Clin Rheumatol (2005) 24: 162–165 DOI 10.1007/s10067-004-0995-3
CASE REPORT
Sybille Liautaud Æ Ahmed J. Khan Shireesha R. Nalamasu Æ Irene J. Tan Anekwe E. Onwuanyi
Variable atrioventricular block in systemic lupus erythematosus
Received: 18 May 2004 / Accepted: 18 June 2004 / Published online: 26 October 2004 Clinical Rheumatology 2004
Abstract Systemic lupus erythematosus (SLE), a connective tissue disease characterized by the production of auto-antibodies and immune complexes, can affect all organs including the heart. The involvement of the conduction system in SLE has been less commonly described. We report a case of an asymptomatic 45year-old woman with SLE referred to the emergency department (ED) for thrombocytopenia, and was found to have alternating first- and second-degree atrioventricular block (AVB) during routine electrocardiographic screening for hospital admission. Serial electrocardiograms (ECG) done in the ED when compared to those recorded 24 h prior revealed progression from mild first-degree AVB (PR interval = 216 ms) to significant first-degree AVB (PR interval = 510 ms), followed by second-degree AVB
S. Liautaud (&) Division of Pulmonary and Critical Care, Department of Medicine, Mount Sinai School of Medicine, 164-04, 85th Avenue, Jamaica, NY 11432, USA E-mail:
[email protected] A. J. Khan Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Wayne State University School of Medicine, Detroit, MI, USA S. R. Nalamasu Mercy Hospital, Grayling, MI, USA I. J. Tan Division of Rheumatology, Department of Medicine, Mount Sinai School of Medicine, Queens Hospital Center, Jamaica, NY, USA A. E. Onwuanyi Section of Cardiology and Clinical Research Center, Morehouse School of Medicine, Atlanta, GA, USA
(Mobitz type I—Wenckebach phenomenon). The conduction abnormalities recorded over a 28-h period resolved with corticosteroid treatment. Review of the literature on the disruption of the cardiac conduction system in SLE is discussed. Keywords AntiRo/SSa Æ Atrioventricular block Æ Cardiac conduction abnormalities Æ Lupus flare Æ Steroids Æ Systemic lupus erythematosus
Abbreviations ANA: Antinuclear antibody Æ AV: Atrioventricula Æ AVB: Atrioventricular block Æ BBB: Bundle branch block Æ CHB: Complete heart block Æ CK-MB: Creatine kinase MB fraction Æ dsDNA: Double-stranded deoxyribonucleic acid Æ ECG: Electrocardiogram(s) Æ ED: Emergency department Æ La/SS-B: Sjogren syndrome associated antigen B Æ RNP: Ribonucleoprotein Æ Ro/SS-A: Sjogren syndrome associated antigen A Æ SLE: Systemic lupus erythematosus Æ Sm: Smith antibody
Introduction Systemic lupus erythematosus (SLE) is a connective tissue disease characterized by the production of autoantibodies and immune complexes. SLE can affect any organ system including the heart. The involvement of the heart may be diffuse, or localized to a particular portion of the heart, such as the pericardium, the myocardium, the endocardium/the valves, the conduction system, or the coronary arteries. Prevalence of cardiac involvement in SLE varies according to whether a clinical or pathologic series is being considered. Overall, the prevalence of cardiac involvement in SLE is estimated to be more than 50% [1, 2]. Prevalence of pericarditis is reported as 12–40%, myocarditis 10%, and endocarditis 13–74% [1–3]. Conduction abnormalities in association
163
with SLE is less commonly described [1, 4, 5]. We report a case and review the literature on the derangement of cardiac conduction system in SLE.
