Psoriasis treatment by aseem

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Treatment incl Biologics, Systemic, Topicals, Phototherapy, Climatic Dead Sea Therapy et al, also encompassing Treatment issues and newer therapeutic scoring systems.

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Psoriasis treatment by aseem

  1. 1. TREATMENT MODALITIES IN PSORIASIS
  2. 2. PSORIASIS Psoriasis is a Chronic, incurable, disfiguring, inflammatory, progressive disorder characterized by Erythematous, Scaly, Indurated Plaques present predominantly over Extensor Surfaces and Scalp, progressing to involve Nails / Joints as the disease progresses
  3. 3. IMPLICATIONS • PHYSICAL / PSYCHOLOGICAL BURDEN • HAMPERS QoL / WORK / SOCIAL OUTLOOK / PERCEPTION OF SELF • CAFETERIA APPROACH TO TREATMENT • NON-COMPLIANCE TO COMPLEX REGIMENS / NONADHERENCE TO TOPICALS / LONG-TERM COMPLICATIONS OF SYTEMIC AGENTS / SEASONAL EXACERBATIONS should be kept in mind
  4. 4. GOALS OF TREATMENT • Reduce Extent of Disease so it doesn’t hamper Daily Quality of Life. • Pt education essential • Discussion of treatment options so that patients know what to expect from treatment in terms of overall results, time scale of improvement and his effort involved in the process. • Consider psychological wellbeing of patient • Salford Score (Severity / Psyhosocial / Interventions) > PASI / SPASI / PGA / NPF-PS / PQoLI
  5. 5. TOPICALS • Stand-alone therapy > 80% Cases / Mainstay ; 1st Line Therapy in Mild-Moderate Psoriasis • Non-compliance = 40% • Cosmetically Unacceptable • Complex Regimens • Time consuming • Improved by Simple Regimens / Patient Education
  6. 6. TOPICALS • • • • • • • Corticosteroids Vitamin D3 Analogues Coal Tar Anthralin Retinoids Calcineurin Inhibitors Emollients
  7. 7. CORTICOSTEROIDS Stabilize Glucocorticoid receptors by induction of phospholipase A2 inhibitory proteins LIPOCORTINS  control the biosynthesis of potent mediators of inflammation such as PGs / LTs by inhibiting the release of their common precursor Arachidonic Acid • Anti-inflammatory / Anti-pruritic
  8. 8. CORTICOSTEROIDS • Superpotent / Potent – Scalp / Limb / Trunk • Mild Potency – Face / Flexures • Initial Clearance for 02 – 04 weeks  Maintainence Doses / Weekend Application OR Dilution / Combination
  9. 9. CORTICOSTEROIDS PROS • Non-irritant (Used on Face / Flexures) • Non-staining (Clothes / Skin) • Ease of L/A and Removal CONS • Folliculitis / Acne / Acneiform Eruptions • May ppt Pustular Psoriasis • Stria / Atrophy / Telangiectasis • Dec Plasma Cortisol levels by Adrenal Suppression • Tachyphylaxis Pregnancy Cat C
  10. 10. CORTICOSTEROIDS : Formulations Ointments Clobetasol Propionate 0.05% Betamethasone Dipropionate 0.05% (Combined with 3% SA) Clob + Vit D3 analogues CLOB BETASALIC SORVATE-C Creams Fluticasone Propionate 0.05% Mometasone Furoate 0.1% FLUTIVATE MOMATE Lotions Clobetasol Propionate 0.05% Clob + 3% SA Clob + SA + Coal Tar Desonide 0.05% CLONATE TOPISAL ULTITAR-CS DESOWEN
  11. 11. CORTICOSTEROIDS : Formulations Shampoos FLUOCINOLONE ACETATE 0.1% SEBOWASH Hydrocolloid / Occlusive Film Dressings Foams CLOBETASOL PROPIONATE 0.05 % Oils / Sprays Deptt) - OLUX-E Trials (Being used by ENT
  12. 12. VITAMIN D3 ANALOGUES MECHANISM OF ACTION • • • • Stabilize Vitamin D Receptors Promote Epidermal Differentiation Inhibit Keratinocyte Proliferation Inhibit Pro-inflamm CK production viz IL-2 / IFN gamma
  13. 13. VITAMIN D3 ANALOGUES • Combiation > Monotherapy • Long-term Therapy safe & effective ADRs Local Irritation / Burning Hypercalcemia Hypervitaminosis D Pregnancy Cat C
  14. 14. VIT D3 FORMULATIONS • CALCITRIOL 0.003% (SORVATE / SORVATE-C) (1,25-dihydroxycholecalciferol) - Natural Active VD3 Metabolite of Synthetic Derivatives:• CALCIPOTRIENE (-OL) 0.005% (PACITREX) • TACALCITOL (1,24-dihydroxycholecalciferol) • MAXACALCITOL (1,25-Dihydroxyoxacalcitriol) 0.0025% • Synergistic Combinations with Corticosteroids / Anthralin • Ointment / Creams
  15. 15. TAZAROTENE • 3rd Gen Topical Retinoid • Metabolized into TAZAROTENIC ACID • (RAR-binding ; affinity for Beta / Gamma) • Normalizes Epidermal Differentiation • Antiproliferative Action
  16. 16. TAZAROTENE • Available as 0.05 / 0.1 % Gel / Cream
  17. 17. TAZAROTENE • ADRs - Local Irritation / Erythema / Photosensitivity / ‘Retinoid Dermatitis’ dosing • Pregnancy Cat X • Combination with Corticosteroids • Phototherapy - UV reduction by 33% LAHS
  18. 18. CALCINEURIN INHIBITORS • Macrolide Antibiotics that bind to FK506Binding Protein to inhibit Calcineurin via Calcium-Calmodulin blockade  Inhibit NFactivated T-cell Proliferation / pro-inflamm IL2 inhibitor • Pimecrolimus 1% / Tacrolimus 0.1% Oint
  19. 19. • aa
  20. 20. CALCINEURIN INHIBITORS • Flexural / Inverse Psoriasis • Local Burning • ? Lymphoma / Neoplastic tendency • ? Use in children < 02 yrs of age • Pregnancy Cat C
  21. 21. COAL TAR • 2000 yrs old (Asphalt used in 20 AD) • By-product of Anerobic, Dry Distillation of Organic Matter • Polyaromatic HCs / Phenol • ‘Liquor Picis Carbonis / Liquor Carbonis Detergens’ - medical prep
  22. 22. COAL TAR • William H Goeckerman (1925) 2-6% Coal Tar in Petrolatum X 02-04 hrs Wash  UV-B Inhibits Epidermal Proliferation by Antimitotic action at Stratum Basale
  23. 23. COAL TAR ADRs • Odour / Stain / Appearance • Contact Derm / Follicultitis / Pruritis • Carcinogenic (Benzapyrene / Anthracin compounds) • Systemic Toxicity (Phenol)
  24. 24. COAL TAR Preparations Baths (120 mL in 150 L Water) Ung Psoriasis (SA 2% LPC 10% Vaseline 100%) Ung LSU (SA 3% LPC 10% Urea 10% Emul 100%) Salytar (SA 3% Tar 6%) Ultitar-CS (Clob 0.05% SA 3% Tar 6%) Foam 2%
  25. 25. COAL TAR
  26. 26. COAL TAR
  27. 27. ANTHRALIN (DITHRANOL) • 1,8-dihydroxy 9-anthrone • Synthesized from natural CHRYSAROBIN (South American Araroba tree bark or Anthrone) • Antiproliferative / Anti-inflammatory
  28. 28. • John Ingram - UV-B therapy followed by
  29. 29. ANTHRALIN • ICD / Folliculitis / Burning • Stains Hair Purple / Green • Stains Skin Brown (Oxidative Product – Anthraquinone) • Stains Clothes / Nails • NO SYSTEMIC TOXICITY • Available as 1% Cream / Shampoo / GC combination • Inconvenient
  30. 30. EMOLLIENTS • • • • Avoid Dryness Limit fissuring Reduce Scaling / Desquamation Controls Pruritis • Increases absorption of Topical Agents by maintaining Hydration
  31. 31. EMOLLIENTS • Ung COCCUS CO (1% SA 1% SULPHUR 3% Coal Tar 3% Camphorated Oil 12% Coconut Oil 100% Vaseline) • COTARYL CREAM (12% Urea 6% Lactic Acid 3% Glycine) • LIQUID PARAFFIN 10-50% • AQUASOFT LOT (70% Aqua + Glycerine)
  32. 32. PHOTOTHERAPY • Antiproliferative / Anti-inflammatory action by Selective Depletion of Epidermal T Cells by Apoptosis • NB-UVB (311 nm) • BB-UVB (290-320 nm) • EXCIMER LASER (308 nm) • Safe in Pregnancy
  33. 33. PHOTOCHEMOTHERAPY • PSORALEN + UV A (320-400 nm) • Photosensitizer Furocoumarin derived from Psorela corylifolia followed by Phototherapy for clearance of lesions • Potent / Higher Side-Effect profile due to Photo-Carcinogenesis
  34. 34. Other Phototherapy Modalities PHOTODYNAMIC THERAPY PHOTOSENSITIZER (Amino-Levulinic Acid) + Tissue 02 + Light Source  ROS CLIMATOTHERAPY EQUATORIAL (SUMMER REMISSION) DEAD SEA THERAPY 400 mbsl ; Salt + Mineral Aerosol ; UV-A Penetrance 02-04 wks
  35. 35. SYSTEMIC THERAPY • Indicated for Severe Psoriasis (>30% BSA) or Recalcitrant Psoriasis or PsA • • • • • • • • • MTX CsA ACITRETIN FUMARIC ACID ESTERS HYDROXYUREA 6-THIOGUANINE MMF SULFASALAZINE BIOLOGICS
  36. 36. • aa
  37. 37. • ss
  38. 38. NEWER AGENTS • ANTI IL-12 / IL-23 (Ustekinumab / Guselkumab) • ZIDOVUDINE (ZDV-AZT) for Retinoid-resistant AIDS-associated Psoriasis • Protein Kinase C-Inhibitor • Gluten-free Diet (16% IgA/G to Gliadin) • Liarozole (Retinoic Acid Metab Blocking Agents RAMBAs) • Somatostatin • Vidofludimus (Crohn’s / Psoriasis) DHODH-I • Newer Biologics (Anti-IL 17)
  39. 39. IXEKIZUMAB • Humanized MAB • Selectively binds and neutralizes IL-17 proinflammatory Cytokines
  40. 40. SECUNIZUMAB • Humanized MAB • Selectively binds to IL-17a, reducing inflammation • 150 mg SC 02-weekly
  41. 41. BRODALUMAB • Pure Human MAB • Selective IL-17 blockade • 140 mg SC 04-weekly • ?? Neutropenia
  42. 42. ITOLIZUMAB • ALZUMAB by Biocon • ‘First in Class’ • Targets CD 6  downregulates T-cell Activation and Maturation, Reduces Pro- inflammatory Cytokines 25 mg / 5 mL @ Rs 7590/1.6 mg/kg SC every 02 weeks
  43. 43. MULTI-AGENT THERAPY • COMBINATION : Low-dose of each agent to prevent ADRs  Clearance  Less toxic continued PUVA + Steroids / Re-PUVA / Etanercept + CsA or MTX • ROTATION : Rotation of multiple drugs to avoid toxicity and resistance MTX  PUVA / CsA  Re / MTX  Re • SEQUENTIAL : Initial Clearance Transition Maintenance (UV A/B)
  44. 44. PREVENTION OF RELAPSE • • • • • • • PSYCHOLOGICAL – Stress / Depression OBESITY – Linkage to Raeven’s Metabolic Syn SMOKING? SEASONAL (WINTER EXACERBATION) Streptococcal Infection with Guttate Psoriasis Trauma (Koebnerization) DRUGS – ANTIMALARIALS / LITHIUM / AEDs / ACE-I / B – BLOCKERS
  45. 45. THANK YOU

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