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  1. 1. Dr. V. J. Tannu Consultant Dermatologist & Cosmetologist M.D., D. D. V., F. R .S. H. (London) Contact: +91 98231 30197 Email: [email_address] Website:
  2. 2. Introduction to Psoriasis <ul><li>Prevalence </li></ul><ul><li>Genetics and Pathogenesis </li></ul><ul><li>Clinical Variants of Psoriasis </li></ul><ul><li>State of the Armamentarium </li></ul>
  3. 3. Prevalence <ul><li>Psoriasis occurs in 2% of the world’s population </li></ul><ul><li>Prevalence in the U.S may be as high as 4.6% </li></ul><ul><li>Highest in Caucasians </li></ul><ul><li>In Africans, African Americans and Asians between 0.4% and 0.7% </li></ul>
  4. 4. Prevalence <ul><li>Equal frequency in males and females </li></ul><ul><li>May occur at any age from infancy to the 10 th decade of life </li></ul><ul><li>First signs of psoriasis </li></ul><ul><ul><li>Females mean age of 27 years </li></ul></ul><ul><ul><li>Males mean age of 29 years </li></ul></ul>
  5. 5. Prevalence <ul><li>Two Peaks of Occurrence </li></ul><ul><ul><li>One at 20-30 years </li></ul></ul><ul><ul><li>One at 50-60 years </li></ul></ul><ul><li>Psoriasis in children </li></ul><ul><ul><li>Low – between 0.5 and 1.1% in children 16 years old and younger </li></ul></ul><ul><ul><li>Mean age of onset - between 8 and 12.5 years </li></ul></ul>
  6. 6. Prevalence <ul><li>Two-thirds of patients have mild disease </li></ul><ul><li>One-third have moderate to severe disease </li></ul><ul><li>Early onset (prior to age 15) </li></ul><ul><ul><li>Associated with more severe disease </li></ul></ul><ul><ul><li>More likely to have a positive family history </li></ul></ul><ul><li>Life-long disease </li></ul><ul><ul><li>Remitting and relapsing unpredictably </li></ul></ul><ul><ul><li>Spontaneous remissions of up to 5 years have been reported in approximately 5% of patients </li></ul></ul>
  7. 7. Genetics and Pathogenesis <ul><li>Psoriasis and the Immune System </li></ul><ul><ul><li>The major histocompatibility complex (MHC) </li></ul></ul><ul><ul><ul><li>Short arm of chromosome 6 </li></ul></ul></ul><ul><ul><li>Histocompatibility Antigens (HLA) </li></ul></ul><ul><ul><ul><li>HLA-Cw6 </li></ul></ul></ul><ul><ul><ul><li>HLA-B13, -B17, -B37, -Bw16 </li></ul></ul></ul><ul><ul><li>T-lymphocyte-mediated mechanism </li></ul></ul>
  8. 8. Psoriasis as a Systemic Disease <ul><li>Koebner Phenomenon </li></ul><ul><li>Elevated ESR </li></ul><ul><li>Increased uric acid levels -> gout </li></ul><ul><li>Mild anemia </li></ul><ul><li>Elevated α 2 -macroglobulin </li></ul><ul><li>Elevated IgA levels </li></ul><ul><li>Increased quantities of Immune Complexes </li></ul>
  9. 9. Psoriasis as a Systemic Disease <ul><li>Psoriatic arthropathy </li></ul><ul><li>Aggravation of psoriasis by systemic factors </li></ul><ul><ul><li>Medication </li></ul></ul><ul><ul><li>Focal infections </li></ul></ul><ul><ul><li>Stress </li></ul></ul><ul><li>Life-threatening forms of psoriasis </li></ul>
  10. 10. Clinical Variants of Psoriasis
