Psoriasis
Psoriasis
(pron.: /sɵˈraɪ.əsɨs/) is an immune-mediated disease that affects the skin. It
is typically a lifelong condition. There is currently no cure, but various
treatments can help to control the symptoms.
Psoriasis
occurs when the immune system mistakes a normal skin cell for a pathogen, and
sends out faulty signals that cause overproduction of new 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. The name psoriasis
(ψωρίασις) is from the Greek language, meaning roughly "itching condition"
(psora "itch" + -sis "action, condition").
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 and toenails 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
arthritis. Between 10% and 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 phenomenon. Various environmental factors have been
suggested as aggravating to psoriasis, including oxidative stress, stress,
withdrawal of systemic corticosteroid, 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.
The symptoms of
psoriasis can manifest in a variety of forms. Variants include plaque, pustular,
guttate, and flexural psoriasis. This section describes each type (with ICD-10
code
Psoriasis
may be classified into nonpustular and pustular types as
follows.
Nonpustular
Psoriasis vulgaris (chronic stationary
psoriasis, plaque-like psoriasis, L40.0) is the most common form of psoriasis.
It affects 80% to 90% of people with psoriasis. Plaque psoriasis typically
appears as raised areas of inflamed skin covered with silvery white scaly skin.
These areas are called plaques.
Psoriatic erythroderma (erythrodermic
psoriasis, L40.85) involves the widespread inflammation and exfoliation of the
skin over most of the body surface. It may be accompanied by severe itching,
swelling and pain. It is often the result of an exacerbation of unstable plaque
psoriasis, particularly following the abrupt withdrawal of systemic treatment.
This form of psoriasis can be fatal, as the extreme inflammation and exfoliation
disrupt the body's ability to regulate temperature and for the skin to perform
barrier functions.
Pustular
Pustular
psoriasis (L40.1–3, L40.82) appears as raised bumps that are filled with
noninfectious pus (pustules). The skin under and surrounding the pustules is red
and tender. Pustular psoriasis can be localised, commonly to the hands and feet
(palmoplantar pustulosis), or generalised with widespread patches occurring
randomly on any part of the body. Types include:
Generalized pustular
psoriasis (pustular psoriasis of von Zumbusch)
Pustulosis palmaris et
plantaris (persistent palmoplantar pustulosis, pustular psoriasis of the Barber
type, pustular psoriasis of the extremities)
Annular pustular
psoriasis
Acrodermatitis continua
Impetigo
herpetiformis
Other
Additional
types of psoriasis include:
Drug-induced psoriasis
Inverse psoriasis
(flexural psoriasis, inverse psoriasis, L40.83–4) appears as smooth inflamed
patches of skin. It occurs in skin folds, particularly around the genitals
(between the thigh and groin), the armpits, under an overweight abdomen
(panniculus), and under the breasts (inframammary fold). It is aggravated by
friction and sweat, and is vulnerable to fungal
infections.
Napkin
psoriasis
Seborrheic-like psoriasis
Guttate
psoriasis (L40.4) is characterized by numerous small, scaly, red or pink,
teardrop-shaped lesions. These numerous spots of psoriasis appear over large
areas of the body, primarily the trunk, but also the limbs and scalp. Guttate
psoriasis is often preceded by a streptococcal infection, typically
streptococcal pharyngitis. The reverse is not true.
Nail
psoriasis (L40.86) produces a variety of changes in the appearance of finger and
toe nails. These changes include discolouring under the nail plate, pitting of
the nails, lines going across the nails, thickening of the skin under the nail,
and the loosening (onycholysis) and crumbling of the
nail.
Psoriatic
arthritis (L40.5) involves joint and connective tissue inflammation. Psoriatic
arthritis can affect any joint, but is most common in the joints of the fingers
and toes. This can result in a sausage-shaped swelling of the fingers and toes
known as dactylitis. Psoriatic arthritis can also affect the hips, knees and
spine (spondylitis). About 10–15% of people who have psoriasis also have
psoriatic arthritis.
The
migratory stomatitis in the oral cavity mucosa and the geographic tongue that
confined to the dorsal and lateral aspects of the tongue mucosa, are believed to
be oral manifestations of psoriasis, as being histologically identical to
cutaneous psoriasis lesions and more prevalent among psoriasis patients,
although these conditions are quite common in the non-psoriatic population,
affecting 1% to 2.5% of the general population.
Signs and
symptoms
Plaque of
psoriasis
An arm
covered with plaque type psoriasis
A person's
arm covered with plaque psoriasis
Psoriasis of
a fingernail
Quality of
life
Severe cases
of psoriasis have been shown to affect health-related quality of life to an
extent similar to the effects of other chronic diseases, such as depression,
hypertension, congestive heart failure or type 2 diabetes. Depending on the
severity and location of outbreaks, individuals may experience significant
physical discomfort and some disability. Itching and pain can interfere with
basic functions, such as self-care, walking, and sleep. Plaques on hands and
feet can prevent individuals from working at certain occupations, playing some
sports, and caring for family members or a home. Plaques on the scalp can be
particularly embarrassing, as flaky plaque in the hair can be mistaken for
dandruff.
Individuals
with psoriasis may also feel self-conscious about their appearance and have a
poor self-image that stems from fear of public rejection and psychosexual
concerns. Psychological distress can lead to significant depression and social
isolation.
