Introduction to Psoriasis

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Nordine AL-Rashidy on Oct 14, 2012 Says :

very nice work for more and more progress.Please send me acoppy. Dr.N ordine M. Abdullah

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very useful slides

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Thanks good work.

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Slide 1 :

1 Introduction to Psoriasis Denise Cook, M.D. Medical Officer Division of Dermatology and Dental Drug Products

Slide 2 :

2 Introduction to Psoriasis Prevalence Genetics and Pathogenesis Clinical Variants of Psoriasis State of the Armamentarium

Slide 3 :

3 Prevalence Psoriasis occurs in 2% of the world’s 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%

Slide 4 :

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

Slide 5 :

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

Slide 6 :

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

Slide 7 :

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

Slide 8 :

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

Slide 9 :

9 Psoriasis as a Systemic Disease Psoriatic arthropathy Aggravation of psoriasis by systemic factors Medication Focal infections Stress Life-threatening forms of psoriasis

Slide 10 :

10 Clinical Variants of Psoriasis

Slide 11 :

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

Slide 12 :

12 Psoriatic Plaque

Slide 13 :

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

Slide 14 :

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

Slide 15 :

15 Chronic Plaque Psoriasis

Slide 16 :

16 Chronic Plaque Psoriasis

Slide 17 :

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

Slide 18 :

18 Widespread Chronic Plaque Psoriasis

Slide 19 :

19 Chronic Psoriasis

Slide 20 :

20 Psoriasis of the Nail

Slide 21 :

21 Psoriasis of the Nail

Slide 22 :

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

Slide 23 :

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

Slide 24 :

24 Guttate Psoriasis

Slide 25 :

25 Life–Threatening Forms of Psoriasis Generalized Pustular Psoriasis Erythrodermic Psoriasis

Slide 26 :

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 40°C Weight loss Muscle Weakness Hypocalcemia Leukocytosis Elevated ESR

Slide 27 :

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

Slide 28 :

28 Generalized Pustular Psoriasis

Slide 29 :

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

Slide 30 :

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

Slide 31 :

31 Erythrodermic Psoriasis

Slide 32 :

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

Slide 33 :

33 State of the Armamentarium Therapies Topical Corticosteroids Topical Vitamin D3 Analogues Topical Retinoids Photo(chemo)therapy Systemic Therapies Oral Parenteral

Slide 34 :

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

Slide 35 :

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

Slide 36 :

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

Slide 37 :

37 Topical Vitamin D3 Analogues Side Effects Cutaneous Burning Stinging Pruritus Skin irritation Tingling of the skin

Slide 38 :

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

Slide 39 :

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

Slide 40 :

40 Topical Tazarotene (con’t) 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

Slide 41 :

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

Slide 42 :

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

Slide 43 :

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

Slide 44 :

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

Slide 45 :

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

Slide 46 :

46 Systemic Therapies Oral Methotrexate Neoral (cyclosporine) Soriatane (acitretin) Parenteral Amevive (alefacept) Raptiva (efalizimab) Enbrel (etanercept)

Slide 47 :

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

Slide 48 :

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

Slide 49 :

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

Slide 50 :

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

Slide 51 :

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

Slide 52 :

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

Slide 53 :

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

Slide 54 :

54 Neoral – Side Effects Possibility of Irreversible renal damage Hypertension Headache Hypertriglyceridemia Hirsutism/hypertrichosis Paresthesia/hyperesthesia Influenza-like symptoms Nausea/vomiting Diarrhea Lethargy Arthralgia

Slide 55 :

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

Slide 56 :

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

Slide 57 :

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

Slide 58 :

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

Slide 59 :

59 Soriatane – Side Effects Those associated with retinoid therapy Cheilitis Alopecia Skin peeling Dry skin Pruritus Rhinitis Xeropthalmia Arthralgia

Slide 60 :

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 < 1% of patients in clinical trials on Soriatane

Slide 61 :

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

Slide 62 :

62 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

Slide 63 :

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

Slide 64 :

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

Slide 65 :

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

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