EDITORIAL
Livedoid Vasculopathy
What Is It?
I
N THIS issue of the ARCHIVES, Papi et al1 report
an exciting advancement in that modern inves-
tigative methods, including assessments of sur-
face expression of platelet P-selectin and circu-
lating levels of interleukin 1b, tumor necrosis
factor a, interleukin 8, interleukin 2, and soluble inter-
leukin 2 receptor, were used to study and compare 2 pa-
tient groups, one with livedoid vasculopathy and the other
with cutaneous small vessel vasculitis, with a group of
healthy controls. Livedoid vasculopathy and cutaneous
small vessel vasculitis have been confused because of se-
mantic and classification problems. Papi and colleagues
compare a group of patients who most likely had vessel-
based disease with an immune-mediated pathogenesis (cu-
taneous small vessel vasculitis) with a group of patients
with a disease with a more vague pathogenesis (livedoid
vasculopathy), possibly related to platelet and local en-
dothelial factors. Their data support the hypothesis that
different mechanisms have a role in the 2 disease enti-
ties, ie, elevation of cytokine levels in cutaneous small
vessel vasculitis and platelet and, to a certain degree, lym-
phocytic activation in livedoid vasculopathy. The prob-
lem is that, as we expand our capabilities to apply basic
investigative laboratory techniques to clinical problems
of vasculitis and/or vasculopathy, we will find ourselves
increasingly handicapped by our inability to communi-
cate clearly regarding disease classification.
See also page 447
There are problems with semantics and classifica-
tion in cutaneous small vessel vasculitis2 and in other vas-
culitic syndromes, including Behçet disease.3 This edito-
rial provides an opportunity to review what may be an even
worse semantic classification problem, one involving live-
doid vasculopathy. I agree with Papi and colleagues that
livedoid vasculopathy represents cutaneous vasculopathy
characterized clinically by painful cutaneous ulcerations
that generally occur on the lower extremities. Confusion
mainly centers on the terms atrophie blanche4,5 and livedo
reticularis.6 I believe that livedoid vasculopathy is only one
cause of atrophie blanche lesions and that it has nothing
to do with livedo reticularis. In my view, one article in which
this distinction was not clearly made was published by Mil-
stone et al.7 I believe that patients with both types of le-
sions were included in their study, which involved the clas-
sification and therapy of atrophie blanche. It is perhaps
worth reviewing the history of atrophie blanche and of li-
vedo reticularis before returning to a discussion of the prob-
lem of livedoid vasculopathy.
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Atrophie blanche was first reported in 1929 by Mil-
ian,8 when he described a particular form of cutaneous
atrophy that he believed was associated with either syphi-
lis or tuberculosis. It seems that he was referring to the
distinctive, painful, ulcerated lesions on the lower ex-
tremities associated with porcelain white, stellate scars.
The term atrophie blanche was used by Degos9 and Nel-
son10 in the 1950s to describe patients with characteris-
tic clinical lesions and histopathologic findings of fibrin-
ous occlusion of dermal blood vessels. Most case series
separated patients with primary idiopathic atrophie
blanche from patients with lesions secondary to stasis der-
matitis and from patients with lesions of atrophie blanche
with collagen vascular diseases.11 All authors were uni-
form in describing ulcers with a narrow border of telan-
giectasia around the stellate scars as opposed to a true
netlike livedo reticularis pattern.
Livedo reticularis has also had numerous names, in-
cluding livedo racemosa. Livedo reticularis is a mottled,
red to blue, reticulated, vascular pattern of the skin that
can develop as a normal physiological reaction to cold
but can also occur in a number of other settings in which
there is persistence despite rewarming.12,13 This desig-
nation has existed since Hebra’s time, and in the mid 1800s
it was applied to a violaceous discoloration of the skin
in a netlike pattern due to a local circulatory distur-
bance.14 A discussion of the differential diagnosis of li-
vedo reticularis is beyond the scope of this review but
includes a number of primary and secondary physiologi-
cal, pharmacological, congenital, and reactive processes
of the skin. I prefer to separate blanchable livedo reticu-
laris from necrosing livedo reticularis. Necrosing livedo
reticularis always requires aggressive medical and der-
matologic evaluation. The differential diagnosis of nec-
rosing livedo reticularis is similar to that of multiple pe-
ripheral gangrene in that both differential diagnoses
include larger vessel vasculitis, such as occurs in pa-
tients with polyarteritis nodosa; hyperviscosity states, in-
cluding hypercoagulable states, polycythemia rubra vera,
and antiphospholipid antibodies; and emboli, which can
occur by various mechanisms, including cholesterol em-
boli, emboli secondary to vessel disease, and even vaso-
spasm, such as can occur in the setting of pheochromo-
cytoma or amantadine hydrochloride administration.
