Case Report
Dermatology 1992:185:296-299

Departments of Dermatology and
Neurology, Catholic University of Leuven.
Belgium

Key Words
Sneddon’s syndrome
Hemostatic examination
Acetylsalicylic acid

Sneddon's Syndrome: Generalized
Livedo reticularis and
Cerebrovascular Disease
Importance of Hemostatic Screening

Abstract
We report two cases of Sneedon’s syndrome. Both cases had widespread livedo
reticularis with repeated cerebrovascular accidents without persistent ncurological deficit. In one case, hemostatic examination revealed an imbalance of plas­
minogen activator-inhibitor values, possibly related to the thrombogenic pro­
pensity of the syndrome. Treatment with acetylsalicylic acid led to normaliza­
tion of hemostatic parameters and resulted in a symptom-free period of more
than 10 months. The importance of hemostatic screening in patients with Sneddon’s syndrome is discussed.

Introduction
Sneddon’s syndrome is a rare entity characterized by
livedo reticularis and cerebrovascular lesions. The nature
and pathogenesis of these associated findings remain
unclear. A possible role of disturbances in coagulation was
already suggested in previous reports [ I ]. In this report, the
role of hemostatic screening in patients with Sneddon’s syn­
drome is discussed.

Case Reports
Cu.se I

A 49-year-old woman had suffered from repeated drop attacks
since 1986 and was admitted for this reason to the Neurology Depart­
ment in july 1989. During the last 2 months drop attacks had appeared
more frequently. Muscle spasms in the right arm and transient global
amnesia accompanied each attack. Memory and intellectual capacities
became impaired and the patient developed a depressive mood. Less
striking for the patient herself was the presence for more than 10 years
of livedo reticularis accentuated on arms and legs. Medication con­
sisted of metoprolo tartrate. 100 mg. captopril. 50 mg. and mianserine
hydrochloride. 30 mg.

More than 10 years before, the patient had taken oral contracep­
tives for a period of 5 years. She did not smoke or drink alcohol. The
family history was noncontributory.
Clinical examination revealed a widespread mottled reticular
livedo on the trunk, arms. legs, backs of the hands, lateral and dorsal
sides of the feet (fig. 1.2 ). The fingers and tocss were cyanotic (fig. 2).
Neurological examination showed impairment of cortical functions:
dyscalculia. constructive apraxia, spatial agnosia, dysnosognosia and
disturbance of recent memory. The patient was obese (weight: 74 kg.
height: 165 cm), and the blood pressure values were elevated (150/90
mm Ilg). Peripheral arterial pulsations were present.
Laboratory tests revealed normal hematological and biochemical
findings except for a slight increase in SGOT: U/l (normal values: 2-19
U/l). SGPT: 58 U/l (normal values: 5-24 U/l) and LDH: 298 U/l (nor­
mal values: 80-240 U/l). Hemostatic examination showed increased
values for fibrinogen degradation products: 45 mg/I (normal values:
< 16 mg/I). Antinuclear antibodies and rheumatoid factor were
absent.
Except for ventricular hypertrophy on echocardiography and rare
ventricular extrasystolcs on Holter monitoring, cardiological assess­
ment revealed no important heart disease. Cerebral four-vessel angi­
ography showed no significant vascular changes. On fundoscopy. vas­
cular signs of arterial hypertension were present reaching stage II.
without evidence of vasculitis. The electro-encephalogram was nor­
mal. An important asymmetrical cortical-subcortical atrophy was
detected on CT scan. Scintillation tomography with (echnetium-99

Prof. I)r. H. Dcgrccf
U Z Leuven. Department of Dermatology
Kapucijnenvoer 33
B-3000 Leuven (Belgium)

© 1992 Karger A G . Basel
1018-8665/92/1854-0296
$ 2.75/0

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J. Devos
J. Bulcke
H. Degree/
B. Michielsen

revealed a diminished blood flow in some cortical areas of the left cer­
ebral hemisphere.
Histological examination of cutaneous biopsy specimens showed
only minimal perivascular infiltration of mononuclear inflammatory
cells in the dermis but no vascular pathology. Direct immunofluores­
cence was negative for deposits og IgG. IgM. IgA or C'3.
No specific treatment was added to the daily medication and spon­
taneous amelioration appeared. The patient is currently free of neuro­
vascular symptoms. However, generalized livedo reticularis persists.
The results of a control blood analysis after 1.5 years were compa­
rable with those of previous examinations. However, hemostatic
screening showed elevated tissue plasminogen activator antigen
(t-PA): 17 jtg/l (normal values: 2-10 pg/l) and normal values of tis­
sue plasminogen activator-inhibitor (PAI-1): 21 pg/l (normal values:
(MO pg/l).

Case 2
Fig. 1. Case 1: widespread livedo reticularis on the trunk.

