Noninfectious Erythematous, - PowerPoint Presentation

Slide1

Noninfectious Erythematous, Papular, and Squamous Diseases

Dr.

Alireza

zeynadini

Meymand

Resident of Dermatology

Kerman medical University of science

Slide2

Acute Urticaria :Interestitial edemaDilated venulesEndothelial sowellingPaucity of inflammatory cells

HISTOPATHOLOGY

Slide3

Chronic urticaria :Interestitial edemaPerivascular & interestitial Mixed – cell infiltrtationLymphocytes , Eosinophils , Neutrophils (variable)

HISTOPATHOLOGY

Slide4

Angioedema :Edema & infiltration into subcutaneous tissueHereditory angioedema :Subcutaneous & submucosal edema without infiltration of inflamatory cells

HISTOPATHOLOGY

Slide5

Urticarial vasculitis :Infiltration around the walls of small blood vessels ( leuckocytoclysis )Low or no deposits of fibrin in vessel wallsSlight to moderate extravasation erythrocytes

HISTOPATHOLOGY

Slide6

Electron microscop : Degranulation mast cell & eosinophil Chronic Urticaria : IgG cross link to alpha chain of receptor IgE RELEASE OF HISTAMINC5 RELEASE O HISTAMINChemotactic mediatores from mast cell induce P- selectin , Eelastin ,ICAM 1 ,VCAM 1 ,Beta 2 integrin on leuckocytes

PATHOGENESIS

Slide7

Deficit in C1 esteras inhibitor : activation C1 activation C1 : activation C2 & C4 activation C2 & C4 : generation of C2 fragment + kinin like activity & finally increased vascular permeability

Hereditary Angioedema

Slide8

Urticarial vasculitis : circulating immune complex in ½ patientsDIF : Strong granula deposits in dermoepidermel junction & perivascular areasPositive IF : in hypocomlementemic form Renal biopsy : GN

IF

Slide9

Primigravid3th trimesterRash starts on the abdomenPruritic papules,erythematous,maybe vesicleProximal part of the extremitiesUsually involutes after deliveryFetal : unaffected

PRURITIC URTICARIAL PAPULES AND PLAQUES OF

PREGNANCY(PUPPP)

Slide10

Superficial & mid-dermal perivascular lymphohistiocytic infiltration Eosinophil,neutrophil , edema of superficial dermisFocal spongiosis , parakeratosis , mild acanthosis

HISTOPATHOLOGY

PUPPP

Slide11

Correlation between PUPPP and increased weight andTwin/triple positive PR (Progestron Receptor) by RT-PCRNonlesional epiderm : not PR positivityPlacenta expresses : paternal factor as cause of PUPPPDIF : negative or non specific

PATHOGENESIS

Slide12

Arcuate & polycyclic area of erythema2 variant : superficial & deepDeep form : palpable erythema + central clearing + absence of surface changesSuperficial form : trailing scale , delicate annular rim of scaleMay up to 10cm and over a several weeksMildly pruriticTrunk and proximal extremitiesMost resolve within 6 wMay persist or recur for years

ERYTHEMA ANNULARE CENTRIFUGUM

Slide13

PHOTO

Slide14

Superficial :superficial privascular tightly cuff lymphohitiocytositic infiltration Endothelial cell swellingFocal extravasatinon of RBCSpongiosisparakeratosis

HISTOPATHOLOGY

EAC

Slide15

Deep :Superficial and deep perivascular tightly cuff lymphohistiocytic infiltration striking coat Sleeve like pattern

HISTOPATHOLOGY

Slide16

Exactly not clearAssociated with :Occult infections,dermatophytosis,candidiasis,medications,rarely malignancy ( lymphoma)Rash has poor response to topical steroids

PATHOGENESIS

Slide17

Secondary syphilis : neumerous plasma cell & histiocytesIntima & endothelial cells are swollenTumid LE :Increased deposits of connective tissue mucin

Differential Diagnosis

Slide18

Very rare but highly characteristicParaneoplastic syndrom,associated with internal malignancy(lung-bronchial,esophageal,breast)Eruption typically very pruritic,cocenteric & parallel bands of erythema & scale ….wood-grain patternTrunk & extremitiesRashes migrate rapidly : up to 1 cm per dayIchthiosis & palmar/plantar hyperkeratosis

ERYTHEMA GYRATUM REPENS

Slide19

Mild acanthosis,spongiosis,parakeratosisSuperficial perivascular lymphohistiocytic infiltration include : eosinophils,neutrophils,melanophages

Histopathology

EGR

Slide20

DIF In lamina densa(BMZ) : Granular deposition of C3 , C4 , IgGSO : IMMUNOGENIC BASIS

Pathogenesis

EGR

Slide21

Synonym : Ashy dermatosisExtensive asymptomatic eruptionDisseminated macules , red active borderCoalescence : large patch with a polycyclic outlineAt first erythematous then blue – grayTrunk , arms , face

ERYTHEMA DYSCHROMICUM PERSTANS

Slide22

Early active stage :Vacoular alteration of the basal layerIn papillary dermis :mild to mod. Perivascular infiltration of lymphocytes,histiocytes,melanophagesExocytosis of lymphocytes into basal layerNecrotic keratinocytesColloid bodiesLate stage :Aggregation of melanophages in the papillary dermis

Histopathology

EDP

Slide23

Many vacoulesWidenig of intercellular spaces & retraction of desmosomesDiscountinuing of subepidermal BMMelanophages in dermisPigmentary incontinence & formation of colloid bodies (vacoular alteration)

