Psoriasis. Andrei Metelitsa, MD, FRCPC, FAAD Clinical Associate Professor, Dermatology, U of C Co-Director, Institute for Skin Advancement

Transcription

1 Psoriasis Andrei Metelitsa, MD, FRCPC, FAAD Clinical Associate Professor, Dermatology, U of C Co-Director, Institute for Skin Advancement

2 Copyright 2017 by Sea Courses Inc. All rights reserved. No part of this document may be reproduced, copied, stored, or transmitted in any form or by any means graphic, electronic, or mechanical, including photocopying, recording, or information storage and retrieval systems without prior written permission of Sea Courses Inc. except where permitted by law. Sea Courses is not responsible for any speaker or participant s statements, materials, acts or omissions.

3 Learning Objectives Discuss Psoriasis Pathogenesis New treatment approaches

4 Overview and Epidemiology of Psoriasis Chronic, immune-mediated inflammatory disease of the skin Affects 2% of people worldwide An estimated 1 million Canadians have psoriasis Nearly one quarter of psoriasis patients have moderate-to-severe disease

5 Overview and Epidemiology of Psoriasis Genetics important 35-90% have family history Can appear at any age but usually 2 peaks y.o y.o.

6 Infections Triggering Factors Bacterial infections (e.g. Streptococcal pharyngitis) HIV more severe psoriasis Drugs Lithium, IFN, beta-blockers, antimalarials Rapid taper of corticosteroids can induce pustular psoriasis Stress Physical trauma (Koebner phenomenon) Cigarette smoking

7 Comorbidities Observed in Psoriasis Patients Cardiovascular/Metabolic comorbidities CVDs or risk factors increased 1 Myocardial infarction (MI; severe psoriasis ~7-fold) 2 Heart failure (~2-fold) 3 Hypertension (~2-fold) 3 Obesity (~2-fold) 3,4 Metabolic syndrome (~2-fold) 5 Increased CV mortality among inpatients (~1.5-fold) 6 Diabetes (~1.5-fold) 3

8 Chronic Plaque Psoriasis Guttate Psoriasis Pustular Psoriasis Inverse Psoriasis Nail psoriasis Sebopsoriasis Erythrodermic psoriasis Psoriatic Arthritis Clinical Variants

9 Chronic Plaque Psoriasis The most common type of psoriasis (90% of patients) Symmetric distribution of red, scaly plaques on elbows, knees, scalp, hands and feet genital involvement in up to 30% of cases Sharp demarcation line between the plaques and unaffected skin Scale is very thick and characteristic

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19 PASI = Psoriasis Area and Severity Index (0-72)

20 DLQI = Dermatology Life Quality Index (0-30)

21 Therapeutic Options in Psoriasis Topical treatments Topical corticosteroids Vitamin D analogues Topical retinoids Coal Tar Topical calcineurins Phototherapy UVB, nuvb PUVA Excimer Laser (308 nm) Traditional systemic treatment Acitretin Methotrexate Cyclosporine Biologics Etanercept Infliximab Adalimumab Ustekinumab Secukinumab Ixekizumab Brodalumab Guselkumab (Apremilast)

22 Topicals Treatments Corticosteroids Most widely used for psoriasis Usually high potency (e.g. clobetasol ungt, clobex spray) (except face and flexural) S/E: atrophy, striae, telangiectasia, hypertichosis, contact dermatitis, HPA axis supression Pulse-dosing prevents tachyphylaxis (3-4 weeks at a time) Vitamin D3 analogues Modulate keratinocyte growth and differentiation and inhibit T lymphocyte activity 2 common preparations: Calcipotriol (Dovonex, Silkis) Calcipotriol + betamethasone diproprionate (Dovobet, Enstilar) Well-tolerated and clinically effective Contraindicated if abnormality in bone or calcium metabolism, renal insufficiency, or pregnancy

23 Other Topicals Treatments Topical Retinoids Normalize epidermal differentiation, potent antiproliferative effect High incidence of irritation at sites of application Not used much these days Coal Tar Liquor carbonis detergens (LCD) is a distilled product Sometimes used for scalp psoriasis (lotions or shampoos) Unpleasant smell Contraindicated in pregnant or lactating women Calcineurin Inhibitors Sometimes used for facial and flexural psoriasis E.g. tacrolimus (protopic 0.1% ungt)

24 Phototherapy Best for guttate or sebopsoriasis PUVA>nUVB>UVB Most offices use nuvb (311 nm) S/E with UVB Short-term: erythema, xerosis Long-term: photoaging and carcinogenesis (nuvb is less carcinogenic) S/E with PUVA Short-term: redness, swelling, occasional blister Long-term: cataracts (need eye protection), dark lentigenes, photocarcinogenesis

