PSORIASIS
Etymology: Gk, psoriasis, itch
Etiology
• Prevalence in is 1-3% and in America and
western
• Lower prevalence rates are found in Japanese
and psoriasis is rare in West Africans
• Psoriasis first appears during 2 peak age
ranges:The first peak occurs in persons aged
16-22 years, and the second occurs in persons
aged 57-60 years
Pathogenesis
• The initiation and maintenance of lesions
requires activated T Lymphocytes
• Drugs suppressing T-cell activity
contribute to the improvement of psoriasis
• An unknown antigen may cause Antigenpresenting cells (APCs) to be activated in
the epidermis
• The APCs internalize and process the
antigen, which is then presented on the
APC surface
• Activated APCs then travel to the lymph
nodes and activate naive T cells by
binding to it
• Binding leads to the recognition of
intracellular adhesion molecule-1 (ICAM-1)
on the surface of the APC by lymphocyte
function-associated antigen-1 (LFA-1) on
the surface of the T cell. This interaction
sends a necessary but insufficient
activation signal to the T cell
• Additional costimulatory signals are sent to
the T cell as a result of several other
interactions
• The net effect of all of these signals is an
activated T cell with enhanced affinity for
endothelial cells
• The activated T cell travels along the
microvasculature into the dermis and then into
the epidermis
• In the skin, activated T cells undergo a second
activation similar to the previous encounter
with APCs in the lymph node
• Reactivated T cells then produce cytokines
(soluble proteins that can exert both direct and
indirect effects on other cells). These
cytokines include interleukin-2 (IL-2) and
interferon-gamma (IFN-g)
• These cytokines induce other cells to produce
TNF-a, IL-8, and granulocyte-macrophage
colony-stimulating factor (GM-CSF)
• Activated T cells and the cytokines cause
aborted maturation and excessive
proliferation of the keratinocytes. The
turnover in the epidermal cells is reduced
from 2 weeks to 1 day. These
histopathological alterations are clinically
evident as plaques
Genetics
• Psoriasis was present in 73% of monozygotic
twins compared with 20% in dizygotic twins
• Psoriasis susceptibility 1 (PSOR1) locus on
chromosome 6 is associated with up to 50%
of cases
• The relative risk of persons bearing the HLACw6 phenotype to develop psoriasis is about
10-fold higher than other persons but only
about 10 % of HLA-Cw6 carriers develop
psoriasis
• When both parents are affected by
psoriasis, the rate in siblings is as high as
50%. When one parent is affected, the
rate is 16.4%
• When neither parent has psoriasis, only
7.8% of siblings of probands are affected
• Other studies have shown that 36-71% of
patients with psoriasis have one relative
who is also affected by psoriasis
Excerbating Factors
Can be divided into local and systemic
factors.
• Local factors
1-Trauma: e g, physical, chemical,
electrical, surgical, infective, and
inflammatory types of injury or even
excessive scratching can aggravate or
precipitate localized psoriasis (Koebner
reaction)
2-Sunlight: Most patients generally
consider sunlight to be beneficial for their
psoriasis. Most report a decrease in illness
severity during the summer months or
periods of increased sun exposure;
however, a small minority find that their
symptoms are aggravated by strong
sunlight
• Systemic factors
1-Infection: Pharyngeal streptococcal infections
have been shown to produce guttate psoriasis.
Some evidence suggests that subclinical
streptococcal colonization or overgrowth could
be responsible for refractory plaque psoriasis.
An increase in psoriasis activity was observed in
HIV infected patients.
2-Drugs: Some drugs cause an exacerbation of
psoriasis. Lithium and withdrawal from systemic
corticosteroids are well known to cause flares of
disease. Beta-blockers, antimalarials, and
nonsteroidal anti-inflammatory drugs (NSAIDs)
have also been implicated.
3-Psychogenic/emotional factors: Many
patients report an increase in psoriasis
severity with psychological stress. A clear
cause-and-effect relationship between
disease exacerbation and stress
unfortunately has not been proven but,
pruritus associated with increased anxiety
or depression may promote scratching and
a Koebner reaction.
4-Smoking: An increased risk of chronic
plaque psoriasis exists in smokers
5-Alcohol: Alcohol is considered a risk
factor for psoriasis
6-Endocrine: Psoriasis severity has been
noted to fluctuate with hormonal changes.
Disease incidence peaks at puberty and
during menopause. Pregnant patients'
symptoms are more likely to improve than
worsenl. In contrast, the disease is more
likely to flare in the postpartum period
Clinically
Symptoms:
• Over 65% of patients complain of itching
• Patients may report that their disease worsens in
the winter and improves in the summer
• The isomorphic phenomenon (Koebner reaction):
38-76% of patients recognize that new lesions
appear at sites of injury 7-14 days after the skin has
been injured
• In some patients, so-called reverse-Koebner
reactions have also been noted in which
preexisting psoriatic plaques actually clear after
injury or trauma to the skin.
