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A 43-Year-Old Man With Antisynthetase Syndrome Presenting With Acute Worsening of Dyspnea43-Year-Old Man With Antisynthetase Syndrome FREE TO VIEW

Hrishikesh S. Kulkarni, MD; Fernando R. Gutierrez, MD; Vladimir Despotovic, MD; Tonya D. Russell, MD
Author and Funding Information

From the Division of Pulmonary and Critical Care (Drs Kulkarni, Despotovic, and Russell), and the Division of Rheumatology (Dr Despotovic), Department of Medicine, Washington University in St. Louis; and the Cardiothoracic Imaging Section (Dr Gutierrez), Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO.

CORRESPONDENCE TO: Hrishikesh S. Kulkarni, MD, Division of Pulmonary and Critical Care, Washington University in St. Louis, 660 S Euclid Ave, Campus Box 8052, St. Louis, MO 63110; e-mail: hkulkarn@dom.wustl.edu


Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2015;147(6):e215-e219. doi:10.1378/chest.14-2402
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A 43-year-old man with antisynthetase syndrome was seen in our pulmonary clinic for worsening dyspnea. He was recently diagnosed with antisynthetase syndrome because he had nonspecific interstitial pneumonitis on a surgical lung biopsy and polymyositis associated with anti-Jo-1 and anti-SSA-52 autoantibodies. Along with his worsening dyspnea, he also had a dry cough, lower extremity edema, and abdominal distension. He had gained 11 kg over 1 month. He had been taking prednisone 40 mg daily 2 months prior, which had been recently weaned to 20 mg daily. He had also been on mycophenolate mofetil but had recently discontinued it on his own.

Figures in this Article

The patient was afebrile and tachycardic (126 beats/min), with a BP of 117/87 mm Hg. He was tachypneic (21 breaths/min), requiring 4 L/min of oxygen at rest to maintain oxygen saturation as measured by pulse oximetry (Spo2) > 92%. He had previously required oxygen only on exertion (3-4 L/min) to maintain Spo2 > 92%. He had fine inspiratory crackles bilaterally. He had normal heart sounds without murmurs or rubs. He had asymmetric pitting edema extending to his knees, greater on the right compared with the left. Distal extremities were cool to touch. He had scaly hands and thickened skin over his metacarpophalangeal joints. He had no new rashes or inflamed joints.

An ECG revealed atrial flutter with 2:1 conduction. There was neither electrical alternans nor low voltages. He was sent to the ED, where he became dyspneic, hypotensive, and clammy after receiving IV metoprolol. He was given 2 L of IV fluids, and a norepinephrine drip was started. He became progressively more hypoxemic, needing 15 L/min oxygen via a nonrebreather to maintain Spo2 > 90%. His brain natriuretic peptide level was 185 pg/mL (normal < 100). His arterial blood gas results showed a pH of 7.38, Paco2 of 29, and Pao2 of 151, suggesting an elevated alveolar-arterial gradient. His troponin peaked at 0.12 ng/mL (normal < 0.03 ng/mL).

A contrast-enhanced chest CT scan showed ground-glass opacities superimposed on his underlying nonspecific interstitial pneumonitis, four-chamber cardiac enlargement, but no central pulmonary embolism (Fig 1). On ICU admission, his left ventricular ejection fraction estimated by transthoracic echocardiography was 10% to 15% (compared with 45% 2 months prior). He had severe global hypokinesis, marked right ventricular enlargement, and severe right ventricular dysfunction. He had biatrial enlargement, a dilated inferior vena cava, and an estimated pulmonary artery systolic pressure of 35 to 40 mm Hg. He had a trace pericardial effusion and a negative shunt study result. Venous oxygen saturation from an internal jugular central venous catheter was low (28%).

Figure Jump LinkFigure 1 –  A, B, CT scan of the chest shows worsening bibasilar ground-glass opacities and new bilateral pleural effusions (A) superimposed on changes consistent with nonspecific interstitial pneumonitis that were present on a scan 1 y prior to the admission (B). The overall contrast transit time was delayed.Grahic Jump Location
What is the probable cause of worsening dyspnea?
What studies would confirm the diagnosis?
Diagnosis: Myocarditis secondary to antisynthetase syndrome. This can be confirmed by endomyocardial biopsy or contrast-enhanced cardiac MRI.

