Subclinical Myocardial Involvement Evaluated by Cardiac Magnetic Resonance Imaging in a Patient with Anti-Ro52/SS-A Antibody-positive Sjögren's Disease Complicated with Polymyositis

Abstract

A 52-year-old woman with myalgia, anti-aminoacyl tRNA synthetase, anti-SS-A/Ro52 antibody positivity, and elevated creatine kinase levels was admitted to our hospital. She was diagnosed with Sjögren's disease (SjD) complicated by polymyositis (PM). No chest symptoms were observed. Although her electrocardiogram and echocardiogram findings were normal, cardiac magnetic resonance imaging (CMRI) revealed myocardial edema and fibrosis with late gadolinium enhancement, elevated extracellular volume, and elevated T2 values. After treatment with prednisolone, the myalgia and CMRI abnormalities improved. This case suggests that CMRI may be useful for the detection and treatment of subclinical myocardial damage in patients with SjD complicated by PM.

Introduction

Polymyositis (PM) and dermatomyositis (DM) are autoimmune diseases characterized by chronic muscle weakness and inflammatory cell infiltration into skeletal muscle. Non-skeletal muscle organs, such as the lungs and intestines, are also affected. Myocardial involvement is common in PM and DM, with a reported incidence ranging from 9% to 72% (1). It is also known that myocardial involvement is a complication of Sjögren's disease (SjD) in approximately 3% of cases (2). Furthermore, an association between anti-Ro52/SS-A antibody positivity and congenital heart block in fetuses has been reported, suggesting myocardial involvement with anti-SS-A/Ro52 antibodies (3). Subclinical symptoms can lead to heart failure, arrhythmias, and myocardial infarction and contribute significantly to mortality (1,3). However, myocardial involvement in patients with PM/DM and SjD is mostly subclinical, and early detection using electrocardiography (ECG) and echocardiography (UCG) is difficult (4). Cardiac magnetic resonance imaging (CMRI) has emerged as a valuable tool for detecting early myocardial involvement, revealing elevated native T1, T2, and extracellular volume (ECV) values in patients with PM and DM (5). CMRI is a noninvasive technique that has been efficiently evaluated for early myocardial involvement (5).

We herein report a case of anti-Ro52/SS-A antibody-positive SjD complicated by PM, in which CMRI was critical for identifying and managing subclinical myocardial involvement.

Case Report

A 52-year-old woman with no significant medical or family history presented with a 3-month history of pleurisy, for which she was treated with antibiotics. Two months before admission, the patient developed extremity edema and myalgia. She was admitted to our hospital because of positive anti-aminoacyl tRNA synthetase (ARS) antibody and elevated inflammatory markers, although other myositis-related autoantibodies, including anti-melanoma differentiation-associated gene 5 antibody, anti-transcription intermediary factor 1-γ antibody, anti-nuclear matrix protein-2 antibody, anti-signal recognition particle antibody, and other autoantibodies, were negative. No skin findings, including Gottron papules, heliotrope rashes, or mechanical hands, were observed.

On the first visit, her creatine kinase (CK), CK-muscle/brain (CK-MB) fraction, aldolase, and troponin I (TnI) levels were within normal limits. However, after admission, her CK, CK-MB, and aldolase levels slightly increased (Table). Electromyography revealed myopathic changes, and a muscle biopsy showed an unequal size of muscle fibers and surrounding lymphocytic infiltration (Fig. 1A). The patient was diagnosed with PM based on positive anti-ARS antibodies.

Table.

Laboratory Findings before and after Treatment.

