Psoriasis - Dr. Ancy George
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This document summarizes treatment options for psoriasis. It begins by describing the pathology and types of psoriasis. Topical therapies discussed include emollients, keratolytic agents, vitamin D analogs, retinoids, and glucocorticoids. Phototherapy options like PUVA, UVB, and Goeckerman therapy are mentioned. Systemic therapies summarized are acitretin, methotrexate, cyclosporine, and TNF-alpha inhibitors like etanercept and infliximab. Newer biologics targeting IL-12/IL-23 and IL-17 are also noted. The document provides an overview of pharmacological management of psoriasis
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Psoriasis - Dr. Ancy George
- 1. DRUGS FOR PSORIASIS Dr. ANCY GEORGE JUNIOR RESIDENT/ DEPT OF PHARMACOLOGY
- 2. CONTENTS 1. Pathology 2. Etiology 3. Types 4. Treatment modalities
- 4. PSORIASIS Chronic inflammatory skin disease - multisystem Incidence – 3.2% population (0.4-2.8%) Presenting features: Well demarcated red plaques with silver scales Scalp, elbow, knees and presacral regions
- 5. PATHOLOGY Inflammatory immune mediated condition Involves cutaneous T cells, dendritic cells and keratinocytes Keratinocytic hyperproliferation Scaly plaques
- 6. ETIOLOGY
- 7. TYPES OF PSORIASIS Chronic plaque psoriasis Erythrodermic psoriasis Guttate psoriasis Pustular psoriasis
- 8. PSORIATIC ARTHRITIS 5-30% of patients with cutaneous psoriasis Severity depends on: Initial presentation at early age Female gender Polyarticular involvement Genetic predisposition
- 9. DRUGS EXACERBATING PSORIASIS β-blockers Lithium Antimalarials Terbinafine Captopril G CSF Hypolipidemics CCB
- 10. MANAGEMENT OF PSORIASIS Topical therapy PUVA Therapy Systemic therapy
- 11. TOPICAL THERAPY 1. Emollients 2. Keratolytic Agents- Salicylic acid 3. Cytostatic agents- Coal tar, Dithranol 4. Vit D3 analogues 5. Retinoids 6. Glucocorticoids
- 12. TOPICAL AGENTS Salt water bath Topical salicylic acid 5-10% Anti inflammatory antipruritic action
- 13. COAL TAR Exerts phototoxic action – exposed to light Relapses common Use declined – carcinogenicity and photo toxicity
- 14. ANTHRALIN Dithranol – ointment/ paste/ paint Anti-proliferative effect Inhibits T- lymphocyte proliferation and epidermal DNA synthesis Don’t apply on face and scalp
- 15. Indication - Mild to moderate or severe psoriasis as 2nd line treatment in combination Contraindications Unstable plaque psoriasis Pustular psoriasis Erythrodermic psoriasis
- 16. VITAMIN D3 ANALOGUES Calcipotriene/ Calcipotriol • Along with corticosteroids • 50 µg/g BID • Ointment, creams, lotion Calcitriol • 3 µg/g BID ointment Tacalcitol • 2µg/g BID daily, ointment, lotions
- 17. RETINOIDS 1st GENERATION 2nd GENERATION 3rd GENERATION Retinol Tretinoin Alitretinoin Isotretinoin Etretinate Acitretin Tazarotene Bexarotene Adapalene 17
- 18. TOPICAL RETINOIDS - TAZAROTENE • Selectively binds to retinoid acid receptors and decrease epidermal proliferation • Cream or gel formulation applied once or twice daily Indication Mild to moderate psoriasis
- 19. GLUCOCORTICOIDS Indications Mild to moderate psoriasis – monotherapy or combination Severe psoriasis- combination with Vit D3 analogue, retinoids, anthralin Monotherapy for flexural or facial psoriasis Contraindications Bacterial, viral, mycotic infections Atrophy of skin
- 20. PHOTO(CHEMO)THERAPY Broadband (290-320nm)or narrow band (311nm)UVB PUVA – Psoralen + UVA Indication Moderate to severe psoriasis as 1st line therapy
- 21. GOECKERMANN THERAPY Combination of UVB & Coal tar EXCIMER LASER Only the involved skin is treated UVB light
- 22. PUVA UVA(320-340nm) with photosensitizing agent psoralen Orally administered- methoxsalen Psoralen intercalate with DNA strand
