Psoriasis
is an autoimmune disease that affects the skin. It occurs when the
immune system mistakes the skin cells as a pathogen, and sends out
faulty signals that speed up the growth cycle of skin cells.
Psoriasis is not contagious. However, psoriasis has been linked to an
increased risk of stroke, and
treating high blood lipid levels may lead to improvement. There are
five types of psoriasis: plaque, guttate, inverse, pustular, and
erythrodermic. The most common form, plaque psoriasis, is commonly
seen as red and white hues of scaly patches appearing on the top
first layer of the epidermis (skin). Some patients, though, have no
dermatological signs or symptoms.
In
plaque psoriasis, skin rapidly accumulates at these sites, which
gives it a silvery-white appearance. Plaques frequently occur on the
skin of the elbows and knees, but can affect any area, including the
scalp, palms of hands and soles of feet, and genitals. In contrast to
eczema, psoriasis is more likely to be found on the outer side of the
joint.
The
disorder is a chronic recurring condition that varies in severity
from minor localized patches to complete body coverage. Fingernails
are frequently affected (psoriatic nail dystrophy) and can be seen as
an isolated sign. Psoriasis can also cause inflammation of the
joints, which is known as psoriatic arthiritis. Between 10—30% of
all people with psoriasis also have psoriatic arthritis.
The
cause of psoriasis is not fully understood, but it is believed to
have a genetic component and local psoriatic changes can be triggered
by an injury to the skin known as the Koebner phenemenon. Various
environmental factors have been suggested as aggravating to
psoriasis, including stress, withdrawal of systemic corticosteroids
as well as other environmental factors, but few have shown
statistical significance. There are many treatments available, but
because of its chronic recurrent nature, psoriasis is a challenge to
treat. Withdrawal of corticosteroids (topical steroid cream) can
aggravate the condition due to the 'rebound effect' of
corticosteroids.
Cause
The
cause of psoriasis is not fully understood. There are two main
hypotheses about the process that occurs in the development of the
disease. The first considers psoriasis as primarily a disorder of
excessive growth and reproduction of skin cells. The problem is
simply seen as a fault of the epidermis and its keratinocyes. The
second hypothesis sees the disease as being an immune-mediated
disorder in
which the excessive reproduction of skin cells is secondary to
factors produced by the immune system. T cells (which normally help
protect the body against infection) become active, migrate to the
dermis and trigger the release of cytokines ( tumour necrosis factor
– alpha, TNFα, in particular) which cause inflammation and the
rapid production of skin cells. It is not known what initiates the
activation of the T cells.
The
immune-mediated model of psoriasis has been supported by the
observation that immunosupressant medications can clear psoriasis
plaques. However, the role of the immune system is not fully
understood, and it has recently been reported that an animal model of
psoriasis can be triggered in mice lacking T cells. Animal models,
however, reveal only a few aspects resembling human psoriasis.
Compromised
skin barrier function has a role in psoriasis susceptibility.
Psoriasis
is a fairly idiosyncratic disease. The majority of people's
experience of psoriasis is one in which it may worsen or improve for
no apparent reason. Studies of the factors associated with psoriasis
tend to be based on small (usually hospital based) samples of
individuals. These studies tend to suffer from representative issues,
and an inability to tease out causal associations in the face of
other (possibly unknown) intervening factors. Conflicting findings
are often reported. Nevertheless, the first outbreak is sometimes
reported following stress (physical and mental), skin injury, and
stresptococcal infection. Conditions that have been reported as
accompanying a worsening of the disease include infections, stress,
and changes in season and climate. Certain medicines, including
lithium salt, beta blockers and the anti-malarial chloroquine have
been reported to trigger or aggravate the disease. Excessive alcohol
consumption, smoking and obesity may exacerbate psoriasis or make the
management of the condition difficult or perhaps these comorbidities
are effects rather than causes.Hairspray, some face creams and hand
lotions, can also cause an outbreak of psoriasis.In 1975, Stefania
Jablonska and collaborators advanced a new theory that special
antibodies tend to break through into the lower layers of the skin
and set up a complex series of chemical reactions.
Immunology
In
psoriasis, immune cells move from the dermis to the epidermis, where
they stimulate skin cells (keratinocytes) to proliferate. Psoriasis
does not seem to be a true autoimmune
disease.In an autoimmune disease, the immune system confuses
an outside antigen with a normal body component, and attacks them
both. But in psoriasis, the inflammation does not seem to be caused
by outside antigens (although DNA does have an immunostimulatory
effect). Researchers have identified many of the immune cells
involved in psoriasis, and the chemical signals they send to each
other to coordinate inflammation. At the end of this process, immune
cells, such as dendritic cells
and T cells, move from the dermis
to the epidermis,
secreting chemical signals, such as tumor necrosis factor-α,
interleukin-1β, and interleukin-6, which cause inflammation, and
interleukin-22, which causes keratinocytes to proliferate.
The
immune system consists of an innate immune system, and an adaptive
immune system.
In
the innate system, immune cells have receptors that have evolved to
target specific proteins and other antigens which are commonly found
on pathogens. In the adaptive immune system, immune cells respond to
proteins and other antigens that they may never have seen before,
which are presented to them by other cells. The innate system often
passes antigens on to the adaptive system. When the immune system
makes a mistake, and identifies a healthy part of the body as a
foreign antigen, the immune system attacks that protein, as it does
in autoimmunity.
