http://informahealthcare.com/mor ISSN 1439-7595 (print), 1439-7609 (online) Mod Rheumatol, 2013; Early Online: 1–4 © 2013 Japan College of Rheumatology DOI: 10.3109/14397595.2013.843744
CASE REPORT
Sinus node dysfunction in adult systemic lupus erythematosus flare: A case report Baris Yilmazer, Mursel Sali, Fulya Cosan, and Ayse Cefle
Mod Rheumatol Downloaded from informahealthcare.com by Lakehead University on 03/19/15 For personal use only.
Department of Rheumatology, Kocaeli University, Faculty of Medicine, Kocaeli, Turkey Abstract
Keywords
Cardiac involvement can affect up to 50% of the systemic lupus erythematosus (SLE) patients but conduction system disturbances in SLE are less commonly described. For an early detection of this complication in the acute phase of SLE a whole cardiovascular examination and periodic electrocardiographic monitoring are recommended. We describe a patient who was diagnosed with flare up of lupus activity manifesting as sinus node dysfunction presenting as profound sinus bradycardia. She was successfully treated with high-dose methylprednisolone therapy.
Methylprednisolone, Sinus bradycardia, Systemic lupus erythematosus
Introduction Cardiac involvement in systemic lupus erythematosus (SLE) has been well documented and may include pericarditis, myocarditis, valvular abnormalities, coronary heart disease and conduction disorders [1]. Immuno-mediated damage, atherosclerotic complications and even adverse effect of the treatment (chloroquineinduced cardiotoxicity) seem to be the mechanisms involved more frequently in the pathophysiology of those disturbances [2–5]. Generally, the literature has not given proper clinical attention to the development of arrhythmias in those patients [6]. Up to now, the evidence related to electrocardiographic disturbances is limited to studies with a small number of patients even though cardiac involvement can affect up to 50% of the cases [7]. To the best of our knowledge, isolated sinoatrial node involvement with sinusal bradycardia has been previously reported just in one case in the literature as an initial presentation of SLE in adults [8].
Case report A 24-year-old female presented with a 10-day history of fever, generalized myalgia, arthralgia, photosensitivity, facial rash, arthritis and dizziness. The patient had a 7-year history of SLE manifested by photosensitivity, malar rash, oral ulcers, arthritis, a positive ANA test and also a 4-year history of WHO class III focal proliferative nephritis which was diagnosed in a different clinic. The patient was on monthly pulse therapy with cyclophosphamide (1000 mg), in the fifth cycle. But she had not gone for control since then. When the patient was admitted to our clinic, she was using hydroxychloroquine 200 mg/d and prednisolone 5 mg/d. Her physical examination in our clinic showed that the temperature was 36°C, the blood pressure was 80/60 mm Hg, the pulse rate was 40 beats/min and the respiratory rate was 16/min. Correspondence to: Dr. Barış Yılmazer, MD, Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Kocaeli University, Umuttepe 41380, Kocaeli, Turkey. E-mail: drbarisyilmazer@ hotmail.com
History Received 5 November 2012 Accepted 2 May 2013 Published online 21 October 2013
The classical 12-lead ECG revealed sinus bradycardia (Figure 1a). The laboratory findings before the treatment are displayed in Table 1. Echocardiography showed normal valvular structure and left systolic and diastolic function. The right ventricular function of the patient was normal, too. Holter ECG monitoring showed her sinusal bradycardia and her mean heart rate was 52 beats/min and QT interval was 410 ms and it was normal. There was no ischemic evidence in ECG so coronary angiography was not done. Myocardial infarction, myocarditis, ischemic heart disease, hypothermia, hypothyroidism, electrolyte imbalance and drug-related bradycardia were excluded by clinical findings and laboratory data. Based on the clinical presentation and laboratory data, sinus node dysfunction and lupus nephritis flare were diagnosed and the patient was initiated with 1 g monthly pulse cyclophosphamide and 1000 mg/d 3 days pulse intravenous methylprednisolone infusion. After high-dose intravenous methylprednisolone infusion, it was observed that her abnormal ECG became normal (Figure 1b). And 3 days later, oral methylprednisolone was continued with 60 mg/d along 4 weeks. After this period of time, methylprednisolone dose gradually reduced until a maintenance dose of 4 mg daily. The laboratory examination which was done after a week showed the following results: white blood cell count, 8550/mm3; erythrocyte sedimentation rate, 18 mm/h [0–20]; C-reactive protein, 0.2 mg/dL [0–0.5]. In the tests that were done during her follow-up, C3 was 99 [90–180 mg/dL] and anti-doublestranded DNA antibody by ELISA was 962 U/mL [N ⬍ 100]. The control echocardiography which was done after 3 months showed that left and right ventricular systolic and diastolic function were normal. The patient is still being followed up successfully with 1 g monthly pulse cyclophosphamide and low dose of oral steroid therapy in our outpatient clinic. During this follow-up sinusal bradycardia was not occured in the patient. The last laboratory examination showed the following results: white blood cell count, 10800/mm3; C-reactive protein, 2.1 mg/dL [0–0.5]; C3, 148 [90–180 mg/dL] and anti-doublestranded DNA antibody by ELISA, negative.
