INTRODUCTION OF PSORIASIS, EPIDEMIOLOGY OF PSORIASIS, CLINICAL FEATURES OF PSORIASIS, PROGNOSIS OF PSORIASIS, HISTOPATHOLOGY OF PSORIASIS, TRIGGERING FACTORS OF PSORIASIS, PATHOGENESIS OF PSORIASIS

3. • DEFINITION: It is a chronic immune-mediated systemic
disorder results from a polygenic predisposition combined
with environmental triggering factors.

4. • The word “psora” means a
desquamative condition or itch.
• The characteristic lesion is a sharply
demarcated erythematous plaque
with micaceous scale, and the
plaques may be localized or
widespread in distribution.
• Natural history: chronic with
intermittent remissions.

5. • Psoriasis is a systemic disease process in which up to 20–30%
of the patients have or will develop psoriatic arthritis. In
addition, in patients with moderate to severe psoriasis, there
is an increased relative risk for metabolic syndrome and
atherosclerotic cardiovascular disease.
• Psoriasis also has a significant impact on patients’
quality of life.

7. • 2% of the world’s population.
• Two-thirds of affected individuals were suffering from
mild psoriasis, while one-third had more severe
involvement.
• Psoriasis can first appear at any age, from infancy to the
eighth decade of life. Two peaks in age of onset have been
reported: one at 20–30 years of age and a second peak
at 50–60 years.
• Age of onset is earlier in women than in men

8. • Are important in psoriasis also play a role in the clinical
course of psoriasis.
• Positive family history has been reported by 35% to 90% of
patients with psoriasis.
• If both parents had psoriasis, the risk of their child
developing psoriasis is 41%.
• There is a two- to three fold increased risk of psoriasis in
monozygotic twins as compared to dizygotic twins.

9. • Psoriasis is associated with HLA-Cw6.
• HLA-Cw6 is strongly linked to the age
of onset of psoriasis 90% of the patients
with early-onset psoriasis, in 50% of
those with late-onset psoriasis.

10. MHC genes resides on chromosome 6

11. • Classic genome-wide linkage analysis
has identified at least nine psoriasis
susceptibility regions (PSORS1–9)in
different chromosomal locations.
• By far the most important genetic
region is PSORS1 (on chromosome
6p), which is estimated to account
for up to 50% of psoriasis risk.
• PSORS1 contains genes such as
HLA-C (with the HLA-Cw6 risk allele)
and corneodesmosin (CDSN).

12. • Most of the genes that have been implicated have immune-related
functions, underscoring the importance of the innate and adaptive
immune systems in the pathogenesis of psoriasis.
• Skin-derivedantimicrobial peptides: expressedat high levels in psoriatic skin.
• Associated genes encode proteins with roles in particular immunologic and
signaling pathways, especially those involving tumor necrosis factor
(TNF), NF-κB, interferons (IFN) and interleukin (IL)-23/Th17 cells.
• In contrast, relatively few genes that encode skin-specific proteins have
been associated with psoriasis.
• The ERAP1 gene encoding an aminopeptidase involved in MHC class I
antigen processing is only associated with psoriasis risk in individuals
carrying the HLA-Cw6 risk allele, providing evidence for the role of an
MHC-restricted antigen and its presentation through HLA-C in the
pathogenesis of psoriasis.

14. PSORIASIS CLASSIFICATION
• No one classification of psoriasis satisfies all the mentioned
requirements. Usually, criteria are intermingled.

15. 1. PSORIASIS VULGARIS (Most common subtype is chronic
plaque psoriasis)
2. GUTTATE PSORIASIS.
3. ERYTHRODERMIC PSORIASIS.
4. PUSTULAR VARIANTS.
5. PSORIATIC ARTHRITIS

16. 1. Scalp psoriasis & sepopsoriasis
2. Nail psoriasis
3. Palmoplantar psoriasis
4. Flexural psoriasis
5. Oral psoriasis
6. Napkin psoriasis
• Psoriasis can present with a spectrum of cutaneous
manifestations. At any one point in time, different variants may
coexist in a particular individual, but the skin lesions all share
the same important hallmarks: erythema, thickening and scale.

17. SYMPTOMS
• The major symptom is disfigurement.
• Over 65% of patients complain of itching.
• Patients may report that their disease worsens in the winter
and improves in the summer.

18. • The most common variant of psoriasis
vulgaris.
• Characterized by sharply
demarcated and erythematous
papulosquamous lesions (Dry, thin,
silvery-white scales).
• Irregular, discoid or oval in shape.

19. Relatively symmetric distribution.

20. • The scalp, elbows, knees and
presacrum are sites of predilection, as
are the hands and feet. The
genitalia are involved in up to 45% of
patient.
• Other sites of predilection include the
umbilicus and the intergluteal cleft
• Plaques may persist for months to years
at the same locations.

21. • Rich red color: often referred to as
'salmon pink‘. This quality of color is
of special diagnostic value to
differentiate psoriasis from eczema in
lesions on the palms, soles and scalp.
• In the fair-skinned individual, the
color is less rich and almost magenta
pink.
• In dark-skinned races, the quality of
the color is lost.

22. • Their highly characteristic sharp
demarcation, psoriatic lesions are
sometimes surrounded by a pale
blanching ring, which is referred to as
Woronoff’s ring.

23. • During exacerbations, psoriatic lesions
often itch. Pinpoint papules surrounding
existing psoriatic plaques indicate that the
patient is in an unstable phase of the
disease. In addition, expanding psoriatic
lesions are characterized by an active
edge with a more intense erythema.
Inflamed lesions may be slightly tender.

24. • The involution of a lesion usually
starts in its center, resulting in annular
psoriatic lesions.
• Annular, well-demarcated,
erythematous plaques with adherent,
silvery-white scales and central
clearing. The elbows, knees, scalp,
intergluteal region, lower back,
periumbilical area, palms, and soles
are often involved.
• The annular pattern occurs with
plaque or pustular psoriasis.

26. • The isomorphic phenomenon
(Koebner reaction): 38-76% of
patients recognize that new lesions
appear at sites of injury 7-14 days
after the skin has been injured
• In some patients, so-called reverse-
Koebner reactions have also been
noted in which preexisting psoriatic
plaques actually clear after injury
or trauma to the skin.

28. • If the superficial silvery white
scales are removed via
curettage (grattage method),
a characteristic coherence is
observed, as if one has scratched
on a wax candle (“signe de la
tache de bougie”).
• Subsequently, a surface
membrane is seen, which will
also come off as a whole.
• If the latter is removed, then a
wet surface is seen with
characteristic pinpoint bleeding.
This finding, called Auspitz sign, is
the clinical reflection of
elongated vessels in the dermal
papillae together with thinning of
the suprapapillary epidermis.

31. Psoriasis geographica:
The borders may resemble a land map

32. GENITAL PSORIASIS

35. It is a method to estimate
severity of psoriasis in order to
evaluate the clinical efficacy
of new treatments.
This is a single score calculated
from the body surface area
involved (utilizing a seven-point
score for involvement in
each of four anatomic areas –
head, upper extremities, trunk
and lower extremities 0 to 6).

36. • and from the scores for
erythema, induration and
scaling (each scored using a
five-point score from 0 to 4).
• Total score ranges 0-72.

38. • Characterized by eruption of small (0.5 to
1.5 cm in diameter) papules over the
upper trunk and proximal extremities.
• More commonly seen in children and
adolescents and is frequently preceded
by an upper respiratory tract infection.
• In over half of the patients, an elevated
antistreptolysin O, antiDNase B or
streptozyme titer is found, indicating a
recent streptococcal throat infection

40. • The disease affects all body sites.
• Erythema is the most prominent feature
with superficial scaling.
• Patients with erythrodermic psoriasis lose
excessive heat because of generalized
vasodilatation, and this may cause
hypothermia.
• Psoriatic skin is often hypohidrotic due to
occlusion of the sweat ducts.
• There is an attendant risk of
hyperthermia in warm climates.

41. • Lower extremity edema is common
secondary to vasodilatation and loss
of protein from the blood vessels into
the tissues.
• High-output cardiac failure and
impaired hepatic and renal function
may also occur.
• Erythrodermic psoriasis may start from
worsening of plaque psoriasis to
involve most body areas or it may be a
response to treatment as a
generalized Koebner reaction.

42. • Onset can be gradual or acute.
• Clues to the diagnosis of psoriatic erythroderma include
previous plaques in classic locations, characteristic nail
changes, and facial sparing.

44. A. Generalized pustular psoriasis: Generalized pustular
psoriasis during pregnancy is also referred to as
impetigo herpetiformis. Four distinct patterns of generalized
pustular psoriasis can be seen
i. von Zumbusch Type.
ii. Annular pattern.
iii. Exanthematic type.
iv. “Localized” pattern.
B. Localized pustular psoriasis:
i. Pustulosis of the palms and soles (palmoplantar
pustulosis.
ii. Acrodermatitis continua of Hallopeau.

45. • It is an unusual rare life-threatening
manifestation of psoriasis, It is
usually preceded by other forms of
the disease.
• The disease occurs abruptly as
attacks characterized by fever
malaise, and leukocytosis that lasts
several days and a sudden
generalized eruption of sterile
pustules 2 to 3 mm in diameter.

46. • Various provoking factors are known
including:
1. Withdrawal of systemic corticosteroids
2. Other systemic therapies: lithium,
aspirin, indomethacin, iodide and
some beta-blockers
3. Infections
4. Irritating topical treatment: coal tar,
dithranol
5. Hypocalcemia.

47. • The pustules are disseminated over the trunk &
extremities, including nail beds, palms, & soles.
• The pustules usually arise on highly painful
erythematous skin, first as patches and then
becoming confluent as the disease becomes
more severe disease & lead to erythroderma.

48. • After several days, the
pustules usually resolve and
extensive scaling is observed.
Sometimes, chronic plaques
of psoriasis, if present, can
resolve.
• Onycholysis and shedding of
nails; hair loss of the telogen
defluvium type, 2–3 months
later; circinate desquamation
of tongue

50. • It is a rare variant of pustular psoriasis.
• Lesions may appear at the onset of
pustular psoriasis, with a tendency to
spread and form enlarged rings, or they
may develop during the course of
generalized pustular psoriasis.
• The characteristic features are pustules in
advancing edge on a ring-like erythema.
• Healing occurs centrally.

51. Annular pustular psoriasis. Multiple annular
inflammatory plaques studded with pustules.
As the lesions enlarge, there can be central
clearing, dry desquamation

52. • lesions are identical to annular
pustular psoriasis but occur during
pregnancy.
• Onset is usually early in the third
trimester and persists until delivery.
• It tends to develop earlier in
subsequent pregnancies.
• It is often associated with
hypocalcaemia.
• There is usually no personal or family
history of psoriasis.

53. • This is an acute eruption of small pustules, abruptly appearing
and disappearing over a few days.
• It usually follows an infection or may occur as a result of
administration of specific medications, e.g. lithium.
• Systemic symptoms usually do not occur.
• There is overlap between this form of pustular psoriasis and
pustular drug eruptions, also referred to as acute generalized
exanthematous pustulosis (AGEP)

54. • Sometimes pustules appear within or at
the edge of existing psoriatic plaques.
• This can be seen during the unstable
phase of chronic plaque psoriasis and
following the application of irritants, e.g.
tars.

55. • Characterized by “sterile” pustules of the
palmoplantar surfaces admixed with
yellow–brown macules scaly
erythematous plaques.
• A minority of patients have chronic
plaque psoriasis elsewhere.
• In contrast to the natural history of
generalized pustular psoriasis, the
pustules remain localized to the
palmoplantar surfaces and the course of
this disease is chronic.

57. • Focal infections and stress have been
reported as triggering factors and
smoking may aggravate the condition.
• Pustulosis of the palms and soles is one
of the entities most commonly
associated with sterile inflammatory
bone lesions, for which there are several
names: chronic recurrent multifocal
osteomyelitis, pustulotic arthro-osteitis,
and SAPHO syndrome. Several
neutrophilic dermatoses are associated
with SAPHO.

58. • Synovitis, Acne, Pustulosis, Hyperostosis, and Osteomyelitis
• Acne fulminans, acne conglobata, pustular psoriasis, and
palmoplantar pustulosis
• Chest wall is most site of musculoskeletal complaints

59. • It is rare sterile, pustular eruption distal portions of
fingers or sometimes toes slowly extends proximally.
• Often triggered by localized trauma or infection at
the distal phalanx (the tip of the digit).
• 80% begin in only one digit, most commonly thumb.
• During acute flare-ups, the skin of the distal phalanx becomes red and scaly
and develops small pustules.
• The pustules often join together and on bursting, reveal a painful, red and
glazed area where new pustules then develop.

60. • Pustulation of the nail bed and nail matrix can
result in onychodystrophy and anonychia (loss of
nail).
• Slowly, the disease can rarely spread proximally to
affect the hand, forearm and/or foot.
• There may be osteolysis resulting in a wasted and
tapered tip of finger or toe.
• Transition into other forms of psoriasis can occur
and may be accompanied by generalized
pustular psoriasis of the Zumbusch type and
annulus migrans of the tongue.

63. • Develops in approximately 10-30 %
of those with psoriasis.
• In approximately 50% of those
affected arthritis appears one
decade after the onset of psoriasis,
whereas in the remainder the onset
occurs with the disease or precedes
it In a minority of patients .
• More prevalent among patients
with relatively severe psoriasis.

64. • Inflammation of the interphalangeal
joints – both distal (DIP mainly) and
proximal (PIP) – of the hands and feet
is the most common presentation of
psoriatic arthritis.
• Involvement of the PIP or both the DIP
and PIP joints of a single digit can
result in the classic “sausage” digit.

67. CLASSIFICATION PSORIATIC ARTHRITIS (Five Types)
1. Mono- and asymmetric oligoarthritis.
2. Arthritis of the distal interphalangeal joints.
3. Rheumatoid arthritis-like presentation.
4. Arthritis mutilans.
5. Spondylitis and sacroiliitis.

68. • Early diagnosis of psoriatic arthritis
is important, as disease
progression often results in loss of
function.
• There are no specific serologic
tests for establishing the diagnosis
of psoriatic arthritis.
• X-Ray: Enthesitis (inflammation of
the insertion points of tendons
and joints into bone).Periosteal
new bone formation.

69. •The blue arrow = a normal joint
space.
• Red arrow = “cup and saucer”
effect of the fourth metatarsal
bone being jammed into the
base of the fourth toe.
•The yellow circle = “Pencil
appearance” destruction
characteristic of the disease.

71. 1. Scalp psoriasis & Sebopsoriasis
2. Nail psoriasis
3. Palmoplantar psoriasis
4. Flexural psoriasis
5. Oral psoriasis
6. Napkin psoriasis

72. • The scalp is one of the most common sites for
psoriasis. Unless there is complete confluence,
the individual lesions are discrete, in contrast
to the less well-defined areas of involvement
in seborrheic dermatitis.
• At times, however, it is not possible to
distinguish seborrheic dermatitis from psoriasis,
and the two disorders may coexist.
• In very severe cases there may be some
temporary mild localised hair loss but scalp
psoriasis does not cause permanent balding.

74. • The back of the head is a common
site for psoriasis, but multiple discrete
areas of the scalp or the whole scalp
may be affected.
• Scalp psoriasis is characterized by
thick silvery-white scale over well-defined
red thickened skin.
• Psoriasis may extend slightly beyond
the hairline (facial psoriasis).

76. • The lesions of psoriasis often advance onto the
periphery of the face, the retroauricular areas and
the upper neck.
• The scales sometimes have an asbestos-like
appearance and can be attached for some
distance to the scalp hairs (pityriasis amiantacea).
• Pityriasis amiantacea can be seen in:
1. Scalp psoriasis is the most common cause
2. Seborrheic dermatitis
3. Secondarily infected atopic dermatitis
4. Tinea capitis (very rare)

78. • Is an overlap between psoriasis and
seborrhoeic dermatitis.
• It is a common clinical entity.
• Localized to seborrheic areas (scalp,
ears, glabella, nasolabial folds, perioral
and presternal areas, and intertriginous
areas).

79. • It presents with erythematous plaques
with less silvery scale than psoriasis and
more yellowish, greasy scale.
• But sebopsoriasis has a deeper red color,
more defined margins and a thicker
scale than typically seen in seborrhoeic
dermatitis alone. It is also less likely to
clear up with anti-dandruff shampoo.
• In the absence of typical findings of
psoriasis elsewhere, distinction from
seborrheic dermatitis is difficult.

82. • Reported in 10–80% of psoriatic patients.
• The fingernails are more affected than toenails.
• Psoriasis affects the nail matrix, nail bed and
hyponychium.
• Nail pitting is the commonest feature occurs due
to small parakeratotic foci in the proximal portion
of the nail matrix.
• Leukonychia and loss of transparency (less
common findings) are due to involvement
of the mid portion of the matrix.
• If the whole nail matrix is involved, a whitish,
crumbly, poorly adherent “nail” is seen.

83. • Psoriatic changes of the nail bed result in
the “oil spot” or “oil drop” phenomenon,
which reflects exocytosis of leukocytes
beneath the nail plate.
• Splinter hemorrhages are the result of
increased capillary fragility.
• Subungual hyperkeratosis and distal
onycholysis are due to parakeratosis of
the distal nail bed. Vigorous removal
of distal subungual debris may be an
exacerbating factor.

87. STOP
• Subungual
hyperkeratosis/
Splinter hemorrhages
• Thickening/
Transparency loss
• Oil spot /
Onycholysis
• Pitting

88. Psoriasis may predominantly affect the
palms and soles in various ways:
1. Typical scaly, red patches similar to
psoriasis elsewhere (Chronic plaque
psoriasis).
2. Generalised thickening and scaling of
the palms and soles (psoriatic
keratoderma).
3. Sheets of tiny yellow-brown pustules
(palmoplantar Pustulosis).

89. • Palms and soles affected by
psoriasis tend to be partially or
completely red, dry and thickened,
less often deep painful fissures.
• It can be quite hard to differentiate
from hand dermatitis and other
forms of keratoderma, but signs of
psoriasis elsewhere may help make
a diagnosis.

91. • Characterized by shiny, smooth, pink to
red, sharply demarcated thin plaques.
• Scaling is usually minimal or absent.
• Often a central fissure in the depth of the
skin crease is seen.
• When flexural areas are the only sites of
involvement, the term “INVERSE” psoriasis is
sometimes used.
• Localized dermatophyte, candidal or
bacterial infections can be a trigger for
flexural psoriasis.

92. Common sites of flexural psoriasis are:
1. Axillae
2. Inguinal
3. Inframammary
4. Umbilicus
5. Penis
6. Vulva
7. Natal (intergluteal) cleft
8. Around the anus
9. Retroauricular

93. Complications of flexural psoriasis include:
1. Irritation from heat and sweat.
2. Secondary fungal infections
particularly Candida albicans.
3. Lichenification from rubbing and
scratching – this is a particular problem
around the anus where faecal material
irritates causing increased itching.
4. Sexual difficulties because of
embarrassment and discomfort.
5. Atrophy of skin due to long term
overuse of strong topical steroids.

97. • Relatively uncommon.
• It is more likely to develop in those with the
more severe forms of psoriasis, especially
pustular psoriasis.
There are several types of oral lesion:
1. Irregular red patches with raised yellow or
white borders, similar to geographic
tongue. This is the most common.
2. Redness of the oral mucosa
3. Ulcers
4. Desquamative gingivitis
5. Pustules (in pustular psoriasis)

98. • Migratory asymptomatic annular erythematous
lesions with hydrated white scale (ANNULUS
MIGRANS) have been observed in patients with
acrodermatitis continua of Hallopeau and
generalized pustular psoriasis.
• It has been postulated to be an oral variant
of psoriasis, as these lesions show several
histologic features of psoriasis.
• However, geographic tongue is a relatively
common condition and is seen in many
nonpsoriatic individuals.

99. • Usually begins between the ages of 3-6
months.
• First appears in the napkin areas as a
confluent persistent, well-circumscribed,
symmetrical, shiny, red, scaly or macerated
plaques; other sites may be involved.
• It usually clears up after a few months to a
year, but may later generalize into plaque
psoriasis on the trunk & limbs.
• Family history common.

101. • Patients with extensive BSA involvement often afraid to be in public or wear
revealing clothing.
• Some patients shed scale constantly onto clothing, furniture, floors, etc.
• Many patients eventually become depressed if disease poorly controlled.
• Patients often motivated to
try anything that might be
effective.

103. • Chronic plaque psoriasis is in most cases a lifelong disease,
manifesting at unpredictable intervals.
• Spontaneous remissions, lasting for variable periods of time,
may occur in the course of psoriasis in up to 50 % of patients.
• The duration of remission ranges from 1 year to several
decades

104. • Guttate psoriasis is often a self-limited disease, lasting from
12 to 16 weeks without treatment. It has been estimated
that one-third to two-thirds of these patients later develop
the chronic plaque type.
• Erythrodermic and generalized pustular psoriasis have a
poorer prognosis, with the disease tending to be severe and
life threatening.

