Psoriasis pathogenesis and Pharmacotherapy

1. Saurabh P. Badole
1

2.  Psoriasis is a long-lasting autoimmune disease characterized by patches of
abnormal skin. These skin patches are typically red, itchy, and scaly.
 The spectrum of disease ranges from mild with limited involvement of small areas
of skin to large, thick plaques to red inflamed skin affecting the entire body
surface.
 Injury to the skin can trigger psoriatic skin changes at that spot, which is known
as the Koebner phenomenon.
 Psoriasis affects all races and both sexes
 The quality of life of patients with psoriasis is often diminished because of the
appearance of their skin.
2

3.  The symptoms of psoriasis vary depending on the types.
 There are five types of psoriasis :
1)Plaque Psoriasis
2)Guttate Psoriasis
3) Inverse psoriasis
4)Pustular Psoriasis
5)Erythrodermic psoriasis
3

4.  Plaque psoriasis is the most common form of the
disease affects about 85-90% people and appears as
raised, red patches covered with a silvery white
buildup of dead skin cells.
 These patches or plaques most often show up on
the scalp, knees, elbows and lower back. They are
often itchy and painful, and they can crack and
bleed.
4

5.  This is the second most common type of psoriasis,
after plaque psoriasis.
 Characterised by numerous small,scaly,droplike
lesions appears pink in colour
 Guttate psoriasis can also be triggered by
 Upper respiratory infections
 Streptococcal infections
 Tonsillitis
 Stress
 Injury to the skin
 Certain drugs (including antimalarials and beta
blockers)
5

6.  Inverse psoriasis (also known as intertriginous
psoriasis) shows up as very red lesions in body
folds. It may appear smooth and shiny.
 It is found in the armpits, groin, under the
breasts and in other skin folds on the body.It is
particularly subject to irritation from rubbing
and sweating because of its location in skin
folds and tender areas.
 It usually lacks the scale associated with
plaque psoriasis due to the moist
environment.
6

7.  Pustular psoriasis is characterized by white pustules
(blisters of noninfectious pus) surrounded by red skin.
The pus consists of white blood cells. It is not an
infection, nor is it contagious.
 It may be limited to certain areas of the body-for
example, the hands and feet.
 A number of factors may trigger pustular psoriasis,
including:
 Internal medications
 Irritating topical agents
 Overexposure to UV light
 Pregnancy
 Systemic steroids
 Infections
 Emotional stress
 Sudden withdrawal of systemic medications or
potent topical steroids
7

8.  Erythrodermic psoriasis is a particularly
inflammatory form of psoriasis that often affects
most of the body surface.
 The symptoms includes :
 Severe redness and shedding of skin over a large area
of the body
 Exfoliation often occurs in large "sheets" instead of
smaller scales
 Skin looks as if it has been burned
 Heart rate increases
 Severe itching and pain
 Body temperature goes up and down, especially on
very hot or cold days
8

9.  Genetic
 Lifestyle
 HIV infection
 Microbes
 Medications
9

10.  Psoriasis has a strong hereditary component, and many genes are associated with it.
 Most of the identified genes relate to the immune system, particularly the major
histocompatibility complex (MHC) and T cells.
 Classic genome-wide linkage analysis has identified nine loci on different
chromosomes associated with psoriasis. They are called psoriasis susceptibility 1
through 9 (PSORS1 through PSORS9).
 Within those loci are genes on pathways that lead to inflammation. Certain variations
(mutations) of those genes are commonly found in psoriasis.
 The major determinant is PSORS1, which probably accounts for 35%–50% of psoriasis
heritability.
 It controls genes that affect the immune system or encode skin proteins that are
overabundant with psoriasis. PSORS1 is located on chromosome 6 in the major
histocompatibility complex (MHC), which controls important immune functions.
10

11.  Three genes in the PSORS1 locus have a strong association with psoriasis
 HLA-C-encodes a MHC class I protein
 CCHCR1-encodes a coiled coil protein that is overexpressed in psoriatic epidermis and
also responsible for regulation of keratinocytes proliferations
 CDSN-encodes corneodesmosin, a protein which is expressed in the granular
and cornified layers of the epidermis and upregulated in psoriasis.
11

12.  It include chronic infections, stress, and changes in season and climate. Others
that might worsen the condition include hot water, scratching psoriasis skin
lesions, skin dryness, excessive alcohol consumption, cigarette smoking, and
obesity.
 Psoriasis tends to be more severe in people infected with HIV.
 The immune response in those infected with HIV is typically characterized
by cellular signals from Th2 subset of CD4+ helper T cells, whereas the immune
response in psoriasis is characterized by a pattern of cellular signals typical
of Th1 subset of CD4+ helper T cells and Th17 helper T cells.
 It is hypothesized that the diminished CD4+-T cell presence causes an
overactivation of CD8+-T cells, which are responsible for the exacerbation of
psoriasis in HIV-positive people.
12

13.  Psoriasis has been described as occurring after strep throat, and may be worsened
by skin or gut colonization with Staphylococcus aureus, Malassezia, and Candida
albicans.
 Drug-induced psoriasis may occur with beta blockers, lithium, antimalarial
medications, non-steroidal anti-inflammatory drugs,terbinafine, calcium channel
blockers, captopril, glyburide, granulocyte colony-stimulating
factor, interleukins, interferons, lipid-lowering drugs, and paradoxically TNF
inhibitors such as infliximab or adalimumab.
13