  11. 11. Characteristic Lesion of Psoriasis <ul><li>Sharply demarcated erythematous plaque with micaceous silvery white scale </li></ul><ul><li>Histopathology </li></ul><ul><ul><li>Thickening of the epidermis </li></ul></ul><ul><ul><li>Tortuous and dilated blood vessels </li></ul></ul><ul><ul><li>Inflammatory infiltrate primarily of lymphocytes </li></ul></ul>
  12. 12. Psoriatic Plaque
  13. 13. Severity of Disease <ul><li>Three Cardinal Signs of Psoriatic Lesions </li></ul><ul><ul><li>Plaque elevation </li></ul></ul><ul><ul><li>Erythema </li></ul></ul><ul><ul><li>Scale </li></ul></ul><ul><li>Body Surface Area </li></ul>
  14. 14. Chronic Plaque Psoriasis <ul><li>Most Common Variant </li></ul><ul><li>Plaques may be as large as 20 cm </li></ul><ul><li>Symmetrical disease </li></ul><ul><li>Sites of Predilection </li></ul><ul><ul><li>Elbows </li></ul></ul><ul><ul><li>Knees </li></ul></ul><ul><ul><li>Presacrum </li></ul></ul><ul><ul><li>Scalp </li></ul></ul><ul><ul><li>Hands and Feet </li></ul></ul>
  15. 15. Chronic Plaque Psoriasis
  16. 16. Chronic Plaque Psoriasis
  17. 17. Chronic Plaque Psoriasis <ul><li>May be widespread – up to 90% BSA </li></ul><ul><li>Genitalia involved in up to 30% of patients </li></ul><ul><li>Most patients have nail changes </li></ul><ul><ul><li>Nail pitting </li></ul></ul><ul><ul><li>“ Oil Spots” </li></ul></ul><ul><ul><li>Involvement of the entire nail bed </li></ul></ul><ul><ul><ul><li>Onychodystrophy </li></ul></ul></ul><ul><ul><ul><li>Loss of nail plate </li></ul></ul></ul>
  18. 18. Psoriasis of the Nail
  19. 19. Psoriasis of the Nail
  20. 20. Symptoms of Chronic Plaque Psoriasis <ul><li>Pruritus </li></ul><ul><li>Pain </li></ul><ul><li>Excessive heat loss </li></ul><ul><li>Patient Complaints </li></ul><ul><ul><li>Unsightliness of the lesions </li></ul></ul><ul><ul><li>Low self-esteem </li></ul></ul><ul><ul><li>Feelings of being socially outcast </li></ul></ul><ul><ul><li>Excessive scale </li></ul></ul>
  21. 21. Guttate Psoriasis <ul><li>Characterized by numerous 0.5 to 1.5 cm papules and plaques </li></ul><ul><li>Early age of onset </li></ul><ul><li>Most common form in children </li></ul><ul><li>Streptococcal throat infection often a trigger </li></ul><ul><li>Spontaneous remissions in children </li></ul><ul><li>Often chronic in adults </li></ul>
  22. 22. Guttate Psoriasis
  23. 23. Life–Threatening Forms of Psoriasis <ul><li>Generalized Pustular Psoriasis </li></ul><ul><li>Erythrodermic Psoriasis </li></ul>
  24. 24. Generalized Pustular Psoriasis <ul><li>Unusual manifestation of psoriasis </li></ul><ul><li>Can have a gradual or an acute onset </li></ul><ul><li>Characterized by waves of pustules on erythematous skin often after short episodes of fever of 39 ˚ to 40 ˚C </li></ul><ul><li>Weight loss </li></ul><ul><li>Muscle Weakness </li></ul><ul><li>Hypocalcemia </li></ul><ul><li>Leukocytosis </li></ul><ul><li>Elevated ESR </li></ul>
  25. 25. Generalized Pustular Psoriasis <ul><li>Cause is obscure </li></ul><ul><li>Triggering Factors </li></ul><ul><ul><li>Infection </li></ul></ul><ul><ul><li>Pregnancy </li></ul></ul><ul><ul><li>Lithium </li></ul></ul><ul><ul><li>Hypocalcemia secondary to hypoalbuminemia </li></ul></ul><ul><ul><li>Irritant contact dermatitis </li></ul></ul><ul><ul><li>Withdrawal of glucocorticosteroids, primarily systemic </li></ul></ul>
