International Journal of Rheumatic Diseases 2015; 18: 800–806

APLAR GRAND ROUND CASE

Cardiac arrhythmias as the initial manifestation of adult

€ gren’s syndrome: a case report and literature
primary Sjo
review
Minrui LIANG,1,2* Liwen BAO,3* Nanqing XIONG,3 Bo JIN,3 Huanchun NI,3
Jinjin ZHANG,3 Hejian ZOU,1,2 Xinping LUO3 and Jian LI3
1
Division of Rheumatology, Huashan Hospital, 2Institute of Rheumatology, Immunology and Allergy, and 3Department of
Cardiology, Huashan Hospital, Fudan University, Shanghai, China

Abstract
Two middle-aged female patients presenting with heart palpitation and electrocardiogram revealed complex car-
diac arrhythmias. A review of systems was positive for dry mouth and transient arthralgia, while laboratory and
instrumental tests enabled us to make the diagnosis of primary Sj€
ogren’s syndrome (pSS). Cardiac electrophysi-
ology revealed atrioventricular node dysfunction and impaired intraventricular conduction. Prednisone therapy
induced a significant improvement in symptoms and electrocardiographic readings. The diagnosis of pSS should
be considered in a patient presenting with complex cardiac arrhythmias.
Key words: Sj€
ogren’s syndrome, cardiac arrhythmias, anti-SSA/Ro antibodies, anti-SSB/La antibodies.

INTRODUCTION CASE REPORT

Primary Sj€ ogren’s syndrome (pSS) is a systemic autoim-
mune disease characterized by lymphocytic infiltration
of exocrine glands accompanied by a variety of
extraglandular manifestations. Female patients with
Sj€
ogren’s syndrome and antibodies against SSA/Ro and
SSB/La have significant increased risk of giving birth to
children with neonatal conduction abnormalities in the
heart, especially complete congenital heart block. It is
supposed that the conduction system in the adult heart
is relatively resistant to injury by anti-SSA and anti-SSB
antibodies. Here we report two cases of combined pSS
with the predominant initial manifestation of complex
cardiac arrhythmias.
Correspondence: Professor Jian Li, M.D., Department of Cardi-
ology, Huashan Hospital, Fudan University, 12 Wulumuqi
Zhong Road, Shanghai 200040, China.
Email: 13816066763@163.com
*These authors contribute equally.
Case I
A 48-year-old woman, with a 3-month history of heart
palpitations, was admitted to the cardiology depart-
ment of Huashan Hospital (Shanghai, China) for fur-
ther assessment. She had no medical history of
hypertension, diabetes, hyperlipidemia or obesity. She
was a housewife and never smoked. At presentation,
physical examination demonstrated irregular heart
rhythms without heart murmur or crackle. Serial 12-
lead electrocardiography showed frequent premature
ventricular contraction (PVC) and intraventricular con-
ductional block (Fig. 1). Chest radiography showed
enlarged heart shadow. Echocardiography indicated
bilateral atrial enlargement, pericardial effusion of very
small size, pulmonary hypertension (pulmonary artery
systolic pressure [PASP] was estimated as 49 mmHg),
impaired diastolic function of left ventricular and
decreased left ventricular ejection fraction (LVEF) of
47%. She was diagnosed with cardiac arrhythmias
resulting from PVC and intraventricular conductional