• Elevated, symmetrical plaques that vary in
size from one to several centimeters. They
have
-Irregular to oval
-Sharply demarcated
boundaries
-Dry, thin, silvery-white
scales variable in amount
and thickness
-Auspitz sign(Grattage
test): Removing the scale
reveals a smooth, red,
glossy membrane with
tiny punctate bleeding
points. These points
represent bleeding from
enlarged dermal
capillaries after removal
of the overlying
epithelium
-Rich red color:often referred to as 'salmon
pink‘. This quality of color is of special
diagnostic value to differentiate psoriasis
from eczema in lesions on the palms,
soles and scalp. In the fair-skinned
individual, the color is less rich and almost
magenta pink. In dark-skinned races, the
quality of the color is lost
Clinical patterns
1-Psoriasis Vulgaris(Plaque-type)
• Seen in approximately 90 % of patients
• Single small papules become confluent,
forming plaques
• Lesions may extend laterally and
become circinate because of the
confluence of several plaques
(psoriasis gyrata)
• The borders may resemble a land map
(psoriasis geographica)
•Annular psoriasis:Ring-like
lesions
• Elephantine
psoriasis is an
uncommon form
characterized by
thickly scaling,
large plaques,
usually on the
lower extremities
• Distribution: The
extensor aspects of the
extremities, particularly
the elbows and knees,
along with scalp, lower
lumbosacral, buttocks,
and genitalia. Other
sites of predilection
include the umbilicus
and the intergluteal cleft
2-Guttate Psoriasis
(Latin Gutta=drop)
• Characterized by eruption
of small (0.5 to 1.5 cm in
diameter) papules over the
upper trunk and proximal
extremities
• Manifests at an early age
• Streptococcal throat
infection frequently
precedes or is concomitant
with the onset or flare
3-Inverse Psoriasis
• Localized in the major skin folds, such as
the axillae, the inguinal and inframammary
areas
• Scaling is usually minimal or absent, and
the lesions appear glossy
• Sweating is impaired in affected areas
4-Psoriatic erythroderma
• The disease affects all
body sites
• Erythema is the most
prominent feature with
superficial scaling
• Patients with erythrodermic psoriasis lose
excessive heat because of generalized
vasodilatation, and this may cause
hypothermia
• Psoriatic skin is often hypohidrotic due to
occlusion of the sweat ducts
• There is an attendant risk of hyperthermia
in warm climates
• Lower extremity edema is common
secondary to vasodilatation and loss of
protein from the blood vessels into the
tissues
• High-output cardiac failure and impaired
hepatic and renal function may also occur
• Erythrodermic psoriasis may start from
worsening of plaque psoriasis to involve
most body areas or it may be a response
to treatment as a generalized Koebner
reaction
5-Pustular Psoriasis
• Several clinical variants of pustular
psoriasis exist:
ِ A-generalized Pustular Psoriasis (Von
Zumbusch Type)
B-annular Pustular Psoriasis
C-impetigo Herpetiformis
D-acrodermatitis Continua Of Hallopeau
A-Generalized pustular psoriasis
(von Zumbusch type)
• It is usually preceded by
other forms of the disease
• The disease occurs as
attacks characterized by
fever that lasts several days
and a sudden generalized
eruption of sterile pustules 2
to 3 mm in
diameter
• The pustules are disseminated over the
trunk and extremities, including the nail
beds, palms, and soles
• The pustules usually arise on highly
erythematous skin,
first as patches and
then becoming
confluent as the
disease becomes
more severe
• The erythema that surrounds the pustules
often spreads and becomes confluent,
leading to erythroderma
• Various provoking factors are known
including withdrawal of oral corticosteroids,
infections, and irritating topical treatment
B-Annular Pustular Psoriasis
• It is a rare variant of
pustular psoriasis
• Lesions may appear at
the onset of pustular
psoriasis, with a tendency
to spread and form
enlarged rings, or they
may develop during the
course of generalized
pustular psoriasis
• The characteristic
features are pustules on a
ring-like erythema
C-Impetigo Herpetiformis
• lesions are identical to annular pustular
psoriasis but occur during pregnancy
• Onset is usually early in
the third trimester and
persists until delivery
• It tends to develop earlier
in subsequent pregnancies