B. Yilmazer et al.
Mod Rheumatol, 2013; Early Online: 1–4
Mod Rheumatol Downloaded from informahealthcare.com by Lakehead University on 03/19/15 For personal use only.
2
Figure 1 a: ECG in the systemic lupus erythematosus flare showed sinus bradycardia (ventricular rate ⫽ 40/min). b: ECG after steroid treatment, normal sinus rhythm (ventricular rate ⫽ 75/min).
Discussion SLE is a connective tissue disease that is characterized by the production of auto-antibodies and immune complexes. Up to 50% of the cases can be affected by cardiac involvement [7]. Pericarditis, myocarditis, valvular abnormalities, coronary heart disease and conduction system disturbance are types of
this cardiac involvement which has been described [1]. Cardiac complications may develop either as incidental findings or in association with a lupus flare. Conduction system disturbances in SLE are less commonly described [9]. The mechanism of arrhythmias in SLE has not been completely clarified and they can be associated with the inflammatory process of pericarditis and myocarditis, atherosclerotic myocardial ischemia or a result of
Sinus node dysfunction in adult systemic lupus erythematosus flare
DOI 10.3109/14397595.2013.843744
Mod Rheumatol Downloaded from informahealthcare.com by Lakehead University on 03/19/15 For personal use only.
Table 1. The laboratory findings in our patient before the treatment. Laboratory investigation Patient value White Blood Cell/mm³ 1780 Granulocytes/mm³ 1420 Lymphocytes/mm³ 259 Eosinophils/mm³ 2 Hemoglobin, g/dL 8.1 Platelet/mm³ 152000 Erythrocyte sedimentation rate, mm/h 67 C-reactive protein, mg/dL 2.06 Sodium, mEq/L 137 Potassium, mEq/L 4.3 Calcium, mg/dL 8.8 Blood urea nitrogen, mg/dL 14 Creatinin, mg/dL 0.55 Lactate dehydrogenase, U/L 194 Alanine transaminase, U/L 7 Aspartate transaminase, U/L 14 Total protein, g/dL 6,3 Albumin, g/dL 3,1 Thyroid–stimulating hormone, mIU/L 3,9 Anti–thyroglobulin antibody, IU/mL ⬍ 20 Anti–thyroid peroxidase antibody, 0.1 IU/mL Antinuclear-antibody (ANA) titer 1/100 homogeneous pattern Anti-double-stranded DNA antibody 1513 (antiDs-DNA), IU/mL C3complemet (C3), mg/dL 68 C4 complemet (C4), mg/dL 10.6 Immunoglobulin (Ig) G, mg/dL 1467 Ig A, mg/dL 242 Ig M, mg/dL 102 Negative Extractable Nuclear Antigen Antibodies (Sjogren’s syndrome A/Ro and B/La, Smith) Anti-cardiolipin antibodies, U/mL Negative 24-h urine protein, mg/day 1397 Total Cholesterol, mg/dL 176 Low-density lipoprotein, mg/dL 99.2 Triglyceride, mg/dL 114
Normal range 4600–10200 2000–6900 600–3400 0–700 12.2–18.1 142000–424000 0–20 0–0.5 136–145 3.5–5.1 8.4–10.2 7–25,7 0.6–1.3 125–245 0–55 5–34 6.4–8.3 3.5–5.0 0.55–4.78 0–64 0–9 Negative ⬍ 100 90–180 10–40 694–1618 70–400 60–263 Negative
Negative ⬍ 150 0–200 0–130 0–150
vasculitis of small vessels with collagen and fibrotic deposits that affect the conduction system [2–4]. Abu-Shakra et al. [10], in a study with 665 SLE patients, identified sudden death as the fourth more common cause of death along 20 years of follow-up. In addition to this, Godeau et al. [11] assessed the relationship between the presence of conduction disruption and mortality. A total of 103 SLE patients with active disease were evaluated; after a 10-year follow-up it was seen that conduction disturbances were present in 17.5% of the patients. And when compared with patients with normal ECG, their mortality rate was seen to be significantly higher. Male gender and electrocardiographic changes were identified as independent risk factors for mortality in this disorder by a Chinese study which has been followed up for more than 30 years with 566 SLE patients [12]. Conduction disturbances with high-grade AV block can be observed in the neonatal period of infants born to mothers with SLE. The mechanism of neonatal heart block is considered to be because of transplacental passage of maternal antibodies with injury of the conduction system by a direct cytotoxic effect of anti-Ro or anti-La antibodies [13–14]. In addition to this, high-grade AV block is a rare complication of SLE in adults which may exist as an initial manifestation or as a sign of antimalarial toxicity or an acute flare-up of the disease [8]. Anti-Ro, anti-La and anti-RNP antibodies have been introduced as markers of cardiac involvement in adults with SLE [8].
