TREATMENT MODALITIES IN PSORIASIS

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

IMPLICATIONS

• PHYSICAL / PSYCHOLOGICAL BURDEN

• HAMPERS QoL / WORK / SOCIAL OUTLOOK / PERCEPTION OF SELF

• CAFETERIA APPROACH TO TREATMENT

• NON-COMPLIANCE TO COMPLEX REGIMENS / NON-ADHERENCE TO TOPICALS / LONG-TERM COMPLICATIONS OF SYTEMIC AGENTS / SEASONAL EXACERBATIONS should be kept in mind

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

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

TOPICALS

• Corticosteroids• Vitamin D3 Analogues• Coal Tar• Anthralin• Retinoids• Calcineurin Inhibitors• Emollients

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

CORTICOSTEROIDS

• Superpotent / Potent – Scalp / Limb / Trunk

• Mild Potency – Face / Flexures

• Initial Clearance for 02 – 04 weeks Maintainence Doses / Weekend Application OR Dilution / Combination

CORTICOSTEROIDSPROS• 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

CORTICOSTEROIDS : FormulationsOintments

Clobetasol Propionate 0.05% CLOBBetamethasone Dipropionate 0.05% BETASALIC(Combined with 3% SA)

Clob + Vit D3 analogues SORVATE-C

Creams Fluticasone Propionate 0.05% FLUTIVATEMometasone Furoate 0.1% MOMATE

LotionsClobetasol Propionate 0.05% CLONATEClob + 3% SA TOPISALClob + SA + Coal Tar ULTITAR-CSDesonide 0.05% DESOWEN

CORTICOSTEROIDS : Formulations

Shampoos FLUOCINOLONE ACETATE 0.1% SEBOWASH

Hydrocolloid / Occlusive Film Dressings

Foams CLOBETASOL PROPIONATE 0.05 % OLUX-E

Oils / Sprays - Trials (Being used by ENT Deptt)

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

VITAMIN D3 ANALOGUES

• Combiation > Monotherapy• Long-term Therapy safe & effective

ADRs Local Irritation / Burning

HypercalcemiaHypervitaminosis D

Pregnancy Cat C

VIT D3 FORMULATIONS• CALCITRIOL 0.003% (SORVATE / SORVATE-C)

(1,25-dihydroxycholecalciferol) - Natural Active Metabolite of VD3

Synthetic Derivatives:-

• CALCIPOTRIENE (-OL) 0.005% (PACITREX)• TACALCITOL (1,24-dihydroxycholecalciferol)• MAXACALCITOL (1,25-Dihydroxyoxacalcitriol) 0.0025%

• Synergistic Combinations with Corticosteroids / Anthralin

• Ointment / Creams

TAZAROTENE

• 3rd Gen Topical Retinoid• Metabolized into TAZAROTENIC ACID • (RAR-binding ; affinity for Beta / Gamma)

• Normalizes Epidermal Differentiation• Antiproliferative Action

TAZAROTENE

• Available as 0.05 / 0.1 % Gel / Cream

TAZAROTENE

• ADRs - Local Irritation / Erythema / Photosensitivity / ‘Retinoid Dermatitis’ LAHS dosing

• Pregnancy Cat X

• Combination with Corticosteroids

• Phototherapy - UV reduction by 33%

CALCINEURIN INHIBITORS

• Macrolide Antibiotics that bind to FK506-Binding Protein to inhibit Calcineurin via Calcium-Calmodulin blockade Inhibit NF-activated T-cell Proliferation / pro-inflamm IL-2 inhibitor

• Pimecrolimus 1% / Tacrolimus 0.1% Oint

• aa

CALCINEURIN INHIBITORS

• Flexural / Inverse Psoriasis

• Local Burning• ? Lymphoma / Neoplastic tendency• ? Use in children < 02 yrs of age

• Pregnancy Cat C

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

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

COAL TAR

ADRs

• Odour / Stain / Appearance• Contact Derm / Follicultitis / Pruritis• Carcinogenic (Benzapyrene / Anthracin

compounds)• Systemic Toxicity (Phenol)

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%

COAL TAR

COAL TAR

ANTHRALIN (DITHRANOL)

• 1,8-dihydroxy 9-anthrone

• Synthesized from natural CHRYSAROBIN (South American Araroba tree bark or Anthrone)

• Antiproliferative / Anti-inflammatory

• John Ingram - UV-B therapy followed by

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

EMOLLIENTS

• Avoid Dryness • Limit fissuring• Reduce Scaling / Desquamation• Controls Pruritis

• Increases absorption of Topical Agents by maintaining Hydration

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)

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

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

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

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

• aa

• ss

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)

IXEKIZUMAB

• Humanized MAB

• Selectively binds and neutralizes IL-17 pro-inflammatory Cytokines

SECUNIZUMAB

• Humanized MAB

• Selectively binds to IL-17a, reducing inflammation

• 150 mg SC 02-weekly

BRODALUMAB

• Pure Human MAB

• Selective IL-17 blockade

• 140 mg SC 04-weekly

• ?? Neutropenia

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

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)

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

THANK YOU