	On admission	After treatment	Normal range	Unit
WBC	17,600	8,000	3,300-8,600	/μL
Hemoglobin	9.0	11.7	11.6-14.8	g/dL
Platelet	447	194	158-348	×103/µL
AST	36	15	13-30	U/L
ALT	19	31	7-23	U/L
γ-GTP	15	22	9-32	U/L
LDH	424	221	124-222	U/L
CK	260	63	41-153	U/L
CK-MB	7	4	<5	ng/mL
Aldolase	26.3	9.7	2.1-6.1	U/L
Troponin I	0.08	0.09	<0.1	ng/mL
CRP	12.11	0.34	<0.2	mg/dL
KL-6	399	543	<500	U/mL
Ferritin	492.8	65.3	20-120	ng/mL
Anti-ARS Ab	26.3	NA	<25	U/L
Anti-Ro/SS-A Ab (CLEIA)	2.2	NA	<10.0	U/mL
Anti-Ro/SS-A Ab (FEIA)	34.0	36.3	<7.0	U/mL

Ab: antibody, ALT: alanine transaminase, ARS: aminoacyl tRNA synthetase, AST: aspartate aminotransferase, CK: creatine kinase, CK-MB: creatinine kinase muscle/brain fraction, CLEIA: chemiluminescent enzyme immunoassay, CRP: C-reactive protein, FEIA: fluorescence enzyme immunoassay, LDH: lactate dehydrogenase, NA: not applicable, WBC: white blood cells, γ-GTP: gamma-glutamyl transpeptidase

Figure 1.

Histopathological findings. A: histopathological image of a muscle biopsy, B: histopathological image of a labial gland biopsy

Chest computed tomography revealed interstitial changes consistent with nonspecific interstitial pneumonia with small bilateral pleural effusions. Although anti-Ro60/SS-A antibody by a chemiluminescent enzyme immunoassay detecting the Ro60 antigen yielded negative results, positive findings for anti-Ro/SS-A antibody were detected by a fluorescent enzyme immunoassay detecting both Ro60 and Ro52 antigens. The anti-Ro52/SS-A antibody level, measured directly in our laboratory using an enzyme-linked immunosorbent assay, was 38 U/mL (control dilution was 0.4 U/mL). In addition, anti-Ro52/SS-A antibodies were 3+ in the myositis-related antibody set test using a multiple simultaneous immunoblotting assay (EUROLINE^Ⓡ, EUROIMMUN, Lübeck, Germany). The ocular surface dye staining test, as measured by the mean change in corneal fluorescein, and Shirmer's test were positive (3 mm/3 mm per 5 min; right/left), as was a stimulated salivary function test with chewing gum, and a minor salivary gland biopsy showed lymphocytic infiltration (focus score ≥1) (Fig. 1B), findings that met the 2016 American College Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria (6). We therefore diagnosed this case as SjD with PM. The severity classification of SjD, according to the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) (7), was 13 points (5 for pulmonary involvement, 6 for muscle symptoms, and 2 for biological findings).

Upon admission, the TnI level was within the normal range, the patient showed no chest symptoms, and ECG did not reveal any abnormalities (Fig. 2A). UCG showed slight pericardial effusion, but the left ventricular function was normal with an ejection fraction (EF) of 67.4% and no diastolic disturbances. There were no findings suggestive of right ventricular load or pulmonary hypertension.

Figure 2.

Electrocardiography (ECG) findings. A: at the first visit, B: when TnI increased on day 9, and C: day 31 of illness.

However, on day 9 of hospitalization, although there were no symptoms, such as chest pain or dyspnea, the TnI value measured for follow-up observation had increased. The patient had no symptoms, and our hospital was unable to immediately perform an imaging evaluation using CMRI; however, the elevated TnI value was suggestive of myocardial involvement. Although repeat UCG revealed that the EF was normal (64.7%), with no evidence of right ventricular overload or pulmonary hypertension, and no abnormalities were observed on ECG (Fig. 2B), it was determined that early therapeutic intervention could prevent the exacerbation of myocardial damage. Therefore, on the day 18 of hospitalization, methylprednisolone (1,000 mg/day for 3 days) was administered, followed by prednisolone (50 mg/day) and tacrolimus (2 mg/day).