3
In the present case, we addressed the issue of bradycardia in a young female. Further evaluation of the bradycardia is required; because if not treated, it is possible that a serious underlying disorder and unfavorable outcome may occur. A detailed history, ECG follow-up and echocardiography, is needed for the differential diagnosis of bradycardia. Holter ECG monitoring is suggested for the evaluation of suspected bradycardia or for a further investigation of documented bradycardia [15]. Cardiac electrophysiological study is an invasive tool for the evaluation of sinus node and cardiac conduction system. It is suggested when the bradycardias exist paroxysmally or cannot be assessed by non-invasive monitoring methods or when a serious underlying mechanism is suspected [16]. Laboratory tests for hypothyroidism, infection, inflammatory disease and connective tissue diseases should be performed. Sinus bradycardia may be a sign of sinus node dysfunction, ischemic heart disease, infiltrative disorders, infections, inflammatory disease, hypothermia, hypothyroidism, raised intracranial pressure, high vagal tone, electrolyte imbalance and certain drug triggerings [17]. In the present report, the young female had no history of chest pain. There was no evidence of myocardial ischemia or infarction, or cardiac conduction disturbance on ECG. Echocardiography showed normal left ventricular global systolic performance and this situation excluded overt myocarditis. Tests of thyroid function and serum electrolytes were normal, too. There were no clinical manifestations of increased intracranial pressure, no hypothermia or no infection, either. No history of the use of drugs which could result in sinus bradycardia was noticed. High-dose cyclophosphamide may produce congestive heart failure acutely or within 2 weeks of administration; a characteristic histopathologic feature is myocardial edema and hemorrhagic necrosis [18]. Her abnormal ECG totally resolved after high-dose intravenous methylprednisolone infusion and recurrence of bradycardia did not occur. After cyclophosphamide treatment the congestive heart failure finding was not seen and the control echocardiography showed normal systolic and diastolic function. Based on the above findings, short-term isolated sinus node dysfunction presenting as profound sinus bradycardia because of SLE is highly suspected. To the best of our knowledge, isolated sinoatrial node involvement with sinusal bradycardia has been previously reported in just one case [8]. In this case, sinus node involvement with significant bradycardia was an initial presentation of SLE. But in our patient, it was in association with a lupus flare. In summary, sinus node dysfunction with profound bradycardia which is a possible cardiac complication may develop either as incidental finding or in association with a lupus flare. We believe that the underlying mechanisms causing sinus node involvement are similar to AV node involvement in SLE. The mechanisms may be including infiltration of fibrotic granulation tissue secondary to inflammation and small vessel vasculitis. A thorough cardiovascular examination and periodic electrocardiographic monitoring are suggested for an early detection of this complication in the acute phase of SLE.
