Vasculitis in erythema induratum of Bazin: A histopathologic

Vasculitis in erythema induratum of Bazin:
A histopathologic study of 101 biopsy specimens
from 86 patients
Sonia Segura, MD,a Ramón M. Pujol, MD,a Felicidade Trindade, MD,b and Luis Requena, MDb
Barcelona and Madrid, Spain
Background: Erythema induratum of Bazin is a mostly lobular panniculitis. There is considerable
controversy in the literature about whether or not vasculitis is a histopathologic requirement to establish
the diagnosis of erythema induratum of Bazin. Even accepting vasculitis as a histopathologic criterion, there
is no agreement about the nature and size of the involved vessels.
Objective: The main goal of our study was to investigate whether or not vasculitis was present in a large
series of cases of erythema induratum of Bazin and, when vasculitis was found, to determine the nature and
localization of the involved vessels.
Methods: We studied 101 skin biopsy specimens from 86 patients with clinicopathologic diagnosis of
erythema induratum of Bazin. Histopathologic criteria required in each case to be included in this study
were: (1) a mostly lobular panniculitis with necrotic adipocytes at the center of the fat lobule; (2)
inflammatory infiltrate within the fat lobule mostly composed of neutrophils in early lesions and
granulomatous infiltrate in fully developed lesions; (3) significant fat necrosis; and (4) absence of other
histopathologic findings that allow a specific diagnosis of other lobular panniculitis different from
erythema induratum of Bazin. We also recorded the nature of the inflammatory cells involving the fat
lobule, and the lesions were classified into two main categories: (1) early lesions, when the inflammatory
infiltrate was mainly composed of neutrophils, with or without leukocytoclasis; and (2) fully developed
lesions, when histiocytes and lipophages were the predominant inflammatory cells within the involved fat
lobule.
Results: Some type of vasculitis was evident in 91 cases (90.09%). A total of 47 biopsy specimens (46.5%)
showed a mostly lobular panniculitis with necrotizing vasculitis involving the small vessels, probably
venules, of the center of the fat lobule. Thirteen biopsy specimens (12.8%) showed a mostly lobular
panniculitis with vasculitis involving both large septal veins and small vessels, probably venules, of the
center of the fat lobule. Twelve biopsy specimens (11.8%) showed a mostly lobular panniculitis with
vasculitis involving large septal veins, with no involvement or other septal or lobular vessels. Ten biopsy
specimens (9.9%) showed a mostly lobular panniculitis with vasculitis involving large septal vessels, both
arteries and veins, and necrotizing vasculitis involving the small vessels, probably venules, of the center of
the fat lobule. Nine biopsy specimens (8.9%) showed a mostly lobular panniculitis with vasculitis involving
large septal vessels, both arteries and veins, but with no involvement of the small blood vessels of the
center of the fat lobule. Finally, 10 biopsy specimens (9.9%) showed a mostly lobular panniculitis without
evidence of septal or lobular vasculitis in serial sections. Associated diseases included history of
extracutaneous tuberculosis (including tuberculosis of the lung, lymph nodes, kidney, or bowel) in 12
cases (13.95%), previous episodes of superficial thrombophlebitis of the lower legs in 3 cases (3.72%),
rheumatoid arthritis in one case (1.16%), Crohn disease in one case (1.16%), chronic lymphocytic leukemia
in two cases (2.32%), hypothyroidism in two cases (2.32%), and positive serology for hepatitis B virus in 4
cases (4.65%) and for hepatitis C virus in 5 cases (5.81%).
From the Departments of Dermatology at Hospital del Mar,
Universitat Autónoma, Barcelona,a and Fundación Jiménez
Dı́az, Universidad Autónoma, Madrid.b
Funding sources: None.
Conflicts of interest: None declared.
Reprints not available from the authors.
Correspondence to: Luis Requena, MD, Department of
Dermatology, Fundación Jiménez Dı́az, Avda. Reyes Católicos
2, 28040-Madrid, Spain. E-mail: [email protected].
0190-9622/$34.00
ª 2008 by the American Academy of Dermatology, Inc.
doi:10.1016/j.jaad.2008.07.030
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840 Segura et al
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Limitations: Serial sections were not performed in all cases. At least 10 sections were studied in each case.
When vasculitis was evident in some of these first 10 sections, no further sections were cut, but when
histopathologic features of vasculitis were not found in the first 10 sections, serial sections throughout the
specimen were performed looking for vasculitis. Because some type of vasculitis was evident in the first 10
sections of 91 cases, serial sections were performed only in the remaining 10 cases and they failed to
demonstrate clear-cut histopathologic features of vasculitis. On the other hand, this is a retrospective study
that was performed from the histopathologic slides of our files, and only the clinical information contained
in the report accompanying the biopsy specimen could be recorded.
Conclusions: In our experience, vasculitis is present in most lesions of erythema induratum of Bazin, and
the nature, location, and size of the involved vessels is, from more to less frequent, as follows: (1) small
venules of the fat lobule; (2) both veins of the connective tissue septa and venules of the fat lobule; (3) only
veins of the connective tissue septa; (4) veins and arteries of the connective tissue septa and venules of the
fat lobule; and (5) veins and arteries of the connective tissue septa. However, in some cases with all
clinicopathologic features of erythema induratum of Bazin vasculitis could not be demonstrated with serial
sections throughout the specimen and, therefore, the presence of vasculitis should be not considered as a
criterion sine qua non for histopathologic diagnosis of erythema induratum of Bazin. ( J Am Acad Dermatol
2008;59:839-51.)
Currently, the terms ‘‘erythema induratum of
Bazin’’ and ‘‘nodular vasculitis’’ are used as synonyms by a majority of authors to describe the most
common variant of mostly lobular panniculitides
with vasculitis. This has not always been the case,
however. This form of panniculitis was originally
described by Bazin1 in 1861, as subcutaneous indurate erythematous plaques appearing mainly on the
back of the lower aspect of legs of middle-aged
women. He classified the process as one of the
erythematous benign scrofulids, using ‘‘scrofulids’’
as a descriptive term to refer to deep erythematous
nodules, and it seems that he did not consider this
panniculitis as a tuberculid. The link between tuberculosis and erythema induratum was emphasized
later, around 1900, mostly by French dermatologists
who included erythema induratum within the spectrum of the tuberculids.2 Almost simultaneously,
identical clinical cases with no evidence of tuberculosis were reported by English authors,3,4 which led
later to the development of the concept of erythema
induratum as nontuberculous in origin by Whitfield.5
In 1945, Montgomery et al6 in the United States
proposed the term ‘‘nodular vasculitis’’ for Whitfield
erythema induratum and described its clinical and
histopathologic features as different from those of
erythema induratum of Bazin. Since then, most
textbooks of dermatology described erythema induratum of Bazin, erythema induratum of Whitfield,
and nodular vasculitis as 3 different entities.7 Still,
some current authors have proposed keeping the
name ‘‘erythema induratum of Bazin’’ for those cases
in which a causative relationship with tuberculosis is
demonstrated and refer to the remainder of cases as
nodular vasculitis. In recent years, however, there
seems to be a consensus considering erythema
induratum of Bazin and nodular vasculitis as the
same entity,8,9 an opinion that we shared.10 Like
erythema nodosum, erythema induratum of Bazin is
currently considered to be a reactive disorder related
to several causative factors, one of which may be
tuberculosis, especially in some geographic areas.11
In our country, tuberculosis is by far the most
important causative factor for erythema induratum
of Bazin, and recent polymerase chain reaction
investigations have demonstrated Mycobacterium
tuberculosis DNA in 77% of the cutaneous biopsy
specimens of patients with this variant of panniculitis.12 Although the frequency varies from some
geographic areas to others, in many countries tuberculosis is still the main causative factor for erythema
induratum of Bazin.13-20 In contrast, in those countries with low prevalence of tuberculosis, this type of
panniculitis may be a reactive process as a result of
other causative factors such as obesity, cold climate,
chronic venous insufficiency, or history of thrombophlebitis of the lower limbs.
Typical erythema induratum of Bazin is a disease
of middle-aged obese women in whom erythematous subcutaneous nodules and plaques appear
on the back of the lower aspects of the legs.
Erythrocyanosis, heavy columnlike calves, erythema
surrounding follicular pores, and cutis marmorata
are frequently associated changes and may be
predisposing factors. Although nonulcerated lesions
may heal without scarring, often subcutaneous nodules become adherent to the skin surface and ulcerate. Healing of these ulcers is usually a slow process
resulting in atrophic scars that allow retrospective
diagnosis in nonactive cases. Erythema induratum of
Bazin is more frequent in obese women with some
degree of venous insufficiency of the lower extremities, and subcutaneous nodules with ulceration
develop mostly during the winter months. Lesions
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Fig 1. Early lesion of erythema induratum of Bazin showing mostly lobular panniculitis with
necrotizing vasculitis involving small vessels of center of fat lobule. A, Scanning power. B,
Higher magnification showing mostly lobular panniculitis. C, Infiltrate of fat lobule was mostly
composed of neutrophils. D, Necrotizing vasculitis involving small blood vessels of center of fat
lobule. (A to D, Hematoxylin-eosin stain; original magnifications: A, 310; B, 340; C, 3200;
D, 3400.)
are usually tender but may be indolent or painful
only on pressure. The course is protracted and
recurrent episodes over years, even decades, are
common. Individual lesions tend to involute, but
new crops appear at irregular intervals. Patients with
erythema induratum of Bazin are otherwise in good
health.
