Psoriasis is a chronic autoimmune condition caused by an overactive immune system that attacks skin cells. This triggers rapid skin cell production, causing a build up of skin cells and characteristic scaling. The main types are plaque, guttate, pustular, inverse, and erythrodermic psoriasis. Treatment focuses on slowing skin cell production and modulating the immune system using topical agents, phototherapy, or systemic drugs like TNF inhibitors.

1. Immunopathology of Psoriasis

2. • Psoriasis is a chronic autoimmune condition that causes the rapid
build-up of skin cells. This build-up of cells causes scaling on the skin’s
surface. Inflammation and redness around the scales is fairly
common. Typical psoriatic scales are whitish-silver and develop in
thick, red patches. Sometimes, these patches will crack and bleed.
• Psoriasis is the result of a sped-up skin production process. Typically,
skin cells grow deep in the skin and slowly rise to the surface.
Eventually, they fall off. The typical life cycle of a skin cell is one
month.

3. • In people with psoriasis, this production process may occur in just a
few days. Because of this, skin cells don’t have time to fall off. This
rapid, overproduction leads to the build-up of skin cells.
• Scales typically develop on joints, such elbows and knees. They may
develop anywhere on the body, including the hands, feet, neck, scalp,
and face. Less common types of psoriasis affect the nails, the mouth,
and the area around genitals.

6. • The 5 types of psoriasis and most common symptoms include:
• Plaque psoriasis: This is the most common type of psoriasis —
about 80 percent of people with the condition have plaque psoriasis.
It causes red, inflamed patches that cover areas of the skin. These
patches are often covered with whitish-silver scales or plaques. These
plaques are commonly found on the elbows, knees, and scalp.
• Guttate psoriasis: Guttate psoriasis is common in childhood. This type
of psoriasis causes small pink spots. The most common sites for
guttate psoriasis include the torso, arms, and legs. These spots are
rarely thick or raised like plaque psoriasis.

7. • Pustular psoriasis: Pustular psoriasis is more common in adults. It causes
white, pus-filled blisters and broad areas of red, inflamed skin. Pustular
psoriasis is typically localized to smaller areas of the body, such as the
hands or feet, but it can be widespread.
• Inverse psoriasis: Inverse psoriasis causes bright areas of red, shiny,
inflamed skin. Patches of inverse psoriasis develop under armpits or
breasts, in the groin, or around skinfolds in the genitals.
• Erythrodermic psoriasis: This type of psoriasis often covers large sections
of the body at once and is very rare. The skin almost appears sunburned.
Scales that develop often slough off in large sections or sheets. It’s not
uncommon for a person with this type of psoriasis to run a fever or
become very ill.

8. • The most common symptoms of plaque psoriasis include:
• red, raised, inflamed patches of skin
• silver-white scales or plaques on the red patches
• dry skin that may crack and bleed
• soreness around patches
• itching and burning sensations around patches
• thick, pitted nails
• painful, swollen joints

9. • immune system
• Psoriasis is an autoimmune condition. Autoimmune conditions are the
result of the body attacking itself. In the case of psoriasis, white blood cells
known as T cells attack the skin cells mistakenly.
• In a typical body, white blood cells are deployed to attack and destroy
invading bacteria and fight infections. The mistaken attack causes the skin
cell production process to go into overdrive. The sped-up skin cell
production causes new skin cells to develop too quickly. They are pushed to
the skin’s surface, where they pile up.
• This results in the plaques that are most commonly associated with
psoriasis. The attacks on the skin cells also cause red, inflamed areas of skin
to develop.

12. Immunologic factors
Some consider psoriasis as an organ-specific autoimmune
disease that is triggered by an activated cellular immune
system and is similar to other immune-mediated diseases such
as Crohn's disease, rheumatoid arthritis, multiple sclerosis and
juvenile-onset diabetes.
All of these fit the definition of an autoimmune disease as "a
clinical syndrome caused by the activation of T cells and B cells,
or both, in the absence of an ongoing infection or other
discernible cause“.

13. Immunologic factors
Psoriasis is related to excess T-cell activity. Experimental models
can be induced by stimulation with streptococcal superantigen, which
cross-reacts with dermal collagen. This small peptide has been shown
to cause increased activity among T cells in patients with psoriasis but
not in control groups. Some of the newer drugs used to treat severe
psoriasis directly modify the function of lymphocytes.

14. Immunologic factors
Specifically, the epidermis is infiltrated by a large number of
activated T cells, which appear to be capable of inducing keratinocyte
proliferation.
A patient with 20% body surface area affected with psoriasis lesions
has around 8 billion blood circulating T cells compared with
approximately 20 billion T cells located in the dermis and epidermis of
psoriasis plaques.

16. Immunologic factors
Deregulated inflammatory process ensues with a large production of
various cytokines (eg, tumor necrosis factor-α [TNF-α], interferon-
gamma, IL-12). Many of the clinical features of psoriasis are explained
by the large production of such mediators.

17. Immunologic factors
Elevated levels of TNF-α specifically are found to correlate with flares of
psoriasis.
T-cell hyperactivity and the resulting proinflammatory mediators (in
this case IL-17/23) play a major role in the pathogenesis of psoriasis.

19. Immunomodulators
Topical Tacrolimus oin has been used in the past for management
of refractory atopic dermatitis. However, multiple studies have shown
effectiveness with psoriasis affecting intertriginous regions as well as
the face. Generally, it seems to be effective in thin-skinned areas.
However, it has become somewhat of a second-line agent given other
studies showing topical steroids may be more effective and potential
serious disease association

20. Immunomodulators
Cyclosporine is an 11-amino acid cyclic peptide and natural product
of fungi. It acts on T-cell replication and activity.
• Cyclosporine is a specific modulator of T-cell function and an agent
that depresses cell-mediated immune responses by inhibiting helper
T-cell function. Preferential and reversible inhibition of T lymphocytes
in the G0 or G1 phase of cell cycle is suggested. The drug binds to
cyclophilin, an intracellular protein, which, in turn, prevents
formation of IL-2 and the subsequent recruitment of activated T cells.

21. Immunomodulators
Alefacept (Amevive) is a recombinant dimeric fusion protein that
binds to CD2 on memory-effector T lymphocytes, thereby inhibiting
the activation of these cells and reducing the number of these cells. It
is indicated for moderate to severe psoriasis. This drug usually is
administered IM.

22. Tumor Necrosis Factor Inhibitors
These agents neutralize the effects of tumor necrosis factor-α (TNF-
α).
Infliximab (Remicad) is a chimeric antibody that binds both the
soluble and transmembrane TNF-α molecules, thereby neutralizing
the effects of TNF-α.
Etanercept (Enbrel) a recombinant human TNF-α receptor protein
fused with the Fc portion of IgG1 that binds to soluble and
membrane-bound TNF-α, thereby neutralizing the effects of TNF-α.

23. Tumor Necrosis Factor Inhibitors
Adalimumab (Humira) is a fully human anti–TNF-α monoclonal
antibody. It binds specifically to soluble and membrane-bound TNF-α,
thereby neutralizing the effects of TNF-α. It is used to treat moderate-
to-severe psoriasis and moderate-to-severe psoriatic
arthritis. weight-based dosing regimens exist for pediatric-aged
patients.

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