The document provides detailed information on the histology, pathogenesis, types, and treatment of psoriasis. It describes the five layers of the epidermis and two regions of the dermis. Psoriasis results from an imbalance of cytokines that leads to abnormal keratinocyte proliferation. The main types discussed are plaque, pustular, guttate, inverse and nail psoriasis. General measures and various topical and systemic treatments are outlined, including coal tar, vitamin D analogues, phototherapy, methotrexate and biologics.

1. ONCOTREX
PSORIASIS
02/09/14
Dr. Harish Lalan
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2. Functions of the Skin
 barrier to physical agents
 protects against mechanical injury
 prevents dehydration of body through fluid loss
 reduces the penetration of UV Radiation
 helps regulate body temperature
 provides a surface for grip
 acts as a sensory organ
 acts as an outpost for immune surveillance
 plays a role in Vitamin D production
 has a
02/09/14 cosmetic association
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3. Histology --Skin
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4. Histology of Skin… contd
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5. EPIDERMIS
STRATUM BASALE
 Deepest layer of the epidermis
 Single layer of columnar or cuboidal cells→stem
cells with mitotic activity
 Renewal of epidermis takes about 3 to 4 weeks
 Melanin is produced by melanocyte cells
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6. EPIDERMIS
STRATUM SPINOSUM
 Irregularly polygonal cells
 Spine-like cytoplasmatic extensions of the
cells which interconnect the cells of this
layer
 Lamellar granules in the cytoplasm of the
spinous cells
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7. EPIDERMIS
STRATUM GRANULOSUM
 One to few layers of flattened cells
 Cytoplasm contains keratohyalin granules
 Lamellar granules release lipids to fill
entire interstitial space
 Nuclei begin to degenerate in the outer
part of stratum granulosum
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8. EPIDERMIS
STRATUM LUCIDUM
 Several layers of flattened dead cells
 Faint nuclear outlines are visible in only
few cells
 Stratum lucidum difficult to identify in
thin skin
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9. EPIDERMIS
STRATUM CORNEUM
 Cells are completely filled with keratin
filaments (horny cells)
 Nuclei can no longer be identified
 Cells are very flat
 Horny cells are constantly shed off
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11. DERMIS
PAPILLARY REGION
 Outer (superficial) region of dermis has bumps
called dermal papillae
 protrusions of dermal connective tissue which
indent the base of the epidermis
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12. DERMIS
RETICULAR REGION
 Lies beneath the papillary layer and consists of
larger, more coarsely textured collagen fibers
 Plus nerves and nerve endings, blood vessels,
sweat glands, and more
Reticular = network
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13. PATHOLOGY
NORMAL SKIN
 From St. Basale to St.
Corneum 4 weeks
 Basal layers divide
every 13-14 days
 Mature differentiate
and shed off ⇒
healthy skin
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PSORIATIC SKIN
 Basal layer to
Corneum 4 days
 Basal layer cells
divide every 1.5 days
 Do not differentiate
thus forming a scaly
inflamed red skin
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16. 02/09/14
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17. PATHOLOGY
• The T cells in the epidermis induce the
changes seen in psoriatic skin and are
also necessary for maintaining lesions.
After T cells have been activated, which
happens when they attach to antigenpresenting cells, they migrate to the
skin and cause the secretion of
cytokines and the exaggeration of the
immunologic process.
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18. PATHOLOGY… contd
• The T cells and secretions of other
inflammatory cells induce changes in the
keratinocytes. These keratinocytes contain a
variety of immunomodulating cytokines, such
as interleukin-1 (IL-1), IL-6, IL-8, and tumor
necrosis factor (TNF), which are each
expressed differently in psoriasis. For
example, expression of IL-8 and TNF is
increased in psoriasis, while the
administration of IL-10 may alleviate
symptoms of the disease.
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19. Initiation
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20. Immubiology of IMID
Immubiology of IMID
Sensitization
Pathogenic T Cell Development
Local Tissue
Tissue damage
Effector/Suppressor Imbalance
Inflammation
Fibrosis
I.M.I.D.
TH2
Eosinophil
Mast/Basophil
APC
Tp
TREG
Neutrophil
Ag
TC
Psoriasis
Macrophage
B
Monocyte
T H1
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21. T Cell Driven Pathology
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22. Psoriasis Pathogenesis
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23. T-Cell Activation in the
Lympnodes
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24. T-Cell Binding & Trafficking….
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25. Psoriatic Cascade
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26. Imbalance of cytokines in IMID
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27. 02/09/14
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28. Common Areas
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29. PSORIASIS
 Psoriasis is a chronic, inflammatory genetic,
noncontagious skin disorder
 appears in many different forms and can
affect any part of the body.
 Commonly affected areas include scalp,
elbows, knees, arms, stomach and back
 Waxing –waning & autoimmune in origin
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30. Waxing & Waning
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31. Types of Psoriasis
 Plaque Psoriasis
 Pustular Psoriasis
 Erythrodermic Psoriasis
 Guttate Psoriasis
 Psoriatic Arthritis
 Inverse Psoriasis
 Nail Psoriasis
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32. Plaque Psoriasis
 Most common form
 Occurs commonly in young adults
 Characterized by sharply, demarcated,
erythematous papules and plaques covered with
silver white scales
 Symmetrical distribution
 Starts small and will enlarge over time
 Raised papules
 Scalp, extensor elbows, knees, back
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34. 02/09/14
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35. Pustular Psoriasis
 Rare, but severe and potentially life threatening
 Acute onset
 Characterized by lesions with a mixture of brown
and white non-infected pustules associated with
erythema and scaling.
 Affects palms and soles symmetrically
 Systemic symptoms include fever and malaise
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36. 02/09/14
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37. 02/09/14
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38. Guttate Psoriasis
 “Drop like”
 Characterized by small, scaly, erythematous
spots of psoriasis
 Occurs abruptly in patients with no prior
history of psoriasis
 Located on trunk and extremities
 Classically follows beta-hemolytic
streptococcal pharyngitis
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39. 02/09/14
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40. Psoriatic Arthritis
 1-5% of psoriasis patients
 Characterized by inflammation, swelling
and destruction of peripheral
interphalangeal joints, knees and ankles
 Elevated rheumatoid factor is NOT seen in
psoriatic arthritis patients
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41. 02/09/14
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42. 02/09/14
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43. Inverse Psoriasis
 Involves interiginous areas: inguinal,
perineal, genital, intergluteal, and axillary
regions
 May be misdiagnosed as fungal or bacterial
infection due to lack of scaling
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44. 02/09/14
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45. Erythrodermic Psoriasis
 Characterized by widespread exfoliation of fine
scales and erythema (> 90% of BSA)
 Symptoms include fever, chills, malaise,
hypothermia, and hypoalbuminemia may be
present
 Pneumonia and renal failure may occur
 High output heart failure may develop in people
with heart disease
 Massive protein loss, dysregulation of core body
temperature, and excessive fluid loss
 Other complications include pustulosis,
arthropathy, and staphylococcal infections
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46. 02/09/14
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47. 02/09/14
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48. Nail Psoriasis
 Characterized by pitting of nails and
localized change in color to tan or brown
 Usually diagnostic of psoriasis
 Unresponsive to most treatments
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49. Impact on Physical Health
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50. Impact on Mental Health
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51. General Measures
 Sunshine
 Baths
 Emollients
 Occlusive dressings
 Rest
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52. Emollients
 Emollients reduce desquamation, may limit
painful fissuring and can act as an
antipruritic
 emollients used are white soft paraffin or
vaseline
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53. Keratolytics
 helpful for descaling plaques for treatment
with more active topical agents
 Keratolytics [salicylic acid usually 5% ]
combined with an emmolient base.
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54. Coal tar
 Stand by therapy since over a century
 cosmetically less acceptable[crude Prep]
 Refined prep [cosmetically good] less active
 0.5–5% in white or yellow soft paraffin
 Irritation common ∴ start with 0.5%
 frequently combined with 1% hydrocortisone
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55. Dithranol (Anthralin)
 Is one of the oldest treatments available for psoriasis
used in conjunction with ultraviolet B (UVB)
phototherapy in indoor patients
 Irritation/burning of un involved skin coupled with
purple–brown discolouration of skin, clothes etc.