25 Oral Methotrexate Indications Proposed mechanism of action Dosing Efficacy Chronic plaque psoriasis, pustular psoriasis, erythrodermic psoriasis, psoriatic arthritis, severe nail psoriasis or poor response to topicals and phototherapy Inhibits DNA synthesis and cell replication; also has specific T-cell suppressive activities 7.5 to 25 mg per week (po or IM); usually combine with folic acid (5 mg po daily) > 60% PASI 75 response (16 weeks) S/E Monitoring required Minor: N/V, Abdominal pain, oral erosions Major: myelosuppression, hepatotoxicity, pneumonitis, pulmonary fibrosis, fetal death or abnormalities Pregnancy X Baseline: CBCD, Liver Function tests (AST, ALT), Creatinine, Hep B and C serology, HIV (if risk), CXR if hx of pulmonary problems, Pregnancy test F/U: Repeat CBCD, LFT, Cr q2 weeks for the first month, then monthly +/- Liver biopsy at cumulitive dose of 1.5 g 1

26 Oral Cyclosporine Indications Proposed mechanism of action Dosing Severe Psoriasis Recalcitrant, treatment-resistant psoriasis Calcineurin inhibitor that interferes with early events in T-cell activation, preventing the production of cytokines (IL-2) and activated T cells 2.5 to 5 mg/kg/day Efficacy > 60% PASI 75 response (16 weeks) S/E Monitoring required Self-limiting: paresthesia, tremor, headache, nausea Other: hypertension, renal dysfunction, hypertrichosis, gingival hyperplasia Labs: hyperkalemia, hyperlipidemia, hyperuricemia, hypomangesemia, Pregnancy C Baseline: CBCD, Liver Function tests (AST, ALT), Creatinine, Lipids, Lytes, Uric acid, Mg, Pregnancy test, Blood pressure F/U: repeat q2 weeks for the first month, then monthly 1

27 Oral Acitretin Indications Severe Psoriasis Erythrodermic or pustular psoriasis Recalcitrant, treatment-resistant psoriasis Proposed mechanism of action Binds to retinoic acid receptor and may contribute by normalizing keratinization and proliferation of epidermis Dosing mg daily Efficacy > 60% PASI 75 response S/E Monitoring required Common: mucocutaneous dryness, elevation of triglycerides, sometimes alopecia Rare: skeletal hyperostosis (DISH), transaminitis, fetal abnormalities, Pregnancy X Avoid use of alcohol (re-esterification to etretinate) Baseline: CBCD, Liver Function tests (AST, ALT), Creatinine, Lipids, Pregnancy test F/U: repeat q2 weeks for the first month, then monthly 1

28 Oral Apremilast (Otezla) Indications Moderate to Severe Psoriasis Psoriatic Arthritis Proposed mechanism of action Apremilast inhibits PDE4, which results in increased intracellular camp levels in inflammatory cells Dosing 30 mg twice daily Efficacy > 30% PASI 75 response S/E Diarrhea, Nausea, Vomiting, Abdominal Pain Headache, URTI Depression Monitoring required None 1

29 Structure and Function of Biologics Etanercept (Enbrel) Infliximab (Remicade) Adalimumab (Humira) Ustekinumab (Stelara) Secukinumab (Cosentyx) Ixekizumab (Taltz) Guselkumab (Tremfya) Human fusion protein Chimeric monoclona l antibody Fully human monoclonal antibody Fully human monoclonal antibody Fully human monoclonal antibody Humanized monoclonal antibody Human monoclonal antibody Blocks TNF-α activity Blocks TNF-α activity Blocks TNF-α activity Blocks IL-12 and IL-23 Inhibits IL- 17A interaction with receptor Inhibits IL- 17A interaction with receptor Inhibits IL-23 (binds p19 subunit) SQ IV infusion SQ SQ SQ SQ SQ 50mg BIWx 12 weeks, then 25mg BIW 5mg/kg infusion at week 0, 2, 6 and q 8 weeks 80mg 1 st week, 40 mg 2 nd week, then 40 mg eow 45 or 90 mg at week 0, 4 and then q 12 weeks 300 mg SC at weeks 0, 1, 2, 3, and 4, then monthly 160 mg at week 0, then 80 mg at weeks 2, 4, 6, 8,10, 12 then q 4 weeks 100mg at week 0, 4 and then q8 weeks

30 Canadian Psoriasis Expert Panel Consensus Biologic Agents Etanercept, Infliximab, Adalimumab, Ustekinumab, Secukinumab, Ixekizumab, Guselkumab

31 PEARLs Psoriasis Novel biologic therapies Systemic disease No longer just a skin condition