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http://lup.sagepub.com/content/early/2014/01/22/0961203313520340
The online version of this article can be found at:

DOI: 10.1177/0961203313520340
published online 22 January 2014 Lupus
Maria L Gonzalez-Suarez, Ahmed A Waheed, David M Andrews, Dana P Ascherman, Xu Zeng and Ali Nayer
Lupus vasculopathy: Diagnostic, pathogenetic and therapeutic considerations

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Lupus (2014) 0, 17
http://lup.sagepub.com
CASE REPORT
Lupus vasculopathy: Diagnostic, pathogenetic and
therapeutic considerations
Maria L Gonzalez-Suarez
1
, Ahmed A Waheed
2
, David M Andrews
3
, Dana P Ascherman
4
, Xu Zeng
5
and Ali Nayer
2
1
Department of Medicine, University of Miami, FL, USA;
2
Division of Nephrology and Hypertension, University of Miami, FL, USA;
3
Department of Pathology, University of Miami, FL, USA;
4
Division of Rheumatology, University of Miami, FL, USA
5
Nephrocor-Bostwick Laboratories, FL, USA
A rare form of vascular disease in systemic lupus erythematosus (SLE), lupus vasculopathy is
characterized by necrosis and accumulation of immunoglobulins (IGs) and complements in
the wall of arterioles and small arteries resulting in luminal narrowing. Lupus vasculopathy
often accompanies lupus nephritis and portends a poor prognosis. Although there is general
agreement on the treatment of lupus nephritis, effective treatment strategies for lupus vasculo-
pathy remain to be defined. We report a 20-year-old woman with SLE who presented with
generalized tonic-clonic seizure. Her immunosuppressive regimen consisted of mycophenolate
mofetil, prednisone and hydroxychloroquine. On physical examination, she was Cushingoid in
appearance and hypertensive. Laboratory tests indicated renal disease. Coagulation studies
disclosed de novo lupus anticoagulant. Magnetic resonance imaging of the brain demonstrated
acute focal cerebral hemorrhage. Echocardiography revealed reduced ejection fraction and
severe mitral regurgitation. Despite high-dose glucocorticoids and mycophenolate mofetil,
renal function remained poor. Kidney biopsy demonstrated lupus vasculopathy and glomer-
ulonephritis. Plasma exchange therapy and intravenous cyclophosphamide were administered.
Over the ensuing four weeks, renal function improved, complement levels increased, autoanti-
body titers decreased and lupus anticoagulant disappeared. In conclusion, lupus vasculopathy
can occur in SLE despite a heavy immunosuppressive regimen. Antiphospholipid antibodies
might be involved in the pathogenesis of lupus vasculopathy. Plasma exchange therapy in
conjunction with intravenous cyclophosphamide may represent an effective treatment strategy
for lupus vasculopathy. Lupus (2014) 0, 17.
Key words: Lupus vasculopathy; lupus nephritis; lupus anticoagulant; antiphospholipid anti-
bodies; cyclophosphamide; plasma exchange
Introduction
A rare form of vascular disease in systemic lupus
erythematosus (SLE), lupus vasculopathy is char-
acterized by necrosis and accumulation of immuno-
globulins (IGs) and complements in the wall of
arterioles and small arteries resulting in luminal
narrowing.
13
Lupus vasculopathy usually accom-
panies lupus nephritis and portends a poor
prognosis. Although the pathogenesis of lupus vas-
culopathy is largely unknown, immunoglobulin
and complement deposition in the blood vessels
suggests immune-mediated vascular injury.
While there is general agreement on the treatment
of lupus nephritis, eective treatment strategies for
lupus vasculopathy remain to be dened.
Here, we report a 20-year-old woman with SLE
who developed lupus vasculopathy, glomerulo-
nephritis, cardiomyopathy and acute focal cerebral
hemorrhage in conjunction with lupus anticoagu-
lant. A treatment strategy consisting of plasma
exchange therapy and intravenous cyclophospha-
mide resulted in clinical and serological remission.
