Introduction to Psoriasis

1
Introduction to Psoriasis

• Denise Cook, M.D.
• Medical Officer
• Division of Dermatology and Dental Drug Products

2
Introduction to Psoriasis

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

3
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

4
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

5
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

6
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

7
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

8
Psoriasis as a Systemic Disease

• Koebner Phenomenon
• Elevated ESR
• Increased uric acid levels ? gout
• Mild anemia
• Elevated a2-macroglobulin
• Elevated IgA levels
• Increased quantities of Immune Complexes

9
Psoriasis as a Systemic Disease

• Psoriatic arthropathy
• Aggravation of psoriasis by systemic factors
• Medication
• Focal infections
• Stress
• Life-threatening forms of psoriasis

10
Clinical Variants of Psoriasis
11
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

12
Psoriatic Plaque
13
Severity of Disease

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

14
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

15
Chronic Plaque Psoriasis
16
Chronic Plaque Psoriasis
17
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

18
Widespread Chronic Plaque Psoriasis
19
Chronic Psoriasis
20
Psoriasis of the Nail
21
Psoriasis of the Nail
22
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

23
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

24
Guttate Psoriasis
25
LifeThreatening Forms of Psoriasis

• Generalized Pustular Psoriasis
• Erythrodermic Psoriasis

26
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

27
Generalized Pustular Psoriasis

• Cause is obscure
• Triggering Factors
• Infection
• Pregnancy
• Lithium
• Hypocalcemia secondary to hypoalbuminemia
• Irritant contact dermatitis
• Withdrawal of glucocorticosteroids, primarily
  systemic

28
Generalized Pustular Psoriasis
29
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

30
Erythrodermic Psoriasis

• Triggering Factors
• Systemic Infection
• Withdrawal of high potency topical or oral
  steroids
• Withdrawal of Methotrexate
• Phototoxicity
• Irritant contact dermatitis

31
Erythrodermic Psoriasis
32
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

33
State of the Armamentarium

• Therapies
• Topical Corticosteroids
• Topical Vitamin D3 Analogues
• Topical Retinoids
• Photo(chemo)therapy
• Systemic Therapies
• Oral
• Parenteral

34
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

35
Topical Corticosteroids

• Side effects associated with use
• Skin atrophy
• Burning and stinging
• Suppression of the hypothalamic-pituitary-adrenal
  (HPA) axis
• This may occur after 2 weeks of use with certain
  topical corticosteroids

36
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

37
Topical Vitamin D3 Analogues

• Side Effects
• Cutaneous
• Burning
• Stinging
• Pruritus
• Skin irritation
• Tingling of the skin

38
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

39
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

40
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

41
Photo(chemo)therapy

• Two types of phototherapy
• Ultraviolet B (UVB)
• Ultraviolet A psoralen (PUVA)

42
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

43
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

44
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

45
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

46
Systemic Therapies

• Oral
• Methotrexate
• Neoral (cyclosporine)
• Soriatane (acitretin)
• Parenteral
• Amevive (alefacept)
• Raptiva (efalizimab)
• Enbrel (etanercept)

47
Methotrexate

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

48
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

49
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

50
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

51
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

52
Neoral

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

53
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

54
Neoral Side Effects

• Possibility of Irreversible renal damage
• Hypertension
• Headache
• Hypertriglyceridemia
• Hirsutism/hypertrichosis
• Paresthesia/hyperesthesia
• Influenza-like symptoms
• Nausea/vomiting
• Diarrhea
• Lethargy
• Arthralgia

55
Neoral

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

56
Soriatane

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

57
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

58
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

59
Soriatane Side Effects

• Those associated with retinoid therapy
• Cheilitis
• Alopecia
• Skin peeling
• Dry skin
• Pruritus
• Rhinitis
• Xeropthalmia
• Arthralgia

60
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 lt 1 of
  patients in clinical trials on Soriatane

61
Soriatane

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

62
Parenteral TherapyAmevive

• 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

63
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

64
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

65
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