© 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd

Figure 1 Serial 12-lead electrocardiography showed frequent premature ventricular contraction (PVC) and intraventricular con-
ductional block.
block. However, there was no history of arrhythmias
nor was there any hints that an overdose of medication
caused the arrhythmias. Further tests were performed to
determine an underlying cause for these findings.
By a careful review of systems, positive for dry mouth
and transient arthralgia of both elbow joints was found.
Laboratory tests showed increased serum troponin
T (TnT) of 0.027 ng/mL (normal ≤ 0.014), myoglobin
of 97.61 ng/mL (25–58), creatine kinase (CK) of
296 U/L (26–192), lactate dehydrogenase (LDH) of
220 U/L (135–214) and normal serum brain natriuretic
peptide (BNP). Furthermore, she had increased erythro-
cyte sedimentation rate (ESR) of 64 mm/h, hyperim-
munglobulinemia (IgG 19.90 g/L [normal 7.51–15.6],
IgA 8.11 g/L [0.82–4.53]). The leukocyte count was not
raised, with a normal white cell differential and normal
serum C-reactive protein (CRP). As the patient’s com-
plaints, physical findings and primary laboratory tests
pointed toward a potential autoimmune disease back-
ground, several tests were subsequently conducted.
She had positive antinuclear antibody (titer, 1 : 1000,
HEp-2), positive anti-SSA (Ro-52) antibodies, and posi-
tive IgM rheumatoid factor (RF) with negative anti-SSA
(Ro-60), SSB, cyclic citrullinated peptide (CCP), Sm,
double-stranded DNA (dsDNA), Scl-70, PM-Scl, antine-
International Journal of Rheumatic Diseases 2015; 18: 800–806
Arrhythmias as initial exhibition in adult pSS
utrophil cytoplasmic antibodies (cANCA), perinuclear
ANCA antibodies (pANCA) and normal levels of C3
and C4 complement factors. Serum cytomegaovirus
(CMV) DNA and Epstein–Barr virus (EBV) DNA
detected by real-time reverse transcription – polymerase
chain reaction, adenovirus (ADV) IgM/IgG and Coxsa-
chie virus (CSV) IgM/IgG detected by enzyme-linked
immunosorbent assay were all negative. Thyroid func-
tion was euthyroid. No monoclonal immunoglobulin
was found in the serum or urine by immunofixation
electrophoresis. Technetium scintigraphy revealed the
reduction of radiotracer uptake and intake in glands of
both sides. Biopsy of a minor labial gland showed
typical lymphocytic infiltrates (Fig. 2a,b). The lympho-
cytes were positive for T lymphocyte marker CD3
(Fig. 2c) and B lymphocyte marker CD19 (Fig. 2d). No
other abnormal laboratory findings were noted. A diag-
nosis of pSS was confirmed following the positive
findings, including hyposalivation, positive salivary
scintigraphy, positive anti-SSA/Ro, and histopatho-
logical signs (focus score, ≥ 1/4 mm2) according to
American College of Rheumatology (ACR) 2012 classi-
fication criteria for pSS.1
Based on the diagnostic criteria for myocarditis pro-
posed by the European Society of Cardiology Working
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M. Liang et al.

(a) (b)

(c) (d)

Figure 2 Biopsy of a minor labial gland was collected from this patient and the histopathologic findings are shown. (a) Hematox-
ylin and eosin (H&E) staining (original magnification 1009); (b) H&E staining (original magnification 4009); (c) immunohisto-
chemical staining for T lymphocyte marker CD3 (original magnification 4009); (d) and B lymphocyte marker CD19 (original
magnification 4009); H&E staining for labial gland biopsy showed lymphocyte-rich inflammatory infiltrate, which was positive
for CD3 and CD19.