• It is often associated with hypocalcemia
• There is usually no personal or family history
of psoriasis
D-Acrodermatitis Continua
of Hallopeau
• It is rare
• sterile, pustular eruption of the
fingers or toes slowly extends
proximally
• Continuous pustulation leads
to nail destruction and atrophy
of the distal phalanx
• It may be associated with generalized
pustular psoriasis of the Zumbusch type
6-Sebopsoriasis
• It is a common clinical entity
• It presents with erythematous plaques with
greasy scales localized to seborrheic
areas (scalp, glabella, nasolabial folds,
perioral and presternal areas, and
intertriginous areas)
• In the absence of typical findings of
psoriasis elsewhere, distinction from
seborrheic dermatitis is difficult
• It may represent a modification of
seborrheic dermatitis by the genetic
background of psoriasis
7- Napkin psoriasis
• Usually begins between the
ages of 3 and 6 months
• First appears in the napkin
areas as a confluent red
area with appearance a few
days later of small red
papules on the trunk that
may also involve the limbs
• These papules have the
typical white scales of
psoriasis
Related Physical Findings
1- NAIL CHANGES IN PSORIASIS
• Found in up to 40 percent of patients
• Nail pitting is the commonest feature
• Onycholysis:white
areas of the nail plate
due to separation of
the nail plate from its
underlying attachment
to the nail bed
• Subungual hyperkeratosis is due to
hyperkeratosis of the
nail bed
• Nail plate crumbling
• Beau’s lines:horizontal,
lines going across the nail
2-Geographic tongue
• Presents as asymptomatic erythematous
patches with serpiginous
borders, resembling a map
• The lesions have a migratory
character
• It has been postulated to be an oral variant of
psoriasis, as these lesions show several
histologic features of psoriasis. However,
geographic tongue is a relatively common
condition and is seen in many nonpsoriatic
individuals
3-Psoriatic Arthritis
• Develops in approximately 10-15 % of
those with psoriasis
• In approximately 50% of those affected
arthritis appears one decade after the
onset of psoriasis, whereas in the
remainder the onset occurs with the
disease or precedes it
The most distinctive features of psoriatic
arthritis are
• Distal interphalangeal joint arthritis
• Dactylitis
• Enthesitis(inflammation of the insertion
points of tendons and joints into bone)
• Periosteal new bone formation
• Asymmetric
oligoarthritis&
spondylitis
•The blue arrow = a normal joint space
• Red arrow = “cup and saucer” effect of the
fourth metatarsal bone being jammed into the
base of the fourth toe
•The yellow circle = “Pencil
appearance”destruction characteristic of the
disease
Modifying Factors
• Obesity :Obese individuals are more likely to
present with severe psoriasis
• Smoking:(<20 cig./day) associated with more
than a twofold increased risk of severe psoriasis
• Infection: Streptococcal throat infection and
guttate psoriasis have been linked
• Drugs: Antimalarials, β blockers, lithium, NSAID,
imiquimod, angiotensin-converting enzyme
inhibitors: Exacerbate psoriasis
Prognosis
• Chronic plaque psoriasis is in most cases
a lifelong disease, manifesting at
unpredictable intervals. Spontaneous
remissions, lasting for variable periods of
time, may occur in the course of psoriasis
in up to 50 % of patients. The duration of
remission ranges from 1 year to several
decades
• Guttate psoriasis is often a self-limited disease,
lasting from 12 to 16 weeks without treatment. It
has been estimated that one-third to two-thirds
of these patients later develop the chronic
plaque type
• Erythrodermic and generalized pustular
psoriasis have a poorer prognosis, with
the disease tending to be severe and
persistent
PASI Score
(Psoriasis Area and Severity Index)
• It is a method to estimate severity of
psoriasis in order to evaluate the clinical
efficacy of new treatments
• Psoriatic plaques are graded based on three
criteria: redness (R), thickness (T), and
scaliness (S)
• Severity is rated on a 0-4 scale (0 for no
involvement up to 4 for severe involvement)
• The highest PASI score is 72; the lowest is 0
Histopathology
• Dilated vessels in
dermal papillae,
perivascular
cuffing with
lymphocytes
• Parakeratosis
• Orthokeratosis of
normal basketweave type
• Loss of granular
layer
• Munro microabscesses i.e.