Conflict of interest None.
References 1. Doria A, Iaccarino L, Sarzi-Puttini P, Atzeni F, Turriel M, Petri M. Cardiac involvement in systemic lupus erythematosus. Lupus. 2005;14:683–6. 2. James TN, Rupe CE, Monto RW. Pathology of the cardıac conductıon system in systemıc lupus erythematosus. Ann Intern Med. 1965;63:402–10. 3. Fonseca E, Crespo M, Sobrino JA. Complete heart block in an adult with systemic lupus erythematosus. Lupus. 1994;3:129–131.
Mod Rheumatol Downloaded from informahealthcare.com by Lakehead University on 03/19/15 For personal use only.
4
B. Yilmazer et al.
4. Bharati S, de la Fuente DJ, Kallen RJ, Freij Y, Lev M. Conduction system in systemic lupus erythematosus with atrioventricular block. Am J Cardiol. 35(2):299–304. 5. Teixeira RA, Filho MM, Benvenuti LA, Costa R, Pedrosa AA, Nishióka SAD. Cardiac damage from chronic use of chloroquine. A case report and review of the literature. Arq Bras Cardiol. 2002;79:85–8. 6. Liautaud S, Khan AJ, Nalamasu SR, Tan IJ, Onwuanyi AE. Variable atrioventricular block in systemic lupus erythematosus. Clin Rheumatol. 2005;24:162–5. 7. D’Cruz D, Khamashta M, Hughes GRV. Cardiovascular manifestations of systemic lupus erythematosus. In: Wallace DJ, Hahn BH, eds. Dubois’ Lupus Erythematosus. Philadelphia: Lippincott William & Wilkins 2001;645–7. 8. Lin Y, Liou YM, Chen JY, Chang KC. Sinus node dysfunction as an initial presentation of adult systemic lupus erythematosus. Lupus. 2011;20:1072–5. 9. Brucato A, Doria A, Frassi M, Castellino G, Franceschini F, Faden D, et al. Pregnancy outcome in 100 women with autoimmune diseases and anti-Ro/SSA antibodies: a prospective controlled study. Lupus. 2002;11(11):716–21. 10. Abu-Shakra M, Urowitz MB, Gladman DD, Gough J. Mortality studies in systemic lupus erythematosus: results from a single center. II. Predictor variables for mortality. J Rheumatol. 1995;22:1265–70.
Mod Rheumatol, 2013; Early Online: 1–4
11. Godeau P, Guillevin L, Fechner J, Bletry O, Herreman G. Disorders of conduction in lupus erythematosus: frequency and incidence in a group of 112 patients. Ann Med Interne (Paris). 1981;132(4):234–40. 12. Xie SK, Feng SF, Fu H. Long term follow-up of patients with systemic lupus erythematosus. J Dermatol. 1998;25(6):367–73. 13. Scott JS, Maddison PJ, Taylor PV, Esscher E, Scott O, Skinner RP. Connective-tissue disease, antibodies to ribonucleoprotein, and congenital heart block. N Engl J Med. 1983;309(4):209–12. 14. Taylor PV, Scott JS, Gerlis LM, Esscher E, Scott O. Maternal antibodies against fetal cardiac antigens in congenital complete heart block. N Engl J Med. 1986;315(11):667–72. 15. Kowey PR, Kocovic DZ. Cardiology patient pages. Ambulatory electrocardiographic recording. Circulation. 2003;108(5):e31–3. 16. Hammill SC, Sugrue DD, Gersh BJ, Porter CB, Osborn MJ, Wood DL, Holmes DR Jr. Clinical intracardiac electrophysiologic testing: technique, diagnostic indications, and therapeutic uses. Mayo Clin Proc. 1986;61(6):478–503. 17. Da Costa D, Brady WJ, Edhouse J. Bradycardias and atrioventricular conduction block. BMJ. 2002;324(7336):535–8. 18. Wynne J. Cardiomyopathy and myocarditis. In: Fauci AS, Braunwald E, Kadper DL, Stephen LH, Longo DL, Jameson JL, Loscalzo J eds. Principles of Internal Medicine. 17th ed. USA: McGraw-Hill; 2008, pp. 1481–88.