Report of a case An asymptomatic 45-year-old woman was seen at the Primary Care Clinic for regular follow up. Blood tests and electrocardiogram (ECG) were obtained. The next day she was called to come to the emergency department (ED) for incidental finding of thrombocytopenia. While in the ED, she admits to having progressive fatigue and polyarthralgias while taking prednisone 5 mg daily. Review of systems was otherwise unrevealing. Four years earlier, following the evaluation for polyarthritis and myositis, the patient was diagnosed with SLE [6]. Laboratory findings at the time included hemolytic anemia, thrombocytopenia, positive antinuclear antibodies (ANA 1:280 in homogeneous pattern), positive anti-Sm, anti-Ro/SS-A, anti-RNP antibodies, and low serum complement levels. This time, her physical examination was unremarkable. Her temperature was 97.8F, blood pressure was 88/60 mm Hg, pulse rate was 68 beats/min, and her respiratory rate was 16/min. There was no alopecia, rash, oral ulcers, gum bleeding, petechiae, or ecchymosis. No lymphadenopathy was appreciated. Her lungs were clear to auscultation with some vesicular breath sounds. The heart sounds were normal with no gallops, murmur or rub. Abdominal examination was normal and rectal examination was heme-negative for occult blood. Musculoskeletal and neurological examinations were unremarkable. Laboratory investigations showed white blood cell count, 3.9·109/l; hemoglobin, 10.6 g/dl; hematocrit, 32.3%; platelet count, 10·109/l; sodium, 144 mEq/l; potassium, 4.6 mEq/l; chloride, 109 mEq/l; bicarbonate, 26 mEq/l; blood urea nitrogen, 16 mg/dl; serum
Fig. 1 a Routine ECG ordered by the clinic showing mild first-degree AVB. b Routine ECG in the ED 24 h later showing significant first-degree AVB. c Follow up ECG in the ED 4 h later showing progression to seconddegree AVB, Mobitz-Type I, Wenckebach phenomenon
creatinine, 0.9 mg/dl; magnesium, 1.7 mg/dl; and calcium, 9.9 mg/dl. Prothrombin and partial thromboplastin times were normal at 11.2 and 24.3 s, respectively. Urinalysis did not reveal any proteinuria or hematuria. The serum C3 and C4 complement levels were low, 79 mg/dl (104–187 mg/dl) and 11 mg/dl (21–87 mg/dl), respectively. Lyme titers were negative. Routine screening ECG in the ED revealed sinus rhythm at 65 beats/min with significant first-degree atrioventricular block (AVB). A comparison was made to an ECG recorded 24 h prior to ED presentation, which revealed sinus rhythm with mild first-degree AVB; the PR interval was 216 ms (Fig. 1a). The initial ECG in the ED showed sinus rhythm with progression to more significant first-degree AVB; the PR interval was 510 ms (Fig. 1b). Subsequent ECG 4 h later demonstrated sinus rhythm with further progression to second-degree AVB (Mobitz type I or Wenckebach phenomenon, in which the P wave and QRS complex get farther apart in successive cycles until the P wave is not followed by a QRS response) (Fig. 1c). Upon repeated questioning, the patient denied any chest pain, dyspnea, dizziness, palpitation, diaphoresis, nausea, or vomiting. She was admitted to the cardiac care unit with a diagnosis of progressive AVB and lupus flare. The patient did not have any clinical evidence of myocarditis (absence of fever, chest pain, diffuse ST-T abnormalities or positive creatine kinase MB fraction (CK-MB)); and acute myocardial infarction was excluded. A 2-D ECG was normal. Treatment with corticosteroids was initiated first with intravenous hydrocortisone 100 mg every 8 h for three doses, followed by oral prednisone 30 mg twice daily. The second-degree AVB reverted back to first-degree AVB, and the first-degree AVB resolved completely within 3 days of therapy. She experienced concurrent improvement of the fatigue, polyarthralgias, pancytopenia, and the low serum complements.