109. • Parakeratosis
• Orthokeratosis of normal basket-weave type
• Loss of granular layer

111. Dilated vessels in dermal papillae, perivascular cuffing with lymphocytes

112. • Munro micro-abscesses
i.e. accumulation of
neutrophil remnants in
the stratum corneum,
surrounded by
parakeratosis

113. • Spongiform pustule of Kogoj: An infiltration of neutrophils into necrotic
Malpighian layer in which the cell walls persist as a sponge-like
network
• Commonly seen in pustular psoriasis

115. • Test tube-like elongation of rete ridges
• Relatively thin suprapapillary plates
• Elongated club-shaped dermal papillae

117. Neutrophils
Parakeratosis

118. Mild Moderate Marked
Hyperkeratosis

119. Mild Moderate Marked
Suprapapillary thinning

120. Mild Moderate Marked
Capillary dilatation

121. • Guttate psoriasis. Superficial
perivascular, predominantly
lymphocytic infiltrate
• Minimal dermal edema.
• The overlying epidermis has
psoriasiform hyperplasia.
• Notice how the stratum
granulosum (on right) disappears
underneath the mound of
parakeratosis in the stratum
corneum (in center)

124. • Fully developed guttate lesion or the marginal zone of an
enlarging psoriatic plaque is designated as an “active
lesion”.
• Exaggerated spongiform pustules of Kogoj and
microabscesses of Munro, the histologic hallmarks of
“active” psoriasis, are seen also in pustular psoriasis.
• Neutrophils are typically prominent in active lesions and in
the marginal zone of expanding plaques,
• Marked edema is seen, especially at the tops of the
papillae in the active lesion.

126. • P: (Pink papules /Plaques /Pinpoint bleeding <Auspitz sign> /Physical
injury <koebner phenomenon>/Pitting of nails)
• S: (Silver scale/Sharp margins)
• O: (Onycholysis/Oil spots)
• R: (Rete Ridges with Regular elongation)
• I: (Itching)
• A: (Arthritis/Abscesses <Munro-Kogoj>/Acanthosis)
• S: (Stratum cornium with retained nuclei <parakeratosis>)
• I: (Immunologic)
• S: (Stratum granulosum absent/Subungual hyperkeratosis/Splinter
hemorrhages)

129. CAN BE DIVIDED INTO LOCAL (EXTERNAL) AND SYSTEMIC FACTORS:
I. Local factors
1. Trauma to the skin
2. Sunlight
II. Systemic factors
1. Infections
2. Endocrine factors
3. Psychogenic stress
4. Drugs
5. Alcohol consumption
6. Smoking
7. Obesity
8. Cold Weather

130. 1. Trauma:
• Physical, chemical, electrical, surgical, infective and
inflammatory types of injury or even excessive
scratching can aggravate or precipitate localized
psoriasis (Koebner phenomenon).
• KP is observed in ~25% of patients with psoriasis.
• A particular patient may be “Koebner -ve” at one
point in time and later become “Koebner +ve”.
• The Koebner phenomenon suggests that psoriasis is
a systemic disease that can be triggered locally in
the skin.
• The lag time between the trauma and the
appearance of skin lesions is usually 2–6 weeks.

131. 2. Sunlight:
• Most patients generally consider sunlight to be
beneficial for their psoriasis. Most report a
decrease in illness severity during the summer
months or periods of increased sun exposure;
however, a small minority find that their
symptoms are aggravated by strong sunlight

132. 1. Infections:
• Pharyngeal streptococcal (most common)
infections have been shown to produce guttate
psoriasis.
• Streptococci can also be isolated from other sites,
e.g. dental abscesses, perianal cellulitis, impetigo.
• An increase in psoriasis activity was observed in HIV
infected patients.
• Localized dermatophyte, candidal or bacterial
infections can be a trigger for flexural psoriasis.

133. 2. Endocrine factors:
• Psoriasis severity has been noted to fluctuate with
hormonal changes. Disease incidence peaks at
puberty and during menopause.
• Pregnant patients' symptoms are more likely to improve
(> 50% of the patients) than worsen (impetigo
herpetiformis). In contrast, the disease is more likely to
flare in the postpartum period.
• Hypocalcemia has been reported to be a triggering
factor for generalized pustular psoriasis. Although active
vitamin D3 analogues improve psoriasis, abnormal
vitamin D3 levels have not been shown to induce
psoriasis.