 Newer microcrystalline formulations of dithranol less
irritant and more cosmetically acceptable
 Direct anti-proliferative effect on epidermal
keratinocytes
 Usage limited for cosmetic unattractiveness
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56. Topical corticosteroids
 High rate of patient compliance due to
cosmetic elegance
 Have potential side-effects, if used without
supervision
 Mild potency --flexures, face, genitalia
 High potency—recalcitrant psoriasis esp on
the hands or feet
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57. Topical corticosteroids……
 Preferable usage for small areas of Plaque
and not in large area involvement
 Limited time duration & under supervision
skin thinning, striae, telangiectasia ,
tachyphylaxis , rapid relapse
 combination or rotation-- coal tar, dithranol,
vitamin D3 analogues or retinoids
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58. Vitamin D3 analogues
 Normalise abnormal epidermal keratinocyte
proliferation and differentiation +antiinflammatory effect
 Effective [6-8wks], clean, safe
 First line therapy for psoriasis irritation of
uninvolved, perilesional skin.
 Hypercalcaemia
 Can be combined with sys. /topical therapy
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59. ROLSICAL
Therapy of choice for mild to moderate
plaque psoriasis
Best efficacy & tolerability amongst all
topical agents inc. vitamin D analogues
Specially useful for sensitive body areas e.g.
face, hairline and body folds
Can be co-prescribed with other topical and
systemic therapy
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60. Rolsical--MOA
Regulates keratinocyte growth,
differentiation & maturation→inhibits
epidermal cell proliferation
Regulates immune stimulation
Inhibits lymphocyte proliferation
Inhibits-IL-1& IL-2 production
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61. Topical retinoid
 Normalise epidermal keratinocyte proliferation
and differentiation
 Tazarotene is applied once daily
 Significant irritation of uninvolved skin
 Combined usage with D3 analogues and
steroids [to enhance efficacy and reduce
irritancy]
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62. Phototherapy
 Used for 70 years as therapy
 UVB monotherapy thrice/week
 Burning and potential carcinogenicity
 UVB often combined with topical Tar
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63. Photochemotherapy
(PUVA)
 Photosensitising medication (psoralen) with
(320–400 nm) ultraviolet A (UVA)
 Cataracts, photoageing & nonmelanoma skin
cancers
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64. Methotrexate
 Is used to treat severe and/or disabling
psoriasis since 1960s.
 Approved by USFDA in 1971 for treatment
of Psoriasis.
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65. Methotrexate - Effectiveness
 Extensive psoriasis, erythrodermic and acute
pustular psoriasis, physically disabling psoriasis of
the palms and soles, psoriasis in the elderly, &
severe psoriatic arthritis.
 Clearance or remission can last for a few weeks to
a year or more after stopping therapy.
 In people with at least 30 percent skin covered
with psoriasis who are not responsive to, or
eligible for, conventional topical or ultraviolet
light treatments (UVB and PUVA).
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66. Methotrexate
 Improvement begins within four to six
weeks.
 Its substantially clears within two or three
months of starting therapy.
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67. Methotrexate
Short Term Side Effects
 Anemia
 Nausea
 Insomnia
 Loss of appetite
 Tiredness
 Temporary hair loss in some patients
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68. Methotrexate
Contraindications
 women who are pregnant
 men or women who are trying to conceive a child
(conception should be avoided during and for at
least 12 weeks after discontinuing MTX therapy)
 people with severe anemia
 people with cirrhosis of the liver
 people with active hepatitis
 people with significant liver or kidney
abnormalities
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69. Methotrexate – MOA
• anti-inflammatory action of MTX is not mediated
by lymphocyte apoptosis, but by the suppression
of T cell activation and adhesion molecules.
• suppression of intercellular adhesion molecule
(ICAM)-1 was adenosine and folate-dependent
• MTX suppression of the skin-homing cutaneous
lymphocyte-associated antigen (CLA) was
adenosine-independent.
• MTX Inhibits Keratinocyte proliferation.