  26. 26. Generalized Pustular Psoriasis
  27. 27. Erythrodermic Psoriasis <ul><li>Classic lesion is lost </li></ul><ul><li>Entire skin surface becomes markedly erythematous with desquamative scaling. </li></ul><ul><li>Often only clues to underlying psoriasis are the nail changes and usually facial sparing </li></ul>
  28. 28. Erythrodermic Psoriasis <ul><li>Triggering Factors </li></ul><ul><ul><li>Systemic Infection </li></ul></ul><ul><ul><li>Withdrawal of high potency topical or oral steroids </li></ul></ul><ul><ul><li>Withdrawal of Methotrexate </li></ul></ul><ul><ul><li>Phototoxicity </li></ul></ul><ul><ul><li>Irritant contact dermatitis </li></ul></ul>
  29. 29. State of the Armamentarium <ul><li>Wide range of therapies for the treatment of moderate to severe psoriasis </li></ul><ul><li>None induce a permanent remission </li></ul><ul><li>All have side effects that can place limits on their use </li></ul>
  30. 30. State of the Armamentarium <ul><li>Therapies </li></ul><ul><ul><li>Topical Corticosteroids </li></ul></ul><ul><ul><li>Topical Vitamin D 3 Analogues </li></ul></ul><ul><ul><li>Topical Retinoids </li></ul></ul><ul><ul><li>Photo(chemo)therapy </li></ul></ul><ul><ul><li>Systemic Therapies </li></ul></ul><ul><ul><ul><li>Oral </li></ul></ul></ul><ul><ul><ul><li>Parenteral </li></ul></ul></ul>
  31. 31. Topical Corticosteroids <ul><li>High potency and Super potent topical steroids </li></ul><ul><li>These include </li></ul><ul><ul><li>Fluocinonide family (cream, ointment, gel) </li></ul></ul><ul><ul><li>Betamethasone dipropionate cream </li></ul></ul><ul><ul><li>Clobetasol propionate family (cream, ointment, gel, foam, lotion) </li></ul></ul><ul><ul><li>Diflorasone diacetate ointment </li></ul></ul><ul><ul><li>Betamethasone dipropionate ointment </li></ul></ul>
  32. 32. Topical Corticosteroids <ul><li>Side effects associated with use </li></ul><ul><ul><li>Skin atrophy </li></ul></ul><ul><ul><li>Burning and stinging </li></ul></ul><ul><ul><li>Suppression of the hypothalamic-pituitary-adrenal (HPA) axis </li></ul></ul><ul><ul><ul><li>This may occur after 2 weeks of use with certain topical corticosteroids </li></ul></ul></ul>
  33. 33. Topical Vitamin D 3 Analogues <ul><li>Prototype for this group is calcipotriene </li></ul><ul><li>3 formulations – cream, ointment, and scalp solution </li></ul><ul><li>Former two are approved for plaque psoriasis </li></ul><ul><li>Latter for moderate to severe psoriasis of the scalp </li></ul>
  34. 34. Topical Vitamin D 3 Analogues <ul><li>Side Effects </li></ul><ul><ul><li>Cutaneous </li></ul></ul><ul><ul><ul><li>Burning </li></ul></ul></ul><ul><ul><ul><li>Stinging </li></ul></ul></ul><ul><ul><ul><li>Pruritus </li></ul></ul></ul><ul><ul><ul><li>Skin irritation </li></ul></ul></ul><ul><ul><ul><li>Tingling of the skin </li></ul></ul></ul>
  35. 35. Topical Retinoids <ul><li>Tazarotene Gel and Cream </li></ul><ul><ul><li>Available in two strengths </li></ul></ul><ul><ul><ul><li>0.05% and 0.1% </li></ul></ul></ul><ul><ul><li>Side Effects </li></ul></ul><ul><ul><ul><li>Pruritus </li></ul></ul></ul><ul><ul><ul><li>Burning/Stinging </li></ul></ul></ul><ul><ul><ul><li>Erythema </li></ul></ul></ul><ul><ul><ul><li>Worsening of psoriasis </li></ul></ul></ul><ul><ul><ul><li>Irritation </li></ul></ul></ul><ul><ul><ul><li>Skin pain </li></ul></ul></ul><ul><ul><ul><li>Hypertriglyceridemia </li></ul></ul></ul>
