Anti-Ro Antibodies and Reversible Atrioventricular Block
N Engl J Med 2013; 368:2335-2337June 13, 2013DOI: 10.1056/NEJMc1300484
To the Editor:Transplacental transfer of anti-Ro antibodies is a well-known cause of conduction defects and permanent atrioventricular block in newborns.1 In adults, conduction disturbances related to these antibodies are rare.2 We report a case of a 26-year-old woman with no history of this condition who was admitted to the hospital through the emergency department after having several syncopal episodes. Electrocardiography (ECG) performed while the patient was at rest showed complete atrioventricular block and ventricular escape rhythm associated with left bundle-branch block (Figure 1AFigure 1Electrocardiographic Findings.). Laboratory evaluation included a positive test for antinuclear antibodies (with the HEp-2 cell substrate) at a titer of 1:320, with a speckled pattern and specificity for extractable nuclear antigens, including antibodies against Ro52 confirmed by means of immunoblot and enzyme-linked immunosorbent assays (first measurement of antibodies, 1.2 U per milliliter). No clinical manifestations of rheumatologic disease were present. Other causes of reversible atrioventricular block were ruled out. The patient had no history of cardiac surgery, ablation procedures, or drug use. There was no evidence of infiltrative diseases (e.g., sarcoidosis or amyloidosis) or myocardial ischemia, nor was there clinical suspicion of infectious diseases that cause conduction disturbances (e.g., Lyme disease or Chagas' disease). Levels of electrolytes and thyrotropin were normal. Transthoracic echocardiography and magnetic resonance imaging were unremarkable. During the first 4 days after admission, the patient had varying degrees of atrioventricular block. An electrophysiological study showed a mildly prolonged HV interval of 62 msec during sinus rhythm (normal values, 35 to 55 msec) and a pathologic response to atrial pacing, with atrioventricular block occurring after the deflection of the bundle of His during continuous stimulation at a fixed cycle length of 490 msec (Figure 1B). Intravenous methylprednisolone was initiated at a dose of 1 mg per kilogram of body weight per day, and 1:1 atrioventricular conduction was subsequently maintained on surface ECG. A second electrophysiological study during treatment showed normal atrioventricular conduction. Maintenance immunosuppressive therapy with azathioprine (at a dose of 100 mg daily) and methylprednisolone (at a dose of 4 mg daily) was initiated and continued for 12 months. Serial anti-Ro (SS-A) levels fluctuated during follow-up and became negative after 1 year. Because of the uncertainty of the outcome, a backup pacemaker was implanted. The patient remained completely asymptomatic for 12 months with sustained normal atrioventricular conduction. In this case of atrioventricular block in an adult patient with positive anti-Ro antibodies, we used electrophysiological testing to localize the conduction defect below the atrioventricular node. This finding, together with left bundle-branch block detected on ECG, suggests specific involvement of the Purkinje fibers. The pathogenesis of cardiac conduction disturbances in adults with positive anti-Ro (SS-A) antibodies remains unclear.3 Experimental studies suggest that anti-Ro antibodies interact with calcium channels and cause reversible inhibition of calcium currents. In fetal hearts, the internalization of these channels leads to apoptosis and fibrosis of the conduction tissue. The presence of a fully developed sarcoplasmic reticulum and the apparent lack of antibody-induced apoptosis in adult cardiomyocytes may explain the differential susceptibility of adult hearts to anti-Ro antibodies2 and, conceivably, the reversibility of the conduction disease in such persons.3 ReferencesIrene Santos-Pardo, M.D. Melania Martínez-Morillo, M.D. Roger Villuendas, M.D. Antoni Bayes-Genis, M.D., Ph.D. Hospital Universitari Germans Trias i Pujol, Badalona, Spain abayes.Disclosure forms provided by the authors are available with the full text of this letter at NEJM.org.