In a 2008
National Psoriasis Foundation survey of 426 psoriasis sufferers, 71 percent
reported the disease was a significant problem in everyday life. More than half
reported significant feelings of self-consciousness (63 percent) and
embarrassment (58 percent). More than one-third said they avoided social
activities and limited dating or intimate interactions.
Many tools
exist to measure quality of life of patients with psoriasis and other
dermatalogical disorders. Clinical research has indicated individuals often
experience a diminished quality of life. A 2009 study looked at the impact of
psoriasis by using interviews with dermatologists and exploring patients
viewpoint. It found that in cases of mild and severe psoriasis, itch contributed
most to the diminished health-related quality of life
(HRQoL).
According to
a study published in 2010 in the Journal of the American Academy of Dermatology,
the reliability of a simple six-point Likert scale for self-assessment of
pruritus (itching) by patients was validated in patients with moderate to severe
plaque psoriasis. This will allow better communication, assessment, as well as
staging and management of itching. It could also allow future studies to
objectively evaluate the effectiveness of therapy directed towards itching, with
consequent improvement in quality of life.
Severity
Distribution
of severity among people with psoriasis
Psoriasis is usually graded as mild
(affecting less than 3% of the body), moderate (affecting 3–10% of the body) or
severe. Several scales exist for measuring the severity of psoriasis. The degree
of severity is generally based on the following factors: the proportion of body
surface area affected; disease activity (degree of plaque redness, thickness and
scaling); response to previous therapies; and the impact of the disease on the
person.
The
Psoriasis Area Severity Index (PASI) is the most widely used measurement tool
for psoriasis. PASI combines the assessment of the severity of lesions and the
area affected into a single score in the range 0 (no disease) to 72 (maximal
disease). Nevertheless, the PASI can be too unwieldy to use outside of trials,
which has led to attempts to simplify the index for clinical
use.
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
keratinocytes. 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 (tumor 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
immunosuppressant 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.[28]
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 streptococcal 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 antimalarial drug 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.[citation needed] 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.
Individuals
suffering from the advanced effects of the human immunodeficiency virus, or HIV,
often exhibit psoriasis. This presents a paradox to researchers, as traditional
therapies that reduce T-cell counts generally cause psoriasis to improve. Yet,
as CD4-T-cell counts decrease with the progression of HIV, psoriasis worsens. In
addition, HIV is typically characterized by a strong Th2 cytokine profile,
whereas psoriasis vulgaris is characterized by a strong Th1 secretion pattern.
It is hypothesized that the diminished CD4-T-Cell presence causes an
overactivation of CD8-T-cells, which are responsible for the exacerbation of
psoriasis in HIV positive patients. It is important to remember that most
individuals with psoriasis are otherwise healthy, and the presence of HIV
accounts for less than 1% of cases. The prevalence of psoriasis in the HIV
positive population ranges from 1 to 6 percent, which is about three times
higher than the normal population. Psoriasis in AIDS sufferers is often severe,
and untreatable with conventional therapy.
Psoriasis
occurs more likely in dry skin than oily or well-moisturized skin, and
specifically after an external skin injury such as a scratch or cut (see Koebner
phenomenon). This is believed to be caused by an infection, in which the
infecting organism thrives under dry skin conditions with minimal skin oil,
which otherwise protects skin from infections. The case for psoriasis is
opposite to the case of athlete's foot, which occurs because of a fungus
infection under wet conditions as opposed to dry in psoriasis. This infection
induces inflammation, which causes the symptoms commonly associated with
psoriasis, such as itching and rapid skin turnover, and leads to drier skin, as
the infecting organism absorbs the moisture that would otherwise go to the skin.
To prevent dry skin and reduce psoriasis symptoms, it is advised to not use
shower scrubs, as they not only damage skin by leaving tiny scratches, but they
also scrape off the naturally occurring skin oil. Additionally, moisturizers can
be applied to moisturize the skin, and lotions used to promote skin oil gland
functions.
Genetics
See also:
List of human leukocyte antigen alleles associated with cutaneous
conditions
Psoriasis
has a large hereditary component, and many genes are associated with it, but it
is not clear how those genes work together. Most of them involve the immune
system, particularly the major histocompatibility complex (MHC) and T cells. The
main value of genetic studies is they identify molecular mechanisms and pathways
for further study and potential drug targets.
Classic
genomewide linkage analysis has identified nine locations (loci) on different
chromosomes associated with psoriasis. They are called psoriasis susceptibility
1 through 9 (PSORS1 through PSORS9). Within those loci are genes. Many of those
genes are on pathways that lead to inflammation. Certain variations (mutations)
of those genes are commonly found in psoriasis.
The major
determinant is PSORS1, which probably accounts for 35–50% of its heritability.
It controls genes that affect the immune system or encode proteins that are
found in the skin in greater amounts in psoriasis. PSORS1 is located on
chromosome 6 in the MHC, which controls important immune functions. Three genes
in the PSORS1 locus have a strong association with psoriasis vulgaris: HLA-C
variant HLA-Cw6, which encodes a MHC class I protein; CCHCR1, variant WWC, which
encodes a coiled protein that is overexpressed in psoriatic epidermis; and CDSM,
variant allele 5, which encodes corneodesmosin, which is expressed in the
granular and cornified layers of the epidermis and upregulated in
psoriasis.
Genome-wide
association scans have identified other genes which are altered to
characteristic variants in psoriasis. Some of these genes express inflammatory
signal proteins, which affect cells in the immune system that are also involved
in psoriasis. Some of these genes are also involved in other autoimmune
diseases.