Case presentation
A 20-year-old woman with relentless SLE devel-
oped a moderately severe headache followed by a
generalized tonic-clonic seizure. Her past medical
history was notable for various manifestations of
Correspondence to: Ali Nayer, Division of Nephrology and
Hypertension, University of Miami, Clinical Research Building, Rm
825, 1120 NW 14th St., Miami, FL 33136, USA.
Email: anayer@med.miami.edu
Received 15 July 2013; accepted 20 December 2013
!
The Author(s), 2014. Reprints and permissions: http://www.sagepub.co.uk/journalsPermissions.nav 10.1177/0961203313520340
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SLE including constitutional symptoms, arthritis,
anemia, pericarditis, valvular heart disease, pleuri-
tis, Raynauds phenomenon, renal disease and
hypertension (Table 1). There was no history of
vascular thrombosis. The patient was never preg-
nant, and lupus anticoagulant was undetectable in
the past. One year prior, renal biopsy revealed dif-
fuse proliferative and crescentic (30%) lupus glom-
erulonephritis. Arteries and arterioles were
unremarkable. Five months prior, echocardiog-
raphy revealed moderate to severe mitral regurgita-
tion and normal ejection fraction.
Upon current presentation, the patient was a
well-developed young African-American woman
who was Cushingoid in appearance. The blood
pressure was 143/118 mm Hg and the pulse was
109 beats/min. Neurological examination was
rather unremarkable. There was a 3/6 systolic
murmur at the apex of the heart with radiation
into the axilla. Laboratory data are summarized
in Table 2. Of note, lupus anticoagulant was
detected. There was no evidence of hemolysis.
Magnetic resonance imaging of the brain showed
acute focal hemorrhage surrounded by edema in
the cortex of the left posterior parietal lobe near
midline (Figure 1(a), (b)). Computed tomography
of the chest revealed moderate cardiomegaly and
a small pericardial eusion (Figure 1(c)).
Transthoracic echocardiography revealed reduced
ejection fraction (40%) and moderate to severe
mitral regurgitation. Renal ultrasonography
demonstrated mildly enlarged kidneys.
The patient was diagnosed with focal cerebral
hemorrhage, cardiomyopathy and lupus nephritis.
On the 3
rd
hospital day, she was pulsed with intra-
venous methylprednisolone (500 mg/day), while
mycophenolate mofetil (MMF) and hydroxychlor-
oquine were continued. On the 8
th
hospital day,
renal biopsy revealed brinoid necrosis of arteries
and arterioles as well as accumulation of eosino-
philic material in the wall of arterioles and small
arteries resulting in severe luminal narrowing
(Figure 2(a),(b)). In addition, focal segmental pro-
liferative and crescentic glomerulonephritis, mild to
moderate interstitial inammation and mild inter-
stitial brosis were noted. Immunouorescence
microscopy demonstrated immunoglobulin (Ig)G
(3), IgM (3), C3 (3) and C1q (3) in the
wall of arteries and arterioles (Figure 2(c)). IgG
(3), IgM (3), IgA (3), C3 (2), C1q (2) in
the glomeruli and IgG (3), IgM (3), IgA (2),
C3 (1), C1q (1) were in the tubular basement
Table 1 Clinical course and selected laboratory data prior to the current presentation
Date Symptoms/findings
SCr Proteinuria ANA dsDNA C3 C4
Management
0.81.2 <0.15 <1:40 <5.0 90180 1040
(mg/dl) (g/day) (titer) (IU/ml) (mg/dl) (mg/dl)
Jan. 2011 Fever, fatigue, joint pain and
swelling, leg edema,
hypertension
0.7 0.4 1:160 >300 74 9 Hospitalized; SLE diagnosed;
started on prednisone and
hydroxychloroquine.
Aug. 2011 Proteinuria, hypertension,
joint pain
0.6 1.1 Positive >300 52 5 Pulse glucocorticoids; MMF
1.5 g bid, lisinopril, and
HCTZ were added.
Dec. 2011 Chest pain, dyspnea,
Raynauds, hypertension,
pericarditis
0.6 0.9 Positive N/A 60 6 Pulse methylprednisolone;
prednisone taper; MMF
1.5 g bid; tacrolimus 1 g bid
added.
May 2012 Chest pain, dyspnea, fever,
hypertension, proteinuria,
hematuria
1.2 1.2 1:160 >300 45 7 Renal biopsy: Diffuse prolif-
erative crescentic glomer-
ulonephritis; prednisone
60 mg/day, MMF 1.5 g bid,
tacrolimus 1.5 g bid,
lisinopril.
Oct. 2012 Dyspnea on exertion, fatigue,
palpitations, tachycardia,
hypertension
0.7 4.0 Positive N/A N/A N/A Echocardiogram: mitral
regurgitation; tacrolimus
2 mg bid; MMF and pred-
nisone continued.
Nov. 2012 Chest pain, dyspnea,
hypertension
0.8 4.5 N/A N/A N/A N/A Pleuritis diagnosed; tacroli-
mus discontinued; MMF
and prednisone continued.
Feb. 2013 Seizure 3.3 6.4 Positive >300 37 4 Current admission
ANA: antinuclear antibodies; bid: twice daily; C3: complement C3; C4: complement C4; dsDNA: antibodies against double-stranded DNA;
HCTZ: hydrochlorothiazide; MMF: mycophenolate mofetil; N/A: not available; SCr: serum creatinine; SLE: systemic lupus erythematosus;
>: greater than. Urinary protein excretion is estimated using a random urine protein-to-creatinine ratio (g/day).
Lupus vasculopathy
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membranes. Ultrastructural examination demon-
strated numerous electron-dense deposits in the
glomeruli, tubular basement membranes and arteri-
oles. A histological diagnosis of lupus vasculopathy
and glomerulonephritis was rendered.
Considering the severity of histological ndings
and the lack of a discernable clinical and
immunological response to high-dose glucocortic-
oids and MMF, plasma exchange therapy was
initiated (Figure 3). One plasma volume was
exchanged with fresh frozen plasma every day for
ve days. However, the patient developed stridor
and acute respiratory distress during her fth
plasma exchange resulting in discontinuation of
Table 2 Laboratory data
Analyte On Admission Reference Range Analyte On Admission Reference Range
Sodium (mmol/l) 144 135145 DRVVT ratio 1.21 <1.20
Potassium (mmol/l) 4.4 3.44.8 Hexagonal phospholipid (sec) Positive <8
Chloride (mmol/l) 113 99109 Anticardiolipin IgG (U/ml) 6.7 <10
Carbon dioxide (mmol/l) 10 2130 Anticardiolipin IgA (U/ml) 6.1 <8
Urea nitrogen (mg/dl) 46 722 Anticardiolipin IgM (U/ml) 5.8 <10
Creatinine (mg/dl) 3.3 0.51.4 Anti-B2GPI IgG (U/ml) <9 <20
Glucose (mg/dl) 178 6599 Anti-B2GPI IgM (U/ml) <9 <20
Calcium (mg/dl) 7.9 8.610.3 ADAMTS-13 activity (%) 81 >66
Albumin (g/dl) 2.4 3.55.5 Protein C activity (%) 87 87187
WBC count (10
3
/mm
3
) 29.9 4.810.8 APC resistance (ratio) >2.1 >2.1
Neutrophil count (x10
3
/mm
3
) 25.4 1.57.0 Protein S activity (%) 76 89167
Hemoglobin (g/dl) 9.6 13.616.7 Anti-thrombin III activity (%) 140 79110
Platelet count (10
3
/mm
3
) 302 130350 Prothrombin mutation
a
Negative Negative
Urinalysis Fibrinogen (mg/dl) 563 200400
Color Yellow Yellow FDP (mg/ml) 520 <5.0
Appearance Clear Clear D-dimer (mg/l FEU) 5.3 0.20.5
pH 6.0 4.67.8 C3 (mg/dl) 37 90180
Specific gravity 1.025 1.0011.035 C4 (mg/dl) 4 1647
Blood 3 Negative ESR (mm/h) 62 020
Protein 3 Negative C-reactive protein (mg/dl) 10.8 <1.0
White blood cells/hpf 02 02 Antinuclear antibodies Positive Negative
Red blood cells/hpf 2550 02 Anti-dsDNA Ab (U/ml) >300 <4.9
Urine protein:creatinine 6.4 0.020.13 Anti-chromatin Ab (U/ml) >8.0 <0.9
Urine toxicology screen Negative Negative Anti-Smith Ab (U/ml) >8.0 <0.9
aPTT (sec) 26.0 24.535.7 Anti-RNP Ab (U/ml) 7.1 <0.9
PT (sec) 10.6 10.112.6 Rheumatoid factor (U/ml) Negative Negative
Ab: antibody; ADAMTS-13: a disintegrin and metalloprotease with thrombospondin-1like domains; AI: antibody index; anti-dsDNA: anti-
double stranded DNA; APC: activated protein C; aPTT: activated partial thromboplastin time; B2GPI: beta-2 glycoprotein I; DRVVT: dilute
Russell viper venom time; ESR: erythrocyte sedimentation rate; FDP: fibrin degradation products; hpf: high power field; IG: immunoglobulin;
PT: prothrombin time; WBC: white blood cell; FEU: fibrinogen equivalent units; RNP: ribonucleoproteins.
a
G20210A. Values out of the reference range are in bold.
Figure 1 Acute cerebral hemorrhage and cardiomegaly. Magnetic resonance imaging of the brain demonstrating (a) and (b) a
focus of acute hemorrhage involving the cortex of the left posterior parietal lobe near midline; (c) computed tomography of the
chest demonstrating cardiomegaly.
Lupus vasculopathy
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plasma exchange therapy. On the 19
th
hospital day,
MMF was switched to intravenous cyclophospha-
mide (750 mg/m
2
).
Over the ensuing four weeks, serum creatinine
concentration declined to 1.6 mg/dl (Figure 3).
Serum levels of antibodies against double-
stranded DNA and Smith antigen declined to
22 U/ml and 4.4 U/ml, respectively. Complement
C3 levels increased to 69 mg/dl, while C4 and
brin degradation products including D-dimer
normalized. Lupus anticoagulant was undetect-
able. The patient was anticoagulated because of
central nervous system (CNS) involvement asso-
ciated with lupus anticoagulant. After receiving
intravenous cyclophosphamide (750 mg/m
2
/
month) for six months, serum creatinine was
1.8 mg/dl, proteinuria 0.5 g/day and blood pres-
sure 128/90 mm Hg.
Discussion
A young woman suering from constitutional,
hematological, musculoskeletal, cardiovascular,
and renal manifestations of SLE is presented. She
developed focal cerebral hemorrhage, cardiomyop-
athy and impaired renal function despite an
immunosuppressive regimen consisting of
MMF, glucocorticoids and hydroxychloroquine.
Coagulation studies disclosed de novo lupus anti-
coagulant. Renal biopsy revealed lupus vasculopa-
thy and nephritis. Plasma exchange therapy in
conjunction with intravenous cyclophosphamide
induced clinical and serological remission.
Vascular disease is SLE can be classied as:
(a) lupus vasculopathy, (b) necrotizing vasculitis,
(c) thrombotic microangiopathies, and (d) acceler-
ated atherosclerosis.
14
Observed in 3.824% of
*
IgG
*
(a) (b) (c)
Figure 2 Histology of the kidney biopsy. (a) A small artery demonstrating accumulation of eosinophilic material in the wall (white
arrows), loss of myocytes (black arrows) and near-total occlusion of the lumen (asterisk); (b) an arteriole showing accumulation of
amorphous material in the wall (bar), medial atrophy (white arrows) and narrowed lumen (asterisk); (c) an arteriole demonstrating
immunoglobulin G deposition in the wall. Tissue sections were stained with hematoxylin and eosin (a) and periodic acid-Schiff (b)
stains. Immunofluorescence micrograph (c). Intima is marked with a bar in (b) and (c).
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
4.5
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41
S
e
r
u
m

c
r
e
a

n
i
n
e

(
m
g
/
d
l
)
Hospi t al day
Methyl-
prednisolone
pulse
Plasma
exchange
CYP
Mycophenolate mofel
Glucocorcoids
47

Renal
biopsy
Figure 3 Renal function and therapeutic interventions during hospitalization. Serum creatinine concentration during hospital-
ization is demonstrated. Gray boxes represent the type and duration of treatments. See text for details. CYP: cyclophosphamide.
Lupus vasculopathy
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renal biopsies from SLE patients, lupus vasculopa-
thy is characterized by accumulation of IGs and
complements in the wall of arterioles and small
arteries resulting in luminal narrowing.
17
Adjacent endothelial cells and medial myocytes fre-
quently demonstrate degenerative features or
necrosis. Lupus vasculopathy is distinguished
from vasculitis by the lack of inammatory cells
in the vessel wall. Although documented predom-
inantly in the kidney, lupus vasculopathy can
involve the heart, joints, spleen, skin, retina and
lungs.
5,8,9
The pathogenesis of lupus vasculopathy is
largely unknown. Accumulation of IGs and com-
plements in the vascular wall suggests immune-
mediated vascular injury.
13
Complements are
activated through the classical, lectin or alternative
pathways.
10
The classical pathway is strongly acti-
vated by immune complexes, which are recognized
by the versatile pattern recognition molecule C1q.
Following target recognition, C1q-associated pro-
tease C1s is activated and cleaves C4 and C2,
thereby resulting in generation of the classical path-
way C3 convertase (C4b2b). C3 cleavage into ana-
phylatoxins C3a and C5a by the C3 convertases
and subsequent C5 cleavage by the C5 convertases
results in the formation of C5a and C5b. The latter
participates in the assembly of the membrane
attack complex (MAC, C5b-9, terminal comple-
ment complex). In the context of complement acti-
vation, C3a and C5a trigger proinammatory
signaling, C3b facilitates phagocytosis and MAC
mediates target cell activation, injury or lysis in a
dose-dependent manner. Of note, C3a and C5a are
potent chemotactic factors for neutrophils, mono-
cytes and macrophages.
10
Therefore, the lack of
inammatory cell inltration into the vessel wall
in lupus vasculopathy remains an enigma. In add-
ition, vascular antigen(s) that provoke a humoral
immune response in lupus vasculopathy are not
characterized.
The development of lupus vasculopathy in our
patient coincided with the appearance of antipho-
spholipid antibodies. Similarly, antibodies to b
2
-
glycoprotein I were detected in the patient with
lupus vasculopathy reported by Wu and col-
leagues.
11
Therefore, it is tempting to speculate
that antiphospholipid antibodies are involved in
the pathogenesis of lupus vasculopathy. However,
antiphospholipid antibodies are highly prevalent in
SLE patients.
12
Therefore, it remains to be seen
whether there is indeed a causal relationship
between antiphospholipid antibodies and lupus
vasculopathy.
Lupus vasculopathy is usually associated with
severe forms of glomerulonephritis and portends a
poor prognosis.
57,9,13
Limited available evidence
supports an aggressive approach in the treatment
of lupus vasculopathy. Sung et al. diagnosed a
16-year-old boy with renal failure and dilated car-
diomyopathy.
9
Renal biopsy demonstrated lupus
vasculopathy. While high-dose glucocorticoids
and plasma infusion improved cardiac function,
renal function deteriorated necessitating renal
replacement therapy. Ma et al. showed that a cyclo-
phosphamide-based regimen consisting of high-
dose glucocorticoids, rituximab, plasma exchange
and intravenous cyclophosphamide led to improve-
ment of renal function in a 16-year-old girl with
lupus vasculopathy.
14
Similarly, Seshan reported
that intravenous glucocorticoids and cyclophos-
phamide improved renal function and reduced pro-
teinuria in a 36-year-old woman with lupus
vasculopathy.
2
Wu et al. reported a 12-year-old
girl who developed acute renal failure and severe
hypertension secondary to lupus vasculopathy and
nephritis.
11
Although high-dose glucocorticoids
and intravenous cyclophosphamide failed to
induce remission, addition of daily plasma
exchange resulted in renal recovery.
Wang et al. compared the ecacy and safety of
intravenous cyclophosphamide to MMF for lupus
vasculopathy and nephritis in a prospective, rando-
mized, open-label clinical trial.
15
All patients
received high-dose intravenous methylprednisolone
followed by prednisone taper. Complete remission
was observed in 44% and 0% of patients treated
with MMF and cyclophosphamide, respectively.
Partial remission occurred in 22% and 27% of
patients treated with MMF and cyclophosphamide,
respectively. Adverse eects were more common in
patients treated with cyclophosphamide. The
authors concluded that MMF was more eective
than intravenous cyclophosphamide in inducing
complete remission and had a more favorable side
eect prole. In contrast, our patient developed
lupus vasculopathy while taking MMF, prednisone
and hydroxychloroquine. Moreover, administra-
tion of high-dose intravenous glucocorticoids
failed to demonstrate a tangible response.
However, intravenous cyclophosphamide in con-
junction with plasma exchange therapy induced
clinical and serological remission.
Plasma exchange represents an adjuvant thera-
peutic strategy for antibody-mediated autoimmune
diseases by removing pathogenic autoantibodies
and circulating immune complexes.
16
In addition,
plasma exchange therapy exerts immunomodula-
tory eects by altering T-cell functions (favoring
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type 2 helper T cell dierentiation) and suppressing
interleukin 2 and interferon gamma production.
16
Although a randomized clinical trial of plasma-
pheresis in lupus nephritis showed no additional
benet beyond standard therapy, plasma exchange
could serve as an adjunct treatment in patients with
severe lupus nephritis who do not respond to the
conventional therapy or those who demonstrate a
rapidly progressive decline in renal function.
1720
Our patient suered from severe hypertension
necessitating hospitalization on several occasions.
Severe recalcitrant hypertension is a common mani-
festation of lupus vasculopathy.
1,2,9,11,13
The patho-
genesis of hypertension in this setting appears to be
a consequence of vascular disease. Sung et al.
hypothesized that lupus vasculopathy leads to a
decline in glomerular perfusion pressure, thereby
stimulating renin secretion and activation of angio-
tensin-aldosterone system.
9
Therefore, judicious
use of angiotensin-converting enzyme inhibitors
and angiotensin receptor blockers may prove eect-
ive in controlling blood pressure in this setting.
Our patient developed pericarditis, mitral valve
regurgitation and cardiomyopathy. Approximately
one-half of patients with SLE develop clinical or
subclinical cardiac disease.
21,22
The pericardium,
myocardium, conduction system, endocardium
including heart valves and coronary arteries can
be aected. Pericarditis is a common cardiac mani-
festation of SLE.
21,22
Echocardiography revealed
thickening of pericardium, pericardial eusion or
both in 1154% of patients with SLE. In autopsy
studies, the prevalence of pericarditis in SLE aver-
aged 56%. Gross examination of the pericardium
revealed brinous or brous thickening with focal
or diuse adhesions between the visceral and par-
ietal layers. Histologically, pericardial disease is
characterized by chronic inammatory changes
and deposition of IGs and complements in the
wall of pericardial blood vessels.
22
Based on the
description in the above-mentioned studies, the his-
topathologic features of the blood vessels in lupus
pericarditis closely mimic those of lupus vasculopa-
thy. Therefore, it is conceivable that lupus vasculo-
pathy is the underlying vascular disease in a subset
of patients with lupus pericarditis. This preliminary
conclusion, however, needs to be further examined.
Valvular heart disease is frequently diagnosed
in patients with SLE.
21,22
Echocardiography
reveals valvular thickening, stenosis, regurgitation
or sterile vegetations (Libman-Sacks endocarditis)
in approximately 60% of SLE patients. Mitral
and aortic valves are more frequently involved
than their counterparts in the right heart.
Valvular heart disease is more common in SLE
patients with antiphospholipid antibodies.