CASE REPORT
Sinus node dysfunction in adult systemic lupus erythematosus flare: A case report Baris Yilmazer, Mursel Sali, Fulya Cosan, and Ayse Cefle
Mod Rheumatol Downloaded from informahealthcare.com by Lakehead University on 03/19/15 For personal use only.
Department of Rheumatology, Kocaeli University, Faculty of Medicine, Kocaeli, Turkey Abstract
Keywords
Cardiac involvement can affect up to 50% of the systemic lupus erythematosus (SLE) patients but conduction system disturbances in SLE are less commonly described. For an early detection of this complication in the acute phase of SLE a whole cardiovascular examination and periodic electrocardiographic monitoring are recommended. We describe a patient who was diagnosed with flare up of lupus activity manifesting as sinus node dysfunction presenting as profound sinus bradycardia. She was successfully treated with high-dose methylprednisolone therapy.
Methylprednisolone, Sinus bradycardia, Systemic lupus erythematosus
Introduction Cardiac involvement in systemic lupus erythematosus (SLE) has been well documented and may include pericarditis, myocarditis, valvular abnormalities, coronary heart disease and conduction disorders [1]. Immuno-mediated damage, atherosclerotic complications and even adverse effect of the treatment (chloroquineinduced cardiotoxicity) seem to be the mechanisms involved more frequently in the pathophysiology of those disturbances [2–5]. Generally, the literature has not given proper clinical attention to the development of arrhythmias in those patients [6]. Up to now, the evidence related to electrocardiographic disturbances is limited to studies with a small number of patients even though cardiac involvement can affect up to 50% of the cases [7]. To the best of our knowledge, isolated sinoatrial node involvement with sinusal bradycardia has been previously reported just in one case in the literature as an initial presentation of SLE in adults [8].
Case report A 24-year-old female presented with a 10-day history of fever, generalized myalgia, arthralgia, photosensitivity, facial rash, arthritis and dizziness. The patient had a 7-year history of SLE manifested by photosensitivity, malar rash, oral ulcers, arthritis, a positive ANA test and also a 4-year history of WHO class III focal proliferative nephritis which was diagnosed in a different clinic. The patient was on monthly pulse therapy with cyclophosphamide (1000 mg), in the fifth cycle. But she had not gone for control since then. When the patient was admitted to our clinic, she was using hydroxychloroquine 200 mg/d and prednisolone 5 mg/d. Her physical examination in our clinic showed that the temperature was 36°C, the blood pressure was 80/60 mm Hg, the pulse rate was 40 beats/min and the respiratory rate was 16/min. Correspondence to: Dr. Barış Yılmazer, MD, Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Kocaeli University, Umuttepe 41380, Kocaeli, Turkey. E-mail: drbarisyilmazer@ hotmail.com
History Received 5 November 2012 Accepted 2 May 2013 Published online 21 October 2013
The classical 12-lead ECG revealed sinus bradycardia (Figure 1a). The laboratory findings before the treatment are displayed in Table 1. Echocardiography showed normal valvular structure and left systolic and diastolic function. The right ventricular function of the patient was normal, too. Holter ECG monitoring showed her sinusal bradycardia and her mean heart rate was 52 beats/min and QT interval was 410 ms and it was normal. There was no ischemic evidence in ECG so coronary angiography was not done. Myocardial infarction, myocarditis, ischemic heart disease, hypothermia, hypothyroidism, electrolyte imbalance and drug-related bradycardia were excluded by clinical findings and laboratory data. Based on the clinical presentation and laboratory data, sinus node dysfunction and lupus nephritis flare were diagnosed and the patient was initiated with 1 g monthly pulse cyclophosphamide and 1000 mg/d 3 days pulse intravenous methylprednisolone infusion. After high-dose intravenous methylprednisolone infusion, it was observed that her abnormal ECG became normal (Figure 1b). And 3 days later, oral methylprednisolone was continued with 60 mg/d along 4 weeks. After this period of time, methylprednisolone dose gradually reduced until a maintenance dose of 4 mg daily. The laboratory examination which was done after a week showed the following results: white blood cell count, 8550/mm3; erythrocyte sedimentation rate, 18 mm/h [0–20]; C-reactive protein, 0.2 mg/dL [0–0.5]. In the tests that were done during her follow-up, C3 was 99 [90–180 mg/dL] and anti-doublestranded DNA antibody by ELISA was 962 U/mL [N ⬍ 100]. The control echocardiography which was done after 3 months showed that left and right ventricular systolic and diastolic function were normal. The patient is still being followed up successfully with 1 g monthly pulse cyclophosphamide and low dose of oral steroid therapy in our outpatient clinic. During this follow-up sinusal bradycardia was not occured in the patient. The last laboratory examination showed the following results: white blood cell count, 10800/mm3; C-reactive protein, 2.1 mg/dL [0–0.5]; C3, 148 [90–180 mg/dL] and anti-doublestranded DNA antibody by ELISA, negative.