CMRI performed on hospital day 31 showed myocardial edema and fibrosis on late gadolinium enhancement, with an increased ECV of 35.1% (normal: 25.3±3.5%) (Fig. 3A, B) and prolonged T2 values of 60 milliseconds (ms) (normal: 52±2 ms) on T2-weighted imaging, indicating significant myocardial inflammation (Fig. 3C). ECG was performed at this time, but the results were the same as those previously reported (Fig. 2C). Although a myocardial biopsy could not be performed because the patient did not consent, based on clinical, laboratory, and imaging findings, the patient was diagnosed with anti-Ro52/SS-A antibody-positive SjD complicated by PM, with subclinical myocardial involvement detected by CMRI.

Figure 3.

Cardiac magnetic resonance imaging. T1 mapping changes in the extracellular volume (ECV), delayed Gd-contrast enhancement, and T2 mapping changes in the ECV suggestive of myocardial edema between the first (A, B, C: day 31 of illness) and second (D, E, F: day 74 of illness) evaluations.

The patient was treated with prednisolone (50 mg/day) after an initial pulse of intravenous methylprednisolone (1,000 mg/day for 3 days) in combination with tacrolimus (2 mg/day) at a trough level of 5.8 ng/mL. Subsequently, the levels of CK and CK-MB decreased and TnI normalized (Fig. 4). Follow-up CMRI on hospital day 74 demonstrated an improvement in myocardial findings, with the ECV reduced to 29.8% (Fig. 3D, E) and T2 values normalized to 54 ms (Fig. 3F).

Figure 4.

Clinical course of laboratory tests and treatment. The progression of myogenic enzyme levels with treatment and the timing of the two CMRI scans are shown. CMRI: cardiac magnetic resonance imaging, MRI: magnetic resonance imaging, PSL: prednisolone, CK: creatinine kinase

Discussion

This case of SjD complicated by PM highlights the importance of CMRI in subclinical detection and monitoring of myocardial involvement. CMRI was used in our patient to identify asymptomatic subclinical myocardial involvement, and treatment with prednisolone and immunosuppressive agents significantly improved the myocardial involvement. Myocardial involvement is common in PM and DM, with reported incidences ranging from 9% to 72% (1). Subclinical myocardial involvement often leads to serious complications and death (1). Lundberg et al. reported that myocardial involvement in PM often progresses, leading to poor outcomes if left undetected (8). Their work emphasized that early detection and intervention in cardiac diseases improves the patient survival and quality of life.

Myocardial involvement is a rare but potentially severe complication of SjD (3). Myocardial involvement in SjD presents as acute fulminant myocarditis or autoimmune myocarditis (9). Anti-Ro52/SS-A antibodies have been reported to be associated with myocardial involvement and atrioventricular block (10). It is important to investigate anti-Ro52/SS-A antibody-positive SjD with myositis for myocardial involvement, even if asymptomatic. SjD complicated by myocardial involvement is characterized by high levels of immunoglobulin G and cardiac and pleural effusion (11). Furthermore, Yokoe et al. reported that patients with SjD with an ESSDAI ≥8 are at a high risk of asymptomatic myocardial involvement on CMRI (12). In the present case, it was not possible to strictly distinguish whether myocardial involvement was caused by PM or anti-Ro52/SS-A antibody-positive SjD, based on previous findings. Inclusion bodies (13) and microvasculopathy (14), which are relatively common in the pathology of myositis in SjD, were absent in our patient. There have also been reports of the clinical importance of anti-Ro52/SS-A antibody-positive PM/DM (10,15). However, since this case met the criteria for SjD in the 2016 ACR/EULAR and had mildly elevated CK despite PM, low anti-ARS antibody levels, pleural and pericardial effusions, a very active ESSDAI of 13 points, and was positive for anti-Ro52/SS-A antibody, we considered the myocardial damage in this case to mainly be caused by SjD.

Acute myocarditis demonstrates lymphocytic infiltration of myocardial tissue (16), and findings similar to the lymphocytic infiltration of skeletal muscle and myofiber damage observed in PM and DM (17). A myocardial biopsy was performed for a pathological evaluation. However, complications occur in 6% of cases, and serious complications, such as cardiac tamponade or perforation, occur in 0.1% to 0.5% of cases (18). False negatives due to an evaluation of only part of the heart are common (19).