Fig. 2. Case I: livedo reticularis on the feet. Cyanotic toes.

toms during a follow-up period of 10 months. Livedo reticularis
remained.

Discussion
Sneddon’s syndrome was first described by Champion
and Rook in 1960 after observation of one case with livedo
reticularis and cerebrovascular lesions. Six other cases were
summarized later on by Sneddon [3]. Subsequently, cases
resembling Sneddon’s original patients have been reported

297

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A 46-ycar-old obese man (weight: 78 kg. height: 166 cm) was
admitted to the hospital for sudden paralysis of the left arm reverting
completely after 5 It. The patient suffered from transient paralysis of
the arms for over 5 years, alternately left and right without sequelae.
Orthostatic hypotension appeared 10 years ago after starting clopamide 5 mg and pindolol 10 mg for arterial hypertension. For more than
15 years, a blue patchy discoloration was present on the back, abdo­
men. arms and knees (fig. 3). The blue-violet discoloration was more
pronounced in the winter time and cold weather. The patient smoked
15 cigarettes a day since the age of 20. Alcohol was seldom used. The
family history revealed that 4 out of 7 brothers had had myocardial
infarctions and all of them were obese. His mother and one brother
suffered from diabetes mcllitus. His father died from widespread ath­
eromatosis.
Dermatological examination showed a bluc-violct-colorcd retic­
ular pattern on the back, abdomen and limbs. Identical lesions were
present on the palms and soles. On pressure, these cutaneous lesions
disappeared. Acrocyanosis was absent. Except for hyperreflexia of the
left arm. neurological examination was normal. Blood pressure values
were 140/100 mm Hg and peripheral arterial pulsations were present.
Routine laboratory tests were within normal limits. Hemostatic
tests, however, showed that t-PA was double the normal value: 18 pg/l
(normal values: 2-10 pg/l) and a fourfold increase of PAI-I: 188 pg/l
(normal values: (M 0 pg/l). Thrombin time was slightly increased: 27 s
(normal values: 18-24 s) and factor XII was elevated: 155% (normal
values: 70-130%). No autoantibodies or rheumatoid factor were
found.
Cardiac examination revealed cardiomegaly on radiography and
very rare atrial and ventricular extrasystoles on Holtcr monitoring.
Duplex scan of the carotid arteries excluded arterial stenosis and a CT
scan of the brain showed a lacunar infarction in the left capsula
interna.
Histologically, skin biopsies w'crc characterized by tin increase in
capillary vessels in the papillary dermis. No anomalies of the vascular
wall were present. Direct immunofluorescence was negative for
deposits of IgG. IgM. IgA or C3.
Because of the hemostatic imbalances, therapy with acetylsalicylic
acid was started. The dosage was 300 mg a day. After 4 months, a
remarkable normalization of hemostatic parameters PAI-1 (27 pg/l).
t-PA (5 pg/l) and thrombin time (20 s) was observed while other labo­
ratory findings remained within normal ranges. No autoantibodies
were detected on repeated examination. The patient continued taking
aspirin daily (300 mg a day) and remained free of neurological symp-

298

Fig. 3. Case 2: livedo reticularis on the abdomen.

9], Grattan et al. [1] suggest that there is a possible role of
intimal proliferation and defects of local coagulation, fibri­
nolysis and tissue plasminogen activator levels in the patho­
genesis of conditions characterized by the presence of anti­
cardiolipin antibodies.
Our two patients suffered from widespread livedo retic­
ularis and transient neurological symptoms. Livedo retic­
ularis preceded the onset of the neurological signs. 10 to 15
years before the diagnosis of Sneddon’s syndrome was pro­
posed. Each neurological insult was followed by complete
remission. Common predisposing risk factors for cerebro­
vascular insults in insults in both of our patients were the
presence of obesity and essential arterial hypertension.
Furthermore, the first patient was taking an oral contracep­
tive since adulthood and the second patient smoked, two
additional factors contributing to the elevated cardiovascu­
lar risk [6, 25,26], In the first case, except for the finding of
an early cortical-subcortical atrophy on CT scan and diminshed cortical blood flow on scintitomography, there were
no immunological or cardiovascular anomalies which could
explain the cutaneous and neurological signs. In the second
case, an infarction in the capsula interna was visualized on
CT on the left side and was therefore unrelated to the paral­
ysis of the left arm. Noteworthy arc the abnormal values of
PAI-1 and t-PA antigen present in this patient, which may
reflect an increased susceptibility to thrombosis and vascularocclusion [22], Indeed, t-PA playsa role in removing the
fibrin which may accumulate in the microvesscls in numer­
ous physiopathologic conditions and which hinders the nor­
mal transfer of oxygen into the tissues and the passage of
blood cells in the vessels. As a consequence, impaired tis-

Dcvos/Bulckc/Dcgreef/Michielsen

Sneddon’s Syndrome

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[4|. In the German literature, livedo reticularis has been
associated with lues by Ehrmann [5] in 1907. and Sneddon's
syndrome was considered as a variant of this case.
Cutaneous manifestations of Sneddon’s syndrome
include widespread livedo reticularis with or without ulcer­
ation, purpura, or painful scarring 111. The cerebrovascular
insults originally described by Sneddon were of limited
nature, often leaving little or no residual disability. On the
other hand, there have been reports of several cases with
livedo and progressive cerebral lesions [10-15] or livedo
combined with severe cerebral deficit [2, 16, 17],
Histopathological findings in biopsies of cutaneous
lesions in Sneddon’s syndrome may be very discrete and
nonspecific [3, 14-16]; however, they have been variously
described as endarteritis obliterans [2,24], endotheliosis of
arterioles in the reticular dermis with occasional thrombo­
sis, focal segmental intimal hyperplasia [6,25] with prolifer­
ation and migration of medial smooth muscle cells through
a discontinuous tunica elastica interna in the ascending
arterioles of the upper subcutis or reticular dermis [23).
Common to all these descriptions is a noninflammatory
thickening of the vessel wall with eventual occlusion of the
lumen, however without vasculitis. Livedo reticularis
would be caused by vascular and/or rheological mech­
anisms leading to stasis of blood in the superficial venous
drainage system and to secondary impaired tissue oxygena­
tion [27]. In the central nervous system where collateral cir­
culation is not as rich, ischemia may result in transient or
permanent damage to vital tissues. Postmortem
examination has been performed in only one patient with
Sneddon’s syndrome: endarteritis obliterans of small and
medium-sized cerebral arteries was found [11], General­
ized livedo reticularis and cerebrovascular insults also
occur in association with long-term intake of oral contra­
ceptives, high nicotine intake and arterial hypertension [6,
25]. The exact noxious interaction of these risk factors on
vascular endothelial cells however remains unclear.
The presence of antiphospholipid antibodies, including
anticardiolipin antibodies, lupus anticoagulans and antiVDRL antibodies in Sneddon's syndrome, has been
reported repeatedly the last few years [1, 4, 8. 18. 20]. A
recent report suggests that antiphospholipid antibodies
bind to nuclear fractions of mammalian cells, indicating
that these antibodies may represent antinuclear antibody
activity [19]. Otoyama et al. [18] reported a case of Sned­
don's syndrome with positive antinuclear antibodies and
anticardiolipins and suggest that the syndrome can be
regarded as a primary antiphospholipid syndrome. Anticardiolopin antibodies predispose to thrombosis and vascu­
lar occlusion by a mechanism as yet not fully understood [8,

sue oxygenation is responsible for transient or permanent
damage to vital tissues and can explain the neurovascular
symptoms. Nevertheless, the increase of these endothelial­
cell-derived factors is not a specific finding and can be seen
in patients with diabetes, hyperlipidemia and chronic
hypertension. Remarkably, the first patient showed ele­
vated t-PA values in the clinically symptom-free period,
which reflects diminished susceptibility to thrombosis or
vascular occlusion. In our patients, anticardiolipins were
absent, even when searched for repeatedly. This is in con­
trast to recent reports which stress the presence of antiphos­
pholipid antibodies in Sneddon’s syndrome and regard
them as pathogenic factors [1, 7, 18]. The rarity of this
peculiar disease which combines cutaneous and neurologi­
cal signs, however, suggests that another not yet defined
factor interferes with the pathogenesis. Our cases suggest
that in the absence of antiphospholipid antibodies hemo­
static abnormalities possibly play a role.
Treatment in Sneddon’s syndrome remains a major
problem, as the exact pathogenesis is unknown and the dis­
ease itself has an intermittent course. Avoidance of factors
predisposing to vascular disease as smoking, oral contra­

ceptives. obesity and hypertension seems to be the first
measure to take. A variety of medical treatments have
been used in Sneddon’s syndrome without a distinct effect:
platelet-inhibiting agents, vasodilators, (3-adrenergic block­
ers and immunosuppressive agents [1,7. 25], Recently, a
therapeutic efficacy of acetylsalicylic acid in cases of Sned­
don’s syndrome has been reported [28. 29]. The Hcmostatometer was used for determining changes in platelet func­
tion under acetylsalicylic acid intake. In these reports,
endothelial cell derived factors were not discussed. Our
first patient remained disease-free without any of the
above-mentioned treatments. In the second case, aspirin
was administered in a dose of 300 mg/day, because of the
finding of abnormal values of t-PA, PAI-1 and thrombin
time, which point to hemostatic disturbances. With this
treatment, hemostatic parameters normalized and neuro­
logical symptoms disappeared.
This report attempts to underline the importance of
extensive examination of hemostasis besides the search for
antiphospholipid antibodies in patients with Sneddon’s syn­
drome. In cases where hemostatic abnormalities are found,
therapy with acetylsalicylic acid can be considered.

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