The reported incidence of cardiac involvement among patients with polymyositis/dermatomyositis (PM/DM) varies between 9% to 72%. This variation is likely attributable to the diagnostic test used. A subgroup of patients with PM/DM have antisynthetase syndrome (ASS), which is a distinct clinical phenotype composed of inflammatory myopathy, interstitial lung disease, Raynaud phenomenon, hyperkeratotic skin changes (mechanic’s hands), and nonerosive arthritis in patients who have antibodies against aminoacyl transfer RNA synthetases. The cardiac involvement in these patients is usually subclinical. Nevertheless, one-third of these patients have acute myocarditis on autopsy. This discrepancy is further compounded by the lack of correlation between the severity of the illness and cardiac involvement, which may happen even when the PM/DM is in remission. Lymphocytic infiltration, active myocarditis, contraction band necrosis, and fibrosis of the conduction system can occur, which partly explains why cardiac involvement is the antecedent cause of death in at least 10% to 20% of patients with PM/DM.

Given its subclinical yet lethal nature, investigators have had variable success in identifying biomarkers of myocarditis in PM/DM. Elevated creatine kinase-MB (isoenzyme) and troponins have historically been touted as markers of myocardial involvement. Nevertheless, regenerating skeletal muscles also produce creatine kinase-MB (isoenzyme) and troponin T, reducing the specificity of these biomarkers in myositis. On the other hand, troponin I is more specific for myocardial damage; it has been found to be positive in only 2.5% of patients with myositis. Hence, persistently elevated troponin I levels in a patient with myositis/ASS should raise a red flag for ongoing myocardial injury.

Echocardiographic abnormalities have been identified in 14% to 62% of the patients with PM/DM. Transthoracic echocardiography can identify chamber hypertrophy and/or enlargement, diastolic dysfunction, hypokinesis, valvular abnormalities, pericardial involvement, and elevation of pulmonary pressures, all of which can be seen with underlying autoimmune myopathies. Yet, the changes associated with inflammation cannot be reliably detected. Hence, gadolinium-diethylenetriamine pentaacetic acid-enhanced cardiac MRI has been increasingly used to identify cardiac involvement in these patients. MRI can help to noninvasively identify the location and extent of myocardial inflammation and can serve as a roadmap if a biopsy is deemed necessary. When compared with endomyocardial biopsy, the diagnostic sensitivity, specificity, and accuracy of cardiac MRI has been found to be 76%, 54%, and 68%, respectively, in all patients with suspected acute or chronic myocarditis. The best diagnostic performance has been observed in patients with suspected acute myocarditis (sensitivity, 81%; specificity, 71%; and accuracy, 79%). Importantly, the kinetics of the characteristic contrast enhancement on MRI markedly improves after the appropriate treatment, suggesting this could be a useful biomarker for diagnosis and response to therapy.

IV high-dose glucocorticoids have been used with considerable success, and clinical improvement is often seen within 72 h. This is usually followed by a prolonged, tapered course over months, along with a steroid-sparing agent such as cyclophosphamide, azathioprine, or mycophenolate mofetil. However, some patients do not respond and need more aggressive therapies. Rituximab has recently been successfully used, with remission persisting even beyond 6 months. Despite resulting in overall clinical improvement, medical therapies may not prevent all complications of cardiac involvement in asymptomatic patients, especially arrhythmias. Hence, periodic follow-up is necessary, with repeat testing to document resolution.

