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 (ICAM1) 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

Napkin psoriasis- 7
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

Beaus 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
appearancedestruction 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, 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

(TacrolimusTarolimus &
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 315380 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
Binds cyclophilin producing
a complex that
blocks calcineurin, reducing
the effect of the
NF-AT in T
cells, resulting
in inhibition of
interleukin 2

Methotrexate
Blocks dihydrofolate reductase
leading to inhibition of purine
and pyrimidine
synthesis. Also
blocks AICAR
transformylase,
leading to accumulation of antiinflammatory
adenosine

Acitretin
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

Methotrexate

Acitretin

Nephrotoxicity
Hypertension
Immunosuppression
Neurotoxicity
Increased risk
of malignancy

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

Methotrexate

Acitretin

BP
Baseline CBC
CMP, Mg, uric
acid, lipids,
urinalysis
Repeat tests
every 2-4 wk,
then every
month along
with BP

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 non-melanoma
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-.

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 TNF receptor.
Binds TNF-
and
neutralizes
its activity

Chimeric
monoclonal
antibody that
has high
specificity,
affinity, and
avidity for
TNF-

Fully human
recombinant
monoclonal
antibody that
specifically
targets TNF

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-
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 self-administered
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