Group in 2012,2 this patient was diagnosed with
immune-mediated myocarditis due to pSS. Continuous
24-h Holter captured complex cardiac arrhythmias,
including PVC (8472 beats/24 h), premature superven-
tricular contraction (1992 beats/24 h), and complete
right bundle branch block. Heart biopsy was not done
because the patient did not consent. In order to
evaluate the electrophysiological changes in her heart,
cardiac electrophysiology was performed. The His-
ventricular (HV) interval was 69.44 ms (normal 35–55)
(Fig. 3) and the atrioventricular node effective refrac-
tory period (AVN-ERP) was 380.56 ms (normal 250–
365) (Fig. 4), which indicated atrioventricular node
dysfunction and impaired intraventricular conduction.
The patient was treated with prednisone 1.5 mg/kg/
day for 5 days, with improvement in clinical and elec-
trocardiographic readings. Also, the serum troponin T,
myoglobin, CK, LDH, IgG and ESR levels returned to
normal. After discharge, the patient tapered the dose of
prednisone 10% per month; in the meantime, she was
also treated with sotalol (80 mg/day). Repeated contin-
uous 24-h Holter 3 months later showed decreased
PVC (1068 times/24 h). And repeated
echocardiography was also performed with normal
results (PASP estimated as 38 mmHg and LVEF of
63%).
Case II
A 61-year-old woman with a 4-year history of heart pal-
pitation was admitted to the cardiology department of
Huashan Hospital. She did not have hypertension, dia-
betes, hyperlipidemia or obesity, and she had a negative
finding in coronary angiography 4 years ago. The treat-
ment of metoprolol 12.5 mg per day could relieve her
symptom to a certain extent. Further 12-lead electrocar-
diography showed frequent ventricular contraction,
intra-atrial conductional block and intraventricular con-
ductional block. In addition, she had elevated BNP of

802 International Journal of Rheumatic Diseases 2015; 18: 800–806


Figure 3 Cardiac electrophysiology was performed to evaluate the electrophysiological changes in the heart of this patient. The
atrial-His (AH) interval was 93.18 ms and HIS-ventricular (HV) interval was 69.44 ms (as indicated by arrows). In our center, the
normal range of AH interval is 60–125 ms, HV interval is 35–55 ms.
857.5 pg/mL (normal < 300) and normal TnT. A chest
X-ray revealed borderline cardiomegaly. Echocardiogra-
phy showed impaired systolic function of the left ven-
tricle with the LVEF of 38%. Continuous 24-h Holter
captured multifocal PVC (6378 times/24 h), premature
superventricular contraction (107 times/24 h) and
complete left bundle branch block. Repeated coronary
angiography showed tiny plaques in the left anterior
descending artery, left circumflex artery and right coro-
nary artery with 30% stenosis. Therefore, this patient
was diagnosed with coronary artery atherosclerosis;
however, the severity of coronary stenosis could not
explain her complex cardiac arrhythmias and cardiac
insufficiency. By a careful review of systems, she com-
plained of dry mouth and described a migratory arthral-
gia lasting for 4 years. In order to reveal the underling
etiology, further tests were performed.
Results of further investigations were as follows: posi-
tive for the anti-SSA (Ro-52) antibody, negative for the
International Journal of Rheumatic Diseases 2015; 18: 800–806
Arrhythmias as initial exhibition in adult pSS
antibodies against SSA (Ro-60), SSB, RF, CCP, Sm,
dsDNA, Scl-70, PM-Scl, cANCA, pANCA, and normal
levels of IgG, IgM, IgA, C3 and C4 complement factors.
Serological tests for viral infection were all negative.
Technetium scintigraphy also revealed the reduction of
radiotracer uptake and intake in glands of both sides.
Biopsy of labial gland showed a typical lymphocytic
infiltration. Therefore, this patient was also diagnosed
with pSS. Ruling out infection, medication, or coronary
heart disease-induced cardiac arrhythmias, clinical find-
ings suggested her complex cardiac arrhythmias and
cardiac insufficiency were closely associated with pSS.
After starting prednisone therapy 0.5 mg/kg/day and
sotalol 80 mg/day, her palpitation and dryness gradu-
ally improved. Repeated 24-h Holter 1 month later
revealed decreased PVC (703 times/24 h) and prema-
ture superventricular contraction (58 times/24 h).
Repeated echocardiography showed improved LVEF of
46%.
803
M. Liang et al.

Figure 4 Cardiac electrophysiology was performed to evaluate the electrophysiological changes in the heart of this patient. The
atrioventricular node effective refractory period (AVN-ERP) was 380.56 ms (as indicated by arrows). In our center, the normal
range of AVN-ERP is 250–365 ms.

