Introduction to Psoriasis

Denise Cook, M.D.

Medical Officer
Division of Dermatology and Dental
Drug Products
Dermatologic and Ophthalmic Drugs Advisory Committee
July 12, 2004

Introduction to Psoriasis

Prevalence
Genetics and Pathogenesis
Clinical Variants of Psoriasis
State of the Armamentarium

Dermatologic and Ophthalmic Drugs Advisory Committee

July 12, 2004

Prevalence
Psoriasis occurs in 2% of the worlds
population
Prevalence in the U.S may be as high
as 4.6%
Highest in Caucasians
In Africans, African Americans and
Asians between 0.4% and 0.7%
Dermatologic and Ophthalmic Drugs Advisory Committee
July 12, 2004

Prevalence
Equal frequency in males and
females
May occur at any age from infancy to
the 10th decade of life
First signs of psoriasis
Females mean age of 27 years
Males mean age of 29 years
Dermatologic and Ophthalmic Drugs Advisory Committee
July 12, 2004

Prevalence
Two Peaks of Occurrence
One at 20-30 years
One at 50-60 years
Psoriasis in children
Low between 0.5 and 1.1% in
children 16 years old and younger
Mean age of onset - between 8 and
12.5 years
Dermatologic and Ophthalmic Drugs Advisory Committee
July 12, 2004

Prevalence
Two-thirds of patients have mild disease
One-third have moderate to severe disease
Early onset (prior to age 15)
Associated with more severe disease
More likely to have a positive family history
Life-long disease
Remitting and relapsing unpredictably
Spontaneous remissions of up to 5 years have
been reported in approximately 5% of patients

Dermatologic and Ophthalmic Drugs Advisory Committee

July 12, 2004

Genetics and Pathogenesis

Psoriasis and the Immune System
The major histocompatibility complex
(MHC)
Short arm of chromosome 6
Histocompatibility Antigens (HLA)
HLA-Cw6
HLA-B13, -B17, -B37, -Bw16
T-lymphocyte-mediated mechanism

Dermatologic and Ophthalmic Drugs Advisory Committee

July 12, 2004

Psoriasis as a Systemic Disease

Koebner Phenomenon
Elevated ESR
Increased uric acid levels gout
Mild anemia
Elevated 2-macroglobulin
Elevated IgA levels
Increased quantities of Immune
Complexes
Dermatologic and Ophthalmic Drugs Advisory Committee
July 12, 2004

Psoriasis as a Systemic Disease

Psoriatic arthropathy
Aggravation of psoriasis by systemic
factors
Medication
Focal infections
Stress
Life-threatening forms of psoriasis
Dermatologic and Ophthalmic Drugs Advisory Committee
July 12, 2004

Clinical Variants of Psoriasis

Dermatologic and Ophthalmic Drugs Advisory Committee

July 12, 2004

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Characteristic Lesion of Psoriasis

Sharply demarcated erythematous
plaque with micaceous silvery white
scale
Histopathology
Thickening of the epidermis
Tortuous and dilated blood vessels
Inflammatory infiltrate primarily of
lymphocytes
Dermatologic and Ophthalmic Drugs Advisory Committee
July 12, 2004

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Psoriatic Plaque

Dermatologic and Ophthalmic Drugs Advisory Committee

July 12, 2004

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Severity of Disease
Three Cardinal Signs of Psoriatic
Lesions
Plaque elevation
Erythema
Scale
Body Surface Area

Dermatologic and Ophthalmic Drugs Advisory Committee

July 12, 2004

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Chronic Plaque Psoriasis

Most Common Variant

Plaques may be as large as 20 cm
Symmetrical disease
Sites of Predilection
Elbows
Knees
Presacrum
Scalp
Hands and Feet
Dermatologic and Ophthalmic Drugs Advisory Committee
July 12, 2004

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Chronic Plaque Psoriasis

Dermatologic and Ophthalmic Drugs Advisory Committee

July 12, 2004

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Chronic Plaque Psoriasis

Dermatologic and Ophthalmic Drugs Advisory Committee

July 12, 2004

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Chronic Plaque Psoriasis

May be widespread up to 90% BSA
Genitalia involved in up to 30% of patients
Most patients have nail changes
Nail pitting
Oil Spots
Involvement of the entire nail bed
Onychodystrophy
Loss of nail plate

