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Cerebral large vessel vasculitis in systemic lupus erythematosus

BC Böckle, D Jara, K Aichhorn, D Junker, T Berger, G Ratzinger and NT Sepp
Lupus published online 26 June 2014
DOI: 10.1177/0961203314541689

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CASE REPORT

Cerebral large vessel vasculitis in systemic lupus erythematosus

BC Böckle1, D Jara2, K Aichhorn1, D Junker3, T Berger4, G Ratzinger1 and NT Sepp1,2
1
Department of Dermatology, Innsbruck Medical University, Austria; 2Barbara Bommer Foundation for Clinical Immunodermatology,
Department of Dermatology, Innsbruck Medical University, Austria; 3Department of Radiology, Innsbruck Medical University, Austria; and
4
Clinical Department of Neurology, Innsbruck Medical University, Austria

Neuropsychiatric systemic lupus erythematosus (NPSLE) is defined by involvement of the

central nervous system in systemic lupus erythematosus (SLE), with a wide range of both
neurological and psychiatric manifestations. Although its aetiopathogenesis is not fully eluci-
dated, NPSLE seems to be a consequence of cerebral vascular pathology including thrombo-
embolism, small-vessel vasculopathy and, in rare cases, true vasculitis. Cerebral vasculitis is
rare, and cerebral large-vessel vasculitis in SLE is even more unusual. We report the case of a
female patient with the diagnosis of SLE. She presented with stroke-like symptoms, headache
and vertigo, and palpable purpura on her legs. Further investigations revealed that she suf-
fered from both vasculitis of the cerebral large vessels and coexisting cutaneous small-vessel
vasculitis. Lupus (2014) 0, 1–5.

Key words: Large-vessel vasculitis; neuropsychiatric systemic lupus erythematosus NPSLE

Case report administered. In 2010 she developed sicca symp-

toms and parotitis. Schirmer’s test and laboratory
In 1999, we diagnosed systemic lupus erythemato- results were consistent with secondary Sjögren’s
sus (SLE) in a 41-year-old Caucasian female Syndrome (SS).
patient. She suffered from severe photosensitivity, In 2011, she presented with severe vertigo, nausea,
arthritis, serositis, and recurrent pericarditis. headache and hypoparesthesia of the right leg sug-
Furthermore, anaemia, leukopenia, high-titre anti- gestive for stroke. She also showed numerous red
nuclear antibodies (ANA) including Ro/SS-A anti- palpable purpura of the lower limbs indicating
bodies, cutaneous leukocytoclastic vasculitis recurrent leukocytoclastic vasculitis (Figure 1 (C),
(Figure 1 (E), (F)) of the lower limbs and neuro- (D)). Pulse, blood pressure and temperature were
logical symptoms due to distal sensory-motor poly- all normal and she was afebrile. Laboratory findings
neuropathy were evident. Due to her severe disease showed anaemia (109 g/l, normal range, 120–157 g/
course with relapses, she required various anti- l), lymphopenia (0.55 G/l; normal range, 0.8–4.00 G/
inflammatory and immunosuppressive drugs. l), mild increase of C-reactive protein (1.34 mg/dl,
Methotrexate, mycophenolate mofetil, corticoster- normal range, 0.00–0.70 mg/dl), elevated neopterin
oids, azathioprine, colchicine, dapsone, and intra- levels (14.1 nmol/l, normal range, 0.0–10.0 nmol/l),
venous immunoglobulins have been administered complement consumption of C4 (>1.6 mg/dl;
as treatment modalities over the past years. normal range, 10.0–40.0 mg/dl) and low entire com-
Despite all that, she had recurrent urticarial-like plement activity (19%; normal range 70–40%).
rashes and palpable purpura of the lower extremi- ANA (1:320), anti-Ro/SS-A and anti-La/SS-B were
ties histologically proven as leukocytoclastic vascu- positive, whereas anti-double stranded DNA, and
litis (Figure 1 (A), (B)). Oral short-term anti-phospholipid antibodies were all negative.
glucocorticoid treatment cycles had to be Serological tests for HIV, hepatitis B, C viruses,
rheumatoid factor and cryoglobulins were repeat-
edly negative.
Correspondence to: Norbert Sepp and Barbara Böckle, Department of Neurological consultation ruled out stroke and
Dermatology, Innsbruck Medical University Anichstrasse 35, 6020
Innsbruck, Austria.
meningitis by clinical investigation. Cerebral mag-
Email: norbert.sepp@i-med.ac.at, barbara.boeckle@i-med.ac.at netic resonance imaging (MRI) including MR angi-
Received 7 May 2013; accepted 30 May 2014 ography (MRA) was conducted (Figure 2).
! The Author(s), 2014. Reprints and permissions: http://www.sagepub.co.uk/journalsPermissions.nav 10.1177/0961203314541689

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Cerebral large vessel vasculitis in SLE

BC Böckle et al.
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Figure 1 Leukocytoclastic vasculitis: Histopathologic findings. Skin biopsy specimens from the upper limb of the patient showing:
perivascular lymphocytic and neutrophilic infiltration of small vessels in the upper and mid dermis. (A, magnification 40)
Extravasation of erythrocytes, fibrinoid necrosis and nuclear debris (leukocytoclasia) were also found. (B, magnification 200)
Clinical picture: palpable purpura and urticarial plaques at the lower limbs indicating small-vessel vasculitis of the skin (C, D,
E, F).