B. Yilmazer et al.
Mod Rheumatol, 2013; Early Online: 1–4
Mod Rheumatol Downloaded from informahealthcare.com by Lakehead University on 03/19/15 For personal use only.
2
Figure 1 a: ECG in the systemic lupus erythematosus flare showed sinus bradycardia (ventricular rate ⫽ 40/min). b: ECG after steroid treatment, normal sinus rhythm (ventricular rate ⫽ 75/min).
Discussion SLE is a connective tissue disease that is characterized by the production of auto-antibodies and immune complexes. Up to 50% of the cases can be affected by cardiac involvement [7]. Pericarditis, myocarditis, valvular abnormalities, coronary heart disease and conduction system disturbance are types of
this cardiac involvement which has been described [1]. Cardiac complications may develop either as incidental findings or in association with a lupus flare. Conduction system disturbances in SLE are less commonly described [9]. The mechanism of arrhythmias in SLE has not been completely clarified and they can be associated with the inflammatory process of pericarditis and myocarditis, atherosclerotic myocardial ischemia or a result of
Sinus node dysfunction in adult systemic lupus erythematosus flare
DOI 10.3109/14397595.2013.843744
Mod Rheumatol Downloaded from informahealthcare.com by Lakehead University on 03/19/15 For personal use only.
Table 1. The laboratory findings in our patient before the treatment. Laboratory investigation Patient value White Blood Cell/mm³ 1780 Granulocytes/mm³ 1420 Lymphocytes/mm³ 259 Eosinophils/mm³ 2 Hemoglobin, g/dL 8.1 Platelet/mm³ 152000 Erythrocyte sedimentation rate, mm/h 67 C-reactive protein, mg/dL 2.06 Sodium, mEq/L 137 Potassium, mEq/L 4.3 Calcium, mg/dL 8.8 Blood urea nitrogen, mg/dL 14 Creatinin, mg/dL 0.55 Lactate dehydrogenase, U/L 194 Alanine transaminase, U/L 7 Aspartate transaminase, U/L 14 Total protein, g/dL 6,3 Albumin, g/dL 3,1 Thyroid–stimulating hormone, mIU/L 3,9 Anti–thyroglobulin antibody, IU/mL ⬍ 20 Anti–thyroid peroxidase antibody, 0.1 IU/mL Antinuclear-antibody (ANA) titer 1/100 homogeneous pattern Anti-double-stranded DNA antibody 1513 (antiDs-DNA), IU/mL C3complemet (C3), mg/dL 68 C4 complemet (C4), mg/dL 10.6 Immunoglobulin (Ig) G, mg/dL 1467 Ig A, mg/dL 242 Ig M, mg/dL 102 Negative Extractable Nuclear Antigen Antibodies (Sjogren’s syndrome A/Ro and B/La, Smith) Anti-cardiolipin antibodies, U/mL Negative 24-h urine protein, mg/day 1397 Total Cholesterol, mg/dL 176 Low-density lipoprotein, mg/dL 99.2 Triglyceride, mg/dL 114
Normal range 4600–10200 2000–6900 600–3400 0–700 12.2–18.1 142000–424000 0–20 0–0.5 136–145 3.5–5.1 8.4–10.2 7–25,7 0.6–1.3 125–245 0–55 5–34 6.4–8.3 3.5–5.0 0.55–4.78 0–64 0–9 Negative ⬍ 100 90–180 10–40 694–1618 70–400 60–263 Negative
Negative ⬍ 150 0–200 0–130 0–150
vasculitis of small vessels with collagen and fibrotic deposits that affect the conduction system [2–4]. Abu-Shakra et al. [10], in a study with 665 SLE patients, identified sudden death as the fourth more common cause of death along 20 years of follow-up. In addition to this, Godeau et al. [11] assessed the relationship between the presence of conduction disruption and mortality. A total of 103 SLE patients with active disease were evaluated; after a 10-year follow-up it was seen that conduction disturbances were present in 17.5% of the patients. And when compared with patients with normal ECG, their mortality rate was seen to be significantly higher. Male gender and electrocardiographic changes were identified as independent risk factors for mortality in this disorder by a Chinese study which has been followed up for more than 30 years with 566 SLE patients [12]. Conduction disturbances with high-grade AV block can be observed in the neonatal period of infants born to mothers with SLE. The mechanism of neonatal heart block is considered to be because of transplacental passage of maternal antibodies with injury of the conduction system by a direct cytotoxic effect of anti-Ro or anti-La antibodies [13–14]. In addition to this, high-grade AV block is a rare complication of SLE in adults which may exist as an initial manifestation or as a sign of antimalarial toxicity or an acute flare-up of the disease [8]. Anti-Ro, anti-La and anti-RNP antibodies have been introduced as markers of cardiac involvement in adults with SLE [8].