Two major
genes under investigation are IL12B on chromosome 5q, which expresses
interleukin-12B; and IL23R on chromosome 1p, which expresses the interleukin-23
receptor, and is involved in T cell differentiation. T cells are involved in the
inflammatory process that leads to psoriasis.
These genes
are on the pathway that ends up upregulating tumor necrosis factor-α and nuclear
factor κB, two genes that are involved in inflammation.
Recently the
first gene directly linked to psoriasis has been identified. Studies have
suggested that a rare mutation in the gene encoding for the CARD14 protein plus
an environmental trigger was enough to cause plaque psoriasis (the most common
form of psoriasis).
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.
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.
Diagnosis
A diagnosis
of psoriasis is usually based on the appearance of the skin; there are no
special blood tests or diagnostic procedures. Sometimes, a skin biopsy, or
scraping, may be needed to rule out other disorders and to confirm the
diagnosis. Skin from a biopsy will show clubbed rete pegs if positive for
psoriasis. Another sign of psoriasis is that when the plaques are scraped, one
can see pinpoint bleeding from the skin below (Auspitz's
sign).
Management
Schematic of
psoriasis treatment ladder
There are a number of different treatment options
for psoriasis. Typically topical agents are used for mild disease, phototherapy
for moderate disease, and systemic agents for severe
disease.
Topical agents
Bath
solutions (epsom salt) and moisturizers, mineral oil, and petroleum jelly may
help soothe affected skin and reduce the dryness which accompanies the build-up
of skin on psoriatic plaques. Medicated creams and ointments applied directly to
psoriatic plaques can help reduce inflammation, remove built-up scale, reduce
skin turn over, and clear affected skin of plaques. Ointment and creams
containing coal tar, dithranol (anthralin), corticosteroids like desoximetasone
(Topicort), fluocinonide, vitamin D3 analogues (for example, calcipotriol), and
retinoids are routinely used. The use of the Finger tip unit may be helpful in
guiding how much topical treatment to use. The mechanism of action of each is
probably different, but they all help to normalise skin cell production and
reduce inflammation. Activated vitamin D and its analogues can inhibit skin cell
proliferation.
Phototherapy
Phototherapy
in the form of sunlight has long been used effectively for treatment.
Wavelengths of 311–313 nm are most effective and special lamps have been
developed for this application. The exposure time should be controlled to avoid
over exposure and burning of the skin. The UVB lamps should have a timer that
will turn off the lamp when the time ends. The amount of light used is
determined by a person's skin type. Increased rates of cancer from treatment
appear to be small.
Psoralen and
ultraviolet A phototherapy (PUVA) combines the oral or topical administration of
psoralen with exposure to ultraviolet A (UVA) light. The mechanism of action of
PUVA is unknown, but probably involves activation of psoralen by UVA light,
which inhibits the abnormally rapid production of the cells in psoriatic skin.
There are multiple mechanisms of action associated with PUVA, including effects
on the skin immune system.
PUVA is
associated with nausea, headache, fatigue, burning, and itching. Long-term
treatment is associated with squamous cell carcinoma (but not with
melanoma).
Systemic
agents
Pictures of
a patient with psoriasis (and psoriatic arthritis) at baseline and 8 weeks after
initiation of infliximab therapy.
Psoriasis that is resistant to topical
treatment and phototherapy is treated by medications taken internally by pill or
injection (systemic). Patients undergoing systemic treatment are required to
have regular blood and liver function tests because of the toxicity of the
medication. Pregnancy must be avoided for the majority of these treatments. Most
people experience a recurrence of psoriasis after systemic treatment is
discontinued.
The three
main traditional systemic treatments are methotrexate, cyclosporine and
retinoids. Methotrexate and cyclosporine are immunosuppressant drugs; retinoids
are synthetic forms of vitamin A. Patients taking methotrexate are prone to
ulcerations. Methotrexate exposure may contribute to post-surgical
events.
A fourth
oral agent, fumaric acid esters (FAE) (brand name Fumaderm®, main active
ingredient dimethyl fumarate (DMF)) is approved only in Germany but widely used
in Europe due to its unique immunemodulatory properties without significant
immunosuppression which makes it suitable for long-term
treatment.
Biologics
are manufactured proteins that interrupt the immune process involved in
psoriasis. Unlike generalised immunosuppressant therapies such as methotrexate,
biologics focus on specific aspects of the immune function leading to psoriasis.
These drugs (interleukin antagonists) are relatively new, and their long-term
impact on immune function is unknown, but they have proven effective in treating
psoriasis and psoriatic arthritis. Biologics are usually given by self-injection
or in a doctor's office. In the United Kingdom in 2005, the British Association
of Dermatologists (BAD) published guidelines for use of biological interventions
in psoriasis. A UK national register called the BAD Biological Register (BADBIR)
has been set up to collect valuable information on side effects and benefits and
will be used to inform doctors on how best to use biological agents and similar
drugs.
Two drugs
that target T cells are efalizumab and alefacept. Efalizumab is a monoclonal
antibody which blocks the molecules that dendritic cells use to communicate with
T cells. It also blocks the adhesion molecules on the endothelial cells that
line blood vessels, which attract T cells. However, it suppressed the immune
system's ability to control normally harmless viruses, which led to fatal brain
infections. Efalizumab was voluntarily withdrawn from the US market in April,
2009 by the manufacturer. Alefacept also blocks the molecules that dendritic
cells use to communicate with T cells and even causes natural killer cells to
kill T cells as a way of controlling inflammation.