collections of
neutrophils in the
horny layer
• Spongiform pustule
of Kogoj: An
infiltration of
neutrophils into
necrotic Malpighian
layer in which the
cell walls persist as
a spongelike
network
• Commonly seen in
pustular psoriasis
• Test tube-like elongation of rete ridges
• Relatively thin suprapapillary plates
Treatment
• Topical
• Phototherapy
• Systemic
I-TOPICAL THERAPY
1-Topical corticosteroids
• They are commonly first-line therapy in
mild to moderate psoriasis and in sites
such as the flexures and genitalia, where
other topical treatments can induce
irritation
• Improvement is usually achieved within 2
to 4 weeks, then maintenance is achieved
by use in the weekends only
• Topical steroids can be classiefied as:
BRAND NAME
GENERIC NAME
CLASS 1 - Superpotent
Dermovate
Clobetasol propionate
Eumovate
Clobetasol butyrate
CLASS 2 - Potent
Betnovate, Betaval, Betaderm
Betamethasone valerate
Diprosone
Betamethasone dipropionate
Elocon
Mometasone furoate
Cutivate
Fluticasone propionate
Topsyn
Fluocinonide
Nericid
Diflucortalone valerate
Topicort
Triamcinolone acetonide
Synalar
Fluocinolone acetonide
CLASS 3 - Mid-Strength
Dermatop
Prednicarbate
Hydrocortisone
Hydrocortisone
Perderm
Alclometasone dipropionate
• Topical steroids under occlusion do have a
limited place in the management of
recalcitrant psoriasis of the scalp, hands,
feet and other areas
• Potent preparations are likely to be
needed on the scalp and knuckles
particularly
• Conversely, the flexures and inner thighs
need much weaker products to avoid
striae
• Tachyphylaxis (decrease in efficacy with
time) of topical steroids in psoriasis is wellestablished
• Long-term topical corticosteroids may cause
striae and adrenal suppression
• Intensive treatment
with the most potent
preparations can
induce generalized pustular psoriasis
• Because of these side effects potent topical
steroids e.g. clobetasol may be used on
alternate day basis
• To avoid systemic effects of class I
glucocorticoid, a maximum of 50 g
ointment may be used per week
• For small plaques (< 4cm), triamcinolone
acetonide aqueous suspension 10 mg/mL
diluted with normal saline is injected into
the lesion
2- Vitamin D Analogues
Calcipotriene (calcipotriol)”Betdaivonex”
• Potent topical corticosteroids are superior
to calcipotriene. But calcipotriene was
more effective than coal tar or anthralin
• The efficacy of calcipotriene is not reduced
with long-term treatment
• Calcipotriene is applied twice daily
• Salicylic acid inactivates calcipotriene
• Hypercalcemia is the only major concern
• When the amount used does not exceed
the recommended 100 g/week,
calcipotriene can be used with a great
margin of safety
• It is often used in combination with or in
rotation with topical corticosteroids in an
effort to maximize therapeutic
effectiveness while minimizing steroidrelated skin atrophy
• Other vitamin D analogues are tacalcitol
and maxacalcitol
• In view of their efficacy, cosmetic
acceptability and relative safety, they may
accepted as first-choice therapies in the
topical treatment of mild to moderate
psoriasis, although cost may be a
problem
3-Coal Tar
• The use of tar to treat skin diseases dates
back nearly 2000 years
• Tar is the dry distillation product of organic
matter heated in the absence of oxygen
• In 1925, Goeckerman introduced “The
Goekerman technique” which uses crude
coal tar and UV light for the treatment of
psoriasis
• Coal tar, in concentrations 5- 20% can be
compounded in creams, ointments, shampoos
and and pastes
• It is often combined with salicylic acid (2-5% ),
which by its keratolytic action leads to better
absorption of the coal tar
• Disadvantages include: allergic reactions,
folliculitis, it has an unwelcome smell and
appearance and can stain clothing and other
items. Coal tar is carcinogenic
4- Tazarotene(zar, Zarotex)
• It is a third-generation retinoid
• It reduces mainly scaling and plaque
thickness, with limited effectiveness on
erythema
• It is available in 0.05 percent and 0.1 %
gels, and a cream
• When used as a monotherapy, a
significant proportion of patients develop
local irritation(especially with the 1%
formulations)
• Efficacy can be enhanced by combination
with mid- to high-potency steroids or UVB
phototherapy but it has been
recommended that UV doses be reduced
by at least one-third if tazarotene is added
in the middle of a course of phototherapy
5-Topical Calcineurin Inhibitors
(Tacrolimus”Tarolimus” &
Pimecrolimus ”Elidel” )
• They inhibit calcineurin, thus blocking both
T-lymphocyte signal transduction and IL-2
transcription
• They are not effective in plaque psoriasis.
However, for treatment of inverse and
facial psoriasis, these agents appear to
provide effective treatment
• The main side effect of these medications
is a burning sensation at application site
• Anecdotal reports of lymph node or skin
malignancy require further evaluation in
controlled studies, and these drugs have a
U.S. Food and Drug Administration (FDA)
“black box warning”
6-Dithranol(Dithranol)
• It is a naturally occurring substance found
in the bark of the araroba tree in South
America
• It is made up in a cream, ointment, or
paste
• It is mainly used on plaques resistant to
other therapies
• It can be combined with UVB phototherapy
with good results using the Ingram
regimen
• Classic anthralin therapy starts with low
concentrations (0.05 to 0.1 percent)
incorporated in petrolatum or zinc paste
combined with salicylic acid 1% and given
once daily. The concentration is increased
weekly in individually adjusted increments
up to 4 percent until the lesions resolve
• Most common side effects are irritant
contact dermatitis and staining of clothing,
skin, hair, and nails
7-Emollients
• Between treatment periods, skin care with
emollients should be performed to avoid
dryness
• Emollients reduce scaling, may limit painful
fissuring, and can help control pruritus
• They are best applied immediately after
bathing or showering
• The use emollients in combination with
topical treatments improves hydration while
minimizing treatment costs
II-PHOTOTHERAPY
Determination of the minimal
erythema dose (MED)
1-The patient wears a
thick cotton shirt which
has 10 small, vertical
holes on its back
2-The patient is
exposed to 50 mj of UV
on the back while all
the holes are opened
3-The first hole is closed and another exposure is
given By that time the skin under the first hole was
exposed to 50 mj of UV while the skin under the
second hole was exposed to 100 mj
4-The second hole is closed and the procedure is
repeated in the same way (closing an hole and
giving a dose) for all the holes
5-After 24-72 hours the skin of the back is examined
and the first skin area showing well-defined
erythema is determined and the amount of UV
causing it is called "the minimal erythema dose"
Dosing
NB-UVB
•Initial dose at
50% of MED
followed by 3
treatments /w
•Lubricate before
ttt
•Increase dose
by at least 10-20%
of the MED
PUVA
Excimer laser
•Initial dose 0.5-2.0
•2-6 MED twice
J/cm2, depending on weekly
skin type followed by
twice weekly
•Increase dose by
40% per week until
erythema, then
maximum 20% per
week until a
maximum of 15 J/cm2
•NB-UVB=Narrow-band Ultraviolet B (Wave length 310-331 nm)
•PUVA=Psoralen +ultraviolet A (Wave length 315–380 nm)
• Excimer laser (Wave length 308 nm)
Efficacy
NB-UVB
PUVA
Excimer laser
> 70%
improvement
study after 4 wk
of treatment
Induces
remission in
70%-90% of
patients
75%
improvement in
72% of patients
in an average of
6.2 treatments
Side Effects
NB-UVB
PUVA
•Photodamage Similar to NBUVB but the
•Polymorphic
risk is higher
light eruption
•Increased risk
of skin aging
and skin cancer
Excimer laser
Erythema,
blisters,
hyperpigmentati
on, and
erosions
Contraindications
NB-UVB
Absolute:
Photosensitivity
disorders
Relative:
Photosensitizing
drugs, melanoma,
and
nonmelanoma
skin cancers
PUVA
Absolute:
Light-sensitizing
disorder,
lactation,
melanoma
Relative:
Age < 10 yr,
pregnancy,
photosensitizing
drugs, nonmelanoma skin
cancers
Excimer laser
As NB-UVB
Devices used
III-SYSTEMIC THERAPY
• CYCLOSPORIN A: Neoral 100mg/ml
Suspension & 100 mg capsules
• METHOTREXATE: Methotrexate 2.5 mg
tab & 50 mg/lm vial
• ACITRETIN: Acitretin 25 mg cap
Mechanism of action
Cyclosporin A
Methotrexate
Acitretin
Binds cyclophilin producing
a complex that
blocks calcineurin, reducing
the effect of the
NF-AT in T
cells, resulting
in inhibition of
interleukin 2
Blocks dihydrofolate reductase
leading to inhibition of purine
and pyrimidine
synthesis. Also
blocks AICAR
transformylase,
leading to accumulation of antiinflammatory
adenosine
Binds to retinoic
acid receptors.
May contribute
to improvement
by normalizing
keratinization
and proliferation
of the epidermis
Dosing
Cyclosporin A
High-dose method:
5 mg/kg daily, then
tapered
Low-dose method:
2.5 mg/kg daily,
increased every 24 wk up to 5 mg/kg
daily, then tapered
Methotrexate
Start with a test
dose of 2.5 mg
and then
gradually
increase dose
until a therapeutic
level is achieved
(average range,
10-15 mg weekly;
maximum, 25-30
mg weekly
Acitretin
Initiate at 2550 mg daily
and escalate
and titrate to
response
Efficacy
Cyclosporin A
Up to 90% of
patients achieve
clearance or
marked
improvement
Methotrexate
May reduce the
severity of
psoriasis by at
least 50% in
more than 75%
of patients
Acitretin
Modestly
effective as
monotherapy
Side effects
Cyclosporin A
•Nephrotoxicity
•Hypertension
•Immunosuppression
•Neurotoxicity
•Increased risk
of malignancy
Methotrexate
Acitretin
•Chronic use
may lead to
hepatic fibrosis
•Fetal abnormalities or death
•Myelosuppression
•Pulmonary
fibrosis
•Hepatotoxicity
•Lipid
abnormalities
•Fetal abnormalities or death
•Alopecia,
mucocutaneous
toxicity
•Hyperostosis
Monitoring
Cyclosporin A
•BP
•Baseline CBC
•CMP, Mg, uric
acid, lipids,
urinalysis
Repeat tests
every 2-4 wk,
then every
month along
with BP
Methotrexate
Acitretin
•Baseline CBC,
CMP, LFTs
Repeat baseline
tests weekly
during dose
escalation, then
every 2 wk. Hold if
WBC ≤ 4.0 ×109/L,
platelet count is <
125 × 109/L, or Hg
< 110 g/L
•Baseline CBC
and CMP
Repeat
laboratory tests
weekly × 6 wk,
then every 2
wk × 2 mo, and
then monthly.
Monitor BP
Contraindications
Cyclosporin A
Absolute:
•Prior bone
marrow
depression
•Pregnancy
•Lactation
Relative:
Renal
abnormalities
Methotrexate
Absolute:
•Inherited
deficiency of
thiopurine
methyltransferase
enzyme due to
increased risk of
myelosuppression
• Liver toxicity
• Pregnancy
Acitretin
Absolute:
•Severe
infections
•Malignancy
Use in Pregnancy
Cyclosporin A
C category
Methotrexate
D category
Acitretin
X category
Studies on animals
revealed teratogenic
or embryocidal
effects and there
are no controlled
studies in women
It should be given
only if the potential
benefit justifies the
potential risk to the
fetus
There is positive
evidence of human
fetal risk, but the
benefits from use in
pregnant women
may be acceptable
despite the risk
(e.g., if the drug is
needed in a lifethreatening
situation)
The drug is
contraindicated in
women who are
or may become
pregnant
REMARKS
CYCLOSPORIN A
• Because the nephrotoxic effects of CsA are
largely irreversible, CsA treatment should be
discontinued if kidney dysfunction and/or
hypertension occur. CsA-induced hypertension
may be treated with calcium antagonists such as
nifedipine
• The most common adverse effects noted in
patients using CsA for short periods of time are
neurologic, including tremors, headache,
paresthesia, and/or hyperesthesia
• Long-term treatment of psoriasis with low-dose
CsA was found to increase risk of nonmelanoma skin cancers
METHOTREXATE
• concomitant administration of folic acid (1
to 5 mg/day) reduces certain side effects,
such as nausea and megaloblastic
anemia, without diminishing the efficacy of
antipsoriatic treatment
• The very long half-life of MTX may
account for its efficacy after weekly
administration and may also help to
explain why its onset of action is rather
slow (therapeutic effects usually require 4
to 8 weeks to become evident)
• In the most recent guidelines, patients with
normal liver function tests and without a
history of liver disease or alcoholism are
not asked to undergo liver biopsy until they
have been treated with a cumulative MTX
dose of 1.0 to 1.5 g. Repeat biopsies are
done approximately 1.0 to 1.5 g thereafter
if liver function test and biopsy findings are
normal
• Some groups have recommended the use
of amino terminal type III procollagen
peptide (PIIINP) assay for screening of
liver fibrosis
• But the FDA has not yet approved the use
of this assay for diagnostic use within the
United States
Another well-known side effect of MTX is
myelosuppression, especially pancytopenia,
which usually occurs in the setting of folate
deficiency. Leucovorin calcium (folinic acid) is
the only antidote for the hematologic toxicity of
MTX. When an overdose is suspected, an
immediate leucovorin dose of 20 mg should
be given parenterally or orally, and
subsequent doses should be given every 6
hours.