164
Discussion Several types of cardiac conduction abnormalities have been described in SLE. Commonly reported conduction disturbances include AVB, such as first- and seconddegree blocks; and intraventricular conduction defects such as bundle branch blocks (BBB) [1, 5]. Complete or third-degree heart block (CHB) has been rarely reported [3, 7–14]. Conduction defects are seen either as incidental findings or in association with a lupus flare [5, 7]. In general, derangement of the cardiac conduction system in SLE more commonly affect the young and the middle-age females. These abnormalities tend to occur later in the course of SLE with an average of 3–20 years of established lupus. Occasionally, however, conduction defects may occur as the initial manifestation of SLE [7, 11]. Systemic lupus erythematosus-associated conduction abnormalities may often resolve spontaneously and may then recur. Consequently, making the diagnosis of SLErelated conduction abnormality may be difficult since the interval ECG may be normal [7, 9, 11, 13]. Godeau et al. [5, 7], in their review of the conduction defects reported in lupus patients, described a slowly progressive involvement of the conduction system over years [6]. In the five cases of CHB reported in their series, left anterior hemi-block followed by right BBB were the initial conduction abnormalities in four cases; and progression to more severe conduction abnormalities occurred over several months [6]. Although conduction disturbances may occur in a slowly progressive manner, incidents of syncope as a result of acute onset of CHB have been reported [3, 7, 9–13]. Our patient developed a progressive AVB in a matter of 24–28 h without any associated cardiac symptoms, and in the clinical setting of a lupus flare. We were struck by the varying severity of the AVB in this patient that resolved with corticosteroid therapy. Similar variability in the severity of atrioventricular (AV) conduction block can be seen in patients with ischemic heart disease. Our patient had a normal stress test several months earlier as part of a work up for a left-sided reproducible chest pain of 2-year duration. The clinical implication of progressive AVB seen in our patient is that, given the lack of cardiac symptomatology, the prevalence of cardiac conduction abnormalities in the form of variable first- and seconddegree AVB may be much higher in SLE than reported in the literature. The etiology of the conduction abnormality in SLE has been linked to an immune-mediated necrotizing arteritis and collagen changes, resulting in focal degeneration and fibrosis of the conduction tissue [4, 7, 9, 14]. Various antibodies have been identified in association with different types of conduction derangements. Researchers have noted a frequent association of maternal anti-Ro/SS-A antibody with congenital CHB in infants [15–19]. Although such association of anti-Ro/ SS-A antibody with CHB has not been demonstrated in
adults, less severe forms of conduction derangement in adults with SLE have been described. Logar et al. [20], in a prospective study involving 67 patients with SLE found a higher incidence of myocarditis and conduction abnormalities in patients with anti-Ro/SS-A antibody. In this series, three of the patients with high-degree heart block had anti-Ro/SS-A antibody [20]. Other antibodies found in association with conduction disturbances in lupus patients include the anti-U1 RNP antibody, which was reported in lupus patients with myocarditis and CHB [3, 8, 9]. The potential implication is that antibodies such as the anti-Ro/SS-A and anti-U1 RNP antibodies may be used as markers of susceptibility for developing clinically significant conduction abnormalities in patients with SLE. Unfortunately, we did not have the results of anti-Ro/SS-A, anti-La/SS-B, anti-Sm, anti-RNP, and anti-dsDNA antibodies for our patient during this admission. While evaluating lupus patients with conduction derangement, it is essential to exclude other causes of conduction abnormalities such as medications. In particular, the antimalarial medications, such as chloroquine and hydroxychloroquine, used in the treatment of SLE have also been associated with AV conduction abnormality [14, 21, 22]. Our patient was not taking any medication other than prednisone. There is currently no consensus regarding the appropriate treatment of cardiac conduction abnormality in SLE patients. In some cases, such as patients with lupus flare and AV conduction abnormalities, treatment with intravenous corticosteroid has been successful [3, 7]. Permanent pacemakers have also been implanted in some patients with high degree AV block [7–10, 12] This case is remarkable for capturing progressive worsening of AV conduction defect over a 28-h period, which resolved after treatment with corticosteroids. In our review of the literature, there were only two other reports describing similar occurrence in lupus patients [3, 21]. In conclusion, cardiac conduction abnormalities associated with SLE appears to be more frequent than generally reported. Clinical studies are needed to determine the true prevalence of conduction abnormality in SLE. Furthermore, the identification of surrogate markers in the adult patients with SLE may be useful for risk stratification and treatment.