Several
monoclonal antibodies (MAbs) target cytokines, the molecules that cells use to
send inflammatory signals to each other. TNF-α is one of the main executor
inflammatory cytokines. Four MAbs (infliximab, adalimumab, golimumab and
certolizumab pegol) and one recombinant TNF-α decoy receptor, etanercept, have
been developed against TNF-α to inhibit TNF-α signaling. Additional monoclonal
antibodies have been developed against pro-inflammatory cytokines IL-12/IL-23
and Interleukin-17 and inhibit the inflammatory pathway at a different point
than the anti-TNF-α antibodies.[38] IL-12 and IL-23 share a common domain, p40,
which is the target of the recently FDA-approved ustekinumab. Ustekinumab
(IL-12/IL-23 blocker) was shown to have higher efficacy than high-dose
etanercept over a 12-week period in patients with
psoriasis.
In 2008, the
FDA approved three new treatment options[48] available to psoriasis patients: 1)
Taclonex Scalp, a new topical ointment for treating scalp psoriasis; 2) the
Xtrac Velocity excimer laser system, which emits a high-intensity beam of
ultraviolet light, can treat moderate to severe psoriasis; and 3) the biologic
drug adalimumab (brand name Humira) was also approved to treat moderate to
severe psoriasis. Adalimumab had already been approved to treat psoriatic
arthritis. The most recent biologic drug that has been approved to treat
moderate to severe psoriasis, as of 2010, is ustekinumab (brand name
Stelara).
Medications
with the least potential for adverse reactions are preferentially employed. If
the treatment goal is not achieved, then therapies with greater potential
toxicity may be used. Medications with significant toxicity are reserved for
severe unresponsive psoriasis. This is called the psoriasis treatment ladder. As
a first step, medicated ointments or creams, called topical treatments, are
applied to the skin. If topical treatment fails to achieve the desired goal,
then the next step would be to expose the skin to ultraviolet (UV) radiation.
This type of treatment is called phototherapy. The third step involves the use
of medications which are taken internally by pill or injection. This approach is
called systemic treatment.
A 2010
meta-analysis compares the change in Psoriasis Area and Severity Index (PASI)
improvement from baseline in 22 trials. The combination therapy for moderate to
severe psoriasis using psoralen with ultraviolet A (PUVA) plus acitretin shows a
97.3% PASI improvement from baseline. Therapy limitations need to be taken into
consideration in the treatment of moderate to severe psoriasis, such as the
increased risk of skin cancer with phototherapy and birth defects with
acitretin.
Alternative
therapy
Some studies
suggest psoriasis symptoms can be relieved by changes in diet and lifestyle.
Fasting periods, low energy diets and vegetarian diets have improved psoriasis
symptoms in some studies and diets supplemented with fish oil (in this study cod
liver oil) have also shown beneficial effects – though evidence is still
inconclusive and more research is needed to determine whether there is any
benefit from diet manipulations. Fish oils are rich in the two omega-3 fatty
acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and contain
vitamin E, furthermore cod liver oil contains vitamin A and vitamin
D.
The severity
of psoriasis symptoms may also be influenced by lifestyle habits related to
alcohol, smoking, weight, sleep, stress and exercise.
It has been
suggested that cannabis might treat psoriasis, due to the anti-inflammatory
properties of its cannabinoids, and their regulatory effects on the immune
system. The adverse effects of cannabis might be avoided with a topical
preparation or by the use of (a) more specific endocannabinoid receptor
agonist(s),
Prognosis
Psoriasis is
typically a lifelong condition. There is currently no cure, but various
treatments can help to control the symptoms. Many of the most effective agents
used to treat severe psoriasis carry an increased risk of significant morbidity
including skin cancers, lymphoma and liver disease. However, the majority of
people's experience of psoriasis is that of minor localized patches,
particularly on the elbows and knees, which can be treated with topical
medication. Psoriasis can get worse over time, but it is not possible to predict
who will go on to develop extensive psoriasis or those in whom the disease may
appear to vanish. Individuals will often experience flares and remissions
throughout their lives. Controlling the signs and symptoms typically requires
lifelong therapy.
According to
one study, psoriasis is linked to 2.5-fold increased risk for nonmelanoma skin
cancer in men and women, with no preponderance of any specific histologic
subtype of cancer. This increased risk could also be attributed to antipsoriatic
treatment.
Epidemiology
Psoriasis
affects both sexes equally, and can occur at any age, although it most commonly
appears for the first time between the ages of 15 and 25
years.
The
prevalence of psoriasis in Western populations is estimated to be around 2–3%.
The prevalence of psoriasis among 7.5 million patients who were registered with
a general practitioner in the United Kingdom was 1.5%. A survey conducted by the
National Psoriasis Foundation (a US-based psoriasis education and advocacy
group) found a prevalence of 2.1% among adult Americans. The study found 35% of
people with psoriasis could be classified as having moderate to severe
psoriasis.
Around
one-third of people with psoriasis report a family history of the disease, and
researchers have identified genetic loci associated with the condition. Studies
of monozygotic twins suggest a 70% chance of a twin developing psoriasis if the
other twin has psoriasis. The concordance is around 20% for dizygotic twins.
These findings suggest both a genetic predisposition and an environmental
response in developing psoriasis.
Within the
United States, psoriasis is most common in the
Northeast.
Prevalence
across different racial groups is similar; race does not appear to be a risk
factor.