Clinical Course

The patient was cardioverted out of atrial flutter and started on amiodarone, dobutamine, heparin, and furosemide drips. A Swan-Ganz catheter and an intraaortic balloon pump were used to manage his cardiogenic shock. On retrospective review, he had elevated serum troponin I levels while being evaluated during his previous episodes of dyspnea prior to his acute presentation, suggesting he had uncontrolled subclinical myocarditis (Fig 2). Hence, given the overall picture, he was diagnosed with myocarditis secondary to ASS. He was given IV methylprednisone 1,000 mg daily for 3 days. His hemodynamic status improved, and he was weaned off the balloon pump. His oxygen requirement reduced to 3 L/min, which was what he used on exertion at home. The diagnosis was strongly supported by gadolinium-diethylenetriamine pentaacetic acid-enhanced cardiac MRI, which showed delayed mesocardial enhancement in the posterior and lateral left ventricular wall, consistent with an infiltrative cardiomyopathy (Fig 3). He was subsequently given a single dose of rituximab 1,000 mg IV, and mycophenolate mofetil was increased to 1,000 mg bid. He was also prescribed prednisone 60 mg daily. He followed up in clinic 1 week after discharge, ambulating using the same amount of oxygen and feeling well off inotropic support. He was given another dose of rituximab 2 weeks after the first dose, which he tolerated well.

Figure Jump LinkFigure 2 –  Trends in troponin-I levels. Troponin trends since initial presentation, which are suggestive of ongoing subclinical myocardial injury in the setting of antisynthetase syndrome.Grahic Jump Location
Figure Jump LinkFigure 3 –  Two-chambered delayed contrast-enhanced cardiac MRI demonstrating posterior wall enhancement of the myocardium in the subepicardial region (white horizontal arrow), sparing the subendocardial region (white vertical arrows). Note the peripheral area of chemical-shift artifact outside the epicardium that results from a small pericardial effusion (dotted arrows), which may be confused for the myocardium. This overall pattern would be atypical for ischemia and is compatible with myocarditis.Grahic Jump Location

  • 1. Myocardial involvement is often subclinical in patients with antisynthetase syndrome but is a poor prognostic factor and a major cause of death.

  • 2. Persistently elevated troponin I in these patients should raise a red flag for ongoing myocardial injury.

  • 3. Cardiac MRI is a useful alternative to endomyocardial biopsy for the diagnosis of acute myocarditis and can also be used to identify response to therapy.

  • 4. Even fulminant myocarditis can respond to high-dose, IV steroids within 72 h. In refractory cases, rituximab has been used with considerable success, resulting in sustained remission.

Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Other contributions: CHEST worked with the authors to ensure that the Journal policies on patient consent to report information were met.

Smith SC, Ladenson JH, Mason JW, Jaffe AS. Elevations of cardiac troponin I associated with myocarditis. Experimental and clinical correlates. Circulation. 1997;95(1):163-168. [CrossRef] [PubMed]
 
Kiely PD, Bruckner FE, Nisbet JA, Daghir A. Serum skeletal troponin I in inflammatory muscle disease: relation to creatine kinase, CKMB and cardiac troponin I. Ann Rheum Dis. 2000;59(9):750-751. [CrossRef] [PubMed]
 
Targoff IN. Laboratory testing in the diagnosis and management of idiopathic inflammatory myopathies. Rheum Dis Clin North Am. 2002;28(4):859-890. [CrossRef] [PubMed]
 
Allanore Y, Vignaux O, Arnaud L, et al. Effects of corticosteroids and immunosuppressors on idiopathic inflammatory myopathy related myocarditis evaluated by magnetic resonance imaging. Ann Rheum Dis. 2006;65(2):249-252. [CrossRef] [PubMed]
 
Lundberg IE. The heart in dermatomyositis and polymyositis. Rheumatology (Oxford). 2006;45(4suppl 4):iv18-iv21. [PubMed]
 
Touma Z, Arayssi T, Kibbi L, Masri AF. Successful treatment of cardiac involvement in dermatomyositis with rituximab. Joint Bone Spine. 2008;75(3):334-337. [CrossRef] [PubMed]
 
Lurz P, Eitel I, Adam J, et al. Diagnostic performance of CMR imaging compared with EMB in patients with suspected myocarditis. JACC Cardiovasc Imaging. 2012;5(5):513-524. [CrossRef] [PubMed]
 