• Several classes of drugs, including
nonsteroidal anti-inflammatory drugs and
sulfonamides, may interact with MTX to
increase toxicity
• MTX is renally excreted and should
therefore not be administered to patients
with impairment in renal function, as MTX
side effects are generally dose-related
ACITRETIN
• The clinical forms most responsive to
acitretin as monotherapy include
generalized pustular and erythrodermic
psoriasis
• Acitretin induces clearance of psoriasis in a
dose-dependent fashion. Overall, higher
starting doses (i.e., ≥50 mg/day) appeared
to clear psoriasis faster but adverse effects
occur more frequently
• Most patients relapse within 2 months
after discontinuing acitretin
• Acitretin should be discontinued if liver
dysfunction, hyperlipidemia, or diffuse
idiopathic hyperostosis develops
Uncommonly used
Systemic drugs
1- Sulfasalazine
• After 8 weeks of treatment 41 % of the
patients had marked improvement, 41 %
had moderate, and 18 % had minimal
improvement
• Dose:1 gm 4 times/day orally
2-Mycophenolate mofetil
• It inhibits T and B lymphocytes
proliferation, thereby suppressing cellmediated immune responses and antibody
formation
• The drug is usually well tolerated with few
side effects
• In a dose between 2 to 3 g daily, a 47 %
improvement was achieved in 12 weeks
IV-BIOLOGIC THERAPY
(Biologics)
• They are proteins produced by living
organisms to block specific molecular
steps important in the pathogenesis of
psoriasis
• Currently available biologics for psoriasis
target either the T cells or block the
inflammatory action of TNF-α.
When to use biologics?
I. Severe disease is defined as PASI
score of 10 or more or a BSA of 10% or
greater or life threatening disease such
as erythrodermic or pustular psoriasis
II. Disease should have been severe for
6 months; resistant to treatment
III.Patients fulfill at least one of following
clinical categories:
1. Have developed or are at higher than
average risk of developing clinically
important drug related toxicity
2. Are unresponsive, to or cannot receive
standard systemic therapy
3. Have disease that requires repeated
inpatient management for control.
4. Have psoriatic arthritis
• some tests that should be done before
starting treatment with biologics:
• Liver function tests
• CBC including platelet count
• A hepatitis panel
• TB testing
Mechanism of action
Alefacept
Efalizumab
Etanercept
Infliximab
Adalimumab
Binds CD2
on T cells,
blocking the
CD2-LFA3
interaction,
thus
interfering
with T-cell
activation
and causing
T-cell
apoptosis
Blocks the
interaction of
LFA-1 with
intercellular
adhesion
molecule-1.
Inhibits T-cell
activation,
trafficking,
and adhesion
to keratinocytes
Human
recombinant,
soluble TNFα receptor.
Binds TNF-α
and
neutralizes its
activity
Chimeric
monoclonal
antibody that
has high
specificity,
affinity, and
avidity for
TNF-α
Fully human
recombinant
monoclonal
antibody that
specifically
targets TNFα
Dosing
Alefacept
Efalizumab
Etanercept
Infliximab
Adalimumab
15 mg IM
once weekly
for 12 weeks
Subcut.
injections.
Conditioning:
0.7 mg/kg.
Maintenance:
1 mg/kg
weekly
25- to 50-mg
injections
subcutaneously twice
weekly
Intravenous
infusions
over 2 h. 510 mg/kg at
weeks 0, 2,
and 6
40-mg
injections
subcutaneously every
other week
Efficacy
Alefacept
Efalizumab
Etanercept
Infliximab
Adalimumab
21% of
patients
achieved a
PASI-75 at
wk 14.
27% of
patients
achieve a
PASI-75 at
12 wk
49% of
patients
given 50 mg
twice/wk
achieved a
PASI-75 at
12 wk
80% of
patients
achieved a
PASI-75 at
wk 10
80% of
patients
achieve
PASI-75 at
12 wk.
PASI-75=75% reduction in PASI scores over treatment
period
Remission duration
Alefacept
Efalizumab
Etanercept
Infliximab
Adalimumab
Average
8 months
about 2
months
Variable and
dose-related
ranging from
70-90 days
highly
variable
between
individuals
and may
depend on
the
initial dose
given
Unknown
Side effects
Alefacept
Efalizumab
Etanercept
Infliximab
Adalimumab
1.Lymphopenia
2.Malignancy
3.Serious
infections
4.Not
recommended for HIV
patients
1.Thrombocytopenia
2.Exacerbation of
psoriasis
3.Serious
infections
1.Pancytopenia
2.Exacerbation of MS
3.Serious
infections
4.Malignancy
5.Worsening
of congestive
heart failure
6.Lupus-like
symptoms
7. Live vaccines should
not be given
1.Infusionrelated
reactions
2.Exacerbation of MS
3.Infections
4,5,6,7 as
Etanercept
1.Cytopenias
2.Injection
site reactions
3.Infections
4,5,6,7 as
Etanercept
Monitoring&Long-term use
Alefacept
Efalizumab
Etanercept
Infliximab
Adalimumab
CD4+ T-cell
counts every
2 wk during
treatment
Regular
platelet
counts
Baseline PPD
Baseline
PPD
Baseline
PPD
Up to nine
courses have
been
administered
over 4-5 yr in
small number
of patients
with
incremental
benefits
PASI responses
continue to
increase to
wk 24 and
maintained in
patients
receiving
long-term
continuous
therapy (up
to 24 mo).