From a histopathologic point of view, erythema
induratum of Bazin is a mostly lobular panniculitis.
At an early stage, the fat lobules are punctuated
throughout by discrete collections of inflammatory
cells, mostly neutrophils. There may be extensive
necrosis of the adipocytes of the fat lobule. These
necrotic adipocytes call for histiocytes that ingest
lipid and become foamy. Epithelioid histiocytes,
multinucleated giant cells, and lymphocytes contribute to the granulomatous appearance of the inflammatory infiltrate in fully developed lesions of
erythema induratum of Bazin. When intense vascular
damage is present, extensive areas of caseous necrosis appear and the lesions show all the histopathologic attributes of a tuberculoid granuloma.
Caseous necrosis may extend to the overlying dermis
and secondarily involve the epidermis with ulceration and discharge of liquefied necrotic fat.
Controversy persists in the literature about whether
or not vasculitis is a histopathologic requirement to
establish the diagnosis of erythema induratum of
Bazin. Even accepting vasculitis as a histopathologic
criterion, there is no agreement about the nature of the
involved vessel. Some investigators consider vasculitis as a characteristic histopathologic finding, but they
fail to establish the nature and the size of the involved
vessels.21 When the nature of the involved vessel is
specifically stated, some authors believe that they are
arteries,22,23 whereas other authors favor a venous
involvement,24,25 and still others consider that both
arteries and veins are involved.26-30 The main goal of
our study was to investigate whether or not vasculitis
was always present in our cases of erythema induratum of Bazin and, when vasculitis was found, to
determine the nature and localization of the involved
vessels. This study also describes the histopathologic
features of the largest published series of erythema
induratum of Bazin.
METHODS
Skin biopsy specimens of 86 patients with clinicopathologic diagnosis of erythema induratum of Bazin
were retrieved from the archives of the departments
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Fig 2. Fully developed lesion of erythema induratum of Bazin showing mostly lobular
panniculitis with necrotizing vasculitis involving small vessels of center of fat lobule. A,
Scanning power. B, Higher magnification showing mostly lobular panniculitis. C, Granulomatous infiltrate involving fat lobule. D, Necrotizing vasculitis of small blood vessels at center of
fat lobule. (A to D, Hematoxylin-eosin stain; original magnifications: A, 310; B, 340; C, 3200;
D, 3400.)
of dermatology at Hospital del Mar, Barcelona, Spain
(22 biopsy specimens from 16 patients: 12 patients
with one biopsy specimen, 2 patients with two biopsy
specimens, and 2 patients with three biopsy specimens) and Fundación Jiménez Dı́az, Madrid, Spain
(79 biopsy specimens from 70 patients: 63 patients
with one biopsy specimen, 5 patients with two biopsy
specimens, and two patients with 3 biopsy specimens). From a clinical point of view, all patients
showed characteristic cutaneous lesions, mostly
consisting of erythematous nodules on the back of
the legs. Eighty patients showed positive cutaneous
delayed hypersensitivity reaction to purified protein
derivative (positive Mantoux test result), whereas 3
patients showed negative Mantoux test result and this
test was not performed in another 3 patients. Clinical
data were obtained from patient’s medical records
and, in each case, the demographic data, including
age and sex, location of the lesions, and associated
diseases, were recorded.
From a histopathologic point of view, the following criteria were required to include each case in this
study: (1) a mostly lobular panniculitis with necrotic
adipocytes at the center of the fat lobule; (2) inflammatory infiltrate within the fat lobule mostly
composed of neutrophils in early lesions and granulomatous infiltrate in fully developed lesions; (3)
significant fat necrosis; and (4) absence of other
histopathologic findings that allow a specific diagnosis of other lobular panniculitis different from
erythema induratum of Bazin. Other types of mostly
lobular panniculitis, including pancreatic panniculitis, alpha-1-antitrypsin deficiencyeassociated panniculitis, sclerosing panniculitis, and lupus panniculitis
were ruled out on the basis of the histopathologic
findings. Infective panniculitis was ruled out when
Gram and periodic acideSchiff stains failed to demonstrate micro-organisms in cases of a mostly neutrophilic lobular panniculitis. Foreign body material was
ruled out throughout polarization in those cases of a
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Fig 3. Early lesion of erythema induratum of Bazin showing mostly lobular panniculitis with
vasculitis involving both large septal veins and small blood vessels of center of fat lobule. A,
Scanning power. B, Higher magnification showing lobular panniculitis with neutrophilic
infiltrate. C, Vasculitis involving large vein at septa. D, Necrotizing vasculitis involving small
blood vessels at center of fat lobule. (A to D, Hematoxylin-eosin stain; original magnifications:
A, 310; B, 340; C, 3200; D, 3400.)
mostly lobular panniculitis with granulomatous
infiltrate.