Dermatologic and Ophthalmic Drugs Advisory Committee

July 12, 2004

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Widespread Chronic Plaque

Psoriasis

Dermatologic and Ophthalmic Drugs Advisory Committee

July 12, 2004

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Chronic Psoriasis

Dermatologic and Ophthalmic Drugs Advisory Committee

July 12, 2004

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Psoriasis of the Nail

Dermatologic and Ophthalmic Drugs Advisory Committee

July 12, 2004

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Psoriasis of the Nail

Dermatologic and Ophthalmic Drugs Advisory Committee

July 12, 2004

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Symptoms of Chronic Plaque

Psoriasis

Pruritus
Pain
Excessive heat loss
Patient Complaints
Unsightliness of the lesions
Low self-esteem
Feelings of being socially outcast
Excessive scale
Dermatologic and Ophthalmic Drugs Advisory Committee
July 12, 2004

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Guttate Psoriasis
Characterized by numerous 0.5 to 1.5
cm papules and plaques
Early age of onset
Most common form in children
Streptococcal throat infection often a
trigger
Spontaneous remissions in children
Often chronic in adults
Dermatologic and Ophthalmic Drugs Advisory Committee
July 12, 2004

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Guttate Psoriasis

Dermatologic and Ophthalmic Drugs Advisory Committee

July 12, 2004

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LifeThreatening Forms of
Psoriasis
Generalized Pustular Psoriasis
Erythrodermic Psoriasis

Dermatologic and Ophthalmic Drugs Advisory Committee

July 12, 2004

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Generalized Pustular Psoriasis

Unusual manifestation of psoriasis
Can have a gradual or an acute onset
Characterized by waves of pustules on
erythematous skin often after short
episodes of fever of 39 to 40C
Weight loss
Muscle Weakness
Hypocalcemia
Leukocytosis
Elevated ESR
Dermatologic and Ophthalmic Drugs Advisory Committee
July 12, 2004

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Generalized Pustular Psoriasis

Cause is obscure
Triggering Factors
Infection
Pregnancy
Lithium
Hypocalcemia secondary to
hypoalbuminemia
Irritant contact dermatitis
Withdrawal of glucocorticosteroids,
primarily systemic
Dermatologic and Ophthalmic Drugs Advisory Committee
July 12, 2004

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Generalized Pustular Psoriasis

Dermatologic and Ophthalmic Drugs Advisory Committee

July 12, 2004

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Erythrodermic Psoriasis
Classic lesion is lost
Entire skin surface becomes
markedly erythematous with
desquamative scaling.
Often only clues to underlying
psoriasis are the nail changes and
usually facial sparing
Dermatologic and Ophthalmic Drugs Advisory Committee
July 12, 2004

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Erythrodermic Psoriasis
Triggering Factors
Systemic Infection
Withdrawal of high potency topical
or oral steroids
Withdrawal of Methotrexate
Phototoxicity
Irritant contact dermatitis
Dermatologic and Ophthalmic Drugs Advisory Committee
July 12, 2004

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Erythrodermic Psoriasis

Dermatologic and Ophthalmic Drugs Advisory Committee

July 12, 2004

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State of the Armamentarium

Wide range of therapies for the
treatment of moderate to severe
psoriasis
None induce a permanent remission
All have side effects that can place
limits on their use

Dermatologic and Ophthalmic Drugs Advisory Committee

July 12, 2004

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State of the Armamentarium

Therapies
Topical Corticosteroids
Topical Vitamin D3 Analogues
Topical Retinoids
Photo(chemo)therapy
Systemic Therapies
Oral
Parenteral
Dermatologic and Ophthalmic Drugs Advisory Committee
July 12, 2004

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Topical Corticosteroids
High potency and Super potent topical
steroids
These include
Fluocinonide family (cream, ointment,
gel)
Betamethasone dipropionate cream
Clobetasol propionate family (cream,
ointment, gel, foam, lotion)
Diflorasone diacetate ointment
Betamethasone dipropionate ointment
Dermatologic and Ophthalmic Drugs Advisory Committee
July 12, 2004

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Topical Corticosteroids
Side effects associated with use
Skin atrophy
Burning and stinging
Suppression of the hypothalamicpituitary-adrenal (HPA) axis
This may occur after 2 weeks of
use with certain topical
corticosteroids
Dermatologic and Ophthalmic Drugs Advisory Committee
July 12, 2004

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Topical Vitamin D3 Analogues

Prototype for this group is
calcipotriene
3 formulations cream, ointment,
and scalp solution
Former two are approved for plaque
psoriasis
Latter for moderate to severe
psoriasis of the scalp
Dermatologic and Ophthalmic Drugs Advisory Committee
July 12, 2004

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Topical Vitamin D3 Analogues

Side Effects
Cutaneous
Burning
Stinging
Pruritus
Skin irritation
Tingling of the skin
Dermatologic and Ophthalmic Drugs Advisory Committee
July 12, 2004