• MTX inhibits dihydrofolate reductase ---
inhibits folate ---
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70. Methotrexate – Dosage
 orally or by intramuscular or subcutaneous
injection
 once (day) in a week
 7.5 mg/25mg in single or divided dosage
(on a single day)
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71. Systemic retinoids
 Acitretin [metabolite of etretinate] is in use
 Acitretin is often combined with PUVA
 Severe psoriasis, Generalised pustular and
palmoplantar pustular psoriasis
 cheilitis and xerosis, alopecia sticky, fragile
skin.
 safety in terms of carcinogenicity or organ
toxicity
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72. Cyclosporine
 Selective immunosuppressive agent
 To be used not > 3-4months at a time
 Effective for recalcitrant severe psoriasis
plaque,erythrodermic&pustular
 Paraesthesiae, hypertrichosis, malaise and gingival
hypertrophy
 Hypertension and nephrotoxicity
 Lymphomas, internal malignancies, skin cancers, and
serious infections
 Not to combine with photo or photochemotherapy
 Cost and toxicity prevent wide usage
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73. Methotrexate action in
rheumatoid arthritis
Clinical improvement was associated with decreased
synthesis of IL-1 beta,TNF-alpha and IL-8 induced by
bacterial lipopolysaccharide, IL-1 alpha and IL-1beta
in PBMC in vitro. These findings suggest that MTX
therapy reverses the inflammatory type of rheumatoid
arthritis (RA) blood mononuclear cells by stimulating
cytokine inhibitor production while inhibiting
inflammatory cytokine release at the same time.
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Br J Rheumatol. 1995 Jul;34(7):602-9.
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74. The changes in expression of ICAM-3, Ki-67,
PCNA, and CD31 in psoriatic lesionsbefore and
after methotrexate treatment.
In post treatment biopsies a decrease in the degree of
epidermal hyperplasia and a significant reduction in
the severity of the inflammatory infiltrate (P<0.05)
were observed. In addition, CD31 and ICAM-3
expression was significantly decreased on dermal
cellular infiltrate, (respectively; P<0.05, P<0.01).
Ki67and PCNA expression were suppressed
concurrently in about 90% of cases (P<0.01).
Arch Dermatol Res. 2005 Dec;297(6):249-55. Epub 2005 Oct 8.
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75. Folate supplementation during
methotrexate therapy for patients with
psoriasis
According to studies reviewed, the use of folate
supplements in patients treated with
methotrexate reduces the incidence of
hepatotoxicity and gastrointestinal intolerance
without impairing the efficacy of
methotrexate..
: J Am Acad Dermatol. 2005 Oct;53(4):652-9.
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76. T Cell Targeting
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77. T Cell Targeters……
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78. T cell targeting agents:
 Alefacept, Efalizumab
 approved for severe plaque psoriasis only.
 contraindicated in the presence of infection
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79. TNF-α Targeting…
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80. Biologics That Target Tumor
Necrosis Factor-alpha
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81. Tumor Necrosis Factor (TNF)
Blockers
 Etanercept, Infliximab and Adalimumab
 Injectables and quite costly
 Reserved for severe psoriasis e.g. pustular
psoriasis
 Congestive
heart
failure,
unmasking
of
demyelinating disease (e.g. optic neuritis and
multiple sclerosis), precipitation of diabetes
mellitus, and hyperthyroidism
 Contraindicated in the presence of infection
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82. Fulfilling an unmet need in psoriasis :
do biologicals hold the key to
improved tolerability?
An increased incidence of lymphomas has been
postulated to be associated with etanercept,
infliximab and adalimumab; serious infections,
such as tuberculosis, have also been reported
with these three biologicals, all of which target
TNF-alpha. Demyelinating disorders, such as
multiple sclerosis, have been reported with
some biologicals as has congestive heart failure.
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Drug Saf. 2006;29(1):49-66.
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83. PSORIASIS
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84. TREATMENT OPTIONS…..
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85. Strategise Rx
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86. ALGORITHM
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87. Treatment Approach
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88. Evaluate Objectively
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89. PASI –a Preffered Measure
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90. PASI –a Preffered Measure
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91. Clin Research & PASI
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92. THANK YOU !
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