The name atrophie blanche, which is a nonspecific
term, is best reserved as a descriptor of morphological ap-
pearance but should be avoided as a diagnosis. Some de-
gree of venous stasis is very common and perhaps very rel-
evant in terms of explaining the distribution of vessel-
based lesions that occur in diseases that affect the lower
 extremities. However, patients with venous stasis who have
a history of venous stasis ulceration or other sequelae, in-
cluding sclerosing panniculitis15; and clinical findings of
stellate scars should be considered to have stellate scar-
ring secondary to the venous stasis disease. Patients with
biopsy-confirmed histological leukocytoclastic vasculitis
and clinical lesions of palpable purpura consistent with
cutaneous small vessel vasculitis, whether it be idio-
pathic or secondary to some other disease, including con-
nective tissue vascular diseases, should be considered to
have stellate scarring secondary to vasculitis. The name
livedoid vasculopathy should be applied only to patients with
the primary idiopathic form of the disease.
Early descriptions of patients with livedoid vascu-
lopathy using the designation livedo vasculitis were
written from the Mayo Clinic.16,17 Schroeter et al16 and
Bard and Winkelmann17 also used the term segmental
hyalinizing vasculitis. Their review of earlier reported
cases, including the article by Feldaker et al,18 showed
that livedo was incorporated into the term livedo
reticularis in the United States in the 1950s. Interpre-
tation of an article by Nelson10 describing thickened,
hyalinized, subepidermal blood vessels led to the
theory suggested by Mayo Clinic authors16,17 that this
was a segmental hyalinizing form of vasculitis. The
concept of a primary vasculitis was said in the mid-
1970s to be supported by findings of fibrin, immuno-
globulin, and complement components localized to
the hyalinized vessel walls in patients with these
lesions.19 In other reports from this period, the asso-
ciation between livedoid vasculopathy and connective
tissue diseases was put forth as additional evidence of
an immune complex–mediated mechanism. Su and
Winkelmann,11 in a 1980 review, and Winkelmann et
al, 20 in 1974, stated that hemosiderosis in patients
with livedoid vasculopathy could produce a patchy
“pseudo livedo” pattern.
My colleagues and I at Wake Forest University
School of Medicine, Winston-Salem, NC, entered into
the debate in 1992 with an article in which we
described 6 patients with characteristic cutaneous
manifestations of what I prefer to call livedoid vascu-
lopathy.21 Patients could enter into our study only if
they had new, active lesions with purpura. Only
patients with primary idiopathic livedoid vasculopathy
were included. Fibrinopeptide A levels were elevated
(P#.001). In all patients, routine histological speci-
mens showed similar findings consisting of prolifera-
tion of superficial dermal blood vessels with a variable
degree of thrombosis, and the interstitium contained
extravacated erythrocytes, hemosiderin deposits, and
scattered lymphocytes. Rare interstitial neutrophils
were present in one specimen, but no neutrophils
were identified within dermal blood vessel walls, and
no neutrophilic nuclear dust was present. The granu-
lar immunofluorescence staining pattern, typical of
immune complex disease, was not seen in any biopsy
specimen. 21 Electron microscopy of small dermal
blood vessels showed basement membrane thickening
and reduplication and, rarely, thrombus formation.
Neutrophils were not observed within vessel walls,
and subendothelial dense deposits consistent with
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immune complexes were absent. Our view remains
that our small study supported numerous anecdotal
suggestions that thrombotic or microcirculatory
mechanisms might be operative in the pathogenesis of
livedoid vasculopathy, not vasculitis. While published
reports suggest that antivasculitis therapy is not effec-
tive, different types of vasculopathy-directed treat-
ment, such as fibrinolytic, anticoagulant, and anti-
platelet therapies, that are anecdotally claimed to be
effective include the combination of phenformin
hydrocloride and ethylestrenol,5 heparin and ticlopi-
dine hydrochloride,22 and aspirin and dipyridamole23
as well as aspirin and pentoxifylline.24 I suspect that
because stellate scarring can occur as a sequela of tis-
sue injury in patients with cutaneous small vessel vas-
culitis, semantic confusions will continue. Authors
investigating this type of patient (as opposed to
patients with primary idiopathic livedoid vasculopa-
thy) will have an easy time showing evidence of vascu-
litis in the lesions of cutaneous small vessel vasculitis!
By being very precise in their patient selection cri-
teria, Papi and associates,1 like Sams24 and McCalmont
et al,21 have included only patients with livedoid vas-
culopathy who do not have underlying disease. Papi
and colleagues have presented what, in my view, is an
interesting study that reveals preliminary differences
between patients with livedoid vasculopathy and those
with cutaneous small vessel vasculitis. Obviously,
these findings will require independent confirmation
and will need to be expanded to help us gain further
understanding into the pathogenesis of both disorders.
Only by using similar systems of patient classification
for inclusion in clinical studies can we make meaning-
ful interpretations of the significance of findings from
complex, evolving basic laboratory techniques as they
are applied to the understanding of clinical disease.
We in dermatology are unfortunately burdened with
confusing designations and historic labels for disease,
and it is difficult to free ourselves from the shackles of
these names. I have used the designation livedoid
vasculopathy; however, it remains obvious that
although the vasculopathy portion of this designation
might be very appropriate, the livedoid portion
remains confusing. I doubt very much whether con-
clusions drawn by Papi and coworkers could be
extrapolated to a group of patients with necrosing
livedo reticularis, some of whom might have antiphos-
pholipid antibodies and some of whom might have
cholesterol emboli. How can we proceed to a more
logical future? History will probably not help us. Res-
urrection of the concept of atrophie blanche adds con-
fusion by including patients who may have stellate
scarring as a result of venous stasis or vasculitis. Live-
doid vasculopathy might be the best name for now, but
that should not deter us from attempting to find a bet-
ter designator in the future.
Joseph L. Jorizzo, MD
Department of Dermatology
Wake Forest University School of Medicine
Medical Center Boulevard
Winston-Salem, NC 27157-1071

REFERENCES
1. Papi M, Didona B, De Pità M, et al. Livedo vasculopathy vs small vessel cutaneous
vasculitis: cytokine and platelet P-selectin studies. Arch Dermatol. 1998;134:447-452.
2. Jorizzo JL. Classification of vasculitis. J Invest Dermatol. 1993;100:1065-1105.
3. Mangelsdorf HC, White WL, Jorizzo JL. Behçet’s disease: report of twenty-five
patients from the United States with prominent mucocutaneous involvement.
J Am Acad Dermatol. 1996;3:745-750.
4. Shornick K, Gilliam JN. Idiopathic atrophie blanche. J Am Acad Dermatol. 1983;
8:792-798.
5. Gilliam JN, Herndon JH, Prystowsky SD, et al. Fibrinolytic therapy for vasculitis
of atrophie blanche. Arch Dermatol. 1974;109:664-667.
6. Champion RH. Livedo reticularis: a review. Br J Dermatol. 1965;77:167-179.
7. Milstone LM, Braverman IM, Lucky P, Fleckman P. Classification and therapy of
atrophie blanche. Arch Dermatol. 1983;119:963-969.
8. Milian G. Les atrophies cutanees syphilitiques. Bull Soc Fr Dermatol Syphilol.
1929;36:865-871.
9. Degos R. Dermatologie. Paris, France: Ernest Flamarian; 1953.
10. Nelson LM. Atrophie blanche en plaque. Arch Dermatol. 1955;72:242-251.
11. Su WPD, Winkelmann RK. Livedoid vasculitis. In: Vasculitis. Philadelphia, Pa:
WB Saunders Co; 1980:297-306.
12. Coleman PWM. Livedo reticularis: signs in the skin of disturbance of blood vis-
cosity and of blood flow. Br J Dermatol. 1975;93:519-529.
13. Ryan TJ, Coleman PWM. Microvascular pattern and blood stasis in skin dis-
ease. Br J Dermatol. 1969;81:563-573.
14. Ebert MH. Livedo reticularis. Arch Dermatol Syphilol. 1927;16:426-441.
15. Jorizzo JL, Zanolli MD, White WL, Greer KE, Solomon AR, Jetton LR. Primary
sclerosing panniculitis: a clinicopathologic assessment. Arch Dermatol. 1991;
127:554-558.
16. Schroeter AL, Diaz Perez JL, Winkelmann RK. Livedo vasculitis (the vasculitis of
atrophie blanche): immunohistopathologic study. Arch Dermatol. 1975;111:188-
193.
17. Bard JW, Winkelmann RK. Livedo vasculitis: segmental hyalinizing vasculitis of
the dermis. Arch Dermatol. 1967;96:489-499.
18. Feldaker M, Hines EA Jr, Kierland RR. Livedo reticularis with ulceration. Circu-
lation. 1956;13:196-216.
19. Schroeter AL, Coleman PW, Jordon RE, Sams WM Jr, Winkelmann RK. Immu-
nofluorescence of cutaneous vasculitis associated with systemic disease. Arch
Dermatol. 1971;104:254-259.
20. Winkelmann RK, Schroeter AL, Kierland RR, Ryan TM. Clinical studies of live-
doid vasculitis (segmental hyalinizing vasculitis). Proc Mayo Clin. 1974;49:746-
750.
21. McCalmont CS, McCalmont TH, Jorizzo JL, White WL, Leshin B, Rothberger H.
Livedovasculitis: vasculitis or thrombotic vasculopathy? Clin Exp Dermatol. 1992;
17:4-8.
22. Jetton RL, Lazarus US. Minidose heparin therapy for vasculitis of atrophie blanche.
J Am Acad Dermatol. 1983;8:23-26.
23. Drucker CR, Duncan WC. Antiplatelet therapy in atrophie blanche and livedo vas-
culitis. J Am Acad Dermatol. 1982;7:359-363.
24. Sams WM Jr. Livedo vasculitis: therapy with pentoxifylline. Arch Dermatol. 1988;
124:684-687.

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