  36. 36. Topical Tazarotene <ul><li>Additional Indications </li></ul><ul><ul><li>0.1% gel - approved for the treatment of facial acne vulgaris of mild to moderate severity </li></ul></ul><ul><ul><li>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 </li></ul></ul>
  37. 37. Topical Tazarotene (con’t) <ul><li>Both products are pregnancy category X </li></ul><ul><li>Are contraindicated in women who are or may become pregnant </li></ul><ul><li>Requirements before and during therapy </li></ul><ul><ul><li>A negative pregnancy test 2 weeks prior </li></ul></ul><ul><ul><li>Therapy initiated during a normal menses </li></ul></ul><ul><ul><li>Women of childbearing potential should use adequate birth control </li></ul></ul>
  38. 38. Photo(chemo)therapy <ul><li>Two types of phototherapy </li></ul><ul><ul><li>Ultraviolet B (UVB) </li></ul></ul><ul><ul><li>Ultraviolet A + psoralen (PUVA) </li></ul></ul>
  39. 39. UVB <ul><li>Two types </li></ul><ul><ul><li>Broadband UVB </li></ul></ul><ul><ul><li>Narrowband UVB (311-313 nm) </li></ul></ul><ul><li>Treatment is time consuming </li></ul><ul><ul><li>2-3 visits/week for several months </li></ul></ul><ul><li>Side effect – possibility of experiencing an acute sunburn reaction </li></ul>
  40. 40. PUVA <ul><li>Consists of ingestion of or topical treatment with a psoralen followed by UVA </li></ul><ul><li>Usually reserved for severe, recalcitrant, disabling psoriasis </li></ul><ul><li>Time consuming – 2-3 visits/wk; at least 6 weeks </li></ul><ul><li>Precautions </li></ul><ul><ul><li>Patients must be protected from further UV light for 24 hours post treatment </li></ul></ul><ul><ul><li>With oral psoralen, wrap around UV-blocking glasses must be worn for 24 hours post treatment </li></ul></ul>
  41. 41. PUVA <ul><li>Side effects with oral psoralen </li></ul><ul><ul><li>Nausea </li></ul></ul><ul><ul><li>Dizziness </li></ul></ul><ul><ul><li>Headache </li></ul></ul><ul><li>Side effects with PUVA </li></ul><ul><ul><li>Early </li></ul></ul><ul><ul><ul><li>Pruritus </li></ul></ul></ul><ul><ul><li>Late </li></ul></ul><ul><ul><ul><li>Skin damage </li></ul></ul></ul><ul><ul><ul><li>Increased risk for skin cancer, particularly squamous cell (SCC) and after 200 - 250 treatments, increased risk for melanoma </li></ul></ul></ul>
  42. 42. Contraindications to PUVA <ul><li>Patients less than 12 years of age </li></ul><ul><li>Patients with a history of light sensitive disease states </li></ul><ul><li>Patients with, or with a history of melanoma </li></ul><ul><li>Patients with invasive SCC </li></ul><ul><li>Patients with aphakia </li></ul>
  43. 43. Systemic Therapies <ul><li>Oral </li></ul><ul><ul><li>Methotrexate </li></ul></ul><ul><ul><li>Neoral (cyclosporine) </li></ul></ul><ul><ul><li>Soriatane (acitretin) </li></ul></ul><ul><li>Parenteral </li></ul><ul><ul><li>Amevive (alefacept) </li></ul></ul><ul><ul><li>Raptiva (efalizimab) </li></ul></ul><ul><ul><li>Enbrel (etanercept) </li></ul></ul>