134. 3. Psychogenic stress:
• Psychogenic stress is a well-established
systemic triggering factor in psoriasis.
• It has been associated with initial
presentations of the disease as well as flares of
pre-existing psoriasis.
• Pruritus associated with increased anxiety or
depression may promote scratching and a
Koebner reaction.

135. 4. Drugs:
• Several drugs have been incriminated as
inducers of psoriasis. Rapid taper of systemic
corticosteroids can induce pustular psoriasis as
well as flares of plaque psoriasis.
• LIMBS
1. L: Lithium
2. I: Interferon
3. M: anti-Malarials
4. B: Beta blockers
5. S: Steroids/NSAIDs

136. 5. Alcohol consumption:
• Alcohol consumption has been associated
with psoriasis.

137. 6. Smoking:
• An increased risk of chronic plaque psoriasis
exists in smokers
• Smoking have a role in the onset of
psoriasis.

138. 7. Obesity:
• Obesity has been associated with psoriasis.
• Some studies have suggested that obesity
appeared to be a consequence of psoriasis,
whereas other studies have suggested that
weight gain often proceeds the development of
psoriasis.

139. 8. Cold Weather:
• Sudden exposure to cold weather can be a
trigger for a flare-up.
• In general, psoriasis symptoms appear more
frequently at high altitudes and in cold weather
climates than in tropical ones.

144. • Psoriasis is regarded as a T-cell-driven disease.
• The role of lymphocyte subsets as well as cytokines involved
in chemotaxis, homing and activation of inflammatory cells
has been extensively investigated, culminating in the
development of novel therapeutic approaches.
• Although some regard psoriasis as an autoimmune disease,
to date no true auto-antigen has been definitively
identified. It is considered immune mediated disease by
both innate & adaptive immune responses.

145. EVIDENCES SUPPORTING INVOLVEMENT OF THE INNATE IMMUNE SYSTEM IN
DEVELOPMENT OF PSORIASIS “6”:
1. DCs in both uninvolved and lesional psoriatic skin have potent
immunostimulatory capacity, There is an increased number of dermal DCs in
psoriatic skin, and they have an enhanced ability to activate T cells when
compared to DCs from normal skin.
2. Natural killer (NK) cells are found in psoriatic skin lesions; they interact with
CD1d on keratinocytes. The resulting production of IFN-γ could contribute
to additional immune stimulation.
3. Neutrophils found in the epidermis, either in spongiform pustules of Kogoj or
in microabscesses of Munro but they are not considered to be the primary
cause of psoriasis.
4. The innate immune cytokines IL-1, IL-6 and TNF-α are upregulated in psoriatic
skin. TNF-α is a particularly relevant cytokine and its importance is
underscored by the therapeutic efficacy of TNF-α inhibitors.
5. Chemokines: Increased presence of several chemokines and their
cognate receptors in psoriatic lesions.
6. AMP: such as (hBD1-2) and secretory leukocyte protease inhibitor (SLPI) and
cathelicidin LL37 are highly expressed in lesional psoriatic skin.

146. EVIDENCES SUPPORTING INVOLVEMENT OF THE ADAPTIVE IMMUNE SYSTEM
IN DEVELOPMENT OF PSORIASIS “6”:
1. The presence of specific T-cell subsets within the epidermis and dermis of lesional skin.
2. Disappearance or development of psoriasis following hematopoietic stem cell
transplantation.
3. Number of drugs that affect T-cell function (e.g. by targeting the IL-2 receptor, CD2,
CD11a and CD4) were found to result in clinical improvement of psoriasis.
4. Analysis of lesional T-cells has shown oligoclonality, possibly triggered by exogenous
microbial or viral antigens or cross-reacting autoantigens, e.g. keratins,DNA, RNA.
5. The association of psoriasis with particular MHC alleles, such as HLA-Cw6, and (in
individuals carrying such alleles) variants in the ERAP1 gene encoding an
aminopeptidase involved in Ag processing.
6. The adaptive immune cytokines:
i. Increased amounts of Th1 cytokines (TNF-α, IFN-γ and IL-2) are observed in psoriasis.
ii. The striking response of psoriasis to ustekinumab (a human monoclonal antibody against
the p40 subunit of IL-12 and IL-23).
iii. Circulating levels of IL-22 (secreted by Th17 & Th22) correlate with disease severity.