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Topical Retinoids
Tazarotene Gel and Cream
Available in two strengths
0.05% and 0.1%
Side Effects
Pruritus
Burning/Stinging
Erythema
Worsening of psoriasis
Irritation
Skin pain
Hypertriglyceridemia
Dermatologic and Ophthalmic Drugs Advisory Committee
July 12, 2004

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Topical Tazarotene
Additional Indications
0.1% gel - approved for the treatment of
facial acne vulgaris of mild to moderate
severity
0.1% cream approved as an adjunctive
agent for use in the mitigation of facial
fine wrinkling, facial mottled hyper- and
hypopigmentation, and benign facial
lentigines in patients who use
comprehensive skin care and sunlight
avoidance programs
Dermatologic and Ophthalmic Drugs Advisory Committee
July 12, 2004

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Topical Tazarotene (cont)

Both products are pregnancy category X
Are contraindicated in women who are or
may become pregnant
Requirements before and during therapy
A negative pregnancy test 2 weeks prior
Therapy initiated during a normal
menses
Women of childbearing potential should
use adequate birth control
Dermatologic and Ophthalmic Drugs Advisory Committee
July 12, 2004

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Photo(chemo)therapy
Two types of phototherapy
Ultraviolet B (UVB)
Ultraviolet A + psoralen (PUVA)

Dermatologic and Ophthalmic Drugs Advisory Committee

July 12, 2004

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UVB
Two types
Broadband UVB
Narrowband UVB (311-313 nm)
Treatment is time consuming
2-3 visits/week for several months
Side effect possibility of
experiencing an acute sunburn
reaction
Dermatologic and Ophthalmic Drugs Advisory Committee
July 12, 2004

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PUVA
Consists of ingestion of or topical treatment with
a psoralen followed by UVA
Usually reserved for severe, recalcitrant,
disabling psoriasis
Time consuming 2-3 visits/wk; at least 6 weeks
Precautions
Patients must be protected from further UV
light for 24 hours post treatment
With oral psoralen, wrap around UV-blocking
glasses must be worn for 24 hours post
treatment
Dermatologic and Ophthalmic Drugs Advisory Committee
July 12, 2004

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PUVA
Side effects with oral psoralen
Nausea
Dizziness
Headache
Side effects with PUVA
Early
Pruritus
Late
Skin damage
Increased risk for skin cancer, particularly
squamous cell (SCC) and after 200 - 250
treatments, increased risk for melanoma
Dermatologic and Ophthalmic Drugs Advisory Committee
July 12, 2004

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Contraindications to PUVA
Patients less than 12 years of age
Patients with a history of light
sensitive disease states
Patients with, or with a history of
melanoma
Patients with invasive SCC
Patients with aphakia
Dermatologic and Ophthalmic Drugs Advisory Committee
July 12, 2004

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Systemic Therapies
Oral
Methotrexate
Neoral (cyclosporine)
Soriatane (acitretin)
Parenteral
Amevive (alefacept)
Raptiva (efalizimab)
Enbrel (etanercept)
Dermatologic and Ophthalmic Drugs Advisory Committee
July 12, 2004

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Methotrexate
Folic acid antagonist
Usually reserved for severe,
recalcitrant, disabling psoriasis
Maximum improvement can be
expected after 8 -12 weeks

Dermatologic and Ophthalmic Drugs Advisory Committee

July 12, 2004

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Contraindications - Methotrexate

Nursing mothers
Patients with alcoholism
Alcoholic liver disease
Other chronic liver disease
Patients with overt or laboratory evidence
of immunodeficiency syndromes
Patients who have preexisting blood
dyscrasias

Dermatologic and Ophthalmic Drugs Advisory Committee

July 12, 2004

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Methotrexate
Pregnancy Category X drug product
Contraindicated in pregnant women
with psoriasis
Pregnancy must be excluded in women
of childbearing potential
Pregnancy should be avoided if either
partner is receiving MTX during and for
a minimum of 3 months after therapy for
male patients and for at least one
ovulatory cycle after therapy for female
patients
Dermatologic and Ophthalmic Drugs Advisory Committee
July 12, 2004

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Methotrexate Side Effects

Acute or chronic hepatotoxicity

Hepatic cirrhosis
Leukopenia
Thrombocytopenia
Anemia, including aplastic anemia
Rarely, interstitial pneumonitis
Stomatitis
Nausea/vomiting
Alopecia
Photosensitivity
Burning of skin lesions
Dermatologic and Ophthalmic Drugs Advisory Committee
July 12, 2004