Zhang L, Wang GC, Ma L, Zu N. Cardiac involvement in adult polymyositis or dermatomyositis: a systematic review. Clin Cardiol. 2012;35(11):686-691. [PubMed]
 
Chatterjee S, Prayson R, Farver C. Antisynthetase syndrome: not just an inflammatory myopathy. Cleve Clin J Med. 2013;80(10):655-666. [CrossRef] [PubMed]
 
Sharma K, Orbai AM, Desai D, et al. Brief report: antisynthetase syndrome-associated myocarditis. J Card Fail. 2014;20(12):939-945. [CrossRef] [PubMed]
 

Figures

Figure Jump LinkFigure 1 –  A, B, CT scan of the chest shows worsening bibasilar ground-glass opacities and new bilateral pleural effusions (A) superimposed on changes consistent with nonspecific interstitial pneumonitis that were present on a scan 1 y prior to the admission (B). The overall contrast transit time was delayed.Grahic Jump Location
Figure Jump LinkFigure 2 –  Trends in troponin-I levels. Troponin trends since initial presentation, which are suggestive of ongoing subclinical myocardial injury in the setting of antisynthetase syndrome.Grahic Jump Location
Figure Jump LinkFigure 3 –  Two-chambered delayed contrast-enhanced cardiac MRI demonstrating posterior wall enhancement of the myocardium in the subepicardial region (white horizontal arrow), sparing the subendocardial region (white vertical arrows). Note the peripheral area of chemical-shift artifact outside the epicardium that results from a small pericardial effusion (dotted arrows), which may be confused for the myocardium. This overall pattern would be atypical for ischemia and is compatible with myocarditis.Grahic Jump Location

Tables

Suggested Readings

Smith SC, Ladenson JH, Mason JW, Jaffe AS. Elevations of cardiac troponin I associated with myocarditis. Experimental and clinical correlates. Circulation. 1997;95(1):163-168. [CrossRef] [PubMed]
 
Kiely PD, Bruckner FE, Nisbet JA, Daghir A. Serum skeletal troponin I in inflammatory muscle disease: relation to creatine kinase, CKMB and cardiac troponin I. Ann Rheum Dis. 2000;59(9):750-751. [CrossRef] [PubMed]
 
Targoff IN. Laboratory testing in the diagnosis and management of idiopathic inflammatory myopathies. Rheum Dis Clin North Am. 2002;28(4):859-890. [CrossRef] [PubMed]
 
Allanore Y, Vignaux O, Arnaud L, et al. Effects of corticosteroids and immunosuppressors on idiopathic inflammatory myopathy related myocarditis evaluated by magnetic resonance imaging. Ann Rheum Dis. 2006;65(2):249-252. [CrossRef] [PubMed]
 
Lundberg IE. The heart in dermatomyositis and polymyositis. Rheumatology (Oxford). 2006;45(4suppl 4):iv18-iv21. [PubMed]
 
Touma Z, Arayssi T, Kibbi L, Masri AF. Successful treatment of cardiac involvement in dermatomyositis with rituximab. Joint Bone Spine. 2008;75(3):334-337. [CrossRef] [PubMed]
 
Lurz P, Eitel I, Adam J, et al. Diagnostic performance of CMR imaging compared with EMB in patients with suspected myocarditis. JACC Cardiovasc Imaging. 2012;5(5):513-524. [CrossRef] [PubMed]
 
Zhang L, Wang GC, Ma L, Zu N. Cardiac involvement in adult polymyositis or dermatomyositis: a systematic review. Clin Cardiol. 2012;35(11):686-691. [PubMed]
 
Chatterjee S, Prayson R, Farver C. Antisynthetase syndrome: not just an inflammatory myopathy. Cleve Clin J Med. 2013;80(10):655-666. [CrossRef] [PubMed]
 
Sharma K, Orbai AM, Desai D, et al. Brief report: antisynthetase syndrome-associated myocarditis. J Card Fail. 2014;20(12):939-945. [CrossRef] [PubMed]
 
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