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PATHOPHYSIOLOGY OF
PSORIASIS
DR. MIKHIN GEORGE THOMAS
PSORIASIS
• Common , chronic, disfiguring, inflammatory and proliferative condition
of the skin, in which both genetic and environmental influences play a
critical role.
HISTORY
• Ancient biblical records 2000 BC
• Corpus hippocraticum
• Galen
• “Psora”= to itch
• Robert Willan- ‘On cutaneous
diseases’ published in 1808
Lithium Acts directly by blocking cell differentiation and Provokes or induces chronic plaque
leading to dysregulation of inflammatory psoriasis, localized or generalized
cytokines and indirectly by ↓ cAMP levels pustular psoriasis and even psoriatic
erythroderma
Antimalarials May trigger psoriasis by inhibiting the enzyme Do not induce psoriasis although they are
transglutaminase known to trigger psoriasis in 18% of
patients
NSAIDs Inhibit the cyclo-oxygenase pathway, leading to accumulation of leukotrienes and hence
may exacerbate psoriasis
Tetracyclines May provoke psoriasis either by inhibiting cAMP or by inducing Koebner’s phenomenon
due to their photosensitizing potential
• angiotensin-converting • calcium-channel blockers
enzyme inhibitors • granulocyte-colony stimulating
factor
• interferons • potassium iodide
• digoxin • penicillin
• progesterone
• clonidine
• morphine
• carbamazepine • acetazolamide
• Valproic acid
HIV INFECTION
• T cells
• Dendritic cells
• Monocytes and macrophages
• Neutrophils
.
• Antigen specific rather than superantigen mediated
• CD 4 and CD 8 subsets
•PLASMACYTOID DENDRITIC
CELLS
• IFN is the key cytokine that activates signal transducer and activator of
transcription 1 (stat1).
• TNF : key cytokine and key regulator of maturation of dc cells and is
responsible for proliferation of resident T cells in unaffected skin
3) T CELL REACTIVATION
Cytokine/Growth
factor Role in psoriasis
TNF-α
Stimulation of keratinocytes to produce IL-8, ICAM-1, TGF-α, β-defensins, .
Enhancement of pro-inflammatory cytokine secreting capacity of Macrophage.
Stimulation of endothelial cell to secrete VEGF.
Increased keratinocyte proliferation.
IFN-γ
Antiproliferative effect on normal keratinocyte in-vitro.
Induction of ICAM-1 expression on keratinocytes and endothelial cells, influencing the trafficking of T
lymphocytes into lesional epidermis.
Stimulation of APC activity and TNF-α release by phagocytes and up regulation of TNF-α receptors
GM-CSF
Increases keratinocyte proliferation and activates neutrophils.
It also stimulates migration and proliferation of endothelial cells.
IL-1 Induction of E-selectin, VCAM-1, ICAM-1 on keratinocytes . These fibroblast-derived factors
in turn stimulate keratinocyte proliferation and differentiation.
IL-2 Is a growth factor and chemo-attractant for T cells
Induces T cell cytotoxicity.
Stimulates NK cell activity.
High doses of IL-2 may induce psoriasis in predisposed patients.
• UNINVOLVED SKIN
• Subclinical morphological and biochemical changes,
lipid biosynthesis
• Changes in stratum corneum
• Changes in levels of phospholipids, free α amino
acids, hydrolytic cells ,dehydrogenases
• Histochemical parakeratosis
INITIAL LESION
FBXL19 (F-box and leucine rich repeat Inhibition of demethylase activity to activate NF-
protein 19) κB
Genes associated with skin barrier function
GJB2 (Gap junction protein β2) , connexin Involved in gap junction formation
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STREPTOCOCCUS
• The time interval between injury and onset of psoriasis : 3 days to 2 years.
• Disease severity
1. inflammatory response
2. nonspecific inflammation initiates
Naïve T cells
Increased exp of
CSDN, small proline
rich proteins, cystatin
A, transglutaminase- I • Inc TEWL
• Dec exp of
Aberrant formation of
aquaporins in str
cornified envelope
Abnormal corneum and str
keratinization spinosum
Decreased expression of
loricin, fillagrin
ROLE OF SKIN BARRIER