Pathogenesis

Slide24

DIF : IgG on necrotic keratinocytes at dermo epidermal junctionImmunohistochemical stain : Tcells CD4+ & CD8+ICAM1 & HLA-DR on basal layerActivation AIM/CD69 & CD94

Pathogenesis

EDP

Slide25

Erythematous urticarial papulesSymmetric distributionTrunk , extensor of extremitiesMiddle agePH : DA or dermographismSimilar to DH but no grouping of lesions

PRURIGO SIMPLEX

Slide26

PHOTO

Slide27

Early papules : mild acanthosis , spongiosis with spongiotiv vesicles , parakeratosisPerivascular lymphocytes infiltrationEosinophils in some casesExcoriated papules :Absence of epiderm with crustHistologic change around hair folliclesDD : DH microabscesses of the tips of dermal papilla & neutrophils + eosinophils + nuclear dust

HistopathologyPRURIGO SIMPLEX

Slide28

A chronic dermatitis , discrete,raised,firm hyperkeratotic papulonodules5 – 12mm or largerExtensores of extremitiesIntensly pruriticMiddle ageWomen moreMay coexist with LSCCause unknown but maybe : Truma,insect bites,atopic background,metabolic or systemic diseases

PRURIGO NODULARIS

Slide29

PHOTO

Slide30

Hyperkeratosis,acanthosisPapillomatosis & irregular downward proliferationPsudoepitheliomatosis hyperplasiaLymphocytic infiltration & vertically collagen bondles in papillary dermisNeural hyperplasiaSilver or cholinesterase stain : number of cutaneous nerve langerhans cells Enlarged dendritic mast cells

HistopathologyPRURIGO NODULARIS

Slide31

first theory :Chronic truma by scratching neural proliferationSecond theory : dermal nerves extreme pruritisOver expression NGF & it’s receptpresNeural proliferation both axon & schwann cells

Pathogenesis

Slide32

Demonestration of nerve fiber by immunostain for :S – 100 ProteinNerofilamentMyelin basic proteinImmunohistochemical :Sensory nerves + sensory neuropeptides Meckel cells in basal layerDD : LSC , Kerathoacanthoma

Pathogenesis

Slide33

divided to :VulgarisGeneralized pustular Localized pustular

PSORIASIS

Slide34

Early psoriasis :Mounds of parakeratosis with neutrophilsthin granular layermoderate acanthosisfocal spongiosisincreased mitotic figuresdilated blood vessels at the tip of the dermal papillaePerivascular infiltrate of lymphocytes and a few neutrophils

Psoriasis Vulgaris

Histopathology

Slide35

well-developed plaque :elongated rete ridgesabsent granular layerParakeratosis with neutrophilsdilated tortuous vessels in the dermal papillaeSuprabasal mitosesthin suprapapillary epidermal platespallor of the upper epidermis

Psoriasis Vulgaris

Histopathology

Slide36

neutrophilic collections : within the parakeratotic cornified layer: Monro within the spinous and granular layer : Kogoj

Kogoj

& Munro

microabscess

Slide37

Section 7 part 2

R. Ahmadi

Slide38

Generalized Pustular Psoriasis

Histopathology:

Spongiform pustule of

kogoj

:

as a

macropustule

in all variants of GPP (

characteristic

)

1

st

: neutrophils migrate upper layer of epidermis

Then aggregate in songlike network of degenerated & thin epidermal cells

2

nd

: ↑ size of pustule then complete cytolysis of epidermal cell & finally

large single cavity

forms with thin epidermal cell at periphery

Neutrophils move of cornified layer become

pyknotic

( appearance of

large

munro

abscess

)

Parakeratosis

& elongation of rete ridges

( as seen in all forms)

Upper dermis

:

lymphocytes & neutrophils

infiltrates

Oral

lesios

: the same as skin

Healing stage

: the same as ordinary psoriasis

Slide39

Slide40

Localized Pustular Psoriasis

Histopathology:

Histologic picture in localized

pustular

& localized annular

pustular

: the same as generalized

pustular

psoriasis

Very early lesion:

1

st

:

spongiosis

+ exocytosis of

lymphocyets

in lower epidermis

( tips of dermal papilla

)

2

nd

(

maybe ) :

intarepidermal

vesicles

contain lymphocytes inside & neutrophils in wall

3

rd

massive exocytosis of neutrophils penetrate wall of

vesicule

Acute form

: leukocytoclastic vasculitis

Slide41

localized

acrodermatitis

continua of

Hallopeau

: nail bed

( matrix

occationally

)

involvment

as

:

marked epithelial hyperplasia

with variable numbers of

spongiform

pustules

orthokeratosis

with mounds of

parakeratosis

with neutrophils.

pustulosis

palmaris

et

plantaris

:

1) fully developed large

intraepidermal

unilocular

pustule

2

) many

neutrophils inside

pusule

3

) small

spongiform pustules

in epidermal wall of bigger pustule

Slide42

Psoriasis and AIDS

Histopathology:

Most cases:

the same as psoriasis

Others:

acanthosis

without

thinning of the

suprapapillary

epidermis

slight

spongiosis

,

rare

necrotic

keratinocyte

a superficial perivascular infiltrate of lymphocytes and

Histiocytes

eosinophils

may be present

Slide43

Pathogenesis of Psoriasis Vulgaris

complex interaction of:

altered

keratinocytic

proliferation and differentiation, inflammation, and immune

dysregulation

Electron

Microscopy:

Relapse

:

early

:

1.

swelling and intercellular widening of endothelial

cells

2.

activated macrophages migrate into the lower

epidermis

3.

then lymphocytes and neutrophils are

seen

Ultrastructurally

(

well developed active lesion

)

tonofilaments

are

decreased

size and number of

keratohyaline

granules

are greatly

reduced

cornified cells

possess thin

tonofilaments

and often retain organelles and a nucleus

as

parakeratotic

cells

Slide44

The intercellular spaces between all epidermal cells are widened

due to

deficiency

in the

glycoprotein-rich cell surface

intercellular adhesion is limited to the

desmosomes

increased rate of

mitosis related

parakeratosis

spongiform pustule of

Kogoj

A)

located

in the uppermost portion of the

spinous

and granular

layers

B)

multilocular

& composed of degenerated and flattened

keratinocytes & neutrophils

Capillary

wider

lumen

bridged

fenestrations and

gaps

edematous

areas in the cytoplasm of endothelial

cells pericytes

myocytes

extravasation

of

RBC ,

inflamatory

cells

thickened multilayered

basement membrane

Slide45

Epidermal Cell-Cycle Kinetics

rate of epidermal cell replication is markedly a

ccelerated

in active lesions

The

mitotic activity

correlate with the

degree of

parakeratosis

( vary in even in same lesion)

alternating layers

of

orthokeratosis

and

parakeratosis

(epidermal growth activity fluctuates in the lesions

)

germinative

cell cycle is

shortened

from 311 to 36

hours

(keratinocytes

proliferate 8 fold faster than

nl

)

aberrant expression of

apoptosis-related molecules

representing suppressed apoptotic

process ( maybe related to ↑ proliferation in psoriasis)

Slide46

Keratinocyte

Differentiation

In psoriatic skin:

basal keratinocytes continue to express

K5/K14

keratins

K1/K10 are replaced

by

hyperproliferation

-associated keratins

K6 and

K16

involucrin

is expressed

prematurely

Keratin 17

:in

upper

suprabasal

keratinocytes (

normaly

in deep outer root sheet)

Immunopathology

T cell mediated

disorder

CD8

+

T-lymphocytes

dominant in the

epidermis ( key

event) (

Nonlesional

skin

not

show)

clonal expansion of epidermal

T-lymphocytes

The activation of T-lymphocytes may be due to bacterial

superantigens

(

such as group A

beta-hemolytic

streptococci)

Slide47

Group A streptococcal-reactive CD8

+

( CD4 lesser

)

has

role in the pathogenesis of both

poststreptococcal

guttate

psoriasis

and

chronic plaque

psoriasis

Activated CD4

+

T-lymphocytes

produce:

interleukin-2

tumor necrosis

factor-alpha (TNF)

stimulate keratinocyte

that cause

interleukin-8

production then

chemotaxsis

of neutrophils & lymphocytes

gamma-interferon

(CD8

+

also produce this)

a)

initiation of psoriatic

lesions

b)

expression of

ICAM-1

in

keratinocytes

then

trafficking of lymphocytes into the epidermis

c

)

IP-10

overexpression

d)

decreased responsiveness of keratinocytes to

IFN

may

cause

hyperproliferation

of

epidermal cells

Slide48

Pathogenesis of Localized

Pustular

Psoriasis

pustulosis

palmaris

et

plantaris

with

psoriasis generally

not related

but

occurrence

of psoriasis in patients with

pustulosis

palmaris

et

plantaris

, reported in 19% to 48% of the

patients

common presence of

spongiform pustules

in the walls of the pustules of

pustulosis

palmaris

et

plantaris

leukotactic

factor identical to that noted in psoriasis

found in

pustulosis

palmaris

et

plantaris

Slide49

Pathogenesis of Psoriasis and

AIDS

Paradoxically

, as T-helper lymphocyte counts decline,

psoriatic

lesions

exacerbate

preterminal

stage

dermatitis improves

( due to

decreased

local production

of alpha

-

IFN

)

IFN serum levels were much

higher

in HIV+ psoriatic

patients

than non

psoriatc

The

immunodysregulation

resulting from HIV infection may trigger psoriasis in those genetically predisposed by carrying

HLA-

Cw

*0602

allele

Human retrovirus-5

has been implicated in the pathogenesis of psoriatic

arthropathy

but not

psoriasis

cellular immune reactions

involved in the pathogenesis of psoriasis may be

similar

in AIDS and non-AIDS patients

Slide50

Differential Diagnosis of Psoriasis

Key diagnosis

mounds

of

parakeratosis

with neutrophils at their summits (Munro

microabscesses

)

spongiform

micropustules

of

Kogoj

in the uppermost layers of the

spinous

layer

Helpful:

Dilatation and tortuosity of capillaries in the

papillae

Slide51

chronic eczematous dermatitis

(atopic dermatitis, nummular dermatitis, or allergic contact dermatitis)

acanthosis

with elongation of the rete ridges and

parakeratosis

=

psoriasis

elongation of rete ridges is

uneven

marked

spongiosis

and especially of

coagulated

serum

are features speaking against psoriasis ( except volar type

)

Eosinophils

(found

in allergic contact dermatitis and mainly in HIV+

patients)

are rarely seen in the psoriatic infiltrate

Slide52

Lichen simplex

chronicus

v.s

. fully developed psoriatic

plaques

prominent granular

layer

more

irregular

acanthosis

, and fibrosis of the papillary dermis

collagen bundles aligned perpendicularly to the skin surface

Seborrheic

dermatitis ( esp. overlap)

Accentuated

spongiosis

, mounds of

parakeratosis

with neutrophils predominantly at the

follicular

ostia

, and more

irregular

acanthosis

Pityriasis

rubra

pilaris

v.s

. well developed lesions

thick

suprapapillary

plates,

broader and shorter

ridges

,

preserved granular layer and alternating

ortho

and

parakeratosis

lacks Munro

microabscesses

and neutrophils in the infiltrate

Slide53

pustular

dermatophytosis

, bacterial impetigo,

pustular

drug eruptions, and

candidiasis

PAS and Gram stains are useful to identify the infectious

microorganisms

aggregates

of neutrophils with pyknotic nuclei within areas of

parakeratosis

may occur in

conditions the same as psoriasis

the

Kogoj

spongiform pustule

the same psoriasis

Slide54

REITER'S DISEASE

triad of urethritis, arthritis, and

conjunctivitis

Young men

a rule the arthritis occurs in attacks and is followed by

recovery

(

some cases

maycause

permanent damage to the affected

joints)

Cutaneous lesions occur in about half of affected

patients

predilection for

glans penis

(

balanitis

circinata

),

the

palms and soles

(

keratoderma

blennorrhagicum

):erythematous, mollusk-like plaques with central

keratotic

excrescences

the

subungual

areas

; hyperkeratosis with

opacification

of the nail plate and eventual shedding of the nail plate may occur

Slide55

Slide56

Histopathology (

REITER'S DISEASE

)

Early

pustular

lesions

spongiform

macropustule

in the upper epidermis

parakeratosis

and elongation of the rete ridges

Aged lesions

The

parakeratotic

cornified

layer

thickened considerably

with the pyknotic nuclei of

neutrophils

Old lesions ( resemble psoriasis)

spongiform pustules

are

no

longer seen

acanthosis

and

orthokeratosis

with only a

few areas of

parakeratosis

Slide57

Pathogenesis

urogenital or gastrointestinal

infections

such as

Chlamydia trachomatis

,

Ureaplasma

urealyticum

,

Shigella

, Salmonella, Campylobacter,

Cyclospora

, and Yersinia

species

Chlamydia trachomatis has been cultured from urethral samples in nearly

half of the patients

Eighty percent of Reiter's disease patients are

HLA-B27

positive

Differential

Diagnosis

The

early spongiform

pustule

v.s

.

pustular

psoriasis

Slightly older lesions

differ

from psoriasis by

markedly thickened cornified layer

Slide58

PARAPSORIASIS

1) Large

plaque

parapsoriasis

and

parapsoriasis

variegata

:

early stages of cutaneous T-cell

lymphoma

2) The

small plaque

parapsoriasis

The small plaque

parapsoriasis

(

digitate

dermatosis

)

Pink

to yellow, slightly scaly, oval or elongated, often finger print-like patches 1 to 5 cm in

diameter,

the

plaques are symmetrically distributed over the trunk and the proximal portions of the extremities following the tension lines of the skin

The eruption is usually asymptomatic, has a chronic course, and tends to

persist

Slide59

Histopathology(

PARAPSORIASIS

)

The small plaque

focal epidermal involvement

e.g. slight

spongiosis

, exocytosis of lymphocytes, mild

acanthosis

, and

parakeratosis

characteristic

finding:

Elongated

mounds of

parakeratosis

with collections of

plasma

above a basket-weave cornified

layer

large plaque

papillary

dermis

:

superficial

perivascular lymphocytic

infiltrate

Differentiation between small & large plaque is difficult

Pathogenesis

CD4

+

T-lymphocytes with a small proportion of the CD8

+

Slide60

Slide61

Relationship to

Lymphoma

small plaque

parapsoriasis

:

benign

disorder

without the potential of transformation into mycosis

fungoides

but

some cases there is a dominant clonal rearrangement of the infiltrating

T-lymphocytes

So

disorder is not related to mycosis

fungoides

where there is clonal T-cell proliferation in both peripheral blood and skin

Slide62

PITYRIASIS ROSEA

self-limited

dermatitis

lasting from 4 to 7

weeks

starts

with a herald patch

followed by a disseminated eruption. The lesions, found chiefly on the trunk, neck, and proximal

extremities

round

to oval salmon-colored patches

following the lines of cleavage and showing peripherally attached,

thin, cigarette paper-like

scales

Several

typical and atypical clinical variants

have been described including

papular

, vesicular, urticarial,

purpuric

, and recurrent

forms

Slide63

Slide64

Histopathology(

PITYRIASIS

ROSEA

)

The patches of the disseminated eruption

superficial

perivascular dermal infiltrate

(lymphocytes

, with occasional

eosinophils

and

histiocytes

)

exocytosis( lymph)

spongiosis

, intracellular edema, mild to moderate

acanthosis

, areas of decreased to absent granular layer, and focal

parakeratosis

Intraepidermal

spongiotic

vesicles

presence

of

extravasated

erythrocytes

in the papillary

dermis

Late lesions

: more

likely to have a

psoriasiform

pattern

The

herald patch

more

pronounced

acanthosis

, deeper and denser perivascular inflammatory infiltrate, and papillary dermal edema

Slide65

Pathogenesis

The cause

still

unknown

human

herpesvirus

7 (HHV-7) is suspected

Cell-mediated immunity

(

may be

)

due to

the presence of activated helper-inducer T-lymphocytes (CD4

+

/HLA-DR

+

) in the epidermal and dermal infiltrate

highly

increased number of Langerhans cells (CD1a

+

)

Differential Diagnosis

superficial

gyrate

erythem

(

milder

forms of

pityriasis

rosea

.

)

small plaque

parapsoriasis

Elongated

mounds of

parakeratosis

with plasma,

sparse

superficial perivascular lymphocytic infiltrate,

minimal

exocytosis and

spongiosis

Slide66

GIANOTTI-CROSTI SYNDROME (PAPULAR ACRODERMATITIS OF CHILDHOOD AND PAPULOVESICULAR ACROLOCATED SYNDROME)

nonpruritic

, symmetrical eruption of monomorphic erythematous papules

on

the face, extremities, and

buttocks

lasting about 3

weeks

lymphadenopathy and hepatitis B viral

infection (link) & several other viruses (

eg

EBV)

Slide67

Histopathology(

GIANOTTI-CROSTI

SYNDROME

)

superficial and mid-dermal perivascular infiltrate

of lymphocytes and

histiocytes

with some lymphocytes extending to the overlying epidermis where there is focal

spongiosis

and

parakeratosis

In

some instances true

lymphocytic vasculitis

has been described

Gianotti-Crosti

sx

(

Epstein-Barr virus

link)

marked

papillary dermal edema

with minimal

spongiosis

and rare

eosinophils

in the dermal

infiltrate

The

inflammatory pattern may also present as a

lichenoid

interface

dermatitis

Slide68

Pathogenesis

CD4

+

T-lymphocytes and about 20% of CD8

+

(suppressor-cytotoxic)

T-lymphocytes

increased number of

Langerhans cells

in the epidermis.

surface

antigen of the hepatitis B virus is

detectable

in the

sera of all cases

of

papular

acrodermatitis

of

childhood

hepatitis

B virus

a

negative

:

studies

for other viruses by means of throat swabs and stool samples and by testing for antibodies

Slide69

MUCOCUTANEOUS LYMPH NODE SYNDROME (KAWASAKI DISEASE)

mucocutaneous

lymph node

syndrome

children under

5 years

of

age

unexplained fever

lasting 5 or more days and of at least four out of five clinical criteria:

(

a) bilateral conjunctivitis

;

(b) erythematous oral mucosa, injected or dry fissured lips, and

strawberry tongue

(c) erythema and indurated edema of

hands

and feet often followed by

periungual

desquamation

(

d) polymorphous skin

rash

(e) cervical

nonsuppurative

lymphadenopathy

Slide70

three

clinical phases:

acute

,

subacute

, and convalescent

.

The first phase is the febrile period in which all the diagnostic signs may be seen

The

rash appears around

the third to fifth day

of illness and may have different morphologic patterns such as

maculopapular

,

morbilliform

,

scarlatiniform

, or

urticarial

cardiovascular complications

account for the death of 2% of the

children

Twenty percent of untreated patients may develop

coronary artery aneurysms

Slide71

Histopathology(

KAWASAKI

DISEASE

)

sparse

perivascular infiltrate of

lymphocytes and

histiocytes

marked

papillary dermal edema

, and dilatation of blood vessels

Mild exocytosis of lymphocytes can be seen

An

uncommon

pustular

variant

shows

sterile

intraepidermal

spongiform pustules

with

neutrophils

Pathogenesis

Predominancy

of CD4

+

T-lymphocytes

and

CD14

+

macrophages

, with only a few CD8

+

T-lymphocytes

and no CD20

+

B-lymphocytes

expression of HLA-DR

Slide72

Lichen

planus

actinicus

, or

pigmentosus

:

mainly in Middle Eastern countries(20-30%)

more common in children or young adults

spring and summer on sun-exposed areas, especially

face

Types:

annular

(the most common type)

pigmented

(resembling

melasma

)

dyschromic

Description:

annular

plaques with central slate blue to light brown pigmentation and well-defined, slightly raised,

hypopigmented

borders

Pruritus

is minimal or

absent

Slide73

The overlap

syndrome(lichen

planus

/lupus

erythematosus

)

at

the same time, skin lesions with clinical, histological, and/or immunological features typical of both diseases

Skin

erythematous

to purplish scaly

patches and plaques, some of them with central

atrophy

predilection for

photodistributed

areas

or

acral

portions of extremities

Slide74

Twenty-nail dystrophy

adults as well as children.

nails:

longitudinal

ridging and distal notching and

splitting

With

time they become thin and

roughened

Other

manifestations of lichen

planus

are usually

absent

In

children, the nail changes tend to involute spontaneously after

a few

years

In familial

cases:

unremitting

course

Congenital

cases have been described

idiopathic

or associated

with

alopecia

areata

, atopic dermatitis, lichen

planus

, or psoriasis

.

Slide75

Malignant

transformation

cutaneous lichen

planus

occurs in less than

1%

of cases

In

hypertrophic lichen

planus

of the

leg (squamous

cell carcinoma or

keratoacanthoma

) :

exceptional

occurrence

squamous

cell carcinoma

:

on

long-standing lesions of lichen

planus

situated on mucous membranes or the vermillion border

The

incidence of carcinoma evolving in oral lichen

planus

is about 0.5%

with a range of 0. 3% to 3

%

Development of carcinoma in ulcers of the feet

rare

(

lesions that had not been previously

grafted)

Slide76

Histopathology(LP):

Typical papules

compact

orthokeratosis

wedge-shaped

hypergranulosis

irregular

acanthosis

vacuolar

alteration of the basal

layer

a

band-like dermal lymphocytic infiltrate in close

approximation

to the

epidermis

Slide77

The cornified

layer:

compact

orthokeratosis

very few, if any,

parakeratotic

cells

( important)

The

granular cells

appear

increased in size

With coarse

and more abundant

keratohyaline

granules

.

Wickham's

striae

:

caused

by a focal increase in the thickness of the granular layer and of the total epidermis

Slide78

The

acanthosis

irregular

and affects the

spinous

layer of the rete ridges as well as the

suprapapillary

plates

keratinocytes of the

spinous

layer

often appear larger and

eosinophilic

rete

ridges:

show irregular lengthening, and some of them are pointed at their lower end, giving them a

saw-toothed

appearance

dermal papillae

between elongated rete ridges are often dome shaped

Slide79

The infiltrate

in

the upper dermis

band-like

and sharply demarcated at its lower border and is composed almost entirely of lymphocytes intermingled with macrophages

.

Melanophages

seen

in the upper dermis, often in considerable

number

old lesions, the cellular infiltrate decreases in density, but the number of

melanophages

increases

Slide80

Slide81

Oral

L

p

parakeratosis

rather than

orthokeratosis

alternating

areas of both types of keratinization with the presence of a granular layer

the

epithelium often is atrophic

Ulcerations through the rupture of vesicles or as a result of necrosis of the atrophic epithelium.

Slide82

lichen

planopilaris

Early lesions :

focally dense,

band

-like

perifollicular

lymphocytic infiltrate at the level of the

infundibulum and the isthmus

v

acuolar

changes of the basal layer of the outer root sheath and

necrotic keratinocytes

orthokeratosis

,

follicular plugging

, and wedge-shaped

hypergranulosis

of the infundibulum

Developed lesions:

perifollicular

fibrosis and epithelial

atrophy

at the level of the infundibulum and isthmus (

hourglass configuration

) .

Slide83

P

seudopelade

of

Brocq

:

end-stage scarring alopecia in which no visible hair follicles remain

The

hyperkeratotic

follicular papules seen on glabrous skin with lichen

planopilaris

of the scalp exhibit similar changes; however,

perifollicular

fibrosis is slight and the does not eventuate in scarring

Slide84

Ulcerative lichen

planus

In ulcerative lichen

planus

, specimens taken from skin

adjacent

to the ulcer generally show active lichen

planus

Slide85

Lichen

planus

actinicus

T

he histology is similar to the typical lichen

planus

but with :

thinning

of the epidermis at the

center

of the lesion

more

evident

pigmentary

incontinence

in the upper dermis.

Slide86

Overlap syndrome _lichen

planus

/lupus

erythematosus

In some cases histologic features

and direct immunofluorescence findings are more consistent with lichen

planus

in others favors lupus

erythematosus

and in another lesions of lichen

planus

that coexist, rather than overlap, with those of lupus

erythematosus

Slide87

Twenty-nail dystrophy

manifestation of diverse underlying processes; therefore, its histology will vary .

Biopsies show typical lichen

planus

involving the nail matrix However,

spongiosis

be prominent as in cases with atopic dermatitis

.

Slide88

Lichen

planus

pemphigoides

biopsies taken from bullae from uninvolved skin show

subepidermal

bullae

with an infiltrate that

not band-like

and contains

eosinophils

.

Slide89

direct immunofluorescence of

perilesional

skin

:

IgG

and C3

in a

linear

arrangement along the basement membrane zone

immunoelectron

microscopy

:

C3

is seen to be localized within the lamina

lucida

, analogous to its location in bullous

pemphigoid

.

circulating

IgG

autoantibodies directed against the bullous

pemphigoid

antigen 180 (

BP180, type XVII collagen

), a

transmembrane

hemidesmosomal

glycoprotein of the basal keratinocytes spans the lamina

lucida

.

Slide90

Electron microscopy (LP)

the basal keratinocytes with their desmosomes and

hemidesmosomes

, show

degenerative

changes

the

tonofilaments

in the basal cells are

decreased

in

early

lesions, they are increased in later lesions

The dermal infiltrate, extending to the epidermis, causes damage to the lamina

densa

The use of

antikeratin

immune sera has resulted in their intense staining

Necrotic keratinocytes often still contain cell organelles, such as

melanosomes

and mitochondria

Slide91

electron microscopic

i

n the vesicular lesions of lichen

planus

:

cytolysis

of basal keratinocytes

the blister cavity situated

below the

spinous

layer.

Slide92

Immunofluorescence ( lichen

planus

)

fibrinogen

deposition demonstrated as

shaggy

deposits at the dermal-epidermal junction

occasionally are there

granular

deposits of

IgM

or

linear deposits of C3 or both

IgG

and C3

in the basement membrane zone.

Slide93

Immunofluorescence

(

lichen

planopilaris

)

deposition of

IgM

and/or IgA,

IgG

, and, rarely, C3

at the level of the infundibulum and isthmus

deposition of

fibrinogen in a shaggy

pattern surrounding the affected follicles.

The

dermal-epidermal junction

is virtually always

negative

for deposition of

immunoreactants

.

Slide94

Immunohistochemistry

The infiltrating cells in lichen

planus

are T-lymphocytes with few B-lymphocytes.

90% are activated T-lymphocytes expressing HLA-DR antigen and some interleukin-2 receptor .

in

older

lesions of oral lichen

planus

the

suppressor T

-lymphocytes predominate

Slide95

In the epidermis adjacent to the infiltrate, basal keratinocytes express

HLA-DR

surface antigen and intercellular adhesion molecule-1 (

ICAM-1

)

Specific conjugations between CD4

+

(helper-inducer) T-lymphocytes and dendritic (HLA-DR

+

) cells and between CD8

+

(cytotoxic-suppressor) T-lymphocytes and degenerated basal keratinocytes have been observed in

lesional

epithelium of oral mucosa.

These cell-to-cell interactions suggest a

cell-mediated immune mechanism

is operative.

Slide96

DDX :

Lichenoid

drug eruptions

differentiated from lichen

planus

by

the presence of

focal

parakeratosis

with concomitant absence of the granular layer

necrotic keratinocytes

in the

basal and

spinous

layers

exocytosis

of lymphocytes to the upper layers of the epidermis

deeper

inflammatory infiltrate with numerous

eosinophils

Slide97

Differentiation from

lichenoid

lupus

erythematosus

is based on:

atrophy

of the epidermis in addition to

acanthosis

absence of eosinophilia of the keratinocytes

in the

spinous

layer

a superficial band-like infiltrate with a superficial and

deep perivascular and

periadnexal

infiltrate

the presence of a

thickened PAS-positive

basement membrane

dermal

mucin

deposits

Slide98

Lichen

planus

_ like keratosis

It

is a common lesion that occurs

on the trunk and upper extremities of adults between the fifth and seventh

decades

.

LPLK

consists of a

nonpruritic

papule

or

slightly indurated plaque that is nearly always solitary, although cases with more than one skin lesion have been

reported.

its

color varies from bright red to

violaceous

to brown

.

Its surface may be smooth or slightly

verrucous

.

Slide99

a

lichenoid

pattern that may be indistinguishable from lichen

planus

.

there is vacuolar alteration of the basal cell layer and a band-like lymphocytic infiltrate that obscures the dermal-epidermal junction.

Necrotic keratinocytes are commonly seen and may be numerous

the epidermis often shows increased eosinophilia,

hypergranulosis

, and hyperkeratosis.

Slide100

In contrast to lichen

planus

parakeratosis

is fairly common

Although usually focal .

eosinophils

and plasma cells

in the infiltrate found in LPLK as opposed to lichen

planus

.

A residual

solar

lentigo

at the edge

of the lesion supports LPLK.

In lichen

planus

,

CD20

+

B cells were fewer

than in LPLK.

Memory T cells express a skin-homing receptor called cutaneous lymphocyte-associated antigen (

CLA

). This antigen is strongly expressed in

lichen

planus

but not in LPLK.

Slide101

KERATOSIS LICHENOIDES

CHRONICA

begins

in adulthood between 20 and 50 years of

age

an extensive eruption, symmetrically distributed, predominantly on dorsal aspects of extremities and trunk consisting of red to

violaceous

papulonodules

covered with a thick, adherent scale and arranged often in a characteristic linear and occasionally reticular

pattern

associated

seborrheic

dermatitis-like eruption of the face,

palmoplantar

hyperkeratosis

and nail

changes with warty hypertrophy of the

periungual

tissues, which has been described

Slide102

KERATOSIS LICHENOIDES CHRONICA

lichenoid

inflammatory pattern with

vacuolar

alteration of the basal cell layer,

necrotic keratinocytes

, and a

band

-like inflammatory infiltrate of

lymphocytes,

histiocytes

, and numerous plasma cells

that obscures the dermal-epidermal junction

acanthosis

&

atrophy

covered by a

hyperkeratotic

cornified

layer showing

focal

parakeratosis

and

follicular plugging

Prominent

dilated dermal capillaries

are seen in cases with associated

telangiectasias

Slide103

LICHEN NITIDUS

Each papule of lichen

nitidus

consists

mixed-cell granulomatous

infiltrate that attached to the lower surface of the epidermis and confined to a

widened dermal papilla

.

The infiltrate composed of lymphocytes, mono- and a few multi-nucleated

epithelioid

histiocytes

.

The dermal infiltrate extends into the overlying epidermis is

flattened

and shows

vacuolar

alteration of the basal cell layer, focal

subepidermal

clefting

, diminished granular layer, and

focal

parakeratosis

.

Transepidermal

perforation of the infiltrate through the thinned epidermis occur

Follicular involvement

in lichen

nitidus

Slide104

Relationship Between Lichen

Planus

and Lichen

Nitidus

lichen

nitidus

:

parakeratosis

and epidermal flattening

Occasional deposits of

fibrinogen

significantly

smaller

proportion of CD4

+

(helper-inducer) and HECA-452

+

(skin-homing receptor) T-lymphocytes, compared to lichen

planus

lichen

planus

:

acanthosis

and hyperkeratosis

globular

deposits of

immunoglobulins

at the dermal-epidermal junction

Slide105

LICHEN

STRIATUS

fairly

uncommon dermatitis

occurs in children from 5 to 15 years of

age

It usually manifests itself as a unilateral eruption along

Blaschko's

lines

on

the extremities, trunk, or neck as either a continuous or an interrupted band composed of minute, slightly raised, erythematous papules, which may have a scaly surface