ECG, UCG, and CMRI are widely used tools for diagnosing and evaluating myocardial involvement in PM/DM, but their sensitivity and specificity vary. Studies on the evaluation of ECG in PM/DM have been conducted, and the frequency of ECG abnormalities ranges from 32.5% to 85% (4). However, all reports have been nonspecific, and no correlation between ECG abnormalities and the severity, activity, or treatment of myocardial involvement in PM/DM has been reported (20). Although ECG abnormalities are relatively frequent in PM/DM, they are not specific to the myocardial lesions. UCG is often performed because it is simple and inexpensive to perform. The most common finding in myocardial lesions in PM/DM is diastolic dysfunction. Fibrosis associated with myocardial inflammation is the pathology of diastolic dysfunction, and as it progresses, it may lead to irreversible heart failure (4). However, previous studies have not been able to statistically prove that patients with PM/DM have cardiac dysfunction, and those without it do not have cardiac dysfunction on UCG (21). There have been no reports of UCG, particularly in asymptomatic cases.

CMRI has emerged as a valuable tool for detecting early myocarditis, revealing elevated native T1, T2, and ECV values in patients with PM and diabetes mellitus (4). CMRI can be used to evaluate regional myocardial changes and diffuse lesions by quantifying myocardial T1 values and measuring the ECV (22,23). Among patients with PM/DM with a normal left ventricular ejection fraction, 54.5% showed positive delayed contrast-enhanced MRI findings, allowing the early detection of myocardial fibrosis before left ventricular dysfunction (24). In the present case, UCG showed a preserved left ventricular ejection fraction but increased ECV and prolonged T2 mapping, suggesting the presence of edema associated with myocardial inflammation. Liu et al. reported that early detection and monitoring of cardiac involvement are crucial for improving the prognosis of patients with PM/DM (4). In our case, CMRI was repeated to assess the improvement in myocardial involvement after treatment and showed improvement in both ECV and T2 mapping. T2 values for myocardial inflammation correlated with tissue water content compared with T1 values. Bohnen et al. (25) reported that, among the various CMRI parameters in patients with and without active myocarditis, only the global T2 showed a significant difference. T2 mapping may be effective in evaluating myocardial damage in patients with PM/DM.

There is no established consensus or guideline for the management of myocardial involvement in autoimmune diseases, such as SjD and PM/DM. However, even in asymptomatic cases, if imaging findings show abnormalities, glucocorticoid-based treatment is recommended. Early administration of high-dose corticosteroids can improve myocardial inflammation and cardiac dysfunction, but delayed treatment can lead to prolonged myocardial damage; therefore, treatment should be initiated as early as possible (26). In the present case, TnI levels increased rapidly during the course of the disease, and although there were no clinical symptoms, the patient was diagnosed with myocardial damage. Treatment was initiated after confirming the CMRI findings; however, because the test could not be performed immediately, treatment with glucocorticoids was initiated, and the degree of improvement was confirmed by CMRI.

Conclusion

This case demonstrates the importance of CMRI for detecting and evaluating myocardial involvement in anti-Ro52/SS-A antibody-positive SjD complicated by PM, particularly when traditional imaging modalities are inconclusive. CMRI, with its ability to quantify myocardial fibrosis and inflammation through techniques such as T1 and T2 mapping, provides critical insights into myocardial pathology that is not apparent on conventional imaging. CMRI findings, particularly elevated ECV and T2 values, reflect diffuse myocardial changes, such as fibrosis and inflammation. In the present patient, these markers improved following immunosuppressive therapy, underscoring the utility of CMRI in monitoring disease progression and treatment response. Early detection and treatment of cardiac involvement in autoimmune diseases may be crucial for improving the prognosis.

Written informed consent for the publication of this report was obtained from the patient by the corresponding author.

The authors state that they have no Conflict of Interest (COI).