  44. 44. Methotrexate <ul><li>Folic acid antagonist </li></ul><ul><li>Usually reserved for severe, recalcitrant, disabling psoriasis </li></ul><ul><li>Maximum improvement can be expected after 8 -12 weeks </li></ul>
  45. 45. Contraindications - Methotrexate <ul><li>Nursing mothers </li></ul><ul><li>Patients with alcoholism </li></ul><ul><li>Alcoholic liver disease </li></ul><ul><li>Other chronic liver disease </li></ul><ul><li>Patients with overt or laboratory evidence of immunodeficiency syndromes </li></ul><ul><li>Patients who have preexisting blood dyscrasias </li></ul>
  46. 46. Methotrexate <ul><li>Pregnancy Category X drug product </li></ul><ul><ul><li>Contraindicated in pregnant women with psoriasis </li></ul></ul><ul><ul><li>Pregnancy must be excluded in women of childbearing potential </li></ul></ul><ul><ul><li>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 </li></ul></ul>
  47. 47. Methotrexate – Side Effects <ul><li>Acute or chronic hepatotoxicity </li></ul><ul><li>Hepatic cirrhosis </li></ul><ul><li>Leukopenia </li></ul><ul><li>Thrombocytopenia </li></ul><ul><li>Anemia, including aplastic anemia </li></ul><ul><li>Rarely, interstitial pneumonitis </li></ul><ul><li>Stomatitis </li></ul><ul><li>Nausea/vomiting </li></ul><ul><li>Alopecia </li></ul><ul><li>Photosensitivity </li></ul><ul><li>Burning of skin lesions </li></ul>
  48. 48. Methotrexate <ul><li>Multiple prescreening tests necessary </li></ul><ul><li>Recommendations for hepatic monitoring </li></ul><ul><ul><li>Periodic LFTs including serum albumin </li></ul></ul><ul><ul><li>Liver biopsy </li></ul></ul><ul><ul><ul><li>Pretherapy or shortly thereafter </li></ul></ul></ul><ul><ul><ul><li>Cumulative dose of 1.5 grams </li></ul></ul></ul><ul><ul><ul><li>After each additional 1.0 to 1.5 grams </li></ul></ul></ul>
  49. 49. Neoral <ul><li>Potent Immunosuppressive </li></ul><ul><li>Adult, non-immunocompromised patients with severe, recalcitrant plaque psoriasis </li></ul><ul><li>Maximum efficacy achieved at 16 weeks of therapy </li></ul>
  50. 50. Contraindications - Neoral <ul><li>Concomitant PUVA or UVB therapy </li></ul><ul><li>Methotrexate or other immunosuppressive agents </li></ul><ul><li>Coal tar or radiation therapy </li></ul><ul><li>Patients with abnormal renal function </li></ul><ul><li>Patients with uncontrolled hypertension </li></ul><ul><li>Patients with malignancies </li></ul><ul><li>Nursing mothers </li></ul>
  51. 51. Neoral – Side Effects <ul><li>Possibility of Irreversible renal damage </li></ul><ul><li>Hypertension </li></ul><ul><li>Headache </li></ul><ul><li>Hypertriglyceridemia </li></ul><ul><li>Hirsutism/hypertrichosis </li></ul><ul><li>Paresthesia/hyperesthesia </li></ul><ul><li>Influenza-like symptoms </li></ul><ul><li>Nausea/vomiting </li></ul><ul><li>Diarrhea </li></ul><ul><li>Lethargy </li></ul><ul><li>Arthralgia </li></ul>
  52. 52. Neoral <ul><li>Multiple prescreening tests are required </li></ul><ul><li>Tests must continue throughout treatment with dosage adjustment as necessary to prevent end-organ damage </li></ul>
