosinophil level was elevated again. Therefore, we increased the dose of prednisolone from 0.5 mg/kg/day (30 mg/day) to 1.0 mg/kg/day (60 mg/day). Subsequently, eosinophilia resolved. Prednisolone dose was reduced by 10 mg/day every week. However, numbness and muscle weakness of the left upper and lower extremities persisted. On day 29, electromyography revealed temporal dispersion of the left radial and left tibial nerves, suggesting mononeuritis multiplex. According to the diagnostic criteria of the Japanese Ministry of Health, Labour and Welfare, and the American College of Rheumatology [3], [4], he was finally diagnosed with EGPA complicated by eosinophilic myocarditis. With the diagnosis of treatment-resistant mononeuritis multiplex, we added 25 g/day intravenous injection of immunoglobulin for 5 days. Thereafter, he continued rehabilitation, and his symptoms improved gradually. He was discharged from our hospital on day 76 with 30 mg/day prednisolone. After discharge, prednisolone was reduced by approximately 10% every month. Finally, we prescribed 10 mg/day prednisolone as a maintenance dose. Although LVEF was not significantly improved, the patient remained free from any cardiovascular events including anginal symptoms during 12 months of follow-up.

Discussion

We successfully treated a patient with EGPA complicated by eosinophilic myocarditis using corticosteroids without any time delay for definite pathological diagnosis. Eosinophilic myocarditis is caused by cytotoxic substances such as eosinophilic cationic protein contained in the granules of eosinophils, which infiltrate the myocardium [5]. Eosinophilic myocarditis is a rare clinical entity, and a standard treatment has not yet been established. Although prednisolone is recommended for treatment of eosinophilic myocarditis, initial and maintenance doses are controversial. A previous article suggested that early administration of high-dose steroid therapy (beginning with prednisolone pulse or half pulse therapy daily for the first few days, and a maintenance dose of 1 mg/kg/day oral prednisolone) should be considered [6]. However, adjusting initial and maintenance doses of prednisolone based on disease severity is advisable. When patients with eosinophilic myocarditis experience pre-cardiac tamponade caused by pericarditis, cardiogenic shock, or pulmonary edema, methylprednisolone steroid pulse therapy may be more effective [1], [5]. In contrast, some comparatively mild cases have been treated with oral prednisolone (30–60 mg/day) [1]. Guidelines from the Japanese Circulation Society (JCS 2009) suggest that steroid therapy with an initial dose of prednisolone (30 mg/day) should be considered in patients with a definite diagnosis of eosinophilic myocarditis [5].

Because our case was not in shock status and transthoracic echocardiography revealed no signs of pre-cardiac tamponade and pericardial effusion, prednisolone was administered at an initial dose of 0.5 mg/kg/day. Although blood tests showed that eosinophil and C-reactive protein levels decreased immediately after administration of prednisolone, eosinophil level increased again 4 days later. Subsequently, we increased the dose of prednisolone by 1.0 mg/kg/day, and eosinophil level decreased. The reason that eosinophil level initially decreased was considered to be an effect of intravenous administration of methylprednisolone (80 mg) to avoid allergic reaction to the contrast media. Consequently, an appropriate dose of prednisolone was considered to be 1 mg/kg/day in this case, and we should have started steroid therapy with this dose.

Previous case reports suggested that early steroid therapy improved cardiac function in patients with eosinophilic myocarditis [6], [7]. However, significant improvement in LVEF was not observed after steroid therapy in the present case. Performing cardiac MRI before and after steroid therapy to evaluate the efficacy of treatment more precisely may have provided more information in this case. Although contractility of the left ventricle was not significantly improved, we believe that early steroid therapy avoided worsening his general condition owing to eosinophilia. Therefore, we concluded that early steroid therapy was essential in this case.

Eosinophilic myocarditis may present in association with a variety of diseases, including allergic conditions, drug hypersensitivity, and parasite infection, although it is sometimes idiopathic [8]. EGPA is also associated with different cardiac manifestations, including heart failure, arrhythmia, angina, and myocarditis [9]. Our present case had a history of bronchial asthma and allergic rhinitis, eosinophilia, and indications of vasculitis (mononeuritis multiplex, myalgia, and linear erythema). These were major clinical findings present in the diagnostic criteria of EGPA [3], [4], and the clinical course was also applicable to the criteria. Eosinophilic myocarditis occurs in 27–47% of patients with EGPA [2]. Furthermore, it is the major cause of early death and poor long-term prognosis among patients with EGPA [2]. Comarmond et al. also reported that cardiac complication is the main independent predictor of death in patients with EGPA [10]. Our present case had eosinophilic infiltration not only in the myocardium, but also in skin erythema, as shown pathologically. To the best of our knowledge, this was a rare case of EGPA with eosinophilic infiltration that was observed pathologically in multiple organs, including the myocardium.

In summary, our case report suggests that eosinophilic myocarditis is one of the serious conditions that may occur in association with systemic disease, including EGPA. We conclude that early diagnosis and treatment with prednisolone may lead to favorable outcomes in patients with EGPA complicated by eosinophilic myocarditis.

Conflict of interest

The authors have no conflicts of interest to disclose.