Figure 2 MRI findings of a cerebral large vessel vasculitis in SLE: Bilateral nonspecific periventricular and subcortical white
matter lesions (white arrows, A,B), hyperintense in fluid-attenuated inversion recovery (FLAIR) sequence (white arrows, A) and
hypointense in T1MR 3D sequences (white arrows, B).

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Cerebral large vessel vasculitis in SLE

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Fluid-attenuated inversion recovery images showed vasculitis resolved and the patient had no further
abnormal nonspecific periventricular and subcor- neurological complaints. However, during tapering
tical white matter lesions bilaterally. MRA demon- of corticosteroid doses she still suffered from epi-
strated vessel pathology of bilateral middle cerebral sodes with recurrent bilateral parotitis. Moreover,
arteries and anterior cerebral arteries strictly invol- she complained about frequent respiratory infec-
ving proximal segments. The pathological vessels tions. Therefore, belimumab was stopped in
had classic beading-like appearance. In conjunction March 2013. Since then, she has been treated with
with the clinical presentation of this patient large- corticosteroids. To date she has shown no exacer-
vessel vasculitis was suspected. However, these bation of the disease. In November 2013 cerebral
vessel abnormalities caused neither haemody- MRT was conducted that showed no alteration of
namic-relevant stenosis nor acute hypoperfusion her vessels (Figure 3).
of adjacent cerebral areas at the time of SLE/SS patients presenting with neurological
investigation. symptoms urge immediate neurological consult-
Clinical neurological examination, neuroimaging ation and cerebral neuroimaging (CT, MRI).
data and laboratory findings led to the diagnosis of However, there is no gold standard for the diagno-
neuropsychiatric systemic lupus erythematosus sis of NPSLE.1 Clinical neurological examination,
(NPSLE) based on large cerebral vessel vasculitis. neuroimaging and laboratory investigations are
Treatment with cyclophosphamide was initiated. useful tools to make the diagnosis.2
The patient received a bolus of cyclophosphamide NSPLE occurs in 13–75% of patients with SLE.
(10 mg/kg body weight) every 4 weeks and con- It exhibits a wide variety of both neurological and
comitant systemic methylprednisolone (0.5 mg/kg psychiatric symptoms.1,3–5
body weight). A week after the first treatment Although its aetiology and pathophysiology are
cycle, both the headache and leukocytoclastic vas- not clear, cerebral vascular tissue injury seems to
culitis of the lower limbs regressed. She received play a pivotal role. Cerebral tissue damage leads to
three further pulses of cyclophosphamide. The distinct findings in neuroimaging consisting of
patient refused further cyclophosphamide adminis- small white matter lesions in periventricular and
tration although there were no adverse events and it subcortical brain regions. However, MRI findings
was effective. After the third cyclophosphamide are absent in up to 40% of all patients with
pulse cutaneous vasculitis recurred. Therefore, the NPSLE.6 In SLE, stroke (either ischaemic or haem-
administration of belimumab was started in orrhagic) and diffuse cerebral vasculopathy are two
September 2012. Arthralgia and cutaneous common causes of central nervous system (CNS)

Figure 3 MRI findings of a cerebral large vessel vasculitis in SLE previous and after immunosuppressive therapy (corticosteroids,
cyclophosphamide and belimumab): Intercerebral time-of-flight (IC-ToF) – MR angiography shows beading-like lesions mainly of
both middle cerebral arteries (MCA) and anterior cerebral arteries (ACA). After administration of immunosuppressive agents
intercerebral time-of-flight (IC-ToF) – MR angiography shows no alteration of vessel (B).

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Cerebral large vessel vasculitis in SLE

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vascular injury. Only 10% of all published cases and showed efficacy for SLE patients with skin
have identified a true vasculitis affecting small- involvement and vasculitis. However, it is not rec-
sized cerebral vessels.7 ommended for lupus nephritis and NPSLE.15
The prevalence of cutaneous vasculitis in Therefore, in accordance with the patient, we
European SLE patients is about 11%. SLE patients have chosen belimumab for further maintenance
with vasculitis have a higher prevalence of livedo therapy.
reticularis, anaemia, erythrocyte sedimentation rate In brief, the combination of relapsing cutaneous
(ESR) >50 mm/h, anti-La/SS-B antibodies and a small-vessel vasculitis and the onset of NPSLE due
higher mean European Consensus Lupus Activity to cerebral large-size vessel involvement with dis-
Measurement (ECLAM) score compared with SLE tinct findings in neuroimaging is unique in the
patients without vasculitis.8 Our patient met four of literature.
these criteria (high ECLAM score, La/SS-B antibo-
dies, anaemia and high ESR). Moreover, this case
confirms recent findings of Fukuda et al.9 who Funding
showed that SLE patients with anti-Ro/SS-A anti-
bodies are more prone to develop cutaneous This research received no specific grant from any
vasculitis. funding agency in the public, commercial, or not-
However, to the best of our knowledge, large for-profit sectors.
cerebral vessel disease in concurrence with small-
vessel disease in the periphery has never been
described before. Interestingly, cutaneous vasculitis Conflict of interest statement
in patients with SLE was not associated with the
occurrence of NPSLE.3 The authors have no conflicts of interest to declare.
Cerebral large vessel vasculitis itself in SLE, as
seen in our patient, is rare. There are only a few
case reports published so far.10,11 All patients with References
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