Onset before
age 40 usually indicates a greater genetic susceptibility and a more severe or
recurrent course of psoriasis
(pron.: /sɵˈraɪ.əsɨs/) is an immune-mediated disease that affects the skin. It
is typically a lifelong condition. There is currently no cure, but various
treatments can help to control the symptoms.
Psoriasis
occurs when the immune system mistakes a normal skin cell for a pathogen, and
sends out faulty signals that cause overproduction of new 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. The name psoriasis
(ψωρίασις) is from the Greek language, meaning roughly "itching condition"
(psora "itch" + -sis "action, condition").
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 and toenails 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
arthritis. Between 10% and 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 phenomenon. Various environmental factors have been
suggested as aggravating to psoriasis, including oxidative stress, stress,
withdrawal of systemic corticosteroid, 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.
The symptoms of
psoriasis can manifest in a variety of forms. Variants include plaque, pustular,
guttate, and flexural psoriasis. This section describes each type (with ICD-10
code
Psoriasis
may be classified into nonpustular and pustular types as
follows.
Nonpustular
Psoriasis vulgaris (chronic stationary
psoriasis, plaque-like psoriasis, L40.0) is the most common form of psoriasis.
It affects 80% to 90% of people with psoriasis. Plaque psoriasis typically
appears as raised areas of inflamed skin covered with silvery white scaly skin.
These areas are called plaques.
Psoriatic erythroderma (erythrodermic
psoriasis, L40.85) involves the widespread inflammation and exfoliation of the
skin over most of the body surface. It may be accompanied by severe itching,
swelling and pain. It is often the result of an exacerbation of unstable plaque
psoriasis, particularly following the abrupt withdrawal of systemic treatment.
This form of psoriasis can be fatal, as the extreme inflammation and exfoliation
disrupt the body's ability to regulate temperature and for the skin to perform
barrier functions.
Pustular
Pustular
psoriasis (L40.1–3, L40.82) appears as raised bumps that are filled with
noninfectious pus (pustules). The skin under and surrounding the pustules is red
and tender. Pustular psoriasis can be localised, commonly to the hands and feet
(palmoplantar pustulosis), or generalised with widespread patches occurring
randomly on any part of the body. Types include:
Generalized pustular
psoriasis (pustular psoriasis of von Zumbusch)
Pustulosis palmaris et
plantaris (persistent palmoplantar pustulosis, pustular psoriasis of the Barber
type, pustular psoriasis of the extremities)
Annular pustular
psoriasis
Acrodermatitis continua
Impetigo
herpetiformis
Other
Additional
types of psoriasis include:
Drug-induced psoriasis
Inverse psoriasis
(flexural psoriasis, inverse psoriasis, L40.83–4) appears as smooth inflamed
patches of skin. It occurs in skin folds, particularly around the genitals
(between the thigh and groin), the armpits, under an overweight abdomen
(panniculus), and under the breasts (inframammary fold). It is aggravated by
friction and sweat, and is vulnerable to fungal
infections.
Napkin
psoriasis
Seborrheic-like psoriasis
Guttate
psoriasis (L40.4) is characterized by numerous small, scaly, red or pink,
teardrop-shaped lesions. These numerous spots of psoriasis appear over large
areas of the body, primarily the trunk, but also the limbs and scalp. Guttate
psoriasis is often preceded by a streptococcal infection, typically
streptococcal pharyngitis. The reverse is not true.
Nail
psoriasis (L40.86) produces a variety of changes in the appearance of finger and
toe nails. These changes include discolouring under the nail plate, pitting of
the nails, lines going across the nails, thickening of the skin under the nail,
and the loosening (onycholysis) and crumbling of the
nail.
Psoriatic
arthritis (L40.5) involves joint and connective tissue inflammation. Psoriatic
arthritis can affect any joint, but is most common in the joints of the fingers
and toes. This can result in a sausage-shaped swelling of the fingers and toes
known as dactylitis. Psoriatic arthritis can also affect the hips, knees and
spine (spondylitis). About 10–15% of people who have psoriasis also have
psoriatic arthritis.
The
migratory stomatitis in the oral cavity mucosa and the geographic tongue that
confined to the dorsal and lateral aspects of the tongue mucosa, are believed to
be oral manifestations of psoriasis, as being histologically identical to
cutaneous psoriasis lesions and more prevalent among psoriasis patients,
although these conditions are quite common in the non-psoriatic population,
affecting 1% to 2.5% of the general population.
Signs and
symptoms
Plaque of
psoriasis
An arm
covered with plaque type psoriasis
A person's
arm covered with plaque psoriasis
Psoriasis of
a fingernail
Quality of
life
Severe cases
of psoriasis have been shown to affect health-related quality of life to an
extent similar to the effects of other chronic diseases, such as depression,
hypertension, congestive heart failure or type 2 diabetes. Depending on the
severity and location of outbreaks, individuals may experience significant
physical discomfort and some disability. Itching and pain can interfere with
basic functions, such as self-care, walking, and sleep. Plaques on hands and
feet can prevent individuals from working at certain occupations, playing some
sports, and caring for family members or a home. Plaques on the scalp can be
particularly embarrassing, as flaky plaque in the hair can be mistaken for
dandruff.
Individuals
with psoriasis may also feel self-conscious about their appearance and have a
poor self-image that stems from fear of public rejection and psychosexual
concerns. Psychological distress can lead to significant depression and social
isolation.
In a 2008
National Psoriasis Foundation survey of 426 psoriasis sufferers, 71 percent
reported the disease was a significant problem in everyday life. More than half
reported significant feelings of self-consciousness (63 percent) and
embarrassment (58 percent). More than one-third said they avoided social
activities and limited dating or intimate interactions.
