MINI-SYMPOSIUM: DERMATOPATHOLOGY

Cutaneous vasculitis associated vasculitides need specific antimicrobial agents; and

coagulopathies require anticoagulant therapy. However, the
distinction between vasculitis and occluding vasculopathy can be
Gudrun Ratzinger difficult because the two processes may be intertwined. Vascu-
Bettina Zelger litis can be missed, because it may trigger vaso-occlusive events,
that overflow the initial pathogenetic signs at the vessel wall (i.e.
Nina Frischhut in septic vasculitis). On the other hand, occluding vasculo-
Bernhard Zelger pathies/coagulopathies may be misinterpreted as vasculitis
because, in due course, they can show inflammation as sign of a
reparative process (lymphocytic vascular reorganization5). In
Abstract this article, we focus on vasculitides of the skin, which is one of
Cutaneous vasculitides are inflammatory diseases starting at and the most commonly affected organs in vasculitis. The Chapel Hill
evolving around the blood vessels of the skin. They should be separated Consensus Conference Nomenclature of Vasculitides has been
from occluding vasculopathies, where the pathological process pre- revised in 2012.6 Additionally, an addendum with the focus on
dominantely starts in the blood. They can be graded according to cutaneous vasculitides7 has recently been published.
their relationship to systemic vasculitides as a cutaneous component Cutaneous vasculitides can be graded according to their rela-
of a systemic vasculitis, as a skin-dominant variant of a systemic vascu- tionship to systemic vasculitides. They can present as a cutaneous
litis or as a cutaneous single organ vasculitis. Diagnostic measures, component of a systemic vasculitis (skin also involved), as a skin-
therapy and prognoses depend greatly on this relationship. For diag- limited or skin-dominant variant of a systemic vasculitis (skin
nostic purposes, a classification based on histopathological features mainly involved), or as an exclusive vasculitis of the skin, which
in asscociation with clinicopathological correlation seems most reliable. differs from systemic vasculitis (cutaneous single organ vasculitis,
We differentiate according to vessel size (small-medium-large) and cSOV) (Table 1). While the latter cannot progress into systemic
involved cell types (leukocytes, macrophages) as well as extravascular vasculitis, a skin-dominant form may do so.
features (necroses, granulomas). Thus, the similarities and overlaps be- Vaculitides could also be classified according to etiological
tween different manifestations become apparent. (hepatitis B, C; herpes) or pathogenetic factors (immune com-
Keywords cutaneous vasculitis; vasculitis; vasculopathy plexes, ANA, c-ANCA or p-ANCA). However, triggers such as
hepatitis B can cause various vasculitic and non-vasculitic pat-
terns such as leukocytoclastic vasculitis, cutaneous polyarteriitis
Introduction nodosa, Sweet syndrome, erythema multiforme or erythema
nodosum. On the other hand, identical patterns such as leukocy-
Vasculopathies are diseases of blood vessels. They comprise in- toclastic vasculitis can be associated with different disorders such
flammatory, neoplastic and genetic disorders. In this article, we as immune complex vasculitis, Henoch-Scho €nlein purpura (IgA-
focus on inflammatory diseases involving blood vessels. positive immune complex vasculitis), lupus erythematosus
Depending on the initiation of the pathogenetic process, we (frequently urticarial vasculitis is an early manifestation of sys-
distinguish categories: vasculitides and variably occluding vas- temic lupus erythematosus), or granulomatosis with polyangiitis
culopathies. Vasculitis1,2 is defined as a process initiating at the (GPA, Wegener granulomatosis, c-ANCA positive vasculitis of
vessel wall with increased numbers of inflammatory cells in and/ skin and internal organs). These findings indicate that the clini-
or around the vessel wall accompanied by vascular damage. In copathological features we see are indeed reaction patterns caused
the contrary, one must separate occluding vasculopathies.3,4 by a variety of etiologic factors or pathogenetic mechanisms.
Here, the pathologic process mostly starts in the blood with Similar to the International Chapel Hill Consensus Conferences
variable occlusion of blood vessels due to hypercoagulability, in (CHCC) on the nomenclature of vasculitides from 20126, we
particular by thrombi and emboli. The distinction between the suggest to classify cutaneous vasculitides using an algorithmic
primary event being vasculitis or occluding coagulopathy has approach of systematic analysis of microscopic findings in asso-
important therapeutic consequences: classical vasculitides ciation with clinicoepathological correlation.5 First, one differen-
benefit from immunosuppressive therapies; microorganism- tiates according to the size between small, medium or large vessel
vasculitis. Large vessels are confined to the aorta, the vena cava
and their big branches. Thus, no true large vessels exist in skin. In
CHCC, medium arteries are the large organ arteries, which also do
Gudrun Ratzinger MD, Department of Dermatology, Venereology not exist in skin. According to CHCC, all vessels of the skin would
and Allergology, Medical University Innsbruck, Innsbruck, Austria.
be small vessels. Yet, in our terminology (for clear differentiation
Conflicts of interest: none declared.
in skin) we use the term medium vessel vasculitis, when arteries
Bettina Zelger MD, Department of Pathology, Medical University or veins of the skin are involved. In the second step, one differ-
Innsbruck, Innsbruck, Austria. Conflicts of interest: none declared. entiates between the subtypes of small (capillaries/arterioles
Nina Frischhut MD, Department of Dermatology, Venereology and versus postcapillary venules) and medium (arteries versus veins)
Allergology, Medical University Innsbruck, Innsbruck, Austria. vessels. Capillaries are found in dermal papillae, in the peri-
Conflicts of interest: none declared. follicular and periglandular connective tissue, between collagen
Bernhard Zelger MD, MSc, Department of Dermatology, Venereology fibers in reticular dermis and within the lobuli of the panniculus.
and Allergology, Medical University Innsbruck, Innsbruck, Austria. Postcapillary venules contribute to the superficial and deep peri-
Conflicts of interest: none declared. vascular plexus; the former at the border between the papillary

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 MINI-SYMPOSIUM: DERMATOPATHOLOGY

and reticular dermis; the latter at the border between the reticular venules (IgA vasculitis). However, the skin-limited form of IgA
dermis and subcutis. Other venules include the interconnecting vasculitis is more common than the systemic form. The cry-
venules between superficial and deep plexus and the septal ve- oglobulinemic vasculitis often is associated with hepatitis C
nules. Arterioles/arteries and veins are found at the boarder of the infection and in many cases a coagulopathy and not a leukocy-
reticular dermis to the subcutis or in the subcutis. toclastic vasculitis. There is a systemic form with skin involve-
In the final step, one differentiates the vascular process ac- ment, but also a skin-limited form.11 Other variants are associated
cording to the predominant type of cells. Leukocytes and their with rheumatoid disorders (rheumatoid neutrophilic dermatosis,
debris (leukocytoclasia, nuclear dust) are characteristic of leu- erythema marginatum), or medications (sulfonamides, barbitu-
kocytoclastic vasculitis. Macrophages in different forms of rates, penicillins). The anti-glomerular basement membrane dis-
granulomas are typical of granulomatous vasculitis with signifi- ease/Goodpasture syndrome mainly affects kidneys and lungs,
cant connective tissue damage. Additionally, extravascular fea- but does not show vasculitic skin lesions.
tures like tissue eosinophilia, blue/red collagenolytic granulomas
or storiform fibrosis can point to find the diagnosis. We do not Histology: the vasculitic process is accentuated around postcapillary
include lymphocytic vasculitis in our algorithm. We tend to see it venules and shows perivascular leukocytoclasia (Figure 1). Addi-
mostly as an epiphenomenon to a basic pathologic process and tionally, we may find fibrin within vessel walls and erythrocyte ex-
find lymphocytes indicative of regenerative/secondary vasculitis travasates. Sometimes, swelling, drop out or increased numbers of
i.e. due to coagulopathies, also recently entitled ”lymphocytic endothelial cells are signs of endothelial cell damage.
vascular reorganization”.5
Comment: leukocytoclastic vasculitis is not a defined disease, but a
Small vessel vasculitides (SVV) reaction pattern, that can be found in the context of various diseases.
Small vessel vasculitides predominately affect small vessels
defined as postcapillary venules, capillaries and arterioles. The Sweet syndrome
major representative of SVV with skin involvement is immune Synonyms: acute febrile neutrophilic dermatosis, Gomm-Button
complex vasculitis, but we additionally find possible precursors disease.
or relatives of ANCA-associated vasculitides. SVV also comprises
several forms of cutaneous single-organ vasculitis (cSOV). Clinic: Sweet syndrome mostly affects adults with female predi-
lection. The arms, neck and face are the preferred locations. One
“Classic leukocytoclastic vasculitis” observes edematous papules to plaques, frequently with a bullous
Clinic: cutaneous IgM/IgG immune complex vasculitis is the most appearance, due to the edema which gives the lesions a juicy
common representative of this group. In most cases, it is an acute aspect. The changes are discrete and multiple, sometimes annular.
form of vasculitis, lasting for days to weeks, sometimes with
recurrent episodes and chronicity for months to years. It may Histology: Sweet syndrome is an acute reaction pattern with peri-
occur at any age, but frequently affects children and young adults. vascular accentuation around postcapillary venules, but compara-
There is no sexual predilection. The legs are the preferred location; tively few inflammatory cells around capillaries. While there is
sometimes the arms and buttock also are affected. Lesions are prominent leukocytoclasia around the venules, fibrin thrombi are
symmetrical, discrete to confluent. One finds macules, urticarial to rare, absent or frequently seen only on serial sections. Most char-
haemorrhagic papules and plaques, vesicles, pustules and ulcers. acteristically there is prominent edema in the papillary dermis.
Usually, it does not show systemic involvement (cSOV). Acute
haemorrhagic purpura (cockade purpura of Seidlmayer- Comment: in our experience, the process described by Sweet in 1964
Finkelstein) is a deep-seated dermal to subcutaneous form of and subsequently by many others is a hodgepodge of several different
leukocytoclastic vasculitis, most commonly presenting as hae- processes.12 One is the pattern described above, which in our expe-
morrhagic nodules on the trunk and extremities in infants and rience best falls into the category of small vessel vasculitis. There are
children. It usually does not show systemic involvement (cSOV). similarities in distribution and appearance with urticarial vasculitis,
However, there are variations of leukocytoclastic vasculitis interstitial granulomatous dermatitis, Wells syndrome, granuloma
with involvement of other organs or association to systemic dis- faciale and erythema elevatum diutinum. Most of these cases are
eases. In urticarial vasculitis,8 urticarial papules to plaques persist caused by drugs or acute infections. Association with neoplasia has
for more than 24 h and heal with hyperpigmentation. Histology is been documented, in particular with haematologic malignancies. In
usually subtle with/without fibrin deposits, erythrocyte extrava- these instances, the clinical presentation may be similar, but histol-
sation and perivascular inflammatory cell infiltrate. The hypo- ogy may reveal neoplastic leukocytes or monocytes. Some cases of
complementemic variant of urticarial vasculitis may be an early myelomonocytic leukemia with Sweet syndrome are better inter-
manifestations of lupus erythematosus, while the normocomple- preted as pyoderma gangrenosum, which in acral location has also
mentemic variant usually appears as cutaneous single-organ been called neutrophilic dermatosis of the dorsal hands.13
vasculitis. Eosinophil-rich leukocytoclastic vasculitis9 may show
flame figures, and there is overlap with both Wells syndrome and Wells syndrome
eosinophilic granulomatosis with polyangiitis (EGPA). In Henoch- Clinic: Wells syndrome most commonly affects adults without
Scho€nlein purpura,10 the characteristic pattern of palpable pur- sexual predilection. The extremities and trunk are preferred.
pura on the lower legs is associated with rheumatic, renal (hae- Lesions are discrete, mostly solitary, occasionally multiple. Pla-
maturia and proteinuria) and gastrointestinal involvement ques, nodules or tumours are frequently deep with a character-
(abdominal pain) and deposition of IgA around postcapillary istic greenish aspect, which is due to the haemorrhage associated

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 MINI-SYMPOSIUM: DERMATOPATHOLOGY

with the vasculitic process. These lesions become in due course arthritis, other systemic autoimmune diseases, methotrexate
yellow to brown, reveal an apple jelly color on diascopy due to therapy or Lyme borreliosis. The exaggeration of this process
macrophages, and at this stage are frequently misinterpreted with or, rarely, without the presence of neutrophils is seen in
clinically as morphea or mycosis fungoides. Vasculitic activity of GPA with large basophilic geographical necrotic lesions.15
disease may be seen as a peripheral red-violet rim and/or hae-
morrhagic papules. Histology: we find polymorphonuclear leukocytes around post-
capillary venules plus leukocytoclasia usually in the deep dermis
Histology: the story of Wells syndrome is similar to Sweet syn- (Figure 2). Sometimes, vasculitis may be subtle or missed and
drome. It is an acute reaction pattern with perivascular accentuation only foci of slightly bluish (“basophilic”) collagen degeneration
around postcapillary venules, frequently in the deep dermis or even surrounded by macrophages may occur. In this case, the differ-
subcutis, but comparatively few inflammatory cells around capil- ential diagnosis is granuloma annulare.
laries. While there is leukocytoclasia around the venules, fibrin
thrombi are rare, absent or found only on serial sections. The acute Comment: interstitial granulomatous dermatitis as well as some
infiltrate most characteristically is dominated by eosinophils which cases of Wells syndrome show tiny spots of necrotic to degenerated
focally cause tissue damage with flame figures. tissue as a sign of an interstitial or soft tissue component. Such forms
will heal with granulomas and later scar tissue and/or fibro-
Comment: in our experience Wells syndrome is a hodgepodge sclerosis. This process is most prominently seen in GPA and EGPA
diagnosis characterized by flame figures due to numerous eo- where the skin is only rarely a major target site. An identical reaction
sinophils. Flame figures can be seen in all entities with promi- pattern can be seen during methotrexate therapy; we think, that in
nent presence of eosinophils as insect bites, bullous pemphigoid, such instances the disease process starts most likely due to toxic
pemphigus vulgaris, or hypereosinophilic syndrome. In our damage of endothelial cells followed by a vasculitic reaction.
experience, the classic presentation as described above best falls
into the category of small vessel vasculitis. There are similarities Granuloma faciale and erythema elevatum diutinum
in distribution and appearance with eosinophil-rich leukocyto- Clinic: granuloma faciale and erythema elevatum et diutinum are
clastic vasculitis and EGPA.14 Patients with Wells syndrome may chronic persistent forms of leukocytoclastic vasculitis, lasting for
develop more severe/obvious signs of vasculitis just as patients months to years. They usually are harmless diseases restricted to
with EGPA in due course may develop patchy haemorrhagic le- the skin (cSOV). Only in rare instances, they can be the early
sions of Wells syndrome with flame figures. In some instances of manifestation of more severe vasculitides such as GPA or EGPA.
Wells syndrome, one sees demarcation of flame figures not only They mostly affect adults without sexual predilection. The
by eosinophils, but also by palisading macrophages. Such foci former occurs on the face, the latter on the dorsal aspects of the
represent the same pathologic feature which in larger dimension limbs. Lesions are symmetrical and discrete. Brown papules,
is seen in EGPA as eosinophilic geographic necrotic lesions due plaques to nodules reveal a characteristic peau d’orange, which
to involvement and occlusion of larger vessels. is due to the infiltrative process in the dermis with sparing of the
papillary dermis and the perifollicular connective tissue.
Interstitial granulomatous dermatitis
Synonym: Winkelmann granuloma. Histology: the vasculitic process manifests with perivascular accen-
tuation of neutrophils and nuclear dust in the background of fibrosing
Clinic: interstitial granulomatous dermatitis predominantly af- dermatitis (storiform fibrosis) (Figure 3). Sometimes, we find
fects adults without sexual predilection. The trunk and extrem- admixture of plasma cells. Originally, eosinophils were described as
ities are preferred sites. Lesions are symmetrical and discrete, prominent feature of granuloma faciale which was also called gran-
sometimes linear (10%). Macules, papules, plaques may be seen, uloma faciale eosinophilicum; we now know that the presence of
sometimes resembling urticarial vasculitis. In linear presenta- eosinophils is quite variable, ranging from prominent to none.
tion, typical cords are found, known due to its linearity as the
rope or railway sign. Interstitial granulomatous dermatitis may Comment: both diseases have been suggested in the context of
occur in the course of GPA, lupus erythematosus, rheumatoid IgG4-related diseases.16

Key points e small vessel vasculitis

 Histopathology: postcapillary venules mainly affected,
leukocytoclasia
 Clinic: pupuric papules, urticarial lesions, plaques and
nodules
 Skin-only or skin-dominant manifestations frequent
 Precursors of more severe vasculitides or manifestation of
systemic diseases possible

Small-to-medium vessel vasculitides

Figure 1 Leukocytoclastic vasculitis. Lymphocytes and neutrophiles These disorders are characterized by a vasculitic process which
as well as leukocytoclasia accentuated aroud postcapillary venules. affects predominantely small, but also medium vessels.17 This
The area of capillaries in the papillar dermis is realtively spared. may occur simultaneously or subsequently. Depending on which

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 MINI-SYMPOSIUM: DERMATOPATHOLOGY

vessel type is affected, lesions may present more as macules, suffer from preexisting and/or concomitant atopic dermatitis,
patches, papules and plaques in small vessel disease or nodules allergic rhinitis, and/or asthma. There is variable expression of
and tumours in medium vessel affection. Other organs also perinuclear-ANCA (p-ANCA; antigen is myeloperoxidase).20
usually show signs and symptoms of the vasculitic process. EGPA is a rare disease and affects all ages and ethnic groups
Organ involvement may precede, occur simultaneously with or without sexual predilection. Internal organ involvement is usu-
follow skin lesions. The main representatives of this group are ally mild. Gut, lung, heart, kidney, central and peripheral nerve
the ANCA (anti-neutrophil-cytoplasmatic-antibodies)-associated system may be affected. Macules, patches, papules and plaques
vasculitides. They can be further classified by serology as serum of small vessel vasculitis are most commonly seen on the trunk,
positive for ANCAs or ANCA-negative.6 while nodules and tumours of medium vessel vasculitis occur on
the head, arms or trunk. There may be an early haemorrhagic
Granulomatosis with Polyangiitis (GPA) character. Later, brown pigmentation similar to urticarial
Synonym: Wegener’s granulomatosis. vasculitis may mimic morphea or early mycosis fungoides.
Clinic: GPA18 is a classical small-to-medium vessel disease pattern.
Histology: we find perivascular and intramural leukocytoclasia
It is characterized by frequent involvement of ear-nose-throat, lungs
around postcapillary venules and larger vessels of skin and sub-
and kidneys (known by acronym as ELK organs) plus the possible
cutis (Figure 5). Additionally, collagen degeneration with variable
presence of anti-neutrophilic cytoplasmic antibodies (c-ANCA; an-
basophilic to usually more eosinophilic necrotic lesions sur-
tigen is proteinase 3). Skin involvement occurs in 30% of patients
rounded by palisading macrophages (granulomas) can be found.
usually in due course of disease.19 There are monosymptomatic
The acute infiltrate most characteristically is dominated by eo-
variants with eye, ear-nose-throat (ENT) or other system involve-
sinophils which focally cause tissue damage with flame figures.
ment which may persist for years. c-ANCA may be negative.
Nevertheless, c-ANCA is an important clue and sometimes indica-
Comment: EGPA is the exaggeration of the process which starts
tive of progression, but not a least common denominator of disease
as eosinophilic leukocytoclastic vasculitis or leukocytoclastic
and as such an epiphenomenon and not a basic pathologic process.
vasculitis, type Wells syndrome.14
GPA affects all ages and ethnic groups with some predilection of
white individuals and without sexual predilection. Patients present Microscopic polyangiitis (MPA)
with edematous to haemorrhagic and/or necrotic plaques, nodules, Clinic: MPA is a small-to-medium vessel vasculitis with frequent
tumours or ulcers. In the lungs massive haemorrhage is character- involvement of internal organs, in particular kidney, and variable
istic, while the kidneys show early glomerulonephritis which causes ANCA, in particular p-ANCA expression.21 It is extraordinarily
haematuria, proteinuria and in due course a decrease in glomerular rare in skin, but a common cause of glomerulonephritis. MPA
filtration rate up to renal failure and dialysis. affects all ages and ethnic groups without sexual predilection.
One finds macules, urticarial to haemorrhagic papules and pla-
Histology: we find perivascular and intramural leukocytoclasia
ques, vesicles, pustules and ulcers. There are no dermatologic
around postcapillary venules and larger vessels of skin and
features that would clinically separate MPA from leukocyto-
subcutis (Figure 4). Additionally, collagen degeneration with
clastic vasculitis or early GPA. Necrotizing glomerulonephritis is
variable basophilic necrotic lesions surrounded by palisading
very common, pulmonary capillaritis often occurs.
macrophages (blue/red collagenolytic granulomas) can be found.
Histology: we find the vasculitic process accentuated around
Comment: granulomatosis in GPA is the exaggeration of the
postcapillary venules and larger vessels of the skin and the subcutis,
process which starts as interstitial granulomatous dermatitis.
but restricted to the vessel site without formation of granulomas.
Eosinophilic granulomatosis with polyangiitis (EGPA)
Key points e small-to-medium vessel vasculitis
Synonym: Churg-Strauss syndrome.
 Histopathology: postcapillary venules and bigger vessels,
Clinic: EGPA is a classical small-to-medium vessel disease similar with necroses and granulomas (except in MPA)
to GPA, but with prominence of eosinophils. Patients frequently  Clinic: purpuric papules, urticarial lesions, nodules
 systemic involvement frequent
 ANCA expression variable

Medium-to-medium/large vessel vasculitides

We use the term medium-to-medium/large vessel vasculitis,
because the affected vessels in the skin are medium size, but the
corresponding extracutaneous vessels may be large ones (aorta
and its branches). These disorders are further differentiated into
those with a prominent intramural vasculitic component and
those with a prominent extravascular/interstitial/soft tissue
component. In the former, pathologic changes are mostly
Figure 2 Interstitial granulomatous dermatitis. Diffuse infiltrate of restricted to the arterioles and arteries without significant
neutrophils, nuclear dust, macrophages and some lymphocytes with involvement of surrounding connective tissue. In the latter,
collagen degeneration. Early palisading granuloma. vasculitis may be covered by necrotic tissue in the dermis and

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 MINI-SYMPOSIUM: DERMATOPATHOLOGY

Nodular vasculitis (NVA)

Clinic: nodular vasculitis mostly affects older females. The calves
are the preferred location, and patients are frequently overweight.
Lesions consist of nodules to tumours and are usually asymptom-
atic. However, they may become fluctuant and drain oily liquidized
fat. There is no systemic involvement to be found (cSOV).

Histology: nodular vasculitis shows medium vessel disease together

with necrotic lesions and granuloma formation. It affects arteries and
veins of the subcutis, muscles and deep tissues. We find perivascular,
intramural and intraluminal leukocytoclasia in association with
Figure 3 Granuloma faciale. Mixed infiltrate of neutrophils, nuclear caseating necrotic tissues surrounded by palisading (foamy) mac-
dust, and eosinophils, accentuated around postcapillary venules; note
rophages and giant cells (Langhans type-tuberculous granulomas).
sparing of inflammation around capillaries in dermal papillae as well as
in periadnexal connective tissue.
Comment: some authors regard veins as the primary site of pa-
thology. In our experience, arteries are usally primarily affected.
even more in the subcutaneous tissue. Clinically, these lesions Nodular vasculitis is an unspecific reaction pattern which may
present as nodules and tumours. There are representatives with occur in a variety of instances. The most common associations
and without systemic involvement. are with hepatitis B and tuberculosis, but also hepatitis C and
The three major forms of medium vessel vasculitis are poly- HIV infection. When associated with tuberculosis, the disease is
arteriitis nodosa (PAN), nodular vasculitis/erythema induratum also known as erythema induratum Bazin.24
Bazin (NVA) and Kawasaki disease. The latter is characterized
by arteritis associated with mucocutaneous lymph node syn- Giant cell arteritis (GCA)
drome and usually occurs in infants and young children. Cuta- Clinic: GCA mainly affects females of 70 and more years. In most
neous vasculitis is not a characteristic feature, while cases, vessels of the skin are not involved. In case of skin
nonvasculitic mucocutaneous features may occur. involvement, the preferred sites are the forehead, the temple
The two major forms of medium/large vessel vasculitis are (temporal arteriitis) as well as ophthalmic and lingual arteries.
giant cell arteritis (GCA) and Takayasu arteritis. The latter Involvement of internal organs can be asymptomatic or cause
mainly affects the aorta and its major branches and does not serious problems and may precede head and neck lesions. 50%
show any vasculitic skin involvement. of patients have a history of polymyalgia rheumatica.
In early stages one finds painful cords along the artery, which
Polyarteriitis nodosa (PAN) in due course shrink and become hard. Ulceration of the scalp
Previously known as panarteriitis nodosa. Synonyms: Kussmaul- may occur; necrotic lesions of tongue and other tissues are also
Maier disease, periarteriitis nodosa. seen.25 Patients may develop visual difficulties as well as nausea
and tinnitus. Rapid blindness is a frequent complication, if diag-
Clinic: PAN is a disease of adults; men are more often affected nosis is delayed or appropriate therapy is not started promptly.
than women. Clinically, characteristic linear nodules with/ The erythrocyte sedimentation rate is exceptionally high.
without ulcers occur on the lower extremities; and the process is
symmetrical. In addition patients suffer from arthralgia (often of Histology: giant cell arteriitis, is a classical large-to-medium vessel
the ankle joint) and show livedo racemosa (starburst pattern) disease predominantely affecting the aorta and its branches with a
due to flow disturbances caused by partial to complete vascular predilection for the branches of the carotid and vertebral arteries.
occlusion from vasculitis with thrombi. The primary systemic The involved skin arteries are located in the subcutis, muscles or
form of PAN may show skin involvement. However, involve- deeper tissues. Characteristic giant cells, most prominent close to
ment of internal organs is uncommon in the cutaneous variant of the internal elastic membrane, are found. The pathology is mainly
PAN. Affection of adjacent skeletal muscle or peripheral nerves restricted to the vessel site with formation of granulomas; however,
has been reported. However, there is no agreement, whether
these findings would justify the diagnosis of systemic PAN.7
ANCA are usually negative.

Histology: PAN is a classic medium vessel disease pattern which

affects arteries located at the border between the dermis and
subcutis or in subcutis (Figure 6). In contrast to microscopic
polyangiitis, PAN always affects arteries but not postcapillary
venules. The pathology is restricted to the vessel site, no extra-
vascular/interstitial/soft tissue granulomas can be found.22

Comment: cutaneous lymphocytic thrombophilic (macular)

Figure 4 Granulomatosis with polyangiitis. Nodular to diffuse infiltrate of
arteriitis (cSOV) may be an early or indolent stage of cutaneous neutrophils and nuclear dust accentuated around postcapillary venules.
polyarteriitis nodosa.23 Basophilic tissue damage indicating focus of early granuloma formation.

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 MINI-SYMPOSIUM: DERMATOPATHOLOGY

description of these entities is beyond the scope of an article

focusing on histopathology of cutaneous vasculitides.

Conclusion
Cutaneous vasculitides are a heterogenous group that have been
classified according to different principles like clinicopathologic
findings, etiology, pathogenesis, prognosis or therapeutic options.
Additionally, morphologic terms and names of important scientists
have been used. Thus, the similarities and overlaps between these
manifestations were rather concealed. A classification based on
Figure 5 Eosinophilic granulomatosis with polyangiitis. Diffuse dermal clinicopathological features starting from leukocytoclastic vascu-
to subcutaneous infiltrate of neutrophils, nuclear dust and prominent litis as a central reaction pattern may find some basic order which
eosinophils. Note large and small vessel vasculitis with geographic can lead to easier understanding in a complicated field. A
eosinophilic necrotic areas.

extravascular/interstitial/soft tissue granulomas are missing or

“only” complication to ulceration. Cutaneous vasculitides
Cutaneous Skin- Cutaneous
Comment: early giant cell arteriitis may also show only a subtle involvement of dominant single-organ
inflammatory infiltrate of lymphocytes around vasa vasorum and/ systemic variant vasculitis
or vessels of surrounding adventitia. In our experience this can be vasculitis
an early or indolent (reparative) stage of temporal arteriitis.26
Small vessel vasculitis
Key points e medium-to-medium/large vessel IgM/IgG vasculitis - - D
vasculitis IgA vasculitis D D -
 Histopathology: arteries of the deep dermis and subcutis Hypocomplementemic D D -
 Clinic: nodules and ulcers urticarial vasculitis
 Systemic involvement in PAN possible, in NVA absent, in Normocomplementemic - - D
GCA predominant urticarial vasculitis
Eosinophil-rich - D -
Variable vessel vasculitides vasculitis
Variable vessel vasculitides can affect vessels of any size or type. Cryoglobulinemic D D -
Behc‚et’s disease and Cogan’s syndrome are the two main rep- vasculitis
resentatives. Behc‚et’s disease can present as a systemic vasculitis Sweet syndrome - D -
with a cutaneous component or as a skin limited mucocutaneous Wells syndrome - D -
vasculitis in absence of systemic vasculitis, while Cogan’s syn- Interstitial - D -
drome rarely shows cutaneous involvement. A detailed granulomatous
dermatitis
Anti-glomerular - - -
basement membrane
disease
Small-to-medium vessel vasculitis
Granulomatosis with D D -
polyangitis
Eosinophilic D D -
granulomatosis with
polyangitis
Microscopic polyangitis D D -
Medium-to medium/large vessel vasculitis
Polyarteriitis nodosa D D -
Nodular vasculitis - - D
Kawasaki disease - - -
Giant cell arteriitis D - -
Takayasu arteriitis - - -
Figure 6 Cutaneous polyarteriitis nodosa. Artery at the dermis-subcutis Variable vessel vasculitis
border, occluded by fibrin. Inflammation of vessel wall by lymphocytes, Behc‚et’s disease D D -
macrophages and some admixture of neutrophils and nuclear dust. Cogan’s syndrome D - -
Note prominent corona of capillaries around this artery due to vasa
vasorum induced by inflammation. No formation of granulomas. Table 1

DIAGNOSTIC HISTOPATHOLOGY 27:1 11 Ó 2020 Published by Elsevier Ltd.

 MINI-SYMPOSIUM: DERMATOPATHOLOGY

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