148. PHASES OF IMMUNOPATHOGENESIS OF PSORIASIS
1. Initiation phase
2. Innate immune response
3. Adaptive immune response
4. Epidermal hyperproliferation

150. 1. Initiation phase
• In genetically predisposed individuals with
occurrence of triggering environmental
factors complexes of self DNA or RNA
(from stressed keratinocytes) plus
antimicrobial peptide LL37.
• This leads to a breaking of tolerance to self
nucleic acids and explains the start of the
inflammatory cascade in psoriasis.

151. 2. Innate immune response
• Self DNA or RNA / LL37 complex trigger
IFN-α release by plasmacytoid dendritic
cells (pDCs) via a Toll-like receptor 9
(TLR9)-dependent mechanism thereby
activating dermal DCs (dDCs).
• Activated dDCs start migration to
regional lymph node.

152. 3. Adaptive immune
response
• dDCs present an as-yet-unknown
antigen (either of self or of microbial
origin) to naïve T cells and (via secretion
of different types of cytokines by DCs)
costimulatory signals are sent to the T
cell as a result of several other
interactions promote their differentiation
into T helper 1 (Th1), Th17 and Th22 cells.

153. 3. Adaptive immune response
• Th1 cells expressing CLA, CXCR3 and CCR4.
• Th17 cells expressing CLA, CCR4 and CCR6.
• Th22 cells expressing CCR4 and CCR10.
• These cells migrate via lymphatic and blood
vessels into psoriatic dermis, attracted by the
keratinocyte-derived chemokines CCL20, CXCL9–
11 and CCL17. CLA Expressed on their surface
binds to E-selectin on vascular endothelium of the
affected area of the skin.

154. 3. Adaptive immune response
• At the dermal–epidermal junction, memory CD8 +
cytotoxic T cells (Tc1) expressing very-late antigen-1
(VLA-1) bind to collagen IV, allowing entry into the
epidermis and contributing to disease pathogenesis
by releasing both Th1 and Th17 cytokines.

155. 4. Epidermal hyperproliferation
• Th1 cells release IFN-γ, TNF-α and IL-2 which amplify the
inflammatory cascade, acting on keratinocytes and dDCs.
• Th17 cells secrete IL-17A and IL-17F (and also IFN-γ and IL-
22), which stimulate keratinocyte proliferation and its
release of β-defensin 1/2, S100A7/8/9 and the neutrophil-recruiting
chemokines CXCL1, CXCL3, CXCL5 and CXCL8.
• Th22 cells secrete IL-22, which induces further release of
keratinocyte-derived T cell-recruiting chemokines.
• Keratinocytes also release vascular endothelial growth
factor (VEGF), basic fibroblast growth factor (bFGF), and
angiopoietin (Ang), thereby promoting neoangiogenesis.

156. 4. Epidermal hyperproliferation
• Neutrophils infiltrate the stratum corneum and
produce reactive oxygen species (ROS) and
α-defensin with antimicrobial activity, as well
as CXCL8, IL-6 and CCL20.
• Cross-talk between keratinocytes, producing
TNF-α, IL-1β and transforming growth factor-β
(TGF-β), and fibroblasts, which in turn release
keratinocyte growth factor (KGF), epidermal
growth factor EGF) and TGF-β, contribute to
tissue reorganization and deposition of
extracellular matrix (e.g. collagen,
proteoglycans).

157. 4. Epidermal hyperproliferation
• Keratinocytes within psoriatic plaques express
STAT-3. STAT-3 induced the upregulation of a
number of genes relevant for psoriasis, such as
those encoding ICAM-1 and TGF-α; the latter
has been shown to stimulate proliferation of
keratinocytes in psoriasis via an autocrine loop.
• As STAT-3 is activated by a variety of cytokines
including IL-22 as well as IL-6, IL-20 and IFN-γ,
this could represent a link between
keratinocyte activation and immune cells in
the development of the psoriatic lesion.

158. Hyperproliferation
of keratinocytes

159. Role of TNF-α in the pathogenesis of
psoriasis:
• Elevated concentration in lesional skin.
• Induces migration & maturation of DCs.
• Stimulates proinflammatory cytokines production.
• Induces proliferation of keratinocytes.
• Induces vascular proliferation.

160. • Psoriasis and psoriatic arthritis: Dr Arvind Kaul, Royal Free Hospital
• Bolognia 3rd ed
• http://dermnetnz.org
• Google images