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Methotrexate
Multiple prescreening tests necessary
Recommendations for hepatic monitoring
Periodic LFTs including serum albumin
Liver biopsy
Pretherapy or shortly thereafter
Cumulative dose of 1.5 grams
After each additional 1.0 to 1.5 grams

Dermatologic and Ophthalmic Drugs Advisory Committee

July 12, 2004

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Neoral
Potent Immunosuppressive
Adult, non-immunocompromised
patients with severe, recalcitrant
plaque psoriasis
Maximum efficacy achieved at 16
weeks of therapy

Dermatologic and Ophthalmic Drugs Advisory Committee

July 12, 2004

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Contraindications - Neoral
Concomitant PUVA or UVB therapy
Methotrexate or other immunosuppressive
agents
Coal tar or radiation therapy
Patients with abnormal renal function
Patients with uncontrolled hypertension
Patients with malignancies
Nursing mothers

Dermatologic and Ophthalmic Drugs Advisory Committee

July 12, 2004

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Neoral Side Effects

Possibility of Irreversible renal damage

Hypertension
Headache
Hypertriglyceridemia
Hirsutism/hypertrichosis
Paresthesia/hyperesthesia
Influenza-like symptoms
Nausea/vomiting
Diarrhea
Lethargy
Arthralgia
Dermatologic and Ophthalmic Drugs Advisory Committee
July 12, 2004

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Neoral
Multiple prescreening tests are
required
Tests must continue throughout
treatment with dosage adjustment as
necessary to prevent end-organ
damage

Dermatologic and Ophthalmic Drugs Advisory Committee

July 12, 2004

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Soriatane
Oral retinoid approved for the
treatment of severe psoriasis in
adults
Significant improvement can be
achieved with 8 weeks of therapy

Dermatologic and Ophthalmic Drugs Advisory Committee

July 12, 2004

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Soriatane - Contraindications
Patients with severely impaired liver
or kidney function
Patients with chronic abnormally
elevated blood lipid values
Patients who are taking methotrexate
Ethanol use when on therapy and for
2 months following therapy in female
patients
Dermatologic and Ophthalmic Drugs Advisory Committee
July 12, 2004

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Soriatane
Pregnancy Category X drug product
as it is a human teratogen
Contraindicated in pregnant females
or those who intend to become
pregnant during therapy or any time
up to three years post therapy

Dermatologic and Ophthalmic Drugs Advisory Committee

July 12, 2004

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Soriatane Side Effects

Those associated with retinoid therapy
Cheilitis
Alopecia
Skin peeling
Dry skin
Pruritus
Rhinitis
Xeropthalmia
Arthralgia
Dermatologic and Ophthalmic Drugs Advisory Committee
July 12, 2004

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Soriatane Side Effects

Laboratory Abnormalities
Hypertriglyceridemia (66%)
Decreased HDL (40%)
Hypercholesterolemia (33%)
Elevated liver function tests (33%)
Elevated alkaline phosphatase (10-25%)
Hyperglycemia (10-25%)
Elevated CPK (10-25%)
Hepatitis and jaundice occurred in < 1% of
patients in clinical trials on Soriatane
Dermatologic and Ophthalmic Drugs Advisory Committee
July 12, 2004

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Soriatane
Multiple prescreening tests must be
obtained
Continued monitoring throughout
therapy necessary with possible
dosage adjustment

Dermatologic and Ophthalmic Drugs Advisory Committee

July 12, 2004

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Parenteral Therapy
Amevive
Immunosuppressive dimeric fusion
protein
Extracellular CD2-binding portion
of the human leukocyte function
antigen-3 (LFA-3)
Linked to the Fc portion of human
IgG1
Dermatologic and Ophthalmic Drugs Advisory Committee
July 12, 2004

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Amevive
Indicated for the treatment of adult
patients with moderate to severe
chronic plaque psoriasis
With 12 weeks of therapy, a disease
state of clear or almost clear was
achieved by 11% (via IV) and 14% (via
IM) of patients, respectively

Dermatologic and Ophthalmic Drugs Advisory Committee

July 12, 2004

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Amevive Side Effects

Dose dependent reduction in
circulating CD4+ and CD8+ T
lymphocytes
Should not be administered to
patients with low CD4+ counts
CD4+ counts must be monitored
before and weekly throughout
therapy
Dermatologic and Ophthalmic Drugs Advisory Committee
July 12, 2004

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Amevive Side Effects

Lymphopenia
Increase risk of malignancies
Skin cancer BCC and SCC
Lymphoma
Serious infections requiring
hospitalization
Risk of reactivation of chronic, latent
infections
Hypersensitivity reactions
Dermatologic and Ophthalmic Drugs Advisory Committee
July 12, 2004

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