Many tools
exist to measure quality of life of patients with psoriasis and other
dermatalogical disorders. Clinical research has indicated individuals often
experience a diminished quality of life. A 2009 study looked at the impact of
psoriasis by using interviews with dermatologists and exploring patients
viewpoint. It found that in cases of mild and severe psoriasis, itch contributed
most to the diminished health-related quality of life
(HRQoL).
According to
a study published in 2010 in the Journal of the American Academy of Dermatology,
the reliability of a simple six-point Likert scale for self-assessment of
pruritus (itching) by patients was validated in patients with moderate to severe
plaque psoriasis. This will allow better communication, assessment, as well as
staging and management of itching. It could also allow future studies to
objectively evaluate the effectiveness of therapy directed towards itching, with
consequent improvement in quality of life.
Severity
Distribution
of severity among people with psoriasis
Psoriasis is usually graded as mild
(affecting less than 3% of the body), moderate (affecting 3–10% of the body) or
severe. Several scales exist for measuring the severity of psoriasis. The degree
of severity is generally based on the following factors: the proportion of body
surface area affected; disease activity (degree of plaque redness, thickness and
scaling); response to previous therapies; and the impact of the disease on the
person.
The
Psoriasis Area Severity Index (PASI) is the most widely used measurement tool
for psoriasis. PASI combines the assessment of the severity of lesions and the
area affected into a single score in the range 0 (no disease) to 72 (maximal
disease). Nevertheless, the PASI can be too unwieldy to use outside of trials,
which has led to attempts to simplify the index for clinical
use.
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
keratinocytes. 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 (tumor 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
immunosuppressant 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.[28]
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 streptococcal 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 antimalarial drug 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.[citation needed] 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.
Individuals
suffering from the advanced effects of the human immunodeficiency virus, or HIV,
often exhibit psoriasis. This presents a paradox to researchers, as traditional
therapies that reduce T-cell counts generally cause psoriasis to improve. Yet,
as CD4-T-cell counts decrease with the progression of HIV, psoriasis worsens. In
addition, HIV is typically characterized by a strong Th2 cytokine profile,
whereas psoriasis vulgaris is characterized by a strong Th1 secretion pattern.
It is hypothesized that the diminished CD4-T-Cell presence causes an
overactivation of CD8-T-cells, which are responsible for the exacerbation of
psoriasis in HIV positive patients. It is important to remember that most
individuals with psoriasis are otherwise healthy, and the presence of HIV
accounts for less than 1% of cases. The prevalence of psoriasis in the HIV
positive population ranges from 1 to 6 percent, which is about three times
higher than the normal population. Psoriasis in AIDS sufferers is often severe,
and untreatable with conventional therapy.
Psoriasis
occurs more likely in dry skin than oily or well-moisturized skin, and
specifically after an external skin injury such as a scratch or cut (see Koebner
phenomenon). This is believed to be caused by an infection, in which the
infecting organism thrives under dry skin conditions with minimal skin oil,
which otherwise protects skin from infections. The case for psoriasis is
opposite to the case of athlete's foot, which occurs because of a fungus
infection under wet conditions as opposed to dry in psoriasis. This infection
induces inflammation, which causes the symptoms commonly associated with
psoriasis, such as itching and rapid skin turnover, and leads to drier skin, as
the infecting organism absorbs the moisture that would otherwise go to the skin.
To prevent dry skin and reduce psoriasis symptoms, it is advised to not use
shower scrubs, as they not only damage skin by leaving tiny scratches, but they
also scrape off the naturally occurring skin oil. Additionally, moisturizers can
be applied to moisturize the skin, and lotions used to promote skin oil gland
functions.
Genetics
See also:
List of human leukocyte antigen alleles associated with cutaneous
conditions
Psoriasis
has a large hereditary component, and many genes are associated with it, but it
is not clear how those genes work together. Most of them involve the immune
system, particularly the major histocompatibility complex (MHC) and T cells. The
main value of genetic studies is they identify molecular mechanisms and pathways
for further study and potential drug targets.
Classic
genomewide linkage analysis has identified nine locations (loci) on different
chromosomes associated with psoriasis. They are called psoriasis susceptibility
1 through 9 (PSORS1 through PSORS9). Within those loci are genes. Many of those
genes are on pathways that lead to inflammation. Certain variations (mutations)
of those genes are commonly found in psoriasis.
The major
determinant is PSORS1, which probably accounts for 35–50% of its heritability.
It controls genes that affect the immune system or encode proteins that are
found in the skin in greater amounts in psoriasis. PSORS1 is located on
chromosome 6 in the MHC, which controls important immune functions. Three genes
in the PSORS1 locus have a strong association with psoriasis vulgaris: HLA-C
variant HLA-Cw6, which encodes a MHC class I protein; CCHCR1, variant WWC, which
encodes a coiled protein that is overexpressed in psoriatic epidermis; and CDSM,
variant allele 5, which encodes corneodesmosin, which is expressed in the
granular and cornified layers of the epidermis and upregulated in
psoriasis.
Genome-wide
association scans have identified other genes which are altered to
characteristic variants in psoriasis. Some of these genes express inflammatory
signal proteins, which affect cells in the immune system that are also involved
in psoriasis. Some of these genes are also involved in other autoimmune
diseases.