Histopathologic criteria required to establish a
diagnosis of vasculitis included swelling of endothelial cells, leukocytoclasis, fibrinoid changes in vessel
walls, and neutrophils in and around vessel walls.
This vasculitis, the main goal of our study, was not
initially considered as criterion sine qua non to
include a case in this study when all other characteristic histopathologic features of erythema induratum of Bazin were present. However, because
vasculitis was evident in most cases, we recorded in
all those cases the nature, size, and localization of the
involved blood vessel. We also recorded the nature
of the inflammatory cells involving the fat lobule,
and the lesions were classified into two main categories: (1) early lesions, when the inflammatory
infiltrate was mainly composed of neutrophils, with
or without leukocytoclasis; and (2) fully developed
lesions, when histiocytes and lipophages were
the predominant inflammatory cells within the involved fat lobule. Skin biopsy specimens were fixed
in 10% buffered formalin, processed, and paraffin
embedded according to conventional techniques.
Hematoxylin-eosin stain was performed in sections
of each case and, in selected cases, elastic tissue stain
with orcein was performed to determine the nature
of the vessels involved by vasculitis. At least 10
sections were studied in each case. When vasculitis
was evident in some of these first 10 sections, no
further sections were cut, but when histopathologic
features of vasculitis were not found in the first 10
sections, serial sections throughout the specimen
were performed, looking for vasculitis.
RESULTS
Briefly, the clinical features of the 86 patients were
the following: 69 patients were female and 17 were
male. Age ranged from 23 to 81 years (median 55.8
years). All patients showed erythematous subcutaneous nodules in the back of the legs, and in 10 cases
there were also some scattered erythematous nodules on the front of the legs or on the thighs. Two
female patients also showed erythematous nodules
involving the buttocks and one female patient had
lesions involving both the lower and upper limbs
and the trunk. Most patients had new bouts of lesions
or worsening of pre-existing nodules during the
winter. Associated diseases included history of
extracutaneous tuberculosis (including tuberculosis
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Fig 4. Fully developed lesion of erythema induratum of Bazin showing mostly lobular
panniculitis with vasculitis involving both large septal veins and small vessels, probably
venules, of center of fat lobule. A, Scanning power. B, Higher magnification showing lobular
panniculitis with granulomatous infiltrate. C, Vasculitis involving large vein at septa. D,
Necrotizing vasculitis involving small blood vessels at center of fat lobule. (A to D,
Hematoxylin-eosin stain; original magnifications: A, 310; B, 340; C, 3200; D, 3400.)
of the lung, lymph nodes, kidney, or bowel) in 12
cases (13.95%), previous episodes of superficial
thrombophlebitis of the lower legs in 3 cases
(3.72%), rheumatoid arthritis in one case (1.16%),
Crohn disease in one case (1.16%), chronic lymphocytic leukemia in two cases (2.32%), hypothyroidism
in two cases (2.32%), and positive serology for
hepatitis B virus in 4 cases (4.65%) and for hepatitis
C virus in 5 cases (5.81%).
Histopathologically, some type of vasculitis was
evident in the first 10 sections of 91 cases (90.09%). In
the remaining 10 biopsy specimens (9.9%), serial
sections failed to demonstrate clear-cut histopathologic features of vasculitis. In all, 47 biopsy specimens (46.5%) showed a mostly lobular panniculitis
with necrotizing vasculitis involving the small vessels, probably venules, of the center of the fat lobule.
There was no involvement of the septal vessels
(small or large septal vessels). This vasculitic pattern
was seen both in early lesions (with neutrophilic
infiltrate in the fat lobule, 23 cases [22.7%]) (Fig 1)
and in fully developed lesions (with granulomatous
infiltrate within the fat lobule, 24 cases [23.7%])
(Fig 2). Thirteen biopsy specimens (12.8%) showed
a mostly lobular panniculitis with vasculitis involving
both large septal veins and small vessels, probably
venules, of the center of the fat lobule. This vasculitic
pattern was seen both in early lesions (5 cases [4.9%])
(Fig 3) and in fully developed lesions (8 cases [7.9%])
(Fig 4). Twelve biopsy specimens (11.8%) showed a
mostly lobular panniculitis with vasculitis involving
large septal veins, with no involvement or other
septal or lobular vessels. This vasculitic pattern was
seen both in early lesions (2 cases [1.9%]) (Fig 5) and
in fully developed lesions (10 cases [9.9%]) (Fig 6).