23
Echocardiography disclosed mitral regurgitation
in 38% of SLE patients with antiphospholipid anti-
bodies and in 12% of those without. Similarly,
mitral valve vegetation was diagnosed in 16% of
SLE patients with antiphospholipid antibodies
and in only 1.2% of those without. Our patient
developed moderate to severe mitral valve regurgi-
tation and was found to have lupus anticoagulant.
Transesophageal echocardiography did not show
vegetations. While afterload reduction therapy
was continued, she was referred to cardiac surgery
for potential surgical treatment.
Although early diagnosis and improved manage-
ment of SLE has reduced the incidence of clinically
relevant myocardial disease, it remains a serious
manifestation.
21,22
Myocardial disease is mainly
secondary to myocarditis and atherosclerotic cor-
onary artery disease. Lupus myocarditis is charac-
terized by perivascular and interstitial mononuclear
inammatory cell inltration, cardiac myocyte
injury and myocardial brosis. Myocardial disease
in SLE can also be secondary to small-vessel dis-
ease characterized by vascular thrombosis, regen-
erative/degenerative features of endothelial cells
and perivascular inammation. Jain et al. reported
a 24-year-old White woman with concurrent SLE
and antiphospholipid syndrome who had small-
vessel disease on endomyocardial biopsy.
22
In the
case reported by Sung et al., myocardial disease
occurred in conjunction with lupus vasculopathy
in the kidney.
9
High-dose glucocorticoids and
plasma infusion led to improved myocardial con-
tractility. Our patient developed reduced ejection
fraction along with elevated cardiac enzymes (six-
and three-fold increase in troponin I and creatine
kinase MB, respectively) indicating myocardial
injury. Although endomyocardial biopsy was not
performed, myocardial disease occurred in conjunc-
tion with lupus vasculopathy in the kidney and de
novo lupus anticoagulant.
Cerebrovascular disease and seizure disorder are
two of the 19 neuropsychiatric manifestations of
SLE.
24
In a study by Sanna et al. involving 323
SLE patients, the overall prevalence of neuro-
psychiatric manifestations was 57%.
12
Cerebrovascular disease and seizure disorder were
diagnosed in 14.5% and 8.3% of patients, respect-
ively. The prevalence of antiphospholipid antibo-
dies in this cohort was 39.3%. While
anticardiolipin antibodies and lupus anticoagulant
were detected in 27.5% and 11.8% of patients,
respectively, approximately 10% of patients had
both anticardiolipin antibodies and lupus anti-
coagulant.
12
Cerebrovascular disease and seizure
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L Gonzalez-Suarez et al.
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Lupus
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disorder were independently and signicantly asso-
ciated with antiphospholipid antibodies. Therefore,
long-term anticoagulation has been recommended
for SLE patients with severe focal lesions of the
CNS such as vascular thrombosis associated with
antiphospholipid antibodies.
25
In a retrospective
observational study involving 26 patients with
neuropsychiatric manifestations of SLE, plasma-
pheresis either alone or in conjunction with cyclo-
phosphamide led to improvement (74%) or
stabilization (13%) of the clinical status.
26
The
American Society for Apheresis has recommended
plasmapheresis in the treatment of severe SLE
involving the CNS as second-line therapy, either
as a stand-alone treatment or in conjunction with
other treatment modalities.
27
Our patient developed
a generalized tonic-clonic seizure as a result of acute
focal cerebral hemorrhage probably secondary to
cerebrovascular disease. She received plasma
exchange therapy as part of the therapeutic regimen
for her aggressive systemic disease. Considering the
hemorrhagic nature of the CNS lesion in our
patient, anticoagulation was delayed until four
weeks after presentation. No side eects related to
anticoagulation were noted.
Final diagnosis: lupus vasculopathy, lupus neph-
ritis, cardiomyopathy and acute focal cerebral hem-
orrhage in conjunction with lupus anticoagulant.
Funding
This research received no specic grant from any
funding agency in the public, commercial or not-
for-prot sectors.
Conflict of interest
None declared.
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