Two major
genes under investigation are IL12B on chromosome 5q, which expresses
interleukin-12B; and IL23R on chromosome 1p, which expresses the interleukin-23
receptor, and is involved in T cell differentiation. T cells are involved in the
inflammatory process that leads to psoriasis.
These genes
are on the pathway that ends up upregulating tumor necrosis factor-α and nuclear
factor κB, two genes that are involved in inflammation.
Recently the
first gene directly linked to psoriasis has been identified. Studies have
suggested that a rare mutation in the gene encoding for the CARD14 protein plus
an environmental trigger was enough to cause plaque psoriasis (the most common
form of psoriasis).
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.
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.
Diagnosis
A diagnosis
of psoriasis is usually based on the appearance of the skin; there are no
special blood tests or diagnostic procedures. Sometimes, a skin biopsy, or
scraping, may be needed to rule out other disorders and to confirm the
diagnosis. Skin from a biopsy will show clubbed rete pegs if positive for
psoriasis. Another sign of psoriasis is that when the plaques are scraped, one
can see pinpoint bleeding from the skin below (Auspitz's
sign).
Management
Schematic of
psoriasis treatment ladder
There are a number of different treatment options
for psoriasis. Typically topical agents are used for mild disease, phototherapy
for moderate disease, and systemic agents for severe
disease.
Topical agents
Bath
solutions (epsom salt) and moisturizers, mineral oil, and petroleum jelly may
help soothe affected skin and reduce the dryness which accompanies the build-up
of skin on psoriatic plaques. Medicated creams and ointments applied directly to
psoriatic plaques can help reduce inflammation, remove built-up scale, reduce
skin turn over, and clear affected skin of plaques. Ointment and creams
containing coal tar, dithranol (anthralin), corticosteroids like desoximetasone
(Topicort), fluocinonide, vitamin D3 analogues (for example, calcipotriol), and
retinoids are routinely used. The use of the Finger tip unit may be helpful in
guiding how much topical treatment to use. The mechanism of action of each is
probably different, but they all help to normalise skin cell production and
reduce inflammation. Activated vitamin D and its analogues can inhibit skin cell
proliferation.
Phototherapy
Phototherapy
in the form of sunlight has long been used effectively for treatment.
Wavelengths of 311–313 nm are most effective and special lamps have been
developed for this application. The exposure time should be controlled to avoid
over exposure and burning of the skin. The UVB lamps should have a timer that
will turn off the lamp when the time ends. The amount of light used is
determined by a person's skin type. Increased rates of cancer from treatment
appear to be small.
Psoralen and
ultraviolet A phototherapy (PUVA) combines the oral or topical administration of
psoralen with exposure to ultraviolet A (UVA) light. The mechanism of action of
PUVA is unknown, but probably involves activation of psoralen by UVA light,
which inhibits the abnormally rapid production of the cells in psoriatic skin.
There are multiple mechanisms of action associated with PUVA, including effects
on the skin immune system.
PUVA is
associated with nausea, headache, fatigue, burning, and itching. Long-term
treatment is associated with squamous cell carcinoma (but not with
melanoma).
Systemic
agents
Pictures of
a patient with psoriasis (and psoriatic arthritis) at baseline and 8 weeks after
initiation of infliximab therapy.
Psoriasis that is resistant to topical
treatment and phototherapy is treated by medications taken internally by pill or
injection (systemic). Patients undergoing systemic treatment are required to
have regular blood and liver function tests because of the toxicity of the
medication. Pregnancy must be avoided for the majority of these treatments. Most
people experience a recurrence of psoriasis after systemic treatment is
discontinued.
The three
main traditional systemic treatments are methotrexate, cyclosporine and
retinoids. Methotrexate and cyclosporine are immunosuppressant drugs; retinoids
are synthetic forms of vitamin A. Patients taking methotrexate are prone to
ulcerations. Methotrexate exposure may contribute to post-surgical
events.
A fourth
oral agent, fumaric acid esters (FAE) (brand name Fumaderm®, main active
ingredient dimethyl fumarate (DMF)) is approved only in Germany but widely used
in Europe due to its unique immunemodulatory properties without significant
immunosuppression which makes it suitable for long-term
treatment.
Biologics
are manufactured proteins that interrupt the immune process involved in
psoriasis. Unlike generalised immunosuppressant therapies such as methotrexate,
biologics focus on specific aspects of the immune function leading to psoriasis.
These drugs (interleukin antagonists) are relatively new, and their long-term
impact on immune function is unknown, but they have proven effective in treating
psoriasis and psoriatic arthritis. Biologics are usually given by self-injection
or in a doctor's office. In the United Kingdom in 2005, the British Association
of Dermatologists (BAD) published guidelines for use of biological interventions
in psoriasis. A UK national register called the BAD Biological Register (BADBIR)
has been set up to collect valuable information on side effects and benefits and
will be used to inform doctors on how best to use biological agents and similar
drugs.
Two drugs
that target T cells are efalizumab and alefacept. Efalizumab is a monoclonal
antibody which blocks the molecules that dendritic cells use to communicate with
T cells. It also blocks the adhesion molecules on the endothelial cells that
line blood vessels, which attract T cells. However, it suppressed the immune
system's ability to control normally harmless viruses, which led to fatal brain
infections. Efalizumab was voluntarily withdrawn from the US market in April,
2009 by the manufacturer. Alefacept also blocks the molecules that dendritic
cells use to communicate with T cells and even causes natural killer cells to
kill T cells as a way of controlling inflammation.