Ten biopsy specimens (9.9%) showed a mostly
lobular panniculitis with vasculitis involving large
septal vessels, both arteries and veins, and necrotizing vasculitis involving the small vessels, probably
venules, of the center of the fat lobule. This vasculitic
pattern was only seen in biopsy specimens of early
stages of erythema induratum of Bazin (Fig 7). Nine
biopsy specimens (8.9%) showed a mostly lobular
panniculitis with vasculitis involving large septal
vessels (both arteries and veins), but with no involvement of the small blood vessels of the center of
the fat lobule. This vasculitic pattern was seen both
in biopsy specimens of early lesions (8 cases [7.9%]
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Fig 5. Early lesion of erythema induratum of Bazin showing mostly lobular panniculitis with
vasculitis involving large septal veins, with no involvement or other septal or lobular vessels.
A, Scanning power. B, Higher magnification showing lobular panniculitis. C, Inflammatory
infiltrate of fat lobule was mainly composed of neutrophils. D, Vasculitis involving large vein at
septa. (A to D, Hematoxylin-eosin stain; original magnifications: A, 310; B, 340; C and
D, 3200.)
(Fig 8) and in fully developed lesions (one biopsy
specimen [0.9%]). In all cases with some type of
vasculitis (91 cases, 90.09%), vascular damage was
seen in all of the 10 performed sections, it was
located at the center of the panniculitic process (Figs
1 to 8), and there was not any case in which vasculitis
was identified without inflammation of the surrounding subcutaneous tissue. We did not find any
relationship between the presence of histologic
ulceration and the nature of the inflamed vessels,
because histologic ulceration was evident only in 8
cases (7.9%), and two of them (1.9%) showed vasculitis involving large arteries and veins of the septa
of the subcutaneous septa, whereas the remaining 6
ulcerated cases (5.94%) showed vasculitis involving
the small blood vessels of the fat lobule without any
damage of the large arteries or veins of the connective tissue septa. Extravasated red cells were seen in
the vicinity of the inflamed vessels in most cases.
Finally, 10 biopsy specimens (9.9%), showed a
mostly lobular panniculitis without evidence of septal or lobular vasculitis in serial sections and this
pattern with no vasculitis was seen both in early
lesions (two cases [1.9%]) (Fig 9) and in fully
developed lesions (8 cases [7.9%]) (Fig 10). From
these 10 biopsy specimens without evidence of
vasculitis in serial sections, two biopsy specimens
were from the same patient. Another 3 patients with
two biopsy specimens showed septal large venous
vasculitis in one biopsy specimen, but no evidence
of vasculitis was seen in the other one. The remaining 5 biopsy specimens without vasculitis belonged
to patients with only one biopsy specimen. Table I
summarized the histopathologic features of our
series.
DISCUSSION
In our experience, veins of the connective tissue
septa and small venules of the fat lobule are the most
common blood vessels affected by vasculitis in
erythema induratum of Bazin, because 90.9% of
our cases showed some type of venous vasculitis,
whereas arteries and arterioles were only involved in
18.8% of the cases, and in all these cases with arterial
vasculitis, some type of venous vasculitis was concomitantly identified. In other words, no case with
exclusive arterial or arteriolar vasculitis was found in
our series. It was also remarkable that arterial and
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Fig 6. Fully developed lesion of erythema induratum of Bazin showing mostly lobular
panniculitis with vasculitis involving large septal veins, with no involvement or other septal or
lobular vessels. A, Scanning power. B, Higher magnification showing lobular panniculitis.
C, Granulomatous inflammatory infiltrate involving fat lobule. D, Vasculitis involving large
vein at septa. (A to D, Hematoxylin-eosin stain; original magnifications: A, 310; B, 340; C and
D, 3200.)
arteriolar vasculitis was mostly seen in biopsy specimens with a predominant neutrophilic infiltrate
involving the fat lobule (there was only one case
with involvement of both large arteries and veins of
the septa and granulomatous infiltrate at the fat
lobule), which probably indicates that involvement
of arterial vessels of the subcutaneous fat is only
present in early stages of the evolution of the lesions.
Curiously enough, in 10 biopsy specimens of this
series, which showed all stereotypical clinicopathologic features of erythema induratum of Bazin, serial
sections throughout the specimens failed to identify
clear-cut histopathologic features of vasculitis.