Table 1 Summary of cases of cardiac arrhythmias in Sj€

ogren’s syndrome (SS)
Country No. SS cases Types of cardiac arrhythmias Anti-SSA/SSB antibodies References
USA 1 Complete atrioventricular block SSA (Ro-52 and Ro-60) Lee et al.6
Korea 1 Complete atrioventricular block SSA Sung et al.7
USA 1 Complete atrioventricular block SSA (Ro-60) and SSB Baumgart et al.8
Turkey 40 Atrial electromechanical delay No association Akyel et al.9
Italy 12 QT interval prolongation SSA Lazzerini et al.10
Complex ventricular arrhythmias
(Lown classes 2–5)
Italy 16 QT interval prolongation SSA (Ro-52) Lazzerini et al.11

of pSS patients presenting complex cardiac arrhythmias

DISCUSSION as their significant initial manifestation. On the other
This case report of two patients illustrates the associa- hand, the detailed description of the functions of
tion of pSS and complex cardiac arrhythmias. To our impulse formation and the conduction system of the
knowledge, this is the first case report in the literature heart in adult pSS patients has not been reported. For

804 International Journal of Rheumatic Diseases 2015; 18: 800–806


the first case, cardiac electrophysiology was performed
and showed atrioventricular node dysfunction and
impaired intraventricular conduction, which provides
additional support for the hypothesis that anti-SSA (Ro-
52) was associated with conduction defect in adult pSS
patients, although the adult conduct system was
thought to be relatively resistant to anti-SSA/Ro anti-
body damage. Also, the treatment of prednisone
induced significant symptomatic and laboratory
improvement in these two patients. Obvious cardiac
arrhythmia is rare in pSS, so their associations and clini-
cal significance are not well defined. Based on this clini-
cal report, pSS with cardiac arrhythmias are
summarized here (Table 1).
Patients with pSS, compared with health controls,
were more likely to have cardiac arrhythmias.3 Also a
Sj€
ogren’s syndrome mother with anti-SSA antibodies is
associated with congenital heart block in newborns.4
However, anti-SSA autoantibody is believed to be safe
from damaging the adult atrioventricular (AV) node.5
Nevertheless, there are some reports of an adult AV
block in Sj€ogren’s syndrome.6–8 Interestingly, the clini-
cal manifestations of cardiac arrhythmias and the asso-
ciated antibodies in Sj€ ogren’s syndrome remain a
debated issue (Table 1).
However, the pathological basis of cardiac arrhyth-
mias in pSS is far from clear. It is described an autopsy
case following the sudden death of a young female
patient with pSS, and the autopsy showed that the ste-
nosis of the lumen in both sinoatrial (SA) node and AV
node arteries and lymphocyte infiltration in the bundle
of His, which may have led to fatal arrhythmias.12
The role of anti-SSA/SSB autoantibodies in the path-
ogenesis of heart block needs to be discussed. Maternal
sera containing antibodies against SSA and SSB ribonu-
cleoproteins (positive IgG) inhibited L-type Ca current
in isolated cardiac myocytes and induced sinus brady-
cardia in a murine model of congenital heart block
(CHB), and further study showed that maternal anti-
bodies interact directly with the pore-forming alpha
(1)-subunit of Ca channels.13,14 And rather than a 60-
kDa anti-Ro antibody, a 52-kDa antibody was a more
specific cause of the conduction abnormality.15
On the basis of our observations in these two cases,
the significance of cardiac involvement must be inter-
preted cautiously for patients with pSS in the light of
the clinical scenario. Also, the possibility of pSS should
be given attention in patients with complex cardiac ar-
rhythmias, and corticosteroid therapy seemed to elicit
good response in these patients.
International Journal of Rheumatic Diseases 2015; 18: 800–806
Arrhythmias as initial exhibition in adult pSS
CONFLICTS OF INTEREST
The authors have no competing interests to declare.
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International Journal of Rheumatic Diseases 2015; 18: 800–806