References 1. Moder KG, Miller TD, Tazelaar HD (1999) Cardiac involvement in systemic lupus erythematosus. Mayo Clin Proc 74:275– 284 2. Chang RW (1982) Cardiac manifestations of SLE. Clin Rheum Dis 8:197–205 3. Bilazarian SD, Taylor AJ, Brezinski D, Hochberg MC, Guarnieri T et al (1989) High-grade atrioventricular heart block in an adult with systemic lupus erythematosus: the association of nuclear ribonucleoprotein (U1 RNP) antibodies, a case report and review of the literature. Arthritis Rheum 32:1170–1174
165 4. James TN, Rupe CE, Monto RW (1965) Pathology of cardiac conduction system in systemic lupus erythematosus. Ann Intern Med 63:402–410 5. Godeau P, Guillevin L, Fechner J, Herreman G, Wechsler B (1981) Cardiac involvement in systemic lupus erythematosus. 103 cases (in French). Nouv Presse Med 10:2175–2178 6. Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ et al (1982) The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 25:1271–1277 7. Godeau P, Guillevin L, Fechner J, Bletry O, Herreman G (1981) Disorders of conduction in lupus erythematosus: frequency and incidence in a group of 112 patients (in French). Ann Med Interne (Paris) 132: 234–240 8. Mevorach D, Raz E, Shalev O, Steiner I, Ben-Chetrit E (1993) Complete heart block and seizures in an adult with systemic lupus erythematosus: a possible pathophysiologic role for antiSSA/Ro and anti-SSB/La autoantibodies. Arthritis Rheum 36:259–262 9. Fonseca E, Crespo M, Sobrino JA (1994) Complete heart block in an adult with systemic lupus erythematosus. Lupus 3:129– 131 10. Hover AR, Koppes GM (1979) Atrial standstill and complete heart block in systemic lupus erythematosus. Chest 76:230–231 11. Maier WP, Ramirez HE, Miller SB (1987) Complete heart block as the initial manifestation of systemic lupus erythematosus. Arch Intern Med 147:170–171 12. Martinez-Costa X, Ordi J, Barbera J, Selva A, Bosch J et al (1991) High grade atrioventricular heart block in 2 adults with systemic lupus erythematosus. J Rheumatol 18:1926–1928 13. Moffit GR (1965) Complete atrioventricular dissociation with Stoke-Adams attacks due to disseminated lupus erythematosus. Ann Intern Med 63:508–511
14. Bharati S, de la Fuente DJ, Kallen RJ, Freij Y, Lev M (1975) Conduction system in systemic lupus erythematosus with atrioventricular block. Am J Cardiol 35:299–304 15. Scott JS, Maddison PJ, Taylor PV, Esscher E, Scott O et al (1983) Connective tissue disease, antibodies to ribonucleoprotein, and congenital heart block. N Engl J Med 309:209–212 16. Taylor PV, Scott JS, Gerlis LM, Esscher E, Scott O (1986) Maternal antibodies against fetal cardiac antigens in congenital complete heart block. N Engl J Med 315:667–672 17. Lee LA, Coulter S, Erner S, Chu H (1987) Cardiac immunoglobin deposition in congenital complete heart block associated with maternal anti-Ro autoantibodies. Am J Med 83:793–796 18. Deng JS, Bair LW Jr, Shen-Schwarz S, Ramsey-Goldman R, Medsger T Jr (1987) Localization of Ro (SS-A) antigen in the cardiac conduction system. Arthritis Rheum 30:1232–1238 19. Alexander E, Buyon JP, Provost TT, Guarnieri T (1992) AntiRo/SS-A antibodies on the pathophysiology of congenital heart block in neonatal lupus syndrome, an experimental model. In vitro electrophysiologic and immunocytochemical studies. Arthritis Rheum 35:176–189 20. Logar D, Kveder T, Rozman B, Dobovisek J (1990) Possible association between anti-Ro antibodies and myocarditis or cardiac conduction defects in adults with systemic lupus erythematosus. Ann Rheum Dis 49:627–629 21. Comin-Colet J, Sanchez-Corral MA, Alegre-Sancho JJ, Valverde J, Lopez-Gomez D et al (2001) Complete heart block in an adult with systemic lupus erythematosus and recent onset of hydroxychloroquine therapy. Lupus 10:59–62 22. Reuss-Borst M, Berner B, Wulf G, Muller GA (1999 Complete heart block as a rare complication of treatment with chloroquine. J Rheumatol 26:1394–1395