3
In the present case, we addressed the issue of bradycardia in a young female. Further evaluation of the bradycardia is required; because if not treated, it is possible that a serious underlying disorder and unfavorable outcome may occur. A detailed history, ECG follow-up and echocardiography, is needed for the differential diagnosis of bradycardia. Holter ECG monitoring is suggested for the evaluation of suspected bradycardia or for a further investigation of documented bradycardia [15]. Cardiac electrophysiological study is an invasive tool for the evaluation of sinus node and cardiac conduction system. It is suggested when the bradycardias exist paroxysmally or cannot be assessed by non-invasive monitoring methods or when a serious underlying mechanism is suspected [16]. Laboratory tests for hypothyroidism, infection, inflammatory disease and connective tissue diseases should be performed. Sinus bradycardia may be a sign of sinus node dysfunction, ischemic heart disease, infiltrative disorders, infections, inflammatory disease, hypothermia, hypothyroidism, raised intracranial pressure, high vagal tone, electrolyte imbalance and certain drug triggerings [17]. In the present report, the young female had no history of chest pain. There was no evidence of myocardial ischemia or infarction, or cardiac conduction disturbance on ECG. Echocardiography showed normal left ventricular global systolic performance and this situation excluded overt myocarditis. Tests of thyroid function and serum electrolytes were normal, too. There were no clinical manifestations of increased intracranial pressure, no hypothermia or no infection, either. No history of the use of drugs which could result in sinus bradycardia was noticed. High-dose cyclophosphamide may produce congestive heart failure acutely or within 2 weeks of administration; a characteristic histopathologic feature is myocardial edema and hemorrhagic necrosis [18]. Her abnormal ECG totally resolved after high-dose intravenous methylprednisolone infusion and recurrence of bradycardia did not occur. After cyclophosphamide treatment the congestive heart failure finding was not seen and the control echocardiography showed normal systolic and diastolic function. Based on the above findings, short-term isolated sinus node dysfunction presenting as profound sinus bradycardia because of SLE is highly suspected. To the best of our knowledge, isolated sinoatrial node involvement with sinusal bradycardia has been previously reported in just one case [8]. In this case, sinus node involvement with significant bradycardia was an initial presentation of SLE. But in our patient, it was in association with a lupus flare. In summary, sinus node dysfunction with profound bradycardia which is a possible cardiac complication may develop either as incidental finding or in association with a lupus flare. We believe that the underlying mechanisms causing sinus node involvement are similar to AV node involvement in SLE. The mechanisms may be including infiltration of fibrotic granulation tissue secondary to inflammation and small vessel vasculitis. A thorough cardiovascular examination and periodic electrocardiographic monitoring are suggested for an early detection of this complication in the acute phase of SLE.