PASI response continues
to increase to
wk 24. Large
databases in
patients with
other
immunologic
diseases
indicate safety
Large
databases
in patients
with other
immunologic
diseases
indicate
relative
safety
Expected to
be similar to
other TNF-α
inhibitors
Use in Pregnancy
Alefacept
Efalizumab
Etanercept
Ctegory B
Animalreproduction
studies have
not demonstrated a
fetal risk but
there are no
controlled
studies in
pregnant
Ctegory C
Ctegory B
Studies on
animals
revealed
teratogenic or
embryocidal
effects and
there are no
controlled
studies in
women
Infliximab
Adalimumab
Ctegory B
Ctegory B
How Supplied
Alefacept
Efalizumab
Etanercept
Infliximab
Adalimumab
AMEVIVE®
vial contains
15 mg
lyophilized
powder
alefacept that
yields 0.5 mL
of reconstituted solution
RAPTIVA®
vial contains
lyophilized
powder that
yields 100
mg/mL of
efalizumab of
reconstituted
solution
ENBREL®
prefilled
syringes
available in
25 & 50 mg
strengths
REMICADE ®
vial contains
100 mg
lyophilized
powder
infliximab
HUMIRA ®
prefilled
syringe that
delivers 40
mg of
Adalimumab
Cost/year
$18,735
Cost/year
$21,385
Cost/year
$17,160
Cost/year
$26,320
Cost/year
$20,186
REMARKS
• Alefacept was the first biological agent
approved by
the FDA in January 2003 for the treatment
of patients with moderate to severe
chronic plaque psoriasis
• Efalizumab currently, is the only biological
agent approved for continuous
administration and can be selfadministered as weekly subcutaneous
injections
• Etanercept:The current license
recommends intermittent courses no
longer than 24 week
• Infliximab: once significant disease relapse
has occurred, repeat infusions do not
achieve the same rate of disease
clearance as that seen on the initial three
dose induction treatment
Choice of agent to use
• Etanercept should be considered the first
choice for patients with significant
uncontrolled psoriatic arthritis
• Infliximab is useful in clinical circumstances
requiring rapid disease control e.g. in
unstable erythrodermic orpustular psoriasis
due to it very rapid onset of action and high
response rate
• Efalizumab should be considered the first
choice for patients with a high risk of latent
TB or with evidence of demyelinating disease
Treatment of certain
sites
Scalp
• Mild (no thick plaques)
Tar or ketoconazole shampoos followed by
betamethasone valerate, 1% lotion; if
refractory, clobetasol propionate, 0.05%
scalp application
• Severe (Thick, adherent plaques):
Removal of scales from plaques before
active treatment by 10% salicylic acid in
mineral oil, covered with a plastic cap and
left on overnight.
• After shedding of scales, fluocinolone
cream or lotion with the scalp covered with
plastic or a shower cap, left on overnight
or for 6 h. When the thickness of the
plaques is reduced, clobetasol propionate,
0.05% lotion, can be used for
maintenance. If unsuccessful or rapid
recurrence or if associated with
generalized psoriasis, consider systemic
treatment
Nails
• Injection of the nail fold with intradermal
triamcinolone acetonide (3 mg/mL) is effective
but painful and impractical when all nails are
involved
• PUVA is somewhat effective when administered
in special hand-and-foot lighting units providing
high-intensity UVA
• Long-term systemic retinoids (acitretin, 0.5
mg/kg) are also effective, as are systemic MTX
Inverse psoriasis
• Initiate therapy with topical steroids but as
these are atrophy-prone regions, steroids
should be applied for only limited periods
of time;then switch to topical vitamin D
derivatives or tazarotene or topical
tacrolimus or pimecrolimus. If resistant or
recurrent, consider systemic therapy
Guttate Psoriasis
• Treat streptococcal infection with
antibiotics.
• Narrow-band UVB irradiation is the most
effective. If it fails, try PUVA
Generalized Pustular Psoriasis
• Patients should be hospitalized and treated
in the same manner as patients with
extensive burns
• Rapid suppression and resolution of lesions
is achieved by oral retinoids (acitretin, 50
mg/d). Supportive measures should include
fluid intake, IV antibiotics to prevent
septicemia, cardiac support, temperature
control, topical lubricants, and antiseptic
baths
• Systemic steroids to be used only as rescue
intervention as rapid tachyphylaxis occurs
Psoriatic Arthritis
• MTX, once-a-week schedule as outlined
above
• Infliximab or etanercept are highly
effective