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Proposed
model of psoriasis pathogenesis highlighting the role of IFN-α-primed
moDCs, TLR stimulation and T lymphocytes.Under inflammatory
conditions, blood-derived monocytes are potential precursors of skin
DCs. GM-CSF necessary for DC development is produced by a variety of
cell types in skin (neutrophils, keratinocytes, macrophages, mast
cells, lymphocytes and fibroblasts). IFN-α (a physiological factor
for DC development) is mainly produced by pDCs. Stressed
keratinocytes (through environmental factors including viral
infections) release self-DNA and self-RNA that form complexes with
the cathelicidin antimicrobial peptide LL37. Self-DNA-LL37 and
self-RNA-LL37 complexes activate pDCs to produce IFN-α.
Self-RNA-LL37 complexes and viral ssRNA directly promote the
phenotypical and functional maturation of IFN-α-primed moDCs. Other
factors released by stressed keratinocytes include IL-1β, IL-6 and
TNF-α, which very likely influence IFN-α-primed moDC development.
Furthermore IFN-α-primed moDCs produce IFN-α and IFN-γ themselves
further contributing to their own maturation. In vivo under
inflammatory conditions other cytokines such as IL-1β, IL-6 and
TNF-α and IFN-γ are also present in the psoriatic inflammatory
infiltrate produced by lymphocytes, macrophages, fibroblasts, NK T
cells and keratinocytes therefore IFN-α-primed moDCs are influenced
by a variety of proinflammatory cytokines. Mature IFN-α-primed moDCs
then possibly migrate to the skin-draining lymph nodes where they
promote naive T cell differentiation into Th1 and/or Th17 cells
through IL-12 and IL-23. These T cells migrate via lymphatic and
blood vessels into psoriatic dermis and contribute to the formation
of a psoriatic plaque. Th1 cells produce TNF-α and IFN-γ, which
also stimulate keratinocyte proliferation. Th17 cells secrete IL-17A,
IL-17F and IL-22, which stimulate keratinocyte proliferation and the
release of proinflammatory cytokines, antimicrobial peptides and
chemokines. Th1 and Th17 cells can directly interact with monocytes
by producing GM-CSF, TNF-α and IFN-γ and instruct these cells to
differentiate into specialized moDC subsets. Figure is modified from
Ref. 7. Reproduced with permission from John Wiley & Sons, Inc.
All rights reserved. Abbreviations: moDC, monocyte-derived dendritic
cell; GM-CSF, granulocyte/macrophage colony-stimulating factor; IFN,
interferon; IL, interleukin; LL37, cathelicidin antimicrobial
peptide; NK, natural killer; pDC, plasmacytoid dendritic cell; ssRNA,
single-stranded RNA; Th, T-helper; TNF, tumour necrosis factor.
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In
psoriasis, DNA is an inflammatory stimulus. DNA stimulates the
receptors on plasmacytoid dendritic cells, which produce
interferon-α, an immune stimulatory signal (cytokine). In psoriasis,
keratinocytes produce antimicrobial peptides. In response to
dendritic cells and T cells, they also produce cytokines, such as
interleukin-1, interleukin-6, and tumor necrosis factor-α, which
signals more inflammatory cells to arrive and produces further
inflammation.
Dendritic
cells bridge the innate and adaptive immune system. They are
increased in psoriatic lesions and induce the proliferation of T
cells and type 1 helper T cells. Certain dendritic cells can produce
tumor necrosis factor-α, which calls more immune cells and
stimulates more inflammation. Targeted immunotherapy, and psoralen
and ultraviolet A (PUVA) therapy, reduces the number of dendritic
cells.
T
cells move from the dermis into the epidermis. They are attracted to
the epidermis by alpha-1 beta-1 integrin, a signalling molecule on
the collagen in the epidermis. Psoriatic T cells secrete interferon-γ
and interleukin-17. Interleukin-17 is also associated with
interleukin-22. Interleukin-22 induces keratocytes to proliferate.
One
hypothesis is that psoriasis involves a defect in regulatory T cells,
and in the regulatory cytokine interleukin-10.
Is
psoriasis curable?
No,
psoriasis is not currently curable. However, it can go into remission
and show no signs of disease. Ongoing research is actively making
progress on finding better treatments and a possible cure in the
future.
What
is the treatment for psoriasis?
There
are many effective treatment choices for psoriasis. The best
treatment is individually determined by the treating physician and
depends, in part, on the type of disease, the severity, and the total
body area involved.
For
mild disease that involves only small areas of the body (like less
than 10% of the total skin surface), topical (skin applied) creams,
lotions, and sprays may be very effective and safe to use.
Occasionally, a small local injection of steroids directly into a
tough or resistant isolated psoriasis plaque may be helpful.
For
moderate to severe disease that involves much larger areas of the
body (like 20% or more of the total skin surface), topical products
may not be effective or practical to apply. These cases may require
ultra-violet light treatments or systemic (total body treatments such
as pills or injections) medications. Internal medications usually
have greater risks.
For
psoriatic arthritis, systemic medications are generally required to
stop the progression of permanent joint destruction. Topical
therapies are not effective.
It
is important to keep in mind that as with any medical condition, all
medications carry possible side effects. No medication is 100%
effective for everyone, and no medication is 100% safe. The decision
to use any medication requires thorough consideration and discussion
with your physician. The risks and potential benefit of medications
have to be considered for each type of psoriasis and the individual
patient. Some patients are not bothered at all by their skin symptoms
and may not want any treatment. Other patients are bothered by even
small patches of psoriasis and want to keep their skin clear.
Everyone is different and, therefore, treatment choices also vary
depending on the patient's goals and expressed wishes.
An
approach to minimize the toxicity of some of these medicines has been
commonly called "rotational" therapy. The idea is to change
the antipsoriasis drug every six to 24 months in order to minimize
the possible side effects from any one type of therapy or medication.
In
another example, a patient who has been using strong topical steroids
over large areas of their body for prolonged periods may benefit from
stopping the steroids for a while and rotating onto a different
therapy like calcitriol (Vectical), light therapy, or an injectable
biologic.
