not permitted.

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© 2017 EDIZIONI MINERVA MEDICA Giornale Italiano di Dermatologia e Venereologia 2018 April;153(2):173-84
Online version at http://www.minervamedica.it DOI: 10.23736/S0392-0488.17.05839-4

REVIEW
R H E U M AT O L O G I C D E R M AT O ( PAT H O ) L O G Y:
HOW THE MICROSCOPE CAN HELP THE CLINICIAN

Histopathological aspects of psoriasis

and its uncommon variants
Caterina FERRELI  1  *, Anna L. PINNA  1, Luca PILLONI  2, Carlo F. TOMASINI  3, Franco RONGIOLETTI  1

1Sectionof Dermatology, Department of Medical Science and Public Health, University of Cagliari, Cagliari, Italy; 2Section of Pathology,
Department of Surgery, University of Cagliari, Cagliari, Italy; 3Section of Dermatology, Department of Medical Science and Infectious
Diseases, University of Pavia, Pavia, Italy
*Corresponding author: Caterina Ferreli, via Ospedale 54, 09124 Cagliari, Italy. E-mail: ferreli@unica.it

A B S TRA C T
Psoriasis is a chronic complex multisystem, inflammatory, skin disorder that causes vasodilatation and hyperproliferation of keratinocytes,
whose clinical expression includes a thickened, erythematous skin, often covered with silver gray scales. Psoriasis is a unique disease where
both autoimmune and autoinflammatory responses coexist and the balance between the two components is essential in determining its clinical
and histopathological presentation. Adaptive immune responses prevail in chronic plaque psoriasis while innate and autoinflammatory responses
predominate in pustular psoriasis. The histopathology of psoriasis is easily recognizable when the disease involves the typical sites such as the
extensor surfaces. Although a biopsy is rarely required in case of classic psoriasis, in atypical and controversial conditions, histopathological
examination remains the main diagnostic tool that can help in differentiating psoriasis from other dermatoses. In this review, we will discuss the
histopathological pictures of the different clinical variants of psoriasis giving some clues to drive the correct diagnosis when the clinical aspects
are not enough indicative of the disease.
(Cite this article as: Ferreli C, Pinna AL, Pilloni L, Tomasini CF, Rongioletti F. Histopathological aspects of psoriasis and its uncommon variants. G
Ital Dermatol Venereol 2018;153:173-84. DOI: 10.23736/S0392-0488.17.05839-4)
Key words: Psoriasis - Pathology - Hyperplasia - Inflammation.

P soriasis is a chronic multifactorial skin disease,

which affects 2-3% of the world’s population 1
with an incidence that varies in the different areas of
the hemisphere. The disease seems to be the result of a
deregulated interplay between immune cells, skin ke-
ratinocytes and the environment leading to a persistent
inflammatory process modulated by activated T-cells
and proinflammatory cytokines.2 It is characterized by
hyperproliferation of keratinocytes due to an increase
turnover and vasodilatation, resulting in a thickened, in-
flamed skin, covered with polystratified silvery scales.
or other proprietary information of the Publisher.
responses seem to prevail in chronic plaque psoriasis,5
whereas innate and autoinflammatory responses pre-
dominate in pustular psoriasis 6 and in other clinical
subtypes in the spectrum between plaque and pustular
psoriasis.
Although the histopathologic features of psoriasis
have been well documented, its diagnosis is usually a
clinically one  7, 8 based also upon the context in which
the dermatitis arise, and some ancillary signs such as the
nails involvement.9, 10 The histological examination is
most helpful in atypical, widespread or treatment-mod-

As in other multifactorial diseases, the clinical pheno- ified psoriasis (drug effect or drug side effect) or per-
type of psoriasis may manifest in several clinically dif- haps when an overlap between two or more distinctive
ferent subtypes that are driven by distinctive autoim- dermatoses exist.9 In these cases, the histopathological
mune/autoinflammatory process.3, 4 Adaptive immune examination is the main way to discriminate between

Vol. 153 - No. 2 Giornale Italiano di Dermatologia e Venereologia 173

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FERRELI HISTOPATHOLOGICAL ASPECTS OF PSORIASIS

psoriasis and other skin diseases. Until now, the micro-
scopic features of the different forms of psoriasis, when
non-classic or atypical, have no established criteria.11
Moreover psoriasis is a dynamic process and the histo-
pathological features modify according with the age of
the disease and vary whether it is early or resolving.12
Classic psoriasis
Classic plaque psoriasis is the most common vari-
ant, affecting 80-90% of patients.13 It is characterized
by scaling, salmon-colored erythematous macules, pap-
ules, and well-demarcated plaques, covered with a sil-
very white scale, most commonly localized on the ex-
tensor surfaces of the knees, elbows, scalp, and trunk.
From a histopathologic point of view, both epidermal
and dermal modification are present.14 At scanning
magnification,15 the epidermis shows a regular psoriasi-
form hyperplasia with elongated rete ridges even in size
and length as the intercalated dermal papillae; higher
mitotic activity of basal and suprabasal keratinocytes,
sometimes enlarged club shaped rete ridges, and supra-
papillary plate thinning (Figure 1A). As expression of
abnormal keratinization, there is confluent parakera-
tosis and hypogranulosis. Neutrophils tend to migrate
from the dermis into the epidermis and may form col-
lections in the corneum, named Munro-Sabouraud’s mi-
cro abscesses, or in the stratum spinosum as spongiform
pustule of Kogoj. Munro-Sabouraud’s microabscesses
are one of the more characteristic histological features
of early psoriasis.16 The alternate collection of neutro-
phils between layers of parakeratosis is another pathog-
nomonic sign of psoriasis (Figure 1B-F).
Features of inflammation can be observed throughout
the dermis in classic psoriasis; prominent and dilated
tortuous vessels, and slight edema of the papillary der-
mis, are typical signs (Figure 2A, B). Significant over-
expression of VEGF and CD34 has been documented

A B C D
Figure 1.—A) Classic psoriasis; B) psoriasiform hyperplasia, parakeratosis with regular elongation of rete ridges and characteristic bulbous enlarge-
ment of the tips with mutual elongation of dermal papillae (H&E stain, 5×); C) parakeratosis and thinned suprapapillary plate (H&E stain, 40×);
D) Munroe microabscesses with basal and suprabasal mitosis (H&E stain, 60×).
or other proprietary information of the Publisher.

A B C
Figure 2.—A) Eruptive psoriasis; B) dilated tortuous capillaries and fine fibrillary collagen, with thinning of the suprapapillary plate; plasma and
neutrophils outside the ectasic capillaries configuring the “squirting papilla” (H&E stain, 40×); C) lymphocytes and granulocytes infiltrate the ede-
matous dermis, and extravasation of erythrocytes (H&E stain, 20×).

174 Giornale Italiano di Dermatologia e Venereologia April 2018

not permitted. It is not permitted to remove, cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, log
means which may allow access to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use i
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HISTOPATHOLOGICAL ASPECTS OF PSORIASIS FERRELI
in psoriatic skin, suggesting that angiogenesis plays an
important role in genesis and development of psoriasis
vulgaris.17 Exocytosis of lymphocytes into the epider-
mis overlying the vessels, usually associated with mild
spongiosis is also seen (Figure 2A, B).18 CD4+ and CD8+
T-cells, are found in clinically well developed lesions,
with a predominance of CD8+ T-cells in the epidermis 19
and of CD4+ T-cells in the dermis.12 Moreover a sepa-
rate population of T-helper, the Th17 cells, are present
in psoriatic lesions producing IL-17A and IL-22.18, 20
Differences exists in relation of the age of the lesion. 21
The early manifestations of psoriasis can be nonspecif-
ic, with a prevalence of dermal modifications, such as
dermal edema, dilatation and congestion of vessels 18
and a sparse superficial perivascular T-lymphocytic in-
filtrate.12 Subsequently, minimal spongiosis develops
associated with rare T-lymphocytes and/or neutrophils
exocytosis. Neutrophils may fill the lumen of the ves-
sels.18 Later slight epidermal hyperplasia, with neu-
trophils and small mounds of parakeratosis containing
neutrophils are seen with a superficial inflammatory in-
filtrate of mononucleated cells, neutrophils, Langerhans
cells, and indeterminate cells,22 without eosinophils.
Extravasated erythrocytes can be present, particularly
in acute onset (Figure  2C).23 Lymphatic channels are
also increased.24
Well-established lesions show prominent psoriasi-
form epidermal hyperplasia, with pallor of the super-
ficial layers of the epidermis, regular elongation of rete
ridges with characteristic bulbous enlargement of their
tips sparing the suprapapillary area that is thin. Dermal
papillae are elongated containing fibrillary collagen
with tortuous and dilated capillaries. Confluent paraker-
atosis and Munro’s microabscesses are present in most
cases. Spongiosis is minimal or absent. A perivascular
inflammatory infiltrate made by T lymphocytes,18 fewer
Langerhans cells, CD163-positive spindle-shaped mac-
rophages and very occasional neutrophils are found in
the papillary dermis. Plasma cells and eosinophils are
usually absent;18 some exocytosis of lymphocytes is ob-
served in the lower layers of epidermis.25 The increased
keratinocyte proliferation, due to the increased mitotic
activity within the basal and suprabasal layers, is asso-
or other proprietary information of the Publisher.
ciated with an increase in the apoptotic rate, in concert
with a reduction of bcl-2 expression in basal cells.26 The
expression of Ki-67 is increased, confirming an increase
of the mitotic activity.27 In psoriatic skin, basal kerati-
Vol. 153 - No. 2 Giornale Italiano di Dermatologia e Venereologia 175
nocytes maintain expression of keratins typical of basal
keratinocytes (K5 and K14) whereas the keratins typi-
cal of suprabasal cells (K1 and K10) are replaced by so
called hyperproliferation-associated keratins, K6 and
K16, in addition to K17.28
Late resolving lesions are mainly characterized by
acanthosis and elongation of rete ridges with conspicu-
ous enlargement of the tips associated with narrowing
of the bases with some “bridging” formation.12, 23 The
stratum corneum restarts to become orthokeratotic with
a reconstitution of a granular layer.12 A residual mild
superficial fibrosis 12 with capillary dilatation and tortu-
osity are the only remnant clues of the disease.12, 23
Sebopsoriasis
Sebopsoriasis is an overlap between seborrheic der-
matitis and psoriasis in which findings of both diseases
coexist. It has a prevalence of 5.3% of psoriatic pa-
tients.29 Although strong histological criteria differenti-
ating seborrheic dermatitis from psoriasis do not exist,30
those favoring psoriasis are: mounds of parakeratosis
with neutrophils, spongiform micropustules of Kogoj,
clubbed and evenly elongated rete ridges and higher mi-
totic figures. Irregular acanthosis, follicular hyperkera-
tosis, shoulder parakeratosis, spongiosis, microvesicles
and exocytosis of lymphocytes coupled with the lack of
any strong criteria for psoriasis are indicative of sebor-
rheic dermatitis (Figure 3A).31
Follicular psoriasis
Follicular psoriasis is an under diagnosed condition
due to a lack of awareness. For this reason, an exact
prevalence is not known. It manifests with erythema-
tous scaly papules located mainly on trunk and limbs.
Histological features, as for classic psoriasis, vary with
the duration of the lesion. Established lesions show fol-
licular dilatation and plugging, marked ostial parakera-
tosis and hypogranulosis with a neutrophilic infiltrate.32
The dermal inflammatory infiltrate is both perivascular
and perifollicular. The main differential diagnosis is
with pityriasis rubra pilaris which demonstrates irregu-
lar acanthosis, focal or confluent hypergranulosis and
parakeratosis alternating in the vertical and horizontal
directions, and lack of neutrophils in the stratum cor-
neum (Figure 3B).33
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means which may allow access to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use i
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FERRELI HISTOPATHOLOGICAL ASPECTS OF PSORIASIS

A B

C D
Figure 3.—A) Sebopsoriasis; B) follicular hyperkeratosis and parakeratosis on the shoulder, associated with lymphocytic exocytosis (H&E stain,
10×) and follicular dilatation and plugging (inset), marked ostial parakeratosis and hypogranulosis with a neutrophilic infiltrate (H&E stain, 40×);
C) oral psoriasis; D) geographic tongue showing subepithelial infiltrates with predominance of neutrophils, and diffuse exocytosis, forming micro-
abscesses and, in some cases, pustules (H&E stain, 60×).

Oral psoriasis we have subepithelial infiltrates with predominance of

A number of immune related conditions affecting the
gastrointestinal tract are associated with psoriasis 34 and
recently the term ‘oral psoriasis’ has become widely ac-
cepted.35 Oral manifestation of psoriasis are rare and
most commonly involve mucosal membranes of the
tongue, cheeks and gums.36 They can be divided into
two groups: psoriasis-specific lesions, and non-specific
lesions.37 The specific manifestation are characterized
by histopathological features similar to that of skin pso-
riasis. The non-specific lesions are mainly represented
or other proprietary information of the Publisher.
neutrophils, and diffuse exocytosis, forming microab-
scesses and, in some cases, pustules. Vascular ectasia in
the chorion is more prominent in the clinically erythem-
atous areas.39 In fissured tongue, there is an increased
thickness of the lamina propria, that is infiltrated by a
mixed inflammatory infiltrate, hyperplasia of rete ridges
and neutrophilic microabscesses in the upper epithelial
layers (Figure 3C, D).40
Flexural psoriasis

by geographic tongue and fissured tongue.38 In this Flexural (intertriginous or inverse) psoriasis is a form
case, the diagnosis of oral psoriasis can be made when of psoriasis in which the most evident clinical differ-
skin and oral mucosal lesions, confirmed histopatho- ence from the classical plaque-type psoriasis is the lack
logically, occur simultaneously. In geographic tongue, of desquamation at the flexural areas.41 It affects be-

176 Giornale Italiano di Dermatologia e Venereologia April 2018

not permitted. It is not permitted to remove, cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, log
means which may allow access to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use i
This document is protected by international copyright laws. No additional reproduction is authorized. It is permitted for personal use to download and save only one file and print only one copy of this Article. It is not permitted to make additional copies
(either sporadically or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other
©
COPYRIGHT 2018 EDIZIONI MINERVA MEDICA
HISTOPATHOLOGICAL ASPECTS OF PSORIASIS FERRELI

tween 3% and 7% of the patients with psoriasis; how-
ever, the actual incidence is still unknown.39 The lesions
are well demarcated, erythematous and often showing,
because of the moist, a shiny/glazed appearance. from a
histopathologic point of view, the reduction of the scal-
ing is reflected by similarly decreased presence of epi-
dermal hyperplasia, and more pronounced spongiosis
(Figure  4A). A decreased amount of lesional CD161+
cells has been found in the dermis of flexural psoriatic
lesions as a result from chronic microbial challenge in
this area. Kogoj’s and Munro-Sabouraud’s collections
of neutrophils associated with thickening of the Malpi-
ghian layer, elongation of the papillae, hypogranulosis
and parakeratosis have also been described.41
Genital psoriasis
Although an overlap between flexural and genital
psoriasis exists, genital psoriasis is not considered a
form of flexural psoriasis; indeed, 38% of patients with
genital psoriasis did not have a flexural skin involve-
ment.42 Genital psoriasis, with a prevalence rate be-
tween 11.7% and 38% 43 is one of the most uncomfort-
able form with a strong impact on patients’ quality of
life.44, 45 Histologically, there is no apparent difference
between genital and non-genital psoriasis. We have epi-
dermal hyperplasia, less scaling, more prominent exo-
cytosis (Figure 4B, C). However, the typical character-
istics of psoriasis may be less evident on the mucosal
side of vulvar and penile psoriatic lesions. Mucosal in-
volvement often elicits less epidermal hyperplasia and
less scaling as compared with other cutaneous sites, but
spongiosis can be more prominent.12
Palmoplantar psoriasis
Palmoplantar psoriasis represents a variant of psoria-
sis that develops on the palms and soles. It can be as-
sociated with many different psoriatic patterns but pre-
dominantly accompanies pustular lesions. This clinical

A B
or other proprietary information of the Publisher.

C D
Figure 4.—A) Flexural psoriasis; B) marked reduction of the stratum corneum and dominance of the dermal alterations (H&E stain, 10×); C) genital
psoriasis; D) epidermal hyperplasia and less scaling, exocytosis more prominent (this epidermal hyperplasia can be absent on biopsies taken on the
mucosal side) (H&E stain, 60×).

Vol. 153 - No. 2 Giornale Italiano di Dermatologia e Venereologia 177

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means which may allow access to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use i
This document is protected by international copyright laws. No additional reproduction is authorized. It is permitted for personal use to download and save only one file and print only one copy of this Article. It is not permitted to make additional copies
(either sporadically or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other
©
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FERRELI HISTOPATHOLOGICAL ASPECTS OF PSORIASIS

A B

C D
Figure 5.—A) Palmoplantar psoriasis; B) regular epidermal hyperplasia, multiple foci of parakeratosis, placed vertically, alternating with ortho-
hyperkeratosis and dilated capillaries favor the diagnosis of psoriasis (H&E stain, 5×); C) nail psoriasis; D) neutrophils in the nail bed epithelium
associated by hyperkeratosis, parakeratosis, serum globules and hemorrhage in the stratum corneum (H&E stain, 40×).

variant accounts for 3-4% of all psoriasis cases.46 Psoria-
sis on the palms and soles is sometimes hardly to be dif-
ferentiated from contact dermatitis,47, 48 because in this
anatomic area the two diseases can have common char-
acteristics like the dyshidrotic features.49 Well-demar-
cated, erythematous, scaly plaques of the palms and/or
soles characterize palmoplantar psoriasis. Occasionally
vesicles and commonly fissures and hyperkeratosis are
seen.46 Haydin et al. found multiple parakeratotic foci,
placed vertically, alternating with ortho-hyperkeratosis,
to be considered in favor of palmoplantar psoriasis.49
Regular epidermal hyperplasia and marked parakerato-
sis were found to be more frequent in psoriasis than in
contact dermatitis and, by immunohistochemistry, the
findings of irregular epidermal hyperplasia and a higher
number of S100 protein-positive dendritic cells favor
or other proprietary information of the Publisher.
sent in contact dermatitis. Some diagnostic confusion
initially does exist because when the psoriasis has an
acute onset the spongiosis is prevailing and, as a clue on
palms and soles, it is often restricted to the lower epi-
dermis. In this cases, initial biopsies show intense spon-
giosis and some vesiculation, mounds of parakeratosis
containing neutrophils, dilated vessels in the papillary
dermis, and a mild, superficial perivascular infiltrate of
lymphocytes (Figure  5A).18 The presence of multiple
parakeratotic foci placed vertically and alternating with
ortho-hyperkeratosis, favored a diagnosis of psoriasis.49
Neutrophils and serum are often present in the para-
keratotic layers in palmoplantar psoriasis, but it is very
uncommon for the neutrophils to be at the summit of
the parakeratotic mounds.18 In case of pompholyx, the
non-allergic dyshidrotic eczema, multiple foci of para-

the diagnosis of contact dermatitis.47 Moreover eosino- keratosis, irregular epidermal hyperplasia and thinning
phils, which are common in allergic contact dermatitis, of rete ridges are observed. However, dyskeratotic cells,
are not typically seen in lesions of psoriasis.12 Dilated papillary dermal edema, dilated capillaries are not sig-
and tortuous capillaries in the dermis are generally ab- nificantly different from psoriasis.50

178 Giornale Italiano di Dermatologia e Venereologia April 2018

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means which may allow access to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use i
This document is protected by international copyright laws. No additional reproduction is authorized. It is permitted for personal use to download and save only one file and print only one copy of this Article. It is not permitted to make additional copies
(either sporadically or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other
©
COPYRIGHT 2018 EDIZIONI MINERVA MEDICA
HISTOPATHOLOGICAL ASPECTS OF PSORIASIS FERRELI
Nail psoriasis
Nail psoriasis can be the sole manifestation of a
psoriatic disease presenting with pitting, onycholysis,
subungual hyperkeratosis, and nail discoloration, but
sometimes the changes are so destructive that can lead
to functional and social impairments.51 The prevalence
of nail involvement in psoriasis patients varies between
15% and 79%.52 The diagnosis of psoriatic nail disease
without cutaneous psoriasis can be challenging but this
type of psoriasis is rarely biopsied because of the aes-
thetic complain consequent to the procedure. Psoriasis
can affect any part of the nail unit, but most changes
occur in the horny layer of the bed and of nail plate.
Histopathology is characterized by the presence of neu-
trophils in the nail bed epithelium associated, as minor
criteria, by hyperkeratosis, parakeratosis, serum glob-
ules and hemorrhage in the stratum corneum, focal hy-
pogranulosis and psoriasiform hyperplasia of the nail
bed (Figure 5B). In a study analyzing 42 patients, the
most common histological pattern was hyperkeratosis
with parakeratosis in the distal portion of the nail bed
and in the hyponychium associated with variable neu-
trophil exocytosis into the parakeratotic layers. Spon-
giosis is a common feature of nail psoriasis. In most
cases PAS stain is necessary before making a diagnosis
of nail psoriasis because onychomycosis and psoriasis
may show similar histopathology.50
Peculiar clinical variants
There is a group of psoriasis in which prevails the
autoinflammatory process, due to a loss-of-function
mutation in the IL-36 receptor antagonist (IL36RN, or
DITRA). The clinical presentation is characterized by
generalized pustular psoriasis 53 and/or localized pustu-
lar forms of psoriasis,54 but typically does not increase
susceptibility to chronic plaque psoriasis dominated by
an autoimmune process.55 The other peculiar clinical
subtypes of psoriasis, such as erythrodermic and inverse
psoriasis, oral psoriasis and localized pustular forms
of psoriasis have IL-36 responses in-between those of
or other proprietary information of the Publisher.
plaque and pustular psoriasis. In these cases, each clini-
cal phenotype, seems to represents a different balance
between autoimmune and autoinflammatory immune
processes.4
Vol. 153 - No. 2 Giornale Italiano di Dermatologia e Venereologia 179
Pustular psoriasis
Pustular psoriasis is traditionally classified into gen-
eralized and localized forms. According to the ERAS-
PEN Network (European Rare and Severe Psoriasis Ex-
pert Network) in generalized pustular psoriasis (GPP)
we have a primary (relapsing or persistent), sterile, mac-
roscopically visible pustules on non-acral skin, with or
without systemic inflammation. This occurs both with
or without psoriasis vulgaris.56 Therefore, this not in-
cludes cases where pustulation is restricted to psoriatic
plaques.
The main clinical variants of generalized pustular pso-
riasis (GPP) embrace acute GPP (of von Zumbusch) and
subacute GPP (generalized annular pustular psoriasis).57
The exact prevalence of generalized pustular psoriasis
(GPP) is unknown, but the condition appears to be rare.58
It is characterized by the abrupt development of wide-
spread, painful erythematous patches or thin plaques
that rapidly become covered with numerous small sterile
pustules, that can coalesce in larger collections of “lakes
of pus.” The pustules resolve within several days, leav-
ing erythema and extensive scaling. The histopathologi-
cal diagnostic feature reflect the acute onset of the mani-
festation, as the pustular eruption occurs before the time
necessary to produce the typical epidermal hyperplastic
changes 12 and is dominated by the presence of intraepi-
dermal pustules at various stages of development.18 In
these cases, we observe parakeratosis and elongation
of the rete ridges configuring very slight psoriasiform
hyperplasia with numerous neutrophils migrating from
the dermal capillaries into the epidermis, forming sub-
corneal pustules overlying focal spongiform pustules of
Kogoj. The pustules are localized between degenerated
and flattened keratinocytes within the upper Malpighian
layer of the epidermis.12 Similarly to other variants, the
neutrophils of the spongiform pustule eventually migrate
into the stratum corneum and assume the appearance of
a Munro microabscess. A superficial perivascular lym-
pho/histiocytic infiltrate and dilated tortuous vessels are
seen in the dermal papillae (Figure 6A, B).
Acute generalized exanthematous pustolosis (AGEP)
is a rare acute drug induced eruption characterized by
diffuse edematous erythema covered by numerous non-
follicular sterile pustules and associated by fever and
peripheral blood leukocytosis. This condition can be
particularly difficult to distinguish from GPP, especially
in patients with IL36RN mutations.59-61 Eosinophils and
not permitted. It is not permitted to remove, cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, log
means which may allow access to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use i
This document is protected by international copyright laws. No additional reproduction is authorized. It is permitted for personal use to download and save only one file and print only one copy of this Article. It is not permitted to make additional copies
(either sporadically or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other
©
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FERRELI HISTOPATHOLOGICAL ASPECTS OF PSORIASIS

A B

C D
Figure 6.—A) Pustular psoriasis; B) slight epidermal hyperplasia, exocytosis of neutrophils migrating forming subcorneal pustules and large spongi-
form pustules of Kogoj; degenerated and flattened keratinocytes delimitate the collection of neutrophils; extravasation of erythrocytes between a
lymphohistiocytic infiltrate and neutrophilic infiltrate in the dermis (H&E stain, 5×); C) acrodermatitis of Hallopeau; D) epidermal hyperplasia,
elongation of the rete ridges and thinned suprapapillary plates, neutrophils aggregated in subcorneal collection; dermal papillae enlarged, occupied
by tortuous vessels surrounded by lymphocytes (H&E stain, 60×).

necrotic keratinocytes and vasculitic changes are among
the histological findings that suggest a diagnosis of AGEP
rather than GPP.62
Acrodermatitis of Hallopeau
Acrodermatitis continua of Hallopeau (ACH) is a
rare, chronic, sterile, pustular eruption that predomi-
or other proprietary information of the Publisher.
sis, consdidering that some cases of ACH may progress
to GPP. (IL36RN homozygous missense mutation sup-
ports this hypothesis).64 The microscopic features show
regular acanthosis of the epidermis, with elongation of
the rete ridges, hyperkeratosis, parakeratosis and, like in
pustular psoriasis, neutrophils aggregated in subcorneal
collection delineated by flattened degenerated keratino-
cytes. Dermal papillae are enlarged over a thinned su-

nantly affects the fingertips with nail involvement.39 Its prapapillary plates. They are occupied by tortuous ves-
incidence is difficult to estimate given the rarity of the sels, associated with inflammatory infiltrate composed
disease.63 Although some authors consider ACH a dis- of small lymphocytes with perivascular disposition.
tinct entity, it is more likely a variant of pustular psoria- Thinning of the epidermis and severe atrophy of the

180 Giornale Italiano di Dermatologia e Venereologia April 2018

not permitted. It is not permitted to remove, cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, log
means which may allow access to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use i
This document is protected by international copyright laws. No additional reproduction is authorized. It is permitted for personal use to download and save only one file and print only one copy of this Article. It is not permitted to make additional copies
(either sporadically or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other
©
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HISTOPATHOLOGICAL ASPECTS OF PSORIASIS FERRELI
papillary dermis may be evident in areas of longstand-
ing disease.65 Changes in the nail bed in patients suf-
fering from ACH are acanthosis, presence of variable
numbers of spongiform pustules, focal hypergranulosis
and microabscesses of Munro (Figure 6C, D).66
Erythrodermic psoriasis
Generalized erythroderma has an estimated prevalence
of 1-2.25% among psoriatic patients,67 often precipitated
by a prior systemic infection or steroid therapy. It is char-
acterized by erythema, edema, pruritus, ill-defined psori-
atic plaques, scaling, hair loss, and occasionally exuda-
tive lesions and palmoplantar or diffuse desquamation.
Often some psoriatic characteristics are maintained 68 or
additional symptoms can help in the clinical diagnosis
but, since erythroderma can be a consequence of a va-
riety of diseases, histological criteria indicative of the
psoriatic origin can be of extreme help for the manage-
ment of these patients.69 Even though there are no yet
histologic criteria universally defined for erythrodermic
psoriasis, the skin biopsy in these cases is a must. One
of the features that can be distinctive and indicative of
a psoriatic origin of the erythroderma, is the presence of
wider dermal papillae with more consistent dilatation of
capillaries and extravasated erythrocytes within edema-
tous dermal papillae associated with perivascular and in-
terstitial infiltration of lymphocytes and histiocytes;68 the
stratum corneum is almost completely absent due to an
extremely accelerated turnover (Figure 7A, B).12
Psoriatic arthritis
Psoriatic arthritis (PsA) affects 10-40% of patients
with psoriasis with a peak onset in late 20 to 40 sec-
or other proprietary information of the Publisher.
A B
Figure 7.—A) Erythrodermic psoriasis; B, C) presence of wider dermal papillae with more consistent dilatation of capillaries, extravasated erythro-
cytes within edematous dermal papillae associated with perivascular and interstitial infiltration of lymphocytes and histiocytes. The stratum corneum
is almost completely absent (H&E stain, 10× and 60×).
Vol. 153 - No. 2 Giornale Italiano di Dermatologia e Venereologia 181
onds. Skin lesions may be coincident or precede arthrit-
ic symptoms in most patients, and many patients with
psoriasis are not aware of their PsA.70 Some psoriatic
manifestation, more than others, have a close correla-
tion with the presence of joint involvement and may
also correlate with PsA’s severity.71 In general, nail dys-
trophy, but also scalp lesions, and intergluteal/perianal
lesions have been found to be associated with a higher
risk of PsA development. Moreover, patients with se-
vere psoriasis seems to manifest higher risk of arthritis
than patients with mild psoriasis.70 Nails alterations are
the more frequent psoriatic manifestations associated
with PsA, and may represent a part of the enthesitis;
in this setting, onycholysis has the strongest associa-
tion.72 Acrodermatitis continua of Hallopeau affects
distal parts of the hands and feet, including the nails.
It is not often associated with PsA but in extensive and
longstanding disease may result in sclerosis and osteo-
lytic alteration of the underlying bone, particularly the
distal phalanges.73 All this cutaneous manifestation do
not exhibits a histopathological picture that can evocate
the association with the joint involvement.
Old and new treatment effects on histology
Histological modification in psoriasis under treat-
ment are documented since long time 74 and in some
way reflect the pictures of spontaneous resolving pso-
riasis.12, 18, 23 The residual mild superficial dermal fibro-
sis, the augmented fibroblasts in the papillary dermis 23
with persistence of dermal capillary dilatation and tor-
tuosity, and progressive diminution in the inflamma-
tory infiltrate, are the only histopathologic clues of this
stage.12 In relation to the drug used to treat psoriasis,
modifications of the inflammatory infiltrate and/or the
C
not permitted. It is not permitted to remove, cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, log
means which may allow access to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use i
This document is protected by international copyright laws. No additional reproduction is authorized. It is permitted for personal use to download and save only one file and print only one copy of this Article. It is not permitted to make additional copies
(either sporadically or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other
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COPYRIGHT 2018 EDIZIONI MINERVA MEDICA
FERRELI HISTOPATHOLOGICAL ASPECTS OF PSORIASIS
epithelial component of the psoriatic lesions are seen.
Disappearance of neutrophils and prominent apoptosis
has been demonstrated after zinc pyrithione treatment
of psoriasis.75 Resolution of epidermal hyperplasia,
confirmed by keratin 16 expression, has been showed in
patients treated with bath PUVA and has been correlated
with the reduction in intraepidermal T lymphocytes as-
sociated with a marked reduction of epidermal CD1a+
Langerhans cells.76 Erosions and ulcerations on psoriat-
ic lesions or inflammatory flare of pre-existing psoriatic
plaques can be typically observed during methotrexate
overdosage.77-79 Lastly, anti TNF alpha drugs may in-
duce a paradoxical psoriasiform eruption as a side ef-
fect.80-82 In this setting, three histopathological patterns
of the eruption have been described: one closely similar
to psoriasis and the other two respectively characterized
by a lichenoid pattern and a sterile pustular follicular
reaction pattern. This reactions pattern can be found
contemporarily in the same patient or with different
timing. The feature that can help distinguishing the pso-
riasiform pattern from primary psoriasis is the presence
of eosinophils and plasma cells in the infiltrate.83 The
lichenoid reaction is characterized by focal mounds of
parakeratosis and a deeper inflammatory infiltrate with
a variable number of eosinophils and numerous plasma
cells. The presence of parakeratosis, unusual in lichen-
oid reaction, can explain the psoriasiform clinical pre-
sentation. The follicular reaction seems to be a psoriatic
pustular eruption with the presence of eosinophils. This
last element, coupled with the negativity of microbio-
logical culture, represents the main differential diagnos-
tic feature.81
Conclusions
Psoriasis is a complex disease whose immunopatho-
genesis involves an interaction between an abnormal
innate and adaptive immune response to environmen-
tal factors.2, 5 The complex interplay between cytokine
networks and immune cell types is translated into the
histopathological pictures.9, 11, 20, 24, 26
The histopathology of classic psoriasis is very well
known and reproducible, although skin biopsy is rarely
or other proprietary information of the Publisher.
performed in typical cases. Histopathology is helpful in
less typical clinical variant where the identification of
subtle clues is fundamental for the completion of the
diagnosis and the individuation of the appropriate treat-
182 Giornale Italiano di Dermatologia e Venereologia April 2018
ment. In this review, we have analyzed the histopatho-
logical pictures of the different clinical variants of pso-
riasis giving some clues to drive the correct diagnosis
when the clinical aspects are not enough indicative of
the disease. However, in some situations, an adequate
follow-up with multiple punch biopsies over time may
be required to establish the definitive diagnosis.
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(either sporadically or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other
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means which may allow access to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use i
This document is protected by international copyright laws. No additional reproduction is authorized. It is permitted for personal use to download and save only one file and print only one copy of this Article. It is not permitted to make additional copies
(either sporadically or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other
©
COPYRIGHT 2018 EDIZIONI MINERVA MEDICA
FERRELI HISTOPATHOLOGICAL ASPECTS OF PSORIASIS

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Conflicts of interest.—The authors certify that there is no conflict of interest with any financial organization regarding the material discussed in the manuscript.
Article first published online: December 15, 2017. - Manuscript accepted: November 30, 2017. - Manuscript received: October 31, 2017.
or other proprietary information of the Publisher.

184 Giornale Italiano di Dermatologia e Venereologia April 2018