- 23. Oral methoxsalen 10-70 mg (0.4-0.6 mg/kg) 1.5-2 hr before UVA exposure Remission for 3-6 months ADR Phototoxic reaction, pruritus, hypetrichosis Photo ageing, Melanoma
- 24. SYSTEMIC THERAPY
- 25. ACITRETIN 2nd generation synthetic retinoid Suppress inflammation Indication - Recalcitrant pustular psoriasis Teratogenic Eliminated slowly
- 26. ETRETINATE 2nd generation retinoid Inhibits keratinization and proliferation Combined with PUVA therapy
- 27. CYTOTOXIC AND IMMUNOSUPPRESSANT DRUGS METHOTREXATE Moderate to severe psoriasis MOA – suppress immunocompetent cells Decrease the expression of CLA positive T cells 10-25 mg once weekly as single dose Psoriatic arthritis Hepatic cirrhosis on long term use
- 28. CYCLOSPORINE Inhibits production of IL-12 Refractory cases of psoriasis ADR - HTN, Renal toxicity
- 29. CYTOKINES INVOLVED IN PSORIASIS
- 31. TNF- α INHIBITORS Reduces inflammation Decreases keratinocyte proliferation Decreases vascular adhesion
- 35. ETANERCEPT Binds both TNF alpha and beta Plaque psoriasis and psoriatic arthritis Pediatric psoriasis
- 36. INFLIXIMAB Chronic severe plaque psoriasis and psoriatic arthritis ADALIMUMAB Plaque psoriasis and psoriatic arthritis
- 37. Golimumab Once a month s.c. injection Certolizumab s.c. injection of 200 mg Plaque psoriasis & Psoriatic arthritis
- 38. IL 12/23 INHIBITORS USTEKINUMAB Moderate to severe plaque psoriasis and psoriatic arthritis RISANKIZUMAB For moderate to severe psoriasis For candidates of phototherapy and systemic therapy
- 39. GUSELKUMAB (2017) Plaque psoriasis TILDRAKIZUMAB (2018) Subcutaneous injection
- 40. IL 17 INHIBITORS IL 17 stimulation causes increased keratinocyte expression of inflammatory cytokines SECUKINUMAB Moderate to severe plaque psoriasis in adults
- 41. IXEKIZUMAB – Plaque psoriasis and psoriatic arthritis 160 mg s.c. 80 mg twice weekly BRODALUMAB (2017) Moderate to severe psoriasis s.c.
- 42. JAK INHIBITORS TOFACITINIB Rheumatic Arthritis Demonstrated efficacy in psoriatic arthritis Oral tablet
- 43. T CELL ACTIVATION INHIBITORS Efalizumab Chronic moderate to severe plaque psoriasis Withdrawn in 2009 – progressive multifocal leucoencephalopathy Alefacept Moderate to severe chronic plaque psoriasis 7.5mg once a week i.v. / 15mg once a week i.m. for 12 weeks
- 44. PDE4 INHIBITORS APREMILAST Decreases inflammatory cytokines Moderate to severe plaque psoriasis and psoriatic arthritis in adults ADR – Weight loss and depression
- 49. THANK YOU
Editor's Notes
- Auspitz sign – bleeding points on scale removal
- Th 1 pre-dominated inflammatory autoimmune disease
- According to area of manifestations Scalp, Flexural, Nail, Oral mucosa
- Emollients – Soothe or soften the skin – paraffin, cocoa butter apllied after bath – 3 times a day Cytostatic agents – death or inhibition of growth or dividing of a cell
- crude preparation containing phenolic compounds 2 hrs before bath – wash off
- 80% patients experience total clearing of psoriasis within 3-5 weeks of treatment in IP setting
- Unstable – poorly defied plaques – can lead to erythrodermic
- Vit D3 inhibits epidermal proliferation suppress proliferation of keratinocytes and enhance differentiation respond in 4-8 weeks
- Prodrug - Tazarotenic acid
- Type I O2 independent Type II O2 dependent energy transfer ROS
- Inhibition of amino-imidazolecarboxamide ribonucleotide(AICAR) transformylse and thymidylate synthetase Cutaneous lymphocyte associated antigen
- Tolypocladium inflatum MYCOPHENOLATE MOFETIL (MMF)
- Pro-inflammatory cytokines – TNFα, IFNγ, IL12, IL23, IL17
- IL 12 promotes Th1 activity thereby TNF alpha and gamma production IL23 activates Th17 cells that produce IL 17A ( regulates tissue inflammation and autoimmune response)
- ADR Nasopharyngitis, URTI, diarrhea
- Recombinant IL 4 in preclinical stage for psoriasis
- Oral agent
- CREB – cAmp response element binding protein
- Apart from this, stress management, CBT
- Diet -