Pathogenesis of psoriasis

A) Cellular participants in psoriasis :

Development and maintenance of psoriatic plaque is dependent on pathologic collaboration of :
1- T lymphocytes (CD4 and CD8 T cells) ,
2- Natural killer & Natural Killer T ( NKT) cells ,
3- Dendritic antigen-presenting cells ( such as Langerhans cells, plasmacytoid dendritic cells (pDCs) , mature myeloid DC subsets )

1- T – Cells : Psoriasis is a T cell–driven

driven disease.
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The best-characterized
characterized T cells are the CD4 and CD8 subsets. The activated T cells that infiltrate the skin express the memory phenotype (CD45RO )
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Predominantly of the memory phenotype (CD45RO ), these cells express the cutaneous lymphocyte antigen (CLA), (CLA)
a ligand for E-selectin ( which is selectively expressed on skin capillaries )a therefore provides them with access to the skin :
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- CD8 T cells , which migrates from dermis into epidermis.
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- CD4 T cells are predominantly located in the upper dermis making contact with dermal dendritic cells resulting in
their activation .

Maintenance of psoriatic lesions

a novel subset of CD4+ T cells, stimulated by IL-23 and characterized by IL-17 produc/on,, may play an important role in maintaining chronic
inflammation in psoriasis.

2- Natural Killer and Natural Killer T Cells.

- Natural killer (NK) cells are major producers of IFN-γ and serve as a bridge between
n innate and acquired immunity.

3- Dendritic antigen-presenting cells: such as Langerhans cells, plasmacytoid dendritic cells (pDCs) , mature myeloid DC subsets .
- These DC subsets are responsible for activation of infiltrating T cells, by cell-cell
cell interaction of which immunologic synapse
is central for antigen recognition.
- Many accessory molecules involved
nvolved in immunological synapse ( e.g. lymphocyte function-associated
associated antigen-1(LFA-1)
antigen , Cytotoxic T-
lymphocyte antigen-4)

Treatments directed primarily against key co-stimulatory

co molecules expressed by antigen-presenting
presenting DCs markedly improve psoriasis

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Regulatory T cells (CD4 CD25 subset)
• This subset in psoriasis has impaired inhibitory function and thus , failure to suppress T-cell
cell proliferation resulting in
unrestrained T-cell dervied cytokines such as IFN-γ, IL2 ,
cell proliferation, and chronic over production of chemkines and Th1-dervied
TNF-α .
The psoria c plaque is characterized by the predominance of cytokines produced by Th1 cells (IFN-γ,
(IFN IL2, and TNF-α) over
those produced by Th2 cells (IL-4, IL-5,
5, and IL-10).
IL

Therapeutic targeting of TNF-aa with biologic agents as infliximab has proven important role of this mediator of inflammation in psoriasis.

B) Epidermal Keratinocyte proliferation :

Keratinocytes
1- Hyperproliferation
2- Abnormal differentiation.
3- Resistance to apoptosis

• Overproduction of these cytokines & growth factors target epidermal keratinocytes to hyperproliferate (by alteration of the cell
kine7cs of kera7nocytes with a shortening of the cell cycle from 311 to 36 h, resul7ng in 28 7mes the normal produc7on of epidermal cells)
, develop in abnormal terminal differentiation program, and become resistant to apoptotic signals.

• Members of the epidermal growth factor (EGF) family induce their own production in keratinocytes, including:
includ
• transforming growth factor-α,
• amphiregulin (ARE6),
• heparin-binding EGF-like
like growth factor.
Activation of the EGF receptor stimulates keratinocyte production of vascular endothelial growth factor (VEGF), resulting in
neoangiogenesis which support epidermal hyperproliferation.
 Differential diagnosis of psoriasis
Large Geographic Scalp Psoriasis Inverse Psoriasis
Small Scaling Plaques Plaques

1- Tinea corporis : 1- Seborrheic 1- Tinea,

KOH examination is mandatory, particularly in single lesions. 1- Tinea corporis
dermatitis, 2- candidiasis,
2- Discoid/nummular eczema
2- mycosis 2- Tinea capitis . 3- intertrigo,
3- Cutaneous T-cell
cell lymphoma (CTCL) fungoides
Psoriasis 4- Seborrheic dermatitis.
dermatitis 4- extramammary Paget
Vulgaris may be indistinguishable in sites involved and disease
morphology;
5- Lichen simplex chronicus. 5- Glucagonoma
may complicate psoriasis as a result of pruritus. syndrome
6- Psoriasiform drug eruptions 6- Langerhans cell
especially beta blockers, gold, and methyldopa. histiocytosis
7- Mycosis fungoides
goides 7- Hailey-Hailey disease
scaling plaques can be an initial stage of mycosis
fungoides. Biopsy.

8- Pityriasis rubra pilaris

9- Subacute cutaneous lupus erythematosus

1- Any maculopapular drug eruption,

Acute Guttate 2- secondary syphilis,
Psoriasis 3- pityriasis rosea
4- Pityriasis lichenoides chronic
5- Lichen planus

Most Likely
induced erythroderma
1- Drug-induced
2- Eczema
ERYTHRODERMIC 3- CTCL/Sézary syndrome
4- Pityriasis rubra pilaris

Most Likely
1- Impetigo
2- Superficial candidiasis
3- Reactive arthritis syndrome
4- Superficial folliculitis
Consider
1- Pemphigus foliaceus
PUSTULAR 2- Immunoglobulin A pemphigus
3- Sneddon-Wilkinson
Wilkinson disease
(subcorneal pustular dermatosis)
4- Migratory necrolytic erythema
5- Transient neonatal pustular melanosis
6- Acropustulosis of infancy
7- Acute generalized exanthematous
Pustulosis .

COMPLICATIONS :

1- Patients with psoriasis have an increased morbidity and mortality from cardiovascular events, particularly those
with severe and long duration of psoriasis skin disease.
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2- Risk of myocardial infarction is particulary elevated in younger patients with severe psoriasis.
3- Increased relative risk of lymphoma, ( particularly in patients with more severe disease ).
4- Psoriasis is emotionally disabling, carrying with it significant psychosocial difficulties.
Emotional difficulties arise from concerns about appearance, resulting in lowered self-esteem,
self esteem, social rejection, guilt,
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embarrassment, emptiness, sexual problems, and impairment of professional ability.

5- The presence of pruritus and pain can aggravate these symptoms.

6- psychological stress can also lead to depression and anxiety.