Furthermore, in one patient of our series, who
showed all classic clinicopathologic features of erythema induratum of Bazin, two biopsies were
performed from two separate episodes of the panniculitic process and no evidence of vasculitis was
found in either of the two biopsy specimens,
whereas another 3 patients with two biopsy specimens showed vasculitis of the large septal veins in
one biopsy specimen, but no histopathologic features of vasculitis could be identified in the other
one. Therefore, although rare, some cases of
erythema induratum of Bazin may show all classic
clinicopathologic features of the disorder, except
vasculitis, and thus the term ‘‘erythema induratum of
Bazin’’ is more accurate than ‘‘nodular vasculitis’’ to
name this process.
A review of the literature and of the most famous
textbooks of dermatology and dermatopathology
reveals considerable variation about whether or not
vasculitis is present in the cutaneous lesions of
erythema induratum of Bazin. Even in those cases
in which vasculitis is accepted by the investigators as
a characteristic histopathologic feature, controversy
exists about the size, the nature, and the location of
the involved vessels. Thus, in some textbooks, vasculitis is described as a characteristic histopathologic
finding of erythema induratum of Bazin, but the
nature, size, and location of the involved vessels are
not established.21 Ackerman22 believes that ‘‘nodular
vasculitis is so named because clinically the lesion is a
nodule, and microscopically it is an arteritis. This
severe vasculitis, in which neutrophils, lymphocytes,
and histiocytes participate, involves a muscular arteria and eventuates in ischemic changes within
the lobule or portions of the lobules supplied by
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Fig 7. Early lesion of erythema induratum of Bazin
showing mostly lobular panniculitis with vasculitis involving large septal vessels, both arteries and veins, and
necrotizing vasculitis involving small vessels of center of
fat lobule. A and H, Scanning power. B and I, Mostly
lobular panniculitis with involvement of large vein of
septa. C and J, Higher magnification showing vasculitis
involving large vein of septa. D and K, In other areas with
lobular panniculitis vasculitis involved arteries of septa. E
and L, Higher magnification showing involvement of
septal artery. F, Neutrophilic infiltrate in fat lobule. G,
the affected artery.’’ In our opinion, however, the
involved vessel illustrated by Ackerman22 as an
example of nodular vasculitis (erythema induratum
of Bazin) is better interpreted as a vein rather than as
an artery. In our view, this is a frequent mistake in the
histopathologic study of the panniculitides and vasculitides involving the subcutaneous fat of the lower
legs, because in these areas the veins of the connective tissue septa of the subcutis show a thicker and
more compact muscular layer than the veins of the
subcutis in other areas of the skin and they often are
misinterpreted as arteries.23 Black,24 in agreement
with Ackerman,22 also considers that arteries are the
vessels mainly involved in the lesions of erythema
induratum of Bazin. In contrast, Degos,25 in his
textbook of dermatology, considered that erythema
induratum of Bazin is a mostly lobular panniculitis
with vasculitis mainly involving the veins of the
connective tissue septa of the subcutis. A venous
vasculitis is also postulated by McKee et al26 in their
last edition of Pathology of the Skin, because they
wrote: ‘‘The histologic features [of nodular vasculitis]
combine septal and lobular changes with the presence of vasculitis being a sine qua non (Fig. 9.79). In a
biopsy from an established lesion, the septa are
widened and chronically inflamed (Fig. 9.80). Acute
vasculitis, affecting veins and venules with a heavy
inflammatory cell infiltrate consisting of neutrophils,
lymphocytes and histiocytes is typically present,
sometimes accompanied by vessel wall necrosis
and thrombosis.’’ McKee et al26 failed to establish
the location of the involved vessels, but because they
considered that both veins and venules were involved, we deduce that they interpreted that the
venous vessels of both the connective tissue septa
and the fat lobule were involved. Patterson27 considered that ‘‘vasculitis is frequently present and can
involve small or medium-size vessels (Fig. 100.8). It
may be predominantly neutrophilic, lymphocytic or
granulomatous,’’ but he did not establish whether the
involved vessels were arterial or venous, or whether
the vasculitic process involved the septa, the fat
lobule, or both. Other authors believe that both
venous and arterial blood vessels are involved in
lesions of erythema induratum of Bazin, but discrepancy still persists about the size of the vessels,
because whereas some of them considered that large
veins and arteries are affected,28 others stated that
Necrotizing vasculitis involving small blood vessels at
center of fat lobule. (A to G, Hematoxylin-eosin stain;
original magnifications: A, 310; B and D, 340; C, E, and F,
3200; G, 3400. H to L, Elastic tissue stain; original
magnifications: H, 310; I and K, 340; J and L, 3200.)
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Fig 8. Early lesion of erythema induratum of Bazin showing mostly lobular panniculitis with
vasculitis involving large septal vessels, both arteries and veins, but with no involvement of
small blood vessels of center of fat lobule. A, Scanning power. B, Involvement of both artery
and vein of septa. C, Involved artery shows intense fibrinoid necrosis of tunica intima. D,
Despite intense fibrinoid necrosis of artery, internal elastic membrane is still discernible. (A to
D, Hematoxylin-eosin stain; original magnifications: A, 310; B, 340; C, 3200; D, 3400.)
only small and medium arteries and veins are involved,29 and finally others described involvement of
all sizes of arteries and veins.30 Curiously, even within
the same textbook, there are discrepancies between
different chapters, because in a textbook edited by
Farmer and Hood, Pathology of the Skin, Olsen31
considered in the chapter of vasculitis that nodular
vasculitis was ‘‘a panarteritis involving a small to
medium-sized artery, typically in the subcutis,’’
whereas Dahl and Su,32 in their chapter of panniculitis, dealing with erythema induratum of Bazinnodular vasculitis, described that ‘‘vasculitis, usually
lymphohistiocytic, involves venules, veins, and even
arterioles and small arteries in the pannicular septae.’’
In a recent series of 20 patients with erythema
induratum of Bazin-nodular vasculitis, the lesions
were histopathologically classified into two types:
focal panniculitis (type I) and diffuse panniculitis
(type II). In type I erythema induratum of Bazinnodular vasculitis, only one artery or a small blood
vessel within the fat lobule was involved by neutrophilic vasculitis. In type II erythema induratum of
Bazin-nodular vasculitis, several blood vessels of
different sizes both in the septa and the fat lobule
showed features of neutrophilic vasculitis. Necrosis
of the adipocytes and inflammatory response were
more intense in type II.33 In our opinion, this
classification is difficult to apply in a particular
case, because the intensity of inflammation of the
fat lobules often varies from one lobule to another
within the same biopsy specimen. Furthermore, in
our experience this system of classification is not of
practical use, because in the cases that we are
reporting in this series we did not find correlation
between the intensity of inflammatory infiltrate
within the fat lobule and the number, size, nature,
and location of the involved blood vessels of the
subcutis. Moreover, in some cases of erythema
induratum of Bazin with all the stereotypical clinicopathologic features of erythema induratum of
Bazin-nodular vasculitis, serial sections throughout
the block of a subcutaneous nodule did not demonstrate findings of vasculitis. Therefore, we do not
consider vasculitis as a sine qua non criterion to
establish the diagnosis of erythema induratum of
Bazin when other characteristic findings are present.
Another major problem in dealing with small
blood vessel vasculitis in the context of neutrophilic
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Segura et al 849
VOLUME 59, NUMBER 5
Fig 9. Early lesion of erythema induratum of Bazin. Serial sections failed to demonstrate
vasculitis. A, Scanning power. B, Higher magnification showing mostly lobular panniculitis.
C, Inflammatory infiltrate of fat lobule was mostly composed of neutrophils. D, Still higher
magnification showing neutrophils and some nuclear dust, but no evidence of vasculitis. (A to
D, Hematoxylin-eosin stain; original magnifications: A, 310; B, 340; C, 3200; D, 3400.)
lobular panniculitis is the question of whether or not
the vascular injury is primary. Cutaneous vasculitis
can be classified into primary, secondary, or incidental.34 Primary vasculitis is idiopathic and implies
that the vascular insult is the predominant pathogenic factor in the process. Examples of primary
cutaneous vasculitis include most cases of cutaneous
leukocytoclastic vasculitis, polyarteritis nodosa,
giant cell arteritis, and antineutrophilic cytoplasmic
antibodyepositive vasculitis syndromes, including
Wegener granulomatosis, Churg-Strauss syndrome,
and microscopic polyangiitis. In contrast, secondary
vasculitis is caused by and part of a known disease,
and although inflammation is also directed at vessel
wall constituents, there is one more process in wider,
often inflammatory syndromes. Secondary cutaneous
vasculitic
syndromes
include
lupus
erythematosus vasculitis, rheumatoid vasculitis, malignancy-induced vasculitis, infection-induced vasculitis, and drug-induced vasculitis. Finally,
incidental vasculitis refers to focal vasculitis found
within a predominantly neutrophilic infiltrate, such
as in venous ulcers of the lower legs or in early
lesions of herpes simplex and herpes zoster, and it is
accepted that this incidental vasculitis has no
pathogenic role in the process and the vascular
collateral damage is caused by a nonvasculitic insult
to the vessels. Inflammation is not directed at the
vessel, but the vessels are damaged because they are
in the vicinity of the insult.34 In this sense, it might be
interpreted that the leukocytoclastic vasculitis involving the small blood vessels of the fat lobule seen
in early lesions of erythema induratum of Bazin with
a mostly neutrophilic infiltrate within the fat lobule
was a secondary infective vasculitis as a result of M
tuberculosis or even an incidental vasculitis within a
neutrophilic infiltrate. However, there are several
features that militate against these possibilities.
Concerning infective vasculitis, M tuberculosis has
been demonstrated by polymerase chain reaction
techniques in cases of erythema induratum of Bazin
of some countries, but not in cases from other
geographic areas and, if the process is the same in
all areas,8-10 another pathogenic factor besides M
tuberculosis must be involved in the process. Finally,
the vasculitic process involving the small blood
vessels of the fat lobules in most of our cases of
erythema induratum of Bazin can not be interpreted
as an incidental vasculitis. First of all, necrotizing
leukocytoclastic vasculitis of the small blood vessels
850 Segura et al
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NOVEMBER 2008
Fig 10. Fully developed lesion of erythema induratum of Bazin. Serial sections failed to
demonstrate vasculitis. A, Scanning power. B, Higher magnification showing mostly lobular
panniculitis. C, Granulomatous infiltrate involving fat lobule. D, Higher magnification of
histiocytic infiltrate with no evidence of vasculitis. (A to D, Hematoxylin-eosin stain; original
magnifications: A, 310; B, 340; C, 3200; D, 3400.)
Table I. Type of involved vessels in vasculitis in 101 biopsy specimens from 86 patients with erythema
induratum of Bazin
Lobular venules
Lobular venules 1
septal veins
Septal veins
47 Cases (46.5%)
13 Cases (12.8%)
12 Cases (11.8%)
- EL: 23 cases
(22.7%)
- FDL: 24 cases
(23.7%)
- EL: 5 cases
(4.9%)
- FDL: 8 cases
(7.9%)
- EL: 2 cases
(1.9%)
- FDL: 10 cases
(9.9%)
Lobular venules 1
septal veins 1
septal arteries
10 Cases (9.9%)
(All cases were EL)
Septal veins 1
septal arteries
No vasculitis
9 Cases (8.9%)
10 Cases (9.9%)
- EL: 8 cases
(7.9%)
- FDL: 1 case
(0.9%)
- EL: 2 cases
(1.9%)
- FDL: 8 cases
(7.9%)
EL, Early lesions (mostly neutrophilic infiltrate); FDL, fully developed lesions (mostly histiocytic infiltrate).
was seen not only in early lesions of our series, but
also in many biopsy specimens from fully developed
lesions with a predominantly granulomatous infiltrate involving the fat lobule. Second, besides erythema induratum of Bazin, there are several other
panniculitic processes with a predominantly neutrophilic infiltrate within the fat lobule, such as neutrophilic lobular panniculitis or subcutaneous Sweet
syndrome, pancreatic panniculitis, alpha-1-antitrypsin deficiencyeassociated panniculitis, infective panniculitis, and factitial panniculitis, which do no show
leukocytoclastic vasculitis of the small blood vessels
of the fat lobule.35 Therefore, we think that the most
common type of vasculitis seen in biopsy specimens
of erythema induratum of Bazin has pathogenic
significance and it must be considered as primary
vasculitis.
In conclusion, although there is no consensus
about the nature, size, and location of the involved
vessels in erythema induratum of Bazin, on the basis
of the findings of this series, we consider vasculitis as
almost always present in lesions of erythema induratum of Bazin, and the nature, location, and size of
the involved vessels is, from more to less frequent, as
follows: (1) small venules of the fat lobule; (2) both
veins of the connective tissue septa and venules of the
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Segura et al 851
VOLUME 59, NUMBER 5
fat lobule; (3) only veins of the connective tissue
septa; (4) veins and arteries of the connective tissue
septa and venules of the fat lobule; and (5) veins and
arteries of the connective tissue septa. Because some
type of vasculitis is seen both in early and fully
developed lesions and because vasculitis is more
consistently present in lesions of erythema induratum
of Bazin than in other mostly lobular panniculitis, we
think that vasculitis plays an important role in the
pathogenesis of this process. However, vasculitis
should not be considered as a criterion sine qua non
for histopathologic diagnosis of erythema induratum
of Bazin when all other clinicopathologic features of
the process are consistent with that diagnosis.
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