  53. 53. Soriatane <ul><li>Oral retinoid approved for the treatment of severe psoriasis in adults </li></ul><ul><li>Significant improvement can be achieved with 8 weeks of therapy </li></ul>
  54. 54. Soriatane - Contraindications <ul><li>Patients with severely impaired liver or kidney function </li></ul><ul><li>Patients with chronic abnormally elevated blood lipid values </li></ul><ul><li>Patients who are taking methotrexate </li></ul><ul><li>Ethanol use when on therapy and for 2 months following therapy in female patients </li></ul>
  55. 55. Soriatane <ul><li>Pregnancy Category X drug product as it is a human teratogen </li></ul><ul><li>Contraindicated in pregnant females or those who intend to become pregnant during therapy or any time up to three years post therapy </li></ul>
  56. 56. Soriatane – Side Effects <ul><li>Those associated with retinoid therapy </li></ul><ul><ul><li>Cheilitis </li></ul></ul><ul><ul><li>Alopecia </li></ul></ul><ul><ul><li>Skin peeling </li></ul></ul><ul><ul><li>Dry skin </li></ul></ul><ul><ul><li>Pruritus </li></ul></ul><ul><ul><li>Rhinitis </li></ul></ul><ul><ul><li>Xeropthalmia </li></ul></ul><ul><ul><li>Arthralgia </li></ul></ul>
  57. 57. Soriatane – Side Effects <ul><li>Laboratory Abnormalities </li></ul><ul><ul><li>Hypertriglyceridemia (66%) </li></ul></ul><ul><ul><li>Decreased HDL (40%) </li></ul></ul><ul><ul><li>Hypercholesterolemia (33%) </li></ul></ul><ul><ul><li>Elevated liver function tests (33%) </li></ul></ul><ul><ul><li>Elevated alkaline phosphatase (10-25%) </li></ul></ul><ul><ul><li>Hyperglycemia (10-25%) </li></ul></ul><ul><ul><li>Elevated CPK (10-25%) </li></ul></ul><ul><li>Hepatitis and jaundice occurred in < 1% of patients in clinical trials on Soriatane </li></ul>
  58. 58. Soriatane <ul><li>Multiple prescreening tests must be obtained </li></ul><ul><li>Continued monitoring throughout therapy necessary with possible dosage adjustment </li></ul>
  59. 59. Parenteral Therapy Amevive <ul><li>Immunosuppressive dimeric fusion protein </li></ul><ul><ul><li>Extracellular CD2-binding portion of the human leukocyte function antigen-3 (LFA-3) </li></ul></ul><ul><ul><li>Linked to the Fc portion of human IgG1 </li></ul></ul>
  60. 60. Amevive <ul><li>Indicated for the treatment of adult patients with moderate to severe chronic plaque psoriasis </li></ul><ul><li>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 </li></ul>
  61. 61. Amevive – Side Effects <ul><li>Dose dependent reduction in circulating CD4+ and CD8+ T lymphocytes </li></ul><ul><ul><li>Should not be administered to patients with low CD4+ counts </li></ul></ul><ul><ul><li>CD4+ counts must be monitored before and weekly throughout therapy </li></ul></ul>
  62. 62. Amevive – Side Effects <ul><li>Lymphopenia </li></ul><ul><li>Increase risk of malignancies </li></ul><ul><ul><li>Skin cancer – BCC and SCC </li></ul></ul><ul><ul><li>Lymphoma </li></ul></ul><ul><li>Serious infections requiring hospitalization </li></ul><ul><li>Risk of reactivation of chronic, latent infections </li></ul><ul><li>Hypersensitivity reactions </li></ul>
  63. 63. Dr. V. J. Tannu Consultant Dermatologist & Cosmetologist M.D., D. D. V., F. R .S. H. (London) Contact: +91 98231 30197 Email: [email_address] Website: