Lupus (2010) 19, 1340–1343

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CASE REPORT

Livedoid vasculopathy and recurrent thrombosis in a patient with

lupus: seronegative antiphospholipid syndrome?
B Sopeña1,3, MT Pérez-Rodrı́guez1, A Rivera1, JA Ortiz-Rey2, J Lamas1 and MC Freire-Dapena1
1
Internal Medicine Department, Thrombosis and Vasculitis Unit, Complexo Hospitalario Universitario de Vigo, Spain;
2
Pathology Department, Complexo Hospitalario Universitario de Vigo, Spain; and 3Faculty of Medicine, University
of Santiago de Compostela, Spain

Livedoid vasculopathy is a rare condition which predominantly affects young women. It is

characterized by intense painful purpuric maculae in the legs, ankles and feet, due to throm-
bosis of the small and medium-sized dermal vessels, in the absence of vasculitis. Livedoid
vasculopathy has been frequently associated with hypercoagulable states and antiphospholipid
syndrome. We describe a 34-year-old White woman suffering from systemic lupus erythema-
tosus, livedo reticularis, haemolytic anaemia, severe thrombocytopenia and recurrent venous
thrombosis who was admitted to the hospital for extremely painful purpuric lesions in her
lower limbs. The clinical and histological findings were diagnostic of livedoid vasculopathy.
Once the initial sub-therapeutic international normalized ratio levels were corrected, livedoid
vasculopathy did not recur. Tests for antiphospholipid antibodies were repeatedly negative.
This case, the first reported of livedoid vasculopathy in a patient with seronegative
antiphospholipid syndrome and systemic lupus erythematosus, draws attention to livedoid
vasculopathy, a thrombotic dermopathy that may be under-diagnosed in patients with
antiphospholipid syndrome. Lupus (2010) 19, 1340–1343.

Key words: livedoid vasculopathy; seronegative antiphospholipid syndrome; systemic lupus

erythematosus

Introduction
diagnosing APS was 71%,5 the modifications intro-
duced in 2006 appear to improve the specificity but
The term seronegative antiphospholipid syndrome at the expense of reducing the sensitivity even fur-
(APS) was formally proposed in 2003 by Hughes ther.6 Most of the experts in this area agree that,
and Khamashta in order to include all those over time, we have accumulated enough experience
patients with symptoms which are suggestive of to support the existence of seronegative APS in
APS in which lupus anticoagulant (LA), anticar- clinical practice.1,7–10 Thus, once other hypercoa-
diolipin antibodies (aCL) and anti-b2-glycoprotein gulable disorders have been completely excluded,
1 antibodies were consistently undetected.1 Since the presence of clinical criteria of APS, together
then, the existence of seronegative APS has been with other suggestive manifestations, such as
controversial,2,3 and the latest definition of APS thrombocytopenia and livedo reticularis, in the
(revised Sapporo criteria for APS) neither considers absence of antiphospholipid antibodies (aPL),
nor permits the possibility of such a diagnosis.4 allows us to consider seronegative APS.
Nevertheless, it should be taken into account that Livedoid vasculopathy (LV) is a rare condition
these criteria were developed for classification pur- characterized by highly painful purpuric maculae in
poses and, therefore, do not always reflect daily the legs, ankles and feet, due to dermal thrombosis
clinical practice. In fact, it is estimated that if the of the small and medium-sized vessels, in the
sensibility of the 1999 Sapporo criteria for absence of vasculitis.11 Most authors agree that
LV is primarily associated with procoagulable dis-
orders and APS.12,13 Although frequently reported
Correspondence to: Bernardo Sopeña, MD, PhD, Internal Medicine
Department (eleventh floor), C/Pizarro 22, 36204-VIGO (Pontevedra),
in dermatological series, LV has surprisingly little
Spain. Email: bsopena@gmail.com representation in the APS published series. No case
Received 7 March 2010; accepted 4 May 2010 of LV was specifically recorded in a recent study of
! The Author(s), 2010. Reprints and permissions: http://www.sagepub.co.uk/journalsPermissions.nav 10.1177/0961203310373783

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 Livedoid vasculopathy and recurrent thrombosis in a patient with lupus: seronegative APS?
B Sopeña et al.
1341
14
cutaneous manifestations of APS and in a series
of 1000 patients with APS.15 We describe the first
case of livedoid vasculopathy associated with sero-
negative APS in a patient diagnosed with systemic
lupus erythematosus (SLE).

Case report

A 34-year-old white woman was admitted to our

hospital for extremely painful skin lesions in her
lower limbs. SLE had been diagnosed when she
was 26 years old, and since then she has presented
several episodes of acute lupus pneumonitis and
autoimmune haemolytic anaemia. Four years Figure 1 Area of focal necrosis with detachment of the
before admission she was diagnosed with WHO epidermis (haematoxylin and eosin; magnification  200).
class IV lupus nephritis and successfully treated
with corticosteroids plus monthly intravenous
bolus of cyclophosphamide. One year later (with
complete remission of her nephropathy) a sponta-
neous deep venous thrombosis of the right femoral
vein was diagnosed by Doppler ultrasonography. A
complete coagulopathy study, which included aCL,
LA, protein C, protein S, homocysteine, factor V
Leyden, anti-thrombin-III and prothrombin gene
mutation (G20210A), was negative. Treatment
with coumarinic acid at an international normal-
ized ratio (INR) of 2–3 for 6 months was pre-
scribed. Six months after oral anticoagulation was
discontinued a new episode of spontaneous
deep vein thrombosis at the level of the popliteal,
tibio-peroneal and left anterior tibial veins was
diagnosed. Since then the patient has been on
Figure 2 The small and medium-sized arterial and venous
dicoumarin treatment. A new complete coagulopa- vessels of the deep dermis presented a fibrinous vascular occlu-
thy study was again negative. Antiphospholipid sion with partial endothelization of the thrombi and red cell
antibodies (aCL and LA) were repeatedly negative. extravasation without mural inflammatory infiltration (haema-
On admission, the patient presented with a week- toxylin and eosin; magnification  600).
long history of intense pain in both feet. Her lower
extremities revealed livedo reticularis and painful with focal necrosis of the epidermis and annexes
purpuric maculae in her internal ankles that with no evidence of vasculitis (Figures 1 and 2).
extended to the toes of both feet. Results from a Deposits of immunoglobulin and complement
complete haematological and biochemical study, were not detected by direct immunofluorescence
including urine sediment and 24-h proteinuria, testing. aPL (on this occasion with anti-b2-glyco-
were normal. Anti-DNA (detected by indirect protein 1 antibodies) were tested and remained neg-
immunofluorescence using Crithidia luciliae) was ative. Clinical improvement was achieved without
positive 1/320, C3 55 mg/dL (normal range relapses after oral anticoagulation was optimized
84–167 mg/dL) and C4 5 mg/dL (normal range and hydroxychloroquine was started.
16–31 mg/dL), with no other clinical signs of Eight years after the LV episode the patient suf-
lupus activity. A Doppler ultrasonography study fered a severe thrombocytopenia, which reached
of both legs was negative for deep vein thrombosis. a nadir of 5000 platelets/mm3, and responded
She was taking prednisone (10 mg/day), azathio- completely to corticosteroids. Nevertheless, when
prine (100 mg/day) and acenocoumarol with an steroid dose was tapered to less than 15 mg daily
INR of 1.09 on admission. A deep cutaneous the platelet count decreased to below 40,000 plate-
biopsy revealed an ischaemic injury of the skin lets/mm3, which forced us to suspend the
Lupus

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 Livedoid vasculopathy and recurrent thrombosis in a patient with lupus: seronegative APS?
B Sopeña et al.
1342

acenocumarole on various occasions. A complete The diagnosis of seronegative APS in patients

thrombophylia study, including once again aCL with SLE is especially challenging since both
IgG and IgM, anti-b2-glycoprotein 1 antibodies entities share many symptoms and signs.15
(all of them measured by standardized enzyme- Nonetheless, our patient in addition to LV had
linked immunosorbent assay [ELISA]) and LA other clinical manifestations which were suggestive
(detected by clotting assays according to the guide- of APS. Autoimmune haemolytic anaemia was
lines of the International Society on thrombosis observed in 10% of patients with APS15 and in
and haemostasis) were negative.4 Rituximab was 3.8% of patients with SLE without aCL antibo-
prescribed with an excellent response to date, dies.21 On the other hand, up to 74% of SLE
10 months after its administration. patients with haemolytic anaemia have aCL anti-
bodies.22 For some authors the presence of positive
Coombs haemolysis in patients with SLE must be
Discussion considered as a marker of APS.22 Thrombo-
cytopenia (<100,000 platelets/mm3) is observed in
20% of patients with SLE frequently associated
Since LV was originally described with the name
with secondary APS.15 Severe thrombocytopenia
of ‘atrophie blanche en plaque’ by Milian in 1929, (<20,000 platelets/mm3) has been reported in only
different terms such as livedo reticularis with ulcer- 2.2% of SLE patients, in most cases associated with
ations, segmental hyalinizing vasculitis and livedo aCL antibodies.23,24 We have found no studies that
vasculitis, and more recently the acronym establish the prevalence of aCL in SLE patients
PURPLE (painful purpuric ulcers with reticular pat- with severe thrombocytopenia. Also, recurrent
tern of the lower extremities) have been imprecisely deep vein thrombosis is significantly more frequent
used to refer to this dermatologic disorder and have in SLE associated with APS. The risk of a single
contributed to generating terminological and con- episode of vein thrombosis has been estimated in
ceptual confusion.11,13 In the early stages of LV 6% at 20 years in SLE patients without detectable
painful small purpuric maculae or papules typically LA, rising to 50% in those cases with positive
appear in the lower limbs. Usually, they are bilateral LA.25,26
and can progress to superficial ulcerations, which In conclusion, our SLE patient has a hypercoa-
are generally accompanied by livedo reticularis.11,16 gulable state identical to APS except for the persis-
The irregularly shaped ulcers heal eventually to tent negativity of LA and aPL antibodies. Using
leave behind stellated, porcelain-white scars named the term ‘seronegative APS’, although it changes
atrophie blanche (the final stage of LV).11,17 neither the prognosis nor the therapy, may help
Although the pathogenesis of LV is not fully under- the patients and their doctors to better understand
stood, most authors agree that it reflects a hypercoa- their disease and to explore the clinical possibilities
gulable state.11–13,16–19 The definite diagnosis of LV of APS in real clinical practice.1 In addition, the
is made when the biopsy of the affected skin shows clinical case presented here draws attention to
proliferation of the superficial dermal vessels with LV, a thrombotic dermopathy that may be under-
intraluminal thrombosis, erythrocytic extravasa- diagnosed in the series of patients with APS.
tion, haemosiderin deposits and scarce lymphocytes,
in the absence of leukocytes and neutrophilia.11,13,17
The immunofluorescence study of the cutaneous References
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