14. Any triggering stimulus may
be genetic
mutation,drug,microbial
infection
Stimulates inflammatory
cascade in dermis
involving dendritic
cells, macrophages, and T
cells
These immune cells move
from the dermis to the
epidermis
Secrete inflammatory chemical signals
(cytokines) such as interleukin-
36γ, tumor necrosis factor-
α, interleukin-1β, interleukin-6,
and interleukin-22
Results in premature proliferation of
keratinocytes
Skin cells replaced in every 3–5 days
rather than the usual 28–30 days
Psoriasis
14

15.  Body surface area(BSA) – Severity is determined by how much of body surface area is
affected
 Mild psoriasis - < 5%
 Moderate - 5-10%
 Severe - > 10 %
(1% of BSA is equivalent to palm of patient)
 Psoriasis Area Severity Index(PASI)- It measures the overall severity and extent
of psoriasis by assessing BSA and intensity of redness,thickness and scaling.Score of
this is in between 0-72
 0 score –No disease
 72 score –Maximal disease
15

16.  There is no exact cure for psoriasis but it can be controlled using some treatment
options which includes according to severity of disease condition :
 Topical therapy (for mild )
 Phototherapy (for moderate )
 Systemic Therapy (for severe psoriasis )
 Non Biologic
 Biologic
16

17.  Emollient
 Sooth,smooth and hydrate the skin. Also allow the other topical agents to be absorbed
better.
 Vitamin D Analogues (E.g.Calcipotriol)
 Available as cream,ointment and lotion.
 Vitamin D has Corticosteroid Sparing Effect due to increase expression of Mitogen
Activated Protein Kinase Phosphate-1 (MAPKP1) which is essential for glucocorticoid
mediated anti-inflammatory and immunosuppressive effect.
 Should not be use with calcium or vitamin D supplements may leads to hypercalcaemia
 Salicylic Acid
 Act as keratolytic agent removes excess growth of epidermal cells from lesions.
 Coal Tar
 Derived from coal used in the concentration of 0.5-5%
 Slows the rapid growth of skin cells,restores the skin appearance and also helps to reduce
the inflammation,itching and scaling.
 Overuse may lead to skin cancer. 17

18.  Dithranol (Anthracene Derivative)
 Known as short contact therapy because it stain the skin therefore need to rinse off after
10-30 minutes of application.
 It acts by accumulating in the mitochondria and interefere with energy production along
with inhibition of DNA replication by free radical generation which results in slowing of
excess cell division.
 Topical Corticosteroids (E.g. hydrocortisone cream 1%)
18

19.  Phototherapy in the form of sunlight has long been used for psoriasis.
 Phototherapy or light therapy, involves exposing the skin to ultraviolet light on a
regular basis and under medical supervision.
 It includes :
 Ultraviolet light B (UVB)
 Psoralen+UVA
 Laser treatment
Ultraviolet light B (UVB)
 Present in natural sunlight, ultraviolet B (UVB) is an effective treatment for psoriasis.
UVB penetrates the skin and slows the growth of affected skin cells.
 There are two types of UVB treatment, broad band and narrow band.
 The major difference between them is that narrow band UVB light bulbs release a smaller
range of ultraviolet light.
 Narrow-band UVB is similar to broad-band UVB in many ways. Narrow-band UVB clears
psoriasis faster and produces longer remissions than broad-band UVB. It also may be
effective with fewer treatments per week than broad-band UVB.
19

20.  UVB can be combined with other topical or systemic agents to enhance efficacy, but some
of these may increase photosensitivity and burning, or shorten remission.
 Combining UVB with systemic therapies may increase efficacy dramatically and allow for
lower doses of the systemic medication to be used.
 Contraindicated in Erythrodermic psoriasis due to risk of erythema and skin cancer.
 Psoralen+UVA(PUVA)
 Like UVB, ultraviolet light A (UVA) is present in sunlight. Unlike UVB, UVA is relatively
ineffective unless used with a light-sensitizing medication psoralen(Psoralea coryfolia;
Febaceae) which is administered topically or orally. This process is called PUVA.
 It slows down excessive skin cell growth and can clear psoriasis symptoms for varying
periods of time.
 Stable plaque psoriasis, guttate psoriasis, and psoriasis of the palms and soles are most
responsive to PUVA treatment.
20

21.  Laser Treatment
Excimer laser
 The excimer laser—recently approved by the Food and Drug Administration (FDA) for
treating chronic, localized psoriasis plaques—emits a high-intensity beam of ultraviolet
light B (UVB).
 The excimer laser can target select areas of the skin affected by mild to moderate
psoriasis, and research indicates it is a particularly effective treatment for scalp
psoriasis.
21

22.  Systemic medications are prescription drugs that work throughout the
body.
 They are usually used for individuals with moderate to severe psoriasis and
psoriatic arthritis. Systemic medications are also used in those who are not
responsive or are unable to take topical medications or UV light therapy.
BIOLOGIC NON-BIOLOGIC
 Adalimumab Methotrexate
 Etanercept Acitretin(Retinoid agent)
 Infliximab Ciclosporin
 Ixekizumab
 Ustekinumab (2016 approved)
 Guselkumab (2017 approved)
 Tildrakizumab (2018 approved)
22

23. 23

24. Diagnosis
with PASI
PASI Score
PASI ≤ 10
Mild
Topical Agent
worseningRemains mild
continue with topical
agent
PSAI >10
Moderate to
severe
Non biologic systemic
therapy or
phototherapy
If PSAI <10 If PSAI > 10
Continue with
systemic therapy or
phototherapy
Biologic therapy
24

25.  https://www.psoriasis.org/about-psoriasis
 https://en.wikipedia.org/wiki/Psoriasis
 https://www.medicinenet.com/psoriasis/article.html
 American Academy of Dermatology
 British Association of Dermatology
25

26. 26