Conflict of interest None.
References 1. Doria A, Iaccarino L, Sarzi-Puttini P, Atzeni F, Turriel M, Petri M. Cardiac involvement in systemic lupus erythematosus. Lupus. 2005;14:683–6. 2. James TN, Rupe CE, Monto RW. Pathology of the cardıac conductıon system in systemıc lupus erythematosus. Ann Intern Med. 1965;63:402–10. 3. Fonseca E, Crespo M, Sobrino JA. Complete heart block in an adult with systemic lupus erythematosus. Lupus. 1994;3:129–131.
Mod Rheumatol Downloaded from informahealthcare.com by Lakehead University on 03/19/15 For personal use only.
4
B. Yilmazer et al.
4. Bharati S, de la Fuente DJ, Kallen RJ, Freij Y, Lev M. Conduction system in systemic lupus erythematosus with atrioventricular block. Am J Cardiol. 35(2):299–304. 5. Teixeira RA, Filho MM, Benvenuti LA, Costa R, Pedrosa AA, Nishióka SAD. Cardiac damage from chronic use of chloroquine. A case report and review of the literature. Arq Bras Cardiol. 2002;79:85–8. 6. Liautaud S, Khan AJ, Nalamasu SR, Tan IJ, Onwuanyi AE. Variable atrioventricular block in systemic lupus erythematosus. Clin Rheumatol. 2005;24:162–5. 7. D’Cruz D, Khamashta M, Hughes GRV. Cardiovascular manifestations of systemic lupus erythematosus. In: Wallace DJ, Hahn BH, eds. Dubois’ Lupus Erythematosus. Philadelphia: Lippincott William & Wilkins 2001;645–7. 8. Lin Y, Liou YM, Chen JY, Chang KC. Sinus node dysfunction as an initial presentation of adult systemic lupus erythematosus. Lupus. 2011;20:1072–5. 9. Brucato A, Doria A, Frassi M, Castellino G, Franceschini F, Faden D, et al. Pregnancy outcome in 100 women with autoimmune diseases and anti-Ro/SSA antibodies: a prospective controlled study. Lupus. 2002;11(11):716–21. 10. Abu-Shakra M, Urowitz MB, Gladman DD, Gough J. Mortality studies in systemic lupus erythematosus: results from a single center. II. Predictor variables for mortality. J Rheumatol. 1995;22:1265–70.
Mod Rheumatol, 2013; Early Online: 1–4
11. Godeau P, Guillevin L, Fechner J, Bletry O, Herreman G. Disorders of conduction in lupus erythematosus: frequency and incidence in a group of 112 patients. Ann Med Interne (Paris). 1981;132(4):234–40. 12. Xie SK, Feng SF, Fu H. Long term follow-up of patients with systemic lupus erythematosus. J Dermatol. 1998;25(6):367–73. 13. Scott JS, Maddison PJ, Taylor PV, Esscher E, Scott O, Skinner RP. Connective-tissue disease, antibodies to ribonucleoprotein, and congenital heart block. N Engl J Med. 1983;309(4):209–12. 14. Taylor PV, Scott JS, Gerlis LM, Esscher E, Scott O. Maternal antibodies against fetal cardiac antigens in congenital complete heart block. N Engl J Med. 1986;315(11):667–72. 15. Kowey PR, Kocovic DZ. Cardiology patient pages. Ambulatory electrocardiographic recording. Circulation. 2003;108(5):e31–3. 16. Hammill SC, Sugrue DD, Gersh BJ, Porter CB, Osborn MJ, Wood DL, Holmes DR Jr. Clinical intracardiac electrophysiologic testing: technique, diagnostic indications, and therapeutic uses. Mayo Clin Proc. 1986;61(6):478–503. 17. Da Costa D, Brady WJ, Edhouse J. Bradycardias and atrioventricular conduction block. BMJ. 2002;324(7336):535–8. 18. Wynne J. Cardiomyopathy and myocarditis. In: Fauci AS, Braunwald E, Kadper DL, Stephen LH, Longo DL, Jameson JL, Loscalzo J eds. Principles of Internal Medicine. 17th ed. USA: McGraw-Hill; 2008, pp. 1481–88.