Several
monoclonal antibodies (MAbs) target cytokines, the molecules that cells use to
send inflammatory signals to each other. TNF-α is one of the main executor
inflammatory cytokines. Four MAbs (infliximab, adalimumab, golimumab and
certolizumab pegol) and one recombinant TNF-α decoy receptor, etanercept, have
been developed against TNF-α to inhibit TNF-α signaling. Additional monoclonal
antibodies have been developed against pro-inflammatory cytokines IL-12/IL-23
and Interleukin-17 and inhibit the inflammatory pathway at a different point
than the anti-TNF-α antibodies.[38] IL-12 and IL-23 share a common domain, p40,
which is the target of the recently FDA-approved ustekinumab. Ustekinumab
(IL-12/IL-23 blocker) was shown to have higher efficacy than high-dose
etanercept over a 12-week period in patients with
psoriasis.
In 2008, the
FDA approved three new treatment options[48] available to psoriasis patients: 1)
Taclonex Scalp, a new topical ointment for treating scalp psoriasis; 2) the
Xtrac Velocity excimer laser system, which emits a high-intensity beam of
ultraviolet light, can treat moderate to severe psoriasis; and 3) the biologic
drug adalimumab (brand name Humira) was also approved to treat moderate to
severe psoriasis. Adalimumab had already been approved to treat psoriatic
arthritis. The most recent biologic drug that has been approved to treat
moderate to severe psoriasis, as of 2010, is ustekinumab (brand name
Stelara).
Medications
with the least potential for adverse reactions are preferentially employed. If
the treatment goal is not achieved, then therapies with greater potential
toxicity may be used. Medications with significant toxicity are reserved for
severe unresponsive psoriasis. This is called the psoriasis treatment ladder. As
a first step, medicated ointments or creams, called topical treatments, are
applied to the skin. If topical treatment fails to achieve the desired goal,
then the next step would be to expose the skin to ultraviolet (UV) radiation.
This type of treatment is called phototherapy. The third step involves the use
of medications which are taken internally by pill or injection. This approach is
called systemic treatment.
A 2010
meta-analysis compares the change in Psoriasis Area and Severity Index (PASI)
improvement from baseline in 22 trials. The combination therapy for moderate to
severe psoriasis using psoralen with ultraviolet A (PUVA) plus acitretin shows a
97.3% PASI improvement from baseline. Therapy limitations need to be taken into
consideration in the treatment of moderate to severe psoriasis, such as the
increased risk of skin cancer with phototherapy and birth defects with
acitretin.
Alternative
therapy
Some studies
suggest psoriasis symptoms can be relieved by changes in diet and lifestyle.
Fasting periods, low energy diets and vegetarian diets have improved psoriasis
symptoms in some studies and diets supplemented with fish oil (in this study cod
liver oil) have also shown beneficial effects – though evidence is still
inconclusive and more research is needed to determine whether there is any
benefit from diet manipulations. Fish oils are rich in the two omega-3 fatty
acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and contain
vitamin E, furthermore cod liver oil contains vitamin A and vitamin
D.
The severity
of psoriasis symptoms may also be influenced by lifestyle habits related to
alcohol, smoking, weight, sleep, stress and exercise.
It has been
suggested that cannabis might treat psoriasis, due to the anti-inflammatory
properties of its cannabinoids, and their regulatory effects on the immune
system. The adverse effects of cannabis might be avoided with a topical
preparation or by the use of (a) more specific endocannabinoid receptor
agonist(s),
Prognosis
Psoriasis is
typically a lifelong condition. There is currently no cure, but various
treatments can help to control the symptoms. Many of the most effective agents
used to treat severe psoriasis carry an increased risk of significant morbidity
including skin cancers, lymphoma and liver disease. However, the majority of
people's experience of psoriasis is that of minor localized patches,
particularly on the elbows and knees, which can be treated with topical
medication. Psoriasis can get worse over time, but it is not possible to predict
who will go on to develop extensive psoriasis or those in whom the disease may
appear to vanish. Individuals will often experience flares and remissions
throughout their lives. Controlling the signs and symptoms typically requires
lifelong therapy.
According to
one study, psoriasis is linked to 2.5-fold increased risk for nonmelanoma skin
cancer in men and women, with no preponderance of any specific histologic
subtype of cancer. This increased risk could also be attributed to antipsoriatic
treatment.
Epidemiology
Psoriasis
affects both sexes equally, and can occur at any age, although it most commonly
appears for the first time between the ages of 15 and 25
years.
The
prevalence of psoriasis in Western populations is estimated to be around 2–3%.
The prevalence of psoriasis among 7.5 million patients who were registered with
a general practitioner in the United Kingdom was 1.5%. A survey conducted by the
National Psoriasis Foundation (a US-based psoriasis education and advocacy
group) found a prevalence of 2.1% among adult Americans. The study found 35% of
people with psoriasis could be classified as having moderate to severe
psoriasis.
Around
one-third of people with psoriasis report a family history of the disease, and
researchers have identified genetic loci associated with the condition. Studies
of monozygotic twins suggest a 70% chance of a twin developing psoriasis if the
other twin has psoriasis. The concordance is around 20% for dizygotic twins.
These findings suggest both a genetic predisposition and an environmental
response in developing psoriasis.
Within the
United States, psoriasis is most common in the
Northeast.
Prevalence
across different racial groups is similar; race does not appear to be a risk
factor.
Onset before
age 40 usually indicates a greater genetic susceptibility and a more severe or
recurrent course of psoriasis