Slide106

LICHEN STRIATUS

superficial perivascular inflammatory infiltrate of lymphocytes admixed with

histiocytes

in the papillary dermis the infiltrate may have a

band

-like distribution with extension into the lower portion of the epidermis, where

vacuolar

alteration of the basal layer and

necrotic keratinocytes

the papillary dermis occasionally contains

melanophages

spongiosis

and intracellular edema

often associated with

exocytosis

of lymphocytes and focal

parakeratosis

Slide107

A

very distinctive feature

:

presence of inflammatory infiltrate in the

reticular dermis around hair follicles and

eccrine

glands

Pathogenesis:

the inflammatory cells reaching the epidermis are

CD8

+

(suppressor-cytotoxic) T-lymphocytes with the

Langerhans cells

population in the epidermis either decreased or increased

Differential Diagnosis:

In contrast to lichen

striatus

, the inflammatory infiltrate of lichen

nitidus

is only focally present in widened dermal papillae and contains more

histiocytes

.

The presence of epidermal

spongiosis

and a deeper dermal inflammatory infiltrate around adnexal structures are features rarely in lichen

planus

.

Slide108

INFLAMMATORY LINEAR VERRUCOUS EPIDERMAL

NEVUS

persistent

, linear, intensely pruritic

lesion composed

of erythematous, slightly

verrucous

, scaly papules arranged in one or several

lines

Although

the usual time of onset is early childhood, the disease may arise in adults

(

The most common location is on a lower extremity

.

ILVEN in association with arthritis

and

lichen

amyloidosus

has been reported

.

ILVEN is considered to be a variant of epidermal nevi

Slide109

ILVEN:

hyperkeratosis with

foci of

parakeratosis

, moderate

acanthosis

, elongation and thickening of the rete ridges with a

psoriasiform

appearance,

papillomatosis

, and, occasionally,

slight

spongiosis

with exocytosis

of lymphocytes

sharply demarcated

alternation

of

orthokeratosis

and

parakeratosis

in the

cornified

layer

Underneath the

parakeratotic

areas, there is mild exocytosis of lymphocytes and slight

spongiosis

The papillary dermis shows a mild to moderate perivascular inflammatory infiltrate of lymphocytes and

histiocytes

.

Slide110

Differential Diagnosis

ILVEN, in contrast to lichen

striatus

, is pruritic and persistent

.

Histologically,

lichen

striatus

tends to have a

lichenoid

pattern, and

ILVEN a

psoriasiform

pattern.

While

alternating

orthokeratosis

and

parakeratosis

can be seen in

psoriasis

and occasionally

Munro

microabscesses

can be found in ILVEN

, the differential diagnosis of these two entities could be sometimes difficult to assess and

clinicopathologic

correlation is necessary

Slide111

PITYRIASIS RUBRA

PILARIS

follicular

keratotic

papules and

perifollicular

erythema that coalesce to form orange-red scaly plaques

that

contain islands of normal-appearing skin

.As

the erythema extends, the follicular component is often

lost

The lesions spread caudally and may progress to a generalized

erythroderma

Other

clinical findings are

palmoplantar

keratoderma

and scaling of the face and scalp.

Slide112

PRP:

acanthosis

with

broad and short rete ridges

,

slight

spongiosis

,

thick

suprapapillary

plates, focal or confluent

hypergranulosis

, and

alternating

orthokeratosis

and

parakeratosis

oriented in both

vertical and horizontal

directions

In the dermis, there is a mild superficial perivascular lymphocytic infiltrate and moderately dilated blood vessels

Areas corresponding to follicular papules show

dilated infundibula filled out with an

orthokeratotic

plug

, and often display

perifollicular

shoulders of

parakeratosis

and a mild

perifollicular

lymphocytic infiltrate

Slide113

Pityriasis

Lichenoides

In

pityriasis

lichenoides

chronica

, the mild form,

:

superficial perivascular infiltrate composed of lymphocytes that

extends into the epidermis

, where there is

vacuolar

alteration of the basal layer,

mild

spongiosis

a few necrotic

keratinocytes

confluent

parakeratosis

Melanophages

and small numbers of

extravasated

erythrocytes

are commonly seen in the papillary dermis

Slide114

In PLEVA, the more severe form

,:

perivascular and dense band-like

, predominantly lymphocytic infiltrate in the papillary dermis that extends into the reticular dermis in a

wedge-shaped pattern

that obscures the dermal-epidermal junction with pronounced

vacuolar

alteration of the basal layer, marked

exocytosis

of lymphocytes and

erythrocytes

, and

intercellular and intracellular edema

leading to variable

degrees of epidermal necrosis

The overlying

cornified

layer shows

parakeratosis

and a scaly crust with neutrophils in the more severe cases

Variable degrees of

papillary dermal edema

, endothelial swelling, and

extravasated

erythrocytes are seen in the majority of cases

Slide115

Pathogenesis

Most of the cells are activated T-lymphocytes (HLA-DR

+

/CD3

+

) that express CD7 and rarely lack other T-cell antigens (CD2, CD5)

Two constant findings in PLEVA :

the predominance of CD8

+

(cytotoxic-suppressor) over CD4

+

(helper-inducer) T-lymphocytes in the infiltrate

the expression of HLA-DR on the surrounding keratinocytes , suggesting a direct cytotoxic